Pushing the envelope through the Global Financing Facility: potential impact of mobilising additional support to scale-up life-saving interventions for women, children and adolescents in 50 high-burden countries.

INTRODUCTION: The Global Financing Facility (GFF) was launched to accelerate progress towards the Sustainable Development Goals (SDGs) through scaled and sustainable financing for Reproductive, Maternal, Newborn, Child and Adolescent Health and Nutrition (RMNCAH-N) outcomes. Our objective was to estimate the potential impact of increased resources available to improve RMNCAH-N outcomes, from expanding and scaling up GFF support in 50 high-burden countries. METHODS: The potential impact of GFF was estimated for the period 2017-2030. First, two scenarios were constructed to reflect conservative and ambitious assumptions around resources that could be mobilised by the GFF model, based on GFF Trust Fund resources of US$2.6 billion. Next, GFF impact was estimated by scaling up coverage of prioritised RMNCAH-N interventions under these resource scenarios. Resource availability was projected using an Excel-based model and health impacts and costs were estimated using the Lives Saved Tool (V.5.69 b9). RESULTS: We estimate that the GFF partnership could collectively mobilise US$50-75 billion of additional funds for expanding delivery of life-saving health and nutrition interventions to reach coverage of at least 70% for most interventions by 2030. This could avert 34.7 million deaths-including preventable deaths of mothers, newborns, children and stillbirths-compared with flatlined coverage, or 12.4 million deaths compared with continuation of historic trends. Under-five and neonatal mortality rates are estimated to decrease by 35% and 34%, respectively, and stillbirths by 33%. CONCLUSION: The GFF partnership through country- contextualised prioritisation and innovative financing could go a long way in increasing spending on RMNCAH-N and closing the existing resource gap. Although not all countries will reach the SDGs by relying on gains from the GFF platform alone, the GFF provides countries with an opportunity to significantly improve RMNCAH-N outcomes through achievable, well-directed changes in resource allocation.

Fertility and HIV following universal access to ART in Rwanda: a cross-sectional analysis of Demographic and Health Survey data.

BACKGROUND: HIV infection is linked to decreased fertility and fertility desires in sub-Saharan Africa due to biological and social factors. We investigate the relationship between HIV infection and fertility or fertility desires in the context of universal access to antiretroviral therapy introduced in 2004 in Rwanda. METHODS: We used data from 3532 and 4527 women aged 20-49 from the 2005 and 2010 Rwandan Demographic and Health Surveys (RDHS), respectively. The RDHSs included blood-tests for HIV, as well as detailed interviews about fertility, demographic and behavioral outcomes. In both years, multiple logistic regression was used to assess the association between HIV and fertility outcomes within three age categories (20-29, 30-39 and 40-49 years), controlling for confounders and compensating for the complex survey design. RESULTS: In 2010, we did not find a difference in the odds of pregnancy in the last 5 years between HIV-seropositive and HIV-seronegative women after controlling for potential biological and social confounders. Controlling for the same confounders, we found that HIV-seropositive women under age 40 were less likely to desire more children compared to HIV-seronegative women (20-29 years adjusted odds ratio (AOR) = 0.31, 95% CI: 0.17, 0.58; 30-39 years AOR = 0.24, 95% CI: 0.14, 0.43), but no difference was found among women aged 40 or older. No associations between HIV and fertility or fertility desire were found in 2005. CONCLUSIONS: These findings suggest no difference in births or current pregnancy among HIV-seropositive and HIV-seronegative women. That in 2010 HIV-seropositive women in their earlier childbearing years desired fewer children than HIV-seronegative women could suggest more women with HIV survived; and stigma, fear of transmitting HIV, or realism about living with HIV and prematurely dying from HIV may affect their desire to have children. These findings emphasize the importance of delivering appropriate information about pregnancy and childbearing to HIV-infected women, enabling women living with HIV to make informed decisions about their reproductive life.

High HIV prevalence and associated risk factors among female sex workers in Rwanda.

Human immunodeficiency virus (HIV) prevalence is often high among female sex workers (FSWs) in sub-Saharan Africa. Understanding the dynamics of HIV infection in this key population is critical to developing appropriate prevention strategies. We aimed to describe the prevalence and associated risk factors among a sample of FSWs in Rwanda from a survey conducted in 2010. A cross-sectional biological and behavioral survey was conducted among FSWs in Rwanda. Time-location sampling was used for participant recruitment from 4 to 18 February 2010. HIV testing was done using HIV rapid diagnostic tests (RDT) as per Rwandan national guidelines at the time of the survey. Elisa tests were simultaneously done on all samples tested HIV-positive on RDT. Proportions were used for sample description; multivariable logistic regression model was performed to analyze factors associated with HIV infection. Of 1338 women included in the study, 1112 consented to HIV testing, and the overall HIV prevalence was 51.0%. Sixty percent had been engaged in sex work for less than five years and 80% were street based. In multivariable logistic regression, HIV prevalence was higher in FSWs 25 years or older (adjusted odds ratio [aOR] = 1.83, 95% [confidence interval (CI): 1.42-2.37]), FSWs with consistent condom use in the last 30 days (aOR = 1.39, [95% CI: 1.05-1.82]), and FSWs experiencing at least one STI symptom in the last 12 months (aOR = 1.74 [95% CI: 1.34-2.26]). There was an inverse relationship between HIV prevalence and comprehensive HIV knowledge (aOR = 0.65, [95% CI: 0.48-0.88]). HIV prevalence was high among a sample of FSWs in Rwanda, and successful prevention strategies should focus on HIV education, treatment of sexually transmitted infections, and proper and consistent condom use using an outreach approach.

Operating Characteristics of a Tuberculosis Screening Tool for People Living with HIV in Out-Patient HIV Care and Treatment Services, Rwanda.

BACKGROUND: The World Health Organization (WHO) 2010 guidelines for intensified tuberculosis (TB) case finding (ICF) among people living with HIV (PLHIV) includes a recommendation that PLHIV receive routine TB screening. Since 2005, the Rwandan Ministry of Health has been using a five-question screening tool. Our study objective was to assess the operating characteristics of the tool designed to identify PLHIV with presumptive TB as measured against a composite reference standard, including bacteriologically confirmed TB. METHODS: In a cross-sectional study, the TB screening tool was routinely administered at enrolment in outpatient HIV care and treatment services at seven public health facilities. From March to September 2011, study enrollees were examined for TB disease irrespective of TB screening outcome. The examination consisted of a chest radiograph (CXR), three sputum smears (SS), sputum culture (SC) and polymerase chain reaction line-probe assay (Hain test). PLHIV were classified as having "laboratory-confirmed TB" with positive results on SS for acid-fast bacilli, SC on Lowenstein-Jensen medium, or a Hain test. RESULTS: Overall, 1,767 patients were enrolled and screened of which; 1,017 (57.6%) were female, median age was 33 (IQR, 27-41), and median CD4+ cell count was 385 (IQR, 229-563) cells/mm3. Of the patients screened, 138 (7.8%) were diagnosed with TB of which; 125 (90.5%) were laboratory-confirmed pulmonary TB. Of 404 (22.9%) patients who screened positive and 1,363 (77.1%) who screened negative, 79 (19.5%) and 59 (4.3%), respectively, were diagnosed with TB. For laboratory-confirmed TB, the tool had a sensitivity of 54.4% (95% CI 45.3-63.3), specificity of 79.5% (95% CI 77.5-81.5), PPV of 16.8% and NPV of 95.8%. CONCLUSION: TB prevalence among PLHIV newly enrolling into HIV care and treatment was 65 times greater than the overall population prevalence. However, the performance of the tool was poorer than the predicted performance of the WHO recommended TB screening questions.

HIV surveillance in Rwanda: readiness assessment to transition from antenatal care-based to prevention of mother-to-child transmission program-based HIV surveillance.

BACKGROUND: In 2013, the World Health Organization (WHO) recommended that for efficiency and ethical considerations, transitioning from antenatal clinic-based surveillance to prevention of mother-to-child transmission (PMTCT)-based routine data should be investigated. An assessment of the readiness for this transition was carried out in Rwanda in 2011 and 2013. METHODS: This assessment applied the WHO recommended method. Individual HIV rapid testing at site was compared to antenatal surveillance results at all existing 30 sites, involving 13 292 women. In addition, PMTCT HIV testing quality assurance and PMTCT routine data quality were assessed at 27 out of the 30 sites. RESULTS: All sentinel sites provided PMTCT services and had a high uptake of HIV testing (more than 90%). At all sites, PMTCT data were recorded in longitudinal and standardized antenatal clinic registers. Twenty-six out of 27 sites had HIV result completeness above 90%. A positive percentage agreement of 97.5% and negative percentage agreement of 99.9% were observed between routine PMTCT and sero-surveillance HIV test results. Of 27 sites, 25 scored more than 80% in all phases of HIV testing quality assurance. CONCLUSIONS: According to WHO standards, Rwanda antenatal care HIV sero-surveillance is ready to transition to PMTCT-based sero-surveillance.

A Mixed Outbreak of Epidemic Typhus Fever and Trench Fever in a Youth Rehabilitation Center: Risk Factors for Illness from a Case-Control Study, Rwanda, 2012.

In August 2012, laboratory tests confirmed a mixed outbreak of epidemic typhus fever and trench fever in a male youth rehabilitation center in western Rwanda. Seventy-six suspected cases and 118 controls were enrolled into an unmatched case-control study to identify risk factors for symptomatic illness during the outbreak. A suspected case was fever or history of fever, from April 2012, in a resident of the rehabilitation center. In total, 199 suspected cases from a population of 1,910 male youth (attack rate = 10.4%) with seven deaths (case fatality rate = 3.5%) were reported. After multivariate analysis, history of seeing lice in clothing (adjusted odds ratio [aOR] = 2.6, 95% confidence interval [CI] = 1.1-5.8), delayed (≥ 2 days) washing of clothing (aOR = 4.0, 95% CI = 1.6-9.6), and delayed (≥ 1 month) washing of beddings (aOR = 4.6, 95% CI = 2.0-11) were associated with illness, whereas having stayed in the rehabilitation camp for ≥ 6 months was protective (aOR = 0.20, 95% CI = 0.10-0.40). Stronger surveillance and improvements in hygiene could prevent future outbreaks.

Combination Antiretroviral Therapy for HIV in Rwandan Adults: Clinical Outcomes and Impact on Reproductive Health up to 24 Months.

Adult women (n = 113) and men (n = 100) initiating combination antiretroviral therapy (cART) and women not yet eligible for cART (n = 199) in Kigali, Rwanda, were followed for 6-24 months between 2007 and 2010. In the cART groups, 21% of patients required a drug change due to side effects and 11% of patients had virological failure (defined as >1,000 HIV RNA copies/mL) after 12 months of cART. About a third of the pregnancies since HIV diagnosis were unintended. The proportion of women in the pre-cART group using modern contraception other than condoms (50%) was similar to women in the general population, but this proportion was only 25% in women initiating cART. Of the women who carried at least one pregnancy to term since having been diagnosed HIV-positive, a third reported to have participated in a prevention-of-mother-to-child-transmission (PMTCT, option A) intervention. Many patients were coinfected with herpes simplex virus type 2 (79-92%), human papillomavirus (38-53%), and bacterial sexually transmitted infections (STIs) with no differences between groups. We applaud the Rwandan government for having strengthened family planning and PMTCT services and for having introduced HPV vaccination in recent years, but additional work is needed to strengthen STI and HPV-related cancer screening and management in the HIV-positive population.

Safety and effectiveness of combination antiretroviral therapy during the first year of treatment in HIV-1 infected Rwandan children: a prospective study.

BACKGROUND: With increased availability of paediatric combination antiretroviral therapy (cART) in resource limited settings, cART outcomes and factors associated with outcomes should be assessed. METHODS: HIV-infected children <15 years of age, initiating cART in Kigali, Rwanda, were followed for 18 months. Prospective clinical and laboratory assessments included weight-for-age (WAZ) and height-for-age (HAZ) z-scores, complete blood cell count, liver transaminases, creatinine and lipid profiles, CD4 T-cell count/percent, and plasma HIV-1 RNA concentration. Clinical success was defined as WAZ and WAZ >-2, immunological success as CD4 cells ≥500/mm3 and ≥25% for respectively children over 5 years and under 5 years, and virological success as a plasma HIV-1 RNA concentration <40 copies/mL. RESULTS: Between March 2008 and December 2009, 123 HIV-infected children were included. The median (interquartile (IQR) age at cART initiation was 7.4 (3.2, 11.5) years; 40% were <5 years and 54% were female. Mean (95% confidence interval (95%CI)) HAZ and WAZ at baseline were -2.01 (-2.23, -1.80) and -1.73 (-1.95, -1.50) respectively and rose to -1.75 (-1.98, -1.51) and -1.17 (-1.38, -0.96) after 12 months of cART. The median (IQR) CD4 T-cell values for children <5 and ≥5 years of age were 20% (13, 28) and 337 (236, 484) cells/mm3 respectively, and increased to 36% (28, 41) and 620 (375, 880) cells/mm3. After 12 months of cART, 24% of children had a detectable viral load, including 16% with virological failure (HIV-RNA>1000 c/mL). Older age at cART initiation, poor adherence, and exposure to antiretrovirals around birth were associated with virological failure. A third (33%) of children had side effects (by self-report or clinical assessment), but only 9% experienced a severe side effect requiring a cART regimen change. CONCLUSIONS: cART in Rwandan HIV-infected children was successful but success might be improved further by initiating cART as early as possible, optimizing adherence and optimizing management of side effects.

"Let's talk about sex": a qualitative study of Rwandan adolescents' views on sex and HIV.

OBJECTIVE: This qualitative study explored the views and experiences of adolescents with perinatally acquired HIV in Kigali, Rwanda, regarding sex, love, marriage, children and hope for the future. DESIGN: The study enrolled 42 adolescents who had received combination antiretroviral therapy for at least 12 months, and a selection of their primary caregivers. Study methods included 3 multiple day workshops consisting of role-playing and focus group discussions (FGDs) with adolescents, 8 in-depth interviews with adolescents, and one FGD with caregivers. RESULTS: The adolescents reported experiencing similar sexual needs and dilemmas as most other adolescents, but with an added layer of complexity due to fears related to HIV transmission and/or rejection by partners. They desired more advice from their parents/caregivers on these topics. Although they struggled with aspects of sex, love, marriage and having children, most agreed that they would find love, be married and have children in the future. The two most discussed HIV-related anxieties were how and when to disclose to a (potential) sex/marriage partner and whether to have children. However, most adolescents felt that they had a right to love and be loved, and were aware of prevention-of-mother-to-child-transmission (PMTCT) options in Rwanda. Adolescents generally spoke about their future role in society in a positive manner. CONCLUSION: Strengthening the life skills of HIV-positive adolescents, especially around HIV disclosure and reduction of HIV transmission, as well as the support skills of parents/caregivers, may not only reduce onward HIV transmission but also improve quality of life by reducing anxiety.

Long-term effectiveness of combination antiretroviral therapy and prevalence of HIV drug resistance in HIV-1-infected children and adolescents in Rwanda.

OBJECTIVE: To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy. METHODS: A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed. RESULTS: Four hundred twenty-four patients were enrolled with a median age of 10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17% underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5 years had CD4 ≥350 cells/mm and in 74% (95% confidence interval: 62-84) of younger children CD4% was ≥25. CD4 values and age at combination antiretroviral therapy initiation were independently associated with CD4 outcomes; 124 (29%) had HIV-1 RNA ≥1000 copies/mL, with no significant predictors. Sensitivity for weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15-42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52 samples tested, ≥1 mutations were observed in 91% (nucleoside reverse transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16 (31%) and ≥3 thymidine analogue-associated mutations in 7 (13%). CONCLUSION: Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of children with treatment failure in whom genotyping was performed demonstrated multiple HIV drug resistance mutations. Neither clinical condition nor CD4 cells were good indicators for treatment failure.

Towards the burden of human leptospirosis: duration of acute illness and occurrence of post-leptospirosis symptoms of patients in the Netherlands.

BACKGROUND: Leptospirosis is a global zoonotic disease. Although important for the assessment of the burden of leptospirosis, data on the duration of the illness and the occurrence of post-leptospirosis complaints are not well documented. Hence the main objective of this study was to estimate the occurrence of persistent complaints and duration of hospital stay in laboratory confirmed leptospirosis patients in the Netherlands during 1985 to 2010. Additionally, several risk factors potentially impacting on the occurrence of post-leptospirosis complaints were investigated. METHODS/PRINCIPAL FINDINGS: The duration of the acute phase of leptospirosis was 16 days (IQR 12-23); 10 days (IQR 7-16) were spent hospitalized. Eighteen fatal cases were excluded from this analysis. Complaints of leptospirosis patients by passive case investigations (CPC) derived from files on ambulant consultations occurring one month after hospital discharge, revealed persistent complaints in 108 of 236 (45.8%) laboratory confirmed cases. Data on persistent complaints after acute leptospirosis (PCAC), assessed in 225 laboratory confirmed leptospirosis cases collected through questionnaires during 1985-1993, indicated 68 (30.2%) PCAC cases. Frequently reported complaints included (extreme) fatigue, myalgia, malaise, headache, and a weak physical condition. These complaints prolonged in 21.1% of the cases beyond 24 months after onset of disease. There was no association between post-leptospirosis complaints and hospitalization. However, individuals admitted at the intensive care unit (ICU) were twice as likely to have continuing complaints after discharge adjusting for age and dialysis (OR 2.0 95% CI 0.8-4.8). No significant association could be found between prolongation of complaints and infecting serogroup, although subgroup analysis suggest that infection with serogroups Sejroe (OR 4.8, 95%CI 0.9-27.0) and icterohaemorrhagiae (OR 2.0, 95%CI 0.9-4.3 CI) are more likely to result in CPC than infections with serogroup Grippotyphosa. CONCLUSION/SIGNIFICANCE: In addition to the acute disease, persistent complaints have an impact on the burden of leptospirosis.

Malaria prevalence, spatial clustering and risk factors in a low endemic area of Eastern Rwanda: a cross sectional study.

BACKGROUND: Rwanda reported significant reductions in malaria burden following scale up of control intervention from 2005 to 2010. This study sought to; measure malaria prevalence, describe spatial malaria clustering and investigate for malaria risk factors among health-centre-presumed malaria cases and their household members in Eastern Rwanda. METHODS: A two-stage health centre and household-based survey was conducted in Ruhuha sector, Eastern Rwanda from April to October 2011. At the health centre, data, including malaria diagnosis and individual level malaria risk factors, was collected. At households of these Index cases, a follow-up survey, including malaria screening for all household members and collecting household level malaria risk factor data, was conducted. RESULTS: Malaria prevalence among health centre attendees was 22.8%. At the household level, 90 households (out of 520) had at least one malaria-infected member and the overall malaria prevalence for the 2634 household members screened was 5.1%. Among health centre attendees, the age group 5-15 years was significantly associated with an increased malaria risk and a reported ownership of ≥4 bednets was significantly associated with a reduced malaria risk. At the household level, age groups 5-15 and >15 years and being associated with a malaria positive index case were associated with an increased malaria risk, while an observed ownership of ≥4 bednets was associated with a malaria risk-protective effect. Significant spatial malaria clustering among household cases with clusters located close to water- based agro-ecosystems was observed. CONCLUSIONS: Malaria prevalence was significantly higher among health centre attendees and their household members in an area with significant household spatial malaria clustering. Circle surveillance involving passive case finding at health centres and proactive case detection in households can be a powerful tool for identifying household level malaria burden, risk factors and clustering.

Low primary and secondary HIV drug-resistance after 12 months of antiretroviral therapy in human immune-deficiency virus type 1 (HIV-1)-infected individuals from Kigali, Rwanda.

Treatment outcomes of HIV patients receiving antiretroviral therapy (ART) in Rwanda are scarcely documented. HIV viral load (VL) and HIV drug-resistance (HIVDR) outcomes at month 12 were determined in a prospective cohort study of antiretroviral-naïve HIV patients initiating first-line therapy in Kigali. Treatment response was monitored clinically and by regular CD4 counts and targeted HIV viral load (VL) to confirm drug failure. VL measurements and HIVDR genotyping were performed retrospectively on baseline and month 12 samples. One hundred and fifty-eight participants who completed their month 12 follow-up visit had VL data available at month 12. Most of them (88%) were virologically suppressed (VL≤1000 copies/mL) but 18 had virological failure (11%), which is in the range of WHO-suggested targets for HIVDR prevention. If only CD4 criteria had been used to classify treatment response, 26% of the participants would have been misclassified as treatment failure. Pre-therapy HIVDR was documented in 4 of 109 participants (3.6%) with an HIVDR genotyping results at baseline. Eight of 12 participants (66.7%) with virological failure and HIVDR genotyping results at month 12 were found to harbor mutation(s), mostly NNRTI resistance mutations, whereas 4 patients had no HIVDR mutations. Almost half (44%) of the participants initiated ART at CD4 count ≤200 cell/µl and severe CD4 depletion at baseline (<50 cells/µl) was associated with virological treatment failure (p = 0.008). Although the findings may not be generalizable to all HIV patients in Rwanda, our data suggest that first-line ART regimen changes are currently not warranted. However, the accumulation of acquired HIVDR mutations in some participants underscores the need to reinforce HIVDR prevention strategies, such as increasing the availability and appropriate use of VL testing to monitor ART response, ensuring high quality adherence counseling, and promoting earlier identification of HIV patients and enrollment into HIV care and treatment programs.

Prospective evaluation of three rapid diagnostic tests for diagnosis of human leptospirosis.

BACKGROUND: Diagnosis of leptospirosis by the microscopic agglutination test (MAT) or by culture is confined to specialized laboratories. Although ELISA techniques are more common, they still require laboratory facilities. Rapid Diagnostic Tests (RDTs) can be used for easy point-of-care diagnosis. This study aims to evaluate the diagnostic performance of the RDTs LeptoTek Dri Dot, LeptoTek Lateral Flow, and Leptocheck-WB, prospectively. METHODOLOGY: During 2001 to 2012, one or two of the RDTs at the same time have been applied prior to routine diagnostics (MAT, ELISA and culture) on serum specimens from participants sent in for leptospirosis diagnosis. The case definition was based on MAT, ELISA and culture results. Participants not fulfilling the case definition were considered not to have leptospirosis. The diagnostic accuracy was determined based on the 1(st) submitted sample and paired samples, either in an overall analysis or stratified according to days post onset of illness. RESULTS: The overall sensitivity and specificity for the LeptoTek Dri Dot was 75% respectively 96%, for the LeptoTek Lateral Flow 78% respectively 95%, and for the Leptocheck-WB 78% respectively 98%. Based on the 1(st) submitted sample the sensitivity was low (51% for LeptoTek Dri Dot, 69% for LeptoTek Lateral Flow, and 55% for Leptocheck-WB), but substantially increased when the results of paired samples were combined, although accompanied by a lower specificity (82% respectively 91% for LeptoTek Dri Dot, 86% respectively 84% for LeptoTek Lateral Flow, and 80% respectively 93% for Leptocheck-WB). CONCLUSIONS: All three tests present antibody tests contributing to the diagnosis of leptospirosis, thus supporting clinical suspicion and contributing to awareness. Since the overall sensitivity of the tested RDTs did not exceed 80%, one should be cautious to rely only on an RDT result, and confirmation by reference tests is strongly recommended.

High seroprevalence of HBV and HCV infection in HIV-infected adults in Kigali, Rwanda.

BACKGROUND: Data on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce. METHODS: HBV status was assessed at baseline and Month 12, and anti-HCV antibodies at baseline, in a prospective cohort study of HIV-infected patients in Kigali, Rwanda: 104 men and 114 women initiating antiretroviral therapy (ART) at baseline, and 200 women not yet eligible for ART. RESULTS: Baseline prevalence of active HBV infection (HBsAg positive), past or occult HBV infection (anti-HBc positive and HBsAg negative) and anti-HCV was 5.2%, 42.9%, and 5.7%, respectively. The active HBV incidence rate was 4.2/1,000 person years (PY). In a multivariable logistic regression model using baseline data, participants with WHO stage 3 or 4 HIV disease were 4.19 times (95% CI 1.21-14.47) more likely to have active HBV infection, and older patients were more likely to have evidence of past exposure to HBV (aRR 1.03 per year; 95%CI 1.01-1.06). Older age was also positively associated with having anti-HCV antibodies (aOR 1.09; 95%CI 1.04-1.14) while having a higher baseline HIV viral load was negatively associated with HCV (aOR 0.60; 95% CI 0.40-0.98). The median CD4 increase during the first 12 months of ART was lower for those with active HBV infection or anti-HCV at baseline. Almost all participants (88%) with active HBV infection who were on ART were receiving lamivudine monotherapy for HBV. CONCLUSION: HBV and HCV are common in HIV-infected patients in Rwanda. Regular HBsAg screening is needed to ensure that HIV-HBV co-infected patients receive an HBV-active ART regimen, and the prevalence of occult HBV infection should be determined. Improved access to HBV vaccination is recommended. Active HCV prevalence and incidence should be investigated further to determine whether HCV RNA PCR testing should be introduced in Rwanda.

Living situation affects adherence to combination antiretroviral therapy in HIV-infected adolescents in Rwanda: a qualitative study.

INTRODUCTION: Adherence to combination antiretroviral therapy (cART) is vital for HIV-infected adolescents for survival and quality of life. However, this age group faces many challenges to remain adherent. We used multiple data sources (role-play, focus group discussions (FGD), and in-depth interviews (IDI)) to better understand adherence barriers for Rwandan adolescents. Forty-two HIV positive adolescents (ages 12-21) and a selection of their primary caregivers were interviewed. All were perinatally-infected and received (cART) for ≥ 12 months. Topics discussed during FGDs and IDIs included learning HIV status, disclosure and stigma, care and treatment issues, cART adherence barriers. RESULTS: Median age was 17 years, 45% female, 45% orphaned, and 48% in boarding schools. We identified three overarching but inter-related themes that appeared to influence adherence. Stigma, perceived and experienced, and inadvertent disclosure of HIV status hampered adolescents from obtaining and taking their drugs, attending clinic visits, carrying their cARTs with them in public. The second major theme was the need for better support, in particular for adolescents with different living situations, (orphanages, foster-care, and boarding schools). Lack of privacy to keep and take medication came out as major barrier for adolescents living in congested households, as well the institutionalization of boarding schools where privacy is almost non-existent. The third important theme was the desire to be 'normal' and not be recognized as an HIV-infected individual, and to have a normal life not perturbed by taking a regimen of medications or being forced to disclose where others would treat them differently. CONCLUSIONS: We propose better management of HIV-infected adolescents integrated into boarding school, orphanages, and foster care; training of school-faculty on how to support students and allow them privacy for taking their medications. To provide better care and support, HIV programs should stimulate caregivers of HIV-infected adolescents to join them for their clinic visits.

Human leptospirosis trends, the Netherlands, 1925-2008.

To increase knowledge of leptospirosis in the Netherlands and identify changing trends of this disease over time, we analyzed historical passive surveillance reports for an 84-year period (1925-2008). We found that 2,553 mainly severe leptospirosis cases were diagnosed (average annual incidence rate 0.25 cases/100,000 population). The overall case-fatality rate for patients with reported leptospirosis was 6.5% but decreased over the period, probably because of improved treatment. Ninety percent of reported leptospirosis cases were in male patients. Most autochthonous leptospirosis infections were associated with recreational exposures, but 15.5% of the cases were attributed to accidents that resulted in injury and to concomitant water contact. Since the end of the 1950s, the proportion of imported infections gradually increased, reaching 53.1% of the total during 2005-2008. Most (80.1%) imported infections were associated with sporting and adventurous vacation activities.

Antiretroviral therapy drug adherence in Rwanda: perspectives from patients and healthcare workers using a mixed-methods approach.

Rwanda has achieved high enrollment into antiretroviral therapy (ART) programs but data on adherence after enrollment are not routinely collected. We used a mixed-methods approach (standardized questionnaires, pill counts, focus group discussions, and in-depth interviews) to determine levels of and barriers to ART adherence from the perspective of both patients and healthcare workers (HCW). Data were available from 213 patients throughout the first year on ART; 58 of them and 23 HCW participated in a qualitative sub-study. Self-reported adherence was high (96% of patients reporting more than 95% adherence), but adherence by pill count was significantly lower, especially in the first 3 months. In the standardized interviews, patients mostly reported that they "simply forgot" or "were away from home" as reasons for nonadherence. The qualitative research identified three interrelated constructs that appeared to negatively influence adherence: stigma, difficulty coming to terms with illness, and concealment of illness. Both standardized questionnaires and the qualitative research identified poverty, disruption to daily routines, factors related to regimen complexity and side effects, and service-related factors as barriers to adherence. We conclude that regular triangulation of different sources of adherence data is desirable to arrive at more realistic estimates. We propose that program monitoring and evaluation cycles incorporate more in-depth research to better understand concerns underlying reasons for nonadherence reported in routine monitoring.

Hepatitis B virus prevalence and vaccine response in HIV-infected children and adolescents on combination antiretroviral therapy in Kigali, Rwanda.

OBJECTIVE: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in a cohort of HIV-infected Rwandan children and adolescents on combination antiretroviral therapy (cART), and the success rate of HBV vaccination in those children found to be HBV negative. METHODS: HIV-infected children and adolescents (age 8-17 years) receiving cART with CD4 T-cells count ≥200 cells/mm and/or ≥15% and without prior HBV vaccination (by history, vaccination cards and clinic records) underwent serologic testing for past (negative HBV surface antigen [HBsAg] with positive antibody to HBV core antigen [cAb] and to HBsAg [anti-HBs]) or active HBV infection (positive HBsAg). Children with any positive HBV serologic tests were excluded from further vaccination; all others completed 3 HBV immunizations with 10 µg of ENGERIX-B. Anti-HBs titer was measured 4-6 weeks after the last immunization. RESULTS: Of 88 children, 6 (7%) children had active HBV infection and 8 (9%) had past HBV infection. The median (interquartile range) age, CD4 T-cell count and cART duration were 12.3 (10.1-13.9) years, 626 (503 to 942) cells/mm and 1.9 (1.5-2.7) years, respectively. Seventeen children had detectable plasma HIV-1 RNA. Seventy-3 children completed 3 immunizations with median (interquartile range) postimmunization anti-HBs concentration of 151 mIU/mL (1.03-650). Overall, 52 children (71%, 95% confidence interval: 61-82) developed a protective anti-HBs response. HIV-1 RNA and CD4 T-cell count were independent predictors of a protective anti-HBs response. Protective anti-HBs response was achieved in 82% of children with undetectable HIV-1 RNA and 77% with CD4 T cells ≥350/mm. CONCLUSIONS: The substantial HBV prevalence in this cohort suggests that HIV-infected Rwandan children should be screened for HBV before cART initiation. HIV viral suppression and CD4 T cells ≥350/mm favored the likelihood of a protective response after HBV vaccination.