Outbreak of Cutaneous Leishmaniasis in Peruvian Military Personnel Undertaking Training Activities in the Amazon Basin, 2010

ArticleMilitary personnel deployed to the Amazon Basin are at high risk for cutaneous leishmaniasis (CL). We responded to an outbreak among Peruvian Army personnel returning from short-term training in the Amazon, conducting active case detection, lesion sample collection, and risk factor assessment. The attack rate was 25% (76/303); the incubation period was 2–36 weeks (median = 8). Most cases had one lesion (66%), primarily ulcerative (49%), and in the legs (57%). Real-time polymerase chain reaction (PCR) identified Leishmania (Viannia) braziliensis (59/61 = 97%) and L. (V.) guyanensis (2/61 = 3%). Being male (risk ratio [RR] = 4.01; P = 0.034), not wearing long-sleeve clothes (RR = 1.71; P = 0.005), and sleeping in open rooms (RR = 1.80; P = 0.009) were associated with CL. Sodium stibogluconate therapy had a 41% cure rate, less than previously reported in Peru (70%; P < 0.001). After emphasizing pre-deployment education and other basic prevention measures, trainees in the following year had lower incidence (1/278 = 0.4%; P < 0.001). Basic prevention can reduce CL risk in deployed militaries.The outbreak response was supported by the Peruvian Army Health Command COSALE and the Peruvian Ministry of Health through the General Epidemiology Directorate and the Health Directorate II, south Lima, and the. In addition, partial support was provided by grants CO497_11_L1 and CO466_11_L1 of the Global Emerging Infections Surveillance and Response System (AFHSC/GEIS) of the U.S. Department of Defense and the training grant 2D43 TW007393 awarded to the U.S. Naval Medical Research Unit No. 6 (NAMRU-6) by the Fogarty International Center of the National Institutes of Health (FIC/NIH). This study is part of the dissertation of Marianela Ore for a Masters in Epidemiological Research offered jointly by the Universidad Peruana Cayetano Heredia (UPCH) and NAMRU-6

A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys

SummaryAntigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans

Symptoms and Immune Markers in Plasmodium/Dengue Virus Co-infection Compared with Mono-infection with Either in Peru.

Malaria and dengue are two of the most common vector-borne diseases in the world, but co-infection is rarely described, and immunologic comparisons of co-infection with mono-infection are lacking.We collected symptom histories and blood specimens from subjects in a febrile illness surveillance study conducted in Iquitos and Puerto Maldonado, Peru, between 2002-2011. Nineteen symptoms and 18 immune markers at presentation were compared among those with co-infection with Plasmodium/dengue virus (DENV), Plasmodium mono-infection, and DENV mono-infection. Seventeen subjects were identified as having Plasmodium/DENV co-infection and were retrospectively matched with 51 DENV mono-infected and 44 Plasmodium mono-infected subjects. Those with Plasmodium mono-infection had higher levels of IL-4, IL-6, IL-10, IL-12, IL-13, IL-17A, IFN-γ, and MIP1-α/CCL3 compared with DENV mono-infection or co-infection; those with Plasmodium mono-infection had more cough than those with DENV mono-infection. Subjects with DENV mono-infection had higher levels of TGF-β1 and more myalgia than those with Plasmodium mono-infection. No symptom was more common and no immune marker level was higher in the co-infected group, which had similar findings to the DENV mono-infected subjects.Compared with mono-infection with either pathogen, Plasmodium/DENV co-infection was not associated with worse disease and resembled DENV mono-infection in both symptom frequency and immune marker level

Case reports and case series of co-infection with <i>Plasmodium</i> and dengue virus.

<p>Case reports and case series of co-infection with <i>Plasmodium</i> and dengue virus.</p

Next-Generation Sequencing of \u3ci\u3ePlasmodium vivax\u3c/i\u3e Patient Samples Shows Evidence of Direct Evolution in Drug-Resistance Genes

Understanding the mechanisms of drug resistance in Plasmodium vivax, the parasite that causes the most widespread form of human malaria, is complicated by the lack of a suitable long-term cell culture system for this parasite. In contrast to P. falciparum, which can be more readily manipulated in the laboratory, insights about parasite biology need to be inferred from human studies. Here we analyze the genomes of parasites within 10 human P. vivax infections from the Peruvian Amazon. Using nextgeneration sequencing we show that some P. vivax infections analyzed from the region are likely polyclonal. Despite their polyclonality we observe limited parasite genetic diversity by showing that three or fewer haplotypes comprise 94% of the examined genomes, suggesting the recent introduction of parasites into this geographic region. In contrast we find more than three haplotypes in putative drug-resistance genes, including the gene encoding dihydrofolate reductase-thymidylate synthase and the P. vivax multidrug resistance associated transporter, suggesting that resistance mutations have arisen independently. Additionally, several drug-resistance genes are located in genomic regions with evidence of increased copy number. Our data suggest that whole genome sequencing of malaria parasites from patients may provide more insight about the evolution of drug resistance than genetic linkage or association studies, especially in geographical regions with limited parasite genetic diversity

Serum levels of immune markers among patients with <i>Plasmodium</i>/DENV co-infection, DENV mono-infection, and <i>Plasmodium</i> mono-infection.

<p>Serum levels were analyzed by 17-plex cytokine array (Biorad Laboratories) for all immune markers except TGF-β1, which was measured by an R&D Systems ELISA kit. Three immune markers were excluded (GM-CSF, IL-5, and IL-2) from this analysis because more than 25% of the values fell below the limit of detection of the assays. Horizontal bars represent group median and inter-quartile range. Red dotted lines show lower limit of detection for each immune marker. Units on the y-axis are log 10 transformed scales of analyte concentration in ng/mL for all immune markers except for TGF-β1, which is represented in μg/mL. * p<0.05 for group comparison by the Kruskal-Wallis test followed by post-hoc Dunn’s pair-wise comparison.</p

Characteristics of the co-infected, dengue virus mono-infected, and <i>Plasmodium</i> mono-infected groups.

<p>Characteristics of the co-infected, dengue virus mono-infected, and <i>Plasmodium</i> mono-infected groups.</p

Matched group comparisons of inflammatory marker levels in subjects with co-infection, dengue virus mono-infection, and <i>Plasmodium</i> mono-infection using random effect regression.

<p>Matched group comparisons of inflammatory marker levels in subjects with co-infection, dengue virus mono-infection, and <i>Plasmodium</i> mono-infection using random effect regression.</p