6320 research outputs found
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A randomised trial to assess the safety and efficacy of artemether-lumefantrine (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwanda
No full textWe tested the efficacy and safety of chlorproguanil/dapsone co-administered with artesunate (CD+A) for the treatment of uncomplicated Plasmodium falciparum malaria in children compared with amodiaquine+sulfadoxine/pyrimethamine (AQ+SP) at two different sites in Rwanda. The trial was open label and 800 patients were randomly assigned to AQ+SP (n=400) or CD+A (n=400). Patients were hospitalised for 3 days and then followed-up weekly until Day 28 after treatment. Clinical and parasitological outcomes were recorded. Results showed that neither treatment was adequately efficacious. At one site, the adequate clinical and parasitological response (ACPR), PCR-adjusted, was 73.3% in the CD+A arm and 87.8% in the AQ+SP arm (P<0.001), and at the second site the ACPR, PCR-adjusted, was 70.5% in the CD+A arm and 38.1% in the AQ+SP arm (P<0.001). The combination CD+A is considered an alternative to, or replacement for, SP in Africa because CD has been shown to be effective in patients for whom SP treatment has failed and, with its short half-life, it is expected to exert less selection pressure for resistant parasites than SP. However, the results of this trial indicate that in an area of high SP resistance, CD+A may not be the best choice. [ClinicalTrials.gov identifier: NCT00461578]
Epidemiological dynamics of antimonial resistance in Leishmania donovani; genotyping reveals a polyclonal population structure among naturally-resistant clinical isolates from Nepal
No full textPentavalent antimonials (SbV) are the first line drug against leishmaniasis worldwide, but drug resistance is increasingly reported, particularly in the Indian sub-continent, where it represents a major threat for the control of anthroponotic visceral leishmaniasis (VL). In order to understand the epidemiological dynamics of antimonial resistance in anthroponotic VL, we analysed here the population structure of 24 Leishmania donovani stocks isolated from anthroponotic VL-patients from Eastern Nepal: 13 SbV-naturally resistant and 11 SbV-sensitive, as demonstrated by in vitro drug susceptibility assays. The parasites were genotyped by PCR-RFLP analysis of kDNA minicircles and by microsatellite analysis and the encountered polymorphism revealed a polyclonal structure among resistant isolates. Furthermore, analysis of paired samples obtained from the same patients before treatment and after failure revealed primary as well as acquired resistance. The hypothesis of independent events of drug resistance emergence is proposed and confronted to alternative explanations. Our results show the dynamics of drug resistance epidemiology and highlight the importance of surveillance networks
Classification of sporadic Creutzfeldt-jacob disease based on clinical and neuropathological characteristics
No full textCreutzfeldt-Jakob disease (CJD) is a rare and fatal neurodegenerative disease of unknown cause. Patients are usually aged between 50 and 75 and typical clinical features include rapidly progressive dementia associated with myoclonus and a characteristic electroencephalographic pattern. Neuropathological examination reveals cortical spongiform change, hence the term 'spongiform encephalopathy'. Several statistical techniques were applied to classify patients with sporadic CJD (sCJD), based on clinical and neuropathological investigation. We focus on the classification of neuropathologically confirmed sCJD patients. In order to obtain a classification rule that correctly classifies this type of patients and at the same time controls the overall error rate, we apply several classification techniques, which in general, produce comparable results. The boosting method produces the best results and the variable 14-3-3 protein in cerebrospinal fluid plays the most important role in the prediction of neuropathologically confirmed sCJD
Building capacity for improved veterinary epidemiosurveillance in southern Africa
No full textA workshop to produce recommendations on training requirements for improved epidemiosurveillance of livestock diseases in southern Africa was organised at the Department of Veterinary Tropical Diseases in the Veterinary Faculty of the University of Pretoria. It was attended by 23 persons representing 10 different southern African countries. The majority of the participants were actively involved in veterinary epidemiosurveillance and many of them were members of the SADC Epidemiology and Informatics Subcommittee. Discussions focused on (i) epidemiosurveillance networks and their 2 main components, i.e. (ii) diagnosis and (iii) information flow. The debates were guided by 3 questions; (i) what are the requirements for an effective network, (ii) what cannot be achieved with existing capacity and (iii) how can the current capacity be improved. Workshop participants developed lists of realistic capacity building needs, which were divided into structural needs and training requirements. Structural needs mainly concerned communication means and quality assurance. With regard to training, the need for appropriate continuing education of all actors at the various disease management levels (non-professional, para-professional, professional) was expressed. Special emphasis was put on capacity building at the lowest level, i.e. the livestock owner and the para-professionals at the community level. At the international level, it was felt that special emphasis should be put on building capacity to improve the understanding of international agreements on trade in animals and animal products and to improve the capacity of negotiating such agreements
Molecular detection of Ehrlichia ruminantium infection in Amblyomma variegatum ticks in The Gambia
No full textIn West Africa, losses due to heartwater disease are not known because the incidence/prevalence has not been well studied or documented. To develop a diagnostic tool for molecular epidemiology, three PCR-based diagnostic assays, a nested pCS20 PCR, a nested map1 PCR and a nested reverse line blot (RLB) hybridization assay, were evaluated to determine their ability to detect infection in vector ticks, by applying them simultaneously to A. variegatum field ticks to detect Ehrlichia ruminantium, the causative agent of heartwater. The nested pCS20 PCR assay which amplified the pCS20 gene fragment showed the highest detection performance with a detection rate of 16.6%; the nested map1 PCR, which amplified the gene encoding the major antigenic protein1 (map1 gene) showed a detection rate of 11% and the RLB, based on the 16S rDNA sequence of anaplasma and ehrlichial species, detected 6.2%. The RLB, in addition, demonstrated molecular evidence of Ehrlichia ovina, Anaplasma marginale and Anaplasma ovis infections in The Gambia. Subsequently, the pCS20 assay was applied to study the prevalence and distribution of E. ruminantium tick infection rates at different sites in five divisions of The Gambia. The rates of infection in the country ranged from 1.6% to 15.1% with higher prevalences detected at sites in the westerly divisions (Western, Lower River and North Bank; range 8.3-15.1%) than in the easterly divisions (Central River and Upper River; range 1.6-7.5%). This study demonstrated a gradient in the distribution of heartwater disease risk for susceptible livestock in The Gambia which factor must be considered in the overall design of future upgrading programmes
Immune reconstitution inflammatory syndrome in an HIV/TB co-infected patient four years after starting antiretroviral therapy
No full textThe Immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy for HIV is well known.We describe an HIV seropositive woman, presenting 2 IRIS episodes associated with Mycobacterium tuberculosis. Exceptional was that the last episode occurred 4 years after initiating antiretroviral treatment, when her CD4+ lymphocyte count had been around 300 cells/mm3 for one year
Predictors of long-term viral failure among Ugandan children and adults treated with antiretroviral therapy
No full textNot the final published versionBACKGROUND: HIV RNA viral load testing is costly and is generally unavailable in resource-limited settings. We identified predictors of viral failure and documented genotypic mutations in a subset of patients with viral failure after 12 months on antiretroviral therapy (ART). METHODS: From April 2004 to June 2005, consecutive treatment-naive patients beginning ART at a university clinic in Uganda were enrolled. Clinical information, CD4 cell count, and HIV RNA level were collected at baseline and every 3 to 6 months. Independent predictors of viral failure were identified using multivariate logistic regression. Genotypic drug resistance for 8 patients with viral failure at 12 months was measured at baseline and at 6 and 12 months. RESULTS: Five hundred twenty-six adults and 250 children (0 to 18 years of age) were started on first-line ART regimens and followed for 12 months. Outcomes could not be assessed in 13% of patients (79 died and 21 were withdrawn). Children were almost twice as likely to have viral failure compared with adults (26% vs. 14%; P = 0.0001). In adults, the sole independent predictor of viral failure was treatment with stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP) versus zidovudine (ZDV)/3TC/efavirenz (EFV) (odds ratio [OR] = 2.59, 95% confidence interval [CI]: 1.20 to 5.59). In children, independent predictors of viral failure included male gender (OR = 2.44, 95% CI: 1.20 to 4.93), baseline CD4% <5 (OR = 2.69, 95% CI: 1.28 to 5.63), and treatment with d4T/3TC/NVP versus ZDV/3TC/EFV (OR = 2.46, 95% CI: 1.23 to 4.90). All 8 patients with viral breakthrough and genotypic drug resistance results had nonnucleoside reverse transcriptase inhibitor (NNRTI)- and 3TC-associated mutations. CONCLUSIONS: These data demonstrate the effectiveness of ART in a low-resource setting. Children and patients of all ages taking the d4T/3TC/NVP regimen were more likely to have viral failure. Our data suggest that viral failure occurring 6 months or more after the start of ART regimens commonly used in Uganda is likely to be associated with NNRTI- and 3TC-resistant virus
Severe dengue virus infection in travelers; risk factors and laboratory indicators
No full textBACKGROUND: Dengue fever is the most common arboviral disease in travelers. In countries where dengue virus is endemic, sequential (secondary) infections with different dengue virus serotypes are associated with disease severity. Data on severity and secondary infection rates in a population of travelers are lacking. METHODS: Intensified surveillance of dengue fever in travelers was performed within the European Network on Surveillance of Imported Infectious Diseases. Data were collected at 14 European clinical referral centers between 2003 and 2005. RESULTS: A total of 219 dengue virus infections imported from various regions of endemicity were reported. Serological analysis revealed a secondary immune response in 17%. Spontaneous bleeding was observed in 17 (8%) patients and was associated with increased serum alanine and aspartate aminotransferase levels and lower median platelet counts. Two (0.9%) patients fulfilled the World Health Organization (WHO) case definition for dengue hemorrhagic fever. However, 23 (11%) travelers had severe clinical manifestations (internal hemorrhage, plasma leakage, shock, or marked thrombocytopenia). A secondary immune response was significantly associated with both spontaneous bleeding and other severe clinical manifestations. CONCLUSIONS: In travelers, severe dengue virus infections are not uncommon but may be missed if the WHO classification is strictly applied. High liver enzyme levels and low platelet counts could serve as indicators of disease severity