A randomised trial of a Haemophilus influenzae type b conjugate vaccine in a developing country for the prevention of pneumonia--ethical considerations.

In 1993 a placebo-controlled field trial of a Haemophilus influenzae type b (Hib) conjugate vaccine was started in The Gambia. At that time Hib conjugate vaccines had been shown to be efficacious in Europe and North America for the prevention of Hib meningitis. However doubts remained about their value in developing countries, where the epidemiology of Hib disease is quite different and the most important manifestation of Hib disease is pneumonia. The ethical issues facing the investigators before and during the trial are outlined in this paper, along with the views of the different groups involved in the trial. The trial demonstrated the efficacy of the vaccine in this setting and revealed the proportion of childhood pneumonia that is likely due to Hib, which was much higher than had previously been estimated. Since the completion of the trial Hib vaccines are now recommended for use in developing countries by the World Health Organization, largely based on the results of this trial. After a delay of 17 months following the completion of the trial, national Hib vaccination was started in The Gambia in 1997 using vaccine provided by a donation from industry.

Immunogenicity of two efficacious outer membrane protein-based serogroup B meningococcal vaccines among young adults in Iceland.

Serum bactericidal activity (SBA) and ELISA antibody levels elicited by two efficacious serogroup B meningococcal vaccines were measured in a controlled trial involving 408 15- to 20-year-olds. Subjects were given two doses at a 6-week interval of a serogroup B or control vaccine. Response was defined as > or = 4-fold rise in antibody level. After two doses of the Finlay Institute (Havana) vaccine at 12 months, the proportions of SBA and ELISA responders were not different from those of the control group (15% and 17% [vaccine] vs. 13% and 9% [control], P > .05). After two doses of the National Institute of Public Health (Oslo) vaccine, there were more SBA and ELISA responders than in the control group (47% and 34% [vaccine] vs. 10% and 1% [control]) or the Finlay Institute vaccine group (P < .05 for both). SBA and ELISA may be insensitive correlates for protective efficacy for some outer membrane protein-based serogroup B meningococcal vaccines.

Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide-protein conjugate vaccine.

Two hundred twenty-one Gambian children vaccinated previously with one, two, or three doses of a meningococcal conjugate vaccine or two doses of polysaccharide vaccine before the age of 6 months were revaccinated at the age of 18-24 months with either meningococcal polysaccharide, conjugate, or inactivated polio vaccines. Children who had previously received one, two, or three doses of conjugate vaccine had significantly (P < .001) higher anti-group C meningococcal antibody levels following revaccination than did children vaccinated with a polysaccharide vaccine for the first time. Children vaccinated previously with two doses of polysaccharide vaccine had a lower group C antibody response than did control children. Group A antibody responses following revaccination of children who had previously received polysaccharide or conjugate vaccine were not significantly higher than those in control children. Thus, immunologic memory was probably induced by the group C but not by the group A component of the conjugate vaccine.

A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants.

The safety and immunogenicity of a group A plus group C meningococcal polysaccharide-CRM197 conjugate vaccine was evaluated in 304 8- to 10-week-old Gambian infants. Infants were immunized with one, two, or three doses of conjugate vaccine or with two doses of a meningococcal A plus C polysaccharide vaccine. The conjugate vaccine produced few systemic side effects, and local reactions were similar to those produced by the polysaccharide vaccine. Postvaccination group A meningococcal polysaccharide antibody levels, measured by ELISA, increased progressively after one, two, or three doses of conjugate vaccine. However, one dose of conjugate vaccine given at the age of 6 months induced a higher group C meningococcal antibody response than did two doses of conjugate vaccine given at 2 and 6 months. Two doses of conjugate vaccine induced higher levels of antibody than did two doses of polysaccharide vaccine. Thus, this new meningococcal conjugate vaccine proved to be safe and immunogenic.

A point-source foodborne listeriosis outbreak: documented incubation period and possible mild illness.

Listeria bacteremia occurred in 2 pregnant women whose only common exposure was attendance at a party. The incubation period, the possibility of mild disease due to Listeria infection, and foods associated with risk of disease were evaluated. Ten (28%) of 36 party attenders met a case definition, which included isolation of Listeria monocytogenes from blood or stool or two of the following: fever, musculoskeletal symptoms, nausea, vomiting, diarrhea. One of 25 stool cultures was positive. The 2 blood isolates and 1 stool isolate were serotype 4b and identical by enzyme typing. The incubation periods for illness in the 2 pregnant women were 19 and 23 days. Consumption of large amounts of shrimp, nonalcoholic beverages, Camembert cheese, and cauliflower was significantly associated with illness. Eating shrimp remained a significant risk factor for illness after controlling for consumption of other foods. This study suggests a milder illness may exist in healthy persons who consume foods contaminated with L. monocytogenes and demonstrates a prolonged incubation period for disease.

Pneumococcal polysaccharide vaccine efficacy. An evaluation of current recommendations.

OBJECTIVE: To determine pneumococcal polysaccharide vaccine efficacy in selected populations at risk for serious pneumococcal infection for whom vaccination is currently recommended and to assess duration of protection after vaccination. DESIGN: Vaccine efficacy was estimated using indirect cohort analysis to compare the proportion of pneumococcal infections caused by serotypes included in the vaccines of vaccinated and unvaccinated persons who were identified during 14 years of national surveillance. SETTING: Hospital laboratories in the United States that submitted pneumococcal isolates to the Centers for Disease Control and Prevention between May 1978 and April 1992. PARTICIPANTS: A total of 2837 persons older than 5 years who had pneumococcus isolated from blood or cerebrospinal fluid. RESULTS: Overall efficacy for preventing infection caused by serotypes included in the vaccine was 57% (95% confidence interval [CI], 45% to 66%). Efficacy among persons with diabetes mellitus was 84% (95% CI, 50% to 95%); with coronary vascular disease, 73% (95% CI, 23% to 90%); with congestive heart failure, 69% (95% CI, 17% to 88%); with chronic pulmonary diseases, 65% (95% CI, 26% to 83%); and with anatomic asplenia, 77% (95% CI, 14% to 95%). Efficacy was not documented for patients with alcoholism or cirrhosis, sickle cell disease, chronic renal failure, lymphoma, leukemia, or multiple myeloma, although sample sizes were small for these groups. Efficacy for immunocompetent persons older than 65 years was 75% (95% CI, 57% to 85%). Efficacy did not decline with increasing interval after vaccination: 5 to 8 years after vaccination it was 71% (95% CI, 24% to 89%), and 9 years or more after vaccination it was 80% (95% CI, 16% to 95%). CONCLUSIONS: Intensified efforts to improve pneumococcal vaccine coverage among certain populations for whom vaccination is currently recommended is indicated, but universal revaccination is not warranted at this time.

Comparison of prevention strategies for neonatal group B streptococcal infection. A population-based economic analysis.

BACKGROUND: Intrapartum antibiotics can prevent early-onset neonatal group B streptococcal (GBS) disease but have not been widely used. Obstacles include difficulty in implementing screening for GBS colonization and uncertainty about cost-effectiveness. The GBS vaccines for disease prevention are now being developed. METHODS: We developed a decision analysis model and used standard cost-effectiveness and cost-benefit analysis methods. We compared the outcomes and costs of the recent practice of no intervention with those expected for three prevention strategies: (1) intrapartum antibiotics administered to colonized women with labor complications, (2) an alternative strategy that does not require screening but uses epidemiologic criteria and labor complications to target intrapartum antibiotics, and (3) maternal vaccination. We used data from multistate population-based surveillance to estimate the potential impact of each strategy on disease and costs in the United States. RESULTS: Intrapartum antibiotic prophylaxis of high-risk women identified by screening could prevent approximately 3300 cases (47% of neonatal disease) annually in the United States and could save approximately $16 million in direct medical costs. Chemoprophylaxis of high-risk women identified using epidemiologic criteria could potentially be equally effective (3200 cases prevented) and would avoid the logistical difficulties of screening; the net savings would be approximately $66 million. Vaccinating 80% of pregnant women with a vaccine that prevents 80% of cases among infants born at or after 34 weeks of gestation would prevent approximately 4100 neonatal cases annually with a net savings of $131 million. CONCLUSIONS: Universal prenatal screening for GBS and chemoprophylaxis of colonized women with labor complications is likely to be cost-beneficial in the United States. Development of alternative strategies should be further explored for populations in which GBS screening is impractical. Continued development of a GBS vaccine is an important public health priority.

Outbreak of early onset group B streptococcal sepsis.

During January and August, 1990, 23 cases of early onset Group B Streptococcus (GBS) disease occurred in a Kansas City, MO, hospital with an attack rate of 14/1000 live births, compared with an annual rate of 1.2 cases/1000 live births for 1988 through 1989. Case infants were compared with controls matched by birth weight, race, maternal age and day of delivery and to a second group of infants of mothers colonized with GBS to identify risk factors and consider intervention strategies during the outbreak. The presence of multiple serotypes among the invasive strains suggested that the outbreak was not caused by a common source. Case mothers were more likely than control mothers to have chorioamnionitis, intrapartum fever or rupture of membranes > 12 hours, and premature case infants were more likely to have a history of rupture of membranes before onset of labor. Multiparous mothers of case infants were more likely to have a history of spontaneous abortion (odds ratio, 6.7; 95% confidence interval, 1.0 to 45.9). No single factor could explain the increase in GBS disease. If intrapartum antibiotic prophylaxis had been used for selected GBS carriers based on presence of either rupture of membranes > 12 hours, intrapartum maternal fever or preterm labor, 7.4% of all deliveries would have received antibiotics and 73% of cases could potentially have been prevented. We conclude that identification of colonized mothers with perinatal risk factors and use of intrapartum antibiotics could be expected to prevent substantial disease during an outbreak of early onset GBS disease.

Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era.

OBJECTIVE: Effective Haemophilus influenzae type b (Hib) conjugate vaccines were first licensed for use in US children at least 18 months old in December 1987 and for infants at least 2 months old in October 1990. We evaluated trends in Hib disease associated with licensure of Hib conjugate vaccines. DESIGN: Data from two sources, an intensive laboratory-based active surveillance system and the National Bacterial Meningitis Reporting System (NBMRS), were used separately to evaluate disease incidence. Data from vaccine manufacturers on Hib vaccine doses distributed in the United States were compared with trends in Hib disease incidence. RESULTS: The age-specific incidence of Hib disease among children less than 5 years old decreased by 71% from 37 per 100,000 persons in 1989 to 11 per 100,000 persons in 1991 (active surveillance data). Haemophilus influenzae meningitis incidence decreased by 82% between 1985 and 1991 (NBMRS data). Increases in doses of Hib vaccine distributed in the United States coincided with steep declines in Hib disease. Both surveillance systems showed decreased rates of Hib disease in infants less than 1 year old before vaccine was licensed for use in this age group. Haemophilus influenzae type b disease incidence in persons at least 12 years old and pneumococcal meningitis incidence in children less than 5 years old did not change substantially during the same period; therefore, decreased Hib disease in children less than 5 years old is not likely to be explained solely by changes in surveillance sensitivity or decreases in bacterial disease due to changes in medical practice. CONCLUSION: Our data suggest that conjugate vaccines have already had a marked impact on the incidence of Hib disease in the United States, preventing an estimated 10,000 to 16,000 cases of Hib disease in 1991. The decline of disease in infants less than 1 year old before licensure for this age group warrants further investigation.

Public health policy for preventing violence.

The current epidemic of violence in America threatens not only our physical health but also the integrity of basic social institutions such as the family, the communities in which we live, and our health care system. Public health brings a new vision of how Americans can work together to prevent violence. This new vision places emphasis on preventing violence before it occurs, making science integral to identifying effective policies and programs, and integrating the efforts of diverse scientific disciplines, organizations, and communities. A sustained effort at all levels of society will be required to successfully address this complex and deeply rooted problem.

PIP: Violence is a major contribution to premature death, disability, and injury. In America, there is an epidemic of violence, which threatens not only the physical health, but also the integrity of basic social institutions such as the family, the communities, and the health care system of the public. In this paper, the new vision for violence prevention embodied in the public health approach is discussed. It shifts the focus of the society in the way violence is addressed, from reacting to the problem to changing the social, behavioral, and environmental factors that cause violence. The emphasis is on preventing violence before it occurs, making science integral in identifying effective policies and programs, and integrating the efforts of diverse scientific disciplines, organizations, and communities. A sustained and coordinated effort to prevent violence will be necessary at all levels of society to address this complex and deeply rooted problem.

Risk factors for deaths in children under 5 years old in Bagamoyo district, Tanzania.

We conducted a population based case control study of deaths in children < 5 years old from Bagamoyo District, Tanzania, to evaluate factors associated with death, and factors associated with not utilizing Government health care system. Six hundred and ten children who died between 1 July, 1986 and 30 June 1987 were enrolled as cases; 1,160 healthy control children were selected by multistage random cluster sampling. Twenty-five percent of deaths were ascribed to pneumonia based on "verbal autopsy"; 39% of acute respiratory deaths occurred in children < 6 months of age. In a multivariate analysis, significant independent associations were found with mother as sole decision maker for treatment (O.R = 0.13; 95% C:I. 0.07, 0.22); use of water from village well, pond, or river vs. tap water (O.R. = 11.86; 95% C.I., 5.46, 25.72); the child eating with others (O.R. = 9.42; 95% C.I. 5.68, 15.62) and the child sleeping in the room where cooking is done (O.R. = 2.78; 95% C.I. 1.79, 4.33). Overall only 45% of families utilized Government health care (village health worker, dispensary or health centre) during their child's terminal illness. Families utilizing Government health care were significantly more likely to say that the mother alone could make treatment decision (O.R. = 2.49, 95% C.I. 1.39, 4.46), and to be closer to a dispensary. The main reasons for not utilizing Government health care were 'traditional medicine is better' (41%) and 'no drugs available' (38%).

Comparative efficacy of oral rifampin and topical chloramphenicol in eradicating conjunctival carriage of Haemophilus influenzae biogroup aegyptius. Brazilian Purpuric Fever Study Group.

Persistent conjunctival carriage of the Haemophilus influenzae biogroup aegyptius (Hae) strain (BPF clone) responsible for Brazilian purpuric fever (BPF) has been documented. Topical chloramphenicol is routinely used to treat conjunctivitis in areas affected by BPF in Brazil. Although the BPF clone is susceptible to chloramphenicol, we observed a number of children treated with topical chloramphenicol for conjunctivitis who still developed BPF. During an investigation of an outbreak of BPF in Mato Grosso State, Brazil, we compared oral rifampin (20 mg/kg/day for 4 days) with topical chloramphenicol for eradication of conjunctival carriage of H. influenzae biogroup aegyptius among children with presumed BPF clone conjunctivitis. Conjunctival samples were taken for culture on the day treatment was initiated and a mean of 8 and 21 days later. At 8 days the eradication rates for oral rifampin and topical chloramphenicol were 100 and 44%, respectively (P = 0.003); at 21 days they were 100 and 50% (P = 0.01). Oral rifampin was more effective than topical chloramphenicol for eradication of the BPF clone and may be useful in prevention of BPF.

Epidemic meningococcal disease in Nairobi, Kenya, 1989. The Kenya/Centers for Disease Control (CDC) Meningitis Study Group.

An epidemic of meningococcal disease occurred in Nairobi, Kenya, during 1989, outside the "meningitis belt" of sub-Saharan Africa. About 3800 cases occurred between April and November (250/100,000 population). The case-fatality rate was 9.4% among hospitalized patients. Areas that included Nairobi's largest slums had particularly high attack rates. The epidemic displayed an unusual age distribution, with high attack rates among those 20-29 years old. A vaccination campaign was conducted. By early January, the weekly case count had fallen to 25 from a high of 272 (in September). A case-control study estimated the vaccine efficacy to be 87% (95% confidence interval, 67%-95%). A model estimated that the vaccination campaign reduced the number of cases by at least 20%. Multilocus enzyme electrophoretic typing demonstrated that the strain responsible for this large epidemic is closely related to strains that caused other recent epidemics, documenting further spread of what may be a particularly virulent clonal complex of group A Neisseria meningitidis.