Prevalence of drug-resistant mutations in newly diagnosed drug-naïve HIV-1-infected individuals in a treatment site in the Waterberg district, Limpopo province

Aim. We studied the prevalence of resistance mutations in drugnaïve HIV-infected individuals at the Bela-Bela treatment site to gather information on the presence of antiretroviral (ARV) drug-resistant viruses in drug-naïve populations, so as to improve treatment guidance. Subjects and methods. Drug-naïve HIV-1-infected individuals were sequentially recruited between February 2008 and December 2008 from individuals visiting the voluntary counselling and testing (VCT) services of the Bela-Bela HIV/AIDS Wellness Clinic. Viral subtyping was done by phylogenetic analysis; drug-resistant mutations were determined according to the Stanford HIV Drug Resistance Interpretation and the International AIDS Society-USA Guidelines. Results. A drug-resistant mutation prevalence of 3.5% (95% confidence interval 0.019796 - 0.119077) comprising Y181C and L33F was observed; 98% of the viruses were HIV-1 subtype C on the protease (PR) and reverse transcriptase (RT) gene regions. Conclusion. The prevalence of drug-resistant mutations in drug-naïve persons may be low in Bela-Bela after 8 years of access to antiretroviral treatment (ART), and resistance testing before initiating treatment may not be needed

A call to action: Addressing the reproductive health needs of women with drug-resistant tuberculosis

Although there is substantial risk to maternal and neonatal health in the situation of pregnancy during treatment for rifampicin-resistant tuberculosis (RR-TB), there is little evidence to guide clinicians as to how to manage this complexity. Of the 49 680 patients initiated on RR-TB treatment from 2009 to 2014 in South Africa, 47% were women and 80% of them were in their reproductive years (15 - 44). There is an urgent need for increased evidence of the safety of RR-TB treatment during pregnancy, increased access to contraception during RR-TB treatment, and inclusion of reproductive health in research on the prevention and treatment of TB

Opportunities from a new disease for an old threat: extending COVID-19 efforts to address tuberculosis in South Africa

The COVID-19 pandemic and phased nationwide lockdown have impacted negatively on individuals with tuberculosis (TB) and routine TB services. Through a literature review and the perspective of members of a national TB Think Tank task team, we describe the impact of the pandemic and lockdown on TB patients and services as well as the potential long-term setback to TB control in South Africa (SA). Strategies to mitigate risk and impact are explored, together with opportunities to leverage synergies from both diseases to the benefit of the National TB Programme (NTP). With the emergence of COVID-19, activities to address this new pandemic have been prioritised across all sectors. Within the health system, the health workforce and resources have been redirected away from routine services towards the new disease priority. The social determinants of health have deteriorated during the lockdown, potentially increasing progression to TB disease and impacting negatively on people with TB and their households, resulting in additional barriers to accessing TB care, with early reports of a decline in TB testing rates. Fewer TB diagnoses, less attention to adherence and support during TB treatment, poorer treatment outcomes and consequent increased transmission will increase the TB burden and TB-related mortality. People with TB or a history of TB are likely to be vulnerable to COVID-19. Modifications to current treatment practices are suggested to reduce visits to health facilities and minimise the risks of COVID 19 exposure. The COVID-19 pandemic has the potential to negatively impact on TB control in TB-endemic settings such as SA. However, there are COVID-19-related health systems-strengthening developments that may help the NTP mitigate the impact of the pandemic on TB control. By integrating TB case finding into the advanced screening, testing, tracing and monitoring systems established for COVID-19, TB case finding and linkage to care could increase, with many more TB patients starting treatment. Similarly, integrating knowledge and awareness of TB into the increased healthcare worker and community education on infectious respiratory diseases, behavioural practices around infection prevention and control, and cough etiquette, including destigmatisation of mask use, may contribute to reducing TB transmission. However, these potential gains could be overwhelmed by the impact of increasing poverty and other social determinants of health on the burden of TB

Tuberculosis control in South Africa: Successes, challenges and recommendations

Tuberculosis (TB) remains a global health threat, and South Africa (SA) has one of the world’s worst TB epidemics driven by HIV. Among the 22 countries with the highest burden of TB, SA has the highest estimated incidence and prevalence of TB, the second highest number of diagnosed multidrug-resistant TB cases, and the largest number of HIV-associated TB cases. Although SA has made notable progress in reducing TB prevalence and deaths and improving treatment outcomes for new smear-positive TB cases, the burden of TB remains enormous. SA has the means to overcome this situation. In addition to better implementing the basics of TB diagnosis and treatment, scaling up the use of Xpert MTB/RIF as a replacement for sputum smear microscopy, strengthening case finding in and beyond healthcare facilities and a greater focus on TB prevention for people living with HIV, particularly earlier initiation of and scaling up antiretroviral therapy and scaling up continuous isoniazid preventive therapy, will have a substantial impact on TB control. New TB drugs, diagnostics and vaccines are required to further accelerate progress towards improved TB control in SA and beyond.

Medical causes of admissions to hospital among adults in Africa: a systematic review.

BACKGROUND: Despite the publication of several studies on the subject, there is significant uncertainty regarding the burden of disease among adults in sub-Saharan Africa (sSA). OBJECTIVES: To describe the breadth of available data regarding causes of admission to hospital, to systematically analyze the methodological quality of these studies, and to provide recommendations for future research. DESIGN: We performed a systematic online and hand-based search for articles describing patterns of medical illnesses in patients admitted to hospitals in sSA between 1950 and 2010. Diseases were grouped into bodily systems using International Classification of Disease (ICD) guidelines. We compared the proportions of admissions and deaths by diagnostic category using χ2. RESULTS: Thirty articles, describing 86,307 admissions and 9,695 deaths, met the inclusion criteria. The leading causes of admission were infectious and parasitic diseases (19.8%, 95% confidence interval [CI] 19.6-20.1), respiratory (16.2%, 95% CI 16.0-16.5) and circulatory (11.3%, 95% CI 11.1-11.5) illnesses. The leading causes of death were infectious and parasitic (17.1%, 95% CI 16.4-17.9), circulatory (16%, 95% CI 15.3-16.8) and digestive (16.2%, 95% CI 15.4-16.9). Circulatory diseases increased from 3.9% of all admissions in 1950-59 to 19.9% in 2000-2010 (RR 5.1, 95% CI 4.5-5.8, test for trend p<0.00005). The most prevalent methodological deficiencies, present in two-thirds of studies, were failures to use standardized case definitions and ICD guidelines for classifying illnesses. CONCLUSIONS: Cardiovascular and infectious diseases are currently the leading causes of admissions and in-hospital deaths in sSA. Methodological deficiencies have limited the usefulness of previous studies in defining national patterns of disease in adults. As African countries pass through demographic and health transition, they need to significantly invest in clinical research capacity to provide an accurate description of the disease burden among adults for public health policy

Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda

YesSETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment.OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality.DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality.RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality.CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda

Epidemiology of drug-resistant tuberculosis among children and adolescents in South Africa, 2005-2010

OBJECTIVE : To describe the demographic and clinical characteristics of children and adolescents diagnosed with resistance to any anti-tuberculosis drug (drug-resistant tuberculosis; DR-TB) in South Africa. DESIGN : We retrospectively reviewed medical records of all children (<13 years) and adolescents (13 to <18 years) with DR-TB at specialty hospitals in four South African provinces from 2005 to 2010. RESULTS : During the review period, 774 children and adolescents (median age 11.3 years) were diagnosed with DR-TB at selected facilities. A high proportion of patients had a history of previous TB treatment (285/631; 45.2%), human immunodeficiency virus (HIV) infection (375/685; 54.7%), contact with a TB case (347/454; 76.4%), and smear-positive (443/729; 60.8%), cavitary (253/680, 38.7%) disease. Eighty-two per cent of patients with HIV infection received antiretroviral therapy. Of 626 patients diagnosed with multidrug-resistant TB (MDR-TB), 561 (89.6%) received a regimen consistent with national guidelines; the median length of treatment was 22 months (IQR 16-25). Among 400 patients with any DR-TB and a known outcome, 20.3% died during treatment. CONCLUSION : Pediatric DR-TB in these provinces is characterized by complex clinical features at diagnosis, with one in five children dying during treatment. History of previous treatment and contact with a TB patient indicate opportunities for earlier diagnosis and treatment to improve outcomes.U.S. Agency for International Development and U.S. Centers for Disease Control and Prevention, with additional support from the South Africa National Institute for Communicable Diseases and the South African Medical Research Council.http://www.ingentaconnect.comcontent/iuatld/ijtld2015-12-01hb201

Implementing novel regimens for drug-resistant TB in South Africa : what can the world learn?

CITATION: Ndjeka, N. et al. 2020. Implementing novel regimens for drug-resistant TB in South Africa: what can the world learn?. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 24(10):1073–1080. doi:10.5588/ijtld.20.0174The original publication is available at https://www.ingentaconnect.com/content/iuatld/ijtldWorldwide uptake of new drugs in the treatment of rifampicin-resistant tuberculosis (RR-TB) has been extremely low. In June 2018, ahead of the release of the updated WHO guidelines for the management of RR-TB, South Africa announced that bedaquiline (BDQ) would be provided to virtually all RR-TB patients on shorter or longer regimens. South Africa has been the global leader in accessing BDQ for patients with RR-TB, who now represent 60% of the global BDQ cohort. The use of BDQ within a shorter modified regimen has generated the programmatic data underpinning the most recent change in WHO guidelines endorsing a shorter, injectable-free regimen. Progressive policies on access to new drugs have resulted in improved favourable outcomes and a reduction in mortality among RR-TB patients in South Africa. This supported global policy change. The strategies underpinning these bold actions include close collaboration between the South African National TB Programme and partners, introduction of new TB diagnostic tools in closely monitored conditions and the use of locally generated programmatic evidence to inform country policy changes. In this paper, we summarise a decade´s work that led to the bold decision to use a modified, short, injectable-free regimen with BDQ and linezolid under carefully monitored programmatic conditions.https://www.ingentaconnect.com/content/iuatld/ijtld/2020/00000024/00000010/art00016Publishers versio

Comparison of Xpert MTB/RIF with Other Nucleic Acid Technologies for Diagnosing Pulmonary Tuberculosis in a High HIV Prevalence Setting: A Prospective Study

In this prospective, real-world cohort study nested within a national screening program for tuberculosis, Lesley Scott and colleagues compare the performance of Xpert MTB/RIF on a single sputum sample with different TB sputum detection technologies

MDR/XDR-TB management of patients and contacts: Challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities