Sabin Nsanzimana

A smartphone dongle for diagnosis of infectious diseases at the point of care

A smartphone accessory can perform a point-of-care test that simultaneously detects three infectious disease markers from fingerprick whole blood in 15 min, as operated by health care workers trained on a software app. Dongle + app = mobile test for sexually transmitted diseases There are thousands of health-related “apps” for smartphones, from tracking sleep patterns to recording heart rate to logging caloric intake. The power of such apps in connecting resource-limited communities to health care workers and, in turn, to proper and immediate care is now emerging. In this issue, Laksanasopin and colleagues describe a microfluidic-based diagnostic test for HIV and syphilis that attaches to (and is powered by) the iPod’s headphone jack. The mobile test also comes complete with an easy-to-use app, flashing test results on-screen in under 15 min. The test is based on the standard immunoassay but uses gold-labeled antibodies to detect HIV and syphilis antigens in only 2 μl of whole blood, and then silver reagents to amplify the resulting signal. The authors deployed the dongle in Rwanda, testing its sensitivity and specificity on 96 patients. Evaluated side by side with the gold standard tests for HIV and syphilis, the dongle produced results with a sensitivity and specificity needed for making treatment decisions in the field. In a survey, a vast majority of patients reported satisfaction with dongle performance. After a few next-generation tweaks, including reducing the size of the dongle, the entire diagnostic package is ready for adoption in resource-poor clinics and communities, to improve detection of HIV and syphilis and empower health care workers to administer timely and appropriate treatments. This work demonstrates that a full laboratory-quality immunoassay can be run on a smartphone accessory. This low-cost dongle replicates all mechanical, optical, and electronic functions of a laboratory-based enzyme-linked immunosorbent assay (ELISA) without requiring any stored energy; all necessary power is drawn from a smartphone. Rwandan health care workers used the dongle to test whole blood obtained via fingerprick from 96 patients enrolling into care at prevention of mother-to-child transmission clinics or voluntary counseling and testing centers. The dongle performed a triplexed immunoassay not currently available in a single test format: HIV antibody, treponemal-specific antibody for syphilis, and nontreponemal antibody for active syphilis infection. In a blinded experiment, health care workers obtained diagnostic results in 15 min from our triplex test that rivaled the gold standard of laboratory-based HIV ELISA and rapid plasma reagin (a screening test for syphilis), with sensitivity of 92 to 100% and specificity of 79 to 100%, consistent with needs of current clinical algorithms. Patient preference for the dongle was 97% compared to laboratory-based tests, with most pointing to the convenience of obtaining quick results with a single fingerprick. This work suggests that coupling microfluidics with recent advances in consumer electronics can make certain laboratory-based diagnostics accessible to almost any population with access to smartphones.

Rwanda 20 years on: investing in life

Two decades ago, the genocide against the Tutsis in Rwanda led to the deaths of 1 million people, and the displacement of millions more. Injury and trauma were followed by the effects of a devastated health system and economy. In the years that followed, a new course set by a new government set into motion equity-oriented national policies focusing on social cohesion and people-centred development. Premature mortality rates have fallen precipitously in recent years, and life expectancy has doubled since the mid-1990s. Here we reflect on the lessons learned in rebuilding Rwandas health sector during the past two decades, as the country now prepares itself to take on new challenges in health-care delivery.

Causes of hospital admission among people living with HIV worldwide: a systematic review and meta-analysis

BACKGROUND Morbidity associated with HIV infection is poorly characterised, so we aimed to investigate the contribution of different comorbidities to hospital admission and in-hospital mortality in adults and children living with HIV worldwide. METHODS Using a broad search strategy combining terms for hospital admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify studies reporting cause of hospital admission in people living with HIV. We focused on data reported after 2007, the period in which access to antiretroviral therapy started to become widespread. We estimated pooled proportions of hospital admissions and deaths per disease category by use of random-effects models. We stratified data by geographical region and age. FINDINGS We obtained data from 106 cohorts, with reported causes of hospital admission for 313 006 adults and 6182 children living with HIV. For adults, AIDS-related illnesses (25 119 patients, 46%, 95% CI 40-53) and bacterial infections (14 034 patients, 31%, 20-42) were the leading causes of hospital admission. These two categories were the most common causes of hospital admission for adults in all geographical regions and the most common causes of mortality. Common region-specific causes of hospital admission included malnutrition and wasting, parasitic infections, and haematological disorders in the Africa region; respiratory disease, psychiatric disorders, renal disorders, cardiovascular disorders, and liver disease in Europe; haematological disorders in North America; and respiratory, neurological, digestive and liver-related conditions, viral infections, and drug toxicity in South and Central America. For children, AIDS-related illnesses (783 patients, 27%, 95% CI 19-34) and bacterial infections (1190 patients, 41%, 26-56) were the leading causes of hospital admission, followed by malnutrition and wasting, haematological disorders, and, in the African region, malaria. Mortality in individuals admitted to hospital was 20% (95% CI 18-23, 12 902 deaths) for adults and 14% (10-19, 643 deaths) for children. INTERPRETATION This review shows the importance of prompt HIV diagnosis and treatment, and the need to reinforce existing recommendations to provide chemoprophylaxis and vaccination against major preventable infectious diseases to people living with HIV to reduce serious AIDS and non-AIDS morbidity. FUNDING None.

Life expectancy among HIV-positive patients in Rwanda: a retrospective observational cohort study

BACKGROUND Rwanda has achieved substantial progress in scaling up of antiretroviral therapy. We aimed to assess the effect of increased access to antiretroviral therapy on life expectancy among HIV-positive patients in two distinct periods of lower and higher antiretroviral therapy coverage (1997-2007 and 2008-11). METHODS In a retrospective observational cohort study, we collected clinical and demographic data for all HIV-positive patients enrolled in care at 110 health facilities across all five provinces of Rwanda. We included patients aged 15 years or older with a known enrolment date between 1997 and 2014. We constructed abridged life tables from age-specific mortality rates and life expectancy stratified by sex, CD4 cell count, and WHO disease stage at enrolment in care and initiation of antiretroviral therapy. FINDINGS We included 72,061 patients in this study, contributing 213,983 person-years of follow-up. The crude mortality rate was 33·4 deaths per 1000 person-years (95% CI 32·7-34·2). Life expectancy for the overall cohort was 25·6 additional years (95% CI 25·1-26·1) at 20 years of age and 23·3 additional years (95% CI 22·9-23·7) at 35 years of age. Life expectancy at 20 years of age in the period of 1997-2007 was 20·4 additional years (95% CI 19·5-21·3); for the period of 2008-11, life expectancy had increased to 25·6 additional years (95% CI 24·8-26·4). Individuals enrolling in care with CD4 cell counts of 500 cells per μL or more, and with WHO disease stage I, had the highest life expectancies. INTERPRETATION This study adds to the growing body of evidence showing the benefit to HIV-positive patients of early enrolment in care and initiation of antiretroviral therapy. FUNDING Bill & Melinda Gates Foundation.

Patient-Reported Barriers to Adherence to Antiretroviral Therapy: A Systematic Review and Meta-Analysis

Background Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities. Methods and Findings We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%–45.4%; adolescents 63.1%, 95% CI 46.3%–80.0%; children/caregivers 29.2%, 95% CI 20.1%–38.4%), being away from home (adults 30.4%, 95% CI 25.5%–35.2%; adolescents 40.7%, 95% CI 25.7%–55.6%; children/caregivers 18.5%, 95% CI 10.3%–26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%–35.0%; adolescents 32.4%, 95% CI 0%–75.0%; children/caregivers 26.3%, 95% CI 15.3%–37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%–18.3%; adolescents 25.7%, 95% CI 17.7%–33.6%; children 15.1%, 95% CI 3.9%–26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%–16.1%) and adolescents (28.8%, 95% CI 11.8%–45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%–15.3%; children/caregivers 22.3%, 95% CI 10.2%–34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%–18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%–11.4%). Health service–related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%–21.9%) and stock outs (adults 16.1%, 95% CI 11.7%–20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children. Conclusions Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence.

Cell phone-based and internet-based monitoring and evaluation of the National Antiretroviral Treatment Program during rapid scale-up in Rwanda: TRACnet 2004-2010.

Background:Monitoring and evaluation of antiretroviral treatment (ART) scale-up has been challenging in resource-limited settings. We describe an innovative cell-phone-based and internet-based reporting system (TRACnet) utilized in Rwanda. Methods:From January 2004 to June 30, 2010, all health facilities with ART services submitted standardized monthly aggregate reports of key indicators. National cohort data were analyzed to examine trends in characteristics of patients initiating ART and cumulative cohort outcomes. Estimates of HIV-infected patients eligible for ART were obtained from Joint United Nations Program on HIV/AIDS (Estimation and Projection Package-Spectrum, 2010). Results:By June 30, 2010, 295 (65%) of 451 health centers, District and referral hospitals provided ART services; of these, 255 (86%) were located outside Kigali, the capital. Cell phone–based and internet-based reporting was used by 253 (86%) and 42 (14%), respectively. As of June 30, 2010, 83,041 patients were alive on ART, 6171 (6%) had died, and 9621 (10%) were lost-to-follow-up. Of those alive on ART, 7111 (8.6%) were children, 50,971 (61.4%) were female, and 1823 (2.2%) were on a second-line regimen. The proportion of all patients initiating ART at World Health Organization clinical stages 3 and 4 declined from 65% in 2005 to 27% in 2010. National ART coverage of eligible patients increased from 13% in 2005 to 79% in 2010. Conclusions:Rwanda has successfully expanded ART access and achieved high national ART coverage among eligible patients. TRACnet captured essential data about the ART program during rapid scale-up. Cell phone-based and internet-based reporting may be useful for monitoring and evaluation of similar public health initiatives in other resource-limited settings.

HIV care continuum in Rwanda: a cross-sectional analysis of the national programme

BACKGROUND Rwanda has made remarkable progress towards HIV care programme with strong national monitoring and surveillance. Knowledge about the HIV care continuum model can help to improve outcomes in patients. We aimed to quantify engagement, mortality, and loss to follow-up of patients along the HIV care continuum in Rwanda in 2013. METHODS We collated data for individuals with HIV who participated in the national HIV care programme in Rwanda and calculated the numbers of individuals or proportions of the population at each stage and the transition probabilities between stages of the continuum. We calculated factors associated with mortality and loss to follow-up by fitting Cox proportional hazards regression models, one for the stage of care before antiretroviral therapy (ART) initiation and another for stage of care during ART. FINDINGS An estimated 204,899 individuals were HIV-positive in Rwanda in 2013. Among these individuals, 176,174 (86%) were in pre-ART or in ART stages and 129,405 (63%) had initiated ART by the end of 2013. 82·1% (95% CI 80·7-83·4) of patients with viral load measurements (n=3066) were virally suppressed (translating to 106,371 individuals or 52% of HIV-positive individuals). Mortality was 0·6% (304 patients) in the pre-ART stage and 1·0% (1255 patients) in the ART stage; 2247 (3·9%) patients were lost to follow-up in pre-ART stage and 2847 (2·2%) lost in ART stage. Risk factors for mortality among patients in both pre-ART and ART stages included older age, CD4 cell count at initiation, and male sex. Risk factors for loss to follow-up among patients at both pre-ART and ART stages included younger age (age 10-29 year) and male sex. INTERPRETATION The HIV care continuum is a multitrajectory pathway in which patients have many opportunities to leave and re-engage in care. Knowledge about the points at which individuals are most likely to leave care could improve large-scale delivery of HIV programmes. FUNDING The Bill & Melinda Gates Foundation.

Shared learning in an interconnected world: innovations to advance global health equity

The notion of “reverse innovation”--that some insights from low-income countries might offer transferable lessons for wealthier contexts--is increasingly common in the global health and business strategy literature. Yet the perspectives of researchers and policymakers in settings where these innovations are developed have been largely absent from the discussion to date. In this Commentary, we present examples of programmatic, technological, and research-based innovations from Rwanda, and offer reflections on how the global health community might leverage innovative partnerships for shared learning and improved health outcomes in all countries.

HIV-free survival among nine- to 24-month-old children born to HIV-positive mothers in the Rwandan national PMTCT programme: a community-based household survey

BackgroundOperational effectiveness of large-scale national programmes for the prevention of mother to child transmission (PMTCT) of HIV in sub-Saharan Africa remains limited. We report on HIV-free survival among nine- to 24-month-old children born to HIV-positive mothers in the national PMTCT programme in Rwanda.MethodsWe conducted a national representative household survey between February and May 2009. Participants were mothers who had attended antenatal care at least once during their most recent pregnancy, and whose children were aged nine to 24 months. A two-stage stratified (geographic location of PMTCT site, maternal HIV status during pregnancy) cluster sampling was used to select mother-infant pairs to be interviewed during household visits. Alive children born from HIV-positive mothers (HIV-exposed children) were tested for HIV according to routine HIV testing protocol. We calculated HIV-free survival at nine to 24 months. We subsequently determined factors associated with mother to child transmission of HIV, child death and HIV-free survival using logistic regression.ResultsOut of 1448 HIV-exposed children surveyed, 44 (3.0%) were reported dead by nine months of age. Of the 1340 children alive, 53 (4.0%) tested HIV positive. HIV-free survival was estimated at 91.9% (95% confidence interval: 90.4-93.3%) at nine to 24 months. Adjusting for maternal, child and health system factors, being a member of an association of people living with HIV (adjusted odds ratio: 0.7, 95% CI: 0.1-0.995) improved by 30% HIV-free survival among children, whereas the maternal use of a highly active antiretroviral therapy (HAART) regimen for PMTCT (aOR: 0.6, 95% CI: 0.3-1.07) had a borderline effect.ConclusionsHIV-free survival among HIV-exposed children aged nine to 24 months is estimated at 91.9% in Rwanda. The national PMTCT programme could achieve greater impact on child survival by ensuring access to HAART for all HIV-positive pregnant women in need, improving the quality of the programme in rural areas, and strengthening linkages with community-based support systems, including associations of people living with HIV.

Determinants of circumcision and willingness to be circumcised by Rwandan men, 2010

BackgroundMale Circumcision (MC) has been recommended as one of the preventive measures against sexual HIV transmission by the World Health Organization (WHO). Rwanda has adopted MC as recommended but the country is a non-traditionally circumcising society. The objective was to explore knowledge and perception of Rwandan men on Male Circumcision (MC) and to determine the factors associated with the willingness to be circumcised and to circumcise their sons.MethodsThis cross sectional study was conducted in 29 districts of Rwanda between January and March 2010. Data were collected using a structured questionnaire among men aged 15-59 years. The rate of MC was measured and its perception from respondents, and then the factors associated with the willingness to go for MC were analysed using multiple logistic regressions.ResultsA total of 1098 men were interviewed. Among respondents 17% (95% CI 14-19%) reported being circumcised. About three-quarter (72%) could define MC, but 37% of adolescent could not. Half of the participants were willing to get circumcised and 79% of men would accept circumcision for their sons. The main motivators for MC were its benefits in HIV/STI prevention (69%) and improving hygiene (49%). Being too old was the main reason (32%) reported by men reluctant to undergo MC and younger men were afraid of pain in particular those less than 19 years old (42%). The willingness to circumcise was significantly associated with younger age, living in the Eastern Province, marital status, and the knowledge of the preventive role of circumcision.ConclusionsAdolescents and young adults were more willing to be circumcised. It is critical to ensure the availability of pain free services in order to satisfy the increasing demand for the scale up of MC in Rwanda.