Patrice Wendling

The blockade of interleukin-1 with anakinra improves glycemic control in patients with type 2 diabetes mellitus, according to results of a double-blind, parallel-group trial.

Researchers said improved glycemic control most likely was due to enhanced beta-cell secretory function (N. Engl. J. Med. 2007;356:1517–26).

“Further studies are needed to test higher doses of anakinra, to evaluate its long-term use, and to test interleukin-1 antagonists that have a prolonged half-life, with the aim of preventing beta-cell destruction and promoting beta-cell regeneration in type 2 diabetes,” wrote Dr. Claus Larsen, Steno Diabetes Center, Gentofte, Denmark, and associates.

In the 13-week trial, the researchers randomized 34 patients to 100 mg of anakinra (Kineret) once daily by subcutaneous self-administration, and 36 patients to placebo.

Glycated hemoglobin levels were significantly lower in the anakinra group after 4 weeks compared to the placebo group (an absolute reduction of 0.36%). The average absolute difference in glycated hemoglobin levels between baseline and 13 weeks was a reduction of 0.33% in the anakinra group and an increase of 0.13% in the placebo group.

Also at 13 weeks, beta-cell function increased in the anakinra group and decreased in the placebo group. The ratio of proinsulin to insulin was significantly lower in the anakinra group.

Levels of C-reactive protein and interleukin-6 were significantly lower after both 4 and 13 weeks in the anakinra group than in the placebo group.

Neither baseline values nor changes in levels of C-reactive protein or interleukin-6 were significantly correlated with changes in glycated hemoglobin levels in the anakinra group. This suggests that “reduced systemic inflammation did not play an important part in improved insulin secretion,” the researchers wrote.

However, “the response to anakinra might also be attributable to mildly improved insulin sensitivity resulting from reduced systemic inflammation,” Dr. Kristina Rother, of the National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md., suggested in an accompanying article (N. Engl. J. Med. 2007;356:1499–1501).

The researchers said the short duration and the lack of dose finding are weaknesses of the study, which was supported by several foundations, the Center for Clinical Studies at the University of Zürich, the European Union, and Novo Nordisk. The study drug was donated by Amgen.

Several of the authors report having an equity interest, receiving grant support, or being an employee of Novo Nordisk.

The blockade of interleukin-1 with anakinra improves glycemic control in patients with type 2 diabetes mellitus, according to results of a double-blind, parallel-group trial.

Researchers said improved glycemic control most likely was due to enhanced beta-cell secretory function (N. Engl. J. Med. 2007;356:1517–26).

“Further studies are needed to test higher doses of anakinra, to evaluate its long-term use, and to test interleukin-1 antagonists that have a prolonged half-life, with the aim of preventing beta-cell destruction and promoting beta-cell regeneration in type 2 diabetes,” wrote Dr. Claus Larsen, Steno Diabetes Center, Gentofte, Denmark, and associates.

In the 13-week trial, the researchers randomized 34 patients to 100 mg of anakinra (Kineret) once daily by subcutaneous self-administration, and 36 patients to placebo.

Glycated hemoglobin levels were significantly lower in the anakinra group after 4 weeks compared to the placebo group (an absolute reduction of 0.36%). The average absolute difference in glycated hemoglobin levels between baseline and 13 weeks was a reduction of 0.33% in the anakinra group and an increase of 0.13% in the placebo group.

Also at 13 weeks, beta-cell function increased in the anakinra group and decreased in the placebo group. The ratio of proinsulin to insulin was significantly lower in the anakinra group.

Levels of C-reactive protein and interleukin-6 were significantly lower after both 4 and 13 weeks in the anakinra group than in the placebo group.

Neither baseline values nor changes in levels of C-reactive protein or interleukin-6 were significantly correlated with changes in glycated hemoglobin levels in the anakinra group. This suggests that “reduced systemic inflammation did not play an important part in improved insulin secretion,” the researchers wrote.

However, “the response to anakinra might also be attributable to mildly improved insulin sensitivity resulting from reduced systemic inflammation,” Dr. Kristina Rother, of the National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md., suggested in an accompanying article (N. Engl. J. Med. 2007;356:1499–1501).

The researchers said the short duration and the lack of dose finding are weaknesses of the study, which was supported by several foundations, the Center for Clinical Studies at the University of Zürich, the European Union, and Novo Nordisk. The study drug was donated by Amgen.

Several of the authors report having an equity interest, receiving grant support, or being an employee of Novo Nordisk.

The blockade of interleukin-1 with anakinra improves glycemic control in patients with type 2 diabetes mellitus, according to results of a double-blind, parallel-group trial.

Researchers said improved glycemic control most likely was due to enhanced beta-cell secretory function (N. Engl. J. Med. 2007;356:1517–26).

“Further studies are needed to test higher doses of anakinra, to evaluate its long-term use, and to test interleukin-1 antagonists that have a prolonged half-life, with the aim of preventing beta-cell destruction and promoting beta-cell regeneration in type 2 diabetes,” wrote Dr. Claus Larsen, Steno Diabetes Center, Gentofte, Denmark, and associates.

In the 13-week trial, the researchers randomized 34 patients to 100 mg of anakinra (Kineret) once daily by subcutaneous self-administration, and 36 patients to placebo.

Glycated hemoglobin levels were significantly lower in the anakinra group after 4 weeks compared to the placebo group (an absolute reduction of 0.36%). The average absolute difference in glycated hemoglobin levels between baseline and 13 weeks was a reduction of 0.33% in the anakinra group and an increase of 0.13% in the placebo group.

Also at 13 weeks, beta-cell function increased in the anakinra group and decreased in the placebo group. The ratio of proinsulin to insulin was significantly lower in the anakinra group.

Levels of C-reactive protein and interleukin-6 were significantly lower after both 4 and 13 weeks in the anakinra group than in the placebo group.

Neither baseline values nor changes in levels of C-reactive protein or interleukin-6 were significantly correlated with changes in glycated hemoglobin levels in the anakinra group. This suggests that “reduced systemic inflammation did not play an important part in improved insulin secretion,” the researchers wrote.

However, “the response to anakinra might also be attributable to mildly improved insulin sensitivity resulting from reduced systemic inflammation,” Dr. Kristina Rother, of the National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md., suggested in an accompanying article (N. Engl. J. Med. 2007;356:1499–1501).

The researchers said the short duration and the lack of dose finding are weaknesses of the study, which was supported by several foundations, the Center for Clinical Studies at the University of Zürich, the European Union, and Novo Nordisk. The study drug was donated by Amgen.

Several of the authors report having an equity interest, receiving grant support, or being an employee of Novo Nordisk.

KANSAS CITY, MO. — In the rush to mandate the human papillomavirus vaccine, several implementation issues, not the least of which is cost, remain unresolved, Dr. Howard Backer said at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Private providers can expect to pay between $10,000 and $15,000 in vaccine inventory per month when adding in the human papillomavirus (HPV) vaccine approved for use in girls and women aged 9-26 years. For a multiprovider practice with five to six physicians who provide childhood vaccines, inventory costs could add up to about $100,000 a month.

“A lot of them aren't willing to put out that much money up front when it may take months before they're reimbursed,” said Dr. Backer, immunization branch chief, California Department of Health Services in Sacramento, and chair of the Association of Immunization Managers.

The American Medical Association and American Academy of Pediatrics are working on ways of addressing this. But for now, it means a lot of providers aren't jumping into HPV vaccinations. “They thought it was a good idea until they looked at what it really meant to buy that much vaccine for their practice[s],” he said.

In addition, reimbursement for vaccine administration costs, which include staff time, storage equipment, injection supplies, and possibly even insurance against vaccine loss, is woefully inadequate. It is often about $5-$10 per administered dose, and probably should be at least 20%–25% above vaccine cost, which is approximately $120 per dose, with three doses required over 6 months.

Private providers can sign up with the federal Vaccines for Children (VFC) program, which allows clinicians to receive free vaccines for qualified individuals up to age 18. But this leaves two problem populations—women aged 19-26 years, and the underinsured, whose insurance may not cover vaccinations.

Dr. Backer presented a recent Association for Immunization Managers survey of 50 program managers that shows 72% of states provide HPV vaccine to VFC-eligible children. About half (53%) of the program managers use Medicaid funds to cover vaccinations for women aged 19-26 years, whereas very few cover the underinsured in the private (22%) or public (30%) settings.

“It's a challenge to fund this vaccine across the spectrum of girls and women for whom it is recommended,” he said in an interview. “The numbers are increasing as the states add funding or pass insurance mandates, but I doubt it will reach 100% coverage for 9- to 26-year-old females.”

Many private insurance companies have not yet decided if they will cover the vaccine, and some states have been hesitant to commit beyond the 11- to 12-year-old age group until they receive the necessary state appropriations and are reassured they will have enough vaccine for the VFC population. Still, a number of new nontraditional vaccine providers such as STD clinics, family planning offices, and pharmacies are expressing interest in the vaccine. Although enthusiastic, many have a poor understanding of vaccine implementation issues and lack the necessary office infrastructure, Dr. Backer said.

Moreover, some of the new partners, such as ob.gyns., want to provide only the HPV vaccine. Under VFC rules, providers are supposed to offer all vaccines for which the patient is eligible.

It is unclear whether an exemption will be made for these new partners. Currently, permission is granted on an individual basis by the CDC to states that want to obtain exemptions or add new rules to the VFC program requirements.

Finally, Dr. Backer questioned whether the emergence of nontraditional HPV vaccine providers would jeopardize the medical home model, upon which the VFC program was based, if patients opt to bypass their physician's office in favor of their local pharmacy.

A lot of providers 'thought it was a good idea until they looked at what it really meant to buy that much vaccine.' DR. BACKER

KANSAS CITY, MO. — In the rush to mandate the human papillomavirus vaccine, several implementation issues, not the least of which is cost, remain unresolved, Dr. Howard Backer said at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Private providers can expect to pay between $10,000 and $15,000 in vaccine inventory per month when adding in the human papillomavirus (HPV) vaccine approved for use in girls and women aged 9-26 years. For a multiprovider practice with five to six physicians who provide childhood vaccines, inventory costs could add up to about $100,000 a month.

“A lot of them aren't willing to put out that much money up front when it may take months before they're reimbursed,” said Dr. Backer, immunization branch chief, California Department of Health Services in Sacramento, and chair of the Association of Immunization Managers.

The American Medical Association and American Academy of Pediatrics are working on ways of addressing this. But for now, it means a lot of providers aren't jumping into HPV vaccinations. “They thought it was a good idea until they looked at what it really meant to buy that much vaccine for their practice[s],” he said.

In addition, reimbursement for vaccine administration costs, which include staff time, storage equipment, injection supplies, and possibly even insurance against vaccine loss, is woefully inadequate. It is often about $5-$10 per administered dose, and probably should be at least 20%–25% above vaccine cost, which is approximately $120 per dose, with three doses required over 6 months.

Private providers can sign up with the federal Vaccines for Children (VFC) program, which allows clinicians to receive free vaccines for qualified individuals up to age 18. But this leaves two problem populations—women aged 19-26 years, and the underinsured, whose insurance may not cover vaccinations.

Dr. Backer presented a recent Association for Immunization Managers survey of 50 program managers that shows 72% of states provide HPV vaccine to VFC-eligible children. About half (53%) of the program managers use Medicaid funds to cover vaccinations for women aged 19-26 years, whereas very few cover the underinsured in the private (22%) or public (30%) settings.

“It's a challenge to fund this vaccine across the spectrum of girls and women for whom it is recommended,” he said in an interview. “The numbers are increasing as the states add funding or pass insurance mandates, but I doubt it will reach 100% coverage for 9- to 26-year-old females.”

Many private insurance companies have not yet decided if they will cover the vaccine, and some states have been hesitant to commit beyond the 11- to 12-year-old age group until they receive the necessary state appropriations and are reassured they will have enough vaccine for the VFC population. Still, a number of new nontraditional vaccine providers such as STD clinics, family planning offices, and pharmacies are expressing interest in the vaccine. Although enthusiastic, many have a poor understanding of vaccine implementation issues and lack the necessary office infrastructure, Dr. Backer said.

Moreover, some of the new partners, such as ob.gyns., want to provide only the HPV vaccine. Under VFC rules, providers are supposed to offer all vaccines for which the patient is eligible.

It is unclear whether an exemption will be made for these new partners. Currently, permission is granted on an individual basis by the CDC to states that want to obtain exemptions or add new rules to the VFC program requirements.

Finally, Dr. Backer questioned whether the emergence of nontraditional HPV vaccine providers would jeopardize the medical home model, upon which the VFC program was based, if patients opt to bypass their physician's office in favor of their local pharmacy.

A lot of providers 'thought it was a good idea until they looked at what it really meant to buy that much vaccine.' DR. BACKER

KANSAS CITY, MO. — In the rush to mandate the human papillomavirus vaccine, several implementation issues, not the least of which is cost, remain unresolved, Dr. Howard Backer said at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Private providers can expect to pay between $10,000 and $15,000 in vaccine inventory per month when adding in the human papillomavirus (HPV) vaccine approved for use in girls and women aged 9-26 years. For a multiprovider practice with five to six physicians who provide childhood vaccines, inventory costs could add up to about $100,000 a month.

“A lot of them aren't willing to put out that much money up front when it may take months before they're reimbursed,” said Dr. Backer, immunization branch chief, California Department of Health Services in Sacramento, and chair of the Association of Immunization Managers.

The American Medical Association and American Academy of Pediatrics are working on ways of addressing this. But for now, it means a lot of providers aren't jumping into HPV vaccinations. “They thought it was a good idea until they looked at what it really meant to buy that much vaccine for their practice[s],” he said.

In addition, reimbursement for vaccine administration costs, which include staff time, storage equipment, injection supplies, and possibly even insurance against vaccine loss, is woefully inadequate. It is often about $5-$10 per administered dose, and probably should be at least 20%–25% above vaccine cost, which is approximately $120 per dose, with three doses required over 6 months.

Private providers can sign up with the federal Vaccines for Children (VFC) program, which allows clinicians to receive free vaccines for qualified individuals up to age 18. But this leaves two problem populations—women aged 19-26 years, and the underinsured, whose insurance may not cover vaccinations.

Dr. Backer presented a recent Association for Immunization Managers survey of 50 program managers that shows 72% of states provide HPV vaccine to VFC-eligible children. About half (53%) of the program managers use Medicaid funds to cover vaccinations for women aged 19-26 years, whereas very few cover the underinsured in the private (22%) or public (30%) settings.

“It's a challenge to fund this vaccine across the spectrum of girls and women for whom it is recommended,” he said in an interview. “The numbers are increasing as the states add funding or pass insurance mandates, but I doubt it will reach 100% coverage for 9- to 26-year-old females.”

Many private insurance companies have not yet decided if they will cover the vaccine, and some states have been hesitant to commit beyond the 11- to 12-year-old age group until they receive the necessary state appropriations and are reassured they will have enough vaccine for the VFC population. Still, a number of new nontraditional vaccine providers such as STD clinics, family planning offices, and pharmacies are expressing interest in the vaccine. Although enthusiastic, many have a poor understanding of vaccine implementation issues and lack the necessary office infrastructure, Dr. Backer said.

Moreover, some of the new partners, such as ob.gyns., want to provide only the HPV vaccine. Under VFC rules, providers are supposed to offer all vaccines for which the patient is eligible.

It is unclear whether an exemption will be made for these new partners. Currently, permission is granted on an individual basis by the CDC to states that want to obtain exemptions or add new rules to the VFC program requirements.

Finally, Dr. Backer questioned whether the emergence of nontraditional HPV vaccine providers would jeopardize the medical home model, upon which the VFC program was based, if patients opt to bypass their physician's office in favor of their local pharmacy.

A lot of providers 'thought it was a good idea until they looked at what it really meant to buy that much vaccine.' DR. BACKER

KANSAS CITY, MO. — In the rush to mandate the human papillomavirus vaccine, several implementation issues, not the least of which is cost, remain unresolved, Dr. Howard Backer said at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Private providers can expect to pay between $10,000 and $15,000 in vaccine inventory per month when adding in the human papillomavirus (HPV) vaccine approved for use in girls and women aged 9–26 years.

For a multiprovider practice with five to six physicians who provide childhood vaccines, inventory costs could add up to about $100,000 a month.

“A lot of them aren't willing to put out that much money up front when it may take months before they're reimbursed,” said Dr. Backer, immunization branch chief, California Department of Health Services in Sacramento, and chair of the Association of Immunization Managers.

The American Medical Association and American Academy of Pediatrics are working on ways of addressing this. But for now, it means a lot of providers aren't jumping into HPV vaccinations.

“They thought it was a good idea until they looked at what it really meant to buy that much vaccine for their practice[s],” he said.

In addition, reimbursement for vaccine administration costs, which include staff time, storage equipment, injection supplies, and possibly even insurance against vaccine loss, is woefully inadequate. It is often about $5-$10 per administered dose, and probably should be at least 20%–25% above vaccine cost, which is approximately $120 per dose, with three doses required over 6 months.

Private providers can sign up with the federal Vaccines for Children (VFC) program, which allows clinicians to receive free vaccines for qualified individuals up to age 18.

But this leaves two problem populations—women ages 19–26 years, and the underinsured, whose insurance may not cover vaccinations.

Dr. Backer presented a recent Association for Immunization Managers survey of 50 program managers that shows 72% of states provide HPV vaccine to VFC-eligible children. About half (53%) of the program managers use Medicaid funds to cover vaccinations for women ages 19–26 years, whereas very few cover the underinsured in the private (22%) or public (30%) settings.

“It's a challenge to fund this vaccine across the spectrum of girls and women for whom it is recommended,” he said in an interview. “The numbers are increasing as the states add funding or pass insurance mandates, but I doubt it will reach 100% coverage for 9- to 26-year-old females.”

Many private insurance companies have not yet decided if they will cover the vaccine, and some states have been hesitant to commit beyond the 11- to 12-year-old age group until they receive the necessary state appropriations and are reassured they will have enough vaccine for the VFC population.

Still, a number of new nontraditional vaccine providers such as STD clinics, family planning offices, and pharmacies are expressing interest in the vaccine. Although enthusiastic, many have a poor understanding of vaccine implementation issues and lack the necessary office infrastructure, Dr. Backer said.

“Quality assurance is a major issue,” he said. “I would submit … that our standard VFC AFIX [Assessment, Feedback, Incentive, eXchange] visit is not going to work for these nontraditional providers.”

Moreover, some of the new partners, such as ob.gyns., want to provide only the HPV vaccine. Under VFC rules, providers are supposed to offer all vaccines for which the patient is eligible.

“I think we can get gynecologists to give HPV, but it's probably too much to tell them to give Tdap and meningococcal and other vaccines at the same time, at least until they get their program up and running,” he said.

It is unclear whether an exemption will be made for these new partners. Currently, permission is granted on an individual basis by the CDC to states that want to obtain exemptions or add new rules to the VFC program requirements.

It's also unknown whether new VFC requirements can be added to ensure that HPV immunizations given by nontraditional providers are entered into an immunization registry or whether notification of the vaccinations will be sent to primary care providers. Finally, Dr. Backer questioned whether the emergence of nontraditional HPV vaccine providers would jeopardize the medical home model, upon which the VFC program was based, if patients opt to bypass their physician's office in favor of their local pharmacy.

A recent survey showed 72% of states provide HPV vaccine to VFC-eligible children. DR. BACKER

KANSAS CITY, MO. — In the rush to mandate the human papillomavirus vaccine, several implementation issues, not the least of which is cost, remain unresolved, Dr. Howard Backer said at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Private providers can expect to pay between $10,000 and $15,000 in vaccine inventory per month when adding in the human papillomavirus (HPV) vaccine approved for use in girls and women aged 9–26 years.

For a multiprovider practice with five to six physicians who provide childhood vaccines, inventory costs could add up to about $100,000 a month.

“A lot of them aren't willing to put out that much money up front when it may take months before they're reimbursed,” said Dr. Backer, immunization branch chief, California Department of Health Services in Sacramento, and chair of the Association of Immunization Managers.

The American Medical Association and American Academy of Pediatrics are working on ways of addressing this. But for now, it means a lot of providers aren't jumping into HPV vaccinations.

“They thought it was a good idea until they looked at what it really meant to buy that much vaccine for their practice[s],” he said.

In addition, reimbursement for vaccine administration costs, which include staff time, storage equipment, injection supplies, and possibly even insurance against vaccine loss, is woefully inadequate. It is often about $5-$10 per administered dose, and probably should be at least 20%–25% above vaccine cost, which is approximately $120 per dose, with three doses required over 6 months.

Private providers can sign up with the federal Vaccines for Children (VFC) program, which allows clinicians to receive free vaccines for qualified individuals up to age 18.

But this leaves two problem populations—women ages 19–26 years, and the underinsured, whose insurance may not cover vaccinations.

Dr. Backer presented a recent Association for Immunization Managers survey of 50 program managers that shows 72% of states provide HPV vaccine to VFC-eligible children. About half (53%) of the program managers use Medicaid funds to cover vaccinations for women ages 19–26 years, whereas very few cover the underinsured in the private (22%) or public (30%) settings.

“It's a challenge to fund this vaccine across the spectrum of girls and women for whom it is recommended,” he said in an interview. “The numbers are increasing as the states add funding or pass insurance mandates, but I doubt it will reach 100% coverage for 9- to 26-year-old females.”

Many private insurance companies have not yet decided if they will cover the vaccine, and some states have been hesitant to commit beyond the 11- to 12-year-old age group until they receive the necessary state appropriations and are reassured they will have enough vaccine for the VFC population.

Still, a number of new nontraditional vaccine providers such as STD clinics, family planning offices, and pharmacies are expressing interest in the vaccine. Although enthusiastic, many have a poor understanding of vaccine implementation issues and lack the necessary office infrastructure, Dr. Backer said.

“Quality assurance is a major issue,” he said. “I would submit … that our standard VFC AFIX [Assessment, Feedback, Incentive, eXchange] visit is not going to work for these nontraditional providers.”

Moreover, some of the new partners, such as ob.gyns., want to provide only the HPV vaccine. Under VFC rules, providers are supposed to offer all vaccines for which the patient is eligible.

“I think we can get gynecologists to give HPV, but it's probably too much to tell them to give Tdap and meningococcal and other vaccines at the same time, at least until they get their program up and running,” he said.

It is unclear whether an exemption will be made for these new partners. Currently, permission is granted on an individual basis by the CDC to states that want to obtain exemptions or add new rules to the VFC program requirements.

It's also unknown whether new VFC requirements can be added to ensure that HPV immunizations given by nontraditional providers are entered into an immunization registry or whether notification of the vaccinations will be sent to primary care providers. Finally, Dr. Backer questioned whether the emergence of nontraditional HPV vaccine providers would jeopardize the medical home model, upon which the VFC program was based, if patients opt to bypass their physician's office in favor of their local pharmacy.

A recent survey showed 72% of states provide HPV vaccine to VFC-eligible children. DR. BACKER

KANSAS CITY, MO. — In the rush to mandate the human papillomavirus vaccine, several implementation issues, not the least of which is cost, remain unresolved, Dr. Howard Backer said at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Private providers can expect to pay between $10,000 and $15,000 in vaccine inventory per month when adding in the human papillomavirus (HPV) vaccine approved for use in girls and women aged 9–26 years.

For a multiprovider practice with five to six physicians who provide childhood vaccines, inventory costs could add up to about $100,000 a month.

“A lot of them aren't willing to put out that much money up front when it may take months before they're reimbursed,” said Dr. Backer, immunization branch chief, California Department of Health Services in Sacramento, and chair of the Association of Immunization Managers.

The American Medical Association and American Academy of Pediatrics are working on ways of addressing this. But for now, it means a lot of providers aren't jumping into HPV vaccinations.

“They thought it was a good idea until they looked at what it really meant to buy that much vaccine for their practice[s],” he said.

In addition, reimbursement for vaccine administration costs, which include staff time, storage equipment, injection supplies, and possibly even insurance against vaccine loss, is woefully inadequate. It is often about $5-$10 per administered dose, and probably should be at least 20%–25% above vaccine cost, which is approximately $120 per dose, with three doses required over 6 months.

Private providers can sign up with the federal Vaccines for Children (VFC) program, which allows clinicians to receive free vaccines for qualified individuals up to age 18.

But this leaves two problem populations—women ages 19–26 years, and the underinsured, whose insurance may not cover vaccinations.

Dr. Backer presented a recent Association for Immunization Managers survey of 50 program managers that shows 72% of states provide HPV vaccine to VFC-eligible children. About half (53%) of the program managers use Medicaid funds to cover vaccinations for women ages 19–26 years, whereas very few cover the underinsured in the private (22%) or public (30%) settings.

“It's a challenge to fund this vaccine across the spectrum of girls and women for whom it is recommended,” he said in an interview. “The numbers are increasing as the states add funding or pass insurance mandates, but I doubt it will reach 100% coverage for 9- to 26-year-old females.”

Many private insurance companies have not yet decided if they will cover the vaccine, and some states have been hesitant to commit beyond the 11- to 12-year-old age group until they receive the necessary state appropriations and are reassured they will have enough vaccine for the VFC population.

Still, a number of new nontraditional vaccine providers such as STD clinics, family planning offices, and pharmacies are expressing interest in the vaccine. Although enthusiastic, many have a poor understanding of vaccine implementation issues and lack the necessary office infrastructure, Dr. Backer said.

“Quality assurance is a major issue,” he said. “I would submit … that our standard VFC AFIX [Assessment, Feedback, Incentive, eXchange] visit is not going to work for these nontraditional providers.”

Moreover, some of the new partners, such as ob.gyns., want to provide only the HPV vaccine. Under VFC rules, providers are supposed to offer all vaccines for which the patient is eligible.

“I think we can get gynecologists to give HPV, but it's probably too much to tell them to give Tdap and meningococcal and other vaccines at the same time, at least until they get their program up and running,” he said.

It is unclear whether an exemption will be made for these new partners. Currently, permission is granted on an individual basis by the CDC to states that want to obtain exemptions or add new rules to the VFC program requirements.

It's also unknown whether new VFC requirements can be added to ensure that HPV immunizations given by nontraditional providers are entered into an immunization registry or whether notification of the vaccinations will be sent to primary care providers. Finally, Dr. Backer questioned whether the emergence of nontraditional HPV vaccine providers would jeopardize the medical home model, upon which the VFC program was based, if patients opt to bypass their physician's office in favor of their local pharmacy.

A recent survey showed 72% of states provide HPV vaccine to VFC-eligible children. DR. BACKER

Decades ago, researchers banded together to help fight childhood leukemia and, in doing so, transformed the disease from a virtual death sentence to one that the vast majority of children survive.

Researchers at Baltimore's Kennedy Krieger Institute are hoping to repeat that success with the debut this month of the Interactive Autism Network (IAN), the nation's first online autism registry.

“IAN will affect the entire research process and accelerate it manyfold,” Dr. Paul Law, director of the project, said in an interview. “For leukemia, it was a gradual process that took 30 years. It's my hope the answers for autism will come faster than that.”

Through IAN, families of children with autism spectrum disorders can participate in a national online research project or they can be linked to other local and national research projects for which they qualify. By year's end, project organizers hope they will have the largest collection of family-provided data ever compiled on autism spectrum disorders.

Of the 250 families that participated as pilot registrants, 80% had never participated in any autism research, even though many of them live in the Baltimore area with access to several major medical institutions. Still others live in remote areas of the country like upper North Dakota, where IAN may be the only research project available, said Dr Law, a pediatrician whose own son was diagnosed with autism in the 1990s.

For researchers, IAN provides access to an invaluable database and a potential pool of study participants. For example, if a researcher is interested in studying 8- to 10-year-old children with autism and a history of regression living in a particular region, he or she can contact the network to determine how many children meet the specific criteria. E-mails will then be sent by the network to the families, notifying them of the study. The names of the families will not be divulged, leaving families in control of their privacy.

Typically, researchers rely on broadly targeted recruitment vehicles such as newspaper advertisements, e-mail lists, and local autism support groups. Few are successful because “they put the burden on families, whereas IAN finds them in a very deliberate and qualified way,” explained Dr. Law, director of informatics at the institute.

Families that live near urban areas have access to more facilities for evaluation and are overrepresented in current autism studies, said Dr. Michael Burke, chairman of pediatrics at St. Agnes Hospital, a community hospital in Baltimore. Using the Internet will allow a much broader base of participants for autism research and allow broader access to available resources, he commented on the project.

With 1 in 150 children now estimated to have autism spectrum disorders, according to the Centers for Disease Control and Prevention, IAN is attractive to Autism Speaks, a nonprofit association that provided $6 million to fund IAN through 2008. Not only does IAN link researchers with families, but it's a safe place families can go for evidence-based research and a sense of community, Mr. Mark Roithmayr, president of Autism Speaks, said in an interview.

Once given a diagnosis of autism by their pediatric care provider, families of children with autism spectrum disorders are faced with a host of day-to-day issues and often feel alone. It's also challenging for families and their physician to keep up with and interpret the latest autism news, whether it be new genetics findings or the recent widely publicized claim that autism is caused by watching too much television.

“It's an additional resource that's out there that has scientific credibility and also has community safety,” Mr. Roithmayr said. “Knowledge is empowerment.”

The site, www.IANproject.org

Greater access to study participants should improve the planning of clinical trials and quicken the pace of research. But Dr. Law suggests IAN also could encourage more Internet-mediated research on autism and affect how other disease states are studied as well. That would allow the family in North Dakota and others affected by disease to participate in a variety of research projects rather than being constrained by geography.

“It would certainly promote research and facilitate investigators being able to obtain a large enough data set for the different types of autism,” said Dr. Chris Johnson, co-chair of the American Academy of Pediatrics Autism Expert Panel and medical director, Village of Hope, Center for Children with Disabilities in San Antonio. “One of the problems with the genetics research thus far is sometimes trying to compare apples to oranges when you've got children with Asperger's being compared to children with more severe autism and mental retardation and they are all thrown together in the autism spectrum disorders.”

The network is free to all users, and all information provided is governed by the privacy and security rules of the Health Insurance Portability and Accountability Act.

Joan DiPietro, R.N., who has experience implementing a surgical information system in a hospital, participated in the beta testing for IAN and said that it satisfied her concerns about privacy. She admits being cautious about providing any information on her son and on his diagnosis of Asperger's syndrome, and she was curious about what questions would be asked and how the information would be passed back and forth.

Still, she felt it was safe, easy to use, and provided a variety of content in the margins, such as frequently asked questions, that moves a parent through the process.

Ultimately, IAN may help sharpen the public's focus on the reality that there is no magic cure for autism spectrum disorders but rather a course of scientific discovery that must be followed. “If there is anything that we can eventually find that is causing all these children to have autism, it's going to happen through research as opposed to someone saying they have the magic answer,” Ms. DiPietro said in an interview.

Decades ago, researchers banded together to help fight childhood leukemia and, in doing so, transformed the disease from a virtual death sentence to one that the vast majority of children survive.

Researchers at Baltimore's Kennedy Krieger Institute are hoping to repeat that success with the debut this month of the Interactive Autism Network (IAN), the nation's first online autism registry.

“IAN will affect the entire research process and accelerate it manyfold,” Dr. Paul Law, director of the project, said in an interview. “For leukemia, it was a gradual process that took 30 years. It's my hope the answers for autism will come faster than that.”

Through IAN, families of children with autism spectrum disorders can participate in a national online research project or they can be linked to other local and national research projects for which they qualify. By year's end, project organizers hope they will have the largest collection of family-provided data ever compiled on autism spectrum disorders.

Of the 250 families that participated as pilot registrants, 80% had never participated in any autism research, even though many of them live in the Baltimore area with access to several major medical institutions. Still others live in remote areas of the country like upper North Dakota, where IAN may be the only research project available, said Dr Law, a pediatrician whose own son was diagnosed with autism in the 1990s.

For researchers, IAN provides access to an invaluable database and a potential pool of study participants. For example, if a researcher is interested in studying 8- to 10-year-old children with autism and a history of regression living in a particular region, he or she can contact the network to determine how many children meet the specific criteria. E-mails will then be sent by the network to the families, notifying them of the study. The names of the families will not be divulged, leaving families in control of their privacy.

Typically, researchers rely on broadly targeted recruitment vehicles such as newspaper advertisements, e-mail lists, and local autism support groups. Few are successful because “they put the burden on families, whereas IAN finds them in a very deliberate and qualified way,” explained Dr. Law, director of informatics at the institute.

Families that live near urban areas have access to more facilities for evaluation and are overrepresented in current autism studies, said Dr. Michael Burke, chairman of pediatrics at St. Agnes Hospital, a community hospital in Baltimore. Using the Internet will allow a much broader base of participants for autism research and allow broader access to available resources, he commented on the project.

With 1 in 150 children now estimated to have autism spectrum disorders, according to the Centers for Disease Control and Prevention, IAN is attractive to Autism Speaks, a nonprofit association that provided $6 million to fund IAN through 2008. Not only does IAN link researchers with families, but it's a safe place families can go for evidence-based research and a sense of community, Mr. Mark Roithmayr, president of Autism Speaks, said in an interview.

Once given a diagnosis of autism by their pediatric care provider, families of children with autism spectrum disorders are faced with a host of day-to-day issues and often feel alone. It's also challenging for families and their physician to keep up with and interpret the latest autism news, whether it be new genetics findings or the recent widely publicized claim that autism is caused by watching too much television.

“It's an additional resource that's out there that has scientific credibility and also has community safety,” Mr. Roithmayr said. “Knowledge is empowerment.”

The site, www.IANproject.org

Greater access to study participants should improve the planning of clinical trials and quicken the pace of research. But Dr. Law suggests IAN also could encourage more Internet-mediated research on autism and affect how other disease states are studied as well. That would allow the family in North Dakota and others affected by disease to participate in a variety of research projects rather than being constrained by geography.

“It would certainly promote research and facilitate investigators being able to obtain a large enough data set for the different types of autism,” said Dr. Chris Johnson, co-chair of the American Academy of Pediatrics Autism Expert Panel and medical director, Village of Hope, Center for Children with Disabilities in San Antonio. “One of the problems with the genetics research thus far is sometimes trying to compare apples to oranges when you've got children with Asperger's being compared to children with more severe autism and mental retardation and they are all thrown together in the autism spectrum disorders.”

The network is free to all users, and all information provided is governed by the privacy and security rules of the Health Insurance Portability and Accountability Act.

Joan DiPietro, R.N., who has experience implementing a surgical information system in a hospital, participated in the beta testing for IAN and said that it satisfied her concerns about privacy. She admits being cautious about providing any information on her son and on his diagnosis of Asperger's syndrome, and she was curious about what questions would be asked and how the information would be passed back and forth.

Still, she felt it was safe, easy to use, and provided a variety of content in the margins, such as frequently asked questions, that moves a parent through the process.

Ultimately, IAN may help sharpen the public's focus on the reality that there is no magic cure for autism spectrum disorders but rather a course of scientific discovery that must be followed. “If there is anything that we can eventually find that is causing all these children to have autism, it's going to happen through research as opposed to someone saying they have the magic answer,” Ms. DiPietro said in an interview.

Decades ago, researchers banded together to help fight childhood leukemia and, in doing so, transformed the disease from a virtual death sentence to one that the vast majority of children survive.

Researchers at Baltimore's Kennedy Krieger Institute are hoping to repeat that success with the debut this month of the Interactive Autism Network (IAN), the nation's first online autism registry.

“IAN will affect the entire research process and accelerate it manyfold,” Dr. Paul Law, director of the project, said in an interview. “For leukemia, it was a gradual process that took 30 years. It's my hope the answers for autism will come faster than that.”

Through IAN, families of children with autism spectrum disorders can participate in a national online research project or they can be linked to other local and national research projects for which they qualify. By year's end, project organizers hope they will have the largest collection of family-provided data ever compiled on autism spectrum disorders.

Of the 250 families that participated as pilot registrants, 80% had never participated in any autism research, even though many of them live in the Baltimore area with access to several major medical institutions. Still others live in remote areas of the country like upper North Dakota, where IAN may be the only research project available, said Dr Law, a pediatrician whose own son was diagnosed with autism in the 1990s.

For researchers, IAN provides access to an invaluable database and a potential pool of study participants. For example, if a researcher is interested in studying 8- to 10-year-old children with autism and a history of regression living in a particular region, he or she can contact the network to determine how many children meet the specific criteria. E-mails will then be sent by the network to the families, notifying them of the study. The names of the families will not be divulged, leaving families in control of their privacy.

Typically, researchers rely on broadly targeted recruitment vehicles such as newspaper advertisements, e-mail lists, and local autism support groups. Few are successful because “they put the burden on families, whereas IAN finds them in a very deliberate and qualified way,” explained Dr. Law, director of informatics at the institute.

Families that live near urban areas have access to more facilities for evaluation and are overrepresented in current autism studies, said Dr. Michael Burke, chairman of pediatrics at St. Agnes Hospital, a community hospital in Baltimore. Using the Internet will allow a much broader base of participants for autism research and allow broader access to available resources, he commented on the project.

With 1 in 150 children now estimated to have autism spectrum disorders, according to the Centers for Disease Control and Prevention, IAN is attractive to Autism Speaks, a nonprofit association that provided $6 million to fund IAN through 2008. Not only does IAN link researchers with families, but it's a safe place families can go for evidence-based research and a sense of community, Mr. Mark Roithmayr, president of Autism Speaks, said in an interview.

Once given a diagnosis of autism by their pediatric care provider, families of children with autism spectrum disorders are faced with a host of day-to-day issues and often feel alone. It's also challenging for families and their physician to keep up with and interpret the latest autism news, whether it be new genetics findings or the recent widely publicized claim that autism is caused by watching too much television.

“It's an additional resource that's out there that has scientific credibility and also has community safety,” Mr. Roithmayr said. “Knowledge is empowerment.”

The site, www.IANproject.org

Greater access to study participants should improve the planning of clinical trials and quicken the pace of research. But Dr. Law suggests IAN also could encourage more Internet-mediated research on autism and affect how other disease states are studied as well. That would allow the family in North Dakota and others affected by disease to participate in a variety of research projects rather than being constrained by geography.

“It would certainly promote research and facilitate investigators being able to obtain a large enough data set for the different types of autism,” said Dr. Chris Johnson, co-chair of the American Academy of Pediatrics Autism Expert Panel and medical director, Village of Hope, Center for Children with Disabilities in San Antonio. “One of the problems with the genetics research thus far is sometimes trying to compare apples to oranges when you've got children with Asperger's being compared to children with more severe autism and mental retardation and they are all thrown together in the autism spectrum disorders.”

The network is free to all users, and all information provided is governed by the privacy and security rules of the Health Insurance Portability and Accountability Act.

Joan DiPietro, R.N., who has experience implementing a surgical information system in a hospital, participated in the beta testing for IAN and said that it satisfied her concerns about privacy. She admits being cautious about providing any information on her son and on his diagnosis of Asperger's syndrome, and she was curious about what questions would be asked and how the information would be passed back and forth.

Still, she felt it was safe, easy to use, and provided a variety of content in the margins, such as frequently asked questions, that moves a parent through the process.

Ultimately, IAN may help sharpen the public's focus on the reality that there is no magic cure for autism spectrum disorders but rather a course of scientific discovery that must be followed. “If there is anything that we can eventually find that is causing all these children to have autism, it's going to happen through research as opposed to someone saying they have the magic answer,” Ms. DiPietro said in an interview.

NEW YORK — Significant differences are apparent in the rates of mania and types of externalizing comorbidity between children, adolescents, and adults with bipolar disorder, Dr. Gabrielle A. Carlson reported at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

The onset of bipolar disorder (BD) also seems to vary depending on gender, said Dr. Carlson, professor of psychiatry and pediatrics and director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Among adults, the mood changes characteristic of mania include grandiosity, marked euphoria, and irritability, with associated racing thoughts, mood lability, and increased psychomotor activity.

But symptoms differ among younger patients with the disorder.

“It's irritability and aggression that's grabbing us by the lapels with bipolar disorder in children and adolescents,” Dr. Carlson said. “It's not that they're coming in euphoric … saying they're on cloud nine or president of the United States.”

A growing body of evidence also suggests that differences exist in bipolar disorder based on age at onset, Dr. Carlson said.

A recent study by Dr. Gabriele Masi and colleagues involved 136 consecutive patients, including 80 with bipolar disorder onset before 12 years of age and 56 with adolescent-onset BD (J. Child Adolesc. Psychopharmacol. 2006;16:679–85).

Compared with the adolescent-onset bipolar disorder, patients with childhood-onset were significantly more likely to be male (67.5% vs. 48%) and to have a comorbidity with ADHD (39% vs. 9%) and oppositional defiant disorder (ODD) (36% vs. 11%).

An episodic rather than a chronic course also was significantly more likely to occur in adolescents with the disorder than among children with it (77% vs. 42.5%).

Similar trends were identified in a study now in press by Dr. Carlson and her colleagues that compared 89 patients with BD onset at ages 15–29 years and 34 patients with bipolar disorder onset after age 30.

The patients with earlier-onset bipolar disorder were twice as likely to be male than were the adult-onset patients (55% vs. 26.5%). They also had significantly higher rates of ADHD or oppositional defiant disorder or conduct disorder (26% vs. 9%).

Prospective data are limited, but juvenile-onset bipolar disorder appears to be more chronic and treatment refractory than does adult-onset bipolar disorder.

“Episodes remit more quickly the older you are,” Dr. Carlson said.

Those with very early onset are unlikely to have only one episode. They also take longer to recover from an episode, and are less likely to remit completely between episodes.

However, it remains unclear whether this particular pattern is a reflection of incomplete episode remission or, on the other hand, complications of a comorbid condition, Dr. Carlson explained.

Unpublished secondary analyses of an earlier study by Dr. Carlson and colleagues (Am. J. Psychiatry 2002;159:307–9) identifies significant differences by age of onset in functional outcome after a bipolar episode.

Among 89 patients with bipolar disorder onset at age 15–29 years, 15% of them had a Global Assessment of Functioning score of less than 50 after an episode, compared with 12% of those with bipolar disorder onset after an age of 30 years.

“The combination of externalizing symptoms [ADHD and ODD] and serious mood lability is noxious, impairing, and often enduring,” Dr. Carlson said.

“Intervention is clearly justified; prevention is clearly justified. But we cannot conclude that classic manic depression is the outcome and lifetime medication is justified,” she added.

NEW YORK — Significant differences are apparent in the rates of mania and types of externalizing comorbidity between children, adolescents, and adults with bipolar disorder, Dr. Gabrielle A. Carlson reported at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

The onset of bipolar disorder (BD) also seems to vary depending on gender, said Dr. Carlson, professor of psychiatry and pediatrics and director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Among adults, the mood changes characteristic of mania include grandiosity, marked euphoria, and irritability, with associated racing thoughts, mood lability, and increased psychomotor activity.

But symptoms differ among younger patients with the disorder.

“It's irritability and aggression that's grabbing us by the lapels with bipolar disorder in children and adolescents,” Dr. Carlson said. “It's not that they're coming in euphoric … saying they're on cloud nine or president of the United States.”

A growing body of evidence also suggests that differences exist in bipolar disorder based on age at onset, Dr. Carlson said.

A recent study by Dr. Gabriele Masi and colleagues involved 136 consecutive patients, including 80 with bipolar disorder onset before 12 years of age and 56 with adolescent-onset BD (J. Child Adolesc. Psychopharmacol. 2006;16:679–85).

Compared with the adolescent-onset bipolar disorder, patients with childhood-onset were significantly more likely to be male (67.5% vs. 48%) and to have a comorbidity with ADHD (39% vs. 9%) and oppositional defiant disorder (ODD) (36% vs. 11%).

An episodic rather than a chronic course also was significantly more likely to occur in adolescents with the disorder than among children with it (77% vs. 42.5%).

Similar trends were identified in a study now in press by Dr. Carlson and her colleagues that compared 89 patients with BD onset at ages 15–29 years and 34 patients with bipolar disorder onset after age 30.

The patients with earlier-onset bipolar disorder were twice as likely to be male than were the adult-onset patients (55% vs. 26.5%). They also had significantly higher rates of ADHD or oppositional defiant disorder or conduct disorder (26% vs. 9%).

Prospective data are limited, but juvenile-onset bipolar disorder appears to be more chronic and treatment refractory than does adult-onset bipolar disorder.

“Episodes remit more quickly the older you are,” Dr. Carlson said.

Those with very early onset are unlikely to have only one episode. They also take longer to recover from an episode, and are less likely to remit completely between episodes.

However, it remains unclear whether this particular pattern is a reflection of incomplete episode remission or, on the other hand, complications of a comorbid condition, Dr. Carlson explained.

Unpublished secondary analyses of an earlier study by Dr. Carlson and colleagues (Am. J. Psychiatry 2002;159:307–9) identifies significant differences by age of onset in functional outcome after a bipolar episode.

Among 89 patients with bipolar disorder onset at age 15–29 years, 15% of them had a Global Assessment of Functioning score of less than 50 after an episode, compared with 12% of those with bipolar disorder onset after an age of 30 years.

“The combination of externalizing symptoms [ADHD and ODD] and serious mood lability is noxious, impairing, and often enduring,” Dr. Carlson said.

“Intervention is clearly justified; prevention is clearly justified. But we cannot conclude that classic manic depression is the outcome and lifetime medication is justified,” she added.

NEW YORK — Significant differences are apparent in the rates of mania and types of externalizing comorbidity between children, adolescents, and adults with bipolar disorder, Dr. Gabrielle A. Carlson reported at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

The onset of bipolar disorder (BD) also seems to vary depending on gender, said Dr. Carlson, professor of psychiatry and pediatrics and director of child and adolescent psychiatry at the State University of New York at Stony Brook.

Among adults, the mood changes characteristic of mania include grandiosity, marked euphoria, and irritability, with associated racing thoughts, mood lability, and increased psychomotor activity.

But symptoms differ among younger patients with the disorder.

“It's irritability and aggression that's grabbing us by the lapels with bipolar disorder in children and adolescents,” Dr. Carlson said. “It's not that they're coming in euphoric … saying they're on cloud nine or president of the United States.”

A growing body of evidence also suggests that differences exist in bipolar disorder based on age at onset, Dr. Carlson said.

A recent study by Dr. Gabriele Masi and colleagues involved 136 consecutive patients, including 80 with bipolar disorder onset before 12 years of age and 56 with adolescent-onset BD (J. Child Adolesc. Psychopharmacol. 2006;16:679–85).

Compared with the adolescent-onset bipolar disorder, patients with childhood-onset were significantly more likely to be male (67.5% vs. 48%) and to have a comorbidity with ADHD (39% vs. 9%) and oppositional defiant disorder (ODD) (36% vs. 11%).

An episodic rather than a chronic course also was significantly more likely to occur in adolescents with the disorder than among children with it (77% vs. 42.5%).

Similar trends were identified in a study now in press by Dr. Carlson and her colleagues that compared 89 patients with BD onset at ages 15–29 years and 34 patients with bipolar disorder onset after age 30.

The patients with earlier-onset bipolar disorder were twice as likely to be male than were the adult-onset patients (55% vs. 26.5%). They also had significantly higher rates of ADHD or oppositional defiant disorder or conduct disorder (26% vs. 9%).

Prospective data are limited, but juvenile-onset bipolar disorder appears to be more chronic and treatment refractory than does adult-onset bipolar disorder.

“Episodes remit more quickly the older you are,” Dr. Carlson said.

Those with very early onset are unlikely to have only one episode. They also take longer to recover from an episode, and are less likely to remit completely between episodes.

However, it remains unclear whether this particular pattern is a reflection of incomplete episode remission or, on the other hand, complications of a comorbid condition, Dr. Carlson explained.

Unpublished secondary analyses of an earlier study by Dr. Carlson and colleagues (Am. J. Psychiatry 2002;159:307–9) identifies significant differences by age of onset in functional outcome after a bipolar episode.

Among 89 patients with bipolar disorder onset at age 15–29 years, 15% of them had a Global Assessment of Functioning score of less than 50 after an episode, compared with 12% of those with bipolar disorder onset after an age of 30 years.

“The combination of externalizing symptoms [ADHD and ODD] and serious mood lability is noxious, impairing, and often enduring,” Dr. Carlson said.

“Intervention is clearly justified; prevention is clearly justified. But we cannot conclude that classic manic depression is the outcome and lifetime medication is justified,” she added.

MIAMI BEACH — Inadvertent misadministration can occur with several new vaccines that are commonly used, Dr. Larry Pickering said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Confusion has occurred with the administration of three vaccines: the newer tetravalent meningococcal conjugate (MCV4) vaccine; the recently licensed tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine; and the new adult zoster vaccine.

The meningococcal polysaccharide vaccine has been used subcutaneously for decades in the United States. But the newer MCV4 vaccine, licensed in the United States in January 2005, is for intramuscular use only.

The different routes of administration create an “automatic opportunity for confusion,” said Dr. Pickering, professor of pediatrics at Emory University and senior advisor to the director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, both in Atlanta.

Indeed, 101 people in seven states have reportedly received subcutaneous administration of the MCV4 vaccine, according to an investigation by the CDC (MMWR 2006;55:1016–17).

There were 12 nonserious adverse events, including 11 local reactions and a report of fever for 1 day among 54 people queried by providers as a result of the investigation.

Serology results from 38 people vaccinated by the subcutaneous route indicate that although their titers were lower than those of patients vaccinated by the intramuscular route, the subcutaneously vaccinated patients were sufficiently protected and didn't need revaccination.

A second kind of vaccine mix-up has been reported involving the two new Tdap vaccines licensed in 2005 for adolescents and adults, and the diphtheria, tetanus, and pertussis (DTaP) vaccine licensed in 1991 for children 6 weeks to 6 years of age.

Both the American Academy of Pediatrics and the CDC have received requests for guidance on what to do when an adolescent is given the infant dose and vice versa.

One of the reasons for the confusion is that the labeling and packaging are very similar for Adacel (Tdap) and Daptacel (DTaP), Dr. Pickering said.

Sanofi Pasteur, maker of Adacel and Daptacel, confirms it has received reports of misadministration, more commonly of adults being given the pediatric formulation, Donna K. Cary, director of public relations for Sanofi, said in an interview.

“For many years, DTaP was just a pediatric product, and it wasn't until just recently that we had Adacel for adults and adolescents, and GlaxoSmithKline has Boostrix,” Ms. Cary said. “I think it's that there is a new vaccine. The packaging is actually quite different.”

The company has started tracking reports of misadministration and is looking at ways to make the two products more distinct, such as noting on the label that Daptacel is for infants, she said. The Adacel label already states it is for adolescents and adults.

Until such changes are made, Dr. Pickering said, he keeps the two vaccines straight in his mind by remembering that Adacel and adult both begin with the letter A.

If an adolescent or adult inadvertently receives DTaP, the vaccine doesn't have to be repeated, although the patient may have increased reactions because the antigen contents are higher, Dr. Pickering said. If Tdap is given to an infant or child, the antigen contents are much lower and the dose will have to be repeated.

The Advisory Committee on Immunization Practices recently received reports of infants receiving the Zostavax vaccine used to prevent herpes zoster in adults 60 years of age or older, and of adults accidentally receiving the Varivax vaccine used to prevent the varicella zoster virus in patients 12 months of age and older.

Even though all varicella products are made from the same varicella-zoster bulk lots, the zoster vaccine concentration is 14 times higher than the varicella vaccine concentration, Dr. Pickering said.

If zoster vaccine is inadvertently given to a small child, reactions might be greater and could include local skin reactions, low-grade fever, and the development of vesicular lesions around the injection site. If the varicella vaccine is given to an adult, it might not work because of the lower vaccine content, he said.

MIAMI BEACH — Inadvertent misadministration can occur with several new vaccines that are commonly used, Dr. Larry Pickering said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Confusion has occurred with the administration of three vaccines: the newer tetravalent meningococcal conjugate (MCV4) vaccine; the recently licensed tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine; and the new adult zoster vaccine.

The meningococcal polysaccharide vaccine has been used subcutaneously for decades in the United States. But the newer MCV4 vaccine, licensed in the United States in January 2005, is for intramuscular use only.

The different routes of administration create an “automatic opportunity for confusion,” said Dr. Pickering, professor of pediatrics at Emory University and senior advisor to the director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, both in Atlanta.

Indeed, 101 people in seven states have reportedly received subcutaneous administration of the MCV4 vaccine, according to an investigation by the CDC (MMWR 2006;55:1016–17).

There were 12 nonserious adverse events, including 11 local reactions and a report of fever for 1 day among 54 people queried by providers as a result of the investigation.

Serology results from 38 people vaccinated by the subcutaneous route indicate that although their titers were lower than those of patients vaccinated by the intramuscular route, the subcutaneously vaccinated patients were sufficiently protected and didn't need revaccination.

A second kind of vaccine mix-up has been reported involving the two new Tdap vaccines licensed in 2005 for adolescents and adults, and the diphtheria, tetanus, and pertussis (DTaP) vaccine licensed in 1991 for children 6 weeks to 6 years of age.

Both the American Academy of Pediatrics and the CDC have received requests for guidance on what to do when an adolescent is given the infant dose and vice versa.

One of the reasons for the confusion is that the labeling and packaging are very similar for Adacel (Tdap) and Daptacel (DTaP), Dr. Pickering said.

Sanofi Pasteur, maker of Adacel and Daptacel, confirms it has received reports of misadministration, more commonly of adults being given the pediatric formulation, Donna K. Cary, director of public relations for Sanofi, said in an interview.

“For many years, DTaP was just a pediatric product, and it wasn't until just recently that we had Adacel for adults and adolescents, and GlaxoSmithKline has Boostrix,” Ms. Cary said. “I think it's that there is a new vaccine. The packaging is actually quite different.”

The company has started tracking reports of misadministration and is looking at ways to make the two products more distinct, such as noting on the label that Daptacel is for infants, she said. The Adacel label already states it is for adolescents and adults.

Until such changes are made, Dr. Pickering said, he keeps the two vaccines straight in his mind by remembering that Adacel and adult both begin with the letter A.

If an adolescent or adult inadvertently receives DTaP, the vaccine doesn't have to be repeated, although the patient may have increased reactions because the antigen contents are higher, Dr. Pickering said. If Tdap is given to an infant or child, the antigen contents are much lower and the dose will have to be repeated.

The Advisory Committee on Immunization Practices recently received reports of infants receiving the Zostavax vaccine used to prevent herpes zoster in adults 60 years of age or older, and of adults accidentally receiving the Varivax vaccine used to prevent the varicella zoster virus in patients 12 months of age and older.

Even though all varicella products are made from the same varicella-zoster bulk lots, the zoster vaccine concentration is 14 times higher than the varicella vaccine concentration, Dr. Pickering said.

If zoster vaccine is inadvertently given to a small child, reactions might be greater and could include local skin reactions, low-grade fever, and the development of vesicular lesions around the injection site. If the varicella vaccine is given to an adult, it might not work because of the lower vaccine content, he said.

MIAMI BEACH — Inadvertent misadministration can occur with several new vaccines that are commonly used, Dr. Larry Pickering said at the annual Masters of Pediatrics conference sponsored by the University of Miami.

Confusion has occurred with the administration of three vaccines: the newer tetravalent meningococcal conjugate (MCV4) vaccine; the recently licensed tetanus toxoid, diphtheria toxoid, and acellular pertussis (Tdap) vaccine; and the new adult zoster vaccine.

The meningococcal polysaccharide vaccine has been used subcutaneously for decades in the United States. But the newer MCV4 vaccine, licensed in the United States in January 2005, is for intramuscular use only.

The different routes of administration create an “automatic opportunity for confusion,” said Dr. Pickering, professor of pediatrics at Emory University and senior advisor to the director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, both in Atlanta.

Indeed, 101 people in seven states have reportedly received subcutaneous administration of the MCV4 vaccine, according to an investigation by the CDC (MMWR 2006;55:1016–17).

There were 12 nonserious adverse events, including 11 local reactions and a report of fever for 1 day among 54 people queried by providers as a result of the investigation.

Serology results from 38 people vaccinated by the subcutaneous route indicate that although their titers were lower than those of patients vaccinated by the intramuscular route, the subcutaneously vaccinated patients were sufficiently protected and didn't need revaccination.

A second kind of vaccine mix-up has been reported involving the two new Tdap vaccines licensed in 2005 for adolescents and adults, and the diphtheria, tetanus, and pertussis (DTaP) vaccine licensed in 1991 for children 6 weeks to 6 years of age.

Both the American Academy of Pediatrics and the CDC have received requests for guidance on what to do when an adolescent is given the infant dose and vice versa.

One of the reasons for the confusion is that the labeling and packaging are very similar for Adacel (Tdap) and Daptacel (DTaP), Dr. Pickering said.

Sanofi Pasteur, maker of Adacel and Daptacel, confirms it has received reports of misadministration, more commonly of adults being given the pediatric formulation, Donna K. Cary, director of public relations for Sanofi, said in an interview.

“For many years, DTaP was just a pediatric product, and it wasn't until just recently that we had Adacel for adults and adolescents, and GlaxoSmithKline has Boostrix,” Ms. Cary said. “I think it's that there is a new vaccine. The packaging is actually quite different.”

The company has started tracking reports of misadministration and is looking at ways to make the two products more distinct, such as noting on the label that Daptacel is for infants, she said. The Adacel label already states it is for adolescents and adults.

Until such changes are made, Dr. Pickering said, he keeps the two vaccines straight in his mind by remembering that Adacel and adult both begin with the letter A.

If an adolescent or adult inadvertently receives DTaP, the vaccine doesn't have to be repeated, although the patient may have increased reactions because the antigen contents are higher, Dr. Pickering said. If Tdap is given to an infant or child, the antigen contents are much lower and the dose will have to be repeated.

The Advisory Committee on Immunization Practices recently received reports of infants receiving the Zostavax vaccine used to prevent herpes zoster in adults 60 years of age or older, and of adults accidentally receiving the Varivax vaccine used to prevent the varicella zoster virus in patients 12 months of age and older.

Even though all varicella products are made from the same varicella-zoster bulk lots, the zoster vaccine concentration is 14 times higher than the varicella vaccine concentration, Dr. Pickering said.

If zoster vaccine is inadvertently given to a small child, reactions might be greater and could include local skin reactions, low-grade fever, and the development of vesicular lesions around the injection site. If the varicella vaccine is given to an adult, it might not work because of the lower vaccine content, he said.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest hit state in the nation, 71 of 113 (63%) cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early enough.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case-investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007.

Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data were available. Because of this and available viral shedding data, the CDC is expected to recommend in a memo to states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest hit state in the nation, 71 of 113 (63%) cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early enough.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case-investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007.

Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data were available. Because of this and available viral shedding data, the CDC is expected to recommend in a memo to states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest hit state in the nation, 71 of 113 (63%) cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early enough.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case-investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007.

Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data were available. Because of this and available viral shedding data, the CDC is expected to recommend in a memo to states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps.

CHICAGO — Magnetic resonance imaging offers significantly higher sensitivity for diagnosing pure ductal carcinoma in situ than does mammography, Dr. Christiane Kuhl said at the annual meeting of the Radiological Society of North America.

She presented data from a prospective study of 137 women in which almost half of all ductal carcinomas in situ (DCIS) and more than half of high-grade DCIS tumors were missed by mammography. The majority of the women studied were not considered at high risk for cancer, said Dr. Kuhl of the University of Bonn, Germany.

“If proper diagnostic criteria are being used, MRI allows the diagnosis of DCIS that goes undetected by mammography and also ultrasound,” she said.

The women were part of a larger study in which 5,612 consecutive patients underwent screening and diagnostic mammography with at least two views, plus spot compression views if necessary, and contrast-enhanced bilateral high-resolution MRI. Of these, 137 were diagnosed with pure noninvasive intraductal cancer. Their mean age was 55 years (range 20–75).

Both mammography and MRI resulted in positive findings for about 50% of all cases; 2% of cases were undetected by both modalities; 8% of cases had positive findings only with mammography; and 40% had positive findings only with MRI. Overall sensitivity for MRI was 90%, compared with 58% for mammography, Dr. Kuhl and colleagues reported.

Sensitivity for low-nuclear-grade tumors (grades 1–2) was 78% for MRI and 71% for mammography. For high-grade tumors, MRI detected 98% of cases, compared with just 49% for mammography.

Sensitivity for ER/PR-negative and HER 2-positive tumors was 100% and 91%, respectively, for MRI compared with 50% and 48% for mammography.

CHICAGO — Magnetic resonance imaging offers significantly higher sensitivity for diagnosing pure ductal carcinoma in situ than does mammography, Dr. Christiane Kuhl said at the annual meeting of the Radiological Society of North America.

She presented data from a prospective study of 137 women in which almost half of all ductal carcinomas in situ (DCIS) and more than half of high-grade DCIS tumors were missed by mammography. The majority of the women studied were not considered at high risk for cancer, said Dr. Kuhl of the University of Bonn, Germany.

“If proper diagnostic criteria are being used, MRI allows the diagnosis of DCIS that goes undetected by mammography and also ultrasound,” she said.

The women were part of a larger study in which 5,612 consecutive patients underwent screening and diagnostic mammography with at least two views, plus spot compression views if necessary, and contrast-enhanced bilateral high-resolution MRI. Of these, 137 were diagnosed with pure noninvasive intraductal cancer. Their mean age was 55 years (range 20–75).

Both mammography and MRI resulted in positive findings for about 50% of all cases; 2% of cases were undetected by both modalities; 8% of cases had positive findings only with mammography; and 40% had positive findings only with MRI. Overall sensitivity for MRI was 90%, compared with 58% for mammography, Dr. Kuhl and colleagues reported.

Sensitivity for low-nuclear-grade tumors (grades 1–2) was 78% for MRI and 71% for mammography. For high-grade tumors, MRI detected 98% of cases, compared with just 49% for mammography.

Sensitivity for ER/PR-negative and HER 2-positive tumors was 100% and 91%, respectively, for MRI compared with 50% and 48% for mammography.

CHICAGO — Magnetic resonance imaging offers significantly higher sensitivity for diagnosing pure ductal carcinoma in situ than does mammography, Dr. Christiane Kuhl said at the annual meeting of the Radiological Society of North America.

She presented data from a prospective study of 137 women in which almost half of all ductal carcinomas in situ (DCIS) and more than half of high-grade DCIS tumors were missed by mammography. The majority of the women studied were not considered at high risk for cancer, said Dr. Kuhl of the University of Bonn, Germany.

“If proper diagnostic criteria are being used, MRI allows the diagnosis of DCIS that goes undetected by mammography and also ultrasound,” she said.

The women were part of a larger study in which 5,612 consecutive patients underwent screening and diagnostic mammography with at least two views, plus spot compression views if necessary, and contrast-enhanced bilateral high-resolution MRI. Of these, 137 were diagnosed with pure noninvasive intraductal cancer. Their mean age was 55 years (range 20–75).

Both mammography and MRI resulted in positive findings for about 50% of all cases; 2% of cases were undetected by both modalities; 8% of cases had positive findings only with mammography; and 40% had positive findings only with MRI. Overall sensitivity for MRI was 90%, compared with 58% for mammography, Dr. Kuhl and colleagues reported.

Sensitivity for low-nuclear-grade tumors (grades 1–2) was 78% for MRI and 71% for mammography. For high-grade tumors, MRI detected 98% of cases, compared with just 49% for mammography.

Sensitivity for ER/PR-negative and HER 2-positive tumors was 100% and 91%, respectively, for MRI compared with 50% and 48% for mammography.

Decades ago, researchers banded together to help fight childhood leukemia and, in doing so, transformed the disease from a virtual death sentence to one that the vast majority of children survive.

Researchers at Baltimore's Kennedy Krieger Institute are hoping to repeat that collaborative success with the debut this month of the Interactive Autism Network (IAN), the nation's first online autism registry.

“IAN will affect the entire research process and accelerate it manyfold,” Dr. Paul Law, director of the project, told CLINICAL NEUROLOGY NEWS in an interview.

Through IAN, families of children with autism spectrum disorders can participate in a national online research project or they can be linked to other local and national research projects for which they qualify. By year's end, project organizers hope they will have the largest collection of family-provided data ever compiled on autism spectrum disorders.

Of the 250 families that participated as pilot registrants, 80% had never participated in any autism research, even though many of them live in the Baltimore area with access to several major medical institutions. Still others live in remote areas of the country like upper North Dakota, where IAN may be the only research project available, said Dr Law, a pediatrician whose own son was diagnosed with autism in the 1990s.

For researchers, IAN provides access to an invaluable database and a potential pool of study participants. For example, if a researcher is interested in studying 8- to 10-year-old children with autism and a history of regression living in a particular region, he or she can contact the network to determine how many children meet the specific criteria. E-mails will then be sent by the network to the families, notifying them of the study. The names of the families will not be divulged, leaving families in control of their privacy.

Typically, researchers rely on broadly targeted recruitment vehicles such as newspaper advertisements, e-mail lists, and local autism support groups. Few are successful because “they put the burden on families, whereas IAN finds them in a very deliberate and qualified way,” said Dr. Law, director of informatics at the institute.

Families that live near urban areas have access to more facilities for evaluation and are overrepresented in current autism studies, said Dr. Michael Burke, chairman of pediatrics at St. Agnes Hospital, a community hospital in Baltimore. Using the Internet will allow a much broader base of participants for autism research and allow broader access to available resources, he commented on the project. With 1 in 150 children now estimated to have autism spectrum disorders, according to the Centers for Disease Control and Prevention, IAN is attractive to Autism Speaks, a nonprofit association that provided $6 million to fund IAN through 2008.

Not only does IAN link researchers with families, but it's a safe place families can go for evidence-based research and a sense of community, Mark Roithmayr, president of Autism Speaks, said in an interview.

Once given a diagnosis of autism by their pediatrician, families of children with autism spectrum disorders are faced with a host of day-to-day issues and often feel alone. It's also challenging for families and their pediatricians to keep up with and interpret the latest autism news, whether it be new genetics findings or the recent widely publicized claim that autism is caused by watching too much television.

The site, www.IANproject.org

Greater access to study participants should improve the planning of clinical trials and quicken the pace of research. But Dr. Law suggests IAN also could encourage more Internet-mediated research on autism and affect how other disease states are studied as well. That would allow the family in North Dakota and others affected by disease to participate in a variety of research projects rather than being constrained by geography.

“It would certainly promote research and facilitate investigators being able to obtain a large enough data set for the different types of autism,” said Dr. Chris Johnson, co-chair of the American Academy of Pediatrics Autism Expert Panel and medical director, Village of Hope, Center for Children with Disabilities in San Antonio. “One of the problems with the genetics research thus far is sometimes trying to compare apples to oranges when you've got children with Asperger's being compared to children with more severe autism and mental retardation and they are all thrown together in the autism spectrum disorders.”

The network is free to all users, and all information provided is governed by the privacy and security rules of the Health Insurance Portability and Accountability Act. For families without computers, the staff at Kennedy Krieger is working on models to provide access, possibly through grassroots organizations or by designing a telephone registration system, Dr. Law said.

Missouri had planned to launch its own autism registry but is now working with Kennedy Krieger to develop a state-level model for state agencies, universities, researchers, and support groups to utilize the national IAN registry.

Decades ago, researchers banded together to help fight childhood leukemia and, in doing so, transformed the disease from a virtual death sentence to one that the vast majority of children survive.

Researchers at Baltimore's Kennedy Krieger Institute are hoping to repeat that collaborative success with the debut this month of the Interactive Autism Network (IAN), the nation's first online autism registry.

“IAN will affect the entire research process and accelerate it manyfold,” Dr. Paul Law, director of the project, told CLINICAL NEUROLOGY NEWS in an interview.

Through IAN, families of children with autism spectrum disorders can participate in a national online research project or they can be linked to other local and national research projects for which they qualify. By year's end, project organizers hope they will have the largest collection of family-provided data ever compiled on autism spectrum disorders.

Of the 250 families that participated as pilot registrants, 80% had never participated in any autism research, even though many of them live in the Baltimore area with access to several major medical institutions. Still others live in remote areas of the country like upper North Dakota, where IAN may be the only research project available, said Dr Law, a pediatrician whose own son was diagnosed with autism in the 1990s.

For researchers, IAN provides access to an invaluable database and a potential pool of study participants. For example, if a researcher is interested in studying 8- to 10-year-old children with autism and a history of regression living in a particular region, he or she can contact the network to determine how many children meet the specific criteria. E-mails will then be sent by the network to the families, notifying them of the study. The names of the families will not be divulged, leaving families in control of their privacy.

Typically, researchers rely on broadly targeted recruitment vehicles such as newspaper advertisements, e-mail lists, and local autism support groups. Few are successful because “they put the burden on families, whereas IAN finds them in a very deliberate and qualified way,” said Dr. Law, director of informatics at the institute.

Families that live near urban areas have access to more facilities for evaluation and are overrepresented in current autism studies, said Dr. Michael Burke, chairman of pediatrics at St. Agnes Hospital, a community hospital in Baltimore. Using the Internet will allow a much broader base of participants for autism research and allow broader access to available resources, he commented on the project. With 1 in 150 children now estimated to have autism spectrum disorders, according to the Centers for Disease Control and Prevention, IAN is attractive to Autism Speaks, a nonprofit association that provided $6 million to fund IAN through 2008.

Not only does IAN link researchers with families, but it's a safe place families can go for evidence-based research and a sense of community, Mark Roithmayr, president of Autism Speaks, said in an interview.

Once given a diagnosis of autism by their pediatrician, families of children with autism spectrum disorders are faced with a host of day-to-day issues and often feel alone. It's also challenging for families and their pediatricians to keep up with and interpret the latest autism news, whether it be new genetics findings or the recent widely publicized claim that autism is caused by watching too much television.

The site, www.IANproject.org

Greater access to study participants should improve the planning of clinical trials and quicken the pace of research. But Dr. Law suggests IAN also could encourage more Internet-mediated research on autism and affect how other disease states are studied as well. That would allow the family in North Dakota and others affected by disease to participate in a variety of research projects rather than being constrained by geography.

“It would certainly promote research and facilitate investigators being able to obtain a large enough data set for the different types of autism,” said Dr. Chris Johnson, co-chair of the American Academy of Pediatrics Autism Expert Panel and medical director, Village of Hope, Center for Children with Disabilities in San Antonio. “One of the problems with the genetics research thus far is sometimes trying to compare apples to oranges when you've got children with Asperger's being compared to children with more severe autism and mental retardation and they are all thrown together in the autism spectrum disorders.”

The network is free to all users, and all information provided is governed by the privacy and security rules of the Health Insurance Portability and Accountability Act. For families without computers, the staff at Kennedy Krieger is working on models to provide access, possibly through grassroots organizations or by designing a telephone registration system, Dr. Law said.

Missouri had planned to launch its own autism registry but is now working with Kennedy Krieger to develop a state-level model for state agencies, universities, researchers, and support groups to utilize the national IAN registry.

Decades ago, researchers banded together to help fight childhood leukemia and, in doing so, transformed the disease from a virtual death sentence to one that the vast majority of children survive.

Researchers at Baltimore's Kennedy Krieger Institute are hoping to repeat that collaborative success with the debut this month of the Interactive Autism Network (IAN), the nation's first online autism registry.

“IAN will affect the entire research process and accelerate it manyfold,” Dr. Paul Law, director of the project, told CLINICAL NEUROLOGY NEWS in an interview.

Through IAN, families of children with autism spectrum disorders can participate in a national online research project or they can be linked to other local and national research projects for which they qualify. By year's end, project organizers hope they will have the largest collection of family-provided data ever compiled on autism spectrum disorders.

Of the 250 families that participated as pilot registrants, 80% had never participated in any autism research, even though many of them live in the Baltimore area with access to several major medical institutions. Still others live in remote areas of the country like upper North Dakota, where IAN may be the only research project available, said Dr Law, a pediatrician whose own son was diagnosed with autism in the 1990s.

For researchers, IAN provides access to an invaluable database and a potential pool of study participants. For example, if a researcher is interested in studying 8- to 10-year-old children with autism and a history of regression living in a particular region, he or she can contact the network to determine how many children meet the specific criteria. E-mails will then be sent by the network to the families, notifying them of the study. The names of the families will not be divulged, leaving families in control of their privacy.

Typically, researchers rely on broadly targeted recruitment vehicles such as newspaper advertisements, e-mail lists, and local autism support groups. Few are successful because “they put the burden on families, whereas IAN finds them in a very deliberate and qualified way,” said Dr. Law, director of informatics at the institute.

Families that live near urban areas have access to more facilities for evaluation and are overrepresented in current autism studies, said Dr. Michael Burke, chairman of pediatrics at St. Agnes Hospital, a community hospital in Baltimore. Using the Internet will allow a much broader base of participants for autism research and allow broader access to available resources, he commented on the project. With 1 in 150 children now estimated to have autism spectrum disorders, according to the Centers for Disease Control and Prevention, IAN is attractive to Autism Speaks, a nonprofit association that provided $6 million to fund IAN through 2008.

Not only does IAN link researchers with families, but it's a safe place families can go for evidence-based research and a sense of community, Mark Roithmayr, president of Autism Speaks, said in an interview.

Once given a diagnosis of autism by their pediatrician, families of children with autism spectrum disorders are faced with a host of day-to-day issues and often feel alone. It's also challenging for families and their pediatricians to keep up with and interpret the latest autism news, whether it be new genetics findings or the recent widely publicized claim that autism is caused by watching too much television.

The site, www.IANproject.org

Greater access to study participants should improve the planning of clinical trials and quicken the pace of research. But Dr. Law suggests IAN also could encourage more Internet-mediated research on autism and affect how other disease states are studied as well. That would allow the family in North Dakota and others affected by disease to participate in a variety of research projects rather than being constrained by geography.

“It would certainly promote research and facilitate investigators being able to obtain a large enough data set for the different types of autism,” said Dr. Chris Johnson, co-chair of the American Academy of Pediatrics Autism Expert Panel and medical director, Village of Hope, Center for Children with Disabilities in San Antonio. “One of the problems with the genetics research thus far is sometimes trying to compare apples to oranges when you've got children with Asperger's being compared to children with more severe autism and mental retardation and they are all thrown together in the autism spectrum disorders.”

The network is free to all users, and all information provided is governed by the privacy and security rules of the Health Insurance Portability and Accountability Act. For families without computers, the staff at Kennedy Krieger is working on models to provide access, possibly through grassroots organizations or by designing a telephone registration system, Dr. Law said.

Missouri had planned to launch its own autism registry but is now working with Kennedy Krieger to develop a state-level model for state agencies, universities, researchers, and support groups to utilize the national IAN registry.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest-hit state in the nation, 71 of 113 (63%) cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early in the course of the disease, he said.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case-investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007, he said. Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data was available.

Because of this and available viral shedding data, the CDC is expected to recommend in a memo to all the states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Good cooperation and communication between local health and student health centers provided follow-up on almost all of the college students. But questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early to avoid missing exams, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps. “Negative results do not rule out disease,” Ms. Hill said.

Delayed recognition of the outbreak, enhanced transmission in colleges, and unrecognized importations all contributed to the outbreak, according to Dr. Dayan. “In addition, two doses of mumps vaccine may confer about 90%–95% vaccine effectiveness, which may result in accumulation of susceptible persons sufficient to sustain transmission and a sizeable outbreak on a periodic basis,” he said. There was no evidence of genetic drift, although the role of waning immunity is unclear.

“However, high MMR vaccine coverage levels and vaccine effectiveness likely prevented thousands of additional mumps cases, the incidence was relatively low, and the disease appeared to be modified with low rates of complications,” Dr. Dayan said.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest-hit state in the nation, 71 of 113 (63%) cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early in the course of the disease, he said.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case-investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007, he said. Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data was available.

Because of this and available viral shedding data, the CDC is expected to recommend in a memo to all the states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Good cooperation and communication between local health and student health centers provided follow-up on almost all of the college students. But questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early to avoid missing exams, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps. “Negative results do not rule out disease,” Ms. Hill said.

Delayed recognition of the outbreak, enhanced transmission in colleges, and unrecognized importations all contributed to the outbreak, according to Dr. Dayan. “In addition, two doses of mumps vaccine may confer about 90%–95% vaccine effectiveness, which may result in accumulation of susceptible persons sufficient to sustain transmission and a sizeable outbreak on a periodic basis,” he said. There was no evidence of genetic drift, although the role of waning immunity is unclear.

“However, high MMR vaccine coverage levels and vaccine effectiveness likely prevented thousands of additional mumps cases, the incidence was relatively low, and the disease appeared to be modified with low rates of complications,” Dr. Dayan said.

KANSAS CITY, MO. — The resurgence of mumps in 2006 was unexpected but provided the medical community with some valuable lessons, two infectious disease experts reported at the National Immunization Conference sponsored by the Centers for Disease Control and Prevention.

Particularly vexing was the presence of cases without the classical presentation of parotitis and the inability to rule out cases based on negative laboratory results, said Dr. Gustavo H. Dayan of the CDC's Division of Viral Diseases, and Measles, Mumps, and Rubella team leader.

In Iowa, the hardest-hit state in the nation, 71 of 113 (63%) cases at two colleges presented without classic symptoms.

Laboratory diagnosis was very challenging because IgM response was usually absent and performance of different IgM assays was variable. Immunoglobulin G was present in many patients at the moment of diagnosis. Viral culture and polymerase chain reaction (PCR) had a low yield, especially when the specimens weren't taken early in the course of the disease, he said.

A viral shedding study using PCR assays in 31 consecutive Kansas cases resulted in only eight positive results. Seven of the eight samples were taken during the first 3 days after the onset of parotitis, Dr. Dayan said.

Surveillance was difficult because the new case-investigation report form was not adequate and different forms were being used by different states, he said. The Council of State and Territorial Epidemiologists clinical case definition of mumps does not include cases with classic complications of mumps without the presence of parotitis for 2 days.

“We really feel that some of the cases at the beginning of the outbreak may have been discarded based on the not very clear clinical symptoms and negative results,” he said. “However, during the outbreak, some of the cases may have been overcounted because the surveillance system was very enhanced and cases without symptoms may have been counted.”

What is known is that the outbreak primarily affected young non-Hispanic white adults, aged 18–24, as well as females and those living on college campuses.

A total of 45 states reported mumps cases in 2006, and 8 states in the Midwest were the most affected. Iowa had the highest incidence at 66/100,000, compared with Minnesota, which had the lowest incidence at 2.8/100,000. Available data from these eight states show that about 43% of the cases had received two doses of mumps vaccine, Dr. Dayan said in an interview.

Overall, 6,330 cases were reported to the National Notifiable Diseases Surveillance System in 2006, and approximately 120 new cases have been reported in 2007, he said. Few infants were affected, and no large school or day care outbreaks were reported. The outbreak did not spread to unvaccinated populations.

The source of the outbreak is not known. But the mumps strain in Iowa and other affected states has been identified as genotype G5, which is the same one that circulated in the United Kingdom throughout the 2004–2006 outbreaks. Virus genotyping in Virginia from a cluster in the latter part of the year isolated the G1 genotype, which suggests a different source of importation, he said.

Compliance with the mumps-isolation recommendation proved challenging. Compliance was 87% for isolation less than 4 days and just 66% for isolation 4 days or more among 133 Kansas students for whom data was available.

Because of this and available viral shedding data, the CDC is expected to recommend in a memo to all the states that the isolation period for mumps be changed to 5 days, Dr. Dayan said.

Kansas changed its viral isolation recommendation to 4 days in early April 2006 but, later that month, reverted to 9 days, which is the period required by Kansas state law and recommended by the CDC, Ms. Jennifer Hill, an epidemiologist with the Kansas Department of Health and Environment, said in a separate presentation during the meeting.

Kansas was the second-hardest hit state in the United States, with 986 cases reported in late 2005–2006; 40% of these were among young adults (18–24 years old), 60% were among women and girls, and 30% were among college students.

Good cooperation and communication between local health and student health centers provided follow-up on almost all of the college students. But questions arose as to whether students should be isolated at home or at school, how long the isolation should last, and who was responsible for their follow-up compliance. Students were told not to go to school for 9 days, but officials received reports some students returned to class early to avoid missing exams, Ms. Hill said.

Kansas also vacillated between one and two doses of mumps vaccine as its definition of adequate protection before ultimately deciding that patients who receive one dose of measles-mumps-rubella (MMR) vaccine are adequately vaccinated. Separate guidelines and algorithms were established for health care workers and day care workers that rely on self-reported vaccination history data.

Immunization history available on 85% of cases revealed that 73% had received one dose of MMR vaccine and 7% were unvaccinated, and 64% of all vaccinated patients had a history of two doses.

Laboratories were able to communicate those results to clinicians, but at times, there weren't enough qualified workers or materials to perform the necessary testing. After the testing, it wasn't clear how to interpret negative results and how to convince local authorities that it was still mumps. “Negative results do not rule out disease,” Ms. Hill said.

Delayed recognition of the outbreak, enhanced transmission in colleges, and unrecognized importations all contributed to the outbreak, according to Dr. Dayan. “In addition, two doses of mumps vaccine may confer about 90%–95% vaccine effectiveness, which may result in accumulation of susceptible persons sufficient to sustain transmission and a sizeable outbreak on a periodic basis,” he said. There was no evidence of genetic drift, although the role of waning immunity is unclear.

“However, high MMR vaccine coverage levels and vaccine effectiveness likely prevented thousands of additional mumps cases, the incidence was relatively low, and the disease appeared to be modified with low rates of complications,” Dr. Dayan said.