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Leptospirosis is a zoonotic disease caused by infection with Leptospira spp. bacteria (1). Pathogenic leptospires live in the kidneys of many mammalian hosts, including rodents, insectivores, and livestock. Leptospires are [...]

A study to compare patient outcome, health care utilization, and costs of on-demand and planned relaparotomy in patients suffering from severe peritonitis was conducted. Results found that in both types of treatment, the mortality rate was the same but observed a substantial reduction in relaparotomies, health care utilization, and medical costs.

Abstract Background During pregnancy, malaria infection with Plasmodium falciparum or Plasmodium vivax is related to adverse maternal health and poor birth outcomes. Diagnosis of malaria, during pregnancy, is complicated by the absence or low parasite densities in peripheral blood. Diagnostic methods, other than microscopy, are needed for detection of placental malaria. Therefore, the diagnostic accuracy of rapid diagnostic tests (RDTs), detecting antigen, and molecular techniques (PCR), detecting DNA, for the diagnosis of Plasmodium infections in pregnancy was systematically reviewed. Methods MEDLINE, EMBASE and Web of Science were searched for studies assessing the diagnostic accuracy of RDTs, PCR, microscopy of peripheral and placental blood and placental histology for the detection of malaria infection (all species) in pregnant women. Results The results of 49 studies were analysed in metandi (Stata), of which the majority described P. falciparum infections. Although both placental and peripheral blood microscopy cannot reliably replace histology as a reference standard for placental P. falciparum infection, many studies compared RDTs and PCR to these tests. The proportion of microscopy positives in placental blood (sensitivity) detected by peripheral blood microscopy, RDTs and PCR are respectively 72% [95% CI 62-80], 81% [95% CI 55-93] and 94% [95% CI 86-98]. The proportion of placental blood microscopy negative women that were negative in peripheral blood microscopy, RDTs and PCR (specificity) are 98% [95% CI 95-99], 94% [95% CI 76-99] and 77% [95% CI 71-82]. Based on the current data, it was not possible to determine if the false positives in RDTs and PCR are caused by sequestered parasites in the placenta that are not detected by placental microscopy. Conclusion The findings suggest that RDTs and PCR may have good performance characteristics to serve as alternatives for the diagnosis of malaria in pregnancy, besides any other limitations and practical considerations concerning the use of these tests. Nevertheless, more studies with placental histology as reference test are urgently required to reliably determine the accuracy of RDTs and PCR for the diagnosis of placental malaria. P. vivax-infections have been neglected in diagnostic test accuracy studies of malaria in pregnancy.

Abstract Background To compare health related quality of life (HR-QoL) in patients surgically treated for secondary peritonitis to that of a healthy population. And to prospectively identify factors associated with poorer (lower) HR-QoL. Design A prospective cohort of secondary peritonitis patients was mailed the EQ-5D and EQ-VAS 6-months following initial laparotomy. Setting Multicenter study in two academic and seven regional teaching hospitals. Patients 130 of the 155 eligible patients (84%) responded to the HR-QoL questionnaires. Results HR-QoL was significantly worse on all dimensions in peritonitis patients than in a healthy reference population. Peritonitis characteristics at initial presentation were not associated with HR-QoL at six months. A more complicated course of the disease leading to longer hospitalization times and patients with an enterostomy had a negative impact on the mobility (p = 0.02), self-care (p < 0.001) and daily activities: (p = 0.01). In a multivariate analysis for the EQ-VAS every doubling of hospital stay decreases the EQ-VAS by 3.8 points (p = 0.015). Morbidity during the six-month follow-up was not found to be predictive for the EQ-5D or EQ-VAS. Conclusion Six months following initial surgery, patients with secondary peritonitis report more problems in HR-QoL than a healthy reference population. Unfavorable disease characteristics at initial presentation were not predictive for poorer HR-QoL, but a more complicated course of the disease was most predictive of HR-QoL at 6 months.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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/mm3respectively, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

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 ≤200cell/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. [ABSTRACT FROM AUTHOR]

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 1st 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 1st 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. Author Summary: Leptospirosis is one of the world's most spread zoonoses causing acute fever. The illness can rapidly develop into a severe, potentially fatal, form with a high mortality rate. Laboratory tests are needed to confirm the diagnosis. Culturing leptospires from patient material can take months to grow. Therefore, most used laboratory tests are based on detection of antibodies against leptospires. The microscopic agglutination test is considered the reference standard but is only performed at specialized laboratories. In this study, we measured the diagnostic accuracy of three rapid diagnostic tests (RDTs) by doing a prospective evaluation during 11 years. These tests produce results within 15 minutes. The overall sensitivities (77%) and specificities (96%) were similar for the RDTs. Evaluating the first submitted specimen resulted in lower sensitivities (51% for LeptoTek Dri Dot, 69% for LeptoTek Lateral Flow, and 55% for Leptocheck-WB). When paired specimens were evaluated, the sensitivity increased although the specificity decreased (82% respectively 91% for LeptoTek Dri Dot, 86% respectively 84% for LeptoTek Lateral Flow, and 80% respectively 93% for Leptocheck-WB). Based on these results confirmation by reference tests is still strongly recommended, although the RDTs contribute to the diagnosis of leptospirosis, thus supporting clinical suspicion and contributing to awareness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study aimed at describing the genetic subtype distribution of HIV-1 strains circulating in Kigali and their epidemiological link with the HIV-1 strains from the five countries surrounding Rwanda. One hundred and thirty eight pol (RT and PR) sequences from 116 chronically- and 22 recently-infected antiretroviral therapy (ART)-naïve patients from Kigali were generated and subjected to HIV drug resistance (HIV-DR), phylogenetic and recombinant analyses in connection with 366 reference pol sequences from Rwanda, Burundi, Kenya, Democratic Republic of Congo, Tanzania and Uganda (Los Alamos database). Among the Rwandan samples, subtype A1 predominated (71.7%), followed by A1/C recombinants (18.1%), subtype C (5.8%), subtype D (2.9%), one A1/D recombinant (0.7%) and one unknown subtype (0.7%). Thirteen unique and three multiple A1/C recombinant forms were identified. No evidence for direct transmission events was found within the Rwandan strains. Molecular characteristics of HIV-1 were similar between chronically and recently-infected individuals and were not significantly associated with demographic or social factors. Our report suggests that the HIV-1 epidemic in Kigali is characterized by the emergence of A1/C recombinants and is not phylogenetically connected with the HIV-1 epidemic in the five neighboring countries. The relatively low level of transmitted HIV-DR mutations (2.9%) reported here indicates the good performance of the ART programme in Rwanda. However, the importance of promoting couples' counseling, testing and disclosure during HIV prevention strategies is highlighted. [ABSTRACT FROM AUTHOR]

Background: There is dilemma as to whether patients infected with the Human Immunodeficiency Virus (HIV) requiring implant orthopaedic surgery are at an increased risk for post-operative surgical site infection (SSI). We conducted a systematic review to determine the effect of HIV on the risk of post-operative SSI and sought to determine if this risk is altered by antibiotic use beyond 24 hours. Methods: We searched electronic databases, manually searched citations from relevant articles, and reviewed conference proceedings. The risk of postoperative SSI was pooled using Mantel-Haenszel method. Results: We identified 18 cohort studies with 16 mainly small studies, addressing the subject. The pooled risk ratio of infection in the HIV patients when compared to non-HIV patients was 1.8 (95% Confidence Interval [CI] 1.3--2.4), in studies in Africa this was 2.3 (95% CI 1.5--3.5). In a sensitivity analysis the risk ratio was reduced to 1.4 (95% CI 0.5--3.8). The risk ratio of infection in patients receiving prolonged antibiotics compared to patients receiving antibiotics for up to 24 hours was 0.7 (95% CI 0.1--4.2). Conclusions: The results may indicate an increased risk in HIV infected patients but these results are not robust and inconclusive after conducting the sensitivity analysis removing poor quality studies. There is need for larger good quality studies to provide conclusive evidence. To better develop surgical protocols, further studies should determine the effect of reduced CD4 counts, viral load suppression and prolonged antibiotics on the risk for infection. [ABSTRACT FROM AUTHOR]

Background: A range of molecular amplification techniques have been developed for the diagnosis of Human African Trypanosomiasis (HAT); however, careful evaluation of these tests must precede implementation to ensure their high clinical accuracy. Here, we investigated the diagnostic accuracy of molecular amplification tests for HAT, the quality of articles and reasons for variation in accuracy. Methodology: Data from studies assessing diagnostic molecular amplification tests were extracted and pooled to calculate accuracy. Articles were included if they reported sensitivity and specificity or data whereby values could be calculated. Study quality was assessed using QUADAS and selected studies were analysed using the bivariate random effects model. Results: 16 articles evaluating molecular amplification tests fulfilled the inclusion criteria: PCR (n = 12), NASBA (n = 2), LAMP (n = 1) and a study comparing PCR and NASBA (n = 1). Fourteen articles, including 19 different studies were included in the meta-analysis. Summary sensitivity for PCR on blood was 99.0% (95% CI 92.8 to 99.9) and the specificity was 97.7% (95% CI 93.0 to 99.3). Differences in study design and readout method did not significantly change estimates although use of satellite DNA as a target significantly lowers specificity. Sensitivity and specificity of PCR on CSF for staging varied from 87.6% to 100%, and 55.6% to 82.9% respectively. Conclusion: Here, PCR seems to have sufficient accuracy to replace microscopy where facilities allow, although this conclusion is based on multiple reference standards and a patient population that was not always representative. Future studies should, therefore, include patients for which PCR may become the test of choice and consider well designed diagnostic accuracy studies to provide extra evidence on the value of PCR in practice. Another use of PCR for control of disease could be to screen samples collected from rural areas and test in reference laboratories, to spot epidemics quickly and direct resources appropriately. Author Summary: A range of molecular amplification techniques has been developed for the diagnosis of HAT, with polymerase chain reaction (PCR) at the forefront. As laboratory strengthening in endemic areas increases, it is expected that the applicability of molecular tests will increase. However, careful evaluation of these tests against the current reference standard, microscopy, must precede implementation. Therefore, we have investigated the published diagnostic accuracy of molecular amplification tests for HAT compared to microscopy for both initial diagnosis as well as for disease staging. Here, PCR tests seem to have an acceptably high specificity and sensitivity for diagnosis of stage I HAT. This conclusion is, however, based on multiple-microscopy based techniques as reference standards, which may have low sensitivity, and a patient population that was not always representative. Future studies should, therefore, first and foremost include those patients for which PCR may become the test of choice. More certainty about the practical value of PCR tests for HAT diagnosis should come from non-accuracy design studies, like feasibility or cost-effectiveness studies. [ABSTRACT FROM AUTHOR]

Available serological diagnostics do not allow the confirmation of clinically suspected leptospirosis at the early acute phase of illness. Several conventional and real-time PCRs for the early diagnosis of leptospirosis have been described but these have been incompletely evaluated. We developed a SYBR Green-based real-time PCR targeting secY and validated it according to international guidelines. To determine the analytical specificity, DNA from 56 Leptospira strains belonging to pathogenic, non-pathogenic and intermediate Leptospira spp. as well as 46 other micro-organisms was included in this study. All the pathogenic Leptospira gave a positive reaction. We found no cross-reaction with saprophytic Leptospira and other micro-organisms, implying a high analytical specificity. The analytical sensitivity of the PCR was one copy per reaction from cultured homologous strain M 20 and 1.2 and 1.5 copy for heterologous strains 1342 K and Sarmin, respectively. In spiked serum & blood and kidney tissue the sensitivity was 10 and 20 copies for M 20, 15 and 30 copies for 1342 K and 30 and 50 copies for Sarmin. To determine the diagnostic sensitivity (DSe) and specificity (DSp), clinical blood samples from 26 laboratory-confirmed and 107 negative patients suspected of leptospirosis were enrolled as a prospective consecutive cohort. Based on culture as the gold standard, we found a DSe and DSp of 100% and 93%, respectively. All eight PCR positive samples that had a negative culture seroconverted later on, implying a higher actual DSp. When using culture and serology as the gold standard, the DSe was lower (89%) while the DSp was higher (100%). DSe was 100% in samples collected within the first - for treatment important - 4 days after onset of the illness. Reproducibility and repeatability of the assay, determined by blind testing kidney samples from 20 confirmed positive and 20 negative rodents both appeared 100%. In conclusion we have described for the first time the development of a robust SYBR Green real-time PCR for the detection of pathogenic Leptospira combined with a detailed assessment of its clinical accuracy, thus providing a method for the early diagnosis of leptospirosis with a well-defined satisfactory performance. [ABSTRACT FROM AUTHOR]

Background: To compare health related quality of life (HR-QoL) in patients surgically treated for secondary peritonitis to that of a healthy population. And to prospectively identify factors associated with poorer (lower) HR-QoL. Design: A prospective cohort of secondary peritonitis patients was mailed the EQ-5D and EQVAS 6-months following initial laparotomy. Setting: Multicenter study in two academic and seven regional teaching hospitals. Patients: 130 of the 155 eligible patients (84%) responded to the HR-QoL questionnaires. Results: HR-QoL was significantly worse on all dimensions in peritonitis patients than in a healthy reference population. Peritonitis characteristics at initial presentation were not associated with HR-QoL at six months. A more complicated course of the disease leading to longer hospitalization times and patients with an enterostomy had a negative impact on the mobility (p = 0.02), self-care (p < 0.001) and daily activities: (p = 0.01). In a multivariate analysis for the EQ-VAS every doubling of hospital stay decreases the EQ-VAS by 3.8 points (p = 0.015). Morbidity during the six-month follow-up was not found to be predictive for the EQ-5D or EQ-VAS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Competing interests: MEBC and KRB are employees of the Global Financing Facility, and DGW and SM work for the Bill & Melinda Gates Foundation, an investor in the GFF.

This study evaluated mid-dosing interval efavirenz plasma concentrations and the influence of CYP2B6 polymorphisms in relation to efficacy, tolerability, and adherence in 97 Rwandan HIV-infected children (3-16 years). Plasma drug concentrations and CYP2B6 polymorphisms were determined. Ten children were excluded for nonadherence. Large intersubject variability in efavirenz plasma concentrations was found. Of the 87 remaining, efavirenz concentrations were therapeutic, supratherapeutic, and subtherapeutic in 67%, 20%, and 14%, respectively. No associations were found between efavirenz concentrations and central nervous system disturbances or virologic failure. Minor allele frequencies were 0.32 (516G>T), 0.33 (785A>G), and 0.09 (983T>C). Polymorphisms in CYP2B6 were strongly associated with high efavirenz levels.

Introduction: Results of the first randomized trial comparing on-demand versus planned-relaparotomy strategy in patients with severe peritonitis (RELAP trial) indicated no clear differences in primary outcomes. We now report the full economic evaluation for this trial, including detailed methods, nonmedical costs, further differentiated cost calculations, and robustness of different assumptions in sensitivity analyses., Methods: An economic evaluation was conducted from a societal perspective alongside a randomized controlled trial in 229 patients with severe secondary peritonitis and an acute physiology and chronic health evaluation (APACHE)-II score >or=11 from two academic and five regional teaching hospitals in the Netherlands. After the index laparotomy, patients were randomly allocated to an on-demand or a planned-relaparotomy strategy. Primary resource-utilization data were used to estimate mean total costs per patient during the index admission and after discharge until 1 year after the index operation. Overall differences in costs between the on-demand relaparotomy strategy and the planned strategy, as well as relative differences across several clinical subgroups, were evaluated., Results: Costs were substantially lower in the on-demand group (mean, 65,768 euro versus 83,450 euro per patient in the planned group; mean absolute difference, 17,682 euro; 95% CI, 5,062 euro to e29,004 euro). Relative differences in mean total costs per patient (approximately 21%) were robust to various alternative assumptions. Planned relaparotomy consistently generated more costs across the whole range of different courses of disease (quick recovery and few resources used on one end of the spectrum; slow recovery and many resources used on the other end). This difference in costs between the two surgical strategies also did not vary significantly across several clinical subgroups., Conclusions: The reduction in societal costs renders the on-demand strategy a more-efficient relaparotomy strategy in patients with severe peritonitis. These differences were found across the full range of healthcare resources as well as across patients with different courses of disease., Trial Registration: ISRCTN51729393.

Introduction: The aim of this study was to determine the long-term prevalence of post-traumatic stress disorder (PTSD) symptomology in patients following secondary peritonitis and to determine whether the prevalence of PTSD-related symptoms differed between patients admitted to the intensive care unit (ICU) and patients admitted only to the surgical ward., Method: A retrospective cohort of consecutive patients treated for secondary peritonitis was sent a postal survey containing a self-report questionnaire, namely the Post-traumatic Stress Syndrome 10-question inventory (PTSS-10). From a database of 278 patients undergoing surgery for secondary peritonitis between 1994 and 2000, 131 patients were long-term survivors (follow-up period at least four years) and were eligible for inclusion in our study, conducted at a tertiary referral hospital in Amsterdam, The Netherlands., Results: The response rate was 86%, yielding a cohort of 100 patients; 61% of these patients had been admitted to the ICU. PTSD-related symptoms were found in 24% (95% confidence interval 17% to 33%) of patients when a PTSS-10 score of 35 was chosen as the cutoff, whereas the prevalence of PTSD symptomology when borderline patients scoring 27 points or more were included was 38% (95% confidence interval 29% to 48%). In a multivariate analyses controlling for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of relaparotomies and length of hospital stay, the likelihood of ICU-admitted patients having PTSD symptomology was 4.3 times higher (95% confidence interval 1.11 to 16.5) than patients not admitted to the ICU, using a PTSS-10 score cutoff of 35 or greater. Older patients and males were less likely to report PTSD symptoms., Conclusion: Nearly a quarter of patients receiving surgical treatment for secondary peritonitis developed PTSD symptoms. Patients admitted to the ICU were at significantly greater risk for having PTSD symptoms after adjusting for baseline differences, in particular age.