Continued attendance in a PrEP program despite low adherence and non-protective drug levels among adolescent girls and young women in Kenya: Results from a prospective cohort study.

BACKGROUND: In sub-Saharan Africa (SSA), adolescent girls and young women (AGYW) ages 15 to 24 years represent <10% of the population yet account for 1 in 5 new HIV infections. Although oral pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) can be highly effective, low persistence in PrEP programs and poor adherence have limited its ability to reduce HIV incidence among women. METHODS AND FINDINGS: A total of 336 AGYW participating in the PEPFAR-funded DREAMS PrEP program in western Kenya were enrolled into a study of PrEP use conducted between 6/2019 to 1/2020. AGYW, who used daily oral TDF/FTC, completed interviews and provided dried blood spots (DBS) for measurement of tenofovir-diphosphate (TFV-DP) concentrations at enrollment and 3 months later, and 176/302 (58.3%, 95% confidence interval [95% CI 52.3 to 63.8]) met our definition of PrEP persistence: having expressed intention to use PrEP and attended both the second interview and an interim refill visit. Among AGYW with DBS taken at the second interview, only 9/197 (4.6%, [95% CI 1.6 to 7.5]) had protective TFV-DP levels (≥700 fmol/punch) and 163/197 (82.7%, [95% CI 77.5 to 88]) had levels consistent with no recent PrEP use (<10 fmol/punch). Perception of being at moderate-to-high risk for HIV if not taking PrEP was associated with persistence (adjusted odds ratio, 10.17 [95% CI 5.14 to 20.13], p < 0.001) in a model accounting for county of residence and variables that had p-value <0.1 in unadjusted analysis (age, being in school, initiated PrEP 2 to 3 months before the first interview, still active in DREAMS, having children, having multiple sex partners, partner aware of PrEP use, partner very supportive of PrEP use, partner has other partners, AGYW believes that a partner puts her at risk, male condom use, injectable contraceptive use, and implant contraceptive use). Among AGYW who reported continuing PrEP, >90% indicated they were using PrEP to prevent HIV, although almost all had non-protective TFV-DP levels. Limitations included short study duration and inclusion of only DREAMS participants. CONCLUSIONS: Many AGYW persisted in the PrEP program without taking PrEP frequently enough to receive benefit. Notably, AGYW who persisted had a higher self-perceived risk of HIV infection. These AGYW may be optimal candidates for long-acting PrEP.

Potential application of the haematology analyser XN-31 prototype for field malaria surveillance in Kenya.

BACKGROUND: Simple and accurate diagnosis is a key component of malaria control programmes. Microscopy is the current gold standard, however it requires extensive training and the results largely rely on the skill of the microscopists. Malaria rapid diagnostic tests (RDT) can be performed with minimal training and offer timely diagnosis, but results are not quantitative. Moreover, some Plasmodium falciparum parasites have evolved and can no longer be detected by existing RDT. Developed by the Sysmex Corporation, the XN-31 prototype (XN-31p) is an automated haematology analyser capable of detecting Plasmodium-infected erythrocytes and providing species differentiation and stage specific parasite counts in venous blood samples without any preparation in approximately one minute. However, factors such as stable electricity supply in a temperature-controlled room, cost of the instrument and its initial set-up, and need for proprietary reagents limit the utility of the XN-31p across rural settings. To overcome some of these limitations, a hub and spoke diagnosis model was designed, in which peripheral health facilities were linked to a central hospital where detection of Plasmodium infections by the XN-31p would take place. To explore the feasibility of this concept, the applicability of capillary blood samples with the XN-31p was evaluated with respect to the effect of sample storage time and temperature on the stability of results. METHODS: Paired capillary and venous blood samples were collected from 169 malaria-suspected outpatients in Homa Bay County Referral Hospital, Kenya. Malaria infections were diagnosed with the XN-31p, microscopy, RDT, and PCR. Capillary blood samples were remeasured on the XN-31p after 24 h of storage at either room (15-25 °C) or chilled temperatures (2-8 °C). RESULTS: Identical results in malaria diagnosis were observed between venous and capillary blood samples processed immediately after collection with the XN-31p. Relative to PCR, the sensitivity and specificity of the XN-31p with capillary blood samples were 0.857 and 1.000, respectively. Short-term storage of capillary blood samples at chilled temperatures had no adverse impact on parasitaemia and complete blood counts (CBC) measured by the XN-31p. CONCLUSION: These results demonstrate the potential of the XN-31p to improve routine malaria diagnosis across remote settings using a hub and spoke model.

Two-fold increase in the HIV viral load suppression rate along with decreased incidence over six years in Ndhiwa sub-county, Kenya.

BACKGROUND: HIV-positive individuals who maintain an undetectable viral load cannot transmit the virus to others. In 2012, an HIV population-based survey was conducted in Ndhiwa sub-county (Kenya) to provide information on the HIV local epidemic. We carried out a second survey 6 years after the first one, to assess progress in HIV diagnosis and care and differences in the HIV prevalence and incidence between the two surveys. METHODS: A cross-sectional, population-based survey using cluster sampling and geospatial random selection was implemented in 2018, using the same design as 2012. Consenting participants aged 15-59 years were interviewed and tested for HIV at home. HIV-positive individuals received viral load testing (viral suppression defined as <1000 copies/ml) and Lag-Avidity EIA assay (to measure recent infection). The 90-90-90 UNAIDS indicators were also assessed. RESULTS: Overall, 6029 individuals were included in 2018. HIV prevalence was 16.9%. Viral suppression among all HIV-positive was 88.3% in 2018 (vs. 39.9% in 2012, p < 0.001). HIV incidence was 0.75% in 2018 vs. 1.90% in 2012 (p = 0.07). In 2018, the 90-90-90 indicators were 93%-97%-95% (vs. 60%-68%-83% in 2012). CONCLUSION: A two-fold increase in the HIV viral load suppression rate along with a decreasing trend in incidence was observed over 6 years in Ndhiwa sub-county. Achieving high rates of viral suppression in HIV populations that can lead to reducing HIV transmission in sub-Saharan contexts is feasible. Nevertheless, we will need further efforts to sustain this progress.

Development and Validation of a Sociodemographic and Behavioral Characteristics-Based Risk-Score Algorithm for Targeting HIV Testing Among Adults in Kenya.

To inform targeted HIV testing, we developed and externally validated a risk-score algorithm that incorporated behavioral characteristics. Outpatient data from five health facilities in western Kenya, comprising 19,458 adults ≥ 15 years tested for HIV from September 2017 to May 2018, were included in univariable and multivariable analyses used for algorithm development. Data for 11,330 adults attending one high-volume facility were used for validation. Using the final algorithm, patients were grouped into four risk-score categories: ≤ 9, 10-15, 16-29 and ≥ 30, with increasing HIV prevalence of 0.6% [95% confidence interval (CI) 0.46-0.75], 1.35% (95% CI 0.85-1.84), 2.65% (95% CI 1.8-3.51), and 15.15% (95% CI 9.03-21.27), respectively. The algorithm's discrimination performance was modest, with an area under the receiver-operating-curve of 0.69 (95% CI 0.53-0.84). In settings where universal testing is not feasible, a risk-score algorithm can identify sub-populations with higher HIV-risk to be prioritized for HIV testing.

Persistence of oral pre-exposure prophylaxis (PrEP) among adolescent girls and young women initiating PrEP for HIV prevention in Kenya.

The Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) Initiative aims to reduce HIV infections among adolescent girls and young women (AGYW) in Africa. Oral pre-exposure prophylaxis (PrEP) is offered through DREAMS in Kenya to eligible AGYW in high burden counties including Kisumu and Homa Bay. This study examines PrEP persistence among AGYW in high burden community-based PrEP delivery settings. We evaluated PrEP persistence among AGYW in the DREAMS PrEP program in Kisumu and Homa Bay using survival analysis and programmatic PrEP refill data collected between March through December 2017. Among 1,259 AGYW who initiated PrEP during the study period, the median persistence time in the program was 56 days (95% CI: 49-58 days) and the proportion who persisted 3 months later was 37% (95% CI: 34-40%). Persistence varied by county (p < 0.001), age at PrEP initiation (p = 0.002), marital status (p = 0.008), transactional sex (p = 0.002), gender-based violence (GBV) experience (p = 0.009) and current school attendance (p = 0.001) at DREAMS enrollment. Persistence did not vary with orphan status, food insecurity, condom use, age at first sexual encounter or engagement in age-disparate sex at DREAMS enrollment. Targeted strategies are needed to improve AGYW retention in the PrEP program.

Integrating pediatric TB services into child healthcare services in Africa: study protocol for the INPUT cluster-randomized stepped wedge trial.

BACKGROUND: Tuberculosis is among the top-10 causes of mortality in children with more than 1 million children suffering from TB disease annually worldwide. The main challenge in young children is the difficulty in establishing an accurate diagnosis of active TB. The INPUT study is a stepped-wedge cluster-randomized intervention study aiming to assess the effectiveness of integrating TB services into child healthcare services on TB diagnosis capacities in children under 5 years of age. METHODS: Two strategies will be compared: i) The standard of care, offering pediatric TB services based on national standard of care; ii) The intervention, with pediatric TB services integrated into child healthcare services: it consists of a package of training, supportive supervision, job aids, and logistical support to the integration of TB screening and diagnosis activities into pediatric services. The design is a cluster-randomized stepped-wedge of 12 study clusters in Cameroon and Kenya. The sites start enrolling participants under standard-of-care and will transition to the intervention at randomly assigned time points. We enroll children aged less than 5 years with a presumptive diagnosis of TB after obtaining caregiver written informed consent. The participants are followed through TB diagnosis and treatment, with clinical information prospectively abstracted from their medical records. The primary outcome is the proportion of TB cases diagnosed among children < 5 years old attending the child healthcare services. Secondary outcomes include: number of children screened for presumptive active TB; diagnosed; initiated on TB treatment; and completing treatment. We will also assess the cost-effectiveness of the intervention, its acceptability among health care providers and users, and fidelity of implementation. DISCUSSION: Study enrolments started in May 2019, enrolments will be completed in October 2020 and follow up will be completed by June 2021. The study findings will be disseminated to national, regional and international audiences and will inform innovative approaches to integration of TB screening, diagnosis, and treatment initiation into child health care services. TRIAL RESISTRATION: NCT03862261, initial release 12 February 2019.

Expanding access to maternal, newborn and primary healthcare services through private-community-government partnership clinic models in rural Kenya: the Ubuntu-Afya kiosk model.

BACKGROUND: Fifteen counties contribute 98.7% of the maternal and newborn morbidity and mortality in Kenya. The dismal maternal and newborn (MNH) outcomes in these settings are mostly attributable to limited access to skilled MNH services. Public health services are stretched and limited in reach, and many social programmes are not sustainably designed. We implemented a network of 16 self-sustaining community medical centres (Ubuntu-Afya Kiosks) in Homa Bay County, to facilitate access to MNH and other primary health services. We investigated the effect of these centres on MNH access indicators over a 2-year period of initial implementation. METHODS: We conducted a baseline and end-line survey in June 2016 and May 2018 respectively, in 10 community health units (CHU) served by Ubuntu-Afya Kiosks. We targeted women of child bearing age, ensuring equal sample across the 10 CHUs. The surveys were powered to detect a 10% increase in the proportion of women who deliver under a skilled birth attendant from a perceived baseline of 55%. Background characteristics of the respondents were compared using Fisher's exact test for the categorical data. STATA 'svy' commands were used to calculate confidence intervals for the proportions taking into account the clustering within CHU. RESULTS: The coverage of antenatal care during previous pregnancy was 99% at end-line compared to 81% at baseline. Seventy one percent of mothers attended at least four antenatal care visits, compared to 64% at baseline. The proportion of women who delivered under a skilled birth attendant during previous pregnancy was higher at end-line (90%) compared to baseline (85%). There was an increase in the proportion of women who had their newborns examined within 2 day of delivery from 74 to 92% at end-line. A considerable proportion of the respondents visited private clinics at end-line (31%) compared to 3% at baseline. CONCLUSIONS: Ubuntu-Afya Kiosks were associated with enhanced access to MNH care, with significant improvements observed in newborn examination within 2 days after delivery. More women sought care from private clinics at end-line compared to baseline, indicating potential for private sector in supporting health service delivery gaps in under-served settings.

Treatment-seeking behaviours of patients with tungiasis in endemic areas of Homa Bay County, Kenya: a mixed-methods study.

BACKGROUND: Tungiasis, an ectoparasitic disease caused by sand fleas, causes suffering to millions of people in the tropics. Although the Kenyan National Policy Guidelines list tungiasis treatments as including disinfectants, flea repellents, and botanical oil, the insufficient knowledge and financial constraints of affected communities have led to neglect and inappropriate self-treatment. Current reports show insignificant progress on educational activities at the community level. Therefore, we investigated community residents' treatment-seeking behaviour concerning tungiasis, using an endemic area of Kenya as the research setting. METHODS: A cross-sectional mixed-methods design was employed. Quantitative data were collected from the participants-410 adults who had experienced tungiasis-using a questionnaire, while qualitative data were collected from 20 older adults to 10 medical staffs using semi-structured individual interviews. The study was conducted in two sub-counties of Homa Bay County, Kenya. RESULTS: Factors significantly correlated with using non-guideline-listed treatments for tungiasis were 'not knowing the causse of tungiasis', 'not seeking treatment from healthcare facilities and traditional healers', and 'wait and see to prevent infection in non-affected members'. The interviews with the older adults revealed 19 self-treatment options for tungiasis, and 40% of the participants opted for self-removal using sharp objects. Only two of these treatments were listed in the guidelines. The most frequently mentioned reason for using a self-treatment option was 'Someone else's idea'. The most frequently mentioned reason for choosing the best self-treatment option was 'Effectiveness'. Interviews with medical staff revealed 11 treatment options; only five of these treatments are listed in the guidelines. The most frequently mentioned reason for selecting/using the treatment was 'Supply situation'. CONCLUSIONS: Residents' socioeconomic factors, cultural factors, and access to appropriate treatment, as well as knowledge of medical staff were significant factors that influenced the residents' tungiasis treatment-seeking behaviours. This study provides feasibility and baseline data to establish an effective, safe, and sustainable treatment for tungiasis.

A pilot study of dimeticone oils versus sodium carbonate treatment for tungiasis: A randomized cohort trial in Homa Bay County, Kenya.

BACKGROUND: Tungiasis is a cutaneous parasitosis caused by the female flea Tunga penetrans. Two-component dimeticone (NYDA) is the only treatment for tungiasis recommended by the World Health Organization; however, this topical drug is not available in Kenya. In Western Kenya, sodium carbonate is commonly used in the treatment of tungiasis. This study evaluated the 7-day cure rates for tungiasis by comparing sodium carbonate and NYDA treatments in Homa Bay County, Kenya. METHODOLOGY/PRINCIPAL FINDINGS: This was a randomized, observer-blinded, parallel-treatment cohort trial. Twenty-three eligible children with 126 flea infections were matched and randomized. All participants received both treatments, with one treatment on each foot. We recorded all health conditions/information, including inflammation scores and adverse events. Observations were performed on days 3, 5, and 7 using a digital microscope to confirm dead or live fleas based on the viability signs. Twenty-three children aged 3-13 years were analyzed. The proportion of dead fleas on day 7 was higher after NYDA treatment than after 5% sodium carbonate treatment (87% versus 64%, respectively, P = 0.01) NYDA. Median survival was 5 days for both treatments; NYDA had significantly higher trend of flea non-viability rate than 5% sodium carbonate (P<0.01). There were no significant differences in the inflammation score or pain/itchiness between the two treatments. On the last day, 14 children indicated their preference for NYDA in future treatment of tungiasis, whereas nine children preferred the 5% sodium carbonate solution. CONCLUSIONS/SIGNIFICANCE: NYDA was significantly more effective than 5% sodium carbonate for tungiasis treatment. Both treatments were safe but the children preferred NYDA more. Future studies with more participants and an extended observation period are warranted to confirm our findings. The findings suggest that NYDA should be made more available in tungiasis endemic area. TRIAL REGISTRATION: UMIN-CTR; UMIN 000044320.

Effect of COVID-19 on paediatric TB service delivery and patients' comfort receiving TB services in Cameroon and Kenya during COVID: a qualitative assessment.

BACKGROUND: The outbreak of COVID-19 has caused a setback to the gains achieved in tuberculosis (TB) control by impairing TB diagnosis, delaying treatment initiation and aggravating TB deaths. This study explored the effect of COVID-19 on paediatric TB services provided through the Catalysing Paediatric TB Innovations (CaP-TB) project among caregivers of children receiving TB services and healthcare workers (HCWs) providing TB services in Cameroon and Kenya. METHODS: From March to September 2021, in-depth interviews (44) were conducted with caregivers whose children under 5 years had gone through TB services and programme managers (10) overseeing the CaP-TB project. Focus group discussions were conducted with HCWs (07) and community health workers (04) supporting TB care services. Transcripts were coded and analysed by using MAXQDA V.12. RESULTS: The COVID-19 pandemic has caused fear and anxiety among HCWs and caregivers. This fear was motivated by stigma related to COVID-19 and affected the ability to screen patients for TB due to the similarity of symptoms with COVID-19. The health-seeking behaviour of patients was affected, as many caregivers avoided hospitals and those accessing the facilities concealed their sickness due to fear of testing positive or being vaccinated. In addition, COVID-19 mitigation strategies implemented by both government and health facilities to curb the spread of the virus limited patient access to paediatric healthcare services. These included temporary closure of health facilities due to COVID-19 infections among staff, transfer of services to other spaces, spacing out patient appointments and reduced time spent with patients. CONCLUSIONS: The outbreak of COVID-19 has induced fear and stigma that affected patients' health-seeking behaviour and provider attitudes towards paediatric TB service delivery. In addition, facility and governmental measures put in place to mitigate COVID-19 impact negatively affected paediatric service delivery. Training for health personnel, timely provision of personal protective equipments and appropriate communication strategies could help mitigate COVID-19 impact on paediatric TB service delivery.

Barriers and misconceptions hindering reduction of intestinal schistosomiasis in Mbita Sub-County, Western Kenya.

BACKGROUND: Community and individual participation are crucial for the success of schistosomiasis control. The World Health Organization (WHO) has highlighted the importance of enhanced sanitation, health education, and Mass Drug Administration (MDA) in the fight against schistosomiasis. These approaches rely on the knowledge and practices of the community to be successful; however, where the community knowledge is low and inappropriate, it hinders intervention efforts. Hence, it is essential to identify barriers and misconceptions related to awareness of schistosomiasis, sources of infection, mode of transmission, symptoms, and control measures. METHODS: This was a mixed-method cross-sectional study involving 1200 pre-school children randomly selected and examined for Schistosoma mansoni infection using the Kato-Katz technique. All parents/guardians of selected children were enrolled for a pre-tested questionnaire survey, while 42 were engaged in focus group discussions (FGDs). The level of knowledge and awareness among parents/guardians about schistosomiasis was evaluated in relation to the infection status of their pre-school children. RESULTS: Among pre-school children, the prevalence of intestinal schistosomiasis was 45.1% (95% CI 41.7-48.5). A majority of parents/guardians (85.5%) had heard about schistosomiasis, and this awareness was associated with the participant's level of education (OR = 0.16, 95% CI 0.08, 0.34). In addition, a positive association was observed between higher educational attainment and knowledge of the causative agent (OR = 0.69, 95% CI 0.49, 0.96). Low education level was significantly associated with limited knowledge of transmission through lake water contact (OR = 0.71, 95% CI 0.52, 0.97) and infection from the lake (OR = 0.33, 95% CI 0.19, 0.57). Notably, parents/guardians who have heard of schistosomiasis could not recognize symptoms of S. mansoni infection, such as abdominal pain (91.8%, 815/888) and blood in the stool (85.1%, 756/888). Surprisingly, 49.8% (442/888) incorrectly identified hematuria (blood in urine), a key sign of S. haematobium, but not S. mansoni, in an endemic area for S. mansoni infection. The majority (82.6%, 734/888) of parents/guardians were unaware that dams are potential infection sites, despite 53.9% (479/888) of their pre-school-aged children testing positive for schistosome infection. CONCLUSIONS: Despite the high level of awareness of intestinal schistosomiasis in the study area, we identified a low level of knowledge regarding its causes, modes of transmission, signs and symptoms and potential sites of transmission within the community. This study emphasizes the need for targeted educational interventions to address the misconceptions and knowledge gaps surrounding intestinal schistosomiasis through tailored community-based programs.

Antiretroviral treatment failure and associated factors among people living with HIV on therapy in Homa Bay, Kenya: A retrospective study.

Despite large numbers of patients accessing antiretroviral treatment (ART) in Kenya, few studies have explored factors associated with virologic failure in Western Kenya, specifically. We undertook a study in Homa Bay County, Kenya to assess the extent of virologic treatment failure and factors associated with it. This was an observational retrospective study conducted from September 2020 to January 2021. Data were abstracted from the records of patients who had been on ART for at least six months at the time of data collection after systematic sampling stratified by age group at ART initiation (0-14 and 15+ years), using probability proportion to the numbers of patients attending the facility. Confirmed viral treatment failure was defined as viral load ≥1000 copies/ml based on two consecutive viral load measurements after at least three months of enhanced adherence counseling. Data were analyzed using descriptive statistics and Cox regression modeling. Of the 2,007 patients sampled, 160 (8.0%) had confirmed virologic treatment failure. Significantly higher virologic treatment failure rates were identified among male patients 78/830 (9.4%) and children 115/782 (14.7%). Factors associated with virologic treatment failure (VTF), were age 0-14 years, adjusted hazard ratio (AHR) 4.42, (95% Confidence Interval [CI], 3.12, 6.32), experience of treatment side effects AHD: 2.43, (95% CI, 1.76, 3.37), attending level 2/3 health facility, AHR: 1.87, (95% CI: 1.29, 2,72), and history of opportunistic infections (OIs), AHR: 1.81, (95% CI, 1.76, 3.37). Children, attendees of level 2/3 health facilities, patients with a history of OIs, and those experiencing treatment side-effects are at risk of VTF. Increased focus on children and adolescents on screening for drug resistance, administration of and adherence to medication, and on effective information and education on side-effects is critical. Additionally, there is need for increased training and support for health care workers at primary level care facilities.

Advanced HIV disease in Homa Bay County, Kenya: Characteristics of newly-diagnosed and antiretroviral therapy-experienced clients.

Advanced HIV disease (AHD) remains a significant burden, despite the widespread use of antiretroviral therapy (ART) programs. Individuals with AHD are at a high risk of death even after starting ART. We characterized treatment naïve and treatment experienced clients presenting with AHD in western Kenya to inform service delivery and program improvement. We conducted a retrospective study using routinely collected program data from October 2016 to September 2019 for AHD clients in eight facilities in Homa Bay County, Kenya. Demographic and clinical data were abstracted from the medical records of AHD clients, defined as HIV-positive clients aged ≥ 5 years with documented CD4 count < 200 cells/mm3 and/or WHO clinical stage II/IV. Associations were assessed using Pearson's chi-square and Mann-Whitney Rank-Sum tests at 5% level of significance. Of the 19,427 HIV clients at the eight facilities, 6649 (34%) had a CD4 count < 200 cells/mm3 or a WHO III/IV stage. Of these, 1845 were randomly selected for analysis. Over half (991) of participants were aged 45 + years and 1040 (56%) were female. The median age was 46.0 years (interquartile range: 39.2-54.5); 1553 (84%) were in care at county and sub-county hospitals; and 1460 (79%) were WHO stage III/IV at enrollment. At ART initiation, 241 (13%) had tuberculosis, 192 (10%) had chronic diarrhea, and 94 (5%) had Pneumocystis jiroveci pneumonia. At the time of data collection, 89 (5%) participants had died and 140 (8%) were lost to follow-up. Eighteen percent (330) of participants were ART-experienced (on ART for ≥ 3 months). The proportions of ART-experienced and -naïve clients regarding age, sex and marital status were similar. However, a higher proportion of ART-experienced clients received care at primary care facilities, (93(28%) vs. 199 (13%); P < .001); were WHO stage 3/4 at AHD diagnosis, 273 (84%) vs. 1187 (79%) (P = .041); and had died or been LTFU, (124 (38%) vs. 105 (7%); P < .001). With increasing prevalence of patients on ART, the proportion of AHD treatment-experienced clients may increase without effective interventions to ensure that these patients remain in care.

Adolescents and young adults are the most undiagnosed of HIV and virally unsuppressed in Eastern and Southern Africa: Pooled analyses from five population-based surveys.

Age and gender disparities within the HIV cascade of care are critical to focus interventions efficiently. We assessed gender-age groups at the highest probability of unfavorable outcomes in the HIV cascade in five HIV prevalent settings. We performed pooled data analyses from population-based surveys conducted in Kenya, South Africa, Malawi and Zimbabwe between 2012 and 2016. Individuals aged 15-59 years were eligible. Participants were tested for HIV and viral load was measured. The HIV cascade outcomes and the probability of being undiagnosed, untreated among those diagnosed, and virally unsuppressed (≥1,000 copies/mL) among those treated were assessed for several age-gender groups. Among 26,743 participants, 5,221 (19.5%) were HIV-positive (69.9% women, median age 36 years). Of them, 72.8% were previously diagnosed and 56.7% virally suppressed (88.5% among those treated). Among individuals 15-24 years, 51.5% were diagnosed vs 83.0% among 45-59 years, p<0.001. Among 15-24 years diagnosed, 60.6% were treated vs 86.5% among 45-59 years, p<0.001. Among 15-24 years treated, 77.9% were virally suppressed vs 92.0% among 45-59 years, p<0.001. Among all HIV-positive, viral suppression was 32.9% in 15-24 years, 47.9% in 25-34 years, 64.9% in 35-44 years, 70.6% in 45-59 years. Men were less diagnosed than women (65.2% vs 76.0%, p <0.001). Treatment among diagnosed and viral suppression among treated was not different by gender. Compared to women 45-59 years, young people had a higher probability of being undiagnosed (men 15-24 years OR: 37.9, women 15-24 years OR: 12.2), untreated (men 15-24 years OR:2.2, women 15-24 years OR: 5.7) and virally unsuppressed (men 15-24 years OR: 1.6, women 15-24 years OR: 6.6). In these five Eastern and Southern Africa settings, adolescents and young adults had the largest gaps in the HIV cascade. They were less diagnosed, treated, and virally suppressed, than older counterparts. Targeted preventive, testing and treating interventions should be scaled-up.

Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy study.

BACKGROUND: Development of rapid biomarker-based tests that can diagnose tuberculosis using non-sputum samples is a priority for tuberculosis control. We aimed to compare the diagnostic accuracy of the novel Fujifilm SILVAMP TB LAM (FujiLAM) assay with the WHO-recommended Alere Determine TB-LAM Ag test (AlereLAM) using urine samples from HIV-positive patients. METHODS: We did a diagnostic accuracy study at five outpatient public health facilities in Uganda, Kenya, Mozambique, and South Africa. Eligible patients were ambulatory HIV-positive individuals (aged ≥15 years) with symptoms of tuberculosis irrespective of their CD4 T-cell count (group 1), and asymptomatic patients with advanced HIV disease (CD4 count <200 cells per µL, or HIV clinical stage 3 or 4; group 2). All participants underwent clinical examination, chest x-ray, and blood sampling, and were requested to provide a fresh urine sample, and two sputum samples. FujiLAM and AlereLAM urine assays, Xpert MTB/RIF Ultra assay on sputum or urine, sputum culture for Mycobacterium tuberculosis, and CD4 count were systematically carried out for all patients. Sensitivity and specificity of FujiLAM and AlereLAM were evaluated against microbiological and composite reference standards. FINDINGS: Between Aug 24, 2020 and Sept 21, 2021, 1575 patients (823 [52·3%] women) were included in the study: 1031 patients in group 1 and 544 patients in group 2. Tuberculosis was microbiologically confirmed in 96 (9·4%) of 1022 patients in group 1 and 18 (3·3%) of 542 patients in group 2. Using the microbiological reference standard, FujiLAM sensitivity was 60% (95% CI 51-69) and AlereLAM sensitivity was 40% (31-49; p<0·001). Among patients with CD4 counts of less than 200 cells per µL, FujiLAM sensitivity was 69% (57-79) and AlereLAM sensitivity was 52% (40-64; p=0·0218). Among patients with CD4 counts of 200 cells per µL or higher, FujiLAM sensitivity was 47% (34-61) and AlereLAM sensitivity was 24% (14-38; p=0·0116). Using the microbiological reference standard, FujiLAM specificity was 87% (95% CI 85-89) and AlereLAM specificity was 86% (95 CI 84-88; p=0·941). FujiLAM sensitivity varied by lot number from 48% (34-62) to 76% (57-89) and specificity from 77% (72-81) to 98% (93-99). INTERPRETATION: Next-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use. FUNDING: ANRS and Médecins Sans Frontières.

Standardized enhanced adherence counseling for improved HIV viral suppression among children and adolescents in Homa Bay and Turkana Counties, Kenya.

Viral suppression is suboptimal among children and adolescents on antiretroviral therapy (ART) in Kenya. We implemented and evaluated a standardized enhanced adherence counseling (SEAC) package to improve viral suppression in children and adolescents with suspected treatment failure in Homa Bay and Turkana. The SEAC package, implemented from February 2019 to September 2020, included: standard procedures operationalizing the enhanced adherence counseling (EAC) process; provider training on psychosocial support and communication skills for children living with HIV and their caregivers; mentorship to providers and peer educators on EAC processes; and individualized case management. We enrolled children and adolescents aged 0 to 19 years with suspected treatment failure (viral load [VL] >1000 copies/mL) who received EAC before standardization as well as those who received SEAC in a pre-post evaluation of the SEAC package conducted in 6 high-volume facilities. Pre-post standardization comparisons were performed using Wilcoxon-Mann-Whitney and Pearson's chi-square tests at a 5% level of significance. Multivariate logistic regression was performed to identify factors associated with viral resuppression. The study enrolled 741 participants, 595 pre- and 146 post-SEAC implementation. All post-SEAC participants attended at least 1 EAC session, while 17% (n = 98) of pre-SEAC clients had no record of EAC attendance. Time to EAC following the detection of high VL was reduced by a median of 8 days, from 49 (interquartile range [IQR]: 23.0-102.5) to 41 (IQR: 20.0-67.0) days pre- versus post-SEAC (P = .006). Time to completion of at least 3 sessions was reduced by a median of 12 days, from 59.0 (IQR: 36.0-91.0) to 47.5 (IQR: 33.0-63.0) days pre- versus post-SEAC (P = .002). A greater percentage of clients completed the recommended minimum 3 EAC sessions at post-SEAC, 88.4% (n = 129) versus 61.1% (n = 363) pre-SEAC, P < .001. Among participants with a repeat VL within 3 months following the high VL, SEAC increased viral suppression from 34.6% (n = 76) to 52.5% (n = 45), P = .004. Implementation of the SEAC package significantly reduced the time to initiate EAC and time to completion of at least 3 EAC sessions, and was significantly associated with viral suppression in children and adolescents with suspected treatment failure.

Feasibility and acceptability of using the novel urine-based FujiLAM test to detect tuberculosis: A multi-country mixed-methods study.

Background: The novel urine-based FujiLAM test identifies tuberculosis in HIV-positive patients but may be challenging to use at point-of-care (POC). Objectives: We assessed the feasibility and acceptability of using the FujiLAM test at point of care in outpatient settings. Methods: We conducted a mixed methods study in four outpatient settings in Kenya, Mozambique, South Africa, and Uganda between November 2020 and September 2021. The test was performed at POC in existing clinic laboratories and consultation spaces. We performed direct observations in the four health facilities, individual questionnaires, proficiency testing evaluations, and individual interviews among healthcare workers performing the FujiLAM test (healthcare workers), and group discussions with programme managers. Results: Overall, 18/19 (95%) healthcare workers and 14/14 (100%) managers agreed to participate in the study. Most assessed healthcare workers, including lay health workers (10/11; 91%), met the minimum required theoretical knowledge and practical skill in performing the FujiLAM test. Most healthcare workers (17/18; 94%) found the FujiLAM test overall "Easy/Very easy" to perform. Some challenges were mentioned: many timed steps (5/18; 28%); ensuring correct incubation period (5/18; 28%); test result readability (4/18; 22%); and difficulties with cartridge buttons (3/18; 17%). Half of the healthcare workers regularly performing the test (4/7; 57%) found it "Easy" to integrate into routine activities. Most healthcare workers and managers believed that any healthcare worker could perform the test after adequate training. Conclusions: Implementing the FujiLAM test in outpatient POC settings is feasible and acceptable to healthcare workers and managers. This test can be performed in various clinic locations by any healthcare worker. The timed, multi-step test procedure is challenging and may affect the workload in resource-constrained health facilities.

Enhancing Malaria Research, Surveillance, and Control in Endemic Areas of Kenya and Ethiopia.

Malaria control programs in Africa encounter daunting challenges that hinder progressive steps toward elimination of the disease. These challenges include widespread insecticide resistance in mosquito vectors, increasing outdoor malaria transmission, lack of vector surveillance and control tools suitable for outdoor biting vectors, weakness in malaria surveillance, and an inadequate number of skilled healthcare personnel. Ecological and epidemiological changes induced by environmental modifications resulting from water resource development projects pose additional barriers to malaria control. Cognizant of these challenges, our International Center of Excellence for Malaria Research (ICEMR) works in close collaboration with relevant government ministries and agencies to align its research efforts with the objectives and strategies of the national malaria control and elimination programs for the benefit of local communities. Our overall goal is to assess the impact of water resource development projects, shifting agricultural practices, and vector interventions on Plasmodium falciparum and P. vivax malaria in Kenya and Ethiopia. From 2017 to date, the ICEMR has advanced knowledge of malaria epidemiology, transmission, immunology, and pathogenesis, and developed tools to enhance vector surveillance and control, improved clinical malaria surveillance and diagnostic methods, and strengthened the capacity of local healthcare providers. Research findings from the ICEMR will inform health policy and strategic planning by ministries of health in their quest to sustain malaria control and achieve elimination goals.

Active pediatric HIV case finding in Kenya and Uganda: A look at missed opportunities along the prevention of mother-to-child transmission of HIV (PMTCT) cascade.

BACKGROUND: Children living with HIV remain undiagnosed due to missed opportunities along the prevention of mother-to-child HIV transmission cascade. This study addresses programmatic gaps in the cascade by describing pregnancy and HIV-related services received by mothers of children newly identified as HIV-positive through active case finding. METHODS: This was a prospective observational cohort (2017-2018) of HIV-positive children <15 years of age newly diagnosed at study facilities and/or surrounding communities in Kenya and Uganda. At enrollment, caregivers were interviewed about maternal and child health and HIV history. Child medical and laboratory information was abstracted at two months post-diagnosis. Descriptive summary statistics were calculated; associations between selected factors and child age at HIV diagnosis were evaluated using generalized estimating equations. RESULTS: 174 HIV-positive children (median age 2.4 years) were enrolled. Among maternal caregivers, 110/132 (83.3%) attended antenatal care and 60 (45.5%) reported testing HIV-negative in antenatal care. Of 41 and 56 women known to be HIV-positive during pregnancy and breastfeeding respectively, 17 (41.5%) and 15 (26.8%) did not receive antiretroviral drugs. Despite known maternal HIV-positive status during pregnancy, 39% of these children were not diagnosed until after two years of age; children were diagnosed at younger ages in Uganda (p = 0.0074) and if mother was the caregiver (p<0.0001). The most common HIV testing points identifying children were outpatient (44.3%) and maternal/child health departments (29.9%). Nearly all children initiated antiretroviral therapy within two weeks of diagnosis. CONCLUSIONS: Multiple missed opportunities for HIV prevention and delays in HIV testing of HIV-exposed children were identified in newly diagnosed children. Findings support critical prevention messaging and retesting of HIV-negative women during pregnancy and breastfeeding, strengthening HIV treatment initiation and follow-up systems and interventions to ensure HIV-positive women receive lifelong antiretroviral therapy throughout the cascade, and broader implementation of community case finding so children not engaged in care receive testing services.

Expanded eligibility for HIV testing increases HIV diagnoses-A cross-sectional study in seven health facilities in western Kenya.

Homa Bay, Siaya, and Kisumu counties in western Kenya have the highest estimated HIV prevalence (16.3-21.0%) in the country, and struggle to meet program targets for HIV testing services (HTS). The Kenya Ministry of Health (MOH) recommends annual HIV testing for the general population. We assessed the degree to which reducing the interval for retesting to less than 12 months increased diagnosis of HIV in outpatient departments (OPD) in western Kenya. We conducted a retrospective analysis of routinely collected program data from seven high-volume (>800 monthlyOPD visits) health facilities in March-December, 2017. Data from persons ≥15 years of age seeking medical care (patients) in the OPD and non-care-seekers (non-patients) accompanying patients to the OPD were included. Outcomes were meeting MOH (routine) criteria versus criteria for a reduced retesting interval (RRI) of <12 months, and HIV test result. STATA version 14.2 was used to calculate frequencies and proportions, and to test for differences using bivariate analysis. During the 9-month period, 119,950 clients were screened for HIV testing eligibility, of whom 79% (94,766) were eligible and 97% (92,153) received a test. Among 92,153 clients tested, the median age was 28 years, 57% were female and 40% (36,728) were non-patients. Overall, 20% (18,120) of clients tested met routine eligibility criteria: 4% (3,972) had never been tested, 10% (9,316) reported a negative HIV test in the past >12 months, and 5% (4,832) met other criteria. The remaining 80% (74,033) met criteria for a RRI of < 12 months. In total 1.3% (1,185) of clients had a positive test. Although the percent yield was over 2-fold higher among those meeting routine criteria (2.4% vs. 1.0%; p<0.001), 63% (750) of all HIV infections were found among clients tested less than 12 months ago, the majority (81%) of whom reported having a negative test in the past 3-12 months. Non-patients accounted for 45% (539) of all HIV-positive persons identified. Percent yield was higher among non-patients as compared to patients (1.5% vs. 1.2%; p-value = <0.001) overall and across eligibility criteria and age categories. The majority of HIV diagnoses in the OPD occurred among clients reporting a negative HIV test in the past 12 months, clients ineligible for testing under the current MOH guidelines. Nearly half of all HIV-positive individuals identified in the OPD were non-patients. Our findings suggest that in the setting of a generalized HIV epidemic, retesting persons reporting an HIV-negative test in the past 3-12 months, and routine testing of non-patients accessing the OPD are key strategies for timely diagnosis of persons living with HIV.