Nellie Lloyd-Evans

Elimination of Haemophilus influenzae type b (Hib) disease from The Gambia after the introduction of routine immunisation with a Hib conjugate vaccine: a prospective study

BACKGROUND Routine immunisation of infants in The Gambia with a Haemophilus influenzae type b (Hib) polysaccharide-tetanus toxoid conjugate vaccine began in May, 1997. We investigated the effectiveness of the vaccine when delivered through the expanded programme on immunisation and the effect of national immunisation on incidence of Hib disease. METHODS Surveillance for Hib disease was maintained in the western half of The Gambia using standard methods with an emphasis on meningitis. We estimated vaccine efficacy using the case control method, and vaccine coverage and population denominators for incidence rates using a cluster sample survey. Prevalence of Hib carriage in a sample of 1-2-year old children attending health centres for vaccination was ascertained with oropharyngeal swabs plated onto antiserum agar. FINDINGS Between May, 1997, and April, 2002, a total of 5984 children were examined for possible Hib infections. 49 children had Hib disease, 36 of whom had meningitis. The annual incidence rates of Hib meningitis before any use of the vaccine (1990-93) dropped from over 200 per 100,000 children aged younger than 1 year to none per 100,000 in 2002, and from 60 to no cases per 100,000 in children younger than 5 years. The prevalence of Hib carriage decreased from 12% to 0.25% (p<0.0001). Two doses of vaccine were needed for direct protection from Hib disease (vaccine efficacy 94%, 95% CI 62-99). Since most children received a protective dose after the age of greatest disease risk, indirect effects were important in reducing disease incidence. INTERPRETATION The Gambian Hib immunisation programme reduced the occurrence of Hib disease despite irregular vaccine supply. The effect of the programme in The Gambia has important implications for the introduction of the vaccine into routine immunisation programmes of other developing countries.

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.

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.

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.

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.

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

Summary 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.

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.

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

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 years 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.

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.