6320 research outputs found
Sort by
Mycobacterium ulcerans triggers T cell immunity followed by local and regional but not systemic immunosuppression
No full textBuruli ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans, characterized by necrotic cutaneous lesions induced by the exotoxin mycolactone. Despite evidence of Th1-mediated protective immunity, M. ulcerans infection has been associated with systemic immunosuppression. We show that early during mouse infection with either mycolactone-positive or negative strains, pathogen-specific IFN-gamma-producing T cells developed in the draining lymph node (DLN). CD4(+) cells migrated to infection foci but progressive infection with virulent M. ulcerans led to the local depletion of recruited cells. Moreover, dissemination of virulent M. ulcerans to the DLN was accompanied by extensive DLN apoptotic cytopathology leading to depletion of CD4(+) T cells and abrogation of IFN-gamma expression. Advanced footpad infection with virulent M. ulcerans did not induce increased susceptibility to systemic co-infection by Listeria monocytogenes. These results show that infection with M. ulcerans efficiently triggers a mycobacteria-specific T cell response in the DLN and that progression of infection with highly virulent M. ulcerans leads to a local and regional suppression of that immune response, but without induction of systemic immunosuppression. These results suggest that prophylactic/therapeutic interventions to prevent dissemination of M. ulcerans to DLN during the early phase of infection would contribute for the maintenance of protective immunity and disease control
International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients
No full textBACKGROUND: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation. METHODOLOGY/FINDINGS: An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05-0.5 parasites/mL whereas specific kDNA tests detected 5.10(-3) par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/microl of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/microl for each DNA stock, 0.5 par/mL and a sensitivity between 83.3-94.4%, specificity of 85-95%, accuracy of 86.8-89.5% and kappa index of 0.7-0.8 compared to consensus PCR reports of the 16 good performing tests and 63-69%, 100%, 71.4-76.2% and 0.4-0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. CONCLUSION/SIGNIFICANCE: This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples
Multiple insecticide resistance: an impediment to insecticide-based malaria vector control program
No full textBACKGROUND: Indoor Residual Spraying (IRS), insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are key components in malaria prevention and control strategy. However, the development of resistance by mosquitoes to insecticides recommended for IRS and/or ITNs/LLINs would affect insecticide-based malaria vector control. We assessed the susceptibility levels of Anopheles arabiensis to insecticides used in malaria control, characterized basic mechanisms underlying resistance, and evaluated the role of public health use of insecticides in resistance selection. METHODOLOGY/PRINCIPAL FINDINGS: Susceptibility status of An. arabiensis was assessed using WHO bioassay tests to DDT, permethrin, deltamethrin, malathion and propoxur in Ethiopia from August to September 2009. Mosquito specimens were screened for knockdown resistance (kdr) and insensitive acetylcholinesterase (ace-1(R)) mutations using AS-PCR and PCR-RFLP, respectively. DDT residues level in soil from human dwellings and the surrounding environment were determined by Gas Chromatography with Electron Capture Detector. An. arabiensis was resistant to DDT, permethrin, deltamethrin and malathion, but susceptible to propoxur. The West African kdr allele was found in 280 specimens out of 284 with a frequency ranged from 95% to 100%. Ace-1(R) mutation was not detected in all specimens scored for the allele. Moreover, DDT residues were found in soil samples from human dwellings but not in the surrounding environment. CONCLUSION: The observed multiple-resistance coupled with the occurrence of high kdr frequency in populations of An. arabiensis could profoundly affect the malaria vector control programme in Ethiopia. This needs an urgent call for implementing rational resistance management strategies and integrated vector control intervention
Matrix metalloproteinase-9 and intercellular adhesion molecule 1 are powerful staging markers for human African trypanosomiasis
No full textObjectives A critical step before treatment of human African trypanosomiasis (HAT) is the correct staging of the disease. As late stage is established when trypanosomes cross the blood-brain barrier and invade the central nervous system, we hypothesized that matrix metalloproteinases and cell adhesion molecules could indicate, alone or in combination, the disease progression from the first to the second stage of HAT. Methods We measured the levels of MMP-2, MMP-9, ICAM-1, VCAM-1 and E-selectin in the cerebrospinal fluid (CSF) of 63 Trypanosoma brucei gambiense-infected patients (15 stage 1 and 48 stage 2). Staging was based on counting of white blood cells (WBC) and/or parasite detection in CSF. Concentrations were obtained either by ELISA or multiplex bead suspension assays, and results were compared with three known HAT staging markers (CXCL10, CXCL8 and H-FABP). Results ICAM-1 and MMP-9 accurately discriminated between stage 1 and stage 2 patients with HAT with 95% sensitivity (SE) for 100% specificity (SP), which was better than CXCL10 (93% SE for 100% SP), one of the most promising known markers. Combination of ICAM-1 and MMP-9 with H-FABP provided a panel that resulted in 100% of SE and SP for staging HAT. Conclusions ICAM-1 and MMP-9, alone or in combination, appeared as powerful CSF staging markers of HAT. Final validation of all newly discovered staging markers on a large multi-centric cohort including both forms of the disease as well as patients with others infections should be performed
Infections with gastrointestinal nematodes, Fasciola and Paramphistomum in cattle in Cambodia and their association with morbidity parameters
No full textPrevalence and seasonal variations of helminth infections and their association with morbidity parameters were studied in traditionally reared Cambodian cattle. Four villages in two provinces of West Cambodia were visited on monthly intervals over a period of 11 months, during which 2391 animals were faecal and blood sampled for parasitological and haematological examinations. The body condition score (BCS), faecal consistency (diarrhoea score, DS), colour of the ocular conjunctivae (FAMACHA((c))) and packed cell volume were determined for each individual animal. The overall proportion of samples that was positive for gastrointestinal nematodes was 52%, 44% and 37% in calves (from 1 to 6 months), young animals (6 to 24 months) and adults (over 24 months), respectively, while geometric mean faecal egg counts (FECs) for each of these age categories were 125, 66 and 15 eggs per gram, respectively. Six genera of strongyles were found in the faecal cultures, i.e. in descending order of occurrence, Cooperia, Oesophagostomum, Haemonchus, Trichostrongylus, Mecistocirrus and Bunostomum. The prevalences of Fasciola and Paramphistomum, estimated by coprological examination, varied between 5-20% and 45-95%, respectively. Logistic mixed models were used to investigate associations of morbidity markers with the presence of parasite infection. A low BCS was associated with gastrointestinal nematode and liver fluke infections, and soft faecal consistency with Paramphistomum infections. However, other factors such as nutritional deficiencies and intercurrent diseases are likely to enhance the effects of parasites and should therefore be considered when using these morbidity parameters as indicators of parasitism
Leishmania taxonomy up for promotion? [letter]
No full textIn this letter, we discuss the basis for a reviewed taxonomy of the Leishmania genus and the practical implications for typing in different clinical or research settings
Schistosomiasis in travellers and migrants
No full textSchistosomiasis is a tropical parasitic disease caused by blood-dwelling fluke worms of the genus Schistosoma whose infective stages, the cercariae, are amplified through mollusks acting as intermediate hosts. People are infected when exposed to fresh water containing cercariae that penetrate the skin. There are however considerable differences in intensity of infection and morbidity, depending on the pattern of exposure and the infective species. In travellers, schistosomiasis differs substantially from infection in endemic populations in many aspects: geography, morbidity, treatment and prevention. In migrants, schistosomiasis manifests itself in a way more akin to what is seen in endemic populations. In this paper we will review the specific issues associated with schistosomiasis in travellers and migrants, with emphasis on the acute disease manifestations in non-immune persons, and on neuroschistosomiasis as a potential severe complication. We discuss new trends in diagnosis and treatment with respect to the specific disease stage, and summarize precautionary measures and novel ways to prevent Schistosoma infection in travellers
A telemedicine service for HIV/AIDS physicians working in developing countries
No full textIn 2003, the Institute of Tropical Medicine (ITM) in Antwerp set up an Internet-based decision support service to assist health-care workers in the management of difficult HIV/AIDS cases. This service is available to physicians working in resource-limited settings. Between April 2003 and December 2009, the telemedicine service received 1058 queries, from more than 40 countries, mostly resource-constrained. In the first six years there were 952 queries, of which 459 (49%) were posted on the web-based telemedicine discussion forum and the rest sent by email. All queries were handled by a co-ordinator who forwarded them to a network of specialists, based at the ITM and at other institutions. The average time to provide a first reply was 24 hours. Almost half of the queries received in the first six years (n = 466) were related to the use of antiretroviral medications. The response rate to a user questionnaire was 19% (73 questionnaires returned out of 387 delivered): half of those (n = 37) came from active users and the remainder (n = 36) from clinicians who had never used the system. The user survey showed that telemedicine advice was valuable in the management of specific cases, and significantly influenced the way that clinicians managed other similar cases subsequently. Nonetheless, there was a declining trend in the rate of use of the service
