Miriam E. Tucker

ATLANTA — The investigational cervical cancer vaccine Cervarix remained highly effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia (CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

It also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains linked to cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women aged over 25 years, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections decrease with age, the risk of persistence increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0−, 1−, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women aged over 25 years is also ongoing. Trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

In the United States, the biologic license application is “on target for submission,” Dr. Dubin said.

ATLANTA — The investigational cervical cancer vaccine Cervarix remained highly effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia (CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

It also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains linked to cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women aged over 25 years, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections decrease with age, the risk of persistence increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0−, 1−, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women aged over 25 years is also ongoing. Trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

In the United States, the biologic license application is “on target for submission,” Dr. Dubin said.

ATLANTA — The investigational cervical cancer vaccine Cervarix remained highly effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia (CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

It also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains linked to cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women aged over 25 years, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections decrease with age, the risk of persistence increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0−, 1−, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women aged over 25 years is also ongoing. Trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

In the United States, the biologic license application is “on target for submission,” Dr. Dubin said.

WASHINGTON — Coccidioides species represent a serious threat to patients taking tumor necrosis factor-α inhibitors, Dr. Andrew Racette said at the annual meeting of the American Academy of Dermatology.

Drugs that inhibit tumor necrosis factor-α (TNF-α) are very effective in treating inflammatory rheumatic and autoimmune diseases, but also decrease resistance to granulomatous pulmonary infections, particularly tuberculosis (Clin. Infect. Dis. 2004;38:1261–5).

However, less information has been published about patients receiving TNF-α inhibitor therapy who develop pulmonary infections caused by Coccidioides, a fungus endemic to the southwestern United States. While most TB cases seen in patients taking TNF-α inhibitors are reactivations of quiescent disease, most of the coccidioidomycosis infections in these patients appear to be new primary infections, said Dr. Racette, a second-year dermatology resident at Western University of Health Sciences, Phoenix.

A total of 31 patients who developed coccidioidomycosis infections while taking TNF-α inhibitors were identified via questionnaires sent to rheumatologists and dermatologists in the Phoenix area. Fourteen were taking infliximab, 10 etanercept, and 7 adalimumab. At the time they developed their infection, 25 were taking other concurrent immunosuppressive medications, including methotrexate, prednisone, and leflunomide. Six patients—four on etanercept and one each on infliximab and adalimumab—were on no other medications.

The patients had a mean age of 57 years (range 29–80) and an average time to infection of 21 months (range 2–73). Most (21) were being treated for rheumatoid arthritis, 3 for psoriatic arthritis, 2 for psoriasis, and 1 patient each for other disorders including ankylosing spondylitis, gout, and Crohn's disease.

Only 1 of 31 patients had a known cocci infection prior to initiating TNF-α inhibitor treatment. Of 20 patients who had chest x-rays prior to treatment, two had abnormal results (left upper lung nodules). Of 17 who had serologies prior to TNF-α inhibitor treatment, all were negative.

The most common presenting symptoms were cough (61%), fever (48%), and fatigue (29%). A nonspecific rash was present at diagnosis in 26%, while another 26% were asymptomatic. The diagnosis was made by serology alone in 17 patients and by pathologic evidence (culture, cytopathology, or biopsy) in the other 14.

All but one were treated with fluconazole 200 mg twice daily (orally for outpatients and intravenously for inpatients). Intravenous amphotericin B was given to patients in the ICU, while one outpatient and one inpatient received voriconazole.

After the infection resolved, 12 patients restarted their medication—6 on infliximab, 3 on etanercept, and 3 on adalimumab. Of those, there was one recurrence of coccidioidomycosis infection, in a patient who was taking etanercept 25 mg twice weekly, prednisone 7 mg/day, and fluconazole 200 mg twice daily who later died of respiratory failure. Eight patients were hospitalized for their infections, three had dissemination of disease, three were treated in the ICU with intubation and mechanical ventilation, and two died.

Based on this case series and published literature, the following recommendations can be made for managing patients living in the southwestern United States who are going to be starting TNF-α inhibitors and those who are already on them, Dr. Racette said:

▸ Do pretreatment screening. This should include a history of prior coccidioidomycosis infection and work environment. Patients who work outdoors are at increased risk. A chest x-ray and Coccidioides serologies should be done to rule out any asymptomatic infection that likely would be exacerbated by the TNF-α inhibitor.

▸ Monitor patients during therapy. This includes asking the patient about cough, fever, and fatigue at each visit. A physical exam also should be performed. Annual chest x-rays and cocci serologies may be worthwhile in higher-risk groups, such as elderly patients and those who work outside, but more data are needed, he said.

▸ Decide whether to resume TNF-α therapy. This is debatable because of the risk for reactivation. It may be safe if patients continue fluconazole and as long as their complement fixation titer remains negative. Surveillance every 2–3 months is key.

WASHINGTON — Coccidioides species represent a serious threat to patients taking tumor necrosis factor-α inhibitors, Dr. Andrew Racette said at the annual meeting of the American Academy of Dermatology.

Drugs that inhibit tumor necrosis factor-α (TNF-α) are very effective in treating inflammatory rheumatic and autoimmune diseases, but also decrease resistance to granulomatous pulmonary infections, particularly tuberculosis (Clin. Infect. Dis. 2004;38:1261–5).

However, less information has been published about patients receiving TNF-α inhibitor therapy who develop pulmonary infections caused by Coccidioides, a fungus endemic to the southwestern United States. While most TB cases seen in patients taking TNF-α inhibitors are reactivations of quiescent disease, most of the coccidioidomycosis infections in these patients appear to be new primary infections, said Dr. Racette, a second-year dermatology resident at Western University of Health Sciences, Phoenix.

A total of 31 patients who developed coccidioidomycosis infections while taking TNF-α inhibitors were identified via questionnaires sent to rheumatologists and dermatologists in the Phoenix area. Fourteen were taking infliximab, 10 etanercept, and 7 adalimumab. At the time they developed their infection, 25 were taking other concurrent immunosuppressive medications, including methotrexate, prednisone, and leflunomide. Six patients—four on etanercept and one each on infliximab and adalimumab—were on no other medications.

The patients had a mean age of 57 years (range 29–80) and an average time to infection of 21 months (range 2–73). Most (21) were being treated for rheumatoid arthritis, 3 for psoriatic arthritis, 2 for psoriasis, and 1 patient each for other disorders including ankylosing spondylitis, gout, and Crohn's disease.

Only 1 of 31 patients had a known cocci infection prior to initiating TNF-α inhibitor treatment. Of 20 patients who had chest x-rays prior to treatment, two had abnormal results (left upper lung nodules). Of 17 who had serologies prior to TNF-α inhibitor treatment, all were negative.

The most common presenting symptoms were cough (61%), fever (48%), and fatigue (29%). A nonspecific rash was present at diagnosis in 26%, while another 26% were asymptomatic. The diagnosis was made by serology alone in 17 patients and by pathologic evidence (culture, cytopathology, or biopsy) in the other 14.

All but one were treated with fluconazole 200 mg twice daily (orally for outpatients and intravenously for inpatients). Intravenous amphotericin B was given to patients in the ICU, while one outpatient and one inpatient received voriconazole.

After the infection resolved, 12 patients restarted their medication—6 on infliximab, 3 on etanercept, and 3 on adalimumab. Of those, there was one recurrence of coccidioidomycosis infection, in a patient who was taking etanercept 25 mg twice weekly, prednisone 7 mg/day, and fluconazole 200 mg twice daily who later died of respiratory failure. Eight patients were hospitalized for their infections, three had dissemination of disease, three were treated in the ICU with intubation and mechanical ventilation, and two died.

Based on this case series and published literature, the following recommendations can be made for managing patients living in the southwestern United States who are going to be starting TNF-α inhibitors and those who are already on them, Dr. Racette said:

▸ Do pretreatment screening. This should include a history of prior coccidioidomycosis infection and work environment. Patients who work outdoors are at increased risk. A chest x-ray and Coccidioides serologies should be done to rule out any asymptomatic infection that likely would be exacerbated by the TNF-α inhibitor.

▸ Monitor patients during therapy. This includes asking the patient about cough, fever, and fatigue at each visit. A physical exam also should be performed. Annual chest x-rays and cocci serologies may be worthwhile in higher-risk groups, such as elderly patients and those who work outside, but more data are needed, he said.

▸ Decide whether to resume TNF-α therapy. This is debatable because of the risk for reactivation. It may be safe if patients continue fluconazole and as long as their complement fixation titer remains negative. Surveillance every 2–3 months is key.

WASHINGTON — Coccidioides species represent a serious threat to patients taking tumor necrosis factor-α inhibitors, Dr. Andrew Racette said at the annual meeting of the American Academy of Dermatology.

Drugs that inhibit tumor necrosis factor-α (TNF-α) are very effective in treating inflammatory rheumatic and autoimmune diseases, but also decrease resistance to granulomatous pulmonary infections, particularly tuberculosis (Clin. Infect. Dis. 2004;38:1261–5).

However, less information has been published about patients receiving TNF-α inhibitor therapy who develop pulmonary infections caused by Coccidioides, a fungus endemic to the southwestern United States. While most TB cases seen in patients taking TNF-α inhibitors are reactivations of quiescent disease, most of the coccidioidomycosis infections in these patients appear to be new primary infections, said Dr. Racette, a second-year dermatology resident at Western University of Health Sciences, Phoenix.

A total of 31 patients who developed coccidioidomycosis infections while taking TNF-α inhibitors were identified via questionnaires sent to rheumatologists and dermatologists in the Phoenix area. Fourteen were taking infliximab, 10 etanercept, and 7 adalimumab. At the time they developed their infection, 25 were taking other concurrent immunosuppressive medications, including methotrexate, prednisone, and leflunomide. Six patients—four on etanercept and one each on infliximab and adalimumab—were on no other medications.

The patients had a mean age of 57 years (range 29–80) and an average time to infection of 21 months (range 2–73). Most (21) were being treated for rheumatoid arthritis, 3 for psoriatic arthritis, 2 for psoriasis, and 1 patient each for other disorders including ankylosing spondylitis, gout, and Crohn's disease.

Only 1 of 31 patients had a known cocci infection prior to initiating TNF-α inhibitor treatment. Of 20 patients who had chest x-rays prior to treatment, two had abnormal results (left upper lung nodules). Of 17 who had serologies prior to TNF-α inhibitor treatment, all were negative.

The most common presenting symptoms were cough (61%), fever (48%), and fatigue (29%). A nonspecific rash was present at diagnosis in 26%, while another 26% were asymptomatic. The diagnosis was made by serology alone in 17 patients and by pathologic evidence (culture, cytopathology, or biopsy) in the other 14.

All but one were treated with fluconazole 200 mg twice daily (orally for outpatients and intravenously for inpatients). Intravenous amphotericin B was given to patients in the ICU, while one outpatient and one inpatient received voriconazole.

After the infection resolved, 12 patients restarted their medication—6 on infliximab, 3 on etanercept, and 3 on adalimumab. Of those, there was one recurrence of coccidioidomycosis infection, in a patient who was taking etanercept 25 mg twice weekly, prednisone 7 mg/day, and fluconazole 200 mg twice daily who later died of respiratory failure. Eight patients were hospitalized for their infections, three had dissemination of disease, three were treated in the ICU with intubation and mechanical ventilation, and two died.

Based on this case series and published literature, the following recommendations can be made for managing patients living in the southwestern United States who are going to be starting TNF-α inhibitors and those who are already on them, Dr. Racette said:

▸ Do pretreatment screening. This should include a history of prior coccidioidomycosis infection and work environment. Patients who work outdoors are at increased risk. A chest x-ray and Coccidioides serologies should be done to rule out any asymptomatic infection that likely would be exacerbated by the TNF-α inhibitor.

▸ Monitor patients during therapy. This includes asking the patient about cough, fever, and fatigue at each visit. A physical exam also should be performed. Annual chest x-rays and cocci serologies may be worthwhile in higher-risk groups, such as elderly patients and those who work outside, but more data are needed, he said.

▸ Decide whether to resume TNF-α therapy. This is debatable because of the risk for reactivation. It may be safe if patients continue fluconazole and as long as their complement fixation titer remains negative. Surveillance every 2–3 months is key.

ATLANTA — Children aged 6 months to 9 years of age who did not receive two doses of vaccine the first time they were immunized against influenza should receive two doses the following season, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended at its winter meeting.

To ensure an adequate immune response, children aged 6 months through 9 years receiving influenza vaccine for the first time are supposed to receive two doses given at least a month apart. But for a variety of reasons, some children receive only one dose. Two studies published in 2006 suggest that these children would be better protected against influenza if they receive two doses the following year, Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases, told the committee.

In one study, when the influenza B antigen was changed for the second season, children who only received one dose in their first season of being vaccinated and one dose in their second season had decreased immunologic response to the influenza B antigen, compared with children who received two doses (Pediatrics 2006;118:e579–85).

The other study showed that, in consecutive seasons when the influenza vaccine antigens were unchanged, effectiveness against influenzalike illness in the second season was significantly less for 6− to 21-month-old children being vaccinated for the first time who received one dose in both seasons, compared with 6− to 21-month-olds who received one dose in their first season and two doses in their second season (J. Pediatr. 2006;149:755–62).

The new ACIP recommendation brings it in line with the American Academy of Pediatrics, which issued the same guideline in October 2006. The American Academy of Family Physicians, which usually follows ACIP's recommendations, will likely change its advice as well, AAFP coliaison Dr. Doug Campos-Outcalt said in an interview.

That recommendation was the only major change that will appear in the ACIP's 2007 influenza statement, which does not add any new age or risk groups for routine immunization, compared with 2006. The statement will continue the advice from last season against the use of amantadine and rimantadine for the treatment or prevention of influenza because resistance to the antivirals among H3N1 strains in the United States was more than 30% this season, Dr. Fiore noted.

The statement will, however, contain some new language. More direct wording will address the lack of scientifically conclusive evidence demonstrating harm from exposure to thimerosal preservative-containing vaccine, and the recommendation that any age- and risk-factor appropriate preparation is acceptable depending on availability. Prior to its vote on the influenza immunization statement, the ACIP heard a presentation by Dr. Jay Lieberman summarizing available data on thimerosal (see accompanying story).

Reinforcement of the need for health care workers to be immunized against influenza will be included in the statement, which also will mention new recommendations from several professional societies that all facilities employing health care workers offer the vaccine and require a written declination for those who choose not to be vaccinated.

New language on the timing of influenza immunization will note that although the ideal time is late September and October, immunization efforts should continue through January and beyond. Peak influenza activity occurs in February or March in most seasons, Dr. Fiore said.

Pediatricians and family physicians who treat children should be aware that the ACIP is gearing up to expand its influenza vaccination recommendations beyond the current ages 6 months to 5 years to include all children aged 5–18 years. A meeting is planned for this summer to consider the scientific and implementation issues, with the goal of implementation for the 2008–2009 flu season, Dr. Ban Mishu Allos, the ACIP's influenza immunization task force chair, told the committee.

Dr. Deborah Wexler, chief of the Immunization Action Coalition, told the committee that universal annual childhood immunization against influenza is already a stated goal of several national, state, and regional professional health care groups.

ATLANTA — Children aged 6 months to 9 years of age who did not receive two doses of vaccine the first time they were immunized against influenza should receive two doses the following season, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended at its winter meeting.

To ensure an adequate immune response, children aged 6 months through 9 years receiving influenza vaccine for the first time are supposed to receive two doses given at least a month apart. But for a variety of reasons, some children receive only one dose. Two studies published in 2006 suggest that these children would be better protected against influenza if they receive two doses the following year, Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases, told the committee.

In one study, when the influenza B antigen was changed for the second season, children who only received one dose in their first season of being vaccinated and one dose in their second season had decreased immunologic response to the influenza B antigen, compared with children who received two doses (Pediatrics 2006;118:e579–85).

The other study showed that, in consecutive seasons when the influenza vaccine antigens were unchanged, effectiveness against influenzalike illness in the second season was significantly less for 6− to 21-month-old children being vaccinated for the first time who received one dose in both seasons, compared with 6− to 21-month-olds who received one dose in their first season and two doses in their second season (J. Pediatr. 2006;149:755–62).

The new ACIP recommendation brings it in line with the American Academy of Pediatrics, which issued the same guideline in October 2006. The American Academy of Family Physicians, which usually follows ACIP's recommendations, will likely change its advice as well, AAFP coliaison Dr. Doug Campos-Outcalt said in an interview.

That recommendation was the only major change that will appear in the ACIP's 2007 influenza statement, which does not add any new age or risk groups for routine immunization, compared with 2006. The statement will continue the advice from last season against the use of amantadine and rimantadine for the treatment or prevention of influenza because resistance to the antivirals among H3N1 strains in the United States was more than 30% this season, Dr. Fiore noted.

The statement will, however, contain some new language. More direct wording will address the lack of scientifically conclusive evidence demonstrating harm from exposure to thimerosal preservative-containing vaccine, and the recommendation that any age- and risk-factor appropriate preparation is acceptable depending on availability. Prior to its vote on the influenza immunization statement, the ACIP heard a presentation by Dr. Jay Lieberman summarizing available data on thimerosal (see accompanying story).

Reinforcement of the need for health care workers to be immunized against influenza will be included in the statement, which also will mention new recommendations from several professional societies that all facilities employing health care workers offer the vaccine and require a written declination for those who choose not to be vaccinated.

New language on the timing of influenza immunization will note that although the ideal time is late September and October, immunization efforts should continue through January and beyond. Peak influenza activity occurs in February or March in most seasons, Dr. Fiore said.

Pediatricians and family physicians who treat children should be aware that the ACIP is gearing up to expand its influenza vaccination recommendations beyond the current ages 6 months to 5 years to include all children aged 5–18 years. A meeting is planned for this summer to consider the scientific and implementation issues, with the goal of implementation for the 2008–2009 flu season, Dr. Ban Mishu Allos, the ACIP's influenza immunization task force chair, told the committee.

Dr. Deborah Wexler, chief of the Immunization Action Coalition, told the committee that universal annual childhood immunization against influenza is already a stated goal of several national, state, and regional professional health care groups.

ATLANTA — Children aged 6 months to 9 years of age who did not receive two doses of vaccine the first time they were immunized against influenza should receive two doses the following season, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended at its winter meeting.

To ensure an adequate immune response, children aged 6 months through 9 years receiving influenza vaccine for the first time are supposed to receive two doses given at least a month apart. But for a variety of reasons, some children receive only one dose. Two studies published in 2006 suggest that these children would be better protected against influenza if they receive two doses the following year, Dr. Anthony Fiore of the CDC's National Center for Immunization and Respiratory Diseases, told the committee.

In one study, when the influenza B antigen was changed for the second season, children who only received one dose in their first season of being vaccinated and one dose in their second season had decreased immunologic response to the influenza B antigen, compared with children who received two doses (Pediatrics 2006;118:e579–85).

The other study showed that, in consecutive seasons when the influenza vaccine antigens were unchanged, effectiveness against influenzalike illness in the second season was significantly less for 6− to 21-month-old children being vaccinated for the first time who received one dose in both seasons, compared with 6− to 21-month-olds who received one dose in their first season and two doses in their second season (J. Pediatr. 2006;149:755–62).

The new ACIP recommendation brings it in line with the American Academy of Pediatrics, which issued the same guideline in October 2006. The American Academy of Family Physicians, which usually follows ACIP's recommendations, will likely change its advice as well, AAFP coliaison Dr. Doug Campos-Outcalt said in an interview.

That recommendation was the only major change that will appear in the ACIP's 2007 influenza statement, which does not add any new age or risk groups for routine immunization, compared with 2006. The statement will continue the advice from last season against the use of amantadine and rimantadine for the treatment or prevention of influenza because resistance to the antivirals among H3N1 strains in the United States was more than 30% this season, Dr. Fiore noted.

The statement will, however, contain some new language. More direct wording will address the lack of scientifically conclusive evidence demonstrating harm from exposure to thimerosal preservative-containing vaccine, and the recommendation that any age- and risk-factor appropriate preparation is acceptable depending on availability. Prior to its vote on the influenza immunization statement, the ACIP heard a presentation by Dr. Jay Lieberman summarizing available data on thimerosal (see accompanying story).

Reinforcement of the need for health care workers to be immunized against influenza will be included in the statement, which also will mention new recommendations from several professional societies that all facilities employing health care workers offer the vaccine and require a written declination for those who choose not to be vaccinated.

New language on the timing of influenza immunization will note that although the ideal time is late September and October, immunization efforts should continue through January and beyond. Peak influenza activity occurs in February or March in most seasons, Dr. Fiore said.

Pediatricians and family physicians who treat children should be aware that the ACIP is gearing up to expand its influenza vaccination recommendations beyond the current ages 6 months to 5 years to include all children aged 5–18 years. A meeting is planned for this summer to consider the scientific and implementation issues, with the goal of implementation for the 2008–2009 flu season, Dr. Ban Mishu Allos, the ACIP's influenza immunization task force chair, told the committee.

Dr. Deborah Wexler, chief of the Immunization Action Coalition, told the committee that universal annual childhood immunization against influenza is already a stated goal of several national, state, and regional professional health care groups.

TORONTO — Questionnaires are as accurate as laboratory tests in screening patients for type 2 diabetes, Dr. Kara A. Nerenberg and her associates reported in a poster at the annual joint meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

“Diabetes screening questionnaires are simple, cheap alternatives to lab tests as initial screening tests,” said Dr. Nerenberg and her associates, of McMaster University, Hamilton, Ont.

A systematic review of data assessing the diagnostic performance of diabetes screening questionnaires yielded 10 studies of eight different questionnaires in 22 global populations with similar prevalences of type 2 diabetes. All of the questionnaires asked about age and obesity, while a majority also assessed hypertension, history of dysglycemia, activity/exercise, diet, family history, and sex.

Sensitivity of the questionnaires ranged from 0.67 (the Finnish DRS-Modified) to 0.82 (the Finnish DRS), and specificity from 0.58 (the Finnish DRS) to 0.74 (the Danish Risk Score). Both the Finnish and Danish scores performed consistently well in the different ethnic populations studied. Overall sensitivity of the questionnaires was 0.58, within the same range as the 0.40–0.60 with fasting plasma glucose and 0.69 for the oral glucose tolerance test.

The data were heterogeneous, however, with most of the variability accounted for by the prevalence of type 2 diabetes in the population being tested, they noted.

The screening questionnaire could be filled out in the waiting room, which would allow the physician to discuss the results with the patient at the same visit and refer those who score high for follow-up with an oral glucose tolerance test, Dr. Nerenberg said in an interview.

TORONTO — Questionnaires are as accurate as laboratory tests in screening patients for type 2 diabetes, Dr. Kara A. Nerenberg and her associates reported in a poster at the annual joint meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

“Diabetes screening questionnaires are simple, cheap alternatives to lab tests as initial screening tests,” said Dr. Nerenberg and her associates, of McMaster University, Hamilton, Ont.

A systematic review of data assessing the diagnostic performance of diabetes screening questionnaires yielded 10 studies of eight different questionnaires in 22 global populations with similar prevalences of type 2 diabetes. All of the questionnaires asked about age and obesity, while a majority also assessed hypertension, history of dysglycemia, activity/exercise, diet, family history, and sex.

Sensitivity of the questionnaires ranged from 0.67 (the Finnish DRS-Modified) to 0.82 (the Finnish DRS), and specificity from 0.58 (the Finnish DRS) to 0.74 (the Danish Risk Score). Both the Finnish and Danish scores performed consistently well in the different ethnic populations studied. Overall sensitivity of the questionnaires was 0.58, within the same range as the 0.40–0.60 with fasting plasma glucose and 0.69 for the oral glucose tolerance test.

The data were heterogeneous, however, with most of the variability accounted for by the prevalence of type 2 diabetes in the population being tested, they noted.

The screening questionnaire could be filled out in the waiting room, which would allow the physician to discuss the results with the patient at the same visit and refer those who score high for follow-up with an oral glucose tolerance test, Dr. Nerenberg said in an interview.

TORONTO — Questionnaires are as accurate as laboratory tests in screening patients for type 2 diabetes, Dr. Kara A. Nerenberg and her associates reported in a poster at the annual joint meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

“Diabetes screening questionnaires are simple, cheap alternatives to lab tests as initial screening tests,” said Dr. Nerenberg and her associates, of McMaster University, Hamilton, Ont.

A systematic review of data assessing the diagnostic performance of diabetes screening questionnaires yielded 10 studies of eight different questionnaires in 22 global populations with similar prevalences of type 2 diabetes. All of the questionnaires asked about age and obesity, while a majority also assessed hypertension, history of dysglycemia, activity/exercise, diet, family history, and sex.

Sensitivity of the questionnaires ranged from 0.67 (the Finnish DRS-Modified) to 0.82 (the Finnish DRS), and specificity from 0.58 (the Finnish DRS) to 0.74 (the Danish Risk Score). Both the Finnish and Danish scores performed consistently well in the different ethnic populations studied. Overall sensitivity of the questionnaires was 0.58, within the same range as the 0.40–0.60 with fasting plasma glucose and 0.69 for the oral glucose tolerance test.

The data were heterogeneous, however, with most of the variability accounted for by the prevalence of type 2 diabetes in the population being tested, they noted.

The screening questionnaire could be filled out in the waiting room, which would allow the physician to discuss the results with the patient at the same visit and refer those who score high for follow-up with an oral glucose tolerance test, Dr. Nerenberg said in an interview.

TORONTO — Children who become obese following surgical removal of craniopharyngiomas exhibit more severe metabolic derangements than do equally obese children who did not have the tumors, Dr. Jill Hamilton reported at the annual joint meeting of the Canadian Diabetes Association and the Canadian Society for Endocrinology and Metabolism.

Craniopharyngioma, a tumor of the hypothalamic-pituitary region, accounts for 9% of all intracranial tumors in children. Although the tumor itself is benign, hypothalamic trauma resulting from its surgical removal often leads to a variety of neurologic and metabolic problems, including morbid obesity in 35%–58% of patients. The mechanism is not clear, but vagally-mediated increased insulin secretion appears to play a role, said Dr. Hamilton, of the University of Toronto and the Hospital for Sick Children, Toronto.

Fifteen children (mean age 15.2 years) with a history of craniopharyngioma treatment and body mass index (BMI) greater than the 95th percentile for age and sex (mean 35.0) were compared with 15 control children matched for both age (mean 14.8 years) and BMI (32.9) who did not have a history of the tumor. There were 8 girls and 7 boys in the craniopharyngioma group, who had a mean Tanner Stage of 3, versus 10 girls and 5 boys in the control group, mean Tanner Stage 4. The two groups did not differ with regard to family history of type 2 diabetes, parental obesity, or in utero exposure to diabetes.

Oral glucose tolerance tests demonstrated significantly higher 2-hour glucose values among the craniopharyngioma children, compared with the controls (137 mg/dL vs. 115.3 mg/dL [7.6 mmol/L vs. 6.4 mmol/L]), as well as significantly elevated insulin levels at 30 minutes and 2 hours. Forty percent of the craniopharyngioma group met diagnostic criteria for either impaired glucose tolerance or type 2 diabetes (previously undiagnosed), compared with none of the controls, Dr. Hamilton reported.

Two-thirds of the craniopharyngioma group versus just 20% of the controls—a significant difference—met pediatric-adapted criteria for the metabolic syndrome, mostly via elevated triglycerides, reduced HDL cholesterol, and impaired glucose tolerance.

Whole-body insulin sensitivity did not differ between the two groups, but the craniopharyngioma patients demonstrated significantly elevated first- and second-phase insulin secretion, she said.

TORONTO — Children who become obese following surgical removal of craniopharyngiomas exhibit more severe metabolic derangements than do equally obese children who did not have the tumors, Dr. Jill Hamilton reported at the annual joint meeting of the Canadian Diabetes Association and the Canadian Society for Endocrinology and Metabolism.

Craniopharyngioma, a tumor of the hypothalamic-pituitary region, accounts for 9% of all intracranial tumors in children. Although the tumor itself is benign, hypothalamic trauma resulting from its surgical removal often leads to a variety of neurologic and metabolic problems, including morbid obesity in 35%–58% of patients. The mechanism is not clear, but vagally-mediated increased insulin secretion appears to play a role, said Dr. Hamilton, of the University of Toronto and the Hospital for Sick Children, Toronto.

Fifteen children (mean age 15.2 years) with a history of craniopharyngioma treatment and body mass index (BMI) greater than the 95th percentile for age and sex (mean 35.0) were compared with 15 control children matched for both age (mean 14.8 years) and BMI (32.9) who did not have a history of the tumor. There were 8 girls and 7 boys in the craniopharyngioma group, who had a mean Tanner Stage of 3, versus 10 girls and 5 boys in the control group, mean Tanner Stage 4. The two groups did not differ with regard to family history of type 2 diabetes, parental obesity, or in utero exposure to diabetes.

Oral glucose tolerance tests demonstrated significantly higher 2-hour glucose values among the craniopharyngioma children, compared with the controls (137 mg/dL vs. 115.3 mg/dL [7.6 mmol/L vs. 6.4 mmol/L]), as well as significantly elevated insulin levels at 30 minutes and 2 hours. Forty percent of the craniopharyngioma group met diagnostic criteria for either impaired glucose tolerance or type 2 diabetes (previously undiagnosed), compared with none of the controls, Dr. Hamilton reported.

Two-thirds of the craniopharyngioma group versus just 20% of the controls—a significant difference—met pediatric-adapted criteria for the metabolic syndrome, mostly via elevated triglycerides, reduced HDL cholesterol, and impaired glucose tolerance.

Whole-body insulin sensitivity did not differ between the two groups, but the craniopharyngioma patients demonstrated significantly elevated first- and second-phase insulin secretion, she said.

TORONTO — Children who become obese following surgical removal of craniopharyngiomas exhibit more severe metabolic derangements than do equally obese children who did not have the tumors, Dr. Jill Hamilton reported at the annual joint meeting of the Canadian Diabetes Association and the Canadian Society for Endocrinology and Metabolism.

Craniopharyngioma, a tumor of the hypothalamic-pituitary region, accounts for 9% of all intracranial tumors in children. Although the tumor itself is benign, hypothalamic trauma resulting from its surgical removal often leads to a variety of neurologic and metabolic problems, including morbid obesity in 35%–58% of patients. The mechanism is not clear, but vagally-mediated increased insulin secretion appears to play a role, said Dr. Hamilton, of the University of Toronto and the Hospital for Sick Children, Toronto.

Fifteen children (mean age 15.2 years) with a history of craniopharyngioma treatment and body mass index (BMI) greater than the 95th percentile for age and sex (mean 35.0) were compared with 15 control children matched for both age (mean 14.8 years) and BMI (32.9) who did not have a history of the tumor. There were 8 girls and 7 boys in the craniopharyngioma group, who had a mean Tanner Stage of 3, versus 10 girls and 5 boys in the control group, mean Tanner Stage 4. The two groups did not differ with regard to family history of type 2 diabetes, parental obesity, or in utero exposure to diabetes.

Oral glucose tolerance tests demonstrated significantly higher 2-hour glucose values among the craniopharyngioma children, compared with the controls (137 mg/dL vs. 115.3 mg/dL [7.6 mmol/L vs. 6.4 mmol/L]), as well as significantly elevated insulin levels at 30 minutes and 2 hours. Forty percent of the craniopharyngioma group met diagnostic criteria for either impaired glucose tolerance or type 2 diabetes (previously undiagnosed), compared with none of the controls, Dr. Hamilton reported.

Two-thirds of the craniopharyngioma group versus just 20% of the controls—a significant difference—met pediatric-adapted criteria for the metabolic syndrome, mostly via elevated triglycerides, reduced HDL cholesterol, and impaired glucose tolerance.

Whole-body insulin sensitivity did not differ between the two groups, but the craniopharyngioma patients demonstrated significantly elevated first- and second-phase insulin secretion, she said.

The U.S. tuberculosis rate hit an all-time low in 2006, but the rate of decline has been slowing while drug-resistant cases continue to pose a threat, the Centers for Disease Control and Prevention said.

There were 13,767 TB cases reported in 2006, a rate of 4.6 per 100,000 population. That number represents a 3.2% decline from the 2005 rate, the lowest recorded since reporting began in 1953. However, the rate of decline has slowed in recent years: The average annual percentage decline in the TB incidence rate was 7.3% per year during 1993–2000, but the rate of decline dropped to just 3.8% per year during 2000–2006, the CDC said (MMWR 2007;56:245–50).

Foreign-born individuals and racial/ethnic minority populations continue to be disproportionately affected by TB in the United States. In 2006, the TB rate among individuals born outside the United States was 9.5 times that of those born in the country, while the rates among blacks, Asians, and Hispanics were 8.4, 21.2, and 7.6 times higher than among whites, respectively.

The proportion of TB cases among foreign-born individuals has increased each year since 1993. In 2006, 56% of those cases were from just five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease initially became infected while abroad. Thus, “if the global TB pandemic remains unmitigated, eliminating TB in the United States will be increasingly difficult,” the CDC said.

A total of 124 cases of multidrug-resistant TB (MDR TB) were reported in 2005, the most recent year for which complete data are available. The proportion of MDR TB cases—defined as resistance to at least two first-line therapies, isoniazid and rifampin—remained constant at 1.2% from 2004 to 2005. In 2005, foreign-born individuals accounted for 81.5% of the 124 MDR TB cases, the CDC said.

The number of extensively drug-resistant TB (XDR TB) cases didn't change substantially from 1993–1999 to 2000–2006, but the characteristics of cases shifted in parallel with the changing epidemiology of TB in general and of MDR TB in particular. During 1993–1999, 32 reported cases met the criteria for XDR TB (resistance to isoniazid and rifampin, and to any second-line fluoroquinolone and at least one injectable drug), compared with 17 during 2000–2006 (MMWR 2007;56:250–3).

As with the overall TB rates, the overall numbers declined while the proportion among foreign-born individuals rose, from 39% in the first period to 76% in the second. Other changes in XDR TB epidemiology included a decrease in the proportion of cases among HIV-infected individuals and an increase in the proportion of patients who are Asian, they said.

Effective treatment of MDR TB requires administration for 18–24 months of 4–6 drugs to which the infecting organism is susceptible, including multiple second-line drugs. Beginning in the 1980s, the use of second-line drugs increased substantially as physicians and TB control programs treated growing numbers of MDR TB cases. Increased use of these drugs resulted in MDR TB strains with extensive resistance to both first- and second-line drugs, the CDC said.

Progress has been made on several new drugs in the past year, with human testing currently being conducted with six agents in five different drug classes. The CDC's TB Trials Consortium, in collaboration with the Global Alliance for TB Drug Development, has completed two preliminary trials with moxifloxacin. Those studies are expected to lay the groundwork for a trial of a treatment-shortening regimen for TB. The consortium is also nearing completion of a trial of a 3-month rifapentine-based treatment for latent TB infection.

ELSEVIER GLOBAL MEDICAL NEWS

The U.S. tuberculosis rate hit an all-time low in 2006, but the rate of decline has been slowing while drug-resistant cases continue to pose a threat, the Centers for Disease Control and Prevention said.

There were 13,767 TB cases reported in 2006, a rate of 4.6 per 100,000 population. That number represents a 3.2% decline from the 2005 rate, the lowest recorded since reporting began in 1953. However, the rate of decline has slowed in recent years: The average annual percentage decline in the TB incidence rate was 7.3% per year during 1993–2000, but the rate of decline dropped to just 3.8% per year during 2000–2006, the CDC said (MMWR 2007;56:245–50).

Foreign-born individuals and racial/ethnic minority populations continue to be disproportionately affected by TB in the United States. In 2006, the TB rate among individuals born outside the United States was 9.5 times that of those born in the country, while the rates among blacks, Asians, and Hispanics were 8.4, 21.2, and 7.6 times higher than among whites, respectively.

The proportion of TB cases among foreign-born individuals has increased each year since 1993. In 2006, 56% of those cases were from just five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease initially became infected while abroad. Thus, “if the global TB pandemic remains unmitigated, eliminating TB in the United States will be increasingly difficult,” the CDC said.

A total of 124 cases of multidrug-resistant TB (MDR TB) were reported in 2005, the most recent year for which complete data are available. The proportion of MDR TB cases—defined as resistance to at least two first-line therapies, isoniazid and rifampin—remained constant at 1.2% from 2004 to 2005. In 2005, foreign-born individuals accounted for 81.5% of the 124 MDR TB cases, the CDC said.

The number of extensively drug-resistant TB (XDR TB) cases didn't change substantially from 1993–1999 to 2000–2006, but the characteristics of cases shifted in parallel with the changing epidemiology of TB in general and of MDR TB in particular. During 1993–1999, 32 reported cases met the criteria for XDR TB (resistance to isoniazid and rifampin, and to any second-line fluoroquinolone and at least one injectable drug), compared with 17 during 2000–2006 (MMWR 2007;56:250–3).

As with the overall TB rates, the overall numbers declined while the proportion among foreign-born individuals rose, from 39% in the first period to 76% in the second. Other changes in XDR TB epidemiology included a decrease in the proportion of cases among HIV-infected individuals and an increase in the proportion of patients who are Asian, they said.

Effective treatment of MDR TB requires administration for 18–24 months of 4–6 drugs to which the infecting organism is susceptible, including multiple second-line drugs. Beginning in the 1980s, the use of second-line drugs increased substantially as physicians and TB control programs treated growing numbers of MDR TB cases. Increased use of these drugs resulted in MDR TB strains with extensive resistance to both first- and second-line drugs, the CDC said.

Progress has been made on several new drugs in the past year, with human testing currently being conducted with six agents in five different drug classes. The CDC's TB Trials Consortium, in collaboration with the Global Alliance for TB Drug Development, has completed two preliminary trials with moxifloxacin. Those studies are expected to lay the groundwork for a trial of a treatment-shortening regimen for TB. The consortium is also nearing completion of a trial of a 3-month rifapentine-based treatment for latent TB infection.

ELSEVIER GLOBAL MEDICAL NEWS

The U.S. tuberculosis rate hit an all-time low in 2006, but the rate of decline has been slowing while drug-resistant cases continue to pose a threat, the Centers for Disease Control and Prevention said.

There were 13,767 TB cases reported in 2006, a rate of 4.6 per 100,000 population. That number represents a 3.2% decline from the 2005 rate, the lowest recorded since reporting began in 1953. However, the rate of decline has slowed in recent years: The average annual percentage decline in the TB incidence rate was 7.3% per year during 1993–2000, but the rate of decline dropped to just 3.8% per year during 2000–2006, the CDC said (MMWR 2007;56:245–50).

Foreign-born individuals and racial/ethnic minority populations continue to be disproportionately affected by TB in the United States. In 2006, the TB rate among individuals born outside the United States was 9.5 times that of those born in the country, while the rates among blacks, Asians, and Hispanics were 8.4, 21.2, and 7.6 times higher than among whites, respectively.

The proportion of TB cases among foreign-born individuals has increased each year since 1993. In 2006, 56% of those cases were from just five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease initially became infected while abroad. Thus, “if the global TB pandemic remains unmitigated, eliminating TB in the United States will be increasingly difficult,” the CDC said.

A total of 124 cases of multidrug-resistant TB (MDR TB) were reported in 2005, the most recent year for which complete data are available. The proportion of MDR TB cases—defined as resistance to at least two first-line therapies, isoniazid and rifampin—remained constant at 1.2% from 2004 to 2005. In 2005, foreign-born individuals accounted for 81.5% of the 124 MDR TB cases, the CDC said.

The number of extensively drug-resistant TB (XDR TB) cases didn't change substantially from 1993–1999 to 2000–2006, but the characteristics of cases shifted in parallel with the changing epidemiology of TB in general and of MDR TB in particular. During 1993–1999, 32 reported cases met the criteria for XDR TB (resistance to isoniazid and rifampin, and to any second-line fluoroquinolone and at least one injectable drug), compared with 17 during 2000–2006 (MMWR 2007;56:250–3).

As with the overall TB rates, the overall numbers declined while the proportion among foreign-born individuals rose, from 39% in the first period to 76% in the second. Other changes in XDR TB epidemiology included a decrease in the proportion of cases among HIV-infected individuals and an increase in the proportion of patients who are Asian, they said.

Effective treatment of MDR TB requires administration for 18–24 months of 4–6 drugs to which the infecting organism is susceptible, including multiple second-line drugs. Beginning in the 1980s, the use of second-line drugs increased substantially as physicians and TB control programs treated growing numbers of MDR TB cases. Increased use of these drugs resulted in MDR TB strains with extensive resistance to both first- and second-line drugs, the CDC said.

Progress has been made on several new drugs in the past year, with human testing currently being conducted with six agents in five different drug classes. The CDC's TB Trials Consortium, in collaboration with the Global Alliance for TB Drug Development, has completed two preliminary trials with moxifloxacin. Those studies are expected to lay the groundwork for a trial of a treatment-shortening regimen for TB. The consortium is also nearing completion of a trial of a 3-month rifapentine-based treatment for latent TB infection.

ELSEVIER GLOBAL MEDICAL NEWS

ATLANTA — The efficacy of Gardasil is becoming more apparent over time, Dr. Eliav Barr said at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

Merck is continuing to follow subjects post marketing, with nearly 3 years of data now available from three of the premarketing trials involving more than 18,000 young women. Among those are 2.4 years for the group that was naive to all four vaccine strains of human papillomavirus (6, 11, 16, and 18) at baseline, 2.9 years for another group that was naive to 14 HPV types, and 2.8 years for a combined group of uninfected and infected women at baseline, said Dr. Barr, program head of HPV Vaccines for Merck Research Laboratories, Blue Bell, Pa.

In the per-protocol investigation comprising only those naive to the vaccine HPV strains, efficacy of the vaccine against HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (AIS) is 99%, down from 100% at the time of licensure. The drop was the result of just one case of HPV 16/18-related CIN3 in a Gardasil recipient (versus 73 cases in the placebo group). An investigation into that one case determined that it was likely caused by contamination, Dr. Barr said.

Efficacy against HPV 16/18-related vulvar and vaginal intraepithelial neoplasia 2/3 remains at 100%, as it was at licensure. Efficacy against any grade of HPV 16/18-related CIN or AIS is now at 96%, compared with 95% at licensure. Efficacy continues to increase over time as more cases of HPV 16/18-related disease occur in placebo recipients. Against all vulvar and vaginal lesions, including warts, the vaccine has stayed 99% effective. It's possible that the few vaccine recipients who did develop lesions—6 CIN/AIS and 2 vulvar/vaginal lesions, compared with 148 and 189, respectively, among placebo recipients—were already infected at baseline, he noted.

In the combined group of those infected and uninfected at baseline, vaccine efficacy is now 41% against CIN 2/3 or AIS (versus 34% at licensure), 71% against vaginal or vulvar intraepithelial neoplasia 2/3 (69% at licensure), 54% against CIN of any grade (46% at licensure), and 78% against vulvar/vaginal lesions including warts, up from 70%.

Preliminary data also suggest cross-protection of the vaccine against lesions caused by nonvaccine strains of HPV.

ATLANTA — The efficacy of Gardasil is becoming more apparent over time, Dr. Eliav Barr said at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

Merck is continuing to follow subjects post marketing, with nearly 3 years of data now available from three of the premarketing trials involving more than 18,000 young women. Among those are 2.4 years for the group that was naive to all four vaccine strains of human papillomavirus (6, 11, 16, and 18) at baseline, 2.9 years for another group that was naive to 14 HPV types, and 2.8 years for a combined group of uninfected and infected women at baseline, said Dr. Barr, program head of HPV Vaccines for Merck Research Laboratories, Blue Bell, Pa.

In the per-protocol investigation comprising only those naive to the vaccine HPV strains, efficacy of the vaccine against HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (AIS) is 99%, down from 100% at the time of licensure. The drop was the result of just one case of HPV 16/18-related CIN3 in a Gardasil recipient (versus 73 cases in the placebo group). An investigation into that one case determined that it was likely caused by contamination, Dr. Barr said.

Efficacy against HPV 16/18-related vulvar and vaginal intraepithelial neoplasia 2/3 remains at 100%, as it was at licensure. Efficacy against any grade of HPV 16/18-related CIN or AIS is now at 96%, compared with 95% at licensure. Efficacy continues to increase over time as more cases of HPV 16/18-related disease occur in placebo recipients. Against all vulvar and vaginal lesions, including warts, the vaccine has stayed 99% effective. It's possible that the few vaccine recipients who did develop lesions—6 CIN/AIS and 2 vulvar/vaginal lesions, compared with 148 and 189, respectively, among placebo recipients—were already infected at baseline, he noted.

In the combined group of those infected and uninfected at baseline, vaccine efficacy is now 41% against CIN 2/3 or AIS (versus 34% at licensure), 71% against vaginal or vulvar intraepithelial neoplasia 2/3 (69% at licensure), 54% against CIN of any grade (46% at licensure), and 78% against vulvar/vaginal lesions including warts, up from 70%.

Preliminary data also suggest cross-protection of the vaccine against lesions caused by nonvaccine strains of HPV.

ATLANTA — The efficacy of Gardasil is becoming more apparent over time, Dr. Eliav Barr said at a meeting of the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

Merck is continuing to follow subjects post marketing, with nearly 3 years of data now available from three of the premarketing trials involving more than 18,000 young women. Among those are 2.4 years for the group that was naive to all four vaccine strains of human papillomavirus (6, 11, 16, and 18) at baseline, 2.9 years for another group that was naive to 14 HPV types, and 2.8 years for a combined group of uninfected and infected women at baseline, said Dr. Barr, program head of HPV Vaccines for Merck Research Laboratories, Blue Bell, Pa.

In the per-protocol investigation comprising only those naive to the vaccine HPV strains, efficacy of the vaccine against HPV 16/18-related cervical intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (AIS) is 99%, down from 100% at the time of licensure. The drop was the result of just one case of HPV 16/18-related CIN3 in a Gardasil recipient (versus 73 cases in the placebo group). An investigation into that one case determined that it was likely caused by contamination, Dr. Barr said.

Efficacy against HPV 16/18-related vulvar and vaginal intraepithelial neoplasia 2/3 remains at 100%, as it was at licensure. Efficacy against any grade of HPV 16/18-related CIN or AIS is now at 96%, compared with 95% at licensure. Efficacy continues to increase over time as more cases of HPV 16/18-related disease occur in placebo recipients. Against all vulvar and vaginal lesions, including warts, the vaccine has stayed 99% effective. It's possible that the few vaccine recipients who did develop lesions—6 CIN/AIS and 2 vulvar/vaginal lesions, compared with 148 and 189, respectively, among placebo recipients—were already infected at baseline, he noted.

In the combined group of those infected and uninfected at baseline, vaccine efficacy is now 41% against CIN 2/3 or AIS (versus 34% at licensure), 71% against vaginal or vulvar intraepithelial neoplasia 2/3 (69% at licensure), 54% against CIN of any grade (46% at licensure), and 78% against vulvar/vaginal lesions including warts, up from 70%.

Preliminary data also suggest cross-protection of the vaccine against lesions caused by nonvaccine strains of HPV.

ATLANTA — Injection site pain is the most frequently reported adverse event following receipt of the quadrivalent human papillomavirus vaccine, Dr. Lauri Markowitz said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Through January 2007, the passive Vaccine Adverse Event Reporting System (VAERS) has received a total of 542 reports associated with Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil), of which 5% were considered serious. No deaths were reported, said Dr. Markowitz of the CDC's National Center for HIV, STD, and TB Prevention.

A total of 2.1 million doses of Merck's HPV vaccine had been distributed through December 2006. The adverse event reporting rate, 25/100,000 doses, is slightly higher than that seen with other vaccines but “not unexpected for a new vaccine,” she noted.

Injection site pain was the most commonly reported adverse event (18%), followed by dizziness (11%), syncope (11%), fever (9%), and nausea (9%). More than 99% occurred in females, reflecting the population for whom the vaccine currently is recommended. Nearly half (47%) of those reporting adverse events were aged 13–18 years, and another 38% were aged 19–26 years. Only 7% were aged 9–12 years, 6% were over 26 years of age, and the rest were less than 9 years.

There were three reported cases of Guillain-Barré syndrome (GBS), two of whom had simultaneously received the meningococcal conjugate vaccine (Menactra) 9 and 13 days earlier. It was not known whether the third GBS case had received other vaccines at the same time. An association between Menactra and GBS has been reported, although it is not yet clear whether the relationship is causal (MMWR 2006;55:1120–4).

Facial palsy was also reported in three cases, all within 1 day of receiving Gardasil. Two of those individuals had received influenza vaccine—one live attenuated and one inactivated—at the same time. The background rate of facial palsy in the general population is 30/100,000 per year.

Physicians are encouraged to report all clinically significant adverse events in patients following receipt of vaccines to VAERS, online at www.vaers.hhs.gov

ATLANTA — Injection site pain is the most frequently reported adverse event following receipt of the quadrivalent human papillomavirus vaccine, Dr. Lauri Markowitz said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Through January 2007, the passive Vaccine Adverse Event Reporting System (VAERS) has received a total of 542 reports associated with Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil), of which 5% were considered serious. No deaths were reported, said Dr. Markowitz of the CDC's National Center for HIV, STD, and TB Prevention.

A total of 2.1 million doses of Merck's HPV vaccine had been distributed through December 2006. The adverse event reporting rate, 25/100,000 doses, is slightly higher than that seen with other vaccines but “not unexpected for a new vaccine,” she noted.

Injection site pain was the most commonly reported adverse event (18%), followed by dizziness (11%), syncope (11%), fever (9%), and nausea (9%). More than 99% occurred in females, reflecting the population for whom the vaccine currently is recommended. Nearly half (47%) of those reporting adverse events were aged 13–18 years, and another 38% were aged 19–26 years. Only 7% were aged 9–12 years, 6% were over 26 years of age, and the rest were less than 9 years.

There were three reported cases of Guillain-Barré syndrome (GBS), two of whom had simultaneously received the meningococcal conjugate vaccine (Menactra) 9 and 13 days earlier. It was not known whether the third GBS case had received other vaccines at the same time. An association between Menactra and GBS has been reported, although it is not yet clear whether the relationship is causal (MMWR 2006;55:1120–4).

Facial palsy was also reported in three cases, all within 1 day of receiving Gardasil. Two of those individuals had received influenza vaccine—one live attenuated and one inactivated—at the same time. The background rate of facial palsy in the general population is 30/100,000 per year.

Physicians are encouraged to report all clinically significant adverse events in patients following receipt of vaccines to VAERS, online at www.vaers.hhs.gov

ATLANTA — Injection site pain is the most frequently reported adverse event following receipt of the quadrivalent human papillomavirus vaccine, Dr. Lauri Markowitz said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Through January 2007, the passive Vaccine Adverse Event Reporting System (VAERS) has received a total of 542 reports associated with Merck's quadrivalent human papillomavirus (HPV) vaccine (Gardasil), of which 5% were considered serious. No deaths were reported, said Dr. Markowitz of the CDC's National Center for HIV, STD, and TB Prevention.

A total of 2.1 million doses of Merck's HPV vaccine had been distributed through December 2006. The adverse event reporting rate, 25/100,000 doses, is slightly higher than that seen with other vaccines but “not unexpected for a new vaccine,” she noted.

Injection site pain was the most commonly reported adverse event (18%), followed by dizziness (11%), syncope (11%), fever (9%), and nausea (9%). More than 99% occurred in females, reflecting the population for whom the vaccine currently is recommended. Nearly half (47%) of those reporting adverse events were aged 13–18 years, and another 38% were aged 19–26 years. Only 7% were aged 9–12 years, 6% were over 26 years of age, and the rest were less than 9 years.

There were three reported cases of Guillain-Barré syndrome (GBS), two of whom had simultaneously received the meningococcal conjugate vaccine (Menactra) 9 and 13 days earlier. It was not known whether the third GBS case had received other vaccines at the same time. An association between Menactra and GBS has been reported, although it is not yet clear whether the relationship is causal (MMWR 2006;55:1120–4).

Facial palsy was also reported in three cases, all within 1 day of receiving Gardasil. Two of those individuals had received influenza vaccine—one live attenuated and one inactivated—at the same time. The background rate of facial palsy in the general population is 30/100,000 per year.

Physicians are encouraged to report all clinically significant adverse events in patients following receipt of vaccines to VAERS, online at www.vaers.hhs.gov

ATLANTA — The investigational cervical cancer vaccine Cervarix remained 100% effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, who is vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98.1%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia(CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

The vaccine also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains associated with cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of all cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women over 25 years of age, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections do decrease with age, the risk of persistence actually increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0−, 1−, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women over 25 years of age is also ongoing, while trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

ATLANTA — The investigational cervical cancer vaccine Cervarix remained 100% effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, who is vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98.1%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia(CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

The vaccine also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains associated with cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of all cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women over 25 years of age, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections do decrease with age, the risk of persistence actually increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0−, 1−, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women over 25 years of age is also ongoing, while trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

ATLANTA — The investigational cervical cancer vaccine Cervarix remained 100% effective through 5.5 years in preventing cervical intraepithelial neoplasia lesions associated with human papillomavirus strains 16 and 18, Dr. Gary Dubin reported at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The finding comes from the second interim analysis of the long-term follow-up phase of GlaxoSmithKline's primary efficacy trial for its bivalent HPV 16/18 vaccine, in which 1,113 women aged 15–25 years were randomized to receive the vaccine or placebo.

Safety, immunogenicity, and efficacy were initially evaluated for up to 27 months (Lancet 2004;365:1757–65), and the first interim analysis of the long-term follow-up phase was performed in October 2005 (Lancet 2006;367:1247–55). The final analysis will come at the end of 2007, said Dr. Dubin, who is vice president and director of GSK's Clinical Development and Medical Affairs, Prophylactic Vaccines, North America.

At 63–64 months following receipt of the first vaccine dose, ELISA titers to HPV strains 16 and 18 were both 11 times higher in the vaccine recipients than in the placebo group. From the end of the initial (27-month) study phase through a mean follow-up of 5.5 years, 1 incident HPV 16/18 infection occurred in a vaccine recipient, compared with 43 infections among the controls, giving a vaccine efficacy of 98.1%. The infection in the one vaccine recipient did not persist at 6 and 12 months, however, whereas 19 controls had persistent infection at 6 months and 9 infections persisted at 12 months.

As had been found at the two previous analyses, no vaccine recipient had HPV 16/18-related cytology classified as atypical squamous cells of undetermined significance (ASCUS) or greater, or cervical intraepithelial neoplasia(CIN) lesions. In contrast, 24 controls had HPV 16/18-related ASCUS or higher and 5 had HPV 16/18 CIN lesions at 5.5 years. Cervarix is formulated with a special adjuvant that has been shown to induce a higher and more persistent immune response, compared with vaccines formulated with aluminum salts only (Vaccine 2006;24:5937–49).

The vaccine also showed evidence of cross-protection against HPV types 45 and 31, the third and fourth most common strains associated with cervical cancer worldwide. Efficacy against incident infection with HPV 45 was 88%, and against HPV-31, 54%. Worldwide, 2.9% of all cervical cancers are attributed to HPV 31, 6.7% to HPV 45, 17.2% to HPV 18, and 53.5% to HPV 16 (Int. J. Cancer 2004;111:278–85).

In a separate immunobridging study involving 666 women aged 15–55 years, HPV 16/18 antibody titers were of the same order of magnitude as those associated with protection in the efficacy study. There is a need for an HPV vaccine in women over 25 years of age, because new infections with HPV cancer types are estimated to occur in 5.3% of women aged 25–55 years. Moreover, although new infections do decrease with age, the risk of persistence actually increases with age. “Our target is that women over 25 years are not denied access to the GSK cervical cancer vaccine,” Dr. Dubin said.

A double-blind, randomized, controlled phase III efficacy trial involving 18,665 women aged 15–25 years in 14 countries is underway. The women received either GSK's HPV vaccine or the hepatitis A vaccine as a control on a 0−, 1−, 6-month vaccination schedule. The required number of events—HPV 16/18-associated CIN2 or higher lesions—were accrued in November 2006. Those data will be presented “in the near future.” A study of the vaccine's efficacy in 5,700 women over 25 years of age is also ongoing, while trials looking at coadministration with other routine adolescent vaccines, safety and immunogenicity in HIV-positive women, and other local registration trials in several countries are planned.

The U.S. tuberculosis rate hit an all-time low in 2006, but the rate of decline has been slowing while drug-resistant cases continue to pose a threat, the Centers for Disease Control and Prevention said.

In 2006, 13,767 TB cases were reported, a rate of 4.6 per 100,000 population. That represents a 3.2% decline from the 2005 rate, the lowest recorded since reporting began in 1953. However, the rate of decline has slowed in recent years: The average annual percentage decline in the TB incidence rate was 7.3% a year during 1993–2000, but the rate of decline dropped to just 3.8% a year during 2000–2006, the CDC said (MMWR 2007;56:245–50).

Foreign-born individuals and racial/ethnic minority populations remain disproportionately affected by TB in the United States. In 2006, the TB rate in individuals born outside the United States was 9.5 times that of those born in the country; rates in blacks, Asians, and Hispanics were 8.4, 21.2, and 7.6 times higher than in whites, respectively.

The proportion of TB cases among foreign-born individuals has increased each year since 1993. In 2006, 56% of those cases were from just five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease initially became infected while abroad. Thus, “if the global TB pandemic remains unmitigated, eliminating TB in the United States will be increasingly difficult,” the CDC said.

A total of 124 cases of multidrug-resistant TB (MDR TB) were reported in 2005, the most recent year for which complete drug susceptibility data are available. The proportion of MDR TB cases—defined as resistance to at least two first-line therapies, isoniazid and rifampin—remained constant at 1.2% from 2004 to 2005. In 2005, foreign-born individuals accounted for 81.5% of the 124 MDR TB cases, the CDC said.

The number of extensively drug-resistant TB (XDR TB) cases didn't change substantially from 1993–1999 to 2000–2006, but the characteristics of cases shifted in parallel with the changing epidemiology of TB in general and of MDR TB in particular. During 1993–1999, 32 reported cases met the criteria for XDR TB (resistance to isoniazid and rifampin, and to any second-line fluoroquinolone and at least one injectable drug), compared with 17 during 2000–2006 (MMWR 2007;56:250–3).

As with the overall TB rates, the overall numbers declined while the proportion among foreign-born individuals rose, from 39% in the first period to 76% in the second. Other changes in XDR TB epidemiology included a decrease in the proportion of cases among HIV-infected individuals and an increase in the proportion of patients who are Asian, they said.

Effective treatment of MDR TB requires administration for 18–24 months of 4–6 drugs to which the infecting organism is susceptible, including multiple second-line drugs. Beginning in the 1980s, the use of second-line drugs increased substantially as physicians and TB control programs treated growing numbers of MDR TB cases. Increased use of these drugs resulted in MDR TB strains with extensive resistance to both first- and second-line drugs, the CDC said.

Some progress has been made on new drugs in the past year, with human testing currently being conducted with six agents in five different drug classes. The CDC's TB Trials Consortium, in collaboration with the Global Alliance for TB Drug Development, has completed two preliminary trials with moxifloxacin. Those studies are expected to lay the groundwork for a trial of a treatment-shortening regimen for TB. The consortium is also nearing completion of a trial of a 3-month rifapentine-based treatment for latent TB infection.

ELSEVIER GLOBAL MEDICAL NEWS

The U.S. tuberculosis rate hit an all-time low in 2006, but the rate of decline has been slowing while drug-resistant cases continue to pose a threat, the Centers for Disease Control and Prevention said.

In 2006, 13,767 TB cases were reported, a rate of 4.6 per 100,000 population. That represents a 3.2% decline from the 2005 rate, the lowest recorded since reporting began in 1953. However, the rate of decline has slowed in recent years: The average annual percentage decline in the TB incidence rate was 7.3% a year during 1993–2000, but the rate of decline dropped to just 3.8% a year during 2000–2006, the CDC said (MMWR 2007;56:245–50).

Foreign-born individuals and racial/ethnic minority populations remain disproportionately affected by TB in the United States. In 2006, the TB rate in individuals born outside the United States was 9.5 times that of those born in the country; rates in blacks, Asians, and Hispanics were 8.4, 21.2, and 7.6 times higher than in whites, respectively.

The proportion of TB cases among foreign-born individuals has increased each year since 1993. In 2006, 56% of those cases were from just five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease initially became infected while abroad. Thus, “if the global TB pandemic remains unmitigated, eliminating TB in the United States will be increasingly difficult,” the CDC said.

A total of 124 cases of multidrug-resistant TB (MDR TB) were reported in 2005, the most recent year for which complete drug susceptibility data are available. The proportion of MDR TB cases—defined as resistance to at least two first-line therapies, isoniazid and rifampin—remained constant at 1.2% from 2004 to 2005. In 2005, foreign-born individuals accounted for 81.5% of the 124 MDR TB cases, the CDC said.

The number of extensively drug-resistant TB (XDR TB) cases didn't change substantially from 1993–1999 to 2000–2006, but the characteristics of cases shifted in parallel with the changing epidemiology of TB in general and of MDR TB in particular. During 1993–1999, 32 reported cases met the criteria for XDR TB (resistance to isoniazid and rifampin, and to any second-line fluoroquinolone and at least one injectable drug), compared with 17 during 2000–2006 (MMWR 2007;56:250–3).

As with the overall TB rates, the overall numbers declined while the proportion among foreign-born individuals rose, from 39% in the first period to 76% in the second. Other changes in XDR TB epidemiology included a decrease in the proportion of cases among HIV-infected individuals and an increase in the proportion of patients who are Asian, they said.

Effective treatment of MDR TB requires administration for 18–24 months of 4–6 drugs to which the infecting organism is susceptible, including multiple second-line drugs. Beginning in the 1980s, the use of second-line drugs increased substantially as physicians and TB control programs treated growing numbers of MDR TB cases. Increased use of these drugs resulted in MDR TB strains with extensive resistance to both first- and second-line drugs, the CDC said.

Some progress has been made on new drugs in the past year, with human testing currently being conducted with six agents in five different drug classes. The CDC's TB Trials Consortium, in collaboration with the Global Alliance for TB Drug Development, has completed two preliminary trials with moxifloxacin. Those studies are expected to lay the groundwork for a trial of a treatment-shortening regimen for TB. The consortium is also nearing completion of a trial of a 3-month rifapentine-based treatment for latent TB infection.

ELSEVIER GLOBAL MEDICAL NEWS

The U.S. tuberculosis rate hit an all-time low in 2006, but the rate of decline has been slowing while drug-resistant cases continue to pose a threat, the Centers for Disease Control and Prevention said.

In 2006, 13,767 TB cases were reported, a rate of 4.6 per 100,000 population. That represents a 3.2% decline from the 2005 rate, the lowest recorded since reporting began in 1953. However, the rate of decline has slowed in recent years: The average annual percentage decline in the TB incidence rate was 7.3% a year during 1993–2000, but the rate of decline dropped to just 3.8% a year during 2000–2006, the CDC said (MMWR 2007;56:245–50).

Foreign-born individuals and racial/ethnic minority populations remain disproportionately affected by TB in the United States. In 2006, the TB rate in individuals born outside the United States was 9.5 times that of those born in the country; rates in blacks, Asians, and Hispanics were 8.4, 21.2, and 7.6 times higher than in whites, respectively.

The proportion of TB cases among foreign-born individuals has increased each year since 1993. In 2006, 56% of those cases were from just five countries: Mexico, the Philippines, Vietnam, India, and China. Most of the foreign-born individuals in the United States who progress from latent TB infection to TB disease initially became infected while abroad. Thus, “if the global TB pandemic remains unmitigated, eliminating TB in the United States will be increasingly difficult,” the CDC said.

A total of 124 cases of multidrug-resistant TB (MDR TB) were reported in 2005, the most recent year for which complete drug susceptibility data are available. The proportion of MDR TB cases—defined as resistance to at least two first-line therapies, isoniazid and rifampin—remained constant at 1.2% from 2004 to 2005. In 2005, foreign-born individuals accounted for 81.5% of the 124 MDR TB cases, the CDC said.

The number of extensively drug-resistant TB (XDR TB) cases didn't change substantially from 1993–1999 to 2000–2006, but the characteristics of cases shifted in parallel with the changing epidemiology of TB in general and of MDR TB in particular. During 1993–1999, 32 reported cases met the criteria for XDR TB (resistance to isoniazid and rifampin, and to any second-line fluoroquinolone and at least one injectable drug), compared with 17 during 2000–2006 (MMWR 2007;56:250–3).

As with the overall TB rates, the overall numbers declined while the proportion among foreign-born individuals rose, from 39% in the first period to 76% in the second. Other changes in XDR TB epidemiology included a decrease in the proportion of cases among HIV-infected individuals and an increase in the proportion of patients who are Asian, they said.

Effective treatment of MDR TB requires administration for 18–24 months of 4–6 drugs to which the infecting organism is susceptible, including multiple second-line drugs. Beginning in the 1980s, the use of second-line drugs increased substantially as physicians and TB control programs treated growing numbers of MDR TB cases. Increased use of these drugs resulted in MDR TB strains with extensive resistance to both first- and second-line drugs, the CDC said.

Some progress has been made on new drugs in the past year, with human testing currently being conducted with six agents in five different drug classes. The CDC's TB Trials Consortium, in collaboration with the Global Alliance for TB Drug Development, has completed two preliminary trials with moxifloxacin. Those studies are expected to lay the groundwork for a trial of a treatment-shortening regimen for TB. The consortium is also nearing completion of a trial of a 3-month rifapentine-based treatment for latent TB infection.

ELSEVIER GLOBAL MEDICAL NEWS