Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

BACKGROUND: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. METHODS: We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. RESULTS: We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. CONCLUSIONS: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).

Usability of pulse oximeters used by community health and primary care workers as screening tools for severe illness in children under five in low resource settings: A cross-sectional study in Cambodia, Ethiopia, South Sudan, and Uganda.

Timely recognition and referral of severely ill children is especially critical in low-resource health systems. Pulse-oximeters can improve health outcomes of children by detecting hypoxaemia, a severity indicator of the most common causes of death in children. Cost-effectiveness of pulse-oximeters has been proven in low-income settings. However, evidence on their usability in community health settings is scarce.This study explores the usability of pulse-oximeters for community health and primary care workers in Cambodia, Ethiopia, South Sudan, and Uganda. We collected observational data, through a nine-task checklist, and survey data, using a five-point Likert scale questionnaire, capturing three usability aspects (effectiveness, efficiency, and satisfaction) of single-probe fingertip and multi-probe handheld devices. Effectiveness was determined by checklist completion rates and task completion rates per checklist item. Efficiency was reported as proportion of successful assessments within three attempts. Standardized summated questionnaire scores (min = 0, max = 100) determined health worker's satisfaction. Influencing factors on effectiveness and satisfaction were explored through hypothesis tests between independent groups (device type, cadre of health worker, country). Checklist completion rate was 78.3% [CI 72.6-83.0]. Choosing probes according to child age showed the lowest task completion rate of 68.7% [CI 60.3%-76.0%]. In 95.6% [CI 92.7%-97.4%] of assessments a reading was obtained within three attempts. The median satisfaction score was 95.6 [IQR = 92.2-99.0]. Significantly higher checklist completion rates were observed with single-probe fingertip devices (p<0.001) and children 12-59 months (p<0.001). We found higher satisfaction scores in South Sudan (p<0.001) and satisfaction varied slightly between devices. From a usability perspective single-probe devices for all age groups should be prioritized for scaled implementation. Further research on easy to use and accurate devices for infants is much needed.

Performance of five pulse oximeters to detect hypoxaemia as an indicator of severe illness in children under five by frontline health workers in low resource settings - A prospective, multicentre, single-blinded, trial in Cambodia, Ethiopia, South Sudan, and Uganda.

BACKGROUND: Low blood oxygen saturation (SpO2), or hypoxaemia, is an indicator of severe illness in children. Pulse oximetry is a globally accepted, non-invasive method to identify hypoxaemia, but rarely available outside higher-level facilities in resource-constrained countries. This study aims to evaluate the performance of different types of pulse oximeters amongst frontline health workers in Cambodia, Ethiopia, South Sudan, and Uganda. METHODS: Five pulse oximeters (POx) which passed laboratory testing, out of an initial 32 potential pulse oximeters, were evaluated by frontline health workers for performance, defined as agreement between the SpO2 measurements of the test device and the reference standard. The study protocol is registered with the Australia New Zealand Clinical Trials Registry (Ref: ACTRrn12615000348550). FINDINGS: Two finger-tip pulse oximeters (Contec and Devon), two handheld pulse oximeters (Lifebox and Utech), and one phone pulse oximeter (Masimo) passed the laboratory testing. They were evaluated for performance on 1,313 children under five years old by 207 frontline health workers between February and May 2015. Phone and handheld pulse oximeters had greater overall agreement with the reference standard (56%; 95% CI 0.52 - 0.60 to 68%; 95% CI 0.65 - 0.71) than the finger-tip POx (31%; 95% CI 0.26 to 0.36 and 47%; 95% CI 0.42 to 0.52). Fingertip POx performance was substantially lower in the 0-2 month olds; having just 17% and 25% agreement. The finger-tip devices more often underreported SpO2 readings (mean difference -7.9%; 95%CI -8.6,-7.2 and -3.9%; 95%CI -4.4,-3.4), and therefore over diagnosed hypoxaemia in the children assessed. INTERPRETATION: While the Masimo phone pulse oximeter performed best, all handheld POx with age-specific probes performed well in the hands of frontline health workers, further highlighting their suitability as a screening tool of severe illness. The poor performance of the fingertip POx suggests they should not be used in children under five by frontline health workers. It is essential that POx are performance tested on children in routine settings (in vivo), not only in laboratories or controlled settings (in vitro), before being introduced at scale. FUNDING: Bill & Melinda Gates Foundation [OPP1054367].

Performance of Four Respiratory Rate Counters to Support Community Health Workers to Detect the Symptoms of Pneumonia in Children in Low Resource Settings: A Prospective, Multicentre, Hospital-Based, Single-Blinded, Comparative Trial.

BACKGROUND: Pneumonia is one of the leading causes of death in children under-five globally. The current diagnostic criteria for pneumonia are based on increased respiratory rate (RR) or chest in-drawing in children with cough and/or difficulty breathing. Accurately counting RR is difficult for community health workers (CHWs). Current RR counting devices are frequently inadequate or unavailable. This study analysed the performance of improved RR timers for detection of pneumonia symptoms in low-resource settings. METHODS: Four RR timers were evaluated on 454 children, aged from 0 to 59 months with cough and/or difficulty breathing, over three months, by CHWs in hospital settings in Cambodia, Ethiopia, South Sudan and Uganda. The devices were the Mark Two ARI timer (MK2 ARI), counting beads with ARI timer, Rrate Android phone and the Respirometer feature phone applications. Performance was evaluated for agreement with an automated RR reference standard (Masimo Root patient monitoring and connectivity platform with ISA CO2 capnography). This study is registered with ANZCTR [ACTRN12615000348550]. FINDINGS: While most CHWs managed to achieve a RR count with the four devices, the agreement was low for all; the mean difference of RR measurements from the reference standard for the four devices ranged from 0.5 (95% C.I. - 2.2 to 1.2) for the respirometer to 5.5 (95% C.I. 3.2 to 7.8) for Rrate. Performance was consistently lower for young infants (0 to < 2 months) than for older children (2 to ≤ 59 months). Agreement of RR classification into fast and normal breathing was moderate across all four devices, with Cohen's Kappa statistics ranging from 0.41 (SE 0.04) to 0.49 (SE 0.05). INTERPRETATION: None of the four devices evaluated performed well based on agreement with the reference standard. The ARI timer currently recommended for use by CHWs should only be replaced by more expensive, equally performing, automated RR devices when aspects such as usability and duration of the device significantly improve the patient-provider experience. FUNDING: Bill & Melinda Gates Foundation [OPP1054367].

Childhood pneumonia diagnostics: community health workers' and national stakeholders' differing perspectives of new and existing aids.

BACKGROUND: Pneumonia heavily contributes to global under-five mortality. Many countries use community case management to detect and treat childhood pneumonia. Community health workers (CHWs) have limited tools to help them assess signs of pneumonia. New respiratory rate (RR) counting devices and pulse oximeters are being considered for this purpose. OBJECTIVE: To explore perspectives of CHWs and national stakeholders regarding the potential usability and scalability of seven devices to aid community assessment of pneumonia signs. DESIGN: Pile sorting was conducted to rate the usability and scalability of 7 different RR counting aids and pulse oximeters amongst 16 groups of participants. Following each pile-sorting session, a focus group discussion (FGD) explored participants' sorting rationale. Purposive sampling was used to select CHWs and national stakeholders with experience in childhood pneumonia and integrated community case management (iCCM) in Cambodia, Ethiopia, Uganda and South Sudan. Pile-sorting data were aggregated for countries and participant groups. FGDs were audio recorded and transcribed verbatim. Translated FGDs transcripts were coded in NVivo 10 and analysed using thematic content analysis. Comparative analysis was performed between countries and groups to identify thematic patterns. RESULTS: CHWs and national stakeholders across the four countries perceived the acute respiratory infection (ARI) timer and fingertip pulse oximeter as highly scalable and easy for CHWs to use. National stakeholders were less receptive to new technologies. CHWs placed greater priority on device acceptability to caregivers and children. Both groups felt that heavy reliance on electricity reduced potential scalability and usability in rural areas. Device simplicity, affordability and sustainability were universally valued. CONCLUSIONS: CHWs and national stakeholders prioritise different device characteristics according to their specific focus of work. The views of all relevant stakeholders, including health workers, policy makers, children and parents, should be considered in future policy decisions, research and development regarding suitable pneumonia diagnostic aids for community use.