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 Previously identified challenges of CDSAs include their limited scope, usability, and outdated clinical content.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.

Ending Neglected Surgical Diseases (NSDs): Definitions, Strategies, and Goals for the Next Decade.

While there has been overall progress in addressing the lack of access to surgical care worldwide, untreated surgical conditions in developing countries remain an underprioritized issue. Significant backlogs of advanced surgical disease called neglected surgical diseases (NSDs) result from massive disparities in access to quality surgical care. We aim to discuss a framework for a public health rights-based initiative designed to prevent and eliminate the backlog of NSDs in developing countries. We defined NSDs and set forth six criteria that focused on the applicability and practicality of implementing a program designed to eradicate the backlog of six target NSDs from the list of 44 Disease Control Priorities 3rd edition (DCP3) surgical interventions. The human rights-based approach (HRBA) was used to clarify NSDs role within global health. Literature reviews were conducted to ascertain the global disease burden, estimated global backlog, average cost per treatment, disability-adjusted life-years (DALYs) averted from the treatment, return on investment, and potential gain and economic impact of the NSDs identified. Six index NSDs were identified, including neglected cleft lips and palate, clubfoot, cataracts, hernias and hydroceles, injuries, and obstetric fistula. Global definitions were proposed as a starting point towards the prevention and elimination of the backlog of NSDs. Defining a subset of neglected surgical conditions that illustrates society's role and responsibility in addressing them provides a framework through the HRBA lens for its eventual eradication.

HIV Prevalence and the HIV Treatment Cascade Among Female Sex Workers in Cross-Border Areas in East Africa.

In cross-border areas of East Africa, sexual networks include partnerships across resident, migrant, and mobile populations, and risky behaviors can coincide with fragmented health services given the challenges of cross-border coordination. Among those most at risk are female sex workers (FSWs). We map HIV prevalence among FSWs in 14 cross-border areas, estimate associations between FSW characteristics and HIV and undiagnosed HIV, and estimate progress towards the UNAIDS 90-90-90 targets. The 2016-2017 East Africa Cross-Border Integrated Health Study recruited 4040 women; 786 were classified as FSWs. Overall HIV prevalence among FSWs was 10.8% (95% CI 8.2%, 13.3%), though area-specific estimates varied considerably. Among FSWs living with HIV, 46.1% (95% CI 33.2%, 59.0%) knew their status, 80.6% (95% CI 66.3%, 94.9%) of FSWs who knew their status were on ART, and 84.8% (95% CI 66.1%, 100.0%) of FSWs on ART were virally suppressed. Results indicate a need for expanded HIV testing.

Access to HIV prevention services in East African cross-border areas: a 2016-2017 cross-sectional bio-behavioural study.

INTRODUCTION: East African cross-border areas are visited by mobile and vulnerable populations, such as men, female sex workers, men who have sex with men, truck drivers, fisher folks and young women. These groups may not benefit from traditional HIV prevention interventions available at the health facilities where they live, but may benefit from services offered at public venues identified as places where people meet new sexual partners (e.g. bars, nightclubs, transportation hubs and guest houses). The goal of this analysis was to estimate availability, access and uptake of prevention services by populations who visit these venues. METHODS: We collected cross-sectional data using the Priorities for Local AIDS Control Efforts sampling method at cross-border locations near or along the land and lake borders of Kenya, Rwanda, Tanzania and Uganda from June 2016-February 2017. This bio-behavioural survey captured information from a probability sample of 11,428 individuals at 833 venues across all areas. Data were weighted using survey sampling weights and analysed using methods to account for the complex sampling design. RESULTS: Among the 85.6% of persons who had access to condoms, 60.5% did not use a condom at their last anal or vaginal sexual encounter. Venues visited by high percentages of persons living with HIV were not more likely than other venues to offer condoms. In 12 of the 22 cross-border areas, male or female condoms were available at less than 33% of the venues visited by persons having difficulty accessing condoms. In 17 of the 22 cross-border areas, education outreach visits in the preceding six months occurred at less than 50% of the venues where participants had low effective use of condoms. CONCLUSIONS: Individuals visiting venues in cross-border areas report poor access to and low effective use of condoms and other prevention services. Availability of HIV prevention services differed by venue and population type and cross-border area, suggesting opportunities for more granular targeting of HIV prevention interventions and transnational coordination of HIV programming.

Improving HIV outreach testing yield at cross-border venues in East Africa.

OBJECTIVE: The aim of this study was to evaluate HIV testing yield under several candidate strategies for outreach testing at venues (i.e. places where people socialize and meet new sex partners) in East Africa cross-border areas. DESIGN: Population-based cross-sectional biobehavioural survey of people who had not been previously diagnosed with HIV found in venues. METHODS: We identified participants who would have been tested for HIV under each of 10 hypothetical outreach testing strategies and calculated the proportion who would have newly tested positive for HIV under each strategy. On the basis of this proportion, we calculated the 'number needed to test' (NNT) to identify one new case of HIV under each strategy. All estimates were obtained by applying survey sampling weights to account for the complex sampling design. RESULTS: If testing was performed at a random sample of venues, 35 people would need to be tested to identify one new case of HIV, but higher yield could be found by limiting testing to venues with specific characteristics. Strategies focusing on women had higher testing yield. Testing women employed by venues would result in highest yield of all strategies examined (NNT = 15), while testing men under age 24 would result in the lowest yield (NNT = 99). CONCLUSION: Quantitatively evaluating HIV testing strategies prior to implementation using survey data presents a new opportunity to refine and prioritize outreach testing strategies for the people and places most likely to result in high HIV testing yield.

The HIV care continuum among resident and non-resident populations found in venues in East Africa cross-border areas.

INTRODUCTION: HIV care and treatment in cross-border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross-border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed. METHODS: Participants (n = 11,410) working or socializing in public places in selected East Africa cross border areas were recruited between June 2016 and February 2017 using the Priorities for Local AIDS Control Efforts method and administered a behavioural survey and rapid HIV test. This approach was designed to recruit a stratified random sample of people found in public spaces or venues in each cross border area. For participants testing positive for HIV, viral load was measured from dried blood spots. The proportion in each step of the cascade was estimated using inverse probability weights to account for the sampling design and informative HIV test refusals. Estimates are reported separately for residents of the cross border areas and non-residents found in those areas. RESULTS: Overall, 43% of participants with HIV found in cross-border areas knew their status, 87% of those participants were on antiretroviral therapy (ART), and 80% of participants on ART were virally suppressed. About 20% of people with HIV found in cross border areas were sampled outside their subdistrict or subcounty of residence. While both resident and non-resident individuals who knew their status were likely to be on ART (85% and 96% respectively), people on ART recruited outside their area of residence were less likely to be suppressed (64% suppressed; 95% CI: 43, 81) compared to residents (84% suppressed; 95% CI: 75, 93). CONCLUSIONS: People living in or travelling through cross-border areas may face barriers in learning their HIV status. Moreover, while non-residents were more likely to be on treatment than residents, they were less likely to be suppressed, suggesting gaps in continuity of care for people in East Africa travelling outside their area of residence despite timely initiation of treatment.

Risk factors for early and late transmission of HIV via breast-feeding among infants born to HIV-infected women in a randomized clinical trial in Botswana.

Risk factors for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breast-feeding were evaluated in a randomized trial. HIV-infected women and their infants received zidovudine as well as single-dose nevirapine or placebo. Infants were randomized to formula-feed (FF) or breast-feed (BF) in combination with zidovudine prophylaxis. Of 1116 at-risk infants, 6 (1.1%) in the FF group and 7 (1.3%) in the BF group were infected between birth and 1 month (P=.99). Maternal receipt of nevirapine did not predict early MTCT in the BF group (P=.45). Of 547 infants in the BF group at risk for late MTCT, 24 (4.4%) were infected. Maternal HIV-1 RNA levels in plasma (P<.001) and breast milk (P<.001) predicted late MTCT. These findings support the safety of 1 month of breast-feeding in combination with maternal and infant antiretroviral prophylaxis. Trial registration. ClinicalTrials.gov identifiers: NCT00197691 and NCT00197652.

Infant morbidity, mortality, and breast milk immunologic profiles among breast-feeding HIV-infected and HIV-uninfected women in Botswana.

BACKGROUND: Infants of human immunodeficiency virus (HIV)-infected women have high mortality, but the immunologic integrity and protection afforded by the breast milk of HIV-infected women is unknown. METHODS: We determined morbidity and mortality by 24 months among breast-fed infants of 588 HIV-infected and 137 HIV-uninfected women followed-up in a clinical trial in Botswana. A matched case-control study compared clinical, behavioral, and breast milk immunologic parameters among 120 HIV-infected women by infant outcome. Breast milk factors were also compared between HIV-infected and HIV-uninfected women. RESULTS: Twenty-four-month mortality was 29.5% among HIV-infected infants, 6.7% among HIV-exposed uninfected infants, and 1.6% among HIV-unexposed infants. No differences were detected in breast milk immunologic profiles of HIV-infected women whose infants were either ill or well. Discontinuation of breast-feeding was the strongest predictor of illness (P<.001). Levels in breast milk of pathogen-specific immunoglobulin (Ig) G and IgA to Haemophilus influenzae, Campylobacter jejuni, Helicobacter pylori, Streptococcus pneumoniae, and innate immune factors were not lower among HIV-infected women than among HIV-uninfected women. CONCLUSIONS: Mortality was higher among HIV-infected and HIV-exposed infants than among HIV-unexposed infants. However, the immunologic profiles of breast milk among HIV-infected women were intact, and discontinuation of breast-feeding was the primary risk for infant morbidity. Thus, the breast milk of HIV-infected women may confer protection against common infant pathogens. TRIAL REGISTRATION: (ClinicalTrials.Gov) identifiers: NCT00197691 and NCT00197652.

Response to antiretroviral therapy after a single, peripartum dose of nevirapine.

BACKGROUND: A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants. METHODS: We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan-Meier method. RESULTS: Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment. CONCLUSIONS: Women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine. (ClinicalTrials.gov number, NCT00197587 [ClinicalTrials.gov].).

Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study.

CONTEXT: Postnatal transmission of human immunodeficiency virus-1 (HIV) via breastfeeding reverses gains achieved by perinatal antiretroviral interventions. OBJECTIVE: To compare the efficacy and safety of 2 infant feeding strategies for the prevention of postnatal mother-to-child HIV transmission. DESIGN, SETTING, AND PATIENTS: A 2 x 2 factorial randomized clinical trial with peripartum (single-dose nevirapine vs placebo) and postpartum infant feeding (formula vs breastfeeding with infant zidovudine prophylaxis) interventions. In Botswana between March 27, 2001, and October 29, 2003, 1200 HIV-positive pregnant women were randomized from 4 district hospitals. Infants were evaluated at birth, monthly until age 7 months, at age 9 months, then every third month through age 18 months. INTERVENTION: All of the mothers received zidovudine 300 mg orally twice daily from 34 weeks' gestation and during labor. Mothers and infants were randomized to receive single-dose nevirapine or placebo. Infants were randomized to 6 months of breastfeeding plus prophylactic infant zidovudine (breastfed plus zidovudine), or formula feeding plus 1 month of infant zidovudine (formula fed). MAIN OUTCOME MEASURES: Primary efficacy (HIV infection by age 7 months and HIV-free survival by age 18 months) and safety (occurrence of infant adverse events by 7 months of age) end points were evaluated in 1179 infants. RESULTS: The 7-month HIV infection rates were 5.6% (32 infants in the formula-fed group) vs 9.0% (51 infants in the breastfed plus zidovudine group) (P = .04; 95% confidence interval for difference, -6.4% to -0.4%). Cumulative mortality or HIV infection rates at 18 months were 80 infants (13.9%, formula fed) vs 86 infants (15.1% breastfed plus zidovudine) (P = .60; 95% confidence interval for difference, -5.3% to 2.9%). Cumulative infant mortality at 7 months was significantly higher for the formula-fed group than for the breastfed plus zidovudine group (9.3% vs 4.9%; P = .003), but this difference diminished beyond month 7 such that the time-to-mortality distributions through age 18 months were not significantly different (P = .21). CONCLUSIONS: Breastfeeding with zidovudine prophylaxis was not as effective as formula feeding in preventing postnatal HIV transmission, but was associated with a lower mortality rate at 7 months. Both strategies had comparable HIV-free survival at 18 months. These results demonstrate the risk of formula feeding to infants in sub-Saharan Africa, and the need for studies of alternative strategies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00197587.

Social consequences of HIV-positive women's participation in prevention of mother-to-child transmission programmes.

Approximately two-third of the worlds HIV/AIDS cases are found in sub-Saharan Africa. The rate of mother-to-child-transmission (MTCT) has been found to lie between 15 and 40%. The aim of this study was to explore the social consequences affecting the experience HIV-positive women have when taking part in a prevention of mother-to-child-transmission programme (PMTCT). Few studies have investigated this earlier. A cross section of 52 participating women enrolled into a PMTCT programme were randomly selected and interviewed, using a structured questionnaire. There were three main findings. The most important consequence of participating was the difficulty associated with the breast-feeding issue. For the women who because of a wish to prevent MTCT are employing formula feeding, this causes suspicion and prejudice amongst people in the local community. Few people influence a woman's decision to take part, as they tend to keep their HIV status to themselves. More information to the general public about HIV and PMTCT programmes will enhance acceptance to HIV, and generate an environment conducive towards participation in PMTCT programmes.