Short and long term retention in antiretroviral care in health facilities in rural Malawi and Zimbabwe.

Despite the successful scale-up of ART services over the past years, long term retention in ART care remains a major challenge, especially in high HIV prevalence and resource-limited settings. This study analysed the short (<12 months) and long (>12 months) term retention on ART in two ART programmes in Malawi (Thyolo district) and Zimbabwe (Buhera district)

Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya

Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse

Borderline rpoB mutations transmit at the same rate as common rpoB mutations in a tuberculosis cohort in Bangladesh

The spread of multidrug-resistant tuberculosis (MDR-TB) is a growing problem in many countries worldwide. Resistance to one of the primary first-line drugs, rifampicin, is caused by mutations in the Mycobacterium tuberculosis rpoB gene. So-called borderline rpoB mutations confer low-level resistance, in contrast to more common rpoB mutations which confer high-level resistance. While some borderline mutations show lower fitness in vitro than common mutations, their in vivo fitness is currently unknown. We used a dataset of 394 whole genome sequenced MDR-TB isolates from Bangladesh, representing around 44 % of notified MDR-TB cases over 6 years, to look at differences in transmission clustering between isolates with borderline rpoB mutations and those with common rpoB mutations. We found a relatively low percentage of transmission clustering in the dataset (34.8 %) but no difference in clustering between different types of rpoB mutations. Compensatory mutations in rpoA, rpoB, and rpoC were associated with higher levels of transmission clustering as were lineages two, three, and four relative to lineage one. Young people as well as patients with high sputum smear positive TB were more likely to be in a transmission cluster. Our findings show that although borderline rpoB mutations have lower in vitro growth potential this does not translate into lower transmission potential or in vivo fitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities

The global pendulum swing towards community health workers in low- and middle-income countries: A scoping review of trends, geographical distribution and programmatic orientations, 2005 to 2014

BACKGROUND: There has been a substantial increase in publications and interest in community health workers (CHWs) in low- and middle-income countries (LMIC) over the last years. This paper examines the growth, geographical distribution and programmatic orientations of the indexed literature on CHWs in LMIC over a 10-year period. METHODS: A scoping review of publications on CHWs from 2005 to 2014 was conducted. Using an inclusive list of terms, we searched seven databases (including MEDLINE, CINAHL, Cochrane) for all English-language publications on CHWs in LMIC. Two authors independently screened titles/abstracts, downloading full-text publications meeting inclusion criteria. These were coded in an Excel spreadsheet by year, type of publication (e.g. review, empirical), country, region, programmatic orientation (e.g. maternal-child health, HIV/AIDS, comprehensive) and CHW roles (e.g. prevention, treatment) and further analysed in Stata14. Drawing principally on the subset of review articles, specific roles within programme areas were identified and grouped. FINDINGS: Six hundred seventy-eight publications from 46 countries on CHWs were inventoried over the 10-year period. There was a sevenfold increase in annual number of publications from 23 in 2005 to 156 in 2014. Half the publications were reporting on initiatives in Africa, a third from Asia and 11 % from the Americas (mostly Brazil). The largest single focus and driver of the growth in publications was on CHW roles in meeting the Millennium Development Goals of maternal, child and neonatal survival (35 % of total), followed by HIV/AIDS (16 %), reproductive health (6 %), non-communicable diseases (4 %) and mental health (4 %). Only 17 % of the publications approached CHW roles in an integrated fashion. There were also distinct regional (and sometimes country) profiles, reflecting different histories and programme traditions. CONCLUSIONS: The growth in literature on CHWs provides empirical evidence of ever-increasing expectations for addressing health burdens through community-based action. This literature has a strong disease- or programme-specific orientation, raising important questions for the design and sustainable delivery of integrated national programmes.Scopu

Management of pregnant women infected with Ebola virus in a treatment centre in Guinea, June 2014

We report two cases of confirmed Ebola virus disease in pregnant women, who presented at the Médecins Sans Frontières Ebola treatment centre in Guéckédou. Despite the very high risk of death, both pregnant women survived. In both cases the critical decision was made to induce vaginal delivery. We raise a number of considerations regarding the management of Ebola virus-infected pregnant women, including the place of amniocentesis and induced delivery, and whether certain invasive medical acts are justified

Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis

Introduction: Adherence to HIV antiretroviral therapy (ART) is a critical determinant of HIV-1 RNA viral suppression and health outcomes. It is generally accepted that HIV-related stigma is correlated with factors that may undermine ART adherence, but its relationship with ART adherence itself is not well established. We therefore undertook this review to systematically assess the relationship between HIV-related stigma and ART adherence. Methods: We searched nine electronic databases for published and unpublished literature, with no language restrictions. First we screened the titles and abstracts for studies that potentially contained data on ART adherence. Then we reviewed the full text of these studies to identify articles that reported data on the relationship between ART adherence and either HIV-related stigma or serostatus disclosure. We used the method of meta-synthesis to summarize the findings from the qualitative studies. Results: Our search protocol yielded 14,854 initial records. After eliminating duplicates and screening the titles and abstracts, we retrieved the full text of 960 journal articles, dissertations and unpublished conference abstracts for review. We included 75 studies conducted among 26,715 HIV-positive persons living in 32 countries worldwide, with less representation of work from Eastern Europe and Central Asia. Among the 34 qualitative studies, our meta-synthesis identified five distinct third-order labels through an inductive process that we categorized as themes and organized in a conceptual model spanning intrapersonal, interpersonal and structural levels. HIV-related stigma undermined ART adherence by compromising general psychological processes, such as adaptive coping and social support. We also identified psychological processes specific to HIV-positive persons driven by predominant stigmatizing attitudes and which undermined adherence, such as internalized stigma and concealment. Adaptive coping and social support were critical determinants of participants’ ability to overcome the structural and economic barriers associated with poverty in order to successfully adhere to ART. Among the 41 quantitative studies, 24 of 33 cross-sectional studies (71%) reported a positive finding between HIV stigma and ART non-adherence, while 6 of 7 longitudinal studies (86%) reported a null finding (Pearson's χ 2=7.7; p=0.005). Conclusions: We found that HIV-related stigma compromised participants’ abilities to successfully adhere to ART. Interventions to reduce stigma should target multiple levels of influence (intrapersonal, interpersonal and structural) in order to have maximum effectiveness on improving ART adherence

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

Rifampicin resistance conferring mutations among Mycobacterium tuberculosis strains in Rwanda

Background: The World Health Organization-endorsed phenotypic and genotypic drug-susceptibility testing (gDST/pDST) assays for the detection of rifampicin-resistant (RR) tuberculosis (TB), may miss some clinically relevant rpoB mutants, including borderline mutations and mutations outside the gDST-targeted hotspot region. Sequencing of the full rpoB gene is considered the reference standard for rifampicin DST but is rarely available in RR-TB endemic settings and when done indirectly on cultured isolates may not represent the full spectrum of mutations. Hence, in most such settings, the diversity and trends of rpoB mutations remain largely unknown. Methods: This retrospective study included rpoB sequence data from a longitudinal collection of RR-TB isolates in Rwanda across 30 years (1991–2021). Results: Of 540 successfully sequenced isolates initially reported as RR-TB, 419 (77.6%) had a confirmed RR conferring mutation. The Ser450 Leu mutation was predominant throughout the study period. The Val170Phe mutation, not covered by rapid gDST assays, was observed in only four patients, three of whom were diagnosed by pDST. Along with the transition from pDST to rapid gDST, borderline RR-associated mutations, particularly Asp435Tyr, were detected more frequently. Borderline mutants were not associated with HIV status but presented lower odds of having rpoA-C compensatory mutations than other resistance-conferring mutations. Conclusion: Our analysis showed changes in the diversity of RR-TB conferring mutations throughout the study period that coincided with the switch of diagnostic tools to rapid gDST. The study highlights the importance of rapid molecular diagnostics reducing phenotypic bias in the detection of borderline rpoB mutations while vigilance for non-rifampicin resistance determinant region mutations is justified in any setting

Scaling Up ART Adherence Clubs in the Public Sector Health System in the Western Cape, South Africa: a Study of the Institutionalisation of a Pilot Innovation

In 2011, a decision was made to scale up a pilot innovation involving ‘adherence clubs’ as a form of differentiated care for HIV positive people in the public sector antiretroviral therapy programme in the Western Cape Province of South Africa. In 2016 we were involved in the qualitative aspect of an evaluation of the adherence club model, the overall objective of which was to assess the health outcomes for patients accessing clubs through epidemiological analysis, and to conduct a health systems analysis to evaluate how the model of care performed at scale. In this paper we adopt a complex adaptive systems lens to analyse planned organisational change through intervention in a state health system. We explore the challenges associated with taking to scale a pilot that began as a relatively simple innovation by a non-governmental organisation

Phenotypic and genotypic resistance to bedaquiline in patients with multi-drug-resistant tuberculosis—experiences from Armenia

Risk factors for baseline bedaquiline (BDQ) resistance, amplification during treatment, and correlations with treatment outcomes are not fully understood. This cohort included Armenian patients with multidrug-resistant TB predominantly fluoroquinolone-resistant enrolled between 2013 and 2015 in a BDQ compassionate use program. BDQ resistance at baseline and during treatment was assessed using MGIT (pDSTMGIT), minimal inhibitory concentration in 7H11 (MIC7H11), and whole-genome sequencing. Risk factors, such as treatment effectiveness or stage of the disease, were analyzed for association with baseline BDQ resistance, acquired BDQ resistance, and treatment outcome. Among 39 patients, baseline BDQ resistance was 6% (2/33) by pDSTMGIT and 7% (2/29) by MIC7H11. All four baseline isolates with an Rv0678 mutation were phenotypically resistant. During treatment, 48% of the patients acquired BDQ resistance by pDSTMGIT, and 52% acquired mutations at various frequencies (97% in Rv0678). None of the factors significantly contributed to baseline or acquired BDQ resistance. Unfavorable treatment outcome (41%) was more frequent in the presence of acquired Rv0678 mutations [odds ratio (OR) 132, 95% confidence interval (CI) 7.43, 2375], phenotypic BDQ resistance (OR 176, 95% CI 6.48, 2423), or MIC increase above or below the critical concentration (both OR 84.3, 95% CI 2.93, 2423) during treatment. For these highly treatment-experienced patients, low baseline prevalence but high incidence of acquired BDQ resistance was observed. Acquisition of mutations in BDQ candidate resistance genes, regardless of their frequency, or increased MICs during treatment, even below the critical concentration, should be seen as a warning sign of resistance amplification and increased risk of unfavorable treatment outcome