A digital health algorithm to guide antibiotic prescription in pediatric outpatient care: a cluster randomized controlled trial.

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.

[Paediatric digital clinical decision support for global health]. / Systèmes d'aide à la décision clinique pour la pédiatrie en santé globale.

Effective, scalable and sustainable strategies to improve quality of care are needed to address the substantial burden of preventable deaths of children under-five in resource-constrained settings. Clinical decision support systems (CDSS), digital tools which generate recommendations for healthcare providers based on patient-specific information, show promise. By strengthening adherence to evidence-based assessment, diagnosis and management and generating high-quality data, CDSS can improve quality care - care that is effective, safe, people-centered, timely, equitable, integrated and efficient. Designing and implementing CDSS that deliver this impact is a complex and iterative process. We advocate for collaboration on developing and evaluating these tools to guide their implementation for maximal impact.

Des stratégies efficaces pour améliorer la qualité des soins sont nécessaires pour réduire les nombreux décès évitables d'enfants de moins de cinq ans dans des contextes aux ressources limitées. Les systèmes d'aide à la décision clinique (SADC) sont des outils numériques générant des recommandations aux prestataires de soins sur la base des informations du patient. En orientant l'évaluation et la prise en charge de façon méthodique, ils peuvent permettre d'améliorer la qualité des soins et de générer des données de qualité. Ainsi, les soins peuvent être plus sûrs, centrés sur la personne, opportuns, équitables, intégrés et efficients. La conception et la mise en œuvre d'un SADC de manière durable est un processus complexe et continu. Nous plaidons pour la collaboration afin de guider leur mise en œuvre pour un impact maximal.

ePOCT+ and the medAL-suite: Development of an electronic clinical decision support algorithm and digital platform for pediatric outpatients in low- and middle-income countries.

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.

Primary Care Case Management of Febrile Children: Insights From the ePOCT Routine Care Cohort in Dar es Salaam, Tanzania.

Aim: To provide insight in the primary health care (PHC) case management of febrile children under-five in Dar es Salaam, and to identify areas for improving quality of care. Methods: We used data from the routine care arm of the ePOCT trial, including children aged 2-59 months who presented with an acute febrile illness to two health centers in Dar es Salaam (2014-2016). The presenting complaint, anthropometrics, vital signs, test results, final diagnosis, and treatment were prospectively collected in all children. We used descriptive statistics to analyze the frequencies of diagnoses, adherence to diagnostics, and prescribed treatments. Results: We included 547 children (47% male, median age 14 months). Most diagnoses were viral: upper respiratory tract infection (60%) and/or gastro-enteritis (18%). Vital signs and anthropometric measurements taken by research staff and urinary testing failed to influence treatment decisions. In total, 518/547 (95%) children received antibiotics, while 119/547 (22%) had an indication for antibiotics based on local guidelines. Antibiotic dosing was frequently out of range. Non-recommended treatments were common (29%), most often cough syrup and vitamins. Conclusion: Our study points to challenges in using diagnostic test results, concerns regarding quality of antibiotic prescriptions, and frequent use of non-evidence-based complementary medicines in PHC in Tanzania. Larger studies on diagnostic and treatments processes in PHC in Tanzania are needed to inform effective solutions to support PHC workers in case management of children.

Assessing the implementation of facility-based HIV testing policies in Malawi, South Africa and Tanzania from 2013-2018: Findings from SHAPE-UTT study.

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.

Implications of HIV treatment policies on the health workforce in rural Malawi and Tanzania between 2013 and 2017: Evidence from the SHAPE-UTT study.

Effective implementation of policies for expanding antiretroviral therapy (ART) requires a well-trained and adequately staffed workforce. Changes in national HIV workforce policies, health facility practices, and provider experiences were examined in rural Malawi and Tanzania between 2013 and 2017. In both countries, task-shifting and task-sharing policies were explicit by 2013. In facilities, the cadre mix of providers varied by site and changed over time, with a higher and growing proportion of lower cadre staff in the Malawi site. In Malawi, the introduction of lay counsellors was perceived to have eased the workload of other providers, but lay counsellors reported inadequate support. Both countries had guidance on the minimum numbers of personnel required to deliver HIV services. However, patient loads per provider increased in both settings for HIV tests and visits by ART patients and were not met with corresponding increases in provider capacity in either setting. Providers reported this as a challenge. Although increasing patient numbers bodes well for achieving universal antiretroviral therapy coverage, the quality of care may be undermined by increased workloads and insufficient provider training. Task-shifting strategies may help address workload concerns, but require careful monitoring, supervision and mentoring to ensure effective implementation.

Investigating the implementation of differentiated HIV services and implications for pregnant and postpartum women: A mixed methods multi-country study.

Universal antiretroviral therapy (ART) for pregnant and postpartum women in sub-Saharan Africa has required adaptations to service delivery. We compared national policies on differentiated HIV service delivery with facility-level implementation, and explored provider and user experiences in rural Malawi, Tanzania and South Africa. Four national policies and two World Health Organization guidelines on HIV treatment for pregnant and postpartum women published between 2013 and 2017 were reviewed and summarised. Results were compared with implementation data from surveys undertaken in 34 health facilities. Eighty-seven in-depth interviews were conducted with pregnant and post-partum women living with HIV, their partners and providers. In 2018, differentiated service policies varied across countries. None specifically accounted for pregnant or postpartum women. Malawian policies endorsed facility-based multi-month scripting for clinically-stable adult ART patients, excluding pregnant or breastfeeding women. In Tanzania and South Africa, national policies proposed community-based and facility-based approaches, for which pregnant women were not eligible. Interview data suggested some implementation of differentiated services for pregnant and postpartum women beyond stipulated policies in all settings. Although these adaptations were appreciated by pregnant and postpartum women, they could lead to frustrations among other users when criteria for fast-track services or multi-month prescriptions were not clear.

Cost variations in prevention of mother-to-child HIV transmission services integrated within maternal and child health services in rural Tanzania.

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.

Implementation and experiences of integrated prevention of mother-to-child transmission services in Tanzania, Malawi and South Africa: A mixed methods study.

Although integration of HIV and maternal health services is recommended by the World Health Organization, evidence to guide implementation is limited. We describe facility-level implementation of policies for integrating HIV care within maternal health services and explore experiences of service users and providers in rural Tanzania (Ifakara), South Africa (uMkhanyakude) and Malawi (Karonga). Policy in all countries included HIV testing during antenatal care (ANC), same-day antiretroviral therapy (ART) initiation for HIV-positive pregnant women, and postpartum referral to ART clinics, between six weeks (Malawi, South Africa) and two years after delivery (Tanzania). All facilities offered HIV testing within ANC, most commonly during the first visit. Although most women were comfortable with HIV testing, some felt that opting out would lead to sub-standard services. Some facilities conducted group post-test counselling for HIV-negative women, raising concerns of unintended HIV status disclosure. ART initiation was offered on the same day, the same room as an HIV diagnosis in >90% of facilities. Women's worries around postpartum referral included having unknown providers, insufficient privacy and queues. Adoption and implementation of policies on integrated HIV and maternal health services varied across settings. Patients' experiences of these policies may influence uptake and retention in care.

Cohort profile: The Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) - A prospective HIV cohort in rural Tanzania.

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.

Prevention of mother-to-child transmission of HIV Option B+ cascade in rural Tanzania: The One Stop Clinic model.

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.

A decade of HIV care in rural Tanzania: Trends in clinical outcomes and impact of clinic optimisation in an open, prospective cohort.

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.

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania: an emerging public health concern.

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.

Implementation and Operational Research: An Integrated and Comprehensive Service Delivery Model to Improve Pediatric and Maternal HIV Care in Rural Africa.

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.

A Case Series of Acquired Drug Resistance-Associated Mutations in Human Immunodeficiency Virus-Infected Children: An Emerging Public Health Concern in Rural Africa.

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.