Effect of age and vaccination with a pneumococcal conjugate vaccine on the density of pneumococcal nasopharyngeal carriage.

BACKGROUND: This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage. METHODS: A cluster-randomized trial was conducted in rural Gambia. In 11 villages (the vaccine group), all residents received 7-valent pneumococcal conjugate vaccine (PCV-7), while in another 10 villages (the control group), only children <30 months old or born during the study period received PCV-7. Cross-sectional surveys (CSSs) were conducted to collect nasopharyngeal swabs before vaccination (baseline CSS) and 4, 12, and 22 months after vaccination. Pneumococcal density was defined using a semiquantitative classification (range, 1-4) among colonized individuals. An age-trend analysis of density was conducted using data from the baseline CSS. Mean pneumococcal density was compared in CSSs conducted before and after vaccination. RESULTS: Mean bacterial density among colonized individuals in the baseline CSS was 2.57 for vaccine-type (VT) and non-vaccine-type (NVT) pneumococci; it decreased with age (P < .001 for VT and NVT). There was a decrease in the density of VT carriage following vaccination in individuals older than 5 years (from 2.44 to 1.88; P = .001) and in younger individuals (from 2.57 to 2.11; P = .070) in the vaccinated villages. Similar decreases in density were observed with NVT within vaccinated and control villages. No significant differences were found between vaccinated and control villages in the postvaccination comparisons for either VT or NVT. CONCLUSIONS: A high density of carriage among young subjects might partly explain why children are more efficient than adults in pneumococcal transmission. PCV-7 vaccination lowered the density of VT and of NVT pneumococcal carriage in the before-after vaccination analysis. CLINICAL TRIALS REGISTRATION: ISRCTN51695599.

Spatial analysis of tuberculosis in an urban west African setting: is there evidence of clustering?

OBJECTIVES: To describe the pattern of tuberculosis (TB) occurrence in Greater Banjul, The Gambia with Geographical Information Systems (GIS) and Spatial Scan Statistics (SaTScan) and to determine whether there is significant TB case clustering. METHODS: In Greater Banjul, where 80% of all Gambian TB cases arise, all patients with TB registered at chest clinics between March 2007 and February 2008 were asked to participate. Demographic, clinical characteristics and GPS co-ordinates for the residence of each consenting TB case were recorded. A spatial scan statistic was used to identify purely spatial and space-time clusters of tuberculosis among permanent residents. RESULTS: Of 1145 recruited patients with TB, 84% were permanent residents with 88% living in 37 settlements that had complete maps available down to settlement level. Significant high- and low-rate spatial and space-time clusters were identified in two districts. The most likely cluster of high rate from both the purely spatial analysis and the retrospective space-time analysis were from the same geographical area. A significant secondary cluster was also identified in one of the densely populated areas of the study region. CONCLUSIONS: There is evidence of significant clustering of TB cases in Greater Banjul, The Gambia. Systematic use of cluster detection techniques for regular TB surveillance in The Gambia may aid effective deployment of resources. However, passive case detection dictates that community-based active case detection and risk factor surveys would help confirm the presence of true clusters and their causes.

Invasive pneumococcal disease in children aged <5 years admitted to 3 urban hospitals in Ibadan, Nigeria.

BACKGROUND: Streptococcus pneumoniae remains a major cause of childhood morbidity and mortality in the world. The introduction of pneumococcal conjugate vaccine in developing countries will be facilitated by a clearer understanding of the disease burden for bacterial causes of pneumonia and meningitis and the prevalent serotypes of S. pneumoniae. METHODS: We conducted a prospective, hospital-based surveillance for a 2-year period involving children aged 2-59 months at 3 urban hospitals in Ibadan, Nigeria, using standard microbiological methods with confirmation and further testing of isolates at the Medical Research Council Laboratories in The Gambia. RESULTS: There were 1210 cases overall: 481 (39.8%) were meningitis, 399 (33.0%) were pneumonia, and 330 (27.2%) were bacteremia clinical syndromes. There were 24 cases of definite meningitis, of which 9 were caused by S. pneumoniae, 11 by Haemophilus influenzae type b, and 4 by Klebsiella species. Of the 90 culture-positive pneumonia cases, 9 were caused by S. pneumoniae, 2 by H. influenzae type b, and 79 by other species. Among cases of bacteremia, the pathogen isolation rate was 28.8% (95 of 330); the isolated species included S. pneumoniae (3 isolates), Staphylococcus aureus (20 isolates), Klebsiella species (13 isolates), Salmonella species (15 isolates), and Escherichia coli (6 isolates). Of the 23 S. pneumoniae isolates, 11 were serotyped; the serotypes found were 5 (5 isolates), 19F (3 isolates), and 4 (3 isolates), and 1 isolate was nontypeable. These isolates were all susceptible to penicillin. Eight of 9 patients with definite pneumococcal meningitis died, whereas all patients with pneumococcal pneumonia and septicemia survived. CONCLUSIONS: Of the pneumococcal serotypes identified, 55% were covered by the licensed 7-valent pneumococcal conjugate vaccine, whereas all are covered by the 10- and 13-valent vaccines.

Long-term morbidity from severe pneumonia in early childhood in The Gambia, West Africa: a follow-up study.

OBJECTIVE: To assess long-term outcomes in severe early childhood pneumonia in The Gambia. DESIGN: Observational cohort study of children hospitalised with severe pneumonia between 1992 and 1994 compared to age, sex, and neighbourhood-matched controls on measures of current general and pulmonary health. RESULTS: Of 83 children successfully traced, 68 of the 69 alive at follow-up agreed to participate. Thirteen per cent of cases and 4% of controls had lung disease clinically or on spirometry. Another 16 (13%) participants had abnormal spirometry but did not meet the American Thoracic Society technical criteria (formally 'inconclusive'). Odds ratios of lung disease among childhood pneumonia cases were 2.93 (95%CI 0.69-12.48, P = 0.1468) with inconclusives omitted; 2.53 (95%CI 0.61-10.59, P = 0.2033) with inconclusives included as normal; and 2.83 (95%CI 1.09-7.36, P = 0.0334) with inconclusives included as lung disease. Among deceased cases, most deaths were reported within weeks of discharge, suggesting a possible connection between admission and subsequent death. CONCLUSION: These African data, while not conclusive, add to previous data suggesting a link between severe early childhood pneumonia and later chronic lung disease. While larger-scale research is needed, increased awareness of possible long-term morbidity in children with severe pneumonia is warranted to limit its impact and optimise long-term health.

Oxygen for treatment of severe pneumonia in The Gambia, West Africa: a situational analysis.

SETTING: Health facilities in The Gambia, West Africa. OBJECTIVES: Oxygen treatment is vital in pneumonia, the leading cause of death in children globally. There are shortages of oxygen in developing countries, but little information is available on the extent of the problem. We assessed national oxygen availability and use in The Gambia, a sub-Saharan African country. METHODS: A government-led team visited 12 health facilities in The Gambia. A modified World Health Organization assessment tool was used to determine oxygen requirements, current provision and capacity to support effective oxygen use. RESULTS: Eleven of the 12 facilities managed severe pneumonia. Oxygen was reliable in three facilities. Requirement and supply were often mismatched. Both oxygen concentrators and oxygen cylinders were used. Suboptimal electricity and maintenance made using concentrators difficult, while logistical problems and cost hampered cylinder use. Children were usually triaged by trained nurses who reported lack of training in oxygen use. Oxygen was given typically by nasal prongs; pulse oximetry was available in two facilities. CONCLUSIONS: National data showed that oxygen availability did not meet needs in most Gambian health facilities. Remedial options must be carefully assessed for real costs, reliability and site-by-site usability. Training is needed to support oxygen use and equipment maintenance.

Measuring the exposure of infants and children to indoor air pollution from biomass fuels in The Gambia.

UNLABELLED: Indoor air pollution (IAP) from biomass fuels contains high concentrations of health damaging pollutants and is associated with an increased risk of childhood pneumonia. We aimed to design an exposure measurement component for a matched case-control study of IAP as a risk factor for pneumonia and severe pneumonia in infants and children in The Gambia. We conducted co-located simultaneous area measurement of carbon monoxide (CO) and particles with aerodynamic diameter <2.5 microm (PM(2.5)) in 13 households for 48 h each. CO was measured using a passive integrated monitor and PM(2.5) using a continuous monitor. In three of the 13 households, we also measured continuous PM(2.5) concentration for 2 weeks in the cooking, sleeping, and playing areas. We used gravimetric PM(2.5) samples as the reference to correct the continuous PM(2.5) for instrument measurement error. Forty-eight hour CO and PM(2.5) concentrations in the cooking area had a correlation coefficient of 0.80. Average 48-h CO and PM(2.5) concentrations in the cooking area were 3.8 +/- 3.9 ppm and 361 +/- 312 microg/m3, respectively. The average 48-h CO exposure was 1.5 +/- 1.6 ppm for children and 2.4 +/- 1.9 ppm for mothers. PM(2.5) exposure was an estimated 219 microg/m3 for children and 275 microg/m3 for their mothers. The continuous PM(2.5) concentration had peaks in all households representing the morning, midday, and evening cooking periods, with the largest peak corresponding to midday. The results are used to provide specific recommendations for measuring the exposure of infants and children in an epidemiological study. PRACTICAL IMPLICATIONS: Measuring personal particulate matter (PM) exposure of young children in epidemiological studies is hindered by the absence of small personal monitors. Simultaneous measurement of PM and carbon monoxide suggests that a combination of methods may be needed for measuring children's PM exposure in areas where household biomass combustion is the primary source of indoor air pollution. Children's PM exposure in biomass burning homes in The Gambia is substantially higher than concentrations in the world's most polluted cities.

Rising ELISPOT count prior to the onset of symptoms of full-blown tuberculosis disease.

The relationship between the T-cell response to mycobacterial antigens and the likelihood of progression to disease has not been defined. We report a rapidly rising ELISPOT count in a 55-year-old man with evidence of Mycobacterium tuberculosis infection prior to the onset of symptoms of disease. This case illustrates the possible utility of quantitative changes in the ELISPOT count in predicting progression from M. tuberculosis infection to disease.

Clinical presentation and outcome of tuberculosis patients infected by M. africanum versus M. tuberculosis.

SETTING: A tuberculosis (TB) case contact study in the Gambia. OBJECTIVE: To test whether Mycobacterium africanum, which has lost around 68 kb compared with M. tuberculosis sensu stricto, causes less severe TB disease. DESIGN: We genotyped mycobacterial isolates and compared clinical and radiological characteristics as well as outcome data of M. africanum-infected TB patients with those infected with M. tuberculosis. RESULTS: Of 317 index cases, 301 had a mycobacterial isolate available, 290 of which had an interpretable spoligotype pattern. Of these, 110 isolates (38%) were M. africanum and 180 (62%) were M. tuberculosis. M. africanum cases had lower body mass indices (17 vs. 17.45 for M. tuberculosis-infected patients, P = 0.029) and their radiographic disease was more extensive (96% vs. 89% had at least moderately severe radiographic changes, P = 0.031). Outcome on treatment was similar (2.8% of human immunodeficiency virus [HIV] negative M. africanum patients died on treatment vs. 3.0% of M. tuberculosis patients, P = 0.95). CONCLUSION: M. africanum causes sputum smear-positive tuberculosis disease that is at least as severe as that caused by M. tuberculosis sensu stricto. Further clinical comparisons may be helpful in smear-negative patients and HIV-TB co-infected patients, and to identify whether there is any difference in time to develop disease.

Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. METHODS: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. FINDINGS: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. INTERPRETATION: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

Identifying ELISPOT and skin test cut-offs for diagnosis of Mycobacterium tuberculosis infection in The Gambia.

SETTING: An urban area, The Gambia. OBJECTIVE: To identify ELISPOT and PPD skin test cut-offs, targeting sensitivity and specificity equivalence. DESIGN: Tuberculosis cases >5 years of age and their household contacts underwent ELISPOT, HIV and PPD skin tests. Cases and contacts sleeping in a different house were used to estimate sensitivity and specificity, providing two planes for estimating cut-offs. Specificity was adjusted for infection from previous exposure using a multivariate discrimination algorithm. RESULTS: The point on the line of intersection of the planes that maximised sensitivity and specificity equivalence occurred at 4 spots (95% confidence interval [CI] 3.5-5, multiplier=0 ) for CFP-10 and 5.5 spots (4.5-8, multiplier=0 for ESAT-6), yielding a sensitivity and specificity of 76% for both antigens. Combining ESAT-6 and CFP-10 using an 'or' statement yielded a maximum equivalence sensitivity and specificity of 76.5% at 6 spots for ESAT-6 and 11.5 spots for CFP-10. For the PPD skin test sensitivity and specificity, an equivalence of 78% occurred at 11 mm induration (9-13 mm). CONCLUSION: An ELISPOT cut-off for ESAT-6 or CFP-10 could be set at 4-8 spot forming units (20-40 spots per million), with little benefit from combining the results. A cut-off of 9-13 mm for the PPD skin test is reasonable when comparing with the ELISPOT.

Childhood pneumonia and crowding, bed-sharing and nutrition: a case-control study from The Gambia.

SETTING: Greater Banjul and Upper River Regions, The Gambia. OBJECTIVE: To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia. DESIGN: A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2-59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season. RESULTS: Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2-8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1-13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2-17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP. CONCLUSION: Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.

Long term outcome of trichiasis surgery in the Gambia.

BACKGROUND: Trichiasis surgery is believed to reduce the risk of losing vision from trachoma. There are limited data on the long term outcome of surgery and its effect on vision and corneal opacification. Similarly, the determinants of failure are not well understood. METHODS: A cohort of people in the Gambia who had undergone surgery for trachomatous trichiasis 3-4 years earlier was re-assessed. They were examined clinically and the conjunctiva was sampled for Chlamydia trachomatis polymerase chain reaction (PCR) and general bacterial culture. RESULTS: In total, 141/162 people were re-examined. Recurrent trichiasis was found in 89/214 (41.6%) operated eyes and 52 (24.3%) eyes had five or more lashes touching the globe. Corneal opacification improved in 36 of 78 previously affected eyes. There was a general deterioration in visual acuity between surgery and follow up, which was greater if new corneal opacification developed or trichiasis returned. Recurrent trichiasis was associated with severe conjunctival inflammation and bacterial infection. C trachomatis was detected in only one individual. CONCLUSIONS: Recurrent trichiasis following surgery is a common potentially sight threatening problem. Some improvement in the cornea can occur following surgery and the rate of visual loss tended to be less in those without recurrent trichiasis. The role of conjunctival inflammation and bacterial infection needs to be investigated further. Follow up of patients is advised to identify individuals needing additional surgical treatment.

A randomised controlled trial of azithromycin following surgery for trachomatous trichiasis in the Gambia.

BACKGROUND/AIM: Trachomatous trichiasis frequently returns following surgery. Several factors may promote recurrence: preoperative disease severity, surgeon ability, surgical procedure, healing responses, and infection. This study investigates whether enhanced control of infection, both of Chlamydia trachomatis and other bacteria, with azithromycin can improve surgical outcome in a trachoma control programme. METHODS: Individuals with trachomatous trichiasis were examined and operated. After surgery patients were randomised to the azithromycin or control group. The azithromycin group and children in their household were given a dose of azithromycin. Antibiotic treatment was repeated at 6 months. All patients were reassessed at 6 months and 12 months. Samples were collected for C trachomatis polymerase chain reaction and general microbiology at each examination. RESULTS: 451 patients were enrolled. 426 (94%) were reassessed at 1 year, of whom 176 (41.3%) had one or more lashes touching the eye and 84 (19.7%) had five or more lashes. There was no difference in trichiasis recurrence between the azithromycin and control group. Recurrent trichiasis was significantly associated with more severe preoperative trichiasis, bacterial infection, and severe conjunctival inflammation at 12 months. Significant variability in outcome was found between surgeons. Visual acuity and symptoms significantly improved following surgery. CONCLUSION: In this setting, with a low prevalence of active trachoma, azithromycin did not improve the outcome of trichiasis surgery conducted by a trachoma control programme. Audit of trichiasis surgery should be routine.

The Gambian Haemophilus influenzae type b vaccine trial: what does it tell us about the burden of Haemophilus influenzae type b disease?

The true burden of disease caused by Haemophilus influenzae type b (Hib) remains a mystery in many parts of the developing world. The most frequent manifestations of Hib disease are pneumonia and meningitis. In developing countries where it has been studied, Hib has proved to be a major cause of infant meningitis, generally occurring with greater frequency, in younger infants and with a worse outcome than in industrialized countries in the prevaccine era. The burden of Hib pneumonia is more difficult to define. Studies from developing countries of pneumonia etiology suggested that Hib was responsible for 5 to 10 of episodes of severe pneumonia. A Gambian study found Hib to be responsible for 7% of cases. However, a recently published trial of a Hib conjugate vaccine in Gambian infants showed that the vaccine prevented 21% of episodes of severe pneumonia in vaccine recipients, suggesting that this is the true contribution of Hib to the burden of severe pneumonia. The same trial demonstrated a mild herd effect, so this figure may be an underestimate. The biases that lead to the underestimation of the contribution of Hib to the pneumonia burden also apply to estimates of the proportion of severe pneumonia caused by Streptococcus pneumoniae. Vaccine trials may reveal the true burden of that pathogen also.

Evaluation of Binax now Streptococcus pneumoniae urinary antigen test in children in a community with a high carriage rate of pneumococcus.

Pneumococcal antigen was present in urine from 49 of 102 well Gambian children. Eighty-nine of the 102 were nasopharyngeal carriers of pneumococci. The positive predictive value for carriage was 96%, and the negative predictive value was 22%. The test is not useful for predicting etiology of disease in populations with a high rate of nasopharyngeal carriage of pneumococci.

The etiology of pneumonia in malnourished and well-nourished Gambian children.

During a 2-year period 159 malnourished children ages 3 months to 5 years with radiologic evidence of pneumonia were investigated to determine the cause of their pneumonia. In addition 119 malnourished children without pneumonia, 119 well-nourished children with pneumonia and 52 well-nourished children without pneumonia were studied as controls. Percutaneous lung aspiration was performed on 35 malnourished and 59 well-nourished children with pneumonia. Bacteria were isolated from the blood, lung or pleural fluid of 28 (18%) malnourished children with pneumonia, 42 (35%) well-nourished children with pneumonia and from the blood of 5 (4%) malnourished children without pneumonia. Streptococcus pneumoniae and Haemophilus influenzae, which were the two organisms isolated most frequently in both groups of children with pneumonia, were found in 17 (11%) malnourished and 39 (33%) well-nourished children with pneumonia. Mycobacterium tuberculosis was detected in 5 malnourished children with pneumonia. A potentially pathogenic virus was identified in 35% of malnourished children with pneumonia and 40% of well-nourished children with pneumonia, and from 25% of children without pneumonia. The viruses identified most frequently were adenovirus and respiratory syncytial virus.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: During November 1990-October 1992 in Banjul, Gambia, providers at a hospital enrolled 159 children with pneumonia and 119 children without pneumonia, 119 well-nourished children with pneumonia, and 52 well-nourished children without pneumonia into a study examining the bacteriologic and virologic etiology of pneumonia. Pneumonia was more common among children with marasmic kwashiorkor (12% of all malnourished children) than among other malnourished children (53% vs. 33%; p 0.05). Most malnourished children (49%) were undernourished. 11% of all malnourished children had kwashiorkor. Laboratory personnel isolated bacteria from 28 (18%) malnourished children with pneumonia, 42 (35%) well-nourished children with pneumonia, and 5 (4%) malnourished children without pneumonia. Among all pneumonia cases, Streptococcus pneumoniae and Haemophilus influenzae were the most prevalent bacteria, especially among the well-nourished children (33% vs. 11%; p 0.001). They were not present in malnourished children without pneumonia. Mycobacterium tuberculosis was isolated in 5 malnourished children with pneumonia. Pathogenic viruses were isolated more often from malnourished children with pneumonia and from well-nourished children with pneumonia than from children without pneumonia (35% and 40%, respectively, vs. 25%; p 0.01). Most common pathogenic viruses were adenovirus and respiratory syncytial virus (RSV). RSV was more common in well-nourished children with pneumonia than malnourished children with pneumonia (13% vs. 6%; p 0.05). Herpes simplex virus was more common in malnourished children with pneumonia than well-nourished children (6% vs. 2%). 25 children had both bacterial and viral pathogens. Only 4 children (all with pneumonia) had the measles virus. These findings suggest that S. pneumoniae and H. influenzae are probably the bacterial causes of pneumonia in both well-nourished and malnourished children in areas with rare cases of measles and kwashiorkor. In these areas, M. tuberculosis may be also a cause of pneumonia in malnourished children, especially if edema is present.

Safety and immunogenicity of a nonavalent pneumococcal vaccine conjugated to CRM197 administered simultaneously but in a separate syringe with diphtheria, tetanus and pertussis vaccines in Gambian infants.

BACKGROUND: Unrelenting high morbidity and mortality have mandated that immunogenic vaccines be used to combat pneumococcal disease in infants. OBJECTIVES: To evaluate the safety and immunogenicity of a nonavalent pneumococcal conjugate vaccine and the antigenic interaction when administered simultaneously with diphtheria, tetanus and pertussis vaccines. METHODS: Two hundred seven infants were randomized to receive three doses of either nonavalent protein conjugate pneumococcal vaccine (PnCV) or inactivated polio vaccine (IPV) at 2, 3 and 4 months of age with routine Expanded Program of Immunization vaccines as scheduled. Vaccinees were visited on Days 1, 2 and 7 to observe local and systemic adverse reactions. Blood was drawn before the first dose and 1 month after the third dose. Antibody concentrations in sera were measured by standardized enzyme-linked immunosorbent assay. Nasopharyngeal carriage of pneumococci was tested at 5 and 9 months of age. RESULTS: No serious reactions were observed. Local induration and tenderness were observed more commonly at the site of administration of diphtheria, tetanus and pertussis vaccines than at the site of administration of IPV or PnCV. Between 79 and 91% achieved >1 microg/ml antibody against specific pneumococcal serotypes. Antibody responses to diphtheria and pertussis antigens were similar in both groups; however, antibody response to tetanus toxoid was significantly lower in infants who received PnCV (geometric mean concentration, 11.1 vs. 17.4; P < 0.001). Nasopharyngeal carriage in PnCV-vaccinated children was reduced but not significantly different from those vaccinated with IPV. CONCLUSION: Simultaneous administration of PnCV with Expanded Program of Immunization vaccines is safe and immunogenic. immune response to the composite antigens is likely to confer protection.

A randomized trial of chloramphenicol vs. trimethoprim-sulfamethoxazole for the treatment of malnourished children with community-acquired pneumonia.

Children in developing countries who present with malnutrition often have infections, particularly pneumonia, at the time of presentation. We evaluated the initial antibiotic management of 144 Gambian children who presented for the first time with malnutrition and who had clinical or radiologic evidence of pneumonia. They were enrolled in a double blind trial of trimethoprim-sulfamethoxazole vs. chloramphenicol. Most children in the study underwent detailed investigations of bacterial and viral etiology as part of another study. The study drug was administered for a week along with oral metronidazole, vitamins and standardized nutritional therapy. Treatment failure was defined as the need for change to parenteral antibiotics during treatment, failure to respond to a week of treatment with the study drug or relapse during the following 2 weeks. There were no differences between the treatment groups in the clinical indicators of severity, etiology or radiologic findings. Thirty-three children were excluded from the analysis because of tuberculosis, inappropriate enrollment or inadequate follow-up. Of the 111 children remaining, 32 (16 in each arm of the study) failed treatment. Clinical failure was not related to in vitro antimicrobial resistance in the 20 cases in which invasive bacterial isolates were obtained. Those who failed treatment were more likely to have had lower chest wall indrawing and positive bacterial cultures than those who were successfully treated. In an area with infrequent antimicrobial resistance of common respiratory pathogens, oral chloramphenicol and trimethoprim-sulfamethoxazole were equally effective in the initial management of malnourished children with community-acquired pneumonia.

The clinical spectrum of respiratory syncytial virus disease in The Gambia.

BACKGROUND: Respiratory syncytial virus (RSV) is a well-recognized cause of lower respiratory tract infections in early childhood in industrialized countries, but less is known about RSV infection in developing countries. METHODS: Four outbreaks of RSV infection that occurred between 1993 and 1996 in The Gambia, West Africa, were studied. RSV was sought by immunofluorescent staining of nasopharyngeal aspirate samples among young children who presented with respiratory infections at three hospitals in the Western Region of the country. RESULTS: Five hundred seventy-four children with RSV infection were identified. The median ages of children seen in 1993 through 1996 were 3, 7, 8 and 5 months, respectively. Sixty-two percent of children <6 months old were boys. Thirteen children (2.4%) had conditions considered to increase the risk of severe RSV infection. On physical examination crepitations were heard in 80% of the children admitted to hospital, whereas wheezes were heard in only 39%. Eighty (16%) children received oxygen because of hypoxemia. Nine of 255 blood cultures (3.5%) were positive: 4 Streptococcus pneumoniae; 2 Haemophilus influenzae type b; 2 Staphylococcus aureus; and 1 Enterobacter agglomerans. Thirteen children died (2.4%). During the 4 study years 90, 25, 75 and 95% of isolates typed were RSV Subgroup A, respectively. CONCLUSIONS: RSV is a significant cause of lower respiratory tract infection in young children in The Gambia, causing epidemics of bronchiolitis. It poses a significant burden on the health system, especially through the demand for supplementary oxygen. The clinical spectrum of RSV disease in The Gambia is similar to that seen in developed countries; concomitant bacterial infections are uncommon.

PIP: Respiratory syncytial virus (RSV) is a well-recognized cause of lower respiratory tract infections during early childhood in industrialized countries. The study of 4 RSV infection outbreaks which occurred during 1993-96 in The Gambia led to the identification of RSV infection in 574 children through the immunofluorescent staining of nasopharyngeal aspirate samples among children of median age 3-8 months who presented with respiratory infections at 3 hospitals in the Western region of the country. 13 children had conditions thought to increase the risk of severe RSV infection, with crepitations heard during physical examinations in 80% of children admitted to the hospital and wheezes heard in 39%. 80 children were given oxygen because of hypoxemia. 9 of 255 blood cultures were positive for the following pathogens: 4 Streptococcus pneumoniae, 2 Haemophilus influenzae type b, 2 Staphylococcus aureus, and 1 Enterobacter agglomerans. 13 children died. 90% of isolates typed during year 1 were RSV subgroup A, 25% in the second year of study, 75% in year 3, and 95% in year 4. These findings demonstrate that RSV is a significant cause of lower respiratory tract infection in young children in The Gambia, causing epidemics of bronchiolitis. It is most likely cost-effective to prevent RSV infection through vaccination.

Etiology of serious infections in young Gambian infants.

BACKGROUND: Despite improvements in infant mortality rates in many developing countries including The Gambia, neonatal mortality remains high and many neonatal deaths are caused by infection. The study described in this paper was conducted to determine the bacterial and viral etiology of serious infections in Gambian infants younger than 91 days old. METHODS: At a first level health facility 497 infants with symptoms that could indicate serious infection were enrolled, of whom 239 with 1 or more signs of serious infection and 55 with no signs were investigated, yielding 17 cases with positive bacterial cultures of blood and/or cerebrospinal fluid. At a nearby pediatric referral hospital 198 infants were seen and 182 were investigated, yielding 35 positive bacterial cultures. RESULTS: There were 15 culture positive cases of meningitis caused by Streptococcus pneumoniae (7), Streptococcus pyogenes (2), Enterobacter cloacae (2), Escherichia coli (1), Haemophilus influenzae type b (1), Streptococcus agalactiae (1) and Salmonella spp. (1). Six of these children died. Thirty-three infants without meningitis had positive blood cultures for Staphylococcus aureus (17), S. pneumoniae (3), Salmonella spp. (5), E. coli (3), other enterobacteria (4) and S. agalactiae (1), of whom 14 died. Nasopharyngeal aspirates from 438 children were investigated for common respiratory viruses. Respiratory syncytial virus was found in 51, influenza A in 46, influenza B in 22, parainfluenza in 26 and adenovirus in 16. Respiratory syncytial virus and influenza A isolates were found most frequently toward the end of the wet season. Nasopharyngeal carriage of S. pneumoniae and H. influenzae was studied in 320 infants recruited during the first year. Of these 184 (58%) were positive for S. pneumoniae and 141 (44%) were positive for H. influenzae, 18 of which were type b. Infants with a bacterial isolate from blood or cerebrospinal fluid were more likely than the rest to die, whereas those with a viral isolate were less likely to die. CONCLUSIONS: The most important causes of serious infections in young Gambian infants are Staphylococcus aureus, S. pneumoniae and Salmonella spp.