Household screening and multidrug-resistant tuberculosis

Of the estimated half a million people who develop multidrug resistant (MDR) tuberculosis each year, less than 7% are diagnosed and only 1 in 5 of these have access to eff ective treatment.1 To control this epidemic, dramatically increased efforts are required to scale up case detection and treatment provision. In The Lancet, Mercedes Becerra and colleagues2 report the yield of additional MDR tuberculosis diagnoses that are found by screening household contacts of index cases in Lima, Peru. This study—the largest of its kind to date—found that more than 2% of 4503 household contacts had active tuberculosis at the time the index case was diagnosed. Incident tuberculosis was also found at a rate of 1624 cases per 100 000 person-years over 4 years follow-up. These results support recommendations for active screening of household contacts of people with MDR tuberculosis,3 and provide valuable lessons for other programmes striving to improve case detection and to reduce community transmission of MDR tuberculosis

The Effect of Complete Integration of HIV and TB Services on Time to Initiation of Antiretroviral Therapy: A Before-After Study.

Studies have shown that early ART initiation in TB/HIV co-infected patients lowers mortality. One way to implement earlier ART commencement could be through integration of TB and HIV services, a more efficient model of care than separate, vertical programs. We present a model of full TB/HIV integration and estimate its effect on time to initiation of ART

Control of a battery energy storage system to compensate for ADN equivalents inaccuracies

peer reviewedThis paper proposes a new application for a Battery Energy Storage System (BESS) connected at distribution level. It consists of controlling the BESS in such a way that the net active and reactive powers entering the distribution network matches as closely as possible the response of a dynamic equivalent model of the latter, used in large-disturbance dynamic simulations of the transmission system. Thus, the BESS compensates for the inevitable inaccuracies of the equivalent, which can be used with higher guarantee of accuracy. The battery is supposed to be available for other purposes at the main substation of the distribution grid. Its active and reactive powers are controlled without resorting to any model of that grid. Simulations results are reported on the CIGRE MV test system. Good performances are found in response to disturbances of various severities

Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration

Article approval pendingWith expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa

A comparison of self-report and antiretroviral detection to inform estimates of antiretroviral therapy coverage, viral load suppression and HIV incidence in Kwazulu-Natal, South Africa

Accurately identifying individuals who are on antiretroviral therapy (ART) is important to determine ART coverage and proportion on ART who are virally suppressed. ART is also included in recent infection testing algorithms used to estimate incidence. We compared estimates of ART coverage, viral load suppression rates and HIV incidence using ART self-report and detection of antiretroviral (ARV) drugs and we identified factors associated with discordance between the methods

Supervised oral HIV self-testing is accurate in rural KwaZulu Natal, South Africa

Objectives: To achieve UNAIDS 90-90-90 targets, alternatives to conventional HIV testing models are necessary in South Africa to increase population awareness of their HIV status. One of the alternatives is oral mucosal transudates-based HIV self-testing (OralST). This study describes implementation of counsellor-introduced supervised OralST in a high HIV prevalent rural area. Methods: Cross-sectional study conducted in two government-run primary healthcare clinics and three Médecins Sans Frontières-run fixed-testing sites in uMlalazi municipality, KwaZulu-Natal. Lay counsellors sampled and recruited eligible participants, sought informed consent and demonstrated the use of the OraQuick(™) OralST. The participants used the OraQuick(™) in front of the counsellor and underwent a blood-based Determine(™) and a Unigold(™) rapid diagnostic test as gold standard for comparison. Primary outcomes were user error rates, inter-rater agreement, sensitivity, specificity and predictive values. Results: A total of 2198 participants used the OraQuick(™) , of which 1005 were recruited at the primary healthcare clinics. Of the total, 1457 (66.3%) were women. Only two participants had to repeat their OraQuick(™) . Inter-rater agreement was 99.8% (Kappa 0.9925). Sensitivity for the OralST was 98.7% (95% CI 96.8-99.6), and specificity was 100% (95% CI 99.8-100). Conclusion: This study demonstrates high inter-rater agreement, and high accuracy of supervised OralST. OralST has the potential to increase uptake of HIV testing and could be offered at clinics and community testing sites in rural South Africa. Further research is necessary on the potential of unsupervised OralST to increase HIV status awareness and linkage to care

Nevirapine-Associated Early Hepatotoxicity: Incidence, Risk Factors, and Associated Mortality in a Primary Care ART Programme in South Africa

BACKGROUND: The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0-2.0% giving an incidence-rate at 102 days of 3.6-7.6 per 100 person-years. Median time to hepatotoxicity was 32 (IQR 28-58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of mother-to-child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality. CONCLUSIONS: The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria

Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection

RATIONALE: Two forms of the IFN-gamma release assay (IFNGRA) to detect tuberculosis infection are available, but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment. OBJECTIVE: To compare the ability of the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold (Cellestis, Melbourne, Australia), and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons. METHODS: A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha, a deprived urban South African community with an HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1,612 per 100,000. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty (74 HIV(+) and 86 HIV(-)) persons were enrolled. A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects (p < 0.01). By contrast, the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test (52 vs. 59%; p = 0.41) or the QuantiFERON-TB Gold test (43 and 46%; p = 0.89). Fair agreement between the Mantoux test (5- and 10-mm cutoffs) and the IFNGRA was seen in HIV-infected people (kappa = 0.52-0.6). By contrast, poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group (kappa = 0.07-0.30, depending on the Mantoux cutoff). The pattern was similar for T-SPOT.TB (kappa = 0.18-0.24). Interpretation: IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis

Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting

The uncertain future of lay counsellors : continuation of HIV services in Lesotho under pressure

Between 2006 and 2011, when antiretroviral therapy (ART) was scaled up in a context of severe human resources shortages, transferring responsibility for elements in human immunodeficiency virus (HIV) care from conventional health workers to lay counsellors (LCs) contributed to increased uptake of HIV services in Lesotho. HIV tests rose from 79 394 in 2006 to 274 240 in 2011 and, in that same period, the number of people on ART increased from 17 352 to 83 624. However, since 2012, the jobs of LCs have been at risk because of financial and organizational challenges. We studied the role of LCs in HIV care in Lesotho between 2006 and 2013, and discuss potential consequences of losing this cadre. Methods included a case study of LCs in Lesotho based on: (1) review of LC-related health policy and planning documents, (2) HIV programme review and (3) workload analysis of LCs. LCs are trained to provide HIV testing and counselling (HTC) and ART adherence support. Funded by international donors, 487 LCs were deployed between 2006 and 2011. However, in 2012, the number of LCs decreased to 165 due to a decreasing donor funds, while administrative and fiscal barriers hampered absorption of LCs into the public health system. That same year, ART coverage decreased from 61% to 51% and facility-based HTC decreased by 15%, from 253 994 in 2011 to 215 042 tests in 2012. The workload analysis indicated that LCs work averagely 77 h per month, bringing considerable relief to the scarce professional health workforce. HIV statistics in Lesotho worsened dramatically in the recent era of reduced support to LCs. This suggests that in order to ensure access to HIV care in an under-resourced setting like Lesotho, a recognized and well-supported counsellor cadre is essential. The continued presence of LCs requires improved prioritization, with national and international support