Risk factors associated with the transmission of Andean cutaneous leishmaniasis.

This is a population-based case-control study of the risk factors associated with the transmission of Andean cutaneous leishmaniasis (uta) with a concurrent design comparing persons who developed uta against persons who did not. Cases and controls were matched by age. sex and place of residence. The unit of analysis was the person . The main exposure groups were: characteristics of the house, environmental characteristics around the house, and behaviour patterns of people. The study was carried out in five endemic regions of Peru. 187 cases and 335 controls were admitted to the study. Using matched and conditional logistic regression, in study areas of Lima & Ancash (region 1) and Piura (region 2) Departments we have identified risk factors which imply that transmission occurs (a) inside houses, (b) outside but close to houses, (c) around houses, but not clearly indoors or outdoors, and (d) away from houses. In region 1 we found three risk factors of type a, using a kerosene lamp (OR=6.6. c.i.:2.2-19.7), having a chimney (OR=4.9, c.i.: 1.9-12.5) and living in a stone house (OR=2.9, c.i.:1.6-5.2), one of type b, cutting wood (OR=7.4, c.i.:2.1-26.4), and three of type c. living in a house > 30 m from road (OR=3.9, c.i.: 1.4-10.7), with a vegetable garden (OR=2.8, c.i.: 1.1-4.1) and living in a house having > 6 persons (OR=4.2, c.i.:l.9-9.7). In region 2, we found four risk factors of type c, living in a house having an earth floor (OR=2.3. c.i.: 1.1-4.7), with cows (OR=1.3, c.i.: 1.1-1.6) and a neighbouring vegetable garden nearby (OR=2.9, c.i.:1.3-6.9), and living > 30 m from a river (OR=3.3, c.i.:3.1-8.4), and one of type d. doing irrigation work at night (OR=2.2, c.i.:1.2-4.2). The variability of risk factors between regions 1 and 2 can be explained by differences in (i) the frequency of exposures and (ii) the importance of factors. We conclude from OR's and PAR'S that much transmission occurs around houses. Certainly, some transmission is indoors: the population attributable risk for factors associated with indoor transmission in region 1 was 79%. suggesting the possibility of uta control by preventing biting in houses. It remains questionable how much transmission goes on outdoors

A Randomised Controlled Trial to Assess the Efficacy of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Falciparum Malaria in Peru

Background. Multi-drug resistant falciparum malaria is an important health problem in the Peruvian Amazon region. We carried out a randomised open label clinical trial comparing mefloquine-artesunate, the current first line treatment in this region, with dihydroartemisinin-piperaquine. Methods and Findings. Between July 2003 and July 2005, 522 patients with P. falciparum uncomplicated malaria were recruited, randomized (260 with mefloquine-artesunate and 262 with dihydroartemisinin-piperaquine), treated and followed up for 63 days. PCR-adjusted adequate clinical and parasitological response, estimated by Kaplan Meier survival and Per Protocol analysis, was extremely high for both drugs (99.6% for mefloquine-artesunate and 98.4% and for dihydroartemisinin-piperaquine) (RR: 0.99, 95%CI [0.97-1.01], Fisher Exact p=0.21). All recrudescences were late parasitological failures. Overall, gametocytes were cleared faster in the mefloquine-artesunate group (28 vs 35 days) and new gametocytes tended to appear more frequently in patients treated with dihydroartemisinin-piperaquine (day 7: 8 ( 3.6%) vs 2 (0.9%), RR: 3.84, 95%CI [0.82-17.87]). Adverse events such as anxiety and insomnia were significantly more frequent in the mefloquine-artesunate group, both in adults and children. Conclusion. Dihydroartemisinin-piperaquine is as effective as mefloquine-artesunate in treating uncomplicated P. falciparum malaria but it is better tolerated and more affordable than mefloquine-artesunate (US$1.0 versus US$18.65 on the local market). Therefore, it should be considered as a potential candidate for the first line treatment of P. falciparum malaria in Peru. Trial Registration. ClinicalTrials.gov NCT00373607 [http://www.clinicaltrials.gov/ct/show/NCT00373607]

Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of the <it>L. (V.) braziliensis </it>isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance of <it>L. (V.) braziliensis </it>to NO and nonresponsiveness to antimony therapy and cytokine production.</p> <p>Methods</p> <p>We evaluated the <it>in vitro </it>toxicity of NO against the promastigotes stages of <it>L. (V.) braziliensis </it>isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from <it>Leishmania </it>infected macrophage were used to measure TNF-α and IL-10 levels.</p> <p>Results</p> <p>Using NaNO₂(pH 5.0) as the NO source, <it>L. (V.) braziliensis </it>isolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) than <it>L. (V.) braziliensis </it>isolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant <it>L. (V.) braziliensis </it>isolated from responsive and refractory patients. NO-resistant <it>L. (V.) braziliensis </it>isolated from refractory patients infected more macrophages stimulated with LPS and IFN-γ at 120 hours than NO-susceptible <it>L. (V.) braziliensis </it>isolated from refractory patients. Also, lower levels of TNF-α were detected in supernatants of macrophages infected with NO-resistant <it>L. (V.) braziliensis </it>as compared to macrophages infected with NO-susceptible <it>L. (V.) braziliensis </it>(p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels.</p> <p>Conclusion</p> <p>These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis.</p