What causes symptoms suggestive of tuberculosis in HIV-positive people with negative initial investigations?

OBJECTIVE: To identify the causes of symptoms suggestive of tuberculosis (TB) among people living with the human immunodeficiency virus (PLHIV) in South Africa. METHODS: A consecutive sample of HIV clinic attendees with symptoms suggestive of TB (1 of cough, weight loss, fever or night sweats) at enrolment and at 3 months, and negative initial TB investigations, were systematically evaluated with standard protocols and diagnoses assigned using standard criteria. TB was 'confirmed' if Mycobacterium tuberculosis was identified within 6 months of enrolment, and 'clinical' if treatment started without microbiological confirmation. RESULTS: Among 103 participants, 50/103 were pre-antiretroviral therapy (ART) and 53/103 were on ART; respectively 68% vs. 79% were female; the median age was 35 vs. 45 years; the median CD4 count was 311 vs. 508 cells/mm³. Seventy-two (70%) had 5% measured weight loss and 50 (49%) had cough. The most common final diagnoses were weight loss due to severe food insecurity (n = 20, 19%), TB (n = 14, 14%: confirmed n = 7; clinical n = 7), other respiratory tract infection (n = 14, 14%) and post-TB lung disease (n = 9, 9%). The basis for TB diagnosis was imaging (n = 7), bacteriological confirmation from sputum (n = 4), histology, lumbar puncture and other (n = 1 each). CONCLUSION: PLHIV with persistent TB symptoms require further evaluation for TB using all available modalities, and for food insecurity in those with weight loss.

Lessons learnt conducting minimally invasive autopsies in private mortuaries as part of HIV and tuberculosis research in South Africa.

Current estimates of the burden of tuberculosis (TB) disease and cause-specific mortality in human immunodeficiency virus (HIV) positive people rely heavily on indirect methods that are less reliable for ascertaining individual-level causes of death and on mathematical models. Minimally invasive autopsy (MIA) is useful for diagnosing infectious diseases, provides a reasonable proxy for the gold standard in cause of death ascertainment (complete diagnostic autopsy) and, used routinely, could improve cause-specific mortality estimates. From our experience in performing MIAs in HIV-positive adults in private mortuaries in South Africa (during the Lesedi Kamoso Study), we describe the challenges we faced and make recommendations for the conduct of MIA in future studies or surveillance programmes, including strategies for effective communication, approaches to obtaining informed consent, risk management for staff and efficient preparation for the procedure.

Les estimations actuelles du poids de la tuberculose (TB) maladie et de la mortalité qui lui est due parmi les patients positifs à l'infection par le virus de l'immunodéficience humaine (VIH) dépendent beaucoup de méthodes indirectes, qui sont moins fiables pour vérifier les causes de décès au niveau individuel et de modèles mathématiques. Une autopsie peu invasive (MIA) est utile au diagnostic de maladies infectieuses, fournit une approximation raisonnable de l'étalon or de la vérification de la cause du décès c'est-à-dire une autopsie diagnostique complète. Si elle est utilisée en routine, elle pourrait améliorer les estimations de mortalité spécifique d'une cause. A partir de nos expériences de MIA sur des adultes positifs au VIH dans des morgues privées d'Afrique du Sud (au cours de l'étude Lesedi Kamoso), nous décrivons les défis rencontrés et faisons des recommandations pour la réalisation de MIA dans des études futures ou des programmes de surveillance, incluant des stratégies de communication efficaces, des approches visant à obtenir un consentement éclairé, une prise en charge du risque pour le personnel et une préparation efficace de la procédure.

Las estimaciones actuales de morbilidad por tuberculosis (TB) y de mortalidad por causas específicas en las personas positivas frente al virus de la inmunodeficiencia humana (VIH) se fundamentan en su mayor parte en métodos indirectos que son menos fiables para determinar las causas de muerte individuales y en modelizaciones matemáticas. La autopsia mínimamente invasiva (MIA) es útil en el diagnóstico de las enfermedades infecciosas, ofrece un sustituto aceptable al método de referencia para determinar la causa de muerte (que es la autopsia diagnóstica completa), y cuando se usa de manera sistemática, mejora las estimaciones de la mortalidad por causas específicas. A partir de su experiencia con la MIA en adultos con infección por el VIH en empresas fúnebres privadas en Suráfrica (durante el estudio Lesedi Kamoso), los autores describen las dificultades que encontraron y formulan recomendaciones que se pueden aplicar en el futuro al realizar la autopsia mínimamente invasiva en estudios de investigación o en programas de vigilancia; se preconizan estrategias de comunicación efectivas, métodos de obtención del consentimiento informado, la gestión de riesgos para el personal y la preparación eficiente del procedimiento.

Isoniazid preventive therapy use among patients on antiretroviral therapy: a missed opportunity.

Isoniazid preventive therapy (IPT) with antiretroviral therapy (ART) reduces incident tuberculosis among patients infected with the human immunodeficiency virus. We describe IPT use among patients on ART at two primary care clinics in South Africa. Of 597 participants interviewed, 100 (16.8%) reported IPT use; 73.4% (365/497) with no reported IPT use were eligible for IPT. IPT use was associated with age <35 years (aOR 1.90, 95%CI 1.18-3.06), and receiving care at one clinic as opposed to the other (aOR 4.72, 95%CI 2.69-7.93). The high proportion of patients on ART eligible for IPT represents a missed opportunity for IPT scale-up.

Spectrum of non-tuberculous mycobacteria identified using standard biochemical testing vs. 16S sequencing.

Non-tuberculous mycobacterial isolates from gold miners were speciated using standard biochemical testing (SBT) and 16S rDNA sequencing. Of 237 isolates tested, SBT identified 126, compared with all 237 identified using sequencing. Of 111 isolates unspeciated by SBT but identified by sequencing, 38 (34.2%) were identified as Mycobacterium gordonae and 8 (7.2%) were new species. Of 126 isolates speciated by both methods, 37 were discordant, with 14/17 M. gordonae isolates incorrectly identified as M. scrofulaceum using SBT. The majority of these were the potentially pathogenic strain D, M. gordonae. Sequencing is preferable where available to guide treatment.

Trends in drug-resistant tuberculosis in a gold-mining workforce in South Africa, 2002-2008.

SETTING AND OBJECTIVE: To describe trends in drug-resistant tuberculosis (TB) in two gold-mining workforces, South Africa, 2002-2008. DESIGN: TB programme data analysis. RESULTS: TB case notification rates decreased between 2002 and 2008 from 4006 to 3018 per 100,000 and from 3192 to 2468/100,000 for Companies A and B, respectively. Human immunodeficiency virus (HIV) prevalence exceeded 80% in TB episodes with known status. The proportion of TB episodes with multidrug-resistant TB (MDR-TB) increased from 6/129 (4.7%) to 17/85 (20.0%) among previously treated cases, and from 4/38 (10.4%) to 7/28 (25.0%) in Companies A and B, respectively (tests for trend, Company A, P < 0.001; Company B, P = 0.304). Case notifications of MDR-TB increased during 2002-2008 from 39.8 to 122.9/100,000/year in Company A and from 7.8 to 96.8/100,000/year in Company B. Coverage of second-line drug susceptibility testing (DST) among MDR-TB episodes was low. Previous treatment exposure was a strong risk factor for MDR-TB (prevalence ratio 8.78, 95%CI 5.94-12.97 in previously treated vs. untreated individuals). CONCLUSION: Despite decreasing TB notifications overall, MDR-TB notifications and proportions of episodes with MDR-TB increased in the larger company. Cure must be ensured in first episodes to prevent acquired resistance. Improved coverage of culture, DST and HIV testing is required to allow treatment to be optimised.

Liquid vs. solid culture for tuberculosis: performance and cost in a resource-constrained setting.

SETTING: National Health Laboratory Services tuberculosis (TB) laboratory, South Africa. OBJECTIVES: To compare Mycobacterium Growth Indicator Tube (MGIT) with Löwenstein-Jensen (LJ) medium with regard to Mycobacterium tuberculosis yield, time to positive culture and contamination, and to assess MGIT cost-effectiveness. DESIGN: Sputum from gold miners was cultured on MGIT and LJ. We estimated cost per culture, and, for smear-negative samples, incremental cost per additional M. tuberculosis gained with MGIT using a decision-tree model. RESULTS: Among 1267 specimens, MGIT vs. LJ gave a higher yield of mycobacteria (29.7% vs. 22.8%), higher contamination (16.7% vs. 9.3%) and shorter time to positive culture (median 14 vs. 25 days for smear-negative specimens). Among smear-negative samples that were culture-positive on MGIT but negative/contaminated on LJ, 77.3% were non-tuberculous mycobacteria (NTM). Cost per culture on LJ, MGIT and MGIT+LJ was respectively US$12.35, US$16.62 and US$19.29. The incremental cost per additional M. tuberculosis identified by standard biochemical tests and microscopic cording was respectively US$504.08 and US$328.10 using MGIT vs. LJ, or US$160.80 and US$$109.07 using MGIT+LJ vs. LJ alone. CONCLUSION: MGIT gives higher yield and faster results at relatively high cost. The high proportion of NTM underscores the need for rapid speciation tests. Minimising contaminated cultures is key to cost-effectiveness.

Clonal expansion of a globally disseminated lineage of Mycobacterium tuberculosis with low IS6110 copy numbers.

Knowledge of the clonal expansion of Mycobacterium tuberculosis and accurate identification of predominant evolutionary lineages in this species remain limited, especially with regard to low-IS6110-copy-number strains. In this study, 170 M. tuberculosis isolates with

Dysentery in patients infected with human immunodeficiency virus in Zimbabwe: an emerging role for Schistosoma mansoni and Escherichia coli O157?

Information on bloody diarrhoea in HIV-positives is scarce. A prospective study was therefore performed, in Zimbabwe, to determine and compare the pathogens associated with bloody diarrhoea in 25 antiretroviral-naïve HIV-infected patients and 15 non-HIV-infected patients. Stool cultures and colonic biopsies were performed. Shigella was isolated from 18 (45%) of the subjects, Schistosoma mansoni from eight (16%), Escherichia coli H7:O157 from three (8%) and Campylobacter jejunii from two (5%). There was no evidence of Salmonella, Entamoeba histolytica or cytomegalovirus infection. Shigella dysenteriae type-1 occurred more often in the HIV-negatives than the HIV-positives (P = 0.02). Although HIV-associated bloody diarrhoea in Zimbabwe appears to be most frequently caused by Shigella, it may also be commonly the result of infection with Sc. mansoni or shiga-toxin-producing E. coli. A larger study specifically to examine the role of Sc. mansoni and E. coli O157 is warranted.

TB infection: an exploratory study of BCG protective properties and the possible role of environmental mycobacteria.

OBJECTIVE: To evaluate the presence of environmental mycobacterial strains and explore the implications for BCG vaccination against TB. DESIGN: Multimethod approach which included structured interviews and medical records examination. Soil and water samples were analysed using standard microbiology methods. SETTING: Beatrice Infectious Diseases Hospital, Public Health laboratories, University of Zimbabwe Medical School and several residential areas in Harare. SUBJECTS: 129 tuberculosis inpatients at Beatrice Infectious Diseases Hospital, 26 Public Health Laboratory technicians handling TB specimens and 51 fourth year medical students. MAIN OUTCOME MEASURES: Vaccination status of TB inpatients, medical students and laboratory technicians, protective efficacy of BCG in all subjects, presence of environmental mycobacterium in the environment. RESULTS: The type of tuberculosis did not differ significantly between vaccinated and non-vaccinated TB patients x2(df = 1) = 0.171 p > 0.05. There was no apparent difference between the revaccinated and non-vaccinated laboratory technicians. One respondent out of each of the revaccinated and non-vaccinated laboratory technicians had developed pulmonary tuberculosis. Among the fourth year medical students, four had positive tuberculin test results, even though they had not been vaccinated at the University clinic. Environmental mycobacteria presumptively identified as Mycobacterium scrofulaceum and Mycobacterium intracellulare were isolated from both the water and soil samples taken from a few selected areas in Harare. Of the 129 TB in-patients, 88 (68.2%) had previously been vaccinated against TB. Similarly among the 51 medical students 44(86.3%) had been vaccinated. Laboratory technicians re-vaccinated on the job were nine out of 26. CONCLUSION: The results obtained seemed to indicate that BCG protective efficacy did wane with time and revaccination appeared not to be useful. Environmental mycobacterium that could influence the BCG efficacy do exist in our environment.