Epidemiology of invasive pneumococcal disease in the Western Region, The Gambia.

BACKGROUND: Streptococcus pneumoniae is a major cause of morbidity and mortality in young children in the developing world. The recent development of pneumococcal polysaccharide/protein conjugate vaccines may make possible prevention of this infection. However, little is known about the epidemiology of invasive pneumococcal disease in children in the developing world. OBJECTIVES: To determine the incidence and epidemiologic features of invasive pneumococcal disease in children resident in a semiurban area of The Gambia. METHOD: The study was part of a large trial of an Haemophilus influenzae type b vaccine that recruited 42 848 children at the age of 2 months during the period March, 1993, to October, 1995. Follow-up of study children continued until December 31, 1995; therefore the first children to enter the trial were followed for 2.5 years and the last for just a few months. During the period of surveillance, 2256 children were investigated for possible invasive pneumococcal disease when they presented to a hospital or health center. RESULTS: We detected 110 cases of pneumococcal disease. Pneumonia was the most common form of invasive pneumococcal disease observed (75.5% of patients). The incidence of pneumococcal disease was 224 [95% confidence interval (CI) 171, 277] per 100,000 child years among children ages 2 to 11 months, 139 (95% CI 93, 184) per 100,000 among children ages 12 to 23 months and 82 (95% CI 21, 143) per 100,000 among children ages 24 to 35 months. Pneumococci of serogroups 14, 6, 5, 23, 19, 46 and 2 were isolated most frequently. Susceptibility to pneumococcal disease was not increased significantly among Haemophilus influenzae type b-vaccinated children. CONCLUSIONS: The pneumococcus is a major cause of bacterial infection in The Gambia. A proposed nine-valent pneumococcal conjugate vaccine for developing countries containing conjugates of serogroups 1, 4, 5, 6, 9, 14, 18, 19 and 23 would cover 74% of cases of invasive pneumococcal disease in children resident in the Western Region of The Gambia.

Risk factors for severe respiratory syncytial virus infection leading to hospital admission in children in the Western Region of The Gambia.

BACKGROUND: Acute lower respiratory tract infections (ALRI) are the major cause of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) infection is the most important viral cause of severe ALRI but only a small proportion of children infected with this virus develop severe disease. To identify possible risk factors for severe RSV infection leading to hospital admission we have carried out a case-control study of Gambian children with RSV infection admitted to hospital. METHODS: In all, 277 children admitted to three hospitals in the Western Region of The Gambia with lower respiratory tract infection due to RSV were compared with 364 control children matched for age and location of residence who had not been admitted to hospital with an ALRI during the RSV season. A detailed questionnaire covering a wide range of potential social, environmental and nutritional risk factors was administered to the child's guardian. RESULTS: Cases came from larger or more crowded compounds than controls; increased risk was particularly associated with greater numbers of children in the age group 3-5 years living in the compound (odds ratio [OR] for > or =2 children in the age group 3-5 years = 9.1, 95% CI: 3.7-28). Cases were more likely to have a sibling who had died (OR = 3.4, 95% CI: 1.7-7). Controls were more likely to have been exposed to smoke from cooking fires (OR for the mother of cases cooking at least once daily = 0.31, 95% CI: 0.14-0.7). Other protective factors were father's nationality and some professions. Vegetables were included in the diet of controls more frequently than in that of cases (OR = 0.16, 95% CI: 0.06-0.46). Mothers of cases complained of asthma more frequently than mothers of controls, but the number of asthmatic mothers was small (4.2 versus 0.5%, P = 0.05). CONCLUSIONS: Risk factors for severe RSV infection identified in this study are not amenable to public health interventions. Prevention of severe infection is likely to require the development of an effective vaccine.

PIP: A case-control study was conducted to identify the potential social and environmental risk factors of hospital admission due to acute lower respiratory tract infections (ALRI) secondary to respiratory syncytial virus (RSV) in Gambia. Included in the study were 277 children admitted to three hospitals in the Western Region of Gambia with ALRI secondary to RSV were compared to 364 control children who suffered ALRI during RSV season but were not admitted. The guardians of children were administered a detailed questionnaire that covered a wide range of potential social, environmental, and nutritional risk factors. Comparison between the two groups was based on the child's age and location of residence. Results showed that the case group comes from larger or more crowded compounds than the control group. Increased risk was particularly associated with greater number of children in the age group 3-5 years living in the compound. The socioeconomic factors did not seem to play a major role in predisposing severe RSV infection. The housing and environmental conditions in the case and control groups were similar, and the educational status of parents in both groups did not differ substantially. In summary, few important differences were found between the case and controls in social and environmental risk factors. The risk factors found do not explain much of the attributable risks, such as maternal asthma.

Factors determining the outcome of treatment of adult smear-positive tuberculosis cases in The Gambia.

SETTING: Health centres in The Gambia, West Africa. OBJECTIVES: To identify factors determining the outcome of treatment of adult tuberculosis cases in a Tuberculosis Control Programme using directly observed treatment. DESIGN: Information on the outcome of treatment was collected on all tuberculosis cases registered with the Tuberculosis Control Programme in 1994 and 1995 and treated under supervision by tuberculosis control staff, nurses or village health workers. Treatment outcome was recorded as cured, completed treatment, failed, defaulted or died. Transferred-out patients were traced and their treatment outcome recorded at the health centre where they had last been seen. RESULTS: Data were analysed for 1357 adult smear-positive tuberculosis cases. Sputum smear conversion 2 months after the start of treatment was observed in 90% of smear-positive cases and was more likely to occur if the initial bacterial load in the sputum was low. The total cure rate was 74.6%. Female tuberculosis patients were more likely to achieve cure than males. Adjusting for sex, the cure rate was higher when treatment was provided by tuberculosis control staff in the main health centres rather than by nurses or village health workers at the peripheral level (odds ratio [OR] = 1.60, 95% confidence interval [CI] 1.23-2.09). The absence of sputum smear conversion after 2 months of chemotherapy was associated with defaulting later during treatment (OR = 2.0, 95% CI 1.15-3.57). Adjusting for age and sex, the death rate during treatment was higher in human immunodeficiency virus (HIV) positive than in HIV-negative tuberculosis patients. CONCLUSION: Directly observed treatment is an effective intervention for improving adherence of tuberculosis patients to treatment in a resource-poor country, provided that drugs are effectively delivered to the most peripheral level, and that health staff are adequately trained and regularly supervised. Patients with high bacterial load in initial sputum smears need to be closely supervised, as they are more likely to default from treatment.

Factors affecting time delay to treatment in a tuberculosis control programme in a sub-Saharan African country: the experience of The Gambia.

SETTING: Rural and urban health centres in The Gambia, West Africa. OBJECTIVES: To estimate the time delay between onset of symptoms and initiation of treatment and identify the risk factors influencing the delay in patients with tuberculosis (TB). DESIGN: Structured interviews with newly diagnosed TB patients aged over 15 years presenting to TB control staff in four health centres. RESULTS: A total of 152 TB patients were interviewed. The median delay from onset of symptoms to commencement of treatment was 8.6 weeks (range 5-17). Delay to treatment was independent of sex, but was shorter in young TB patients. The median delay was longer in rural than in urban areas (12 weeks [range 8.5-17] vs. 8 [4-12], P < 0.01) and in those who did not attend school, but this effect disappeared after adjusting for age and area of residence. Patients who reported haemoptysis as one of their initial symptoms had shorter delays to treatment. There was no relation between duration of delay to treatment and cure rate, but longer delay did increase the risk of death. CONCLUSION: Starting TB patients on treatment as early as possible plays a major role in reducing disease transmission in the community. Key to this is increasing awareness of the signs and symptoms of TB and ensuring easy access to diagnostic facilities and treatment.

Data management for an efficacy trial of a vaccine in the Gambia.

An individually randomised double-blind trial of PRP-T Hib conjugate vaccine was conducted in the Gambia between 1993 and 1995, in which 42,848 children were randomised into one of 10 groups, five corresponding to vaccine and five to placebo. Basic demographic data were collected on all children, and administration details of all doses of EPI vaccines were recorded. In addition, details on all doses of vaccines were recorded on each child's home-based health card; 2,681 episodes of possible Hib disease were investigated and for each episode detailed clinical data were collected. These investigations yielded 50 cases of confirmed Hib disease, which formed the basis of the final efficacy results. In all 50 cases, the data on the children's health card, describing the doses of study vaccine received exactly, matched the vaccination database which was filled with data returned from the clinics. The data-management procedures are described in detail in this paper.

Mycotoxic flora and mycotoxins in smoke-dried fish from Sierra Leone.

Examination of 20 samples of smoke-dried fish of the Ethmolosa sp. commonly called "Bonga", from homes and markets in Njala (Sierra Leone) revealed the presence of 4 Aspergilli species: A. flavus Links ex Fries, A. ochraceus Wilhelm, A. tamarii Kita and A. niger van Tieghem. Fresh or properly preserved smoke-dried fish showed no signs of fungal contamination. Mouldy fish extracts contained varying amounts of aflatoxins B1, G1, G2 and ochratoxin A. Isolates of A. flavus grown on yeast extract sucrose (YES) medium, produced considerable amounts of aflatoxin B1 and G1 and trace amounts of G2. On YES medium A. ochraceus produced large amounts of ochratoxin A but no penicillic acid.

A community trial of ivermectin for onchocerciasis in Sierra Leone: compliance and parasitological profiles after three and a half years of intervention.

We have studied the compliance patterns and the long-term effects of repeated ivermectin at various dosing intervals in a randomized controlled trial. The setting for the trial was six neighbouring communities hyperendemic for onchocerciasis in southern Sierra Leone. A total of 335 subjects attended a survey 18 months after the fifth treatment round. Of those randomized to ivermectin, over 85% had received at least three doses. There was no evidence that women of childbearing age were consistently under-treated, despite the criteria for exclusion from treatment. An intention-to-treat analysis showed that a 6-monthly ivermectin treatment regime satisfactorily suppressed microfilarial loads. Microfilarial repopulation was significantly slower over an 18-month period after multiple doses compared to a single dose. Further analysis of microfilarial repopulation suggests that there is a cumulative suppressive effect after at least the first three doses of ivermectin, and that an annual treatment interval is as effective for short-term microfilarial suppression as a 6-monthly interval.

Tuberculosis contacts but not patients have higher gamma interferon responses to ESAT-6 than do community controls in The Gambia.

The Mycobacterium tuberculosis antigen ESAT-6 has been proposed for tuberculosis immunodiagnosis. In The Gambia, 30% of community controls produced gamma interferon (IFN-gamma) in response to ESAT-6. Increased proportions of responders and intensities of responses were found in household contacts. Responses that were initially low in tuberculosis patients increased after treatment. An ESAT-6 IFN-gamma assay will be of limited use in the diagnosis of tuberculosis in countries where tuberculosis is endemic. Its role in contact tracing should be evaluated further.

Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate vaccine [corrected] for prevention of pneumonia and meningitis in Gambian infants.

BACKGROUND: In developing countries, pneumonia and meningitis due to Haemophilus influenzae type b (Hib) are common in children under age 12 months and the mortality from meningitis is high. Protein-polysaccharide conjugate vaccines have brought Hib disease under control in industrialised countries. We did a double-blind randomised trial in The Gambia to assess the efficacy of a Hib conjugate vaccine for the prevention of meningitis, pneumonia, and other invasive diseases due to Hib. METHODS: Between March, 1993, and October, 1995, 42,848 infants were randomly allocated the conjugate vaccine Hib polysaccharide tetanus protein (PRP-T) mixed with diphtheria-tetanus-pertussis vaccine (DTP), or DTP alone at age 2 months, 3 months, and 4 months. Children who presented with signs of invasive Hib were investigated by blood culture and, where appropriate, by lumbar puncture, chest radiograph, or percutaneous lung aspirate. Children were followed up for between 5 and 36 months. FINDINGS: The median ages at which children received the study vaccine were 11 weeks, 18 weeks, and 24 weeks. 83% of children enrolled received all three doses of vaccine. 17 cases of culture-positive Hib pneumonia, 28 of Hib meningitis, and five of other forms of invasive Hib disease were detected amongst the study children. The efficacy of the vaccine for the prevention of all invasive disease after three doses was 95% (PRP-T vaccinees 1, controls 19 [95% CI 67-100]), for the prevention of Hib pneumonia after two or three doses, 100% (vaccinees 0, controls 10 [55-100]), and for the prevention of radiologically defined pneumonia at any time after enrollment, 21.1% (PRP-T vaccinees 198, controls 251 [4.6-34.9]). INTERPRETATION: PRP-T conjugate Hib vaccine prevented most cases of meningitis and pneumonia due to Hib in Gambian infants. The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20% of episodes of pneumonia in young Gambian children are due to Hib. The introduction of Hib vaccines into developing countries should substantially reduce childhood mortality due to pneumonia and meningitis.