Miriam E. Tucker

ATLANTA — Pertussis in adolescents is an increasingly reported problem across the United States, Margaret M. Cortese, M.D., said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Preliminary data for 2004 include 8,000 cases reported in adolescents, with large numbers in Wisconsin, upstate New York, Colorado, and Massachusetts. More than 100 cases were reported in adolescents in each of 16 states, while 14 states reported more than 500 cases each in persons of all ages. Moreover, although reporting rates have increased, “these numbers are likely only a portion of the true burden,” said Dr. Cortese, a medical officer with the CDC's National Immunization Program.

Her presentation was among the discussion points during a 4-hour session at the Advisory Committee for Immunization Practices (ACIP) meeting devoted to issues surrounding the pertussis disease burden and to the anticipated licensure of two new reduced-antigen tetanus-diphtheria-acellular pertussis (Tdap) vaccines formulated for use in adolescents.

Both candidate vaccines—Sanofi-Pasteur's Adacel and GlaxoSmithKline's Boostrix—will be reviewed this month by the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee, and ACIP is expected to issue recommendations later this year for their use as adolescent boosters.

In Massachusetts—which is the only state that conducts active surveillance for pertussis using a standardized serologic test for diagnosis—there were 1,088 cases of pertussis among adolescents in 2003, compared with 374 in 2002, 331 in 2001, and 869 in 2000. Of those cases, between 45% and 50% were involved in school outbreaks, Dr. Cortese reported.

Because Massachusetts has such an aggressive surveillance and reporting system for pertussis, their rates are typically about 20 times higher than the reported rates of any other state and “probably give a true indication of the rest of the country,” she noted.

Previously published data have documented significant morbidity and high costs associated with pertussis in adolescents. Among 314 children aged 10–17 years identified in Massachusetts, paroxysmal cough was reported in 74%, difficulty sleeping in 77%, difficulty breathing in 72%, post-tussive vomiting in 56%, and weight loss in 33%. A total of 38% were still coughing at the last interview, done a mean 3.4 months following the initial diagnosis (Clin. Infect. Dis. 2004;39:1572–80).

Those 314 were a subset of a larger group of 1,679 adolescents in whom various cost parameters were assessed. The teenagers made a median of two office visits, and 83% reported missing a mean 5.5 school days, while 43% of their parents/caretakers missed a mean 2.4 days of work. Average medical cost (including office visits, chest x-rays, and antibiotics) per case was $256, and average nonmedical cost (mostly in missed work) was $160.

These estimates don't include the costs of prophylactic antibiotics for contacts or the public health response, Dr. Cortese noted.

ATLANTA — Pertussis in adolescents is an increasingly reported problem across the United States, Margaret M. Cortese, M.D., said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Preliminary data for 2004 include 8,000 cases reported in adolescents, with large numbers in Wisconsin, upstate New York, Colorado, and Massachusetts. More than 100 cases were reported in adolescents in each of 16 states, while 14 states reported more than 500 cases each in persons of all ages. Moreover, although reporting rates have increased, “these numbers are likely only a portion of the true burden,” said Dr. Cortese, a medical officer with the CDC's National Immunization Program.

Her presentation was among the discussion points during a 4-hour session at the Advisory Committee for Immunization Practices (ACIP) meeting devoted to issues surrounding the pertussis disease burden and to the anticipated licensure of two new reduced-antigen tetanus-diphtheria-acellular pertussis (Tdap) vaccines formulated for use in adolescents.

Both candidate vaccines—Sanofi-Pasteur's Adacel and GlaxoSmithKline's Boostrix—will be reviewed this month by the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee, and ACIP is expected to issue recommendations later this year for their use as adolescent boosters.

In Massachusetts—which is the only state that conducts active surveillance for pertussis using a standardized serologic test for diagnosis—there were 1,088 cases of pertussis among adolescents in 2003, compared with 374 in 2002, 331 in 2001, and 869 in 2000. Of those cases, between 45% and 50% were involved in school outbreaks, Dr. Cortese reported.

Because Massachusetts has such an aggressive surveillance and reporting system for pertussis, their rates are typically about 20 times higher than the reported rates of any other state and “probably give a true indication of the rest of the country,” she noted.

Previously published data have documented significant morbidity and high costs associated with pertussis in adolescents. Among 314 children aged 10–17 years identified in Massachusetts, paroxysmal cough was reported in 74%, difficulty sleeping in 77%, difficulty breathing in 72%, post-tussive vomiting in 56%, and weight loss in 33%. A total of 38% were still coughing at the last interview, done a mean 3.4 months following the initial diagnosis (Clin. Infect. Dis. 2004;39:1572–80).

Those 314 were a subset of a larger group of 1,679 adolescents in whom various cost parameters were assessed. The teenagers made a median of two office visits, and 83% reported missing a mean 5.5 school days, while 43% of their parents/caretakers missed a mean 2.4 days of work. Average medical cost (including office visits, chest x-rays, and antibiotics) per case was $256, and average nonmedical cost (mostly in missed work) was $160.

These estimates don't include the costs of prophylactic antibiotics for contacts or the public health response, Dr. Cortese noted.

ATLANTA — Pertussis in adolescents is an increasingly reported problem across the United States, Margaret M. Cortese, M.D., said at a meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

Preliminary data for 2004 include 8,000 cases reported in adolescents, with large numbers in Wisconsin, upstate New York, Colorado, and Massachusetts. More than 100 cases were reported in adolescents in each of 16 states, while 14 states reported more than 500 cases each in persons of all ages. Moreover, although reporting rates have increased, “these numbers are likely only a portion of the true burden,” said Dr. Cortese, a medical officer with the CDC's National Immunization Program.

Her presentation was among the discussion points during a 4-hour session at the Advisory Committee for Immunization Practices (ACIP) meeting devoted to issues surrounding the pertussis disease burden and to the anticipated licensure of two new reduced-antigen tetanus-diphtheria-acellular pertussis (Tdap) vaccines formulated for use in adolescents.

Both candidate vaccines—Sanofi-Pasteur's Adacel and GlaxoSmithKline's Boostrix—will be reviewed this month by the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee, and ACIP is expected to issue recommendations later this year for their use as adolescent boosters.

In Massachusetts—which is the only state that conducts active surveillance for pertussis using a standardized serologic test for diagnosis—there were 1,088 cases of pertussis among adolescents in 2003, compared with 374 in 2002, 331 in 2001, and 869 in 2000. Of those cases, between 45% and 50% were involved in school outbreaks, Dr. Cortese reported.

Because Massachusetts has such an aggressive surveillance and reporting system for pertussis, their rates are typically about 20 times higher than the reported rates of any other state and “probably give a true indication of the rest of the country,” she noted.

Previously published data have documented significant morbidity and high costs associated with pertussis in adolescents. Among 314 children aged 10–17 years identified in Massachusetts, paroxysmal cough was reported in 74%, difficulty sleeping in 77%, difficulty breathing in 72%, post-tussive vomiting in 56%, and weight loss in 33%. A total of 38% were still coughing at the last interview, done a mean 3.4 months following the initial diagnosis (Clin. Infect. Dis. 2004;39:1572–80).

Those 314 were a subset of a larger group of 1,679 adolescents in whom various cost parameters were assessed. The teenagers made a median of two office visits, and 83% reported missing a mean 5.5 school days, while 43% of their parents/caretakers missed a mean 2.4 days of work. Average medical cost (including office visits, chest x-rays, and antibiotics) per case was $256, and average nonmedical cost (mostly in missed work) was $160.

These estimates don't include the costs of prophylactic antibiotics for contacts or the public health response, Dr. Cortese noted.

WASHINGTON — Methicillin-resistant Staphylococcus aureus has been transmitted via breast milk, Dawn Terashita Gastelum, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The two reported cases, which resulted in MRSA outbreaks in neonatal intensive care units at two Los Angeles hospitals, suggest that hospital NICUs should consider screening mothers and family members for skin lesions at the time of delivery and obtaining breast milk cultures before infant feedings, said Dr. Terashita Gastelum of the Los Angeles County Department of Health Services.

The first case was in a premature (1,180 g at birth) quadruplet born to an Algerian mother who developed mastitis the day after delivery and was treated with dicloxacillin. Her breast milk was collected 3 days later and fed to the quadruplets. Twelve days after that, the baby girl died of MRSA sepsis.

The bacterium subsequently was found in nasopharyngeal cultures of the mother and her three surviving infants, another infant in the NICU, and the mother's frozen postpartum breast milk samples. Molecular fingerprinting was identical for the four infants and the breast milk, but the mother's nasopharyngeal isolate was different.

“Since the mother was actually colonized by a different strain, it is unlikely that the infants obtained the MRSA during birth or through skin-to-skin contact with the mother. The breast milk is the only known source,” Dr. Terashita Gastelum said.

And, though it is possible to be colonized with two different strains of MRSA, it's rare. On the other hand, “it is easy to imagine that the macerated skin of the nipple on a postpartum woman is more susceptible to infection from any organism,” she said at the conference, sponsored by the American Society for Microbiology.

The second case was an 1,199-g male infant who was fed breast milk the day of birth and developed MRSA sepsis 8 days later. The mother had no sign of mastitis, but MRSA was cultured from her breast milk collected on the day of delivery. Four other infants from the NICU were also positive: two colonized and two infected.

WASHINGTON — Methicillin-resistant Staphylococcus aureus has been transmitted via breast milk, Dawn Terashita Gastelum, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The two reported cases, which resulted in MRSA outbreaks in neonatal intensive care units at two Los Angeles hospitals, suggest that hospital NICUs should consider screening mothers and family members for skin lesions at the time of delivery and obtaining breast milk cultures before infant feedings, said Dr. Terashita Gastelum of the Los Angeles County Department of Health Services.

The first case was in a premature (1,180 g at birth) quadruplet born to an Algerian mother who developed mastitis the day after delivery and was treated with dicloxacillin. Her breast milk was collected 3 days later and fed to the quadruplets. Twelve days after that, the baby girl died of MRSA sepsis.

The bacterium subsequently was found in nasopharyngeal cultures of the mother and her three surviving infants, another infant in the NICU, and the mother's frozen postpartum breast milk samples. Molecular fingerprinting was identical for the four infants and the breast milk, but the mother's nasopharyngeal isolate was different.

“Since the mother was actually colonized by a different strain, it is unlikely that the infants obtained the MRSA during birth or through skin-to-skin contact with the mother. The breast milk is the only known source,” Dr. Terashita Gastelum said.

And, though it is possible to be colonized with two different strains of MRSA, it's rare. On the other hand, “it is easy to imagine that the macerated skin of the nipple on a postpartum woman is more susceptible to infection from any organism,” she said at the conference, sponsored by the American Society for Microbiology.

The second case was an 1,199-g male infant who was fed breast milk the day of birth and developed MRSA sepsis 8 days later. The mother had no sign of mastitis, but MRSA was cultured from her breast milk collected on the day of delivery. Four other infants from the NICU were also positive: two colonized and two infected.

WASHINGTON — Methicillin-resistant Staphylococcus aureus has been transmitted via breast milk, Dawn Terashita Gastelum, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The two reported cases, which resulted in MRSA outbreaks in neonatal intensive care units at two Los Angeles hospitals, suggest that hospital NICUs should consider screening mothers and family members for skin lesions at the time of delivery and obtaining breast milk cultures before infant feedings, said Dr. Terashita Gastelum of the Los Angeles County Department of Health Services.

The first case was in a premature (1,180 g at birth) quadruplet born to an Algerian mother who developed mastitis the day after delivery and was treated with dicloxacillin. Her breast milk was collected 3 days later and fed to the quadruplets. Twelve days after that, the baby girl died of MRSA sepsis.

The bacterium subsequently was found in nasopharyngeal cultures of the mother and her three surviving infants, another infant in the NICU, and the mother's frozen postpartum breast milk samples. Molecular fingerprinting was identical for the four infants and the breast milk, but the mother's nasopharyngeal isolate was different.

“Since the mother was actually colonized by a different strain, it is unlikely that the infants obtained the MRSA during birth or through skin-to-skin contact with the mother. The breast milk is the only known source,” Dr. Terashita Gastelum said.

And, though it is possible to be colonized with two different strains of MRSA, it's rare. On the other hand, “it is easy to imagine that the macerated skin of the nipple on a postpartum woman is more susceptible to infection from any organism,” she said at the conference, sponsored by the American Society for Microbiology.

The second case was an 1,199-g male infant who was fed breast milk the day of birth and developed MRSA sepsis 8 days later. The mother had no sign of mastitis, but MRSA was cultured from her breast milk collected on the day of delivery. Four other infants from the NICU were also positive: two colonized and two infected.

Three recent hospital pertussis outbreaks and one infant death from the disease strongly point to the need for improved recognition and protection against transmission, the Centers for Disease Control and Prevention said.

The cases, from four states, also illustrate the potential benefit of vaccination against Bordetella pertussis in adolescents and adults, because immunity from infant immunization wanes after a decade. No vaccine is currently licensed for persons aged 7 years and above, but two manufacturers have filed for licensure with the Food and Drug Administration for vaccines that combine acellular pertussis, tetanus toxoid, and tetanus toxoid antigens. One would be indicated for persons aged 10-18 years, the other for ages 11-64 years.

All three hospital outbreaks, which occurred in August and September of 2003, involved hospitalized infants with cough illness. In Pennsylvania, a 3-week-old infant was hospitalized with cough, posttussive vomiting, and fever. Pertussis was considered unlikely, the infant wasn't tested for it, and hospital staff did not observe droplet precautions.

The infant was transferred to a referral hospital after 1 day, nasopharyngeal secretions were obtained, and B. pertussis was isolated 16 days later (MMWR 2005;54:67-71).

Meanwhile, the pediatrician who had cared for the infant at the first hospital developed a cough 9 days after exposure. Despite remaining symptomatic, he continued to treat patients—and to have contact with coworkers, family, and friends—without wearing a mask. His nasopharyngeal secretions tested positive 22 days after the initial exposure, while a total of 16 other health care workers and two pediatric patients at the initial hospital developed cough illness and/or tested positive for pertussis.

Hospital infection control personnel subsequently screened exposed employees, treated all who were symptomatic with a 5-day course of azithromycin, and excluded them from work for 5 days. Another 307 close contacts of the symptomatic health care workers were given azithromycin prophylactically, the CDC reported.

The other two outbreaks, in Kentucky and Oregon, also involved acutely ill infants with cough illness, exposed health care workers, and potential transmission to a large number of contacts who subsequently received azithromycin as either treatment or prophylaxis.

All three cases illustrated the difficulties in the diagnosis of pertussis, particularly in older individuals in whom the symptoms during the catarrhal stage are usually nonspecific while the disease is already highly communicable. In infants, diagnosis may be delayed when the presentation is respiratory distress with apnea but without the typical cough.

Also problematic is the lack of adequate diagnostic tests for pertussis. Culture is not sensitive beyond 3 weeks of illness or after antibiotic therapy, polymerase chain reaction for pertussis is not standardized, and no serologic test is available, although the CDC and the FDA are developing one.

A second MMWR report illustrates the fact that incompletely immunized children aged less than 6 months continue to be the most vulnerable to pertussis when the disease is circulating around them (MMWR 2005;54:71-2).

A 29-day-old West Virginia infant was brought to the emergency department with difficulty breathing. The infant's mother had had prolonged paroxysmal cough illness for 3 weeks before the infant's delivery; the father had onset of paroxysmal cough illness 2 weeks before the infant's illness.

The infant had been coughing for 5 days with increasing severity, resulting in posttussive vomiting and choking. At presentation, she was lethargic, tachycardic, and had a mild fever. Laboratory results indicated leukocytosis. Chest x-ray revealed pneumonia, and she developed respiratory failure. She died approximately 30 hours after admission to the pediatric intensive care unit, despite azithromycin treatment for presumed B. pertussis, high-frequency ventilation, nitric oxide administration, and a double-volume exchange transfusion.

The diagnosis of pertussis was based on history, clinical findings, and a positive polymerase chain reaction test. Around the time of the infant's death, two cousins, her paternal grandmother, and a great-grandmother all had cough illness as well.

Caring for Infected Health Workers

Clinical Findings:

▸Incubation period: 7-10 days (range: 4-21 days).

▸Catarrhal stage: 1-2 weeks; coryza, low-grade fever, and mild cough.

▸Paroxysmal stage: 1-6 weeks; paroxysmal cough, posttussive vomiting, and inspiratory “whoop.”

▸Convalescent stage: at least 3 weeks; cough lessens and disappears.

Treatment/Prophylaxis:

▸Macrolides (erythromycin, azithromycin, or clarithromycin) are preferred.

▸Trimethoprim-sulfamethoxazole is an alternative antibiotic for use in persons with allergy or intolerance to macrolides.

Source: Centers for Disease Control and Prevention

Three recent hospital pertussis outbreaks and one infant death from the disease strongly point to the need for improved recognition and protection against transmission, the Centers for Disease Control and Prevention said.

The cases, from four states, also illustrate the potential benefit of vaccination against Bordetella pertussis in adolescents and adults, because immunity from infant immunization wanes after a decade. No vaccine is currently licensed for persons aged 7 years and above, but two manufacturers have filed for licensure with the Food and Drug Administration for vaccines that combine acellular pertussis, tetanus toxoid, and tetanus toxoid antigens. One would be indicated for persons aged 10-18 years, the other for ages 11-64 years.

All three hospital outbreaks, which occurred in August and September of 2003, involved hospitalized infants with cough illness. In Pennsylvania, a 3-week-old infant was hospitalized with cough, posttussive vomiting, and fever. Pertussis was considered unlikely, the infant wasn't tested for it, and hospital staff did not observe droplet precautions.

The infant was transferred to a referral hospital after 1 day, nasopharyngeal secretions were obtained, and B. pertussis was isolated 16 days later (MMWR 2005;54:67-71).

Meanwhile, the pediatrician who had cared for the infant at the first hospital developed a cough 9 days after exposure. Despite remaining symptomatic, he continued to treat patients—and to have contact with coworkers, family, and friends—without wearing a mask. His nasopharyngeal secretions tested positive 22 days after the initial exposure, while a total of 16 other health care workers and two pediatric patients at the initial hospital developed cough illness and/or tested positive for pertussis.

Hospital infection control personnel subsequently screened exposed employees, treated all who were symptomatic with a 5-day course of azithromycin, and excluded them from work for 5 days. Another 307 close contacts of the symptomatic health care workers were given azithromycin prophylactically, the CDC reported.

The other two outbreaks, in Kentucky and Oregon, also involved acutely ill infants with cough illness, exposed health care workers, and potential transmission to a large number of contacts who subsequently received azithromycin as either treatment or prophylaxis.

All three cases illustrated the difficulties in the diagnosis of pertussis, particularly in older individuals in whom the symptoms during the catarrhal stage are usually nonspecific while the disease is already highly communicable. In infants, diagnosis may be delayed when the presentation is respiratory distress with apnea but without the typical cough.

Also problematic is the lack of adequate diagnostic tests for pertussis. Culture is not sensitive beyond 3 weeks of illness or after antibiotic therapy, polymerase chain reaction for pertussis is not standardized, and no serologic test is available, although the CDC and the FDA are developing one.

A second MMWR report illustrates the fact that incompletely immunized children aged less than 6 months continue to be the most vulnerable to pertussis when the disease is circulating around them (MMWR 2005;54:71-2).

A 29-day-old West Virginia infant was brought to the emergency department with difficulty breathing. The infant's mother had had prolonged paroxysmal cough illness for 3 weeks before the infant's delivery; the father had onset of paroxysmal cough illness 2 weeks before the infant's illness.

The infant had been coughing for 5 days with increasing severity, resulting in posttussive vomiting and choking. At presentation, she was lethargic, tachycardic, and had a mild fever. Laboratory results indicated leukocytosis. Chest x-ray revealed pneumonia, and she developed respiratory failure. She died approximately 30 hours after admission to the pediatric intensive care unit, despite azithromycin treatment for presumed B. pertussis, high-frequency ventilation, nitric oxide administration, and a double-volume exchange transfusion.

The diagnosis of pertussis was based on history, clinical findings, and a positive polymerase chain reaction test. Around the time of the infant's death, two cousins, her paternal grandmother, and a great-grandmother all had cough illness as well.

Caring for Infected Health Workers

Clinical Findings:

▸Incubation period: 7-10 days (range: 4-21 days).

▸Catarrhal stage: 1-2 weeks; coryza, low-grade fever, and mild cough.

▸Paroxysmal stage: 1-6 weeks; paroxysmal cough, posttussive vomiting, and inspiratory “whoop.”

▸Convalescent stage: at least 3 weeks; cough lessens and disappears.

Treatment/Prophylaxis:

▸Macrolides (erythromycin, azithromycin, or clarithromycin) are preferred.

▸Trimethoprim-sulfamethoxazole is an alternative antibiotic for use in persons with allergy or intolerance to macrolides.

Source: Centers for Disease Control and Prevention

Three recent hospital pertussis outbreaks and one infant death from the disease strongly point to the need for improved recognition and protection against transmission, the Centers for Disease Control and Prevention said.

The cases, from four states, also illustrate the potential benefit of vaccination against Bordetella pertussis in adolescents and adults, because immunity from infant immunization wanes after a decade. No vaccine is currently licensed for persons aged 7 years and above, but two manufacturers have filed for licensure with the Food and Drug Administration for vaccines that combine acellular pertussis, tetanus toxoid, and tetanus toxoid antigens. One would be indicated for persons aged 10-18 years, the other for ages 11-64 years.

All three hospital outbreaks, which occurred in August and September of 2003, involved hospitalized infants with cough illness. In Pennsylvania, a 3-week-old infant was hospitalized with cough, posttussive vomiting, and fever. Pertussis was considered unlikely, the infant wasn't tested for it, and hospital staff did not observe droplet precautions.

The infant was transferred to a referral hospital after 1 day, nasopharyngeal secretions were obtained, and B. pertussis was isolated 16 days later (MMWR 2005;54:67-71).

Meanwhile, the pediatrician who had cared for the infant at the first hospital developed a cough 9 days after exposure. Despite remaining symptomatic, he continued to treat patients—and to have contact with coworkers, family, and friends—without wearing a mask. His nasopharyngeal secretions tested positive 22 days after the initial exposure, while a total of 16 other health care workers and two pediatric patients at the initial hospital developed cough illness and/or tested positive for pertussis.

Hospital infection control personnel subsequently screened exposed employees, treated all who were symptomatic with a 5-day course of azithromycin, and excluded them from work for 5 days. Another 307 close contacts of the symptomatic health care workers were given azithromycin prophylactically, the CDC reported.

The other two outbreaks, in Kentucky and Oregon, also involved acutely ill infants with cough illness, exposed health care workers, and potential transmission to a large number of contacts who subsequently received azithromycin as either treatment or prophylaxis.

All three cases illustrated the difficulties in the diagnosis of pertussis, particularly in older individuals in whom the symptoms during the catarrhal stage are usually nonspecific while the disease is already highly communicable. In infants, diagnosis may be delayed when the presentation is respiratory distress with apnea but without the typical cough.

Also problematic is the lack of adequate diagnostic tests for pertussis. Culture is not sensitive beyond 3 weeks of illness or after antibiotic therapy, polymerase chain reaction for pertussis is not standardized, and no serologic test is available, although the CDC and the FDA are developing one.

A second MMWR report illustrates the fact that incompletely immunized children aged less than 6 months continue to be the most vulnerable to pertussis when the disease is circulating around them (MMWR 2005;54:71-2).

A 29-day-old West Virginia infant was brought to the emergency department with difficulty breathing. The infant's mother had had prolonged paroxysmal cough illness for 3 weeks before the infant's delivery; the father had onset of paroxysmal cough illness 2 weeks before the infant's illness.

The infant had been coughing for 5 days with increasing severity, resulting in posttussive vomiting and choking. At presentation, she was lethargic, tachycardic, and had a mild fever. Laboratory results indicated leukocytosis. Chest x-ray revealed pneumonia, and she developed respiratory failure. She died approximately 30 hours after admission to the pediatric intensive care unit, despite azithromycin treatment for presumed B. pertussis, high-frequency ventilation, nitric oxide administration, and a double-volume exchange transfusion.

The diagnosis of pertussis was based on history, clinical findings, and a positive polymerase chain reaction test. Around the time of the infant's death, two cousins, her paternal grandmother, and a great-grandmother all had cough illness as well.

Caring for Infected Health Workers

Clinical Findings:

▸Incubation period: 7-10 days (range: 4-21 days).

▸Catarrhal stage: 1-2 weeks; coryza, low-grade fever, and mild cough.

▸Paroxysmal stage: 1-6 weeks; paroxysmal cough, posttussive vomiting, and inspiratory “whoop.”

▸Convalescent stage: at least 3 weeks; cough lessens and disappears.

Treatment/Prophylaxis:

▸Macrolides (erythromycin, azithromycin, or clarithromycin) are preferred.

▸Trimethoprim-sulfamethoxazole is an alternative antibiotic for use in persons with allergy or intolerance to macrolides.

Source: Centers for Disease Control and Prevention

WASHINGTON — Metronidazole is effective in the treatment of non-β-hemolytic streptococcal tonsillitis, Itzhak Brook, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Although group A β-hemolytic streptococcus (GABHS) is one of the major causes of tonsillitis, other aerobic as well as anaerobic organisms have been isolated from both normal and inflamed tonsils. Some of these organisms are believed to be part of the normal flora, said Dr. Brook, professor of pediatrics at Georgetown University, Washington.

The option of using metronidazole (250 mg every 12 hours for 10 days) was offered to 40 children (mean age 9 years) who presented with sore throat and massive tonsillar enlargement plus at least one of the following: anterior cervical adenitis, temperature higher than 38.3° C, and pharyngeal or tonsillar exudates or pharyngeal injection.

Rapid streptococcal antigen tests were negative in all the patients, and cultures of the tonsils showed no growth of β-hemolytic streptococci, including group A. None of the children had Epstein-Barr antibodies on immunofluorescence.

The 20 who chose metronidazole were similar to the 20 who did not with respect to age, race, sex, family size, current clinical findings, and previous antibiotic use.

Compared with the children who remained untreated, those given metronidazole had significantly lower rates of fevers over 38° C after 1 day (11 vs. 17 children) and after 2 days (3 vs. 9 children), fewer sore throats after 1 day (12 vs. 19) and 2 days (9 vs. 16), and lower rates of tonsillar enlargement after 3 days (11 vs. 16) and 5 days (8 vs. 14). Pharyngeal injection at 2 days also was reduced with metronidazole, Dr. Brook reported at the conference, sponsored by the American Society for Microbiology.

One patient who received metronidazole complained of metallic taste, and three had dark urine.

Metronidazole was chosen for this study because it is effective against anaerobic bacteria, which are thought cause inflammation in the tonsils, but has virtually no activity against facultative and aerobic bacteria.

WASHINGTON — Metronidazole is effective in the treatment of non-β-hemolytic streptococcal tonsillitis, Itzhak Brook, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Although group A β-hemolytic streptococcus (GABHS) is one of the major causes of tonsillitis, other aerobic as well as anaerobic organisms have been isolated from both normal and inflamed tonsils. Some of these organisms are believed to be part of the normal flora, said Dr. Brook, professor of pediatrics at Georgetown University, Washington.

The option of using metronidazole (250 mg every 12 hours for 10 days) was offered to 40 children (mean age 9 years) who presented with sore throat and massive tonsillar enlargement plus at least one of the following: anterior cervical adenitis, temperature higher than 38.3° C, and pharyngeal or tonsillar exudates or pharyngeal injection.

Rapid streptococcal antigen tests were negative in all the patients, and cultures of the tonsils showed no growth of β-hemolytic streptococci, including group A. None of the children had Epstein-Barr antibodies on immunofluorescence.

The 20 who chose metronidazole were similar to the 20 who did not with respect to age, race, sex, family size, current clinical findings, and previous antibiotic use.

Compared with the children who remained untreated, those given metronidazole had significantly lower rates of fevers over 38° C after 1 day (11 vs. 17 children) and after 2 days (3 vs. 9 children), fewer sore throats after 1 day (12 vs. 19) and 2 days (9 vs. 16), and lower rates of tonsillar enlargement after 3 days (11 vs. 16) and 5 days (8 vs. 14). Pharyngeal injection at 2 days also was reduced with metronidazole, Dr. Brook reported at the conference, sponsored by the American Society for Microbiology.

One patient who received metronidazole complained of metallic taste, and three had dark urine.

Metronidazole was chosen for this study because it is effective against anaerobic bacteria, which are thought cause inflammation in the tonsils, but has virtually no activity against facultative and aerobic bacteria.

WASHINGTON — Metronidazole is effective in the treatment of non-β-hemolytic streptococcal tonsillitis, Itzhak Brook, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Although group A β-hemolytic streptococcus (GABHS) is one of the major causes of tonsillitis, other aerobic as well as anaerobic organisms have been isolated from both normal and inflamed tonsils. Some of these organisms are believed to be part of the normal flora, said Dr. Brook, professor of pediatrics at Georgetown University, Washington.

The option of using metronidazole (250 mg every 12 hours for 10 days) was offered to 40 children (mean age 9 years) who presented with sore throat and massive tonsillar enlargement plus at least one of the following: anterior cervical adenitis, temperature higher than 38.3° C, and pharyngeal or tonsillar exudates or pharyngeal injection.

Rapid streptococcal antigen tests were negative in all the patients, and cultures of the tonsils showed no growth of β-hemolytic streptococci, including group A. None of the children had Epstein-Barr antibodies on immunofluorescence.

The 20 who chose metronidazole were similar to the 20 who did not with respect to age, race, sex, family size, current clinical findings, and previous antibiotic use.

Compared with the children who remained untreated, those given metronidazole had significantly lower rates of fevers over 38° C after 1 day (11 vs. 17 children) and after 2 days (3 vs. 9 children), fewer sore throats after 1 day (12 vs. 19) and 2 days (9 vs. 16), and lower rates of tonsillar enlargement after 3 days (11 vs. 16) and 5 days (8 vs. 14). Pharyngeal injection at 2 days also was reduced with metronidazole, Dr. Brook reported at the conference, sponsored by the American Society for Microbiology.

One patient who received metronidazole complained of metallic taste, and three had dark urine.

Metronidazole was chosen for this study because it is effective against anaerobic bacteria, which are thought cause inflammation in the tonsils, but has virtually no activity against facultative and aerobic bacteria.

WASHINGTON — A clonal outbreak of community-acquired methicillin-resistant Staphylococcus aureus in Los Angeles County led to a high rate of hospitalizations among children in 2003, Elizabeth Bancroft, M.D., reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Following skin infection outbreaks of MRSA (USA 300; ST:8) in 2002, community-acquired methicillin-resistant S. aureus (CAMRSA) infections in hospitalized children less than 18 years of age was made a reportable condition from May 5 to Nov. 7, 2003. A total of 140 cases were reported between those dates, said Dr. Bancroft of the Los Angeles County Department of Health Services.

Mean age of the children was 6.25 years (range 0-17), 51% were female, 66% were Hispanic, 16% white, 15% black, and the remainder said they were “other.” Their mean length of stay was 5.13 days (range 1-30). Diagnoses included cellulitis in 44%, abscess in 36%, and a combination of the two in 11%.

Prior misdiagnosis as insect or spider bites occurred in 23%, and 75% of those who had been treated with antibiotics were initially treated inappropriately with β-lactams, she said.

Among 82 for whom a caregiver was interviewed, 24 (29%) had household contact with a skin infection within a month of the child's infection. Other nosocomial risk factors were present in 29 (35%), while risk factors for community-acquired infection were present in 38 (46%), including 9 (11%) who had contact with a recently incarcerated person.

Of 83 isolates analyzed, 79 (96%) were consistent with the USA 300; ST:8 CAMRSA genotype, even though many of the children had nosocomial risk factors.

WASHINGTON — A clonal outbreak of community-acquired methicillin-resistant Staphylococcus aureus in Los Angeles County led to a high rate of hospitalizations among children in 2003, Elizabeth Bancroft, M.D., reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Following skin infection outbreaks of MRSA (USA 300; ST:8) in 2002, community-acquired methicillin-resistant S. aureus (CAMRSA) infections in hospitalized children less than 18 years of age was made a reportable condition from May 5 to Nov. 7, 2003. A total of 140 cases were reported between those dates, said Dr. Bancroft of the Los Angeles County Department of Health Services.

Mean age of the children was 6.25 years (range 0-17), 51% were female, 66% were Hispanic, 16% white, 15% black, and the remainder said they were “other.” Their mean length of stay was 5.13 days (range 1-30). Diagnoses included cellulitis in 44%, abscess in 36%, and a combination of the two in 11%.

Prior misdiagnosis as insect or spider bites occurred in 23%, and 75% of those who had been treated with antibiotics were initially treated inappropriately with β-lactams, she said.

Among 82 for whom a caregiver was interviewed, 24 (29%) had household contact with a skin infection within a month of the child's infection. Other nosocomial risk factors were present in 29 (35%), while risk factors for community-acquired infection were present in 38 (46%), including 9 (11%) who had contact with a recently incarcerated person.

Of 83 isolates analyzed, 79 (96%) were consistent with the USA 300; ST:8 CAMRSA genotype, even though many of the children had nosocomial risk factors.

WASHINGTON — A clonal outbreak of community-acquired methicillin-resistant Staphylococcus aureus in Los Angeles County led to a high rate of hospitalizations among children in 2003, Elizabeth Bancroft, M.D., reported in a poster at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Following skin infection outbreaks of MRSA (USA 300; ST:8) in 2002, community-acquired methicillin-resistant S. aureus (CAMRSA) infections in hospitalized children less than 18 years of age was made a reportable condition from May 5 to Nov. 7, 2003. A total of 140 cases were reported between those dates, said Dr. Bancroft of the Los Angeles County Department of Health Services.

Mean age of the children was 6.25 years (range 0-17), 51% were female, 66% were Hispanic, 16% white, 15% black, and the remainder said they were “other.” Their mean length of stay was 5.13 days (range 1-30). Diagnoses included cellulitis in 44%, abscess in 36%, and a combination of the two in 11%.

Prior misdiagnosis as insect or spider bites occurred in 23%, and 75% of those who had been treated with antibiotics were initially treated inappropriately with β-lactams, she said.

Among 82 for whom a caregiver was interviewed, 24 (29%) had household contact with a skin infection within a month of the child's infection. Other nosocomial risk factors were present in 29 (35%), while risk factors for community-acquired infection were present in 38 (46%), including 9 (11%) who had contact with a recently incarcerated person.

Of 83 isolates analyzed, 79 (96%) were consistent with the USA 300; ST:8 CAMRSA genotype, even though many of the children had nosocomial risk factors.

WASHINGTON — Methicillin-resistant Staphylococcus aureus has been transmitted via breast milk, Dawn Terashita Gastelum, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The two reported cases, which resulted in MRSA outbreaks in neonatal intensive care units at two Los Angeles hospitals, suggest that hospital NICUs should consider screening mothers and family members for skin lesions at the time of delivery and obtaining breast milk cultures before infant feedings, said Dr. Terashita Gastelum of the Los Angeles County Department of Health Services.

The first case was in a premature (1,180 g at birth) quadruplet born to an Algerian mother who developed mastitis the day after delivery and was treated with dicloxacillin. Her breast milk was collected 3 days later and fed to the quadruplets and 12 days after that, the baby girl died of MRSA sepsis.

The bacterium subsequently was found in nasopharyngeal cultures of the mother, her three surviving infants, another infant in the NICU, and the mother's frozen postpartum breast milk samples. Molecular fingerprinting was identical for the four infants and the breast milk, but the mother's nasopharyngeal isolate was different.

“Since the mother was actually colonized by a different strain, it is unlikely that the infants obtained the MRSA during birth or through skin-to-skin contact. The breast milk is the only known source,” Dr. Terashita Gastelum told FAMILY PRACTICE NEWS.

“It is easy to imagine that the macerated skin of the nipple on a postpartum woman is more susceptible to infection,” she said at the conference, sponsored by the American Society for Microbiology.

The second case was an 1,199-g male infant born to an African American mother, who was fed her breast milk the day of birth and developed MRSA sepsis 8 days later. This mother had no sign of mastitis, but MRSA was cultured from her breast milk collected on the day of delivery. Four other infants from the NICU were also positive: two colonized and two infected. Isolates from the breast milk and the five cases were identical.

WASHINGTON — Methicillin-resistant Staphylococcus aureus has been transmitted via breast milk, Dawn Terashita Gastelum, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The two reported cases, which resulted in MRSA outbreaks in neonatal intensive care units at two Los Angeles hospitals, suggest that hospital NICUs should consider screening mothers and family members for skin lesions at the time of delivery and obtaining breast milk cultures before infant feedings, said Dr. Terashita Gastelum of the Los Angeles County Department of Health Services.

The first case was in a premature (1,180 g at birth) quadruplet born to an Algerian mother who developed mastitis the day after delivery and was treated with dicloxacillin. Her breast milk was collected 3 days later and fed to the quadruplets and 12 days after that, the baby girl died of MRSA sepsis.

The bacterium subsequently was found in nasopharyngeal cultures of the mother, her three surviving infants, another infant in the NICU, and the mother's frozen postpartum breast milk samples. Molecular fingerprinting was identical for the four infants and the breast milk, but the mother's nasopharyngeal isolate was different.

“Since the mother was actually colonized by a different strain, it is unlikely that the infants obtained the MRSA during birth or through skin-to-skin contact. The breast milk is the only known source,” Dr. Terashita Gastelum told FAMILY PRACTICE NEWS.

“It is easy to imagine that the macerated skin of the nipple on a postpartum woman is more susceptible to infection,” she said at the conference, sponsored by the American Society for Microbiology.

The second case was an 1,199-g male infant born to an African American mother, who was fed her breast milk the day of birth and developed MRSA sepsis 8 days later. This mother had no sign of mastitis, but MRSA was cultured from her breast milk collected on the day of delivery. Four other infants from the NICU were also positive: two colonized and two infected. Isolates from the breast milk and the five cases were identical.

WASHINGTON — Methicillin-resistant Staphylococcus aureus has been transmitted via breast milk, Dawn Terashita Gastelum, M.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The two reported cases, which resulted in MRSA outbreaks in neonatal intensive care units at two Los Angeles hospitals, suggest that hospital NICUs should consider screening mothers and family members for skin lesions at the time of delivery and obtaining breast milk cultures before infant feedings, said Dr. Terashita Gastelum of the Los Angeles County Department of Health Services.

The first case was in a premature (1,180 g at birth) quadruplet born to an Algerian mother who developed mastitis the day after delivery and was treated with dicloxacillin. Her breast milk was collected 3 days later and fed to the quadruplets and 12 days after that, the baby girl died of MRSA sepsis.

The bacterium subsequently was found in nasopharyngeal cultures of the mother, her three surviving infants, another infant in the NICU, and the mother's frozen postpartum breast milk samples. Molecular fingerprinting was identical for the four infants and the breast milk, but the mother's nasopharyngeal isolate was different.

“Since the mother was actually colonized by a different strain, it is unlikely that the infants obtained the MRSA during birth or through skin-to-skin contact. The breast milk is the only known source,” Dr. Terashita Gastelum told FAMILY PRACTICE NEWS.

“It is easy to imagine that the macerated skin of the nipple on a postpartum woman is more susceptible to infection,” she said at the conference, sponsored by the American Society for Microbiology.

The second case was an 1,199-g male infant born to an African American mother, who was fed her breast milk the day of birth and developed MRSA sepsis 8 days later. This mother had no sign of mastitis, but MRSA was cultured from her breast milk collected on the day of delivery. Four other infants from the NICU were also positive: two colonized and two infected. Isolates from the breast milk and the five cases were identical.

Three recent hospital pertussis outbreaks and one infant death from the disease strongly point to the need for improved recognition and protection against transmission, the Centers for Disease Control and Prevention said.

The cases, from four states, also illustrate the potential benefit of vaccination against Bordetella pertussis in adolescents and adults, because immunity from infant immunization wanes after a decade. No vaccine is currently licensed for persons aged 7 years and above, but two manufacturers have filed for licensure with the Food and Drug Administration for vaccines that combine acellular pertussis, tetanus toxoid, and tetanus toxoid antigens. One would be indicated for persons aged 10-18 years, the other for ages 11-64 years.

All three hospital outbreaks, which occurred in August and September of 2003, involved hospitalized infants with cough illness. In Pennsylvania, a 3-week-old infant was hospitalized with cough, posttussive vomiting, and fever. Pertussis was considered unlikely, the infant wasn't tested for it, and hospital staff did not observe droplet precautions.

The infant was transferred to a referral hospital after 1 day, nasopharyngeal secretions were obtained, and B. pertussis was isolated 16 days later (MMWR 2005;54:67-71).

Meanwhile, the physician who had cared for the infant at the first hospital developed a cough 9 days after exposure. Despite remaining symptomatic, he continued to treat patients—and to have contact with coworkers, family, and friends—without wearing a mask. His nasopharyngeal secretions tested positive 22 days after the initial exposure, while a total of 16 other health care workers and two pediatric patients at the initial hospital developed cough illness and/or tested positive for pertussis.

Hospital infection control personnel subsequently screened exposed employees, treated all who were symptomatic with a 5-day course of azithromycin, and excluded them from work for 5 days. Another 307 close contacts of the symptomatic health care workers were given azithromycin prophylactically, the CDC reported.

The other two outbreaks, in Kentucky and Oregon, also involved acutely ill infants with cough illness, exposed health care workers, and potential transmission to a large number of contacts who subsequently received azithromycin as either treatment or prophylaxis.

All three cases illustrated the difficulties in the diagnosis of pertussis, particularly in older individuals in whom the symptoms during the catarrhal stage are usually nonspecific while the disease is already highly communicable. In infants, diagnosis may be delayed when the presentation is respiratory distress with apnea but without the typical cough.

Also problematic is the lack of adequate diagnostic tests for pertussis. Culture is not sensitive beyond 3 weeks of illness or after antibiotic therapy, polymerase chain reaction for pertussis is not standardized, and no serologic test is available, although the CDC and the FDA are developing one.

A second MMWR report illustrates the fact that incompletely immunized children aged less than 6 months continue to be the most vulnerable to pertussis when the disease is circulating around them (MMWR 2005;54:71-2).

A 29-day-old West Virginia infant was brought to the emergency department with difficulty breathing. The infant's mother had had prolonged paroxysmal cough illness for 3 weeks before the infant's delivery; the father had onset of paroxysmal cough illness 2 weeks before the infant's illness.

The infant had been coughing for 5 days with increasing severity, resulting in posttussive vomiting and choking. At presentation, she was lethargic, tachycardic, and had a mild fever. Laboratory results indicated leukocytosis. Chest x-ray revealed pneumonia, and she developed respiratory failure. She died approximately 30 hours after admission to the pediatric intensive care unit, despite azithromycin treatment for presumed B. pertussis, high-frequency ventilation, nitric oxide administration, and a double-volume exchange transfusion.

The diagnosis of pertussis was based on history, clinical findings, and a positive polymerase chain reaction test. Around the time of the infant's death, two cousins, her paternal grandmother, and a great-grandmother all had cough illness as well.

Finding, Treating Pertussis in Health Workers

Clinical Findings

▸ Incubation period: 7-10 days (range: 4-21 days).

▸ Catarrhal stage: 1-2 weeks; coryza, low-grade fever, and mild cough.

▸ Paroxysmal stage: 1-6 weeks; paroxysmal cough, posttussive vomiting, and ins▸ ratory “whoop.”

▸ Convalescent stage: at least 3 weeks; cough lessens and disappears.

Treatment/Prophylaxis

▸ Macrolides (erythromycin, azithromycin, or clarithromycin) are preferred.

▸ Trimethoprim-sulfamethoxazole is an alternative antibiotic for use in persons with allergy or intolerance to macrolides.

Source: Centers for Disease Control and Prevention

Three recent hospital pertussis outbreaks and one infant death from the disease strongly point to the need for improved recognition and protection against transmission, the Centers for Disease Control and Prevention said.

The cases, from four states, also illustrate the potential benefit of vaccination against Bordetella pertussis in adolescents and adults, because immunity from infant immunization wanes after a decade. No vaccine is currently licensed for persons aged 7 years and above, but two manufacturers have filed for licensure with the Food and Drug Administration for vaccines that combine acellular pertussis, tetanus toxoid, and tetanus toxoid antigens. One would be indicated for persons aged 10-18 years, the other for ages 11-64 years.

All three hospital outbreaks, which occurred in August and September of 2003, involved hospitalized infants with cough illness. In Pennsylvania, a 3-week-old infant was hospitalized with cough, posttussive vomiting, and fever. Pertussis was considered unlikely, the infant wasn't tested for it, and hospital staff did not observe droplet precautions.

The infant was transferred to a referral hospital after 1 day, nasopharyngeal secretions were obtained, and B. pertussis was isolated 16 days later (MMWR 2005;54:67-71).

Meanwhile, the physician who had cared for the infant at the first hospital developed a cough 9 days after exposure. Despite remaining symptomatic, he continued to treat patients—and to have contact with coworkers, family, and friends—without wearing a mask. His nasopharyngeal secretions tested positive 22 days after the initial exposure, while a total of 16 other health care workers and two pediatric patients at the initial hospital developed cough illness and/or tested positive for pertussis.

Hospital infection control personnel subsequently screened exposed employees, treated all who were symptomatic with a 5-day course of azithromycin, and excluded them from work for 5 days. Another 307 close contacts of the symptomatic health care workers were given azithromycin prophylactically, the CDC reported.

The other two outbreaks, in Kentucky and Oregon, also involved acutely ill infants with cough illness, exposed health care workers, and potential transmission to a large number of contacts who subsequently received azithromycin as either treatment or prophylaxis.

All three cases illustrated the difficulties in the diagnosis of pertussis, particularly in older individuals in whom the symptoms during the catarrhal stage are usually nonspecific while the disease is already highly communicable. In infants, diagnosis may be delayed when the presentation is respiratory distress with apnea but without the typical cough.

Also problematic is the lack of adequate diagnostic tests for pertussis. Culture is not sensitive beyond 3 weeks of illness or after antibiotic therapy, polymerase chain reaction for pertussis is not standardized, and no serologic test is available, although the CDC and the FDA are developing one.

A second MMWR report illustrates the fact that incompletely immunized children aged less than 6 months continue to be the most vulnerable to pertussis when the disease is circulating around them (MMWR 2005;54:71-2).

A 29-day-old West Virginia infant was brought to the emergency department with difficulty breathing. The infant's mother had had prolonged paroxysmal cough illness for 3 weeks before the infant's delivery; the father had onset of paroxysmal cough illness 2 weeks before the infant's illness.

The infant had been coughing for 5 days with increasing severity, resulting in posttussive vomiting and choking. At presentation, she was lethargic, tachycardic, and had a mild fever. Laboratory results indicated leukocytosis. Chest x-ray revealed pneumonia, and she developed respiratory failure. She died approximately 30 hours after admission to the pediatric intensive care unit, despite azithromycin treatment for presumed B. pertussis, high-frequency ventilation, nitric oxide administration, and a double-volume exchange transfusion.

The diagnosis of pertussis was based on history, clinical findings, and a positive polymerase chain reaction test. Around the time of the infant's death, two cousins, her paternal grandmother, and a great-grandmother all had cough illness as well.

Finding, Treating Pertussis in Health Workers

Clinical Findings

▸ Incubation period: 7-10 days (range: 4-21 days).

▸ Catarrhal stage: 1-2 weeks; coryza, low-grade fever, and mild cough.

▸ Paroxysmal stage: 1-6 weeks; paroxysmal cough, posttussive vomiting, and ins▸ ratory “whoop.”

▸ Convalescent stage: at least 3 weeks; cough lessens and disappears.

Treatment/Prophylaxis

▸ Macrolides (erythromycin, azithromycin, or clarithromycin) are preferred.

▸ Trimethoprim-sulfamethoxazole is an alternative antibiotic for use in persons with allergy or intolerance to macrolides.

Source: Centers for Disease Control and Prevention

Three recent hospital pertussis outbreaks and one infant death from the disease strongly point to the need for improved recognition and protection against transmission, the Centers for Disease Control and Prevention said.

The cases, from four states, also illustrate the potential benefit of vaccination against Bordetella pertussis in adolescents and adults, because immunity from infant immunization wanes after a decade. No vaccine is currently licensed for persons aged 7 years and above, but two manufacturers have filed for licensure with the Food and Drug Administration for vaccines that combine acellular pertussis, tetanus toxoid, and tetanus toxoid antigens. One would be indicated for persons aged 10-18 years, the other for ages 11-64 years.

All three hospital outbreaks, which occurred in August and September of 2003, involved hospitalized infants with cough illness. In Pennsylvania, a 3-week-old infant was hospitalized with cough, posttussive vomiting, and fever. Pertussis was considered unlikely, the infant wasn't tested for it, and hospital staff did not observe droplet precautions.

The infant was transferred to a referral hospital after 1 day, nasopharyngeal secretions were obtained, and B. pertussis was isolated 16 days later (MMWR 2005;54:67-71).

Meanwhile, the physician who had cared for the infant at the first hospital developed a cough 9 days after exposure. Despite remaining symptomatic, he continued to treat patients—and to have contact with coworkers, family, and friends—without wearing a mask. His nasopharyngeal secretions tested positive 22 days after the initial exposure, while a total of 16 other health care workers and two pediatric patients at the initial hospital developed cough illness and/or tested positive for pertussis.

Hospital infection control personnel subsequently screened exposed employees, treated all who were symptomatic with a 5-day course of azithromycin, and excluded them from work for 5 days. Another 307 close contacts of the symptomatic health care workers were given azithromycin prophylactically, the CDC reported.

The other two outbreaks, in Kentucky and Oregon, also involved acutely ill infants with cough illness, exposed health care workers, and potential transmission to a large number of contacts who subsequently received azithromycin as either treatment or prophylaxis.

All three cases illustrated the difficulties in the diagnosis of pertussis, particularly in older individuals in whom the symptoms during the catarrhal stage are usually nonspecific while the disease is already highly communicable. In infants, diagnosis may be delayed when the presentation is respiratory distress with apnea but without the typical cough.

Also problematic is the lack of adequate diagnostic tests for pertussis. Culture is not sensitive beyond 3 weeks of illness or after antibiotic therapy, polymerase chain reaction for pertussis is not standardized, and no serologic test is available, although the CDC and the FDA are developing one.

A second MMWR report illustrates the fact that incompletely immunized children aged less than 6 months continue to be the most vulnerable to pertussis when the disease is circulating around them (MMWR 2005;54:71-2).

A 29-day-old West Virginia infant was brought to the emergency department with difficulty breathing. The infant's mother had had prolonged paroxysmal cough illness for 3 weeks before the infant's delivery; the father had onset of paroxysmal cough illness 2 weeks before the infant's illness.

The infant had been coughing for 5 days with increasing severity, resulting in posttussive vomiting and choking. At presentation, she was lethargic, tachycardic, and had a mild fever. Laboratory results indicated leukocytosis. Chest x-ray revealed pneumonia, and she developed respiratory failure. She died approximately 30 hours after admission to the pediatric intensive care unit, despite azithromycin treatment for presumed B. pertussis, high-frequency ventilation, nitric oxide administration, and a double-volume exchange transfusion.

The diagnosis of pertussis was based on history, clinical findings, and a positive polymerase chain reaction test. Around the time of the infant's death, two cousins, her paternal grandmother, and a great-grandmother all had cough illness as well.

Finding, Treating Pertussis in Health Workers

Clinical Findings

▸ Incubation period: 7-10 days (range: 4-21 days).

▸ Catarrhal stage: 1-2 weeks; coryza, low-grade fever, and mild cough.

▸ Paroxysmal stage: 1-6 weeks; paroxysmal cough, posttussive vomiting, and ins▸ ratory “whoop.”

▸ Convalescent stage: at least 3 weeks; cough lessens and disappears.

Treatment/Prophylaxis

▸ Macrolides (erythromycin, azithromycin, or clarithromycin) are preferred.

▸ Trimethoprim-sulfamethoxazole is an alternative antibiotic for use in persons with allergy or intolerance to macrolides.

Source: Centers for Disease Control and Prevention

LISBON — Women who receive long-term glucocorticoid treatment for congenital adrenal hyperplasia due to 21-hydroxylase deficiency are at risk for decreased bone mineral density, Jeremy A. King, M.D., reported in a poster presentation at the 12th International Congress of Endocrinology.

The risk of decreased bone mineral density (BMD) is particularly high among postmenopausal women with the salt-losing form of 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). The best way to prevent the problem is to avoid oversuppression of adrenal androgens via careful monitoring, said Dr. King of Johns Hopkins University, Baltimore.

Morphologic measurements, serum hormone assays, and BMD assessments were performed in 11 adult women with the salt-losing (SL) form of CAH who had been receiving glucocorticoid replacement therapy since infancy, and in 15 women with the simple virilizing (SV) form of CAH, who had begun glucocorticoid treatment at ages varying from infancy to 22 years. The measurements were also performed in 15 controls, 9 of whom were unaffected sisters (US) of the subjects, and 6 with polycystic ovarian syndrome (PCOS).

Subjects from both CAH groups were significantly shorter than the controls. (See table.) All bone parameters, including z score, T score, and L-spine, were lower in the CAH group.

In addition, levels of 17-hydroxyprogesterone, androstenedione, dehydroepi-androsterone (DHEA), and dehydroepi-androsterone sulfate (DHEAS) were also all significantly lower in the two CAH groups than in the controls, Dr. King reported.

Not surprisingly, adrenal androgens and bone parameters were lower among the 12 postmenopausal CAH patients, compared with the 14 still premenopausal women, he said.

Osteopenia, defined as a T score between -1 and -2.5, was present in 5 of the 11 SL patients (45%) and 2 of the 15 SV patients (13%), compared with just 1 of the 15 controls (7%). There were no differences in age, menopausal status, or cortisol equivalents between the CAH patients with and without osteopenia. However, adrenal androgens were more suppressed in the osteopenic group, he noted.

Interestingly, body mass index also did not differ between the osteopenic and nonosteopenic CAH patients, suggesting that increased BMI alone does not confer protection from low BMD in this population. The SL group had a mean BMI less than that of the controls with PCOS but greater than the US controls. Yet, the SL group still had lower lumbar BMD and lower z scores, compared with both control groups.

LISBON — Women who receive long-term glucocorticoid treatment for congenital adrenal hyperplasia due to 21-hydroxylase deficiency are at risk for decreased bone mineral density, Jeremy A. King, M.D., reported in a poster presentation at the 12th International Congress of Endocrinology.

The risk of decreased bone mineral density (BMD) is particularly high among postmenopausal women with the salt-losing form of 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). The best way to prevent the problem is to avoid oversuppression of adrenal androgens via careful monitoring, said Dr. King of Johns Hopkins University, Baltimore.

Morphologic measurements, serum hormone assays, and BMD assessments were performed in 11 adult women with the salt-losing (SL) form of CAH who had been receiving glucocorticoid replacement therapy since infancy, and in 15 women with the simple virilizing (SV) form of CAH, who had begun glucocorticoid treatment at ages varying from infancy to 22 years. The measurements were also performed in 15 controls, 9 of whom were unaffected sisters (US) of the subjects, and 6 with polycystic ovarian syndrome (PCOS).

Subjects from both CAH groups were significantly shorter than the controls. (See table.) All bone parameters, including z score, T score, and L-spine, were lower in the CAH group.

In addition, levels of 17-hydroxyprogesterone, androstenedione, dehydroepi-androsterone (DHEA), and dehydroepi-androsterone sulfate (DHEAS) were also all significantly lower in the two CAH groups than in the controls, Dr. King reported.

Not surprisingly, adrenal androgens and bone parameters were lower among the 12 postmenopausal CAH patients, compared with the 14 still premenopausal women, he said.

Osteopenia, defined as a T score between -1 and -2.5, was present in 5 of the 11 SL patients (45%) and 2 of the 15 SV patients (13%), compared with just 1 of the 15 controls (7%). There were no differences in age, menopausal status, or cortisol equivalents between the CAH patients with and without osteopenia. However, adrenal androgens were more suppressed in the osteopenic group, he noted.

Interestingly, body mass index also did not differ between the osteopenic and nonosteopenic CAH patients, suggesting that increased BMI alone does not confer protection from low BMD in this population. The SL group had a mean BMI less than that of the controls with PCOS but greater than the US controls. Yet, the SL group still had lower lumbar BMD and lower z scores, compared with both control groups.

LISBON — Women who receive long-term glucocorticoid treatment for congenital adrenal hyperplasia due to 21-hydroxylase deficiency are at risk for decreased bone mineral density, Jeremy A. King, M.D., reported in a poster presentation at the 12th International Congress of Endocrinology.

The risk of decreased bone mineral density (BMD) is particularly high among postmenopausal women with the salt-losing form of 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH). The best way to prevent the problem is to avoid oversuppression of adrenal androgens via careful monitoring, said Dr. King of Johns Hopkins University, Baltimore.

Morphologic measurements, serum hormone assays, and BMD assessments were performed in 11 adult women with the salt-losing (SL) form of CAH who had been receiving glucocorticoid replacement therapy since infancy, and in 15 women with the simple virilizing (SV) form of CAH, who had begun glucocorticoid treatment at ages varying from infancy to 22 years. The measurements were also performed in 15 controls, 9 of whom were unaffected sisters (US) of the subjects, and 6 with polycystic ovarian syndrome (PCOS).

Subjects from both CAH groups were significantly shorter than the controls. (See table.) All bone parameters, including z score, T score, and L-spine, were lower in the CAH group.

In addition, levels of 17-hydroxyprogesterone, androstenedione, dehydroepi-androsterone (DHEA), and dehydroepi-androsterone sulfate (DHEAS) were also all significantly lower in the two CAH groups than in the controls, Dr. King reported.

Not surprisingly, adrenal androgens and bone parameters were lower among the 12 postmenopausal CAH patients, compared with the 14 still premenopausal women, he said.

Osteopenia, defined as a T score between -1 and -2.5, was present in 5 of the 11 SL patients (45%) and 2 of the 15 SV patients (13%), compared with just 1 of the 15 controls (7%). There were no differences in age, menopausal status, or cortisol equivalents between the CAH patients with and without osteopenia. However, adrenal androgens were more suppressed in the osteopenic group, he noted.

Interestingly, body mass index also did not differ between the osteopenic and nonosteopenic CAH patients, suggesting that increased BMI alone does not confer protection from low BMD in this population. The SL group had a mean BMI less than that of the controls with PCOS but greater than the US controls. Yet, the SL group still had lower lumbar BMD and lower z scores, compared with both control groups.

WASHINGTON — The benefits of oseltamivir aren't limited to treating and preventing influenza, Beth L. Nordstrom, Ph.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Oseltamivir (Tamiflu) is indicated for the treatment of influenza in patients aged 1 year and older who have been symptomatic for no more than 2 days, and for prophylaxis of influenza in persons aged 13 years and older.

New data suggest that the drug also reduces the risk of pneumonia in all age groups, and the rates of antibiotic use and hospitalization in the oldest and youngest patients, said Dr. Nordstrom, of Ingenix Epidemiology, Auburndale, Mass.

In a retrospective cohort study sponsored by Hoffmann-La Roche, claims data from a large U.S. insurer containing a diagnosis of influenza from Dec. 1, 1999, through March 31, 2002, were analyzed.

Patients of all ages who had received oseltamivir were at significantly lower risk for pneumonia, particularly the oldest and youngest age groups. Among children aged 1-12 years, the proportion with a diagnosis of pneumonia was 0.7% among the 586 for whom oseltamivir was dispensed on the day of influenza diagnosis, compared with 2.5% of the 17,886 who did not receive oseltamivir, a 66% risk reduction.

In patients aged 13-59, pneumonia was diagnosed in 1.3% of the 10,649 who received the drug, compared with 2.1% of the 41,007 who did not—a reduction of 19%. In adults aged 60 and older, the difference was 1.7% of 463 with oseltamivir versus 8.8% of 3,298 without, a 59% drop.

The impact of oseltamivir on antibiotic dispensing and hospitalization was also greater in the youngest and oldest age groups. Antibiotic use dropped with oseltamivir by 30% in the 1- to 12-year-olds, by 9% in the 13- to 59-year-olds, and by 14% in the 60-plus group. Hospitalizations were reduced by 71% with oseltamivir in the 1- to 12-year-olds, by 25% in the 13- to 59-year age group and 45% in the 60-plus patients, Dr. Nordstrom reported.

WASHINGTON — The benefits of oseltamivir aren't limited to treating and preventing influenza, Beth L. Nordstrom, Ph.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Oseltamivir (Tamiflu) is indicated for the treatment of influenza in patients aged 1 year and older who have been symptomatic for no more than 2 days, and for prophylaxis of influenza in persons aged 13 years and older.

New data suggest that the drug also reduces the risk of pneumonia in all age groups, and the rates of antibiotic use and hospitalization in the oldest and youngest patients, said Dr. Nordstrom, of Ingenix Epidemiology, Auburndale, Mass.

In a retrospective cohort study sponsored by Hoffmann-La Roche, claims data from a large U.S. insurer containing a diagnosis of influenza from Dec. 1, 1999, through March 31, 2002, were analyzed.

Patients of all ages who had received oseltamivir were at significantly lower risk for pneumonia, particularly the oldest and youngest age groups. Among children aged 1-12 years, the proportion with a diagnosis of pneumonia was 0.7% among the 586 for whom oseltamivir was dispensed on the day of influenza diagnosis, compared with 2.5% of the 17,886 who did not receive oseltamivir, a 66% risk reduction.

In patients aged 13-59, pneumonia was diagnosed in 1.3% of the 10,649 who received the drug, compared with 2.1% of the 41,007 who did not—a reduction of 19%. In adults aged 60 and older, the difference was 1.7% of 463 with oseltamivir versus 8.8% of 3,298 without, a 59% drop.

The impact of oseltamivir on antibiotic dispensing and hospitalization was also greater in the youngest and oldest age groups. Antibiotic use dropped with oseltamivir by 30% in the 1- to 12-year-olds, by 9% in the 13- to 59-year-olds, and by 14% in the 60-plus group. Hospitalizations were reduced by 71% with oseltamivir in the 1- to 12-year-olds, by 25% in the 13- to 59-year age group and 45% in the 60-plus patients, Dr. Nordstrom reported.

WASHINGTON — The benefits of oseltamivir aren't limited to treating and preventing influenza, Beth L. Nordstrom, Ph.D., reported in a poster presentation at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Oseltamivir (Tamiflu) is indicated for the treatment of influenza in patients aged 1 year and older who have been symptomatic for no more than 2 days, and for prophylaxis of influenza in persons aged 13 years and older.

New data suggest that the drug also reduces the risk of pneumonia in all age groups, and the rates of antibiotic use and hospitalization in the oldest and youngest patients, said Dr. Nordstrom, of Ingenix Epidemiology, Auburndale, Mass.

In a retrospective cohort study sponsored by Hoffmann-La Roche, claims data from a large U.S. insurer containing a diagnosis of influenza from Dec. 1, 1999, through March 31, 2002, were analyzed.

Patients of all ages who had received oseltamivir were at significantly lower risk for pneumonia, particularly the oldest and youngest age groups. Among children aged 1-12 years, the proportion with a diagnosis of pneumonia was 0.7% among the 586 for whom oseltamivir was dispensed on the day of influenza diagnosis, compared with 2.5% of the 17,886 who did not receive oseltamivir, a 66% risk reduction.

In patients aged 13-59, pneumonia was diagnosed in 1.3% of the 10,649 who received the drug, compared with 2.1% of the 41,007 who did not—a reduction of 19%. In adults aged 60 and older, the difference was 1.7% of 463 with oseltamivir versus 8.8% of 3,298 without, a 59% drop.

The impact of oseltamivir on antibiotic dispensing and hospitalization was also greater in the youngest and oldest age groups. Antibiotic use dropped with oseltamivir by 30% in the 1- to 12-year-olds, by 9% in the 13- to 59-year-olds, and by 14% in the 60-plus group. Hospitalizations were reduced by 71% with oseltamivir in the 1- to 12-year-olds, by 25% in the 13- to 59-year age group and 45% in the 60-plus patients, Dr. Nordstrom reported.

LISBON — Primary insulin-like growth factor deficiency is one and a half times more common than growth hormone deficiency among children with short stature and a deficiency of insulin-like growth factor-1, George M. Bright, M.D., reported at the 12th International Congress of Endocrinology.

Both deficiency groups have low levels of insulin-like growth factor-1 (IGF-1), and the two groups cannot be distinguished clinically. But the difference is important, because children with primary insulin-like growth factor deficiency-1 (IGFD) are often insensitive to growth hormone (GH) therapy and may respond better to IGF-1 replacement, said Dr. Bright, vice president of clinical affairs for Tercica, a biopharmaceutical company based in San Francisco.

The company plans to file a new drug application in early 2005 for the use of recombinant human IGF-1 in children with primary IGFD.

In an observational study of 6,447 children referred for evaluation of short stature to 197 U.S. pediatric endocrinology clinics between 1993 and 1996, 72% actually had short stature, defined as height shorter than 2 standard deviations below the mean. Of those 4,663 children, 42% had IGFD (IGF-1 levels less than 2 standard deviations below the mean). Among those 1,955 children, 40% had growth hormone levels below 5 ng/mL using a Hybritech immunoradiometric assay and were therefore considered to have classical GH deficiency (“secondary IGFD”), and 60% had normal GH levels (above 5 ng/mL), or so-called primary IGFD.

The 1,179 children with primary IGFD and the 776 with GHD were phenotypically similar, with mean ages of 10.6 years and 10.3 years, respectively. The GHD children were slightly shorter (3.3 vs. 3.0 standard deviations below the mean). This difference was statistically significant, but probably not clinically so; it translates to just about 2 cm, Dr. Bright noted.

“The take-home message is that it's difficult to distinguish between primary IGFD and GHD based on presenting clinical characteristics,” he said.

Measuring serum IGF-1 levels alone is also inadequate, since both groups are deficient (−3.0 standard deviation score [SDS] for IGFD and −3.8 SDS for GHD). However, discrimination between the two groups is possible using an “IGF-1 standard deviation score generation test” derived from baseline and stimulated IGF-1 levels from four groups of children (23 with GHD, 22 with a GH receptor mutation, 65 heterozygotes for the mutation, and 72 normal subjects), Dr. Bright said in a separate presentation.

Blood samples taken on day 8 following GH stimulation demonstrated that an IGF-1 cut-point of 2.5 standard deviations below the mean was 95.7% sensitive and 95.5% specific for discriminating between primary IGFD and GHD. In contrast, IGF-1 concentrations alone gave a specificity of only 86.4% (with the same sensitivity). Among the 1,955 children from the observational study with short stature and low IGF-1, that 9.1% improvement in specificity would translate to 178 patients prevented from being misclassified, he said. For a given level of GH exposure, the change in IGF-1 SDS in the IGF-1 generation test might be helpful.

“For example, when there is a robust change in IGF-1 SDS, you can reasonably expect that GH replacement therapy would be useful in the short and long term. But when there is very little change in the [SDS], your treatment of choice would be IGF-1. If it's intermediate, we would need a separate exercise to determine whether the best treatment is GH, IGF-1, or a combination,” Dr. Bright explained.

Earlier this year at the Endocrine Society meeting, Steven Chernausek, M.D., reported Tercica's phase III clinical trial data of recombinant human IGF-1 (rhIGF-1) in 65 children with severe short stature and IGF-1 deficiency caused by GH insensitivity, of whom 54 were treated for at least 1 year (45 had Laron syndrome, 7 had GH antibodies, and 2 had unspecified defects). At the start of therapy, the children had a mean age of 6.5 years (age range 2–10 years), and mean height 88.7 cm (−6.7 SDS). They received twice-daily injections of rhIGF-1 in doses of 80–120 mcg/kg. Mean duration of treatment was 3.6 years.

At 1 year, height velocity had improved from 2.6 cm/year to 8.0 cm/yr, with a mean of 5.3 cm/yr over a period of 8 years. The ratio of bone age to height age decreased from 2.5 at baseline to 1.8 over 3 years in 24 of the patients for whom serial bone age data were available, said Dr. Chernausek, professor of pediatrics at Children's Hospital Medical Center, Cincinnati.

None of the 65 patients dropped out of the study because of adverse events. Hypoglycemia was the most common adverse event attributed to the rhIGF-1 treatment, documented in 26 patients (40%) during the study in contrast to just 12 (18%) prior to starting therapy. Growth of lymphoid tissue was also common, with snoring in 16 patients (25%), tonsillar hypertrophy in 10 (15%), and tonsillectomy/adenoidectomy in 3 (5%).

Five patients (8%) had middle ear effusions at least once, and 16 (25%) had abnormal tympanometry or audiograms, with tube placement in 8 (12%). Increases in the size of the kidneys and spleen by ultrasound occurred in the first 2–3 years of therapy, but no adverse changes of renal function were observed. There were no deaths or neoplasias, Dr. Chernausek reported.

LISBON — Primary insulin-like growth factor deficiency is one and a half times more common than growth hormone deficiency among children with short stature and a deficiency of insulin-like growth factor-1, George M. Bright, M.D., reported at the 12th International Congress of Endocrinology.

Both deficiency groups have low levels of insulin-like growth factor-1 (IGF-1), and the two groups cannot be distinguished clinically. But the difference is important, because children with primary insulin-like growth factor deficiency-1 (IGFD) are often insensitive to growth hormone (GH) therapy and may respond better to IGF-1 replacement, said Dr. Bright, vice president of clinical affairs for Tercica, a biopharmaceutical company based in San Francisco.

The company plans to file a new drug application in early 2005 for the use of recombinant human IGF-1 in children with primary IGFD.

In an observational study of 6,447 children referred for evaluation of short stature to 197 U.S. pediatric endocrinology clinics between 1993 and 1996, 72% actually had short stature, defined as height shorter than 2 standard deviations below the mean. Of those 4,663 children, 42% had IGFD (IGF-1 levels less than 2 standard deviations below the mean). Among those 1,955 children, 40% had growth hormone levels below 5 ng/mL using a Hybritech immunoradiometric assay and were therefore considered to have classical GH deficiency (“secondary IGFD”), and 60% had normal GH levels (above 5 ng/mL), or so-called primary IGFD.

The 1,179 children with primary IGFD and the 776 with GHD were phenotypically similar, with mean ages of 10.6 years and 10.3 years, respectively. The GHD children were slightly shorter (3.3 vs. 3.0 standard deviations below the mean). This difference was statistically significant, but probably not clinically so; it translates to just about 2 cm, Dr. Bright noted.

“The take-home message is that it's difficult to distinguish between primary IGFD and GHD based on presenting clinical characteristics,” he said.

Measuring serum IGF-1 levels alone is also inadequate, since both groups are deficient (−3.0 standard deviation score [SDS] for IGFD and −3.8 SDS for GHD). However, discrimination between the two groups is possible using an “IGF-1 standard deviation score generation test” derived from baseline and stimulated IGF-1 levels from four groups of children (23 with GHD, 22 with a GH receptor mutation, 65 heterozygotes for the mutation, and 72 normal subjects), Dr. Bright said in a separate presentation.

Blood samples taken on day 8 following GH stimulation demonstrated that an IGF-1 cut-point of 2.5 standard deviations below the mean was 95.7% sensitive and 95.5% specific for discriminating between primary IGFD and GHD. In contrast, IGF-1 concentrations alone gave a specificity of only 86.4% (with the same sensitivity). Among the 1,955 children from the observational study with short stature and low IGF-1, that 9.1% improvement in specificity would translate to 178 patients prevented from being misclassified, he said. For a given level of GH exposure, the change in IGF-1 SDS in the IGF-1 generation test might be helpful.

“For example, when there is a robust change in IGF-1 SDS, you can reasonably expect that GH replacement therapy would be useful in the short and long term. But when there is very little change in the [SDS], your treatment of choice would be IGF-1. If it's intermediate, we would need a separate exercise to determine whether the best treatment is GH, IGF-1, or a combination,” Dr. Bright explained.

Earlier this year at the Endocrine Society meeting, Steven Chernausek, M.D., reported Tercica's phase III clinical trial data of recombinant human IGF-1 (rhIGF-1) in 65 children with severe short stature and IGF-1 deficiency caused by GH insensitivity, of whom 54 were treated for at least 1 year (45 had Laron syndrome, 7 had GH antibodies, and 2 had unspecified defects). At the start of therapy, the children had a mean age of 6.5 years (age range 2–10 years), and mean height 88.7 cm (−6.7 SDS). They received twice-daily injections of rhIGF-1 in doses of 80–120 mcg/kg. Mean duration of treatment was 3.6 years.

At 1 year, height velocity had improved from 2.6 cm/year to 8.0 cm/yr, with a mean of 5.3 cm/yr over a period of 8 years. The ratio of bone age to height age decreased from 2.5 at baseline to 1.8 over 3 years in 24 of the patients for whom serial bone age data were available, said Dr. Chernausek, professor of pediatrics at Children's Hospital Medical Center, Cincinnati.

None of the 65 patients dropped out of the study because of adverse events. Hypoglycemia was the most common adverse event attributed to the rhIGF-1 treatment, documented in 26 patients (40%) during the study in contrast to just 12 (18%) prior to starting therapy. Growth of lymphoid tissue was also common, with snoring in 16 patients (25%), tonsillar hypertrophy in 10 (15%), and tonsillectomy/adenoidectomy in 3 (5%).

Five patients (8%) had middle ear effusions at least once, and 16 (25%) had abnormal tympanometry or audiograms, with tube placement in 8 (12%). Increases in the size of the kidneys and spleen by ultrasound occurred in the first 2–3 years of therapy, but no adverse changes of renal function were observed. There were no deaths or neoplasias, Dr. Chernausek reported.

LISBON — Primary insulin-like growth factor deficiency is one and a half times more common than growth hormone deficiency among children with short stature and a deficiency of insulin-like growth factor-1, George M. Bright, M.D., reported at the 12th International Congress of Endocrinology.

Both deficiency groups have low levels of insulin-like growth factor-1 (IGF-1), and the two groups cannot be distinguished clinically. But the difference is important, because children with primary insulin-like growth factor deficiency-1 (IGFD) are often insensitive to growth hormone (GH) therapy and may respond better to IGF-1 replacement, said Dr. Bright, vice president of clinical affairs for Tercica, a biopharmaceutical company based in San Francisco.

The company plans to file a new drug application in early 2005 for the use of recombinant human IGF-1 in children with primary IGFD.

In an observational study of 6,447 children referred for evaluation of short stature to 197 U.S. pediatric endocrinology clinics between 1993 and 1996, 72% actually had short stature, defined as height shorter than 2 standard deviations below the mean. Of those 4,663 children, 42% had IGFD (IGF-1 levels less than 2 standard deviations below the mean). Among those 1,955 children, 40% had growth hormone levels below 5 ng/mL using a Hybritech immunoradiometric assay and were therefore considered to have classical GH deficiency (“secondary IGFD”), and 60% had normal GH levels (above 5 ng/mL), or so-called primary IGFD.

The 1,179 children with primary IGFD and the 776 with GHD were phenotypically similar, with mean ages of 10.6 years and 10.3 years, respectively. The GHD children were slightly shorter (3.3 vs. 3.0 standard deviations below the mean). This difference was statistically significant, but probably not clinically so; it translates to just about 2 cm, Dr. Bright noted.

“The take-home message is that it's difficult to distinguish between primary IGFD and GHD based on presenting clinical characteristics,” he said.

Measuring serum IGF-1 levels alone is also inadequate, since both groups are deficient (−3.0 standard deviation score [SDS] for IGFD and −3.8 SDS for GHD). However, discrimination between the two groups is possible using an “IGF-1 standard deviation score generation test” derived from baseline and stimulated IGF-1 levels from four groups of children (23 with GHD, 22 with a GH receptor mutation, 65 heterozygotes for the mutation, and 72 normal subjects), Dr. Bright said in a separate presentation.

Blood samples taken on day 8 following GH stimulation demonstrated that an IGF-1 cut-point of 2.5 standard deviations below the mean was 95.7% sensitive and 95.5% specific for discriminating between primary IGFD and GHD. In contrast, IGF-1 concentrations alone gave a specificity of only 86.4% (with the same sensitivity). Among the 1,955 children from the observational study with short stature and low IGF-1, that 9.1% improvement in specificity would translate to 178 patients prevented from being misclassified, he said. For a given level of GH exposure, the change in IGF-1 SDS in the IGF-1 generation test might be helpful.

“For example, when there is a robust change in IGF-1 SDS, you can reasonably expect that GH replacement therapy would be useful in the short and long term. But when there is very little change in the [SDS], your treatment of choice would be IGF-1. If it's intermediate, we would need a separate exercise to determine whether the best treatment is GH, IGF-1, or a combination,” Dr. Bright explained.

Earlier this year at the Endocrine Society meeting, Steven Chernausek, M.D., reported Tercica's phase III clinical trial data of recombinant human IGF-1 (rhIGF-1) in 65 children with severe short stature and IGF-1 deficiency caused by GH insensitivity, of whom 54 were treated for at least 1 year (45 had Laron syndrome, 7 had GH antibodies, and 2 had unspecified defects). At the start of therapy, the children had a mean age of 6.5 years (age range 2–10 years), and mean height 88.7 cm (−6.7 SDS). They received twice-daily injections of rhIGF-1 in doses of 80–120 mcg/kg. Mean duration of treatment was 3.6 years.

At 1 year, height velocity had improved from 2.6 cm/year to 8.0 cm/yr, with a mean of 5.3 cm/yr over a period of 8 years. The ratio of bone age to height age decreased from 2.5 at baseline to 1.8 over 3 years in 24 of the patients for whom serial bone age data were available, said Dr. Chernausek, professor of pediatrics at Children's Hospital Medical Center, Cincinnati.

None of the 65 patients dropped out of the study because of adverse events. Hypoglycemia was the most common adverse event attributed to the rhIGF-1 treatment, documented in 26 patients (40%) during the study in contrast to just 12 (18%) prior to starting therapy. Growth of lymphoid tissue was also common, with snoring in 16 patients (25%), tonsillar hypertrophy in 10 (15%), and tonsillectomy/adenoidectomy in 3 (5%).

Five patients (8%) had middle ear effusions at least once, and 16 (25%) had abnormal tympanometry or audiograms, with tube placement in 8 (12%). Increases in the size of the kidneys and spleen by ultrasound occurred in the first 2–3 years of therapy, but no adverse changes of renal function were observed. There were no deaths or neoplasias, Dr. Chernausek reported.