Sustained high fatality during TB therapy amid rapid decline in TB mortality at population level: A retrospective cohort and ecological analysis from Shiselweni, Eswatini.

OBJECTIVES: Despite declining TB notifications in Southern Africa, TB-related deaths remain high. We describe patient- and population-level trends in TB-related deaths in Eswatini over a period of 11 years. METHODS: Patient-level (retrospective cohort, from 2009 to 2019) and population-level (ecological analysis, 2009-2017) predictors and rates of TB-related deaths were analysed in HIV-negative and HIV-coinfected first-line TB treatment cases and the population of the Shiselweni region. Patient-level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient-level and population-level predictors of deaths. RESULTS: Of 11,883 TB treatment cases, 1302 (11.0%) patients died during treatment: 210/2798 (7.5%) HIV-negative patients, 984/8443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV-status. The treatment case fatality ratio remained above 10% in most years. At patient-level, fatality risk was higher in PLHIV (aRR 1.74, 1.51-2.02), and for older age and extra-pulmonary TB irrespective of HIV-status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18-1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47-1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB-LAM testing (aRR 0.65, 0.35-0.90). At population-level, mortality rates decreased 6.4-fold (-147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (-826/100,000 vs. HIV-negative: -23/100,000), the relative population-level mortality risk remained higher in PLHIV (aRR 4.68, 3.25-6.72) compared to the HIV-negative population. CONCLUSIONS: TB-related mortality rapidly decreased at population-level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted.

"It is still very little; I cannot pass it on": a qualitative study of experiences of diagnosis and treatment of acute HIV infection in Eswatini.

Acute and early HIV infection (AEHI) is rarely diagnosed in sub-Saharan Africa, despite its potential contribution to incidence reduction. This qualitative study in Eswatini explored the experiences of health workers, people diagnosed with AEHI, and their partners towards AEHI diagnosis, to inform its scale-up. In-depth interviews were undertaken with 11 women and four men diagnosed with AEHI. Three patients' partners were interviewed about their understanding of AEHI and six health workers were interviewed about experiences of delivering AEHI services. Data were coded inductively and analysed iteratively following the principles of grounded theory. Experiences with AEHI diagnoses were shaped by (i) understanding the nature and consequences of AEHI, and (ii) social norms that influence disclosure and sexual behaviour. AEHI was a new concept for health workers who struggled to explain it to patients, leading to some confusion over their HIV status and misunderstandings around its high transmissibility and prognosis. Disclosure tended to occur to primary partners, if at all, limiting the ability to provide partner services, and one relationship breakdown was reported. If AEHI diagnosis and care interventions are to realise their full potential, it will be essential to reinforce the accompanying counselling sessions and closely monitor for potential social harms.

The introduction of video-enabled directly observed therapy (video-DOT) for patients with drug-resistant TB disease in Eswatini amid the COVID-19 pandemic - a retrospective cohort study.

BACKGROUND: Video-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic. METHODS: This is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis. RESULTS: Of 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30-54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12-0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08-0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309-748) videos per patient and a median FEDO of 92% (IQR 84-97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01-0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03-0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis. CONCLUSIONS: Implementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes.

Implementation of targeted cholera response activities, Cameroon.

Objective: To describe the implementation of case-area targeted interventions to reduce cholera transmission using a rapid, localized response in Kribi district, Cameroon. Methods: We used a cross-sectional design to study the implementation of case-area targeted interventions. We initiated interventions after rapid diagnostic test confirmation of a case of cholera. We targeted households within a 100-250 metre perimeter around the index case (spatial targeting). The interventions package included: health promotion, oral cholera vaccination, antibiotic chemoprophylaxis for nonimmunized direct contacts, point-of-use water treatment and active case-finding. Findings: We implemented eight targeted intervention packages in four health areas of Kribi between 17 September 2020 and 16 October 2020. We visited 1533 households (range: 7-544 per case-area) hosting 5877 individuals (range: 7-1687 per case-area). The average time from detection of the index case to implementation of interventions was 3.4 days (range: 1-7). Oral cholera vaccination increased overall immunization coverage in Kribi from 49.2% (2771/5621 people) to 79.3% (4456/5621 people). Interventions also led to the detection and prompt management of eight suspected cases of cholera, five of whom had severe dehydration. Stool culture was positive for Vibrio cholerae O1 in four cases. The average time from onset of symptoms to admission of a person with cholera to a health facility was 1.2 days. Conclusion: Despite challenges, we successfully implemented targeted interventions at the tail-end of a cholera epidemic, after which no further cases were reported in Kribi up until week 49 of 2021. The effectiveness of case-area targeted interventions in stopping or reducing cholera transmission needs further investigation.

Effect of large-scale mass drug administration for malaria on mortality and morbidity in Angumu health zone, Ituri, Democratic Republic of Congo.

BACKGROUND: Angumu health zone in Ituri, Democratic Republic of Congo, is a highly malaria-endemic area with an overburdened health system and hosting internally displaced persons (IDP). The World Health Organization recommends mass drug administration (MDA) for malaria in complex emergencies. Therefore, three MDA rounds were implemented by Ministry of Public Health and Médecins sans Frontières from September 2020 to January 2021 in four health areas selected for epidemiological (high malaria incidence) and logistic reasons. Reported mortality and morbidity were compared in locations where MDA has been performed and locations where it has not. METHODS: A non-randomized controlled population-based retrospective mortality survey was conducted in March 2021. Two-stage cluster sampling was used in villages; all IDP sites were surveyed with systematic random sampling. The main (mortality rates) and secondary (morbidity) outcomes were estimated and compared between locations where MDA had been conducted and where it had not, using mixed Poisson and binomial regression models respectively. RESULTS: Data was collected for 2554 households and 15470 individuals, of whom 721 died in the 18-month recall period. The under-five mortality rate (U5MR) decreased in the locations where MDA had been implemented from 2.32 [1.48-3.16] "before" the MDA to 1.10 [0.5-1.71] deaths/10,000 children under 5 years/day "after", whereas it remained stable from 2.74 [2.08-3.40] to 2.67 [1.84-3.50] deaths/10,000 children/day in the same time periods in locations where MDA had not been implemented. The U5MR and malaria-specific mortality was significantly higher in non-MDA locations after MDA was implemented (aRR = 2.17 [1.36-3.49] and 2.60 [1.56-4.33], respectively, for all-cause and malaria-specific mortality among children < 5 years). Morbidity (all age and < 5 years, all cause or malaria-specific) appeared lower in MDA locations 2.5 months after last round: reported malaria-specific morbidity was 14.7% [11-18] and 25.0% [19-31] in villages and IDP sites where MDA had been implemented, while it was 30.4% [27-33] and 49.3% [45-54] in villages and IDP sites with no MDA. CONCLUSIONS: Despite traditional limitations associated with non-randomized controlled retrospective surveys, the documented sharp decrease of under-5 mortality and morbidity shows that MDA has the potential to become an important malaria-control tool in emergency settings. Based on these results, new MDA rounds, along with indoor residual spraying campaigns, have been planned in the health zone in 2022. A set of surveys will be conducted before, during and after these rounds to confirm the effect observed in 2021 and assess its duration.

An Automated Literature Review Tool (LiteRev) for Streamlining and Accelerating Research Using Natural Language Processing and Machine Learning: Descriptive Performance Evaluation Study.

BACKGROUND: Literature reviews (LRs) identify, evaluate, and synthesize relevant papers to a particular research question to advance understanding and support decision-making. However, LRs, especially traditional systematic reviews, are slow, resource-intensive, and become outdated quickly. OBJECTIVE: LiteRev is an advanced and enhanced version of an existing automation tool designed to assist researchers in conducting LRs through the implementation of cutting-edge technologies such as natural language processing and machine learning techniques. In this paper, we present a comprehensive explanation of LiteRev's capabilities, its methodology, and an evaluation of its accuracy and efficiency to a manual LR, highlighting the benefits of using LiteRev. METHODS: Based on the user's query, LiteRev performs an automated search on a wide range of open-access databases and retrieves relevant metadata on the resulting papers, including abstracts or full texts when available. These abstracts (or full texts) are text processed and represented as a term frequency-inverse document frequency matrix. Using dimensionality reduction (pairwise controlled manifold approximation) and clustering (hierarchical density-based spatial clustering of applications with noise) techniques, the corpus is divided into different topics described by a list of the most important keywords. The user can then select one or several topics of interest, enter additional keywords to refine its search, or provide key papers to the research question. Based on these inputs, LiteRev performs a k-nearest neighbor (k-NN) search and suggests a list of potentially interesting papers. By tagging the relevant ones, the user triggers new k-NN searches until no additional paper is suggested for screening. To assess the performance of LiteRev, we ran it in parallel to a manual LR on the burden and care for acute and early HIV infection in sub-Saharan Africa. We assessed the performance of LiteRev using true and false predictive values, recall, and work saved over sampling. RESULTS: LiteRev extracted, processed, and transformed text into a term frequency-inverse document frequency matrix of 631 unique papers from PubMed. The topic modeling module identified 16 topics and highlighted 2 topics of interest to the research question. Based on 18 key papers, the k-NNs module suggested 193 papers for screening out of 613 papers in total (31.5% of the whole corpus) and correctly identified 64 relevant papers out of the 87 papers found by the manual abstract screening (recall rate of 73.6%). Compared to the manual full text screening, LiteRev identified 42 relevant papers out of the 48 papers found manually (recall rate of 87.5%). This represents a total work saved over sampling of 56%. CONCLUSIONS: We presented the features and functionalities of LiteRev, an automation tool that uses natural language processing and machine learning methods to streamline and accelerate LRs and support researchers in getting quick and in-depth overviews on any topic of interest.

SARS-CoV-2 Antibody Prevalence and Population-Based Death Rates, Greater Omdurman, Sudan.

In a cross-sectional survey in Omdurman, Sudan, during March-April 2021, we estimated that 54.6% of the population had detectable severe acute respiratory syndrome coronavirus 2 antibodies. Overall population death rates among those >50 years of age increased 74% over the first coronavirus disease pandemic year.

Prevention of mother-to-child transmission of hepatitis B virus in antenatal care and maternity services, Mozambique.

OBJECTIVE: To pilot an intervention on the prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) in an antenatal care and maternity unit in Maputo, Mozambique, during 2017-2019. METHODS: We included HBV in the existing screening programme (for human immunodeficiency virus (HIV) and syphilis) for pregnant women at their first consultation, and followed mother-child dyads until 9 months after delivery. We referred women who tested positive for hepatitis B surface antigen (HBsAg) for further tests, including hepatitis B e antigen (HBeAg) and HBV viral load. According to the results, we proposed tenofovir for their own health or for PMTCT. We administered birth-dose HBV vaccine and assessed infant HBV status at 9 months. FINDINGS: Of 6775 screened women, 270 (4.0%) were HBsAg positive; in those for whom data were available, 24/265 (9.1%) were HBeAg positive and 14/267 (5.2%) had a viral load of > 200 000 IU/mL. Ninety-eight (36.3%) HBsAg-positive women were HIV coinfected, 97 of whom were receiving antiretroviral treatment with tenofovir. Among HIV-negative women, four had an indication for tenofovir treatment and four for tenofovir PMTCT. Of 217 exposed liveborn babies, 181 (83.4%) received birth-dose HBV vaccine, 160 (88.4%) of these < 24 hours after birth. At the 9-month follow-up, only one out of the 134 tested infants was HBV positive. CONCLUSION: Our nurse-led intervention highlights the feasibility of integrating PMTCT of HBV into existing antenatal care departments, essential for the implementation of the triple elimination initiative. Universal birth-dose vaccination is key to achieving HBV elimination.

Correction: Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

[This corrects the article DOI: 10.1371/journal.pmed.1003720.].

Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.

BACKGROUND: Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. METHODS AND FINDINGS: We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron-folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6-8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. CONCLUSIONS: This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.

Rotavirus vaccine efficacy up to 2 years of age and against diverse circulating rotavirus strains in Niger: Extended follow-up of a randomized controlled trial.

BACKGROUND: Rotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger. METHODS AND FINDINGS: From August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy. CONCLUSIONS: Rotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.

The Impact of Same-Day Antiretroviral Therapy Initiation Under the World Health Organization Treat-All Policy.

Rapid initiation of antiretroviral therapy (ART) is recommended for people living with human immunodeficiency virus (HIV), with the option to start treatment on the day of diagnosis (same-day ART). However, the effect of same-day ART remains unknown in realistic public sector settings. We established a cohort of ≥16-year-old patients who initiated first-line ART under a treat-all policy in Nhlangano (Eswatini) during 2014-2016, either on the day of HIV care enrollment (same-day ART) or 1-14 days thereafter (early ART). Directed acyclic graphs, flexible parametric survival analysis, and targeted maximum likelihood estimation (TMLE) were used to estimate the effect of same-day-ART initiation on a composite unfavorable treatment outcome (loss to follow-up, death, viral failure, treatment switch). Of 1,328 patients, 839 (63.2%) initiated same-day ART. The adjusted hazard ratio of the unfavorable outcome was higher, 1.48 (95% confidence interval: 1.16, 1.89), for same-day ART compared with early ART. TMLE suggested that after 1 year, 28.9% of patients would experience the unfavorable outcome under same-day ART compared with 21.2% under early ART (difference: 7.7%; 1.3%-14.1%). This estimate was driven by loss to follow-up and varied over time, with a higher hazard during the first year after HIV care enrollment and a similar hazard thereafter. We found an increased risk with same-day ART. A limitation was that possible silent transfers that were not captured.

Prevalence of malaria in an area receiving seasonal malaria chemoprevention in Niger.

BACKGROUND: Malaria transmission is highly seasonal in Niger. Despite the introduction of seasonal malaria chemoprevention (SMC) in the Magaria District, malaria incidence remains high, and the epidemiology of malaria in the community is not well-understood. METHODS: Four cross-sectional, household-based malaria prevalence surveys were performed in the Magaria District of Niger between October 2016 and February 2018. Two occurred during the peak malaria season and two during the low malaria season. Individuals in each of three age strata (3-59 months, 5-9 years, and 10 years and above) were sampled in randomly-selected households. Capillary blood was collected by fingerprick, thick and thin blood films were examined. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 396 households during the high-season surveys and 266 households during the low-season surveys. RESULTS: Prevalence of parasitaemia was highest in children aged 5-9 years during all four surveys, ranging between 53.6% (95%CI 48.8-63.6) in February 2018 and 73.2% (66.2-79.2) in September 2017. Prevalence of parasitaemia among children aged 3-59 months ranged between 39.6% (33.2-46.4) in February 2018 and 51.9% (45.1-58.6) in October 2016. Parasite density was highest in children aged 3-59 months during all four surveys, and was higher in high season surveys than in low season surveys among all participants. The prevalence of gametocytaemia in children aged 3-59 months ranged between 9.9% (6.5-14.8) in February 2018 and 19.3% (14.6-25.2) in October 2016. The prevalence of gametocytaemia in children aged 5-9 years ranged between 6.3% (3.5-11.1) in February 2018 and 18.5% (12.7-26.1) in October 2016. CONCLUSIONS: Asymptomatic malaria infection is highly prevalent in this area, even during the season with low incidence of clinical malaria. The high prevalence of parasitaemia in children aged 5-9 years warrants considering their inclusion in SMC programmes in this context.

PrEP reminds me that I am the one to take responsibility of my life: a qualitative study exploring experiences of and attitudes towards pre-exposure prophylaxis use by women in Eswatini.

BACKGROUND: Pre-exposure-prophylaxis (PrEP) has been heralded for its potential to put women in control of preventing HIV infection, but uptake and continuation rates have been disappointing in high-incidence settings in sub-Saharan Africa. We explored structural and social factors that influenced PrEP use among young women and pregnant or breastfeeding women in rural Eswatini. METHODS: We conducted two in-depth interviews with ten women on PrEP, and one-time in-depth interviews with fourteen women who declined or discontinued PrEP. Interviews covered decision-making processes around PrEP initiation and experiences with pill-taking. In-depth interviews were conducted with nine health workers, covering experiences in delivering PrEP services, and two focus group discussions were held with men to elicit their perceptions of PrEP. Interviews and discussions were audio-recorded, translated, transcribed and analysed thematically, using an inductive approach. RESULTS: PrEP initiation and use were experienced by many women as empowering them to take control of their health and well-being, and stay HIV free, facilitating them to realise their aspirations relating to motherhood and educational attainment. However, the social norms that defined relationship dynamics with partners or family members either undermined or promoted this empowerment potential. In particular, young women were rarely supported by family members to take PrEP unless it was perceived to be for protecting an unborn child. Stigmatisation of pill-taking through its associations with HIV and the burden of daily pill-taking also contributed to PrEP discontinuation. CONCLUSIONS: Unlike many prevention tools, PrEP enabled women to achieve a sense of control over their lives. Nevertheless, women's agency to continue and adhere to PrEP was influenced by social and structural factors including gender norms, family expectations of young women, relationship dynamics and stigma related to HIV. Future interventions should address these barriers to promote PrEP use among sexually-active women.

"We have to learn to cooperate with each other": a qualitative study to explore integration of traditional healers into the provision of HIV self-testing and tuberculosis screening in Eswatini.

BACKGROUND: Traditional healing plays an important role in healthcare in Eswatini, and innovative collaborations with traditional healers may enable hard-to-reach men to access HIV and tuberculosis diagnostic services. This study explored attitudes towards integration of traditional healers into the provision of HIV self-testing kits and sputum collection containers. METHODS: A qualitative study was conducted in 2019-2020 in Shiselweni region, Eswatini. Eight male traditional healers were trained on HIV and tuberculosis care including distribution of HIV self-testing kits and sputum collection containers. Attitudes towards the intervention were elicited through in-depth interviews with the eight traditional healers, ten clients, five healthcare workers and seven focus group discussions with community members. Interviews and group discussions were conducted in SiSwati, audio-recorded, translated and transcribed into English. Data were coded inductively and analysed thematically. RESULTS: 81 HIV self-testing kits and 24 sputum collection containers were distributed by the healers to 99 clients, with 14% of participants reporting a reactive HIV self-test result. The distribution of sputum containers did not result in any tuberculosis diagnoses, as samples were refused at health centres. Traditional healers perceived themselves as important healthcare providers, and after training, were willing and able to distribute HIV self-test kits and sputum containers to clients. Many saw themselves as peers who could address barriers to health-seeking among Swazi men that reflected hegemonic masculinities and patriarchal attitudes. Traditional healers were considered to provide services that were private, flexible, efficient and non-judgemental, although some clients and community members expressed concerns over confidentiality breaches. Attitudes among health workers were mixed, with some calling for greater collaboration with traditional healers and others expressing doubts about their potential role in promoting HIV and tuberculosis services. Specifically, many health workers did not accept sputum samples collected outside health facilities. CONCLUSIONS: Offering HIV self-testing kits and sputum containers through traditional healers led to high HIV yields, but no TB diagnoses. The intervention was appreciated by healers' clients, due to the cultural literacy of traditional healers and practical considerations. Scaling-up this approach could bridge testing gaps if traditional healers are supported, but procedures for receiving sputum samples at health facilities need further strengthening.

Implementation of community and facility-based HIV self-testing under routine conditions in southern Eswatini.

OBJECTIVES: WHO recommends HIV self-testing (HIVST) as an additional approach to HIV testing services. The study describes the strategies used during phase-in of HIVST under routine conditions in Eswatini (formerly Swaziland). METHODS: Between May 2017 and January 2018, assisted and unassisted oral HIVST was offered at HIV testing services (HTS) sites to people aged ≥ 16 years. Additional support tools were available, including a telephone hotline answered 24/7, HIVST demonstration videos and printed educational information about HIV prevention and care services. Demographic characteristics of HIVST users were described and compared with standard blood-based HTS in the community. HIVST results were monitored with follow-up phone calls and the hotline. RESULTS: During the 9-month period, 1895 people accessed HIVST and 2415 HIVST kits were distributed. More people accessed HIVST kits in the community (n = 1365, 72.0%) than at health facilities (n = 530, 28.0%). The proportion of males and median age among those accessing HIVST and standard HTS in the community were similar (49.3%, 29 years HIVST vs. 48.7%, 27 years standard HTS). In total, 34 (3.9%) reactive results were reported from 938 people with known HIVST results; 32.4% were males, and median age was 30 years (interquartile range 25-36). Twenty-one (62%) patients were known to have received confirmatory blood-based HTS; of these, 20 (95%) had concordant reactive results and 19 (95%) were linked to HIV care at a clinic. CONCLUSION: Integration of HIVST into existing HIV facility- and community-based testing strategies in Eswatini was found to be feasible, and HIVST has been adopted by national testing bodies in Eswatini.

OBJECTIFS: L'OMS recommande l'autotest du VIH (HIVST) comme approche supplémentaire des services de dépistage du VIH. L'étude décrit les stratégies utilisées lors de l'introduction progressive du VIHST dans des conditions de routine à Eswatini (anciennement le Swaziland). MÉTHODES: Entre mai 2017 et janvier 2018, des HIVST orales assistées et non assistées ont été proposés dans les sites des services de dépistage du VIH (HTS) aux personnes âgées de 16 ans et plus. Des outils de soutien supplémentaires étaient disponibles, notamment une permanence téléphonique répondue 24h/24 et 7j/7, des vidéos de démonstration sur le HIVST et des informations éducatives imprimées sur les services de prévention et de soins du VIH. Les caractéristiques démographiques des utilisateurs du VIHST ont été décrites et comparées aux tests sanguins standard des HTS dans la communauté. Les résultats des HIVST ont été contrôlés par des appels téléphoniques de suivi et la hotline. RÉSULTATS: Au cours de la période de 9 mois, 1895 personnes ont eu accès au VIHST et 2415 kits VIHST ont été distribués. Plus de personnes ont eu accès aux kits VIHST dans la communauté (n = 1365, 72,0%) que dans les établissements de santé (n = 530, 28,0%). La proportion d'hommes et l'âge médian parmi ceux qui accèdent au VIHST et au HTS standard dans la communauté étaient similaires (49,3%, 29 ans VIHST vs 48,7%, 27 ans HTS standard). Au total, 34 (3,9%) résultats réactifs ont été signalés chez 938 personnes avec des résultats connus pour le VIHST; 32,4% étaient des hommes et l'âge médian était de 30 ans (intervalle interquartile 25-36). 21 patients (62%) ont reçu un test sanguin de confirmation HTS; parmi ceux-ci, 20 (95%) avaient des résultats réactifs concordants et 19 (95%) ont été reliés aux soins du VIH dans une clinique. CONCLUSION: L'intégration du HIVST dans les structures existantes de dépistage du VIH et les stratégies de dépistage à Eswatini s'est avérée réalisable, et le HIVST a été adopté par les organismes nationaux de dépistage à Eswatini.

Treating HIV-associated cytomegalovirus retinitis with oral valganciclovir and intra-ocular ganciclovir by primary HIV clinicians in southern Myanmar: a retrospective analysis of routinely collected data.

BACKGROUND: Cytomegalovirus retinitis (CMVR) is an opportunistic infection in HIV-infected people. Intraocular or intravenous ganciclovir was gold standard for treatment; however, oral valganciclovir replaced this in high-income countries. Low- and middle-income countries (LMIC) frequently use intraocular injection of ganciclovir (IOG) alone because of cost. METHODS: Retrospective review of all HIV-positive patients with CMVR from February 2013 to April 2017 at a Médecins Sans Frontièrs HIV clinic in Myanmar. Treatment was classified as local (IOG) or systemic (valganciclovir, or valganciclovir and IOG). The primary outcome was change in visual acuity (VA) post-treatment. Mortality was a secondary outcome. RESULTS: Fifty-three patients were included. Baseline VA was available for 103 (97%) patient eyes. Active CMVR was present in 72 (68%) eyes. Post-treatment, seven (13%) patients had improvement in VA, 30 (57%) had no change, and three (6%) deteriorated. Among patients receiving systemic therapy, four (12.5%) died, compared with five (24%) receiving local therapy (p = 0.19). CONCLUSIONS: Our results from the first introduction of valganciclovir for CMVR in LMIC show encouraging effectiveness and safety in patients with advanced HIV. We urge HIV programmes to include valganciclovir as an essential medicine, and to include CMVR screening and treatment in the package of advanced HIV care.

High levels of viral repression, malnutrition and second-line ART use in adolescents living with HIV: a mixed methods study from Myanmar.

BACKGROUND: Adolescents living with HIV/AIDS (ALHIV) are a particularly vulnerable but often overlooked group in the HIV response despite additional disease management challenges. METHODS: All ALHIV (10-19 years), on ART for ≥6 months, presenting to care at a Médecins Sans Frontières (MSF) clinic in Myanmar from January-April 2016 were eligible for the quantitative study component (clinical history, medical examination, laboratory investigation). A subset of these respondents were invited to participate in qualitative interviews. Interviews and focus groups were also conducted with other key informants (care givers, clinicians). RESULTS: Of 177 ALHIV, 56% (100) were aged 9-13 years and 77 (44%) were 14-19. 49% (86) had been orphaned by one parent, and 19% (33) by both. 59% (104) were severely underweight (BMI < 16). 47% presented with advanced HIV (WHO stage III/IV). 93% were virally supressed (< 250 copies/mL). 38 (21%) of ALHIV were on a second-line ART after first-line virological failure. Qualitative interviewing highlighted factors limiting adherence and the central role that HIV counsellors play for both ALHIV patients and caregivers. CONCLUSIONS: Our study shows good clinical, immunological, and virological outcomes for a cohort of Myanmar adolescents living with HIV, despite a majority being severely underweight, presenting with Stage III or IV illness, and the prevalence of comorbid infections (TB). Many treatment and adherence challenges were articulated in qualitative interviewing but emphasized the importance of actively engaging adolescents in their treatment. Comprehensive HIV care for this population must include routine viral load testing and social support programs.

Effect of Artesunate-Amodiaquine on Mortality Related to Ebola Virus Disease.

BACKGROUND: Malaria treatment is recommended for patients with suspected Ebola virus disease (EVD) in West Africa, whether systeomatically or based on confirmed malaria diagnosis. At the Ebola treatment center in Foya, Lofa County, Liberia, the supply of artemether-lumefantrine, a first-line antimalarial combination drug, ran out for a 12-day period in August 2014. During this time, patients received the combination drug artesunate-amodiaquine; amodiaquine is a compound with anti-Ebola virus activity in vitro. No other obvious change in the care of patients occurred during this period. METHODS: We fit unadjusted and adjusted regression models to standardized patient-level data to estimate the risk ratio for death among patients with confirmed EVD who were prescribed artesunate-amodiaquine (artesunate-amodiaquine group), as compared with those who were prescribed artemether-lumefantrine (artemether-lumefantrine group) and those who were not prescribed any antimalarial drug (no-antimalarial group). RESULTS: Between June 5 and October 24, 2014, a total of 382 patients with confirmed EVD were admitted to the Ebola treatment center in Foya. At admission, 194 patients were prescribed artemether-lumefantrine and 71 were prescribed artesunate-amodiaquine. The characteristics of the patients in the artesunate-amodiaquine group were similar to those in the artemether-lumefantrine group and those in the no-antimalarial group. A total of 125 of the 194 patients in the artemether-lumefantrine group (64.4%) died, as compared with 36 of the 71 patients in the artesunate-amodiaquine group (50.7%). In adjusted analyses, the artesunate-amodiaquine group had a 31% lower risk of death than the artemether-lumefantrine group (risk ratio, 0.69; 95% confidence interval, 0.54 to 0.89), with a stronger effect observed among patients without malaria. CONCLUSIONS: Patients who were prescribed artesunate-amodiaquine had a lower risk of death from EVD than did patients who were prescribed artemether-lumefantrine. However, our analyses cannot exclude the possibility that artemether-lumefantrine is associated with an increased risk of death or that the use of artesunate-amodiaquine was associated with unmeasured patient characteristics that directly altered the risk of death.

Programmatic outcomes and impact of rapid public sector antiretroviral therapy expansion in adults prior to introduction of the WHO treat-all approach in rural Eswatini.

OBJECTIVES: To assess long-term antiretroviral therapy (ART) outcomes during rapid HIV programme expansion in the public sector of Eswatini (formerly Swaziland). METHODS: This is a retrospectively established cohort of HIV-positive adults (≥16 years) who started first-line ART in 25 health facilities in Shiselweni (Eswatini) between 01/2006 and 12/2014. Temporal trends in ART attrition, treatment expansion and ART coverage were described over 9 years. We used flexible parametric survival models to assess the relationship between time to ART attrition and covariates. RESULTS: Of 24 772 ART initiations, 6% (n = 1488) occurred in 2006, vs. 13% (n = 3192) in 2014. Between these years, median CD4 cell count at ART initiation increased (113-265 cells/mm3 ). The active treatment cohort expanded 8.4-fold, ART coverage increased 8.0-fold (7.1% in 2006 vs. 56.8% in 2014) and 12-month crude ART retention improved from 71% to 86%. Compared with the pre-decentralisation period (2006-2007), attrition decreased by 5% (adjusted hazard ratio [aHR] 0.95, 95% confidence interval 0.88-1.02) during HIV-TB service decentralisation (2008-2010), by 17% (aHR 0.83, 0.75-0.92) during service consolidation (2011-2012), and by 20% (aHR 0.80, 0.71-0.90) during further treatment expansion (2013-2014). The risk of attrition was higher for young age, male sex, pathological baseline haemoglobin and biochemistry results, more toxic drug regimens, WHO III/IV staging and low CD4 cell count; access to a telephone was protective. CONCLUSIONS: Programmatic outcomes improved during large expansion of the treatment cohort and increased ART coverage. Changes in ART programming may have contributed to better outcomes.

OBJECTIFS: Evaluer les résultats du traitement antirétroviral (ART) à long terme durant l'expansion rapide du programme de lutte contre le VIH dans le secteur public d'Eswatini (anciennement Swaziland). MÉTHODES: Il s'agit d'une cohorte établie de manière rétrospective d'adultes VIH positifs (≥ 16 ans) qui ont commencé un ART de première ligne dans 25 établissements de santé à Shiselweni (Eswatini) entre janvier 2006 et décembre 2014. Les tendances temporelles de l'attrition dans l'ART, de l'extension de la couverture ART ont été décrites sur 9 ans. Nous avons utilisé des modèles de survie paramétriques flexibles pour évaluer la relation entre le temps écoulé avant l'attrition dans l'ART et les covariables. RÉSULTATS: Sur 24.772 initiations à l'ART, 6% (n = 1.488) ont eu lieu en 2006 contre 13% (n = 3.192) en 2014. Entre ces années, le nombre médian de cellules CD4 au début du traitement ART a augmenté (113 à 265 cellules/mm3 ). La cohorte de traitement actif a été multipliée par 8,4, la couverture ART par 8,0 (7,1% en 2006 contre 56,8% en 2014) et la rétention brute sous ART est passée de 71% à 86%. Par rapport à la période antérieure à la décentralisation (2006-2007), l'attrition a diminué de 5% (rapport de risque ajusté [aHR]: 0,95, intervalle de confiance à 95%: 0,88 à 1,02) au cours de la décentralisation des services VIH-TB (2008-2010), de 17% (HR: 0,83; 0,75-0,92) lors de la consolidation du service (2011-2012) et de 20% (HR: 0,80; 0,71-0,90) lors de la poursuite de l'extension du traitement (2013-2014). Le risque d'attrition était plus élevé pour le jeune âge, le sexe masculin, les résultats pathologiques de l'hémoglobine initiale et biochimiques, des schémas thérapeutiques plus toxiques, un stade III/IV de l'OMS et une faible numération des cellules CD4; l'accès au téléphone était protecteur. CONCLUSIONS: Les résultats programmatiques se sont améliorés au cours de l'expansion importante de la cohorte de traitement et de l'augmentation de la couverture ART. Les changements apportés au programme ART peuvent avoir contribué à de meilleurs résultats.