Screening for Hepatocellular Carcinoma among adults with HIV/Hepatitis B coinfection in Zambia: A Pilot Study

Background & aims: Chronic hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA). In an established cohort of HIV/HBV-coinfected individuals on antiretroviral therapy (ART), we piloted an HCC screening initiative at two outpatient clinics in Lusaka, Zambia. Methods: We performed abdominal ultrasound (AUS) and transient elastography in all patients. Results: Among 279 HIV/HBV-coinfected patients, 165 (59.1%) were men, median age was 34 years (interquartile range 28-39) and median CD4 count 246 cells/µl (112-355). While 102 (36.6%) individuals had elevated transaminases, 114 (40.9%) had HBV levels >2000 IU/mL and 59 (24.6%) significant fibrosis. On AUS, 75 (26.9%) participants had hepatomegaly and 69 (24.7%) peri-portal fibrosis. Five patients had a liver lesion >1cm, an indication for confirmatory imaging. Conclusions: In one of the first HCC screening initiatives in SSA, 2% of HIV/HBV-coinfected adults had significant liver lesions, and a quarter had findings suggestive of schistosomiasis-induced liver damage

Incremental Yield of Serial Sputum Cultures for Diagnosis of Tuberculosis among HIV Infected Smear Negative Pulmonary TB Suspects in Kampala, Uganda

Sputum culture is the gold standard for diagnosis of pulmonary tuberculosis (PTB). Although mostly used for research, culture is recommended by the World Health Organization for TB diagnosis among HIV infected smear negative PTB suspects. Even then, the number of sputum samples required remains unspecified. Here, we determined the Incremental Yield (IY) and number of samples required to diagnose an additional PTB case upon second and third serial sputum culture.This was a cross sectional study done between January and March 2011. Serial sputum samples were provided by participants within two days and cultured using Lowenstein Jensen (LJ) and Mycobacteria Growth Indicator Tube (MGIT) methods. A PTB case was defined as a positive culture on either one or both methods. The IY from the second and third serial cultures was determined and the reciprocal of the product of the fractions of IY provided the number of samples required for an additional PTB case. Of the 170 smear negative PTB suspects, 62 (36.5%) met the case definition. The IY of the second sample culture was 12.7%, 23.6% and 12.6% and for the third sample culture was 6.8%, 7.5% and 7.3% with LJ, MGIT and LJ or MGIT, respectively. The number of samples required for an additional PTB case and 95% CI upon the second sample culture were 29.9 (16.6, 156.5), 11.3 (7.6, 21.9) and 20.8 (12.5, 62.7); while for the third sample culture were 55.6 (26.4, 500.4), 35.7 (19.0, 313.8) and 36.1 (19.1, 330.9) by LJ, MGIT and LJ or MGIT respectively.Among HIV infected smear negative PTB suspects in Kampala, 93% of PTB cases are diagnosed upon the second serial sputum culture. The number of cultures needed to diagnose an additional PTB case, ranges from 11–30 and 35–56 by the second and third sputum samples, respectively

Changes in Mycobacterium tuberculosis Genotype Families Over 20 Years in a Population-Based Study in Northern Malawi

BACKGROUND: Despite increasing interest in possible differences in virulence and transmissibility between different genotypes of M. tuberculosis, very little is known about how genotypes within a population change over decades, or about relationships to HIV infection. METHODS AND PRINCIPAL FINDINGS: In a population-based study in rural Malawi we have examined smears and cultures from tuberculosis patients over a 20-year period using spoligotyping. Isolates were grouped into spoligotype families and lineages following previously published criteria. Time trends, HIV status, drug resistance and outcome were examined by spoligotype family and lineage. In addition, transmissibility was examined among pairs of cases with known epidemiological contact by assessing the proportion of transmissions confirmed for each lineage, on the basis of IS6110 RFLP similarity of the M tuberculosis strains. 760 spoligotypes were obtained from smears from 518 patients from 1986-2002, and 377 spoligotypes from cultures from 347 patients from 2005-2008. There was good consistency in patients with multiple specimens. Among 781 patients with first episode tuberculosis, the majority (76%) had Lineage 4 ("European/American") strains; 9% had Lineage 3 ("East-African/Indian"); 8% Lineage 1 ("Indo-Oceanic"); and 2% Lineage 2 ("East-Asian"); others unclassifiable. Over time the proportion of Lineage 4 decreased from >90% to 60%, with an increase in the other 3 lineages (p<0.001). Lineage 1 strains were more common in those with HIV infection, even after adjusting for age, sex and year. There were no associations with drug resistance or outcome, and no differences by lineage in the proportion of pairs in which transmission was confirmed. CONCLUSIONS: This is the first study to describe long term trends in the four M. tuberculosis lineages in a population. Lineage 4 has probably been longstanding in this population, with relatively recent introductions and spread of Lineages1-3, perhaps influenced by the HIV epidemic

A Comparison of Tools Used for Tuberculosis Diagnosis in Resource-Limited Settings: A Case Study at Mubende Referral Hospital, Uganda

This study compared TB diagnostic tools and estimated levels of misdiagnosis in a resource-limited setting. Furthermore, we estimated the diagnostic utility of three-TB-associated predictors in an algorithm with and without Direct Ziehl-Neelsen (DZM).Data was obtained from a cross-sectional study in 2011 conducted at Mubende regional referral hospital in Uganda. An individual was included if they presented with a two weeks persistent cough and or lymphadenitis/abscess. 344 samples were analyzed on DZM in Mubende and compared to duplicates analyzed on direct fluorescent microscopy (DFM), growth on solid and liquid media at Makerere University. Clinical variables from a questionnaire and DZM were used to predict TB status in multivariable logistic and Cox proportional hazard models, while optimization and visualization was done with receiver operating characteristics curve and algorithm-charts in Stata, R and Lucid-Charts respectively.DZM had a sensitivity and specificity of 36.4% (95% CI = 24.9-49.1) and 97.1%(95% CI = 94.4-98.7) compared to DFM which had a sensitivity and specificity of 80.3%(95% CI = 68.7-89.1) and 97.1%(95% CI = 94.4-98.7) respectively. DZM false negative results were associated with patient's HIV status, tobacco smoking and extra-pulmonary tuberculosis. One of the false negative cases was infected with multi drug resistant TB (MDR). The three-predictor screening algorithm with and without DZM classified 50% and 33% of the true cases respectively, while the adjusted algorithm with DZM classified 78% of the true cases.The study supports the concern that using DZM alone risks missing majority of TB cases, in this case we found nearly 60%, of who one was an MDR case. Although adopting DFM would reduce this proportion to 19%, the use of a three-predictor screening algorithm together with DZM was almost as good as DFM alone. It's utility is whoever subject to HIV screening all TB suspects

Evolution of extensively drug-resistant tuberculosis over four decades: whole genome sequencing and dating analysis of Mycobacterium tuberculosis isolates from KwaZulu-Natal.

CAPRISA, 2015.Abstract available in pdf

Faunistic list of Culicoides (Diptera: Ceratopogonidae) from Chinhoyi, Zimbabwe

(Zimbabwe Veterinary Journal, 1998, 29(3): 87-90

Programmatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africa

South Africa shows one of the highest global burdens of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). Since 2002, MDR-TB in South Africa has been treated by a standardized combination therapy, which until 2010 included ofloxacin, kanamycin, ethionamide, ethambutol and pyrazinamide. Since 2010, ethambutol has been replaced by cycloserine or terizidone. The effect of standardized treatment on the acquisition of XDR-TB is not currently known.; We genetically characterized a random sample of 4,667 patient isolates of drug-sensitive, MDR and XDR-TB cases collected from three South African provinces, namely, the Western Cape, Eastern Cape and KwaZulu-Natal. Drug resistance patterns of a subset of isolates were analyzed for the presence of commonly observed resistance mutations.; Our analyses revealed a strong association between distinct strain genotypes and the emergence of XDR-TB in three neighbouring provinces of South Africa. Strains predominant in XDR-TB increased in proportion by more than 20-fold from drug-sensitive to XDR-TB and accounted for up to 95% of the XDR-TB cases. A high degree of clustering for drug resistance mutation patterns was detected. For example, the largest cluster of XDR-TB associated strains in the Eastern Cape, affecting more than 40% of all MDR patients in this province, harboured identical mutations concurrently conferring resistance to isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, ethionamide, kanamycin, amikacin and capreomycin.; XDR-TB associated genotypes in South Africa probably were programmatically selected as a result of the standard treatment regimen being ineffective in preventing their transmission. Our findings call for an immediate adaptation of standard treatment regimens for M/XDR-TB in South Africa