Diagnosis of SARS-CoV-2 infection from breath - a proof-of-concept study

Bioaerosol capture and analysis is emerging as a non-invasive diagnostic method for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this proof-of-concept study conducted in Lesotho, we evaluated the novel and simple AL2 bioaerosol detection device in comparison to conventional nasopharyngeal sampling methods. We demonstrated for the first time that SARS-CoV-2 can be detected using the AL2 bioaerosol capture device. However, studies with a larger sample size are needed to further evaluate this bioaerosol capture device for the detection of SARS-CoV-2

Feasibility of implementing the advanced HIV disease care package as part of community-based HIV/TB activities: a mixed-methods study protocol

INTRODUCTION: Although the advanced HIV disease (AHD) care package reduces morbidity and mortality in people with AHD (defined in people living with HIV as WHO stage 3 or 4, CD4 count <200 cells/microL or age <5 years), it is barely implemented in many countries. A novel point-of-care CD4 test rapidly identifies AHD. We evaluate the feasibility of implementing the AHD care package as part of community-based HIV/tuberculosis services. METHODS AND ANALYSIS: This two-phased study is guided by the Medical Research Council framework for evaluation of complex interventions. Stage 1 is a stakeholder consultation to define tools and indicators to assess feasibility of the AHD care package. Stage 2 is the implementation of the AHD care package during a facility-based tuberculosis diagnostic accuracy study in high-burden HIV/tuberculosis settings. Consenting adults with tuberculosis symptoms in two sites in Lesotho and South Africa are eligible for inclusion. HIV-positive participants are included in the feasibility study and are offered a CD4 test, a tuberculosis-lipoarabinomannan assay and those with CD4 count of </=200 cells/microL a cryptococcal antigen lateral flow assay. Participants are referred for clinical management following national guidelines. The evaluation includes group discussions, participant observation (qualitative strand) and a semistructured questionnaire to assess acceptability among implementers. The quantitative strand also evaluates process compliance (process rating and process cascade) and early outcomes (vital and treatment status after twelve weeks). Thematic content analysis, descriptive statistics and data triangulation will be performed. ETHICS AND DISSEMINATION: The National Health Research and Ethics Committee, Lesotho, the Human Sciences Research Council Research Ethics Committee and Provincial Department of Health, South Africa and the Ethikkommission Nordwest- und Zentralschweiz, Switzerland, approved the protocol. Dissemination will happen locally and internationally at scientific conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04666311

Effectiveness of a peer educator-coordinated preference-based differentiated service delivery model on viral suppression among young people living with HIV in Lesotho: the PEBRA cluster-randomized trial

BACKGROUND: Southern and Eastern Africa is home to more than 2.1 million young people aged 15 to 24 years living with HIV. As compared with other age groups, this population group has poorer outcomes along the HIV care cascade. Young people living with HIV and the research team co-created the PEBRA (Peer Educator-Based Refill of ART) care model. In PEBRA, a peer educator (PE) delivered services as per regularly assessed patient preferences for medication pick-up, short message service (SMS) notifications, and psychosocial support. The cluster-randomized trial compared PEBRA model versus standard clinic care (no PE and ART refill done by nurses) in 3 districts in Lesotho. METHODS AND FINDINGS: Individuals taking antiretroviral therapy (ART) aged 15 to 24 years at 20 clinics (clusters) were eligible. In the 10 clinics randomized to the intervention arm, participants were offered the PEBRA model, coordinated by a trained PE and supported by an eHealth application (PEBRApp). In the 10 control clusters, participants received standard nurse-coordinated care without any service coordination by a PE. The primary endpoint was 12-month viral suppression below 20 copies/mL. Analyses were intention-to-treat and adjusted for sex. From November 6, 2019 to February 4, 2020, we enrolled 307 individuals (150 intervention, 157 control; 218 [71%] female, median age 19 years [interquartile range, IQR, 17 to 22]). At 12 months, 99 of 150 (66%) participants in the intervention versus 95 of 157 (61%) participants in the control arm had viral suppression (adjusted odds ratio (OR) 1.27; 95% confidence interval [CI] [0.79 to 2.03]; p = 0.327); 4 of 150 (2.7%) versus 1 of 157 (0.6%) had died (adjusted OR 4.12; 95% CI [0.45 to 37.62]; p = 0.210); and 12 of 150 (8%) versus 23 of 157 (14.7%) had transferred out (adjusted OR 0.53; 95% CI [0.25 to 1.13]; p = 0.099). There were no significant differences between arms in other secondary outcomes. Twenty participants (11 in intervention and 9 in control) were lost to follow-up over the entire study period. The main limitation was that the data collectors in the control clusters were also young peers; however, they used a restricted version of the PEBRApp to collect data and thus were not able to provide the PEBRA model. The trial was prospectively registered on ClinicalTrials.gov (NCT03969030). CONCLUSIONS: Preference-based peer-coordinated care for young people living with HIV, compared to nurse-based care only, did not lead to conclusive evidence for an effect on viral suppression. TRIAL REGISTRATION: clinicaltrials.gov, NCT03969030, https://clinicaltrials.gov/ct2/show/NCT03969030

Head-to-head comparison of nasal and nasopharyngeal sampling using SARS-CoV-2 rapid antigen testing in Lesotho

OBJECTIVES: To assess the real-world diagnostic performance of nasal and nasopharyngeal swabs for SD Biosensor STANDARD Q COVID-19 Antigen Rapid Diagnostic Test (Ag-RDT). METHODS: Individuals >/=5 years with COVID-19 compatible symptoms or history of exposure to SARS-CoV-2 presenting at hospitals in Lesotho received two nasopharyngeal and one nasal swab. Ag-RDT from nasal and nasopharyngeal swabs were performed as point-of-care on site, the second nasopharyngeal swab used for polymerase chain reaction (PCR) as the reference standard. RESULTS: Out of 2198 participants enrolled, 2131 had a valid PCR result (61% female, median age 41 years, 8% children), 84.5% were symptomatic. Overall PCR positivity rate was 5.8%. The sensitivity for nasopharyngeal, nasal, and combined nasal and nasopharyngeal Ag-RDT result was 70.2% (95%CI: 61.3-78.0), 67.3% (57.3-76.3) and 74.4% (65.5-82.0), respectively. The respective specificity was 97.9% (97.1-98.4), 97.9% (97.2-98.5) and 97.5% (96.7-98.2). For both sampling modalities, sensitivity was higher in participants with symptom duration </= 3days versus /= 80%. The high agreement between nasal and nasopharyngeal sampling suggests that for Ag-RDT nasal sampling is a good alternative to nasopharyngeal sampling

High unreported mortality in children and youth (<25 years) living with HIV who were lost to care from antiretroviral therapy programs in Southern Africa: results from a multi-country tracing study.

BACKGROUND Antiretroviral therapy (ART) program mortality maybe underestimated if deceased patients are misclassified as lost. METHODS We used two-stage inverse probability weighting to account for probability of being: sampled for tracing and found by the tracer. RESULTS Among 680 children and youth aged <25 years on ART who were lost and traced in Southern Africa between October 2017-November 2019, estimated mortality was high at 9.1% (62/680). After adjusting for measured covariates and within-site clustering, mortality remained lower for young adults aged 20-24 years compared to infants aged <2years (adjusted Hazard ratio (aHR): 0.40 (95% confidence interval (CI): 0.31, 0.51)). CONCLUSIONS Our study confirms high unreported mortality in children and youth who are lost and the need for tracing to assess vital status among those who are lost to accurately report on program mortality

Impact of a multi-disease integrated screening and diagnostic model for COVID-19, TB, and HIV in Lesotho

The surge of the COVID-19 pandemic challenged health services globally, and in Lesotho, the HIV and tuberculosis (TB) services were similarly affected. Integrated, multi-disease diagnostic services were proposed solutions to mitigate these disruptions. We describe and evaluate the effect of an integrated, hospital-based COVID-19, TB and HIV screening and diagnostic model in two rural districts in Lesotho, during the period between December 2020 and August 2022. Adults, hospital staff, and children above 5 years attending two hospitals were pre-screened for COVID-19 and TB symptoms. After a positive pre-screening, participants were offered to enroll in a service model that included clinical evaluation, chest radiography, SARS-CoV-2, TB, and HIV testing. Participants diagnosed with COVID-19, TB, or HIV were contacted after 28 days to evaluate their health status and linkage to HIV and/or TB care services. Of the 179160 participants pre-screened, 6623(3.7%) pre-screened positive, and 4371(66%) were enrolled in this service model. Of the total 458 diagnoses, only 17 happened in children. One positive rapid antigen test for SARS-CoV-2 was found per 11 participants enrolled, one Xpert-positive TB case was diagnosed per 85 people enrolled, and 1 new HIV diagnosis was done per 182 people enrolled. Of the 321(82.9%) participants contacted after 28 days of diagnosis, 304(94.7%) reported to be healthy. Of the individuals that were newly diagnosed with HIV or TB, 18/24(75.0%) and 46/51(90.1%) started treatment within 28 days of the diagnosis. This screening and diagnostic model successfully maintained same-day, integrated COVID-19, TB, and HIV testing services, despite frequent disruptions caused by the surge of COVID-19 waves, healthcare seeking patterns, and the volatile context (social measures, travel restrictions, population lockdowns). There were positive effects in avoiding diagnostic delays and ensuring linkage to services, however, diagnostic yields for adults and children were low. To inform future preparedness plans, research will need to identify essential health interventions and how to optimize them along each phase of the emergency response

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women.The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART.Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm(3) at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit.Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population