The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

BACKGROUND: Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. OBJECTIVE: To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. METHODS: Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. RESULTS: Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). CONCLUSION: The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis

Pulmonary Tuberculosis and Drug Resistance in Dhaka Central Jail, the Largest Prison in Bangladesh

There are limited data on TB among prison inmates in Bangladesh. The aim of the study was to determine the prevalence of pulmonary tuberculosis (TB), its drug resistance and risk factors in Dhaka Central Jail, the largest prison in Bangladesh.Cross sectional survey with, active screening of a total number of 11,001 inmates over a period of 2 years. Sputum samples from TB suspects were taken for acid- fast bacilli (AFB) microscopy, culture and drug susceptibility testing. (5.37, 4.02–7.16).The study results revealed a very high prevalence of TB in the prison population in Dhaka Central Jail. Entry examinations and active symptom screening among inmates are important to control TB transmission inside the prison. Identifying undiagnosed smear-negative TB cases remains a challenge to combat this deadly disease in this difficult setting

Physicians are a key to encouraging cessation of smoking among people living with HIV/AIDS: a cross-sectional study in the Kathmandu Valley, Nepal

BackgroundHIV care providers may be optimally positioned to promote smoking behaviour change in their patients, among whom smoking is both highly prevalent and uniquely harmful. Yet research on this front is scant, particularly in the developing country context. Hence, this study describes smoking behaviour among people living with HIV/AIDS (PLWHA) in the Kathmandu Valley of Nepal, and assesses the association between experience of physician-delivered smoking status assessment and readiness to quit among HIV-positive smokers.MethodsWe conducted a cross-sectional survey of PLWHA residing in the Kathmandu Valley, Nepal. Data from 321 adult PLWHA were analyzed using multiple logistic regression for correlates of current smoking and, among current smokers, of motivational readiness to quit based on the transtheoretical model (TTM) of behaviour change.ResultsOverall, 47% of participants were current smokers, with significantly higher rates among men (72%), ever- injecting drug users (IDUs), recent (30-day) alcohol consumers, those without any formal education, and those with higher HIV symptom burdens. Of 151 current smokers, 34% were thinking seriously of quitting within the next 6 months (contemplation or preparation stage of behaviour change). Adjusting for potential confounders, experience of physician-delivered smoking status assessment during any visit to a hospital or clinic in the past 12 months was associated with greater readiness to quit smoking (AOR = 3.34; 95% CI = 1.05,10.61).ConclusionsRoughly one-third of HIV-positive smokers residing in the Kathmandu Valley, Nepal, are at the contemplation or preparation stage of smoking behaviour change, with rates significantly higher among those whose physicians have asked about their smoking status during any clinical interaction over the past year. Systematic screening for smoking by physicians during routine HIV care may help to reduce the heavy burden of smoking and smoking-related morbidity and mortality within HIV-positive populations in Nepal and similar settings

Prevalent infectious tuberculosis in Harare, Zimbabwe: burden, risk factors and implications for control.

SETTING: Harare's high density suburbs. OBJECTIVES: To investigate the burden, duration and risk factors for prevalent tuberculosis (TB) and explore potential control strategies. METHODS: Randomly selected adults had TB culture, symptom screen and human immunodeficiency virus (HIV) serology. Prevalent TB was defined as undiagnosed or still culture-positive. Notification data and HIV prevalence in TB out-patients were used to estimate duration of infectiousness (prevalence/estimated incidence). RESULTS: Among 10 092 participants, 40 (0.40%, 95%CI 0.28-0.54) had prevalent smear-positive TB. HIV (adjusted odds ratio [aOR] 3.1, 95%CI 1.6-6.3, population attributable fraction [PAF] 33%), male sex (aOR 3.1, 95%CI 1.5-6.4, PAF 40%), and overcrowding (PAF 34%) were significant risk factors, with past TB treatment significant for HIV-negative participants only (PAF 7%). Recent household TB contact was not significant (PAF 10%). HIV prevalence was 21.1%; 76.9% of HIV-positive participants were previously untested. Duration of infectiousness was at least 18 weeks in HIV-positive and approximately 1 year in HIV-negative patients. CONCLUSIONS: Overcrowding, male sex and HIV infection were major risk factors for prevalent smear-positive TB. Reducing diagnostic delay may have greater potential to improve the control of prevalent TB than interventions targeted at household contacts, TB treatment outcomes, or TB-HIV interventions under current levels of awareness of HIV status

Diagnostic accuracy of commercial urinary lipoarabinomannan detection in African tuberculosis suspects and patients.

OBJECTIVE: To evaluate a commercially available antigen capture enzyme-linked immunosorbent assay (ELISA) based on detecting lipoarabinomannan (LAM) in urine for the diagnosis of tuberculosis (TB). DESIGN: Consenting TB suspects and registering TB patients prospectively recruited from three hospitals were asked for two sputum specimens for microscopy and culture, urine for LAM testing and blood for human immunodeficiency virus (HIV) testing, with radiological and clinical follow-up for 2 months. RESULTS: Of 427 participants, complete data were available from 397 (307 adult and 23 adolescent TB suspects, and 67 registering TB patients). HIV prevalence was 77%. TB was diagnosed in 195 (49%), including 161 culture-positive patients, and confidently excluded in 114 (29%) participants. LAM ELISA sensitivity was 44% (95%CI 36-52) for culture-confirmed TB (52% in smear-positive patients). Specificity was 89% (95%CI 81-94). Sensitivity was significantly higher in HIV-related TB (52%, 95%CI 43-62, P < 0.001) compared to HIV-negative TB (21%, 95%CI 9-37). Sensitivity in smear-negative patients was low (28%, 95%CI 13-43) for combined HIV-positive and -negative patients. CONCLUSION: Our findings confirm greater sensitivity of urine LAM detection for HIV-related TB. However, both sensitivity and specificity were suboptimal, suggesting that this version cannot confirm or exclude TB in either HIV-infected or non-infected patients

Risk factors for mortality in smear-negative tuberculosis suspects: a cohort study in Harare, Zimbabwe.

OBJECTIVE: To investigate mortality rates and risk factors for death among smear-negative tuberculosis (TB) suspects. DESIGN: Cohort study nested within a cluster-randomised trial of community-based active case finding. Smear-negative TB suspects were followed for 12 months, with home tracing where necessary. We calculated mortality rates and used regression analysis to investigate the relationship between clinical characteristics and death. RESULTS: Between February 2006 and June 2007, 1195 smear-negative TB suspects were followed for 1136.8 person-years. Human immunodeficiency virus (HIV) prevalence was 63.3%. During follow-up, 139 participants died (11.6%) and mortality rates remained high throughout; 119 (16.5%) HIV-positive individuals and 13 (3.1%) HIV-negative individuals died (HR = 5.8, 95%CI 3.3-10.4, P < 0.001). Advanced immunosuppression was the main risk factor for death among HIV-positive participants, with CD4 count < 50 cells/μ l associated with a 13-fold increased risk of death. Antiretroviral treatment (ART) was initiated by only 106 (14.7%), with long delays in accessing care. CONCLUSION: HIV-positive smear-negative TB suspects are at high and sustained risk of death. Current guidelines for the management of HIV-infected TB suspects are limited, and this study adds to evidence that specific policies are required to promote earlier HIV and TB diagnosis and reduce delays in ART initiation

Human immunodeficiency virus, smoking and self-rated health in Harare, Zimbabwe.

SETTING: Twenty-two urban factories in Harare. OBJECTIVE: To determine the relationship between the human immunodeficiency virus (HIV), smoking and self-rated health in a high HIV prevalence urban workforce. DESIGN: Cross-sectional survey. RESULTS: Of 7482 employees, 6111 (82%) consented to interview and anonymous HIV serology; 88% were male; median age was 34 years. HIV prevalence was 19%. Current (median 6 cigarettes per day) and former smoking were reported by 17% and 7%, respectively. Smoking (current or former) was more common among HIV-positive (27%) than -negative participants (17%; P < 0.001). Factors significantly associated with being a smoker on multivariate analysis were being HIV-infected (OR 1.5, 95% CI 1.4-1.7), older age (P < 0.001), non-Christian (OR 1.6, 95% CI 1.2-2.2) and manual job (OR 1.4, 95% CI 1.2-1.6). Women (OR 0.05, 95% CI 0.03-0.11) and the better educated (OR 0.7, 95% CI 0.5-0.9) were significantly less likely to smoke. HIV-positive smokers had the highest risk of reporting poor health (adjusted OR compared to HIV-negative non-smokers 3.4, 95% CI 2.3-5.0). CONCLUSIONS: Smoking was significantly more common among HIV-positive than -negative employees in this predominantly male workforce. There was evidence of a combined effect on self-rated poor health, a variable shown to be a strong independent predictor of mortality in industrialised countries. Interventions to encourage smoking cessation may be an important component of HIV care in Southern Africa

Catastrophic care-seeking costs as an indicator for lung health

Costs incurred during care-seeking for chronic respiratory disease are a major problem with severe consequences for socio-economic status and health outcomes. Most of the published evidence to date relates to tuberculosis (TB) and there is a lack of information for the major non-communicable chronic respiratory diseases: asthma and chronic obstructive pulmonary disease (COPD). International policy is recognising the need to address this problem and measure progress towards eliminating catastrophic care-seeking costs (see the post-2015 TB strategy). Current tools for measuring, defining, and understanding the full consequences of catastrophic care-seeking costs are inadequate. We propose two areas of work which are urgently needed to prepare health systems and countries for the burden of chronic lung disease that will fall on poor populations in the coming 10-20 years: a) Rapid scale up of the number and scope of studies of patient costs associated with chronic non-communicable respiratory disease. b) Work towards deeper understanding and effective measurement of catastrophic care-seeking costs. This will produce a range of indicators, such as dissaving, which can more effectively inform health policy decision-making for lung health. These will also be useful for other health problems. We argue that reduction in care-seeking costs will be a key monitoring indicator for improvements in lung health in particular, and health in general, in the coming 10 to 20 years