Kasang C.,University of Würzburg |
Kalluvya S.,Bugando Medical Center |
Majinge C.,Bugando Medical Center |
Stich A.,Medical Mission Institute |
And 14 more authors.
PLoS ONE | Year: 2011
Background: The World Health Organization (WHO) has recommended guidelines for a HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility criteria for patients include age below 25 years in order to focus on the prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of the participating sites across Africa have so far reported tHIVDR prevalences of below 5%. In this study we investigated whether the rate of HIVDR in patients <25 years is representative for HIVDR in the rest of the therapy-naïve population. Methods and Findings: HIVDR was determined in 88 sequentially enrolled ART-naïve patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged <25 years and 68 patients were aged 25-63 years. The frequency of HIVDR in the study population was 14.8% (95%; CI 0.072-0.223) and independent of NVP-resistance induced by prevention of mother-to-child transmission programs. Patients >25 years had a significantly higher HIVDR frequency than younger patients (19.1%; 95% CI 0.095-0.28) versus 0%, P = 0.0344). In 2 out of the 16 patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma. Conclusions: ART-naïve patients aged over 25 years exhibited significantly higher HIVDR than younger patients. Detection of traces of ARVs in individuals with HIVDR suggests that besides transmission, undisclosed misuse of ARVs may constitute a significant factor in the generation of the observed high HIVDR rate. The current WHO tHIVDR survey that is solely focused on the transmission of HIVDR and that excludes patients over 25 years of age may therefore result in substantial underestimation of the prevalence of HIVDR in the therapy-naïve population. Similar studies should be performed also in other areas to test whether the so far reported optimistic picture of low HIVDR prevalence in young individuals is really representative for the rest of the ART-naïve HIV-infected population. © 2011 Kasang et al.
PubMed | University of Würzburg, Stellenbosch University, HIV Intensive Care Unit, Catholic University of Health and Allied Sciences and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2016
HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients.Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/l, the absence of AIDS-defining symptoms and an ART-nave therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/l.No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 5.70 cells/l compared to -37.42 10.77 cells/l under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men.This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection.ClinicalTrials.gov NCT01299948.
Unnewehr M.,Medizinische Klinik Nord |
Unnewehr M.,University of Munster |
Unnewehr M.,Medical Mission Institute |
Stich A.,Medical Mission Institute
Journal of Korean Medical Science | Year: 2015
In North Korea, the prevalence of hepatitis B is high due to natural factors, gaps in vaccination, and the lack of antiviral treatment. Aid projects are urgently needed, however impeded by North Korea's political and economical situation and isolation. The feasibility of a joint North Korean and German humanitarian hepatitis B prevention program was assessed. Part 1: Hepatitis B vaccination catch-up campaign. Part 2: Implementation of endoscopic ligation of esophageal varices (EVL) by trainings in Germany and North Korea. By vaccinating 7 million children between 2010 and 2012, the hepatitis B vaccination gap was closed. Coverage of 99.23% was reached. A total of 11 hepatitis B-induced liver cirrhosis patients (mean age 41.1 yr) with severe esophageal varices and previous bleedings were successfully treated by EVL without major complications. A clinical standard operating procedure, a feedback system and a follow-up plan were developed. The bi-modal preventive strategy was implemented successfully. Parts of the project can serve as an example for other low-income countries, however its general transferability is limited due to the special circumstances in North Korea. © 2015 The Korean Academy of Medical Sciences.
Gunda D.W.,Catholic University of Health and Allied Sciences |
Kasang C.,University of Würzburg |
Kasang C.,Medical Mission Institute |
Kidenya B.R.,Catholic University of Health and Allied Sciences |
And 6 more authors.
PLoS ONE | Year: 2013
Background:Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania.Materials and Methods:A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12.Results:Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supra-therapeutic ARV plasma drug concentrations.Conclusion:There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine therapeutic drug monitoring (TDM) could assist identifying these patients early and making timely correction to avoid virological failure, poor immunological outcome and prevent associated drug toxicities. Nonetheless, ARV adherence should be strictly emphasized on HIV patients with immunological failure. © 2013 Gunda et al.
Hiltensperger G.,University of Würzburg |
Jones N.G.,University of Würzburg |
Niedermeier S.,University of Würzburg |
Stich A.,Medical Mission Institute |
And 9 more authors.
Journal of Medicinal Chemistry | Year: 2012
Human African trypanosomiasis (HAT) or sleeping sickness is caused by two subspecies of Trypanosoma brucei, Trypanosoma brucei gambiense, and Trypanosoma brucei rhodesiense and is one of Africa's old plagues. It causes a huge number of infections and cases of death per year because, apart from limited access to health services, only inefficient chemotherapy is available. Since it was reported that quinolones such as ciprofloxacin show antitrypanosomal activity, a novel quinolone-type library was synthesized and tested. The biological evaluation illustrated that 4-quinolones with a benzylamide function in position 3 and cyclic or acyclic amines in position 7 exhibit high antitrypanosomal activity. Structure-activity relationships (SAR) are established to identify essential structural elements. This analysis led to lead structure 29, which exhibits promising in vitro activity against T. b. brucei (IC 50 = 47 nM) and T. b. rhodesiense (IC 50 = 9 nM) combined with low cytotoxicity against macrophages J774.1. Screening for morphological changes of trypanosomes treated with compounds 19 and 29 suggested differences in the morphology of mitochondria of treated cells compared to those of untreated cells. Segregation of the kinetoplast is hampered in trypanosomes treated with these compounds; however, topoisomerase II is probably not the main drug target. © 2012 American Chemical Society.
Bringmann G.,University of Würzburg |
Zhang G.,University of Würzburg |
Olschlager T.,Institute for Molecular Infection Biology |
Stich A.,Medical Mission Institute |
And 4 more authors.
Phytochemistry | Year: 2013
Naphthylisoquinoline alkaloids, named ancistectorine A1, N-methylancistectorine A1, ancistectorine A2, 5-epi-ancistectorine A2, ancistectorine A3, ancistectorine B1, and ancistectorine C1, have been isolated from twigs of the Chinese plant Ancistrocladus tectorius. The structural elucidation succeeded by chemical, spectroscopic, and chiroptical methods. Three of these compounds exhibited excellent, and specific, antiplasmodial activities, comparable with that of the as yet most active representative, dioncophylline C. Moreover, the antitumoral activities of two of the main alkaloids in this species was tested. © 2012 Elsevier Ltd. All rights reserved.
Dornemann J.,Charité - Medical University of Berlin |
Dornemann J.,Medical Mission Institute |
Kelly A.H.,London School of Hygiene and Tropical Medicine |
Kelly A.H.,University of Exeter
Maternal and Child Nutrition | Year: 2013
In Haiti, initiation of breastfeeding is high, but early mixed feeding is the norm. In a situation of crisis, mothers' worries about insufficiency of breast milk, disruption of social networks and free unmonitored distribution of breast milk substitutes impact feeding practices. This study was conducted to explore the attitudes, practices and understandings of breastfeeding in the post-earthquake situation in Haiti. A mixed-method study was conducted in Léogâne, Haiti, a town close to the epicentre of the 2010 earthquake. In a household survey, 1131 mothers of children under 24 months were interviewed about feeding practices. In the quantitative component, we conducted 25 in-depth interviews and seven focus group discussions with mothers, grandmothers, traditional birth attendants, fathers and health care professionals. Mothers described breastfeeding as a challenging responsibility to ensure the infants' health. They understood breast milk as a dynamic substance, the quality of which would deteriorate if the mother's diet was poor or if the mother was afflicted with a psychosocial condition called move san or colere, 'bad blood'. To protect the child in these situations, early supplementary feeding is introduced. Only 20% of informants exclusively breastfed infants under 6 months. Because of a lack of confidence in the quality of breast milk, Haitian mothers tend to wean children earlier. The abiding concerns of Haitian mothers over the quality of their breast milk suggest a number of ways - such as dietary advice - that post-earthquake aid agencies could enhance breastfeeding support. © 2012 Blackwell Publishing Ltd.
Gross U.,University of Gottingen |
Amuzu S.K.,Holy Family Hospital |
de Ciman R.,St Francis Xavier Hospital |
Kassimova I.,St Martin Of Porres Hospital |
And 6 more authors.
Emerging Infectious Diseases | Year: 2011
Bacterial distribution and antimicrobial drug resistance were monitored in patients with bacterial bloodstream infections in rural hospitals in Ghana. In 2001?2002 and in 2009, Salmonella enterica serovar Typhi was the most prevalent pathogen. Although most S. enterica serovar Typhi isolates were chloramphenicol resistant, all isolates tested were susceptible to ciprofloxacin.
PubMed | University of Munster and Medical Mission Institute
Type: Journal Article | Journal: Journal of Korean medical science | Year: 2015
In North Korea, the prevalence of hepatitis B is high due to natural factors, gaps in vaccination, and the lack of antiviral treatment. Aid projects are urgently needed, however impeded by North Koreas political and economical situation and isolation. The feasibility of a joint North Korean and German humanitarian hepatitis B prevention program was assessed. Part 1: Hepatitis B vaccination catch-up campaign. Part 2: Implementation of endoscopic ligation of esophageal varices (EVL) by trainings in Germany and North Korea. By vaccinating 7 million children between 2010 and 2012, the hepatitis B vaccination gap was closed. Coverage of 99.23% was reached. A total of 11 hepatitis B-induced liver cirrhosis patients (mean age 41.1 yr) with severe esophageal varices and previous bleedings were successfully treated by EVL without major complications. A clinical standard operating procedure, a feedback system and a follow-up plan were developed. The bi-modal preventive strategy was implemented successfully. Parts of the project can serve as an example for other low-income countries, however its general transferability is limited due to the special circumstances in North Korea.
PubMed | Medical Mission Hospital, University of Würzburg, Bugando Medical Center and Medical Mission Institute
Type: | Journal: BMC infectious diseases | Year: 2015
Sub-Saharan Africa has a high prevalence of hepatitis B virus (HBV) infections. Health care workers (HCWs) are at high risk of contracting HBV infection through their occupation. Vaccination of HCWs against HBV is standard practice in many countries, but is often not implemented in resource-poor settings. We aimed with this cross-sectional study to determine HBV prevalence, HCW vaccination status, and the risk factors for HCWs contracting HBV infection in Tanzania.We enrolled 600 HCWs from a tertiary Tanzanian hospital. Their demographics, medical histories, HBV vaccination details and risk factors for contracting blood-borne infections were collected using a standardized questionnaire. Serum samples were tested for HBV and hepatitis C virus (HCV) markers by ELISA techniques, PCR and an anti-HBs rapid test. HCWs were divided in two subgroups: those at risk of contracting HBV (rHCW 79.2%) via exposure to potentially infectious materials, and those considered not at risk of contracting HBV (nrHCW, 20.8%).The overall prevalence of chronic HBV infection (HBsAg+, anti-HBc+, anti-HBs-) was 7.0% (42/598). Chronic HBV infection was found in 7.4% of rHCW versus 5.6% of nrHCW (p-value=0.484). HCWs susceptible to HBV (HBsAg-, anti-HBc-, anti-HBs-) comprised 31.3%. HBV immunity achieved either by healed HBV infection (HBsAg-, anti-HBc+, anti-HBs+) or by vaccination (HBsAg-, anti-HBc-, anti-HBs+) comprised 36.5% and 20.2%, respectively. 4.8% of participants had indeterminate results (HBsAg-, anti-HBc+, anti-HBc-IgM-, anti-HBs-). Only 77.1% of HCWs who received a full vaccination course had an anti-HBs titer >10 ml/U. An anti-HBs point-of-care test was 80.7% sensitive and 96.9% specific. There was a significantly higher risk for contracting HBV (anti-HBc+) among those HCW at occupational risk (rHCW) of older age (odds ratios (OR) in rHCW 3.297, p<0.0001 vs. nrHCW 1.385, p=0.606) and among those HCW being employed more than 11 years (OR 2.51, p<0.0001***). HCV prevalence was low (HCV antibodies 1.2% and HCV-RNA 0.3%).Chronic HBV infection is common among Tanzanian HCWs. One third of HCWs were susceptible to HBV infection, highlighting the need for vaccination. Due to high prevalence of naturally acquired immunity against HBV pre-testing might be a useful tool to identify susceptible individuals.