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Excessive antibiotic use and antimicrobial resistance are major global public health threats. We developed ePOCT+, a digital clinical decision support algorithm in combination with C-reactive protein test, hemoglobin test, pulse oximeter and mentorship, to guide health-care providers in managing acutely sick children under 15 years old. To evaluate the impact of ePOCT+ compared to usual care, we conducted a cluster randomized controlled trial in Tanzanian primary care facilities. Over 11 months, 23,593 consultations were included from 20 ePOCT+ health facilities and 20,713 from 20 usual care facilities. The use of ePOCT+ in intervention facilities resulted in a reduction in the coprimary outcome of antibiotic prescription compared to usual care (23.2% versus 70.1%, adjusted difference -46.4%, 95% confidence interval (CI) -57.6 to -35.2). The coprimary outcome of day 7 clinical failure was noninferior in ePOCT+ facilities compared to usual care facilities (adjusted relative risk 0.97, 95% CI 0.85 to 1.10). There was no difference in the secondary safety outcomes of death and nonreferred secondary hospitalizations by day 7. Using ePOCT+ could help address the urgent problem of antimicrobial resistance by safely reducing antibiotic prescribing. Clinicaltrials.gov Identifier: NCT05144763., (© 2023. The Author(s).)

Electronic clinical decision support algorithms (CDSAs) have been developed to address high childhood mortality and inappropriate antibiotic prescription by helping clinicians adhere to guidelines. Previously identified challenges of CDSAs include their limited scope, usability, and outdated clinical content. To address these challenges we developed ePOCT+, a CDSA for the care of pediatric outpatients in low- and middle-income settings, and the medical algorithm suite (medAL-suite), a software for the creation and execution of CDSAs. Following the principles of digital development, we aim to describe the process and lessons learnt from the development of ePOCT+ and the medAL-suite. In particular, this work outlines the systematic integrative development process in the design and implementation of these tools required to meet the needs of clinicians to improve uptake and quality of care. We considered the feasibility, acceptability and reliability of clinical signs and symptoms, as well as the diagnostic and prognostic performance of predictors. To assure clinical validity, and appropriateness for the country of implementation the algorithm underwent numerous reviews by clinical experts and health authorities from the implementing countries. The digitalization process involved the creation of medAL-creator, a digital platform which allows clinicians without IT programming skills to easily create the algorithms, and medAL-reader the mobile health (mHealth) application used by clinicians during the consultation. Extensive feasibility tests were done with feedback from end-users of multiple countries to improve the clinical algorithm and medAL-reader software. We hope that the development framework used for developing ePOCT+ will help support the development of other CDSAs, and that the open-source medAL-suite will enable others to easily and independently implement them. Further clinical validation studies are underway in Tanzania, Rwanda, Kenya, Senegal, and India., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We estimated the costs of Option B+ for HIV-infected pregnant women in 12 facilities in Morogoro Region, Tanzania, from a provider perspective. Costs of prevention of mother-to-child (PMTCT) HIV services were measured over 12 months to September 2017 to estimate the average costs per HIV testing episode, per HIV-positive case diagnosed, per patient-year on antiretroviral therapy (ART), and per neonatal HIV care. A one-way sensitivity analysis was undertaken to understand how staffing levels and other core resource inputs affected costs. The total number of HIV testing episodes was 25,593 with 279 HIV cases identified yielding a 1.1% positivity rate. The average cost per testing episode was US$5.49 (range US$2.13 to US$13.93), and the average cost per HIV case detected was US$503.29 (range US$230.61 to US$3330.38). The number of pregnant women initiated on ART was 278. The mean cost per patient-year on ART was US$159.89 (range US$100.91 to US$812.23). The average cost of neonatal HIV care was US$90.09 (range US$41.53 to US$180.26). PMTCT service costs varied widely across facilities due to variations in resource use, number of women testing, and HIV prevalence. The study provides further evidence against generalising cost estimates, and that budgeting and planning requires context specific cost information.

National HIV testing policies aim to increase the proportion of people living with HIV who know their status. National HIV testing policies were reviewed for each country from 2013 to 2018, and compared with WHO guidance. Three rounds of health facility surveys were conducted to assess facility level policy implementation in Karonga (Malawi), uMkhanyakude (South Africa), and Ifakara (Tanzania). A policy 'implementation' score was developed and applied to each facility by site for each round. Most HIV testing policies were explicit and aligned with WHO recommendations. Policies about service coverage, access, and quality of care were implemented in >80% of facilities per site and per round. However, linkage to care and the provision of outreach HIV testing for key populations were poorly implemented. The proportion of facilities reporting HIV test kit stock-outs in the past year reduced over the study period in all sites, but still occurred in ≥17% of facilities per site by 2017. The implementation score improved over time in Karonga and Ifakara and declined slightly in uMkhanyakude. Efforts are needed to address HIV test kit stock-outs and to improve linkage to care among people testing positive in order to reach the 90-90-90 targets.

Objectives: Our objectives were to describe trends in enrolment and clinical outcomes in the open, prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) in the Morogoro region of southern Tanzania, and identify strengths and areas for improvement in the care of HIV-positive individuals in rural Tanzania., Methods: We included adults (≥15 years) and children (<15 years) enrolled in the cohort in 2005-2014. The cohort underwent significant changes from autumn 2012 to optimise care. We evaluated mortality and loss to follow-up (LTFU) using competing risks methods, ART usage, opportunistic infections (OI), co-infections and laboratory abnormalities., Results: Overall, 7010 adults and 680 children were enrolled; enrolment peaked in 2008 but has increased steadily since 2011. Among adults (65% female; median age 37 [interquartile range 31-45] years), the proportion referred from hospital wards quadrupled in 2013-14 versus earlier years. 653 (9%) adults died and 2648 (38%) were LTFU; the five-year cumulative probabilities of death and LTFU were 10.3% and 44.0%, respectively. Among children, 69 (10%) died and 225 (33%) were LTFU. The corresponding five-year probabilities were 12.1% and 39.6%. Adult ART use (regardless of eligibility) increased from 5% in 2005 to 89% in 2014 (similarly among children), with 9% on second-line therapy in 2014 (17% of children). OI diagnoses increased over time; tuberculosis prevalence at enrolment quadrupled from 6% in 2011 to 26% in 2014. The proportion of newly-enrolled participants assessed for laboratory abnormalities peaked at nearly 100% in 2014 (from a minimum of 24%), yet abnormality prevalences remained fairly constant., Conclusions: In this cohort, ART usage improved dramatically and is approaching targets of 90%. Improved screening led to increases in detection of OIs and laboratory abnormalities, suggesting that a large number of these co-morbidities previously went undetected and untreated. Further work will address the high LTFU rates and implications for mortality estimates, and the management and outcomes of co-morbidities.

Background: Strategies to improve the uptake of Prevention of Mother-To-Child Transmission of HIV (PMTCT) are needed. We integrated HIV and maternal, newborn and child health services in a One Stop Clinic to improve the PMTCT cascade in a rural Tanzanian setting., Methods: The One Stop Clinic of Ifakara offers integral care to HIV-infected pregnant women and their families at one single place and time. All pregnant women and HIV-exposed infants attended during the first year of Option B+ implementation (04/2014-03/2015) were included. PMTCT was assessed at the antenatal clinic (ANC), HIV care and labour ward, and compared with the pre-B+ period. We also characterised HIV-infected pregnant women and evaluated the MTCT rate., Results: 1,579 women attended the ANC. Seven (0.4%) were known to be HIV-infected. Of the remainder, 98.5% (1,548/1,572) were offered an HIV test, 94% (1,456/1,548) accepted and 38 (2.6%) tested HIV-positive. 51 were re-screened for HIV during late pregnancy and one had seroconverted. The HIV prevalence at the ANC was 3.1% (46/1,463). Of the 39 newly diagnosed women, 35 (90%) were linked to care. HIV test was offered to >98% of ANC clients during both the pre- and post-B+ periods. During the post-B+ period, test acceptance (94% versus 90.5%, p<0.0001) and linkage to care (90% versus 26%, p<0.0001) increased. Ten additional women diagnosed outside the ANC were linked to care. 82% (37/45) of these newly-enrolled women started antiretroviral treatment (ART). After a median time of 17 months, 27% (12/45) were lost to follow-up. 79 women under HIV care became pregnant and all received ART. After a median follow-up time of 19 months, 6% (5/79) had been lost. 5,727 women delivered at the hospital, 20% (1,155/5,727) had unknown HIV serostatus. Of these, 30% (345/1,155) were tested for HIV, and 18/345 (5.2%) were HIV-positive. Compared to the pre-B+ period more women were tested during labour (30% versus 2.4%, p<0.0001). During the study, the MTCT rate was 2.2%., Conclusions: The implementation of Option B+ through an integrated service delivery model resulted in universal HIV testing in the ANC, high rates of linkage to care, and MTCT below the elimination threshold. However, HIV testing in late pregnancy and labour, and retention during early ART need to be improved.

Background: The Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) is a single-site, open and ongoing prospective cohort of people living with human immunodeficiency virus (PLWHIV) established in 2005 at the Chronic Diseases Clinic of Ifakara (CDCI), within the Saint Francis Referral Hospital (SFRH) in Ifakara, Tanzania. The objectives of KIULARCO are to (i) provide patient and cohort-level information on the outcomes of HIV treatment; (ii) provide cohort-level information on opportunistic infections and comorbidities; (iii) evaluate aspects of human immunodeficiency virus (HIV) care and treatment that have national or international policy relevance; (iv) provide a platform for studies on improving HIV care and treatment in sub-Saharan Africa; and (v) contribute to generating local capacity to deal with the challenges posed by the HIV/AIDS pandemic in this region. Moreover, KIULARCO may serve as a model for other healthcare settings in rural sub-Saharan Africa., Methods: Since 2005, all patients diagnosed with HIV at the Saint Francis Referral Hospital are invited to participate in the cohort, including non-pregnant adults, pregnant women, adolescents, children and infants. The information collected includes demographics, baseline and follow-up clinical data, laboratory data, medication history, drug toxicities, diagnoses and outcomes. Real-time data are captured during the patient encounter through an electronic medical record system that allowed transition to a paperless clinic in 2013. In addition, KIULARCO is associated with a biobank of cryopreserved plasma samples and cell pellets collected from all participants before and at different time-points during antiretroviral treatment., Results: Up to the end of 2016, 12 185 PLWHIV have been seen at the CDCI; 9218 (76%) of whom have been enrolled into KIULARCO and 6965 (76%) of these have received ART from the clinic. Patients on ART attend at least every 3 months, with laboratory monitoring every 6 months. KIULARCO data have been used to generate relevant information regarding ART outcomes, opportunistic infections, non-AIDS comorbidities, prevention of mother-to-child transmission of HIV, paediatric HIV, and mortality and retention in care. Requests for collaborations on analyses can be submitted to the KIULARCO scientific committee., Conclusions: KIULARCO provides a framework for improving the quality of care of people living with HIV in sub-Saharan Africa, to generate relevant information to evaluate ART programmes and to build local capacity to deal with HIV/AIDS. The comprehensiveness of the data collected, together with the biobank spanning over ten years has created a unique research platform in rural sub-Saharan Africa.

Objective: To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania., Design: Prospective cohort study with cross-sectional analysis., Methods: All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM., Results: Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11-13.68], female sex (aOR = 2.57; 95% CI 1.03-6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51-35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4 T-cell percentage (aOR = 0.20; 0.10-0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73-0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure., Conclusion: Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV.

Background: Strategies to improve HIV diagnosis and linkage into care, antiretroviral treatment coverage, and treatment outcomes of mothers and children are urgently needed in sub-Saharan Africa., Methods: From December 2012, we implemented an intervention package to improve prevention of mother-to-child transmission (PMTCT) and pediatric HIV care in our rural Tanzanian clinic, consisting of: (1) creation of a PMTCT and pediatric unit integrated within the reproductive and child health clinic; (2) implementation of electronic medical records; (3) provider-initiated HIV testing and counseling in the hospital wards; and (4) early infant diagnosis test performed locally. To assess the impact of this strategy, clinical characteristics and outcomes were compared between the period before (2008-2012) and during/after the implementation (2013-2014)., Results: After the intervention, the number of mothers and children enrolled into care almost doubled. Compared with the pre-intervention period (2008-2012), in 2013-2014, children presented lower CD4% (16 vs. 16.8, P = 0.08) and more advanced disease (World Health Organization stage 3/4 72% vs. 35%, P < 0.001). The antiretroviral treatment coverage rose from 80% to 98% (P < 0.001), the lost-to-follow-up rate decreased from 20% to 11% (P = 0.002), and mortality ascertainment improved. During 2013-2014, 261 HIV-exposed infants were enrolled, and the early mother-to-child transmission rate among mother-infant pairs accessing PMTCT was 2%., Conclusions: This strategy resulted in an increased number of mothers and children diagnosed and linked into care, a higher detection of children with AIDS, universal treatment coverage, lower loss to follow-up, and an early mother-to-child transmission rate below the threshold of elimination. This study documents a feasible and scalable model for family-centered HIV care in sub-Saharan Africa., Competing Interests: The authors have no conflicts of interest to disclose.

The acquisition of drug-resistance mutations among African children living with in human immunodeficiency virus on antiretroviral treatment has been scarcely reported. This threatens the overall success of antiretroviral programs and the clinical outcomes of children in care. We present a well characterized series of children from rural Tanzania with acquired drug-resistance mutations to contribute to the better understanding of this emerging public health concern.