Chronic High-Level Parasitemia in HIV-Infected Individuals With or Without Visceral Leishmaniasis in an Endemic Area in Northwest Ethiopia: Potential Superspreaders?

BACKGROUND: People with human immunodeficiency virus (PWH) with recurrent visceral leishmaniasis (VL) could potentially drive Leishmania transmission in areas with anthroponotic transmission such as East Africa, but studies are lacking. Leishmania parasitemia has been used as proxy for infectiousness. METHODS: This study is nested within the Predicting Visceral Leishmaniasis in HIV-InfectedPatients (PreLeisH) prospective cohort study, following 490 PWH free of VL at enrollment for up to 24-37 months in northwest Ethiopia. Blood Leishmania polymerase chain reaction (PCR) was done systematically. This case series reports on 10 PWH with chronic VL (≥3 VL episodes during follow-up) for up to 37 months, and 3 individuals with asymptomatic Leishmania infection for up to 24 months. RESULTS: All 10 chronic VL cases were male, on antiretroviral treatment, with 0-11 relapses before enrollment. Median baseline CD4 count was 82 cells/µL. They displayed 3-6 VL treatment episodes over a period up to 37 months. Leishmania blood PCR levels were strongly positive for almost the entire follow-up (median cycle threshold value, 26 [interquartile range, 23-30]), including during periods between VL treatment. Additionally, we describe 3 PWH with asymptomatic Leishmania infection and without VL history, with equally strong Leishmania parasitemia over a period of up to 24 months without developing VL. All were on antiretroviral treatment at enrollment, with baseline CD4 counts ranging from 78 to 350 cells/µL. CONCLUSIONS: These are the first data on chronic parasitemia in PWH from Leishmania donovani-endemic areas. PWH with asymptomatic and symptomatic Leishmania infection could potentially be highly infectious and constitute Leishmania superspreaders. Xenodiagnosis studies are required to confirm infectiousness.

Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: Treatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax. METHODS: This multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia. RESULTS: In the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS: Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167 .).

Adherence to chronic hepatitis B screening guidelines for persons from intermediate to high prevalence Countries.

The adherence to the CDC guideline on screening non-U.S. born persons for hepatitis B virus infection was assessed. A retrospective cohort study was conducted at University of Washington primary care clinics using the electronic medical records. Persons from hepatitis B virus prevalent countries were identified using country of origin and language. Of 2329 eligible for screening, only 617 (26.5%) were screened. The prevalence of HBsAg was 35 (5.7%). Among women of reproductive age (18-44 years, n = 906), 238 (26.3%) were screened, and 7 (2.9%) were HBsAg positive. Low screening practice for chronic hepatitis B infection, and high infection prevalence among those screened was noted. The findings indicate that potentially three out of every one detected case may be missed. Urgent efforts are needed to scale up and consistently implement HBV screening at primary care clinics.

Low antileishmanial drug exposure in HIV-positive visceral leishmaniasis patients on antiretrovirals: an Ethiopian cohort study.

BACKGROUND: Despite high HIV co-infection prevalence in Ethiopian visceral leishmaniasis (VL) patients, the adequacy of antileishmanial drug exposure in this population and effect of HIV-VL co-morbidity on pharmacokinetics of antileishmanial and antiretroviral (ARV) drugs is still unknown. METHODS: HIV-VL co-infected patients received the recommended liposomal amphotericin B (LAmB) monotherapy (total dose 40 mg/kg over 24 days) or combination therapy of LAmB (total dose 30 mg/kg over 11 days) plus 28 days 100 mg/day miltefosine, with possibility to extend treatment for another cycle. Miltefosine, total amphotericin B and ARV concentrations were determined in dried blood spots or plasma using LC-MS/MS. RESULTS: Median (IQR) amphotericin B Cmax on Day 1 was 24.6 µg/mL (17.0-34.9 µg/mL), which increased to 40.9 (25.4-53.1) and 33.2 (29.0-46.6) µg/mL on the last day of combination and monotherapy, respectively. Day 28 miltefosine concentration was 18.7 (15.4-22.5) µg/mL. Miltefosine exposure correlated with amphotericin B accumulation. ARV concentrations were generally stable during antileishmanial treatment, although efavirenz Cmin was below the 1 µg/mL therapeutic target for many patients. CONCLUSIONS: This study demonstrates that antileishmanial drug exposure was low in this cohort of HIV co-infected VL patients. Amphotericin B Cmax was 2-fold lower than previously observed in non-VL patients. Miltefosine exposure in HIV-VL co-infected patients was 35% lower compared with adult VL patients in Eastern Africa, only partially explained by a 19% lower dose, possibly warranting a dose adjustment. Adequate drug exposure in these HIV-VL co-infected patients is especially important given the high proportion of relapses.

Multiple Relapses of Visceral Leishmaniasis in HIV Co-Infected Patients: A Case Series from Ethiopia.

BACKGROUND: Human visceral leishmaniasis (VL) is a life-threatening protozoan disease caused by parasites belonging to the Leishmania donovani complex. Ethiopia has the highest VL-HIV co-infection rate in the world, with several of these patients presenting with repeated episodes of VL disease (ie, relapse). However, we lack data on how HIV patients with multiple VL relapse present clinically, and whether they continue to respond to currently available medicines. METHODS: The medical records of VL-HIV co-infected patients with multiple VL relapses at the Leishmaniasis Treatment and Research Center in Gondar, Ethiopia, between June 2012 and June 2016 were retrieved. Variables on their clinical and laboratory profiles were collected. Descriptive analysis was done to show the characteristics of the VL episodes. RESULT: A total of 48 VL episodes in 12 patients were identified, the median number of episodes per patient was 5 (interquartile range, 4-8 episodes). The median time to relapse was 5 months (interquartile range, 3-5.5 months). Splenomegaly was present in 47 of the episodes (98%), fever or other accompanying symptoms were present in only 66% (32 out of 48). The median tissue parasite grade at VL diagnosis was 6+ (interquartile range, 5+- 6+). All patients were on antiretroviral therapy. The median duration of treatment per episode was 2 months (interquartile range, 2-2 months). All patients achieved parasitological cure at discharge at each episode. CONCLUSIONS: Multiple recurrences of VL diseases were observed in HIV co-infected patients. With recurrent episodes, splenomegaly was found to be the main manifestation, whereas fever was less common. These patients came with recurrence of diseases in <6 months and required prolonged treatment to achieve cure.Further research on prediction, prevention, and better management options for recurrent VL is needed. ORCID ID: https://orcid.org/0000-0002-1410-0454. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Congenital anomalies prevalence in Addis Ababa and the Amhara region, Ethiopia: a descriptive cross-sectional study.

BACKGROUND: During the first three months of pregnancy, the developing embryo may be susceptible to external and internal factors, which may lead to structural and functional congenital anomalies. The main objective of this study was to determine the prevalence of congenital anomalies in Addis Ababa and the Amhara region, Ethiopia. METHODS: A descriptive cross-sectional study was conducted on children 0-17 years of age who visited the 16 selected hospitals in Addis Ababa and the Amhara Region between January 1 and July 5, 2015. The proportions of neonates, infants, and children with external and internal congenital anomalies whether the anomalies were major or minor were estimated. RESULTS: Out of 76,201 children, 1518 of whom 57.6% were male identified with congenital anomalies. The overall proportion of congenital anomaly was 1.99% (95% CI: 1.89-2.091) i.e., 199 per 10,000 children. The proportion of neural tube defects, orofacial clefts, masculo-skeletal system anomalies, syndrome disorders, and cardiovascular system problems were 40.3% 37.7-43, 23.3% 21.3-25.4, 23.1% 20.9-25.2, 8% 6.7-9.4, and 2.6% 1.8-3.4, with a 95% CI, respectively. The majority (72.5%) of the mothers were multigravidae; 38(2.5%) of the mothers and 32(2.1%) of the fathers had history of other children with congenital anomalies. Similarly, 20(1.3%) of the participant children's mothers and 17(1.1%) of the fathers had familial history of congenital anomaly. Iron folate and multivitamin use by mothers during preconception and early pregnancy was found to be low. CONCLUSION: Neural tube defects, orofacial clefts, and musculoskeletal anomalies were the observed prevalent problems. Maternal illness, viral infections, and malnutrition were seen in a significant number of the mothers. Iron folate/folic acid and multivitamin use by the mothers during and before pregnancy was very low.

Long-term Clinical Outcomes in Visceral Leishmaniasis/Human Immunodeficiency Virus-Coinfected Patients During and After Pentamidine Secondary Prophylaxis in Ethiopia: A Single-Arm Clinical Trial.

Background: We have conducted a single-arm trial evaluating monthly pentamidine secondary prophylaxis (PSP) to prevent visceral leishmaniasis (VL) relapse in Ethiopian human immunodeficiency virus-infected patients. Outcomes at 12 months of PSP have been previously reported, supporting PSP effectiveness and safety. However, remaining relapse-free after PSP discontinuation is vital. We now report outcomes and associated factors for a period of up to 2.5 years after initiating PSP, including 1-year follow-up after PSP discontinuation. Methods: The trial had 3 phases: (1) 12 months of PSP; (2) a 6-month PSP extension period if CD4 count was ≤200 cells/µL at month 12; and (3) 12-month follow-up after stopping PSP. The probability of relapse and risk factors were calculated using Kaplan-Meier methods and Cox regression analysis. Results: For the 74 patients included, final study outcomes were as follows: 39 (53%) relapse-free, 20 (27%) relapsed, 5 (7%) deaths, 10 (14%) lost to follow-up. The 2-year risk of relapse was 36.9% (95% confidence interval, 23.4%-55.0%) and was highest for those with a history of VL relapse and low baseline CD4 count. Forty-five patients were relapse-free and in follow-up at month 12 of PSP. This included 28 patients with month 12 CD4 counts >200 cells/µL, remaining relapse-free after PSP discontinuation. Among the 17 with month 12 CD4 count <200 cells/µL, 1 relapsed and 3 were lost during the PSP extension period. During 1-year post-PSP follow-up, 2 patients relapsed and 1 was lost to follow-up. No PSP-related serious adverse events were reported during the PSP-extension/post-PSP follow-up period. Conclusions: It seems safe to discontinue PSP at month 12 CD4 counts of >200 cells/µL. The management of those failing to reach this level remains to be defined. Clinical Trials Registration: NCT01360762.

Development and Evaluation of a Novel Loop-Mediated Isothermal Amplification Assay for Diagnosis of Cutaneous and Visceral Leishmaniasis.

A novel pan-Leishmania loop-mediated isothermal amplification (LAMP) assay for the diagnosis of cutaneous and visceral leishmaniasis (CL and VL) that can be used in near-patient settings was developed. Primers were designed based on the 18S ribosomal DNA (rDNA) and the conserved region of minicircle kinetoplast DNA (kDNA), selected on the basis of high copy number. LAMP assays were evaluated for CL diagnosis in a prospective cohort trial of 105 patients in southwest Colombia. Lesion swab samples from CL suspects were collected and were tested using the LAMP assay, and the results were compared to those of a composite reference of microscopy and/or culture in order to calculate diagnostic accuracy. LAMP assays were tested on samples (including whole blood, peripheral blood mononuclear cells, and buffy coat) from 50 suspected VL patients from Ethiopia. Diagnostic accuracy was calculated against a reference standard of microscopy of splenic or bone marrow aspirates. To calculate analytical specificity, 100 clinical samples and isolates from fever-causing pathogens, including malaria parasites, arboviruses, and bacteria, were tested. We found that the LAMP assay had a sensitivity of 95% (95% confidence interval [CI], 87.2% to 98.5%) and a specificity of 86% (95% CI, 67.3% to 95.9%) for the diagnosis of CL. With VL suspects, the sensitivity of the LAMP assay was 92% (95% CI, 74.9% to 99.1%) and its specificity was 100% (95% CI, 85.8% to 100%) in whole blood. For CL, the LAMP assay is a sensitive tool for diagnosis and requires less equipment, time, and expertise than alternative CL diagnostics. For VL, the LAMP assay using a minimally invasive sample is more sensitive than the gold standard. Analytical specificity was 100%.

Factors associated with congenital anomalies in Addis Ababa and the Amhara Region, Ethiopia: a case-control study.

BACKGROUND: The early stage of embryo development is extremely vulnerable to various teratogenic factors, leading to congenital anomalies. In Ethiopia, a significant number of babies are born with congenital anomalies, but the risk factors for the anomalies have never been studied. Understanding the specific risk factors for congenital anomalies is very essential to provide health education that aims at creating awareness and establishing preventive strategic plan/s. The main objective of this study was to assess the risk factors associated with congenital anomalies in Addis Ababa and the Amhara Region, Ethiopia. METHODS: A case-control study was conducted from January 1- June 30, 2015. The participants were recruited at the purposively selected hospitals in Addis Ababa and the Amhara Region. A total of 207 cases and 207 controls were included in the study. Cases were neonates, infants, and children 0-11 months of age with external and internal major congenital anomalies diagnosed by pediatricians. Controls were neonates, infants, and children 0-11 months of age without external and internal anomalies. Data on sociodemographic characteristics, exposure to risk factors, and reproductive history were collected by face to face interviews with children's mothers/caregivers using a structured questionnaire. Binary logistic regression was employed to explore risk factors associated with the occurrence of the problems. RESULTS: About 87.4% of the children were below 6 months, and 12.6% were between 6 and 11 months. The majority (59.9%) of the children were male, with the M: F sex ratio of 1.49. The mean age of the mothers was 26 years (16-45 years). Unidentified medication use during early pregnancy (AOR = 4.595; 95% CI: 1.868-11.301, P-value = 0.001), maternal alcohol drinking (AOR = 2.394; 95% CI: 1.212-4.726, P-value = 0.012), and exposure to chemicals (AOR = 9.964; 95% CI = 1.238-80.193, P-value = 0.031) were significantly associated with the occurrence of congenital anomalies. Iron folate use (AOR = 0.051; 95% CI: 0.010-0.260, P-value = < 0.001) before and during early pregnancy had a protective effect on congenital anomaly. CONCLUSION: Unidentified medication use, alcohol drinking during early pregnancy, and exposure to chemicals had a significant association with the occurrence of congenital anomalies, whereas iron folate use before and during early pregnancy had a protective effect from congenital anomalies.

The Risk and Predictors of Visceral Leishmaniasis Relapse in Human Immunodeficiency Virus-Coinfected Patients in Ethiopia: A Retrospective Cohort Study.

BACKGROUND: East Africa, where Leishmania donovani is prevalent, faces the highest burden world-wide of visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) coinfection. However, data on the risk and predictors of VL relapse are scarce. Such information is vital to target medical follow-up and interventions to those at highest risk. METHODS: We conducted a retrospective cohort study at a Médecins Sans Frontières-supported health center in northwest Ethiopia. We included adult VL-HIV coinfected patients treated for VL and discharged cured between February 2008 and February 2013. The risk of relapse was calculated using Kaplan-Meier methods, and predictors were determined using Cox regression models. RESULTS: Of the 146 patients included, 140 (96%) were male and the median age was 31 years. At the index VL diagnosis, 110 (75%) had primary VL, 57 (40%) were on antiretroviral therapy (ART), and the median CD4 count was 149 cells/µL. The median follow-up time after cure was 11 months, during which 44 (30%) patients relapsed. The risk of relapse was 15% at 6 months, 26% at 12 months, and 35% at 24 months. Predictors of relapse were: not being on ART at VL diagnosis, ART not initiated during VL treatment, and high tissue parasite load (parasite grade 6+) at VL diagnosis. CONCLUSIONS: The risk of VL relapse in coinfected patients was high, particularly in those not on ART or presenting with a high tissue parasite load. These patients should be preferentially targeted for secondary prophylaxis and/or regular medical follow-up. Timely ART initiation in all coinfected patients is crucial.

Clinical features and treatment response of cutaneous leishmaniasis in North-West Ethiopia.

OBJECTIVE: Cutaneous leishmaniasis (CL) receives far less attention than visceral leishmaniasis. Nevertheless, CL is predominantly caused by a unique species in Ethiopia (L. aethiopica), which is known to cause severe forms such as diffuse (DCL) and mucocutaneous leishmaniasis (MCL). We report on the number and type of CL cases diagnosed, the clinical features, the treatments and treatment outcomes in North-West Ethiopia. METHODS: This is a retrospective chart record analysis of CL patients treated at the Leishmania Research and Treatment Center (LRTC) of the University of Gondar, Ethiopia. RESULTS: From 178 CL patients seen between January 2014 and December 2015, a total of 154 chart records were retrieved. These included 80 localised CL (LCL), 7 DCL and 67 MCL. The median age was 23 years; 71.4% were male. Most (n = 121, 78.6%) of the lesions were on the face. The median time since onset was 12 months (6-24 months), and 28.6% presented after a trial of traditional medicine. The treatment of all forms of CL mainly consisted of 30 days of IM antimonial injections. Of these, 51/133 (38.3%) required treatment extension or change due to nonresponse. Three cases were treated with liposomal amphotericin B or miltefosine (two received the combination), of which two responded well. CONCLUSION: CL was found to be complicated and difficult to treat. MCL was common, and patients presented after long delays. There is an urgent need to look for better treatment options for CL and improve access to care.

Factors associated with the length of delay with tuberculosis diagnosis and treatment among adult tuberculosis patients attending at public health facilities in Gondar town, Northwest, Ethiopia.

BACKGROUND: Early diagnosis and prompt treatment is essential for an effective tuberculosis (TB) control program. However, significant proportion of cases remains undiagnosed and untreated. Delay in diagnosis and treatment increases transmission. Hence, the study assessed the length of delay and associated factors with tuberculosis diagnosis and treatment among adults attending public health facilities in Gondar town, Northwest Ethiopia. METHOD: An institution based cross-sectional study was conducted from February to May, 2016. A total of 296 adults who came to health facilities for treatment for pulmonary TB from February to May, 2016, were included in the study. Data were collected using a structured questionnaire through interviewing and record review, cleaned, coded, and entered into Epi-info version 3.5.3, and transferred into SPSS version 20.0 for further statistical analysis. A p-value of less than 0.05 at multiple linear regression analysis was considered statistically significant. RESULT: The mean duration of the total delay (in days) for tuberculosis diagnosis and initiation of treatment was 41.6 days (SD = 16.6). In this study, the mean duration of patient delay and the median health system delay were 33.9 days (SD = 14) and 5 days (IQR = 4-7), respectively. Total delay for TB diagnosis and treatment was shorter among HIV positive people (ß:-12.62, 95% CI: -20.72,-4.53). Longer patient delay was noted among rural dwellers (ß: 8.0, 95% CI: 5.26, 10.75); increased household income (ß:-0.006, 95% CI: -0.008,-0.004) was associated with a shorter delay. Health system delay was positively associated with seeking care from more than one health care providers (ß: 0.28, 95% CI: 0.23, 0.34) and seeking initial care from primary level health care facilities (ß: 0.10, 95% CI: 0.07, 0.13). CONCLUSION: In this study, the majority of patients faced delayed in seeking health care and continued as sources of infection. Longer days of delay for TB diagnosis and treatment were noted among rural residents, who seek health care from informal care providers, and receive initial care from primary level health care facilities. In contrast, the length of delay for TB diagnosis and treatment was shorter among HIV positive people and individuals with increased household income. Therefore, public awareness on the symptoms of tuberculosis and seeking health care early is essential. Moreover, early diagnosis and treatment, especially among the rural dwellers and the poor should be focused.

Safety and efficacy of liposomal amphotericin B for treatment of complicated visceral leishmaniasis in patients without HIV, North-West Ethiopia.

BACKGROUND: Visceral leishmaniasis (VL) is a protozoan disease that is invariably fatal if left untreated. The disease is found in 70 countries with incidence of 0.2 - 0.4 million cases. The mainstay of treatment in resource limited countries like Ethiopia is antimonials, while use of liposomal amphotericin B is reserved for treatment of complicated VL cases. The aim of this study was to assess the safety and efficacy of liposomal amphotericin B in HIV negative VL patients diagnosed with complications. METHODS: A retrospective chart review was conducted involving records of patients admitted between January 2009 and December 2014. Baseline sociodemographic, clinical, and treatment outcome data were collected. The doses of liposomal amphotericin B and adverse events related to treatment were retrieved. Categorical and continuous variables respectively were analyzed by Chi-square and Mann-Whitney U tests. A p-value of less than 0.05 was considered statistically significant. RESULTS: A total of 147 patients with severe VL were treated with liposomal amphotericin B in total dose ranges of 20 mg/kg to 35 mg/kg. In the overall treatment outcome analysis, initial cure (30 days after start of treatment) was observed in 128 (87.1 %), treatment failures in 10 (6.8 %), interruptions in 2(1.4 %) and deaths in 7 (4.8 %) patients. Initial cure rate at high dose (24-35 mg/kg total dose) was 96.7 % (59/61) versus 80.2 % (69/86) at lower doses (<24 mg/kg); which was significantly higher (P < 0.01), OR = 4.56: 95 %, Confidence Interval (CI) = 1.17 - 20.78). Ten cases (11.8 %) of treatment failure occurred in the low dose treatment group. The most common adverse events (AEs) were hypokalemia in 39 cases (26.5 %) and infusion related reactions in 16 (10.9 %). The frequency of hypokalemia and infusion related reactions were not significantly different between the low and high dose liposomal amphotericin B. CONCLUSION: In HIV negative complicated VL patients, high dose of liposomal amphotericin B was found to have high cure rate at the end of treatment. The appropriate dose for better efficacy needs to be determined. Monitoring serum potassium level during treatment with liposomal amphotericin B should be an essential component of the clinical management of VL.

Hepatitis viruses in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: The existing seroepidemiological data on viral hepatitis in Ethiopia showed a wide variation in prevalence pattern and the clinical and public health burden have been underestimated. The aim of this systematic review and meta-analysis was to provide a clear and comprehensive estimation of viral hepatitis epidemiology and the potential clinical burdens in Ethiopia. METHODS: A comprehensive literature search was carried out from five decades (1968-2015) published studies from biomedical databases; PubMed, Google scholar, Medline and Web of Science. RESULTS: The overall pooled prevalence of hepatitis B virus (HBV) was 7.4% (95%CI: 6.5-8.4). The pooled prevalence among subgroups showed 5.2% (95%CI: 3.7-7.4) in human immunodeficiency virus (HIV) infected individuals, 8.0% (95%CI: 5.9-10.7) in community based studies, 8.4% (95%CI: 5.4-12.7) in blood donors, 11.0% (95%CI: 7.5-15.9) in immigrants and 6.9% (95%CI: 5.6-8.5) in other groups. Among study parameters considered during meta-regression analysis, only study years were associated with a decreasing HBV prevalence rate over time. The overall pooled prevalence of anti-hepatitis C virus antibody (anti-HCV) was 3.1% (95%CI: 2.2-4.4). Unlike HBV, the anti-HCV prevalence in HIV infected individuals was higher (5.5%, 95%CI: 3.8-7.8%, p = 0.01) than the prevalence observed in the other subgroup of study population. Although relatively few data were available, hepatitis virus A (HAV), D (HDV) and E (HEV) were also circulated in Ethiopia. CONCLUSIONS: This review indicates that all types of viral hepatitis origins are endemic in Ethiopia. Adapting a recommended diagnostic and treatment algorithm of viral hepatitis in the routine healthcare systems and implementing prevention and control policies in the general population needs an urgent attention.

Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia--an observational cohort study.

BACKGROUND: In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients. METHODS: A standardised second-line drug (SLD) regimen was used in a non-governmental organisation-Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models. RESULTS: From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥ 24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m(2), p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death. CONCLUSIONS: We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes.

Clinical aspects of paediatric visceral leishmaniasis in North-west Ethiopia.

OBJECTIVE: Visceral leishmaniasis (VL) in north-west Ethiopia is causing an overwhelming case load among adult migrant workers that masked the disease burden in children. This study describes the clinical profile and explores comorbidities in paediatric VL patients. METHODS: A prospective study at two hospitals in this region (Gondar and Humera) was conducted in a year period, 2011-2012. The clinical manifestations and comorbidities such as malnutrition, intestinal parasitosis and vitamin D deficiency and HIV infection were assessed, and treatment outcomes noted. RESULTS: A total of 122 children with VL were detected during the study period with median age of 8.5 years (IQR 5-12 years); 23% were under 5 years. Eighty-five (69.7%) cases were male. The clinical manifestations were similar to the adult patients. High rates of malnutrition, intestinal parasitosis (47.5%) and hypovitaminosis D (56.4%) were detected. The proportion of stunting and wasting was 63% and 22.2% in children aged under five years, and 50.5% and 75.9% in 5-year and older children, respectively, using WHO standard growth curves. Only one child had HIV infection. In 95% of the cases, sodium stibogluconate (20 mg/kg/day for 30 days) was used for treatment. The treatment success rate at end of therapy was 98.3%, but the definitive outcome at 6 months could not be determined because of a high loss to follow-up (80.2%). CONCLUSION: While HIV co-infection was rare, malnutrition, intestinal parasitosis and vitamin D deficiency were frequent indicating the need for further research on their role in the pathophysiology. Meanwhile, systematic assessment and management of malnutrition and intestinal parasitosis in VL programmes is recommended.

Prevalence of tuberculosis and treatment outcome among university students in Northwest Ethiopia: a retrospective study.

BACKGROUND: Universities tend to be highly congregate settings, both in the classroom and in residences, and thus provide special opportunities for large number of persons to be exposed to a person with tuberculosis (TB). Despite the high prevalence of TB in Ethiopia, the TB prevalence and the treatment outcome among students have never been studied. Therefore, this study was aimed at determining the prevalence and treatment outcome of TB among students at University of Gondar from January 2007 to December 2011. METHODS: Data on age, sex, TB type, category, and treatment outcome of students with TB was collected from medical records of University of Gondar Hospital, TB Directly Observed Treatment Short Course (DOTS) clinic. All TB cases diagnosed with smear, culture, and/or radiography were included in the study. RESULTS: During the five year study period in the university, there were an average of 36 students with TB per year out of a mean of 10,036 enrolled students. Smear positive pulmonary TB, smear negative pulmonary TB, and extra pulmonary TB, respectively, were observed in 46 (25.4%), 81 (44.8%) and 54 (29.8%) of the cases. The prevalence of all forms of TB per 100,000 populations in the University ranged from 297.6 in 2009 to 404 in 2011, respectively. The prevalence of TB in the Social Sciences and Humanities Faculty was higher than the one observed in the Medical College. The overall treatment outcome was classified as cured in 36 (19.9%), completed in 91 (50.3%), defaulted in 9 (5%), failed in 3 (1.7%), died in 1 (0.6%), and transferred out in 41 (22.7%) of the cases. Treatment success rate (TSR) among students in University was generally low ranging from 58.1% in 2009 to 82.9% in 2011 with a mean TSR of 70.2%. CONCLUSION: The prevalence of TB is higher in comparison to the national figure among students in University of Gondar. Active surveillance systems could be important to get a clear picture of the TB situation in such settings. Assessing the factors associated with the high prevalence to gear the TB control strategy could also be essential.

Sponsorship in non-commercial clinical trials: definitions, challenges and the role of Good Clinical Practices guidelines.

BACKGROUND: Non-commercial clinical research plays an increasingly essential role for global health. Multiple partners join in international consortia that operate under the limited timeframe of a specific funding period. One organisation (the sponsor) designs and carries out the trial in collaboration with research partners, and is ultimately responsible for the trial's scientific, ethical, regulatory and legal aspects, while another organization, generally in the North (the funder), provides the external funding and sets funding conditions. Even if external funding mechanisms are key for most non-commercial research, the dependence on an external funder's policies may heavily influence the choices of a sponsor. In addition, the competition for accessing the available external funds is great, and non-commercial sponsors may not be in a position to discuss or refuse standard conditions set by a funder. To see whether the current definitions adequately address the intricacies of sponsorship in externally-funded trials, we looked at how a "sponsor" of clinical trials is defined in selected international guidelines, with particular focus on international Good Clinical Practices codes, and in selected European and African regulations/legislations. DISCUSSION: Our limited analysis suggests that the sponsors definition from the 1995 WHO Good Clinical Practices code has been integrated as such into many legislations, guidelines and regulations, and that it is not adequate to cover today's reality of funding arrangements in global health, where the legal responsibility and the funding source are de facto split. In agreement with other groups, we suggest that the international Good Clinical Practices codes should be updated to reflect the reality of non-commercial clinical research. In particular, they should explicitly include the distinction between commercial and non-commercial sponsors, and provide guidance to non-commercial sponsors for negotiating with external funding agencies and other research counterparts. Non-commercial sponsors of clinical trials should surely invest in the development of adequate legal, administrative and management skills. By acknowledging their role and specificities, and by providing them with adapted guidance, the international Good Clinical Practices codes would provide valuable guidance and support to non-commercial clinical research, whose relevance for global health is increasingly evident.

The status of combination therapy for visceral leishmaniasis: an updated review.

For the past 15 years, trials of combination therapy options for visceral leishmaniasis have been conducted with the aim of identifying effective, and safe treatment regimens that were shorter than existing monotherapy regimens and could also prevent or delay the emergence of drug resistance. Although first-line treatment currently relies on combination therapy in east Africa, this is not true in Latin America owing to disappointing trial results, with lower than expected efficacy seen for the combination treatment group. By contrast, several effective combination therapy regimens have been identified through trials on the Indian subcontinent; yet, first-line therapy is still AmBisome monotherapy as the drug is part of a free donation programme and is highly effective in this region. Achieving a short all-oral combination treatment will require new chemical entities, several of which are currently under evaluation. Future studies should systematically include pharmacological substudies to ensure optimal dosing for all patient groups. To achieve maximal impact of new combination treatments, mechanisms to ensure drug availability and access after trials should be established. Enhancing the longevity of current and novel treatments will require effective systems for early detection of emerging drug resistance.

Correction: Acute kidney injury in patients with Visceral Leishmaniasis in Northwest Ethiopia.

[This corrects the article DOI: 10.1371/journal.pone.0252419.].