Veronicah Mugisha

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.

Pregnancy desires, and contraceptive knowledge and use among prevention of mother-to-child transmission clients in Rwanda.

Objective:To understand pregnancy intentions and contraception knowledge and use among HIV-positive and negative women in the national prevention of mother-to-child transmission (PMTCT) program in Rwanda. Design:A cross-sectional survey of 236 HIV-positive and 162 HIV-negative postpartum women interviewed within 12 months of their expected delivery date in 12 randomly selected public-sector health facilities providing PMTCT services. Methods:Bivariate analyses explored fertility intentions, and family planning knowledge and use by HIV status. Multivariate analysis identified socio-demographic and service delivery-related predictors of reporting a desire for additional children and modern family planning use. Results:HIV-positive women were less likely to report wanting additional children than HIV-negative women (8 vs. 49%, P < 0.001), and although a majority of women reported discussing family planning with a health worker during their last pregnancy (HIV-positive 79% vs. HIV-negative 69%, P = 0.057), modern family planning use remained low in both groups (HIV-positive 43% vs. HIV-negative 12%, P < 0.001). Condoms were the most commonly used method among HIV-positive women (31%), whereas withdrawal was most frequently reported among HIV-negative women (19%). In multivariate analysis, HIV-negative women were 16 times more likely to report wanting additional children and nearly 85% less likely to use modern family planning. Women who reported making two or less antenatal care visits were 77% less likely to use modern family planning. Conclusion:Our results highlight success in provision of family planning counseling in PMTCT services in Rwanda. As family planning use was low among HIV-positive and negative women, further efforts are needed to improve uptake of modern methods, including dual protection, in Rwandan PMTCT settings.

High Levels of Adherence and Viral Suppression in a Nationally Representative Sample of HIV-Infected Adults on Antiretroviral Therapy for 6, 12 and 18 Months in Rwanda

Background Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART) in Africa. Methods We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL) measurements. Multivariable logistic regression examined predictors of non-perfect (<100%) 30-day adherence and detectable VL (>40 copies/ml). Results Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months); younger age; reporting severe (vs. no or few) side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of <200 cells/µL); alcohol use; and attending sites which initiated ART services in 2003–2004 and 2005 (vs. 2006–2007); sites with ≥600 (vs. <600 patients) on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL. Conclusions High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors.

Comparing two service delivery models for the prevention of mother-to-child transmission (PMTCT) of HIV during transition from single-dose nevirapine to multi-drug antiretroviral regimens

BackgroundMother-to-child transmission (MTCT) of HIV has been eliminated from the developed world with the introduction of multi-drug antiretroviral (md-ARV) regimens for the prevention of MTCT (PMTCT); but remains the major cause of HIV infection among sub-Saharan African children. This study compares two service delivery models of PMTCT interventions and documents the lessons learned and the challenges encountered during the transition from single-dose nevirapine (sd-nvp) to md-ARV regimens in a resource-limited setting.MethodsProgram data collected from 32 clinical sites was used to describe trends and compare the performance (uptake of HIV testing, CD4 screening and ARV regimens initiated during pregnancy) of sites providing PMTCT as a stand-alone service (stand-alone site) versus sites providing PMTCT as well as antiretroviral therapy (ART) (full package site). CD4 cell count screening, enrolment into ART services and the initiation of md-ARV regimens during pregnancy, including dual (zidovudine [AZT] +sd-nvp) prophylaxis and highly active antiretroviral therapy (HAART) were analysed.ResultsFrom July 2006 to December 2008, 1,622 pregnant women tested HIV positive (HIV+) during antenatal care (ANC). CD4 cell count screening during pregnancy increased from 60% to 70%, and the initiation of md-ARV regimens increased from 35.5% to 97% during this period. In 2008, women attending ANC at full package sites were 30% more likely to undergo CD4 cell count assessment during pregnancy than women attending stand-alone sites (relative risk (RR) = 1.3; 95% confidence interval (CI): 1.1-1.4). Enrolment of HIV+ pregnant women in ART services was almost twice as likely at full package sites than at stand-alone sites (RR = 1.9; 95% CI: 1.5-2.3). However, no significant differences were detected between the two models of care in providing md-ARV (RR = 0.9; 95% CI: 0.9-1.0).ConclusionsAll sites successfully transitioned from sd-nvp to md-ARV regimens for PMTCT. Full package sites offer the most efficient model for providing immunological assessment and enrolment into care and treatment of HIV+ pregnant women. Strengthening the capacity of stand-alone PMTCT sites to achieve the same objectives is paramount.

Determinants of Mortality and Loss to Follow-Up among Adults Enrolled in HIV Care Services in Rwanda

Background Antiretroviral therapy (ART) improves morbidity and mortality in patients with HIV, however high rates of loss to follow-up (LTF) and mortality have been documented in HIV care and treatment programs. Methods We analyzed routinely-collected data on HIV-infected patients ≥15 years enrolled at 41 healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not attending clinic in the last 12 months for pre-ART patients and 6 months for ART patients. For the pre-ART period, sub-distribution hazards models were constructed to estimate LTF and death to account for competing risks. Kaplan-Meier (KM) and Cox proportional hazards models were used for patients on ART. Results 31,033 ART-naïve adults were included, 64% were female and 75% were WHO stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9–11.6%) and 2.9% for death (95%CI 2.7–3.1%). Among pre-ART patients, male gender was associated with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1–1.5) and death (aSHR 1.7, 95%CI 1.4–2.1). Low CD4 count (CD4<100 vs. ≥350 aSHR 0.2, 95%CI 0.1–0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2–0.6) were protective against pre-ART LTF. KM estimates for LTF and death in ART patients at 2 years were 4.4% (95%CI 4.4–4.5%) and 6.3% (95%CI 6.2–6.4%). In patients on ART, male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2–1.7) and death (AHR1.3, 95%CI 1.2–1.5). Mortality was higher for ART patients ≥40 years and in those with lower CD4 count at ART initiation. Conclusions Low rates of LTF and death were founds among pre-ART and ART patients in Rwanda but greater efforts are needed to retain patients in care prior to ART initiation, particularly among those who are healthy at enrollment.

Advanced disease at enrollment in HIV care in four sub-Saharan African countries: change from 2006 to 2011 and multilevel predictors in 2011.

Objectives:To examine changes between 2006 and 2011 in the proportion of HIV-positive patients newly enrolled in HIV care with advanced disease and the median CD4+ cell count at enrollment; and identify patient, facility, and contextual-level factors associated with late enrollment in care in 2011. Design:Cross-sectional over time. Methods:For time-trends analyses, routinely collected patient-level data (307 110 adults newly enrolled in 138 HIV clinical care facilities) in Kenya, Mozambique, Rwanda and Tanzania; and for analyses of correlates, patient-level data (46 201 in 195 facilities), and facility and population-level survey data were used. Late enrollment was defined as CD4+ cell count 350 cells/&mgr;l or less and/or WHO clinical stage 3/4. Results:Late enrollment declined from 69.9 to 57.2% (P < 0.0001); median CD4+ cell count increased from 242 to 292 cells/&mgr;l (Ptrend < 0.0001). In 2011, risk of late enrollment was significantly higher for men and nonpregnant women vs. pregnant women; patients aged above 25 vs. 15–25 years; nonmarried vs. married; and those entering from sites other than prevention of mother-to-child transmission. More extensive HIV testing coverage in the region of a facility was significantly associated with lower risk of late enrollment. Conclusions:Despite improvement, in 2011, 57% of patients entered HIV care who were already antiretroviral therapy-eligible. The lower risk of late enrollment among those referred from prevention of mother-to-child transmission and in regions where HIV testing coverage was higher suggests that innovative approaches to rapidly increase testing uptake among people living with HIV prior to the development of symptoms have the potential to reduce late enrollment in care.

Patient enrolment into HIV care and treatment within 90 days of HIV diagnosis in eight Rwandan health facilities: a review of facility-based registers.

Introduction Access to antiretroviral therapy (ART) has increased greatly in sub-Saharan Africa. However many patients do not enrol timely into HIV care and treatment after HIV diagnosis. We studied enrolment into care and treatment and determinants of non-enrolment in Rwanda. Methods Data were obtained from routine clinic registers from eight health facilities in Rwanda on patients who were diagnosed with HIV at the antenatal care, voluntary counselling-and-testing, outpatient or tuberculosis departments between March and May 2009. The proportion of patients enrolled into HIV care and treatment was calculated as the number of HIV infected patients registered in ART clinics for follow-up care and treatment within 90 days of HIV diagnosis divided by the total number of persons diagnosed with HIV in the study period. Results Out of 482 patients diagnosed with HIV in the study period, 339 (70%) were females, and the median age was 29 years (interquartile range [IQR] 24–37). 201 (42%) enrolled into care and treatment within 90 days of HIV diagnosis. The median time between testing and enrolment was six days (IQR 2–14). Enrolment in care and treatment was not significantly associated with age, sex, or department of testing, but was associated with study site. None of those enrolled were in WHO stage 4. The median CD4 cell count among adult patients was 387 cells/mm3 (IQR: 242–533 cells/mm3); 81 of 170 adult patients (48%) were eligible to start ART (CD4 count<350 cells/mm3 or WHO stage 4). Among those eligible, 45 (56%) started treatment within 90 days of HIV diagnosis. Conclusion Less than 50% of diagnosed HIV patients from eight Rwandan health facilities had enrolled into care and treatment within 90 days of diagnosis. Improving linkage to care and treatment after HIV diagnosis is needed to harness the full potential of ART.

Characteristics and outcomes among older HIV-positive adults enrolled in HIV programs in four sub-Saharan African countries.

Background Limited information exists on adults ≥50 years receiving HIV care in sub-Saharan Africa. Methodology Using routinely-collected longitudinal patient-level data among 391,111 adults ≥15 years enrolling in HIV care from January 2005–December 2010 and 184,689 initiating ART, we compared characteristics and outcomes between older (≥50 years) and younger adults at 199 clinics in Kenya, Mozambique, Rwanda, and Tanzania. We calculated proportions over time of newly enrolled and active adults receiving HIV care and initiating ART who were ≥50 years; cumulative incidence of loss to follow-up (LTF) and recorded death one year after enrollment and ART initiation, and CD4+ response following ART initiation. Findings From 2005–2010, the percentage of adults ≥50 years newly enrolled in HIV care remained stable at 10%, while the percentage of adults ≥50 years newly initiating ART (10% [2005]-12% [2010]), active in follow-up (10% [2005]-14% (2010]), and active on ART (10% [2005]-16% [2010]) significantly increased. One year after enrollment, older patients had significantly lower incidence of LTF (33.1% vs. 32.6%[40–49 years], 40.5%[25–39 years], and 56.3%[15–24 years]; p-value<0.0001), but significantly higher incidence of recorded death (6.0% vs. 5.0% [40–49 years], 4.1% [25–39 years], and 2.8% [15–24 years]; p-valve<0.0001). LTF was lower after vs. before ART initiation for all ages, with older adults experiencing less LTF than younger adults. Among 85,763 ART patients with baseline and follow-up CD4+ counts, adjusted average 12-month CD4+ response for older adults was 20.6 cells/mm3 lower than for adults 25–39 years of age (95% CI: 17.1–24.1). Conclusions The proportion of patients who are ≥50 years has increased over time and been driven by aging of the existing patient population. Older patients experienced less LTF, higher recorded mortality and less robust CD4+ response after ART initiation. Increased programmatic attention on older adults receiving HIV care in sub-Saharan Africa is warranted.

Provider-Initiated HIV Testing and Counselling in Rwanda: Acceptability among Clinic Attendees and Workers, Reasons for Testing and Predictors of Testing

Introduction Routine provider-initiated HIV testing and counselling (PITC) may increase HIV testing rates, but whether PITC is acceptable to health facility (HF) attendees is unclear. In the course of a PITC intervention study in Rwanda, we assessed the acceptability of PITC, reasons for being or not being tested and factors associated with HIV testing. Methods Attendees were systematically interviewed in March 2009 as they left the HF, regarding knowledge and acceptability of PITC, history of testing and reasons for being tested or not. Subsequently, PITC was introduced in 6 of the 8 HFs and a second round of interviews was conducted. Independent factors associated with testing were analysed using logistic regression. Randomly selected health care workers (HCWs) were also interviewed. Results 1772 attendees were interviewed. Over 95% agreed with the PITC policy, both prior to and after implementation of PITC policy. The most common reasons for testing were the desire to know one’s HIV status and having been offered an HIV test by an HCW. The most frequent reasons for not being tested were known HIV status and test not being offered. In multivariable analysis, PITC, age ≥15 years, and not having been previously tested were factors significantly associated with testing. Although workload was increased by PITC, HIV testing rates increased and HCWs overwhelmingly supported the policy. Conclusion Among attendees and HCWs in Rwandan clinics, the acceptability of PITC was very high. PITC appeared to increase testing rates and may be helpful in prevention and early access to treatment.

Adherence to tuberculosis treatment, sputum smear conversion and mortality: a retrospective cohort study in 48 Rwandan clinics.

Background Adherence to treatment and sputum smear conversion after 2 months of treatment are thought to be important for successful outcome of tuberculosis (TB) treatment. Methods Retrospective cohort study of new adult TB patients diagnosed in the first quarter of 2007 at 48 clinics in Rwanda. Data were abstracted from TB registers and individual treatment charts. Logistic regression analysis was done to examine associations between baseline demographic and clinical factors and three outcomes adherence, sputum smear conversion at two months, and death. Results Out of 725 eligible patients the treatment chart was retrieved for 581 (80%). Fifty-six (10%) of these patients took <90% of doses (defined as poor adherence). Baseline demographic characteristics were not associated with adherence to TB treatment, but adherence was lower among HIV patients not taking antiretroviral therapy (ART); p = 0.03). Sputum smear results around 2 months after start of treatment were available for 220 of 311 initially sputum-smear-positive pulmonary TB (PTB+) patients (71%); 175 (80%) had achieved sputum smear conversion. In multivariable analysis, baseline sputum smear grade (odds ratio [OR] = 2.7, 95% Confidence interval [CI] 1.1–6.6 comparing smear 3+ against 1+) and HIV infection (OR 3.0, 95%CI 1.3–6.7) were independent predictors for non-conversion at 2 months. Sixty-nine of 574 patients (12%) with known TB treatment outcomes had died. Besides other known determinants, poor adherence had an independent, strong effect on mortality (OR 3.4, 95%CI 1.4–7.8). Conclusion HIV infection is an important independent predictor of failure of sputum smear conversion at 2 months among PTB+ patients. Poor adherence to TB treatment is an important independent determinant of mortality.