Diabetes mellitus is not a predictor of poor TB treatment outcomes.

OBJECTIVE: To investigate whether diabetes mellitus (DM) influences TB treatment outcomes.METHODS: This was a retrospective observational cohort study of all notified TB cases from a large London TB centre over a 5-year period. WHO criteria were used to define TB treatment outcomes.RESULTS: The prevalence of DM at TB treatment initiation was 15% (126/838). Most patients (83.3%, 105/126) were on hypoglycaemic treatment and well-controlled (median glycated haemoglobin 53.5 mmol/mol). DM patients were older, more likely to be of Asian ethnicity and had a higher pre-treatment weight. Time from presentation to treatment initiation was longer (median 87.5 vs. 63 days; P < 0.001), while they were significantly more comorbid (median Charlson Comorbidity Index 3 vs. 0; P < 0.001). Overall, favourable treatment outcomes were recorded for 89.5% of patients (87.7% vs. 89.8% for DM and non-DM patients respectively, P = 0.52). In multivariable analysis, DM was not associated with unfavourable TB treatment outcomes (OR 0.49, 95% CI 0.23-1.04, P = 0.06). Independent predictors of unfavourable outcome included age, cavitation, chronic neurological disease and malignant neoplasm.CONCLUSIONS: In a well-resourced setting, with predominantly well-controlled DM patients on treatment, DM was not an independent predictor of unfavourable TB treatment outcomes.

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.

Drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis in Ibadan, Nigeria.

BACKGROUND: Information on TB drug resistance profiles and its' associated risk factors are scarce in Nigeria despite the large burden of disease in the country. The study was designed to report drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis (TB) in Ibadan, Nigeria. METHOD: Sputum from consenting pulmonary TB patients were collected and cultured for Mycobacterium tuberculosis (Mtb) at the TB laboratory of the University College Hospital, Ibadan, Nigeria using standard method. Mtb were stored and sent for drug susceptibility testing against first and second-line anti-TB drugs at the MRC Unit, The Gambia and at the Institute of Tropical Medicine, Antwerp, Belgium using BACTEC MGIT 960 and proportion method on solid medium respectively. RESULTS: Of 238 Mtb collected, 124 (52.1%) were viable, 102 (59.65%) non-viable while 12 (7.02%) were contaminated. About half (58.87%) of the Mtb were from previously treated patients, 40 (32.26%) were from new patients while treatment history of 1.1 (8.87%) were unknown. Forty-seven (37.90%) of the 124 Mtb. tested were multidrug resistant (MDR) out of which, 40 (85.10%) were from previously treated patients.. HIV prevalence was 8.69%. Of the 17 MDR-TB from previously treated cases tested for second-line drugs, four (23.53%) were resistant to fluoroquinolones or injectable agents, 13 (76.47%) were susceptible while none was resistant to both of these classes of drugs. CONCLUSION: MDR-TB in Ibadan already demonstrates resistance to second line anti-TB drugs hence management of MDR-TB patients should be strengthened to prevent emergence of extensively drug-resistant TB (XDR-TB).

Management of persistent purulent pericarditis using streptokinase for intrapericardial fibrinolysis.

Purulent pericarditis (PP) is a very serious condition with almost 100% mortality if untreated. Intrapericardial fibrinolysis is a preferred alternative to pericardectomy in the treatment of persistent PP, but there are no consensus guidelines on the standard protocol for this procedure in children. A 9-year-old boy was referred to the Medical Research Council Unit in The Gambia (MRC). He had been unwell for 18 days with a high continuous fever, cough, fast breathing, and dyspnoea on exertion. Prior to referral he had been treated for malaria and pneumonia with no improvement. At the MRC, he was diagnosed with purulent pericarditis caused by Staphylococcus aureus and after admission he was managed for 4 weeks with intravenous antibiotics, pericardial aspirations followed by saline lavage of the pericardium and intrapericardial antibiotic instillation. Despite these measures, massive re-accumulation of the purulent pericardial effusion continued. Once daily intrapericardial instillation of streptokinase at a dose of 18,000 i.u/kg diluted in 50 ml of normal saline, and saline washout of the pericardium after 2 hours was commenced on the 29th day of admission, in addition to the antibiotics. This technique of fibrinolysis employed for 2 days was effective in managing the persistent purulent pericarditis when pericardial aspiration and intravenous and intrapericardial antibiotics failed.

Food intake increases liver stiffness measurements and hampers reliable values in patients with chronic hepatitis B and healthy controls: the PROLIFICA experience in The Gambia.

BACKGROUND: By increasing the hepatic blood circulation, food intake has been suggested to increase liver stiffness measurement (LSM) values in HCV-infected patients. AIM: To investigate prospectively the effects of food intake on LSM in hepatitis B virus (HBV)-infected patients and healthy controls. METHODS: In The Gambia, patients included in the PROLIFICA project are screened for HBV at the community level and then invited for fasting assessment including LSM. Between April 2012 and October 2012, each day, the first five participants were invited to participate in this study. After the initial examination, a standardised 850 Kcal breakfast was provided. Effect of food intake was assessed by examining mean difference of LSM, IQR and IQR/LSM at T0 (fasting LSM1), T30min (LSM2) and T120min (LSM3) respectively. RESULTS: A total of 209 subjects were enrolled in this study (133 were HBV positive, 76 healthy controls). Unreliable measurements occurred more frequently after food intake (5%, 24% and 18% at T0, T30min and T120min respectively). In both groups, median LSM2 was significantly higher than LSM1 [6.2 (IQR: 5.4, 7.9)] vs. 4.9 (4.2, 6.2), P < 0.0001. LSM3 was still higher than the baseline, but lower than LSM2. In multivariable analysis, no factor modified the effect of breakfast on LSM. In a subgroup of patients having liver biopsies, we confirmed that food intake can overestimate liver fibrosis. CONCLUSIONS: Food intake significantly increases liver stiffness measurement and its IQR values in patients with chronic hepatitis B as well as healthy individuals; and also the number of unreliable liver stiffness measurement values.

Foreign Body Aspiration and Tuberculosis: Possible Misdiagnosis

Childhood tuberculosis (TB) is common in developing countries whereas foreign body aspiration is relatively less frequently diagnosed. This report is of a child contact (same household) of a smear-positive index case who presented with suggestive clinical features; and was admitted as a case of pulmonary TB; but subsequently found to have an aspirated foreign body was accounting for his symptoms. Due to the similarity in the clinical features of a delayed clinical presentation of foreign body aspiration with pulmonary TB; clinicians attending to children with chronic respiratory pathology in a TB-endemic area should be mindful of the possibility of a foreign body in the airway and should always carefully review chest radiographs

Transthoracic lung aspiration for the aetiological diagnosis of pneumonia: 25 years of experience from The Gambia.

Pneumonia remains the leading cause of death in young children worldwide. Global pneumonia control depends on a good understanding of the aetiology of pneumonia. Percutaneous transthoracic aspiration culture is much more sensitive than blood culture in identifying the aetiological agents of pneumonia. However, the procedure is not widely practised because of lack of familiarity with it and concerns about potential adverse events. We review the diagnostic usefulness and safety of this procedure over 25 years of its use in research and routine practice at the UK Medical Research Council (MRC), The Gambia, and give a detailed description of the procedure itself. Published materials were identified from the MRC's publication database and systematic searches using the PubMed/Medline and Google search engines. Data from a current pneumonia aetiology study in the unit are included together with clinical experience of staff practising at the unit over the period covered in this review. A minimum of 500 lung aspirates were performed over the period of review. Lung aspiration produces a greater yield of diagnostic bacterial isolates than blood culture. It is especially valuable clinically when pathogens not covered by standard empirical antibiotic treatment, such as Mycobacterium tuberculosis and Staphylococcus aureus, are identified. There have been no deaths following the procedure in our setting and a low rate of other complications, all transient. Lung aspiration is currently the most sensitive method for diagnosing pneumonia in children. With appropriate training and precautions it can be safely used for routine diagnosis in suitable referral hospitals.

Bacteraemia and subsequent vertebral osteomyelitis: a retrospective review of 125 patients.

BACKGROUND: Vertebral osteomyelitis (VO) is associated with considerable morbidity and its incidence seems to be increasing. Haematogenous spread is an important aetiological factor. AIM: The objective was to describe a series of patients with VO and to search for a relationship between preceding bacteraemia and subsequent VO with the same pathogen. DESIGN AND METHODS: A retrospective study of all treated cases of VO in a tertiary hospital over a 10-year period. RESULTS: There were 129 cases of VO (involving 125 patients) that received antimicrobial treatment. Eighty-three (66%) were male and the mean age was 59.5 years (range 1 month to 87 years). The vertebral level involved was lumbar in 66 (53%) cases and thoracic in 35 (28%) cases. Seventy-four cases (59%) had a microbiologically confirmed aetiology. The diagnostic yield from procedures was 46 and 36% from blood culture and bone biopsy, respectively. Staphylococcus aureus was the most common pathogen [38 of 74 (51%) cases]. Nine of 38 (24%) cases of Staphylococcus aureus VO had a preceding bacteraemia with the same pathogen in the previous year. CONCLUSION: Staphylococcus aureus is an important pathogen causing bacteraemia with the ability to cause metastatic complications including VO. The high proportion of cases developing VO following a documented bacteraemia, sometimes many months previously, reinforce the importance of adequate aggressive treatment for bacteraemia. VO must be considered in all patients presenting with back pain up to a year after bacteraemia. Previous bacteraemias with relevant pathogens can help guide antibiotic treatment at presentation of VO and if biopsy cannot be obtained.

Strengthening capacity, collaboration and quality of clinical research in Africa: EDCTP Networks of Excellence.

Developing countries bear 90% of the global disease burden, but only access about 10% of globally available health research funding. Weak south-south networking hampers effective use of limited resources, production of critical mass of quality scientists, career opportunities and incentives to retain the few available scientists. The south must urgently act strategically to accelerate generation of talented scientists, create enabling environment and incentives to retain scientists and attract back those in diaspora. The creation of strong networks of excellence for clinical research among southern academic and research institutions is a novel strategic approach championed by European and Developing Countries Clinical Trials Partnership to achieve the aforementioned goals and mitigate the high disease burden. It will promote strong collaboration, resource sharing and cross-mentorship allowing each partner to grow with complementary capacities that support each other rather than compete negatively. It will enable the south and Africa in particular to participate actively and own the means for solving its own health problems and raise the professional quality and capacity of southern institutions to forge better and equal partnership with northern institutions.

Haematological values from a Gambian cohort--possible reference range for a West African population.

The objective of this study was to establish haematological reference ranges for the West African subregion using a Gambian cohort. We analysed full blood counts from 1279 subjects aged > or =1 year. Anthropometric and body composition measurements were performed. Haematological mean values, medians and 90% reference values were calculated and related to malnutrition in children and thinness and/or obesity in adults. Haemoglobin (Hb) and mean corpuscular volume (MCV) significantly increased with age (P < 0.00001). There were gender-related changes in Hb from 15 years of age (P = 0.001) and for MCV only in adults (P = 0.0002). Hb was significantly reduced in underweight and stunted children (P = 0.0001 and 0.0002, respectively) but was unaffected by thinness or obesity in adults. White blood cell (WBC) and platelet counts were highest under 5 years and declined significantly with age (P < 0.0001 and 0.0001). While, there were no gender-related differences with WBC, there were higher WBC counts in underweight (P = 0.0001) and stunted (P < 0.0001) children. Adult females had significantly higher mean platelet counts compared with males (P = 0.006). The mean and median values of haematological parameters in The Gambia are similar to other standards but the 90% reference range for each parameter encompasses lower values when compared with Western standards.

Value of CT-guided biopsy in the diagnosis of septic discitis.

AIM: To determine the role of CT-guided biopsy in the management of cases of infective discitis. METHODS: Data were examined from a retrospective case series of CT-guided biopsies for the 5-year period ending June 2006. RESULTS: 98 CT-guided biopsies were performed in the study period on 103 patients. Malignancy was diagnosed in 49 episodes. Discitis and paravertebral abscess accounted for 27 cases. Culture was positive in nine of 25 (36%) samples received by the microbiology laboratory. Staphylococcus aureus (four cases) and Mycobacterium tuberculosis (three cases) were the most frequent organisms isolated, followed by group G streptococci and coagulase-negative staphylococci (one case each). Blood cultures were diagnostic in a further nine patients. The main reason for a negative culture was prior antimicrobial therapy. The biopsy changed management in 9/25 (36%) of cases. There were no reported adverse events. CONCLUSION: Septic discitis is a serious condition with a wide variety of infective causes. CT-guided biopsy is a useful tool when the diagnosis of infectious spinal infection is considered in terms of commencing and targeting therapy, and it is a safe and well-tolerated procedure.

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.

Mycobacterium tuberculosis genome-wide screen exposes multiple CD8 T cell epitopes.

Mounting evidence suggests human leucocyte antigen (HLA) class I-restricted CD8(+) T cells play a role in protective immunity against tuberculosis yet relatively few epitopes specific for the causative organism, Mycobacterium tuberculosis, are reported. Here a total genome-wide screen of M. tuberculosis was used to identify putative HLA-B*3501 T cell epitopes. Of 479 predicted epitopes, 13 with the highest score were synthesized and used to restimulate lymphocytes from naturally exposed HLA-B*3501 healthy individuals in cultured and ex vivo enzyme-linked immunospot (ELISPOT) assays for interferon (IFN)-gamma. All 13 peptides elicited a response that varied considerably between individuals. For three peptides CD8(+) T cell lines were expanded and four of the 13 were recognized permissively through the HLA-B7 supertype family. Although further testing is required we show the genome-wide screen to be feasible for the identification of unknown mycobacterial antigens involved in immunity against natural infection. While the mechanisms of protective immunity against M. tuberculosis infection remain unclear, conventional class I-restricted CD8(+) T cell responses appear to be widespread throughout the genome.

Clinical and radiological presentation of 340 adults with smear-positive tuberculosis in The Gambia.

SETTING: Four clinics in The Gambia. OBJECTIVE: To document clinical and radiographic presentations of sputum smear-positive tuberculosis in adults. DESIGN: Newly diagnosed acid-fast bacilli (AFB) smear, culture-positive tuberculosis patients aged > or = 15 years were interviewed and examined, and underwent tuberculin skin testing, HIV testing and chest X-ray reviewed by a chest physician using set criteria. RESULTS: Of 340 patients enrolled (median age 29 years; males 73%), 8.3% were HIV-positive. One-third reported haemoptysis, > 90% reported weight loss and fever, and wasting was the most common sign (69%). Crepitations were the most frequent auscultatory finding (41%). The most common radiological lesion was a patchy infiltrate (> 90%). Cavitation was present in 206 patients (60.6%), most frequently occurred in the upper lung fields, was associated with increasing bacterial load in the sputum, and was less prevalent in HIV-positive patients (45% vs. 62%; P = 0.07). Auscultatory and chest X-ray findings matched only one-third of the time. CONCLUSION: In our setting, wasting is the most common clinical sign of sputum smear-positive tuberculosis. Auscultatory findings correlate poorly with radiological abnormalities. Cavitation is associated with increasing bacterial load in the sputum, and is therefore a strong indicator for early treatment.

Surveillance of drug-resistant Mycobacterium tuberculosis in The Gambia.

To determine the rates of drug-resistant tuberculosis in The Gambia, Mycobacterium tuberculosis isolates obtained from 225 patients during a nationwide survey were tested against isoniazid, rifampicin, ethambutol and streptomycin using the resistance ratio method. Only nine (4%) of the patients had strains that were resistant to one or more drugs. None of the patients with drug-resistant M. tuberculosis had previously been treated for tuberculosis. Drug-resistant tuberculosis is, as yet, not common in The Gambia. Periodic surveys for drug-resistant tuberculosis are recommended to monitor changes that may emerge over time.

Determinants of prognosis among black Africans with hypertensive heart failure.

One hundred and seven consecutive Black Africans hypertensive heart failure patients made of 52 Gambians and 55 Nigerians (51 males + 56 females) aged 53.6 +/- 12.1 years were followed-up for 12 months or till death. One-year survival curve was determined using Kaplan-Meiers method. The survivors and the deceased were compared using univariate and multivariate analysis. Mean blood pressures were 180.4 +/- 28.2 mmHg (range: 130-250 mmHg) systolic and 117.0 +/- 12.9 mmHg (range: 100-160 mmHg) diastolic. Duration of hypertension ranged from 0.5 to 23 years. The rate of undetected hypertension was 44%. Overall one-year survival rate was 71%. Twenty two percent of deaths occurred within the first 3 months of HHF. One-year survival rate among the survivors of this period was 89.4%. A strong negative correlation existed between cumulative survival and the duration of heart failure (y = 0.9812, x(2) = 0.1173, R = 0.965). Compared to the survivors, the deceased had significantly higher systolic blood pressure (191.9 +/- 32.2 mmHg versus 175.1 +/- 25.2 mmHg; P < 0.05), diastolic blood pressure (123.7 +/- 15.8mmHg versus 114.3 +/- 10.3 mmHg; P < 0.05), cardiothoracic index (69.2 +/- 3.9% versus 66.2 +/- 4.2%; P < 0.05) and serum creatinine (148.6 +/- 42.2 umol/L versus 113.8 +/- 36.4 umol/L; P < 0.05). Compared to the patients aged 40 or more years, patients aged below 40 years had significantly lower one-year survival rate (41.7% versus 74.1%; P < 0.05). One-year survival rate was significantly higher among patients on captopril medication than those without (75% versus 52.6%; P < 0.05). However, only serum creatinine had statistically differing values between the deceased and survivors (df = 1 SS = 10272, F = 7.60, p = 0.007). Basic clinical and biochemical parameters could therefore be useful prognostic markers in hypertensive heart failure.

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.