Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease

BackgroundAnthropogenic land use may influence transmission of multi-host vector-borne pathogens by changing diversity, relative abundance, and community composition of reservoir hosts. These reservoir hosts may have varying competence for vector-borne pathogens depending on species-specific characteristics, such as life history strategy. The objective of this study is to evaluate how anthropogenic land use change influences blood meal species composition and the effects of changing blood meal species composition on the parasite infection rate of the Chagas disease vector Rhodnius pallescens in Panama.Methodology/Principal Findings R. pallescens vectors (N = 643) were collected in different habitat types across a gradient of anthropogenic disturbance. Blood meal species in DNA extracted from these vectors was identified in 243 (40.3%) vectors by amplification and sequencing of a vertebrate-specific fragment of the 12SrRNA gene, and T. cruzi vector infection was determined by pcr. Vector infection rate was significantly greater in deforested habitats as compared to contiguous forests. Forty-two different species of blood meal were identified in R. pallescens, and species composition of blood meals varied across habitat types. Mammals (88.3%) dominated R. pallescens blood meals. Xenarthrans (sloths and tamanduas) were the most frequently identified species in blood meals across all habitat types. A regression tree analysis indicated that blood meal species diversity, host life history strategy (measured as rmax, the maximum intrinsic rate of population increase), and habitat type (forest fragments and peridomiciliary sites) were important determinants of vector infection with T. cruzi. The mean intrinsic rate of increase and the skewness and variability of rmax were positively associated with higher vector infection rate at a site.Conclusions/SignificanceIn this study, anthropogenic landscape disturbance increased vector infection with T. cruzi, potentially by changing host community structure to favor hosts that are short-lived with high reproductive rates. Study results apply to potential environmental management strategies for Chagas disease.

Identifying the source of resurgent parasites is paramount to a strategic, successful intervention for malaria elimination. Although the malaria incidence in Panama is low, a recent outbreak resulted in a 6-fold increase in reported cases. We hypothesized that parasites sampled from this epidemic might be related and exhibit a clonal population structure. We tested the genetic relatedness of parasites, using informative single-nucleotide polymorphisms and drug resistance loci. We found that parasites were clustered into 3 clonal subpopulations and were related to parasites from Colombia. Two clusters of Panamanian parasites shared identical drug resistance haplotypes, and all clusters shared a chloroquine-resistance genotype matching the pfcrt haplotype of Colombian origin. Our findings suggest these resurgent parasite populations are highly clonal and that the high clonality likely resulted from epidemic expansion of imported or vestigial cases. Malaria outbreak investigations that use genetic tools can illuminate potential sources of epidemic malaria and guide strategies to prevent further resurgence in areas where malaria has been eliminated.

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Abstract. Anthropogenic disturbance is associated with increased vector-borne infectious disease transmission in wildlife, domestic animals, and humans. The objective of this study was to evaluate how disturbance of a tropical forest landscape impacts abundance of the triatomine bug Rhodnius pallescens , a vector of Chagas disease, in the region of the Panama Canal in Panama. Rhodnius pallescens was collected (n = 1,186) from its primary habitat, the palm Attalea butyracea , in five habitat types reflecting a gradient of anthropogenic disturbance. There was a high proportion of palms infested with R. pallescens across all habitat types (range = 77.1-91.4%). Results show that disturbed habitats are associated with increased vector abundance compared with relatively undisturbed habitats. Bugs collected in disturbed sites, although in higher abundance, tended to be in poor body condition compared with bugs captured in protected forest sites.

BackgroundThis study aims to describe the epidemiological and entomological factors associated with a recent malaria outbreak that occurred in 2012 in a socially marginalized population from Guna Yala Comarca in Panama.MethodsA descriptive and observational study was conducted by analysing demographic and epidemiological data from all malaria cases registered during 2012 in the Comarca Guna Yala, Panama. Malaria intensity indicators were calculated during the study period. Entomological evaluations were performed monthly, from October to December 2012, in the three communities that presented the most intense malaria transmission during the first semester of 2012. Anopheles breeding habitats were also characterized.ResultsDuring the studied period, 6754 blood smears were examined (17.8 % of the total population), and 143 were confirmed as positive for Plasmodium vivax. A significant increase of malaria transmission risk indicators (API: 3.8/1000, SPR: 2.1 %) was observed in Guna Yula, when compared with previous years, and also in comparison with estimates from the whole country. Anopheles albimanus was the most abundant and widespread (877; 72.0 %) vector species found in the three localities, followed by Anopheles punctimacula (231; 19.0 %) and Anopheles aquasalis (110; 9.0 %). Three An. albimanus pools were positive for P. vivax, showing an overall pooled prevalence estimate of 0.014.ConclusionsData analysis confirmed that during 2012 a malaria epidemic occurred in Guna Yala. Panama. This study provides baseline data on the local epidemiology of malaria in this vulnerable region of Panamá. This information will be useful for targeting control strategies by the National Malaria Control Programme.

In this study we investigated the possible role of two CCR5 gene polymorphisms, CCR5Delta32 deletion and CCR5 59029 A-->G promoter point mutation, in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease. These CCR5 polymorphisms were assessed in 85 seropositive (asymptomatic, n=53; cardiomyopathic, n=32) and 87 seronegative individuals. The extremely low frequency (0.009) of the CCR5Delta32 allele in our population did not allow us to analyse its possible influence on T. cruzi infection. We found no differences in the distribution of CCR5 59029 promoter genotype or phenotype frequencies between total chagasic patients and controls. However, we observed that the CCR5 59029-A/G genotype was significantly increased in asymptomatic with respect to cardiomyopathic patients (P=0.02; OR=0.33, 95% CI 0.10-0.94). In addition, the presence of the CCR5 59029-G allele was also increased in asymptomatics when compared with cardiomyopathics (P=0.02; OR=0.35, 95% CI 0.12-0.96). Our data suggest that the CCR5 59029 promoter polymorphism may be involved in a differential susceptibility to chagasic cardiomyopathy.

A major challenge of infectious disease elimination is the need to interrupt pathogen transmission across all vulnerable populations. Ethnic minorities are among the key vulnerable groups deserving special attention in disease elimination initiatives, especially because their lifestyle might be intrinsically linked to locations with high transmission risk. There has been a renewed interest in malaria elimination, which has ignited a quest to understand factors necessary for sustainable malaria elimination, highlighting the need for diverse approaches to address epidemiological heterogeneity across malaria transmission settings. An analysis of malaria incidence among the Guna Amerindians of Panamá over the last 34 years showed that this ethnic minority was highly vulnerable to changes that were assumed to not impact malaria transmission. Epidemic outbreaks were linked with El Niño Southern Oscillations and were sensitive to political instability and policy changes that did not ensure adequate attention to the malaria control needs of the Gunas. Our results illustrate how the neglect of minorities poses a threat to the sustainable control and eventual elimination of malaria in Central America and other areas where ethnic minorities do not share the benefits of malaria control strategies intended for dominant ethnic groups.