Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia.

In developing countries, endemic childhood meningitis is a severe disease caused most commonly by Streptococcus pneumoniae or Haemophilus influenzae type b (Hib). Although many studies have shown that fatality rates associated with meningitis caused by these organisms are high in developing countries, little is known about the long-term outcome of survivors. The purpose of this study was to assess the importance of disabilities following pneumococcal and Hib meningitis in The Gambia. 257 children aged 0-12 years hospitalized between 1990 and 1995 with culture-proven S. pneumoniae (n = 134) or Hib (n = 123) meningitis were included retrospectively in the study. 48% of children with pneumococcal meningitis and 27% of children with Hib meningitis died whilst in hospital. Of the 160 survivors, 89 (55%) were followed up between September 1996 and October 1997. Of the children with pneumococcal meningitis that were traced, 58% had clinical sequelae; half of them had major disabilities preventing normal adaptation to social life. 38% of survivors of Hib meningitis had clinical sequelae, a quarter of whom had major disabilities. Major handicaps found were hearing loss, mental retardation, motor abnormalities and seizures. These data show that despite treatment with effective antibiotics, pneumococcal and Hib meningitis kill many Gambian children and leave many survivors with severe sequelae. Hib vaccination is now given routinely in The Gambia; an effective pneumococcal vaccine is needed.

Haemophilus influenzae type b meningitis in The Gambia after introduction of a conjugate vaccine.

After the introduction of a Haemophilus Influenzae type b (Hib) conjugate vaccine into The Gambia, the annual incidence of Hib meningitis has fallen from more than 200 per 100,000 before vaccination to 21 per 100,000 during the past 12 months.

PIP: This paper reports on the impact of Haemophilus influenzae type b (Hib) conjugate vaccine on the incidence of Hib meningitis in Gambia. The incidence of Hib meningitis among infants younger than 12 months of age in Gambia is greater, and the children affected are younger, compared to children in more developed countries. Between March 1993 and December 1995, children who were administered diphtheria-tetanus-pertussis (DTP) vaccination were randomly assigned a course of Hib conjugate vaccine mixed with DTP or DTP only. In Gambia, DTP vaccinations are recommended at 2, 3, and 4 months of age. The coverage of these vaccinations has been over 85% since 1990. Hib disease has not disappeared from Gambia in the last 2 years since the national immunization program was introduced. However, the incidence rate has declined rapidly, and a longer period of vaccination may be needed to achieve a sufficient herd effect to protect unimmunized children.

Nasopharyngeal carriage of pneumococci in Gambian children and in their families.

BACKGROUND: Nasopharyngeal carriage of pneumococci is prevalent among children in developing countries but little is known about the relationship of nasopharyngeal carriage to invasive disease or about the way in which pneumococci spread within households. OBJECTIVES: To determine the prevalence of nasopharyngeal carriage in healthy and sick Gambian children and to investigate transmission within households. METHODS: Nasopharyngeal swabs were obtained by the per nasal route and cultured for pneumococci on selective media. Pneumococci were serotyped with the use of latex particles coated with type-specific antisera. RESULTS: Pneumococci were isolated from the nasopharynx of 73 (90.1%) of 81 children with invasive pneumococcal disease, 86 (76.1%) of 113 healthy, age-matched control children and 911 (85.1%) of 1071 sick children. Pneumococci belonging to serotypes 1, 14 and 12 were isolated significantly more frequently from cases than from matched controls. In 43 (76.8%) of 56 children with invasive disease, pneumococci isolated from the nasopharynx and from the blood or other sterile site belonged to the same serotype. Pneumococci of the same serotype as the bacterium responsible for invasive disease in a child were obtained from 72 (8.5%) of 843 family members, most frequently from young siblings of the case patients. CONCLUSION: Nasopharyngeal carriage of pneumococci is more prevalent among young Gambian children than among adults and invasive infections are probably acquired more frequently from siblings than from parents. However, further studies are needed to confirm this hypothesis with more discriminating markers than polysaccharide serotyping.

A study of risk factors for pneumococcal disease among children in a rural area of west Africa.

BACKGROUND: Pneumoccal infection is one of the leading causes of pneumonia, meningitis and septicaemia in developing countries. We have investigated possible risk factors for pneumococcal disease among children living in a rural area of The Gambia. METHODS: A prospective case-control study was conducted in which children with pneumococcal infection were identified from among children attending out-patient and under-fives clinics and matched according to age with healthy children selected randomly from the local community. A questionnaire was used to investigate possible nutritional, medical, socioeconomic and environmental risk factors for pneumococcal disease. RESULTS: An increased risk of pneumococcal disease was associated with poor weight gain, a history of serious illness in the previous 6 months, exposure to cigarette smoke or being carried on mother's back while cooking. The risk of pneumococcal disease was reduced among children whose mothers had a personal source of income. CONCLUSIONS: The incidence of pneumococcal disease could be reduced by improving nutrition and taking steps to identify and rehabilitate those children whose weight is faltering or falling. Encouraging mothers to develop greater financial independence may also be beneficial. Reduced exposure to smoke should be promoted by improving ventilation in kitchens, introducing more efficient and less polluting stoves, keeping children away from smoky environments and discouraging parental smoking.

PIP: Pneumococcal infection is a leading cause of pneumonia, meningitis, and septicemia in developing countries. The authors investigated possible risk factors for pneumococcal disease during 1989-91 among children living in the rural Upper River Division of The Gambia. A prospective case-control study approach was used in which 80 children with pneumococcal infection were matched according to age with 159 healthy children randomly selected from the local community. The subjects were of mean age 14.0-14.2 months. A questionnaire was used to identify possible nutritional, medical, socioeconomic, and environmental risk factors for pneumococcal disease. The study found an increased risk of pneumococcal disease to be associated with poor weight gain, a history of serious illness during the previous 6 months, exposure to cigarette smoke, or being carried upon a mother's back while she cooks. The risk of pneumococcal disease was reduced among children whose mothers had a personal source of income. The authors suggest reducing the incidence of pneumococcal disease by improving nutrition and growth monitoring, encouraging mothers to develop greater financial independence, and reducing children's exposure to smoke.

Pneumococcal disease among children in a rural area of west Africa.

BACKGROUND: The pneumococcus is a frequent cause of pneumonia and other serious infections among young children in developing countries. Defining the pattern of pneumococcal infection in these countries is important so that, with the advent of pneumococcal conjugate vaccines, rational vaccination policies can be developed. METHODS: Children younger than 5 years of age who attended clinics in a rural area of The Gambia, West Africa, were screened by assistants during a 2-year period. Children with predefined features suggestive of a diagnosis of pneumonia, meningitis or septicemia were referred to the Medical Research Council Field Station at Basse for investigation. RESULTS: Of 2898 children investigated 103 cases of invasive pneumococcal disease (70 definite and 33 probable) were identified, suggesting that the incidence of this infection in the study community is at least 554/100,000/year in children younger than 1 year of age and 240/100,000/year in those younger than 5 years, rates many times higher than those found in industrialized societies. The mean age of presentation was 15 months; more boys than girls were affected. Cases of pneumonia were encountered 8 times more frequently than those of meningitis. Antibiotic resistance was rarely found and cases of pneumonia, but not meningitis, responded well to treatment. Case-fatality rates in children with pneumonia and meningitis were 1 and 55%, respectively. The most prevalent pneumococcal serotypes were types 6, 14, 19, 1 and 5. CONCLUSION: About 60% of invasive pneumococcal infection in children in this community could potentially be prevented by a nine-valent pneumococcal conjugate vaccine (types 1, 4, 5, 6B, 9, 14, 18, 19F and 23) given at the ages of 2, 3 and 4 months.

Predictors for a positive blood culture in African children with pneumonia.

BACKGROUND: Blood culture isolation rates for children with pneumonia are generally low. Therefore it would be helpful if epidemiologic studies could identify children who have a higher than average chance of yielding a positive culture. METHODS: Simple clinical and laboratory predictors of a positive blood culture were investigated in 1222 children younger than 5 years of age with pneumonia who presented at rural dispensaries in The Gambia, West Africa. RESULTS: A high temperature (chi square for linear trend, 24.1; P < 0.0001), a rapid respiratory rate (chi square for linear trend, 6.33; P = 0.010), dehydration (odds ratio, 2.33; P < 0.001), nasal flaring (odds ratio, 2.06; P = 0.001), grunting (odds ratio, 4.01; P < 0.001), dullness to percussion (odds ratio, 2.31; P < 0.001), bronchial breathing (odds ratio, 2.61; P < 0.001) and diminished breath sounds (odds ratio, 2.07; P < 0.001) were positive predictors for a positive blood culture. Wheezing (odds ratio, 0.16; P < 0.001) and malaria parasitemia (odds ratio, 0.26; P = 0.008) were negative predictors. A combination of these findings were used to assess how the number of cultures taken might be reduced without substantially reducing the yield of positive cultures. For example it was found that exclusion of children with a temperature of < 38.0 degrees C and/or a respiratory rate of < 50/min and/or wheezing would have reduced the number of cultures taken by 55.6% but would have led to a loss of only 31.3% of positive cultures. CONCLUSION: Careful selection of children investigated by blood culture could help to reduce the work required during the preparations for and conduct of pneumococcal vaccine trials.

Potential interventions for the prevention of childhood pneumonia: geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates from children--implications for vaccine strategies.

Streptococcus pneumoniae is a leading cause of fatal bacterial pneumonia in young children. Pneumococcal polysaccharide vaccines have not been promoted for use in young children because many constituent serotypes are not immunogenic in children < 2 years old. Conjugating pneumococcal polysaccharide epitopes to a protein carrier would likely increase vaccine immunogenicity in children. We reviewed published and unpublished pneumococcal serotype and serogroup data from 16 countries on 6 continents to determine geographic and temporal differences in serotype and serogroup distribution of sterile site pneumococcal isolates among children and to estimate coverage of proposed and potential pneumococcal conjugate vaccine formulas. The most common pneumococcal serotypes or groups from developed countries were, in descending order, 14, 6, 19, 18, 9, 23, 7, 4, 1 and 15. In developing countries the order was 6, 14, 8, 5, 1, 19, 9, 23, 18, 15 and 7. Development of customized heptavalent vaccine formulas, one for use in all developed countries and one for use in all developing countries, would not provide substantially better coverage against invasive pneumococcal disease than two currently proposed heptavalent formulas. An optimal nanovalent vaccine for global use would include serotypes 1, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Geographic and temporal variation in pneumococcal serotypes demonstrates the need for a species-wide pneumococcal vaccine.

Importance of enteric bacteria as a cause of pneumonia, meningitis and septicemia among children in a rural community in The Gambia, West Africa.

Two thousand eight hundred ninety-eight children younger than 5 years old were investigated during a 2-year period in a rural area of The Gambia for possible pneumonia, meningitis or septicemia. After clinical examination and appropriate investigations, 1014 children were diagnosed as having pneumonia, 31 as having meningitis and 100 as having septicemia. Nine hundred seven children had a final diagnosis of malaria including 702 who satisfied the World Health Organization criteria for a diagnosis of pneumonia. A bacterial etiology was established in 115 (11%) patients with a final diagnosis of pneumonia, in 25 (81%) with meningitis and in 29 (29%) with suspected septicemia. Overall the pneumococcus was the leading pathogen identified among children with pneumonia and meningitis and ranked third among those with septicemia. However, during the wet season, when malaria transmission was highest, 50% of blood culture isolates obtained from children satisfying the World Health Organization criteria for a diagnosis of pneumonia were Salmonella or coliform species, and the pneumococcus and Haemophilus influenzae type b accounted for only 43% of isolates. Thus enteric bacteria may be as important as those bacteria more usually associated with respiratory disease among children presenting with a clinical picture of pneumonia during the wet season. This finding has important implications for case management and surveillance for antibiotic resistance.

Etiology of acute lower respiratory tract infections in children in a rural community in The Gambia.

Approximately 500 children younger than 5 years old resident in 7 villages in a rural area of The Gambia were monitored closely for 1 year for episodes of acute lower respiratory tract infection (ALRI). Each episode was investigated with antigen detection techniques and antibody assays as well as culture for bacteria and viruses. A pathogen was identified in 76 (34.2%) of 222 cases with clinical signs of ALRI and in 34 (42%) of the 81 cases who, in addition, had radiologic evidence of ALRI. Evidence of infection with a bacterial pathogen, most commonly Streptococcus pneumoniae or Haemophilus influenzae, was obtained in 32 (14.4%) cases with clinical signs of ALRI (23.5% of those with radiologically proved pneumonia). Viral agents were cultured from 42 (19%) of 221 cases but also from 14 (14.6%) of 96 controls some of whom had minor symptoms of upper respiratory tract infection. In the absence of an outbreak of respiratory syncytial virus the viral agents recovered most often were influenza A and adenoviruses.

Etiology of acute lower respiratory tract infections in Gambian children: II. Acute lower respiratory tract infection in children ages one to nine years presenting at the hospital.

Seventy-four children ages 1 to 9 years hospitalized because of severe pneumonia were investigated using blood cultures, lung aspirates, nasopharyngeal aspirates, serology and antigen detection procedures. A bacterial infection was identified in 57 (77%), a viral infection was seen in 25 (34%) and 18 (24%) had mixed viral-bacterial infections. The bacterial pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae found in 61 and 15% of patients, respectively. The viral pathogen most frequently recovered was respiratory syncytial virus (12%). Evidence of Chlamydia pneumoniae strain TWAR and Mycoplasma pneumoniae infection was found in 12 and 4% of cases, respectively. Overall a potential pathogen was identified in 60 (81%) children, with evidence of polymicrobial infection in 30 cases (40.5%). The study provides information on the relative role of different infectious agents in the etiology of severe pneumonia in children in a developing country.

Etiology of acute lower respiratory tract infections in Gambian children: I. Acute lower respiratory tract infections in infants presenting at the hospital.

Ninety infants less than 1 year of age with pneumonia and 43 control infants were investigated for viral and chlamydial infection with the use of culture and serology and for bacterial infection with the use of blood cultures, lung aspirates, antibody assays and antigen detection procedures. One or more potential pathogens were identified in 62 (69%) cases with pneumonia and in 12 (28%) controls. Infection by respiratory viruses was identified in 42 (49%) cases and in 8 (19%) controls. Respiratory syncytial virus was the commonest pathogen identified and was found in 32 cases (37%). Bacterial infections were also common, being found in 27 (30%) cases and 3 (7%) controls, and predominantly involved Streptococcus pneumoniae (20%) or Haemophilus influenzae (11%). Bacterial infections were associated with raised white blood cell counts and were identified more often by antigen detection procedures (68%) than by culture of blood or lung aspirates (34%) or by serology (33%). Mixed viral-bacterial infections were identified in 13 cases (15%). Infection with Chlamydia trachomatis was diagnosed in 2 infants with acute lower respiratory tract infection and in 1 control infant.

Helicobacter pylori in Gambian children with chronic diarrhoea and malnutrition.

Infection with Helicobacter pylori (formerly Campylobacter pylori) was studied by measuring antibody titres to H pylori in Gambian children. Serological evidence of infection was found in 12 of 82 (15%) infants aged less than 20 months; this increased to 62 of 135 (46%) in those aged 40-60 months. Positive serology was found in 41 of 77 (53%) infants with chronic diarrhoea and malnutrition (mean age 19 months, range 5-36) compared with 18 of 70 (26%) of age matched healthy controls and nearly a quarter (12/49, 24%) of age matched undernourished (marasmic) subjects. These data show that infection with H pylori is common in the Gambia and that in infancy this infection is associated with chronic diarrhoea and malnutrition.

Follow-up of Gambian children for a 1-year period after rotavirus infection.

To investigate the hypothesis that rotavirus infection in young children can trigger chronic diarrhoeal disease, a group of cases from a documented epidemic of rotavirus and a group of matched controls were followed for a 1-year period after infection. No evidence of excess chronic diarrhoea or vomiting in the group known to have been infected with rotavirus was found.

Latex agglutination test for diagnosing pneumococcal pneumonia in children in developing countries.

OBJECTIVE: To prepare and assess the sensitivity and specificity of a latex agglutination test specific for the serotype of antigen in diagnosing pneumococcal pneumonia in Gambian children. DESIGN: Comparison of agglutination test specific for serotype with culture of blood and lung aspirates, countercurrent immunoelectrophoresis, and commercial latex agglutination tests in diagnosing pneumococcal pneumonia. Cross reaction studies and investigation of 102 control children to determine specificity of agglutination test specific for serotype. SETTING: General medical ward of Medical Research Council laboratories, The Gambia. PATIENTS: 101 Gambian children aged between 2 months and 10 years admitted with severe pneumonia. INTERVENTIONS: Serum samples were boiled and treated with edetic acid, and urine samples were boiled and concentrated 25 times before testing. END POINT: A latex agglutination test specific for the serotype of pneumococcal antigen that is sensitive and highly specific for detecting pneumococcus in the urine of patients with pneumococcal pneumonia. MEASUREMENTS AND MAIN RESULTS: Concentrated urine samples from 16 of the 21 children (76%) with pneumococcal pneumonia established by results of culture of blood or lung aspirates gave a positive result with the agglutination test specific for serotype, whereas only four of the 102 urine samples obtained from control children without pneumonia gave positive results. The serotypes of antigens detected in the urine of children with pneumococcal pneumonia and the serotypes of pneumococci isolated from cultures of blood or lung aspirates were the same in all cases. CONCLUSIONS: When performed on urine samples the agglutination test specific for serotype has a high specificity and is more sensitive than culture of blood or lung aspirates, commercial agglutination tests, or countercurrent immunoelectrophoresis in identifying pneumococcal pneumonia. It is easy to use and should be especially useful in communities with limited laboratory facilities.

PIP: The objective of this study was to prepare and assess the sensitivity and specificity of a latex agglutination test specific for the serotype of antigen in diagnosing pneumococcal pneumonia in Gambian children. Among the measures evaluated, there was a comparison of agglutination test specific for serotype with blood and lung aspirate cultures, countercurrent immunoelectrophoresis, and commercial latex agglutination tests in the diagnosis of pneumococcal pneumonia. In addition, there were cross-reaction studies and investigation of 102 control children to determine the specificity of agglutination tests specific for the serotype. This evaluation was conducted in a general medical ward of the Medical Research Council Laboratories in the Gambia. 101 Gambian children between the ages of 2 months-10 years with severe pneumonia were included in this study. Serum samples were boiled and treated with edetic acid, and urine samples were boiled and treated with edetic acid, and urine samples were boiled and concentrated 25 times before testing. A latex agglutination test specific for the serotype of the pneumococcal antigen that is sensitive and highly specific the detecting pneumococcus in the urine of patients with pneumococcal pneumonia was conducted. Concentrated urine samples from 16 of 21 children (76%) with pneumococcal pneumonia established by results of culture of blood or lung aspirates gave a positive result with the agglutination test specific for serotype, whereas only 4 of 102 urine samples obtained from control children without pneumonia gave positive results. The serotypes of antigens detected in the urine of children with pneumococcal pneumonia and the serotypes of pneumococci isolated from blood or lung aspirates cultures were the same in all cases. When performed on urine samples, the agglutination test specific for serotype has a high specificity and is more sensitive than the cultures of blood or lung aspirates, commercial agglutination tests, or countercurrent immunoelectrophoresis in identifying pneumococcal pneumonia. It is easy to use and should be most useful in communities where there are limited laboratory facilities.

Assessment of clinical criteria for identification of severe acute lower respiratory tract infections in children.

222 acute lower respiratory tract infections (LRI), as defined by the World Health Organisation, were identified during one year's surveillance of a cohort of 500 Gambian children aged 0 to 4 years. Symptoms and signs at presentation were related to radiological evidence of lobar consolidation, indicating severe LRI. In infants, a fever of greater than 38.5 degrees C, refusal to breast-feed, or the presence of vomiting were the best predictors of severe LRI. In children aged 1 to 4 years, a fever of greater than 38.5 degrees C or a respiratory rate greater than 60/min were the most accurate clinical signs for severe LRI. Chest indrawing did not discriminate severe LRI. These community-based findings differ from results of hospital-based studies.

Trial of co-trimoxazole versus procaine penicillin with ampicillin in treatment of community-acquired pneumonia in young Gambian children.

134 Gambian children under 5 years of age with severe pneumonia (as defined by the World Health Organisation classification of acute respiratory infections) were given either oral co-trimoxazole for 5 days, or a single intramuscular dose of fortified procaine penicillin and 5 days of oral ampicillin. At 2 weeks, there was no significant difference in outcome between the two groups. Co-trimoxazole is much less expensive than ampicillin or procaine penicillin, requires only twice-daily administration, and can be given by health-care staff with little training. The results support the use of co-trimoxazole as the antibiotic of first choice in outpatient management of young children with pneumonia in developing countries.

Chemical disinfection of human rotaviruses: efficacy of commercially-available products in suspension tests.

Suspension tests were conducted on 69 commercial and 7 non-commercial disinfectant formulations to determine which classes of chemicals were most active against human rotavirus (HRV). Virus samples, in the presence of varying levels of organic matter, were exposed to the disinfectants for 1 min. The levels of remaining infectious virus were determined by plaque assay. Products were rated by their ability to reduce the levels of infectious virus by more than 3 log10 in the presence or absence of tryptose phosphate broth (peptides and inorganic salts) or fecal matter. Of the commercially-available products tested, only 25% were rated as highly and 7% as moderately effective. The remaining 68% were either effective only in the absence of any additional organic matter (48%) or were completely ineffective (20%). The majority (64%) of the moderately and highly effective products were further examined for their ability to inactivate greater than 6 log10 of infectious HRV in the presence of fecal matter or tryptose phosphate broth. With one exception, all these products were still effective. Products potentially suitable as topical antiseptics, hard surface disinfectants and instrument soaks were identified. The results emphasize the care that should be exercised in the selection of disinfectants for the control and prevention of rotaviral infections.

Chemical disinfection of human rotavirus-contaminated inanimate surfaces.

Fomites may play a role in the transmission of rotavirus infections, and in view of this, 27 disinfectants were evaluated for their ability to inactivate human rotavirus (HRV) on contaminated non-porous inanimate surfaces. Disks of stainless steel, glass and two types of plastics were contaminated with about 10(7) plaque-forming units of HRV suspended in faecal matter. The inoculum was allowed to dry and an equal volume of the product under test was applied to the contaminated surface. After contact for 1 min, the action of the disinfectant was stopped by dilution. Surviving infectious virus on the disks was determined by plaque assay in MA-104 cells. A product was considered to be effective if it could reduce the virus titre by at least 3 log10. Only 33.3% (9/27) of the formulations tested proved to be effective. Further testing of the effective products, which included antiseptics, instrument soaks and hard-surface disinfectants, showed that all of them could, in fact, reduce the virus titre on contaminated surfaces by at least 6 log10. These findings show the relative resistance of HRV to a wide range of chemical disinfectants in common use, and also emphasize the need for a more thorough evaluation of the virucidal potential of formulations regularly employed in attempts to prevent and control outbreaks of rotaviral diarrhoea.

Institutional outbreaks of rotavirus diarrhoea: potential role of fomites and environmental surfaces as vehicles for virus transmission.

To assess the potential of fomites and environmental surfaces as vehicles in the transmission of rotaviral diarrhoea, disks (1 cm diameter) of various porous and non-porous materials were contaminated with about 10(5) plaque-forming units of the Wa strain of human rotavirus (HRV) suspended in faecal matter. The contaminated disks were then held for 10 days at either room temperature (22 +/- 2 degrees C) or 4 degrees C with the relative humidity (RH) at the high (85 +/- 5%), medium (50 +/- 5%) or low (25 +/- 5%) level. Survival was longer on non-porous surfaces at the lower temperature and at lower humidity. In contrast, survival on porous surfaces was very variable; better on cotton-polyester than on poster card or paper currency on which HRV survived very poorly. These results suggest that under the right environmental conditions, HRV-contaminated objects could play a role in the transmission of rotavirus infections in hospitals, nursing homes and day-care centres.