Biomedical subjects
Publications and source records attributed to Tumani Corrah.
We report a case of purulent pericarditis caused by Staphylococcus aureus in a malnourished 17-month-old child. The clinical features, diagnosis especially the usefulness of non-invasive ultrasound as well as immunological and molecular biology studies, management and outcome of this life threatening condition are discussed.
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BACKGROUND: Studies in Africa investigating health-seeking behaviour by interviewing tuberculosis patients have revealed patient knowledge issues and significant delays to diagnosis. We aimed to study health-seeking behaviour and experience of those with cough in The Gambia and to identify whether they had tuberculosis. METHODS: During a round of a population under 3-monthly demographic surveillance, we identified people >10 years old who had been coughing > or = 3 weeks. A questionnaire was administered concerning demographic data, cough, knowledge, health seeking, and experience at health facilities. Case finding utilised sputum smear and chest X-ray. RESULTS: 122/29,871 coughing individuals were identified. Of 115 interviewed, 93 (81%) had sought treatment; 76 (81.7%) from the health system. Those that visited an alternative health provider first were significantly older than those who visited the health system first (p = 0.03). The median time to seek treatment was 2 weeks (range 0-106). 54 (58.1%) made their choice of provider because they believed it was right. Of those who left the health system to an alternative provider (n = 13): 7 believed it was the best place, 3 cited cost and 2 failure to improve. 3 cases were identified by sputum analysis, 11 more by X-ray; all had visited the health system first. Total 'excess' cough time was 1079 person weeks. CONCLUSION: The majority of people with cough in this population seek appropriate help early. Improved case detection might be achieved through the use of chest X-ray in addition to sputum smear.
BACKGROUND: The HIV-1 epidemic in West Africa is characterized by a slower rise than that in Eastern and Southern Africa. The HIV-2 epidemic in West Africa may be declining, but few long-term data exist. METHODS: In a research clinic in The Gambia, HIV-1 and HIV-2 prevalence trends among all new patients being tested for HIV were examined over a 16 year period (1988 till 2003). In newly diagnosed patients a baseline CD4 count was done. RESULTS: An HIV test was done in 23 363 patients aged 15 years or older. The prevalence of HIV-1 was 4.2% in 1988-91 and rose to 17.5% in 2001-03 (P < 0.0001, chi(2)-test for trend). The prevalence of HIV-2 was 7.0% in 1988-91 and declined to 4.0% in 2001-03 (P < 0.0001). HIV-1 prevalence increased and HIV-2 prevalence decreased with time in logistic regression models adjusting for age, sex, and indication for test (P < 0.0001). Baseline CD4 counts were available for 65% of patients. The median CD4 count was 215 cells/mm3 [interquartile range (IQR) 72-424] for HIV-1, and 274 (IQR 100-549) for HIV-2 infected patients. There was no marked trend of rise or decline in baseline CD4 count in either HIV-1 or HIV-2 infected patients over the study period. Forty-five per cent of newly diagnosed HIV patients had a CD4 count <200 cells/mm3. CONCLUSIONS: These data suggest that HIV-1 prevalence is rising in The Gambia, and that HIV-2 is declining. HIV patients in The Gambia present late and almost half of patients would qualify for anti-retroviral treatment at their first visit.
Simple robust approaches are needed to monitor the prevalence and incidence of HIV in Africa. The aim of this study was to evaluate the use of dried blood spot (DBS) as an alternative to serum or plasma for sentinel surveillance. Paired DBS and blood samples were obtained from 200 patients attending a genito-urinary medicine clinic in West Africa. The gold standard of diagnosis was based on the combination of 3 enzyme-linked immunosorbent assays (ELISA) using serum. The presence of HIV antibodies in eluates of dried blood spots was detected by ELISA, Gelatin Particle Assay (GPA) and Pepti-Lav 1-2 in 5 different testing strategies. All 200 eluates were tested individually, and in addition pools of 5 eluates each were tested. The sensitivity of the testing strategies ranged from 95.0% (83.1 - 99.4%) to 100% and the specificity from 97.5% (93.7 - 99.3%) to 100%. Testing in pools of 5 did not affect sensitivity. Dried blood spots were easy to work with. Test kit and laboratory consumable costs varied between 492 pounds and 1037 pounds (unpooled strategies) and 163 pounds and 421 pounds (pooled). The monospecific ELISAs used in this study are no longer in production; currently available differentiating assays need to be tested. DBS are recommended for sentinel surveillance in Africa.
OBJECTIVE: To build on the previously reported development of a Bayesian probabilistic model for interpreting verbal autopsy (VA) data, attempting to improve the model's performance in determining cause of death and to reassess it. DESIGN: An expert group of clinicians, coming from a wide range geographically and in terms of specialization, was convened. Over a four-day period the content of the previous probabilistic model was reviewed in detail and adjusted as necessary to reflect the group consensus. The revised model was tested with the same 189 VA cases from Vietnam, assessed by two local clinicians, that were used to test the preliminary model. RESULTS: The revised model contained a total of 104 indicators that could be derived from VA data and 34 possible causes of death. When applied to the 189 Vietnamese cases, 142 (75.1%) achieved concordance between the model's output and the previous clinical consensus. The remaining 47 cases (24.9%) were presented to a further independent clinician for reassessment. As a result, consensus between clinical reassessment and the model's output was achieved in 28 cases (14.8%); clinical reassessment and the original clinical opinion agreed in 8 cases (4.2%), and in the remaining 11 cases (5.8%) clinical reassessment, the model, and the original clinical opinion all differed. Thus overall the model was considered to have performed well in 170 cases (89.9%). CONCLUSIONS: This approach to interpreting VA data continues to show promise. The next steps will be to evaluate it against other sources of VA data. The expert group approach to determining the required probability base seems to have been a productive one in improving the performance of the model.
OBJECTIVES: To describe the characteristics of pneumococcal isolates obtained from patients with invasive pneumococcal disease in The Gambia. METHODS: Pneumococcal isolates were obtained from children aged < or =6 years with invasive pneumococcal disease during a Haemophilus influenzae vaccine effectiveness study (1997-2002) and from patients with invasive pneumococcal disease admitted to the MRC hospital, Fajara, for routine care (1996-2003). Isolates were identified, serotyped and tested for antibiotic susceptibility. RESULTS: Five hundred and thirty one pneumococcal isolates were obtained from 518 patients; 55 (10.6%) patients died; 415 isolates (79%) were from blood culture, 84 (16%) from CSF, and 42 (8%) from lung aspirates. Forty serogroups and serotypes were identified; six accounted for 64% and 16 for 86% of all episodes; 33.7% were of serotypes 1 and 5. 23.5% were of a 7-valent vaccine serotype, 57.1% were of a 9-valent vaccine serotype; 56% were of a 7-valent serogroup and 78% were of a 9-valent serogroup. There was a significant increase in the proportion of isolates of non-vaccine serogroup with increasing age (P < 0.0001). Antibiotic resistance had not significantly increased over time; but intermediate non-susceptibility to penicillin had risen and resistance to chloramphenicol had fallen in isolates of vaccine serotype compared with those of non-vaccine serotype. CONCLUSIONS: The majority of invasive pneumococcal disease in The Gambia is caused by pneumococci of relatively few serogroups. A conjugate vaccine would be expected to reduce the pneumococcal disease burden substantially and to have a beneficial effect on pneumococcal antibiotic resistance to penicillins.
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OBJECTIVE: To compare the enzyme-linked immunospot (ELISPOT) assay with the tuberculin skin test (TST) in children for the diagnosis of Mycobacterium tuberculosis infection in the Gambia. METHODS: We divided child contacts of sputum smear-positive tuberculosis cases into 3 age categories (<5, 5-9, and 10-14 years) and assessed agreement between the 2 tests plus their relationship to prior Bacille Calmette-Guerin (BCG) vaccination. We categorized a child's level of M tuberculosis exposure according to where he/she slept relative to a case: the same room, same house, or a different house. The relationship between exposure and test result was assessed by multiple logistic regression. RESULTS: In child contacts of 287 cases, 225 (32.5%) of 693 were positive by TST and 232 (32.3%) of 718 by ELISPOT. The overall agreement between tests was 83% and the discordance was not significant. Both tests responded to the M tuberculosis exposure gradient in each age category. The percentage of those who were TST positive/ELISPOT negative increased with increasing exposure. At the lowest exposure level, the percentage of ELISPOT-positive children who were TST negative was increased compared with the highest exposure level. Neither test had evidence of false positive results because of BCG. CONCLUSIONS: In Gambian children, the ELISPOT is slightly less sensitive than the TST in the diagnosis of M tuberculosis infection from recent exposure, and neither test is confounded by prior BCG vaccination. Evidence of reduced TST sensitivity in subjects with the lowest known recent M tuberculosis exposure suggests that, when maximal sensitivity is important, the 2 tests may be best used together.
BACKGROUND: Currently, reliable efficacy markers for assessment of new interventions against tuberculosis (TB) are limited to disease and death. More precise measurement of the human immune response to Mycobacterium tuberculosis infection may be important. A qualitative enzyme-linked immunospot assay (ELISPOT) result for early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) offers improved specificity over the purified protein derivative (PPD) skin test reaction in the detection of M. tuberculosis infection. We evaluated the quantitative ELISPOT and PPD skin test responses to recent M. tuberculosis exposure. METHODS: We studied quantitative PPD skin test and PPD ELISPOT results in 1052 healthy household contacts of index patients with cases of sputum smear-positive and culture-positive TB in The Gambia, according to a positive or negative ex vivo interferon gamma ELISPOT response to M. tuberculosis-specific antigens (ESAT-6/CFP-10). We then studied the quantitative PPD skin test and PPD ELISPOT results in patient contacts who had positive ESAT-6/CFP-10 results against a natural exposure gradient according to sleeping proximity to a patient with TB. RESULTS: The number of positive results was significantly greater for both PPD skin test and PPD ELISPOT in ESAT-6/CFP-10-positive subjects, compared with others (P<.0001). However, when quantitative PPD skin test and PPD ELISPOT results were compared in ESAT-6/CFP-10-positive subjects, only the ELISPOT count was sensitive to the exposure gradient, increasing significantly according to exposure (P=.009). CONCLUSIONS: The quantitative ELISPOT response to PPD in specific-antigen-positive contacts of patients with TB reflects the infectious load of M. tuberculosis as a result of recent exposure. This finding offers new possibilities for assessment of the efficacy of new interventions, and adjustment should be made for it when relating the early immune response to progression to disease.
BACKGROUND: Identification of basic prognostic indicators of HIV infection is essential before widespread antiretroviral therapy can be implemented in low-technology settings. This study assessed how well body mass index (BMI:kg/m2) predicts survival. METHODS: BMI within 3 months of HIV diagnosis was obtained from 1657 patients aged > or = 15 years, recruited in a seroprevalent clinical cohort in The Gambia since 1992 and followed up at least once. Baseline CD4+ counts and clinical assessment at time of diagnosis were done. RESULTS: The mortality hazard ratio (HR) of those with a baseline BMI <18 compared with those with a baseline BMI > or = 18 was 3.4 (95% CI, 3.0-3.9). The median survival time of those presenting with a BMI <16 was 0.8 years, in contrast to a median survival of 8.9 years for those with a baseline BMI > or = 22. Baseline BMI <18 remained a highly significant independent predictor of mortality after adjustment for age, sex, co-trimoxazole prophylaxis, tuberculosis, reported wasting at diagnosis, and baseline CD4+ cell count (adjusted HR = 2.5, 95% CI 2.0-3.0). Sensitivity and specificity of baseline BMI <18 was comparable to that of a CD4+ count <200 in predicting mortality within 6 months of diagnosis. DISCUSSION: BMI at diagnosis is a strong, independent predictor of survival in HIV-infected patients in West Africa. In the absence of sophisticated clinical and laboratory support, BMI may also prove a useful guide for deciding when to initiate antiretroviral therapy.
BACKGROUND: In sub-Saharan Africa, tuberculosis (TB) is the most frequently diagnosed opportunistic infection and cause of death among HIV-infected patients. HIV-2 has been associated with less immune suppression, slower disease progression and longer survival. OBJECTIVE: To examine whether the incidence of TB and survival after TB are associated with CD4 cell count rather than HIV type. METHODS: Clinical and immunological data were retrospectively evaluated among an open clinic-based cohort of HIV-1- and HIV-2-infected patients to determine incidence of TB (first diagnosis > 28 days after HIV diagnosis) and subsequent mortality. Patients were grouped by CD4 cell count into those with < 200, 200-500 and > 500 x 10 cells/l. RESULTS: Incident TB was diagnosed among 159 of 2012 patients, with 4973 person-years of observation time. In 105/159 (66.0%), the diagnosis was confirmed by direct microscopy or culture. Incidence of TB was highest in the group with < 200 x 10 cells/l (9.1/100 and 8.8/100 person-years in HIV-1 and HIV-2, respectively). Adjusted for CD4 cell count, there was no significant difference in incidence or mortality following TB between HIV-1- and HIV-2-infected patients. Mortality rate was higher in those with incident TB and HIV infection, most markedly in the group with the highest CD4 cell count (hazard ratio, 10.0; 95% confidence interval, 5.1-19.7). CONCLUSION: Adjusted for CD4 cell count, incidence of TB was similar among HIV-1- and HIV-2-infected patients. Mortality rates after TB diagnosis were similar in both groups and high compared with those without TB.
The purified protein derivative (PPD) skin test for Mycobacterium tuberculosis infection lacks specificity. We assessed 2 more specific M. tuberculosis antigens (ESAT-6 and CFP-10) by enzyme-linked immunospot assay (ELISPOT) compared with PPD by ELISPOT and skin test in The Gambia. Of 735 household contacts of 130 sputum smear-positive tuberculosis cases, 476 (65%) tested positive by PPD ELISPOT, 300 (41%) tested positive by PPD skin test, and 218 (30%) tested positive by ESAT-6/CFP-10 ELISPOT. Only 15 (2%) had positive ESAT-6/CFP-10 results and negative PPD results by ELISPOT. With increasing M. tuberculosis exposure, the percentage of subjects who were PPD skin test positive/ESAT-6/CFP-10 ELISPOT negative increased (P<.001), whereas the percentage of subjects who were PPD skin test negative/PPD ELISPOT positive decreased (P=.011). Eighteen (31%) ESAT-6/CFP-10 ELISPOT-positive subjects in the lowest exposure category had negative PPD skin test results. ESAT-6/CFP-10 ELISPOT probably offers increased specificity in the diagnosis of M. tuberculosis infection in this tropical setting of endemicity, at the cost of some sensitivity.
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Fewer people infected with human immunodeficiency virus (HIV) type 2 progress to acquired immunodeficiency syndrome, compared with those infected with HIV-1. To understand the immune mechanisms leading to slow progression in HIV-2 infection, cell-mediated immune responses were compared between the 2 infections in asymptomatic subjects with a CD4 cell count > or =20%. Interferon- gamma release from T lymphocytes and the cytotoxicity of CD8+ T lymphocytes were measured by ELISPOT and 51Cr release assays. The level of responses and the proportion of responders were similar in the 2 infections, despite a 20-fold difference in their geometric mean plasma virus loads. The proliferation of CD4+ T helper cells, which was evaluated by thymidine incorporation, was not different between the 2 infections. Contrary to widely held views, our results suggest that nonprogression in HIV-2 infection may not be due to more vigorous immune responses.
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A characteristic retinopathy associated with a poor prognosis has previously been described in African children with established cerebral malaria. However, relatively little is known about retinal abnormalities in children with severe non-cerebral malaria, the group most at risk of developing the cerebral complications of this disease. In this study the prevalence, pattern, clinical significance and accessibility to clinical examination of this characteristic retinopathy are described in 106 Gambian children admitted consecutively to hospital with severe malaria, including six with established cerebral malaria.
OBJECTIVE: To examine baseline plasma viral loads according to the CD4 cell percentage (CD4%) in HIV-1, HIV-2 and dually infected patients (HIV-D), and to relate these measurements to survival. PATIENTS AND METHODS: A total of 119 HIV-1, 137 HIV-2 and 81 HIV-D-infected patients attending the Medical Research Council clinic in The Gambia were recruited from 1991 according to baseline CD4%, and followed until death or the end of December 2000. HIV-1 and HIV-2 RNA levels were measured by in-house reverse transcriptase polymerase chain reaction assays. RESULTS: The plasma viral load, which varied inversely with CD4%, was similar in HIV-1 singly and dually infected patients, but was significantly higher in HIV-1 than in HIV-2 singly infected patients, except in those with a CD4% less than 14%. HIV-2 plasma viral load in dually infected patients did not vary significantly with CD4%, but was significantly lower than in HIV-2 singly infected patients with CD4% less than 14%. Multivariate analysis showed that only CD4% was independently associated with survival in HIV-1 and HIV-D infections; whereas both CD4% and plasma viral load were independently associated with survival in HIV-2 infections. The mortality rate of HIV-D-infected patients was not significantly different from that of HIV-1-infected patients, but was significantly higher in the absence of HLA B58. CONCLUSION: HIV-2 infection does not alter HIV-1 replication or prolong survival in dually infected patients. In a clinical setting in Africa, where many patients present with advanced disease, CD4% may be a more important predictor of prognosis than plasma viral load.