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Differences in virulence and immune response induced in a murine model by isolates of Mycobacterium ulcerans from different geographic areas
No full textBuruli ulcer (BU) is the third most common mycobacterial disease in immunocompetent hosts. BU is caused by Mycobacterium ulcerans, which produces skin ulcers and necrosis at the site of infection. The principal virulence factor of M. ulcerans is a polyketide-derived macrolide named mycolactone, which has cytotoxic and immunosuppressive activities. We determined the severity of inflammation, histopathology and bacillary loads in the subcutaneous footpad tissue of BALB/c mice infected with 11 different M. ulcerans isolates from diverse geographical areas. Strains from Africa (Benin, Ghana, Ivory Coast) induced the highest inflammation, necrosis and bacillary loads, whereas the strains collected from Australia, Asia (Japan, Malaysia, New Guinea), Europe (France) and America (Mexico) induced mild inflammation. Subsequently, animals were infected with the strain that exhibited the highest (Benin) or lowest (Mexico) level of virulence in order to analyse the local immune response generated. The Mexican strain, which does not produce mycolactone, induced a predominantly T helper type 1 (Th1) cytokine profile with constant high expression of the anti-microbial peptides beta defensins 3 and 4, in co-existence with low expression of the anti-inflammatory cytokines interleukin (IL)-10, IL-4 and transforming growth factor (TGF)-beta. The highly virulent strain from Benin which produces mycolactone A/B induced the opposite pattern. Thus, different local immune responses were found depending on the infecting M. ulcerans strain
Outcomes after chemotherapy with WHO category II regimen in a population with high prevalence of drug resistant tuberculosis
No full textStandard short course chemotherapy is recommended by the World Health Organization to control tuberculosis worldwide. However, in settings with high drug resistance, first line standard regimens are linked with high treatment failure. We evaluated treatment outcomes after standardized chemotherapy with the WHO recommended category II retreatment regimen in a prison with a high prevalence of drug resistant tuberculosis (TB). A cohort of 233 culture positive TB patients was followed through smear microscopy, culture, drug susceptibility testing and DNA fingerprinting at baseline, after 3 months and at the end of treatment. Overall 172 patients (74%) became culture negative, while 43 (18%) remained positive at the end of treatment. Among those 43 cases, 58% of failures were determined to be due to treatment with an inadequate drug regimen and 42% to either an initial mixed infection or re-infection while under treatment. Overall, drug resistance amplification during treatment occurred in 3.4% of the patient cohort. This study demonstrates that treatment failure is linked to initial drug resistance, that amplification of drug resistance occurs, and that mixed infection and re-infection during standard treatment contribute to treatment failure in confined settings with high prevalence of drug resistance
Eating out of home in Vietnamese adolescents: socioeconomic factors and dietary associations
No full textBACKGROUND: Out-of-home (OH) eating in developed countries is associated with suboptimal dietary intakes, but evidence is scarce on the situation in developing countries. OBJECTIVE: The objective of this study was to determine the nutritional contribution of OH eating and related socioeconomic determinants in Vietnamese adolescents. DESIGN: A 24-h recall was used to collect food intake data in a cross-sectional study of 1172 adolescents living in urban and rural areas. Multilevel analysis compared the mean daily intakes of energy, energy density, energy from fat, food groups, vitamin A, iron, and zinc in low, middle, and high consumers of OH food. Socioeconomic associations of OH eating were analyzed in a subsample of 870 adolescents. RESULTS: OH foods contributed 42% of fruit and vegetables, 23% of sodium, 21% of energy, 21% of vitamin A, 21% of iron, and 21% of zinc consumed per day. OH eating was negatively associated with total energy intake and energy density and positively associated with dietary diversity, energy contribution from fat, and consumption of sugar products. In rural areas, OH eating was positively associated with iron, fruit, meat, poultry, and offal intake. Female sex (P < 0.001), residence in urban areas (P < 0.001), and amount of pocket money (P < 0.001) were positively associated with consumption of OH foods. CONCLUSIONS: OH eating added a number of desirable foods and nutrients but was also associated with higher consumption of energy from fat and sugar products. Independent of household wealth and locality, pocket money and sex are important determinants of OH eating
Natural infection of Phlebotomus argentipes with Leishmania and other trypanosomatids in a visceral leishmaniasis endemic region of Nepal
No full textMonitoring Leishmania infection in sand flies is important for understanding the eco-epidemiology of kala-azar and assessing the impact of the recently launched kala-azar control programme in the Indian subcontinent. We applied a PCR technique that targets rRNA genes to estimate the natural incidence of Leishmania infection in sand flies sampled in six villages of the Terai region of Nepal. Amplifications were made on 135 pools of sand flies and confirmed by sequencing. Seven pools were found to be PCR positive: in five of them we identified the rDNA signature found in Leishmania spp., whereas two other pools revealed a sequence compatible with other trypanosomatids. Different methodologies were applied to evaluate the infection rate from pools of unequal size and estimated the infection rate to range from 0.468% to 0.578% for the Leishmania group and from 0.185% to 0.279% for the non-Leishmania group. Our results highlight the diversity of flagellate infections likely to be encountered in Phlebotomus argentipes populations. Our methodology allows clear discrimination of Leishmania from other trypanosomatids and should be applied on larger insect samples or in longitudinal studies
In vitro synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20)
No full textOBJECTIVES: To block the different mechanisms of HIV mucosal transmission, it is likely that use of several microbicide molecules will lead to the best protection against HIV transmission. Indeed, the combination of microbicides with complementary mechanisms of action is expected to increase the antiviral potency of the formulation. METHODS: The gp120-interacting plant lectin HHA ('Hippeastrum hybrid agglutinin'), the non-nucleoside reverse transcriptase inhibitor KRV2110 and the fusion inhibitor enfuvirtide (T20) were combined in 12 drug associations by using the Ray combination design method. Their activity against HIV-1(BaL) was assessed by the lymphocyte infectivity reduction assay and by the single-cycle BaL pseudovirus (PV) assay. In addition, their cell tolerance was evaluated for HEC-1 and HeLa epithelial cell lines, both originating from genital tissue. RESULTS: All evaluated combinations showed synergistic activity in both lymphocyte infectivity reduction and single-cycle BaL PV assays. The combination HHA + KRV2110 resulted in the highest cell viability, whereas the combinations including T20 exhibited a dose-dependent decrease in cell viability, demonstrating the differential tolerance of epithelial cell lines to the combinations. CONCLUSIONS: These observations provide a rational basis for in vitro testing of microbicide candidate molecule combinations, including anti-HIV-1 and cytotoxic cellular assays
Fumonisins exposure from freshly harvested and stored maize and its relationship with traditional agronomic practices in Rombo District, Tanzania
No full textThe exposure to fumonisins from the maize harvest of 2006 (before and after sorting and storage) for 67 families was assessed along with its statistical association with agronomic practices in Rombo, Tanzania. Fumonisins were determined by high-performance liquid chromatography (HPLC) and exposure estimated based on 60 kg body weight and maize intake of 356 g per person day-1. Based on contamination in the unsorted maize, exposure for 27% of the families would exceed the provisional maximum tolerable daily intake of 2 µg kg-1 body weight. The odds ratio of fumonisin exposure from maize hybrid 614 (H614) were: two times higher compared with non-H614 maize (p = 0.089); and five times higher when the maize was grown without fertilizer (p = 0.004). Sorting maize before storage reduced the percentage of families with unacceptable exposures to 6%. Therefore, the results imply that planting of the non-H614 seeds using fertilizers combined with pre-storage sorting of maize significantly minimizes fumonisins exposure in Rombo. A field experiment to verify these findings is needed