Active transmission of human chagas disease in Colima Mexico

Despite efforts to eradicate American trypanosomiasis (AT) and Chagas disease from the Americas, there are still areas of active transmission that can eventually become a source of reinfection in previously controlled regions. Mexico could be one of those areas, where there are no formal preventive control programs despite the presence of communities infested by Triatominae bugs infected with Trypanosoma cruzi. This study explored the prevalence of T. cruzi infection in 405 habitants of 17 communities in the state of Colima, on the Pacific Mexican coast, through a seroepidemiological probabilistic survey. The results revealed a point seroprevalence of 2.4% positive for anti-T. cruzi. In addition, 2 clinical cases of chronic and 2 of acute Chagas disease were detected in the explored communities. These findings confirm the risk of active transmission of AT in Western Mexico, especially in rural and suburban communities infested with intra-domestic triatominae, where control programs should be implemented.     

The role of cholinesterases in chagas disease

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) hydrolyze acetylcholine (ACh) in neural synaptic clefts and are primarily found in erythrocytes and blood plasma, respectively. Besides inactivating ACh, cholinesterases may play a non-classical role in inflammation and in immune response. In a previous study, we reported that BChE levels were decreased in chronic Chagas disease patients presenting the mega syndromes. In this series, we reported that: i) the activity of AChE did not differ between patients and controls, irrespective of the presence or not of the 1057C > A ACHE polymorphism, and ii) the increased BChE levels modestly influenced the AChE activity in Chagas disease.     

Immune suppressor substance in experimental chagas disease

Specific and generalized immune suppression has been reported in several acute and chronic parasitic infections. In Chagas disease, soluble suppressor substances have been demonstrated in murine experimental models, but the nature and origin of these substances remain uncertain. Here, Eddy Liew reviews recent findings on immune suppression in inbred mouse strains infected with Trypanosoma cruzi. He suggests that production of suppressor substances may be an appropriate means to balance host-protective immunity with the possible risk of autoimmune disease, but, because of the apparent genetic restriction of suppressor substance production, raises doubts about its true biological significance.     

Malaria sporozoites: survival, transmission and disease control

A basic fact in malariology is that human malaria infections result from the bite of an infective anopheline mosquito. Without sporozoite transmission there is no malaria. Here, John Beier highlights our understanding of sporozoite biology from the perspective of how sporozoites develop and survive in mosquitoes, how they are transmitted during bloodfeeding, and how key elements in sporozoite-vector relationships present new opportunities for tackling critical questions relevant for disease control.     

Characterization and carbon metabolism in fungi pathogenic to Triatoma infestans, a chagas disease vector

The pathogenicity of Metarhizium anisopliae (Ma) and Beauveria bassiana (Bb) isolates against Triatoma infestans, the major vector of Chagas disease in Argentina is reported. A 100% mortality was achieved with mean lethal times varying form 5.8 (Ma6) to 7.7 (Bb5) or 11.1 days (Bb10). The fatty acid, hydrocarbon, and total lipid patterns were compared for glucose-grown and alkane-grown Bb10 cultures. The alkane-grown cells showed a lipid pattern different from that of glucose-grown cells, with triacylglyercol as the major lipid fraction, whereas sterols prevailed in the glucose-grown cells. A significant reduction in the relative amounts of linoleic acid diminished the unsaturated/saturated fatty acid ratio for alkane-grown cells; in addition, large amounts of heptacosanoic and eicosanoic acids were detected in the saturated fraction. The hydrocarbon profile of Bb10 showed a saturated chain length distribution,with a marked prevalence for straight chains, ranging from n-C18 to n-C37 in the carbon skeleton, with n-C22 as the major component. Alkane-grown cells showed no qualitative changes in their hydrocarbon fraction, but a similar ratio for odd/even carbon chains. After 48-h incubation assays,[1-(14)C]acetate uptake was largely diminished following a period of alkane growth induction. Glucose-grown cells readily incorporated 19% of the labelinto phospholipids, hydrocarbons, triacylglycerols, and free fatty acids. In contrast, incorporation was reduced to 5.3% for alkane-grown cells, accounting only for phospholipid synthesis.     

Lower richness of small wild mammal species and chagas disease risk

A new epidemiological scenario involving the oral transmission of Chagas disease, mainly in the Amazon basin, requires innovative control measures. Geospatial analyses of the Trypanosoma cruzi transmission cycle in the wild mammals have been scarce. We applied interpolation and map algebra methods to evaluate mammalian fauna variables related to small wild mammals and the T. cruzi infection pattern in dogs to identify hotspot areas of transmission. We also evaluated the use of dogs as sentinels of epidemiological risk of Chagas disease. Dogs (n = 649) were examined by two parasitological and three distinct serological assays. kDNA amplification was performed in patent infections, although the infection was mainly sub-patent in dogs. The distribution of T. cruzi infection in dogs was not homogeneous, ranging from 11–89% in different localities. The interpolation method and map algebra were employed to test the associations between the lower richness in mammal species and the risk of exposure of dogs to T. cruzi infection. Geospatial analysis indicated that the reduction of the mammal fauna (richness and abundance) was associated with higher parasitemia in small wild mammals and higher exposure of dogs to infection. A Generalized Linear Model (GLM) demonstrated that species richness and positive hemocultures in wild mammals were associated with T. cruzi infection in dogs. Domestic canine infection rates differed significantly between areas with and without Chagas disease outbreaks (Chi-squared test). Geospatial analysis by interpolation and map algebra methods proved to be a powerful tool in the evaluation of areas of T. cruzi transmission. Dog infection was shown to not only be an efficient indicator of reduction of wild mammalian fauna richness but to also act as a signal for the presence of small wild mammals with high parasitemia. The lower richness of small mammal species is discussed as a risk factor for the re-emergence of Chagas disease.     

Fat tissue regulates the pathogenesis and severity of cardiomyopathy in murine chagas disease

Chronic Chagas cardiomyopathy (CCC) caused by a parasite Trypanosoma cruzi is a life-threatening disease in Latin America, for which there is no effective drug or vaccine. The pathogenesis of CCC is complex and multifactorial. Previously, we demonstrated T. cruzi infected mice lose a significant amount of fat tissue which correlates with progression of CCC. Based on this an investigation was undertaken during both acute and chronic T. cruzi infection utilizing the FAT-ATTAC murine model (that allows modulation of fat mass) to understand the consequences of the loss of adipocytes in the regulation of cardiac parasite load, parasite persistence, inflammation, mitochondrial stress, ER stress, survival, CCC progression and CCC severity. Mice were infected intraperitoneally with 5x10⁴ and 10³ trypomastigotes to generate acute and chronic Chagas models, respectively. Ablation of adipocytes was carried out in uninfected and infected mice by treatment with AP21087 for 10 days starting at 15DPI (acute infection) and at 65DPI (indeterminate infection). During acute infection, cardiac ultrasound imaging, histological, and biochemical analyses demonstrated that fat ablation increased cardiac parasite load, cardiac pathology and right ventricular dilation and decreased survival. During chronic indeterminate infection ablation of fat cells increased cardiac pathology and caused bi-ventricular dilation. These data demonstrate that dysfunctional adipose tissue not only affects cardiac metabolism but also the inflammatory status, morphology and physiology of the myocardium and increases the risk of progression and severity of CCC in murine Chagas disease.     

From re-emergence to hyperendemicity: the natural history of the dengue epidemic in Brazil

Background

Dengue virus (DENV) was reintroduced into Brazil in 1986 and by 1995 it had spread throughout the country. In 2007 the number of dengue hemorrhagic fever (DHF) cases more than doubled and a shift in the age distribution was reported. While previously the majority of DHF cases occurred among adults, in 2007 53% of cases occurred in children under 15 years old. The reasons for this shift have not been determined.

Methods and Findings

Age stratified cross-sectional seroepidemiologic survey conducted in Recife, Brazil in 2006. Serostatus was determined by ELISA based detection of Dengue IgG. We estimated time-constant and time-varying forces of infection of DENV between 1986 and 2006. We used discrete-time simulation to estimate the accumulation of monotypic and multitypic immunity over time in a population previously completely susceptible to DENV. We projected the age distribution of population immunity to dengue assuming similar hazards of infection in future years. The overall prevalence of DENV IgG was 0.80 (n = 1427). The time-constant force of infection for the period was estimated to be 0.052 (95% CI 0.041, 0.063), corresponding to 5.2% of susceptible individuals becoming infected each year by each serotype. Simulations show that as time since re-emergence of dengue goes by, multitypic immunity accumulates in adults while an increasing proportion of susceptible individuals and those with monotypic immunity are among young age groups. The median age of those monotypically immune can be expected to shift from 24 years, 10 years after introduction, to 13 years, 50 years after introduction. Of those monotypically immune, the proportion under 15 years old shifts from 27% to 58%. These results are consistent with the dengue notification records from the same region since 1995.

Interpretation

Assuming that persons who have been monotypically exposed are at highest risk for severe dengue, the shift towards younger patient ages observed in Brazil can be partially explained by the accumulation of multitypic immunity against DENV-1, 2, and 3 in older age groups, 22 years after the re-introduction of these viruses. Serotype specific seroepidemiologic studies are necessary to accurately estimate the serotype specific forces of infection.     

Land, language, and loci: mtDNA in Native Americans and the genetic history of Peru

Despite a long history of complex societies and despite extensive present-day linguistic and ethnic diversity, relatively few populations in Peru have been sampled for population genetic investigations. In order to address questions about the relationships between South American populations and about the extent of correlation between genetic distance, language, and geography in the region, mitochondrial DNA (mtDNA) hypervariable region I sequences and mtDNA haplogroup markers were examined in 33 individuals from the state of Ancash, Peru. These sequences were compared to those from 19 American Indian populations using diversity estimates, AMOVA tests, mismatch distributions, a multidimensional scaling plot, and regressions. The results show correlations between genetics, linguistics, and geographical affinities, with stronger correlations between genetics and language. Additionally, the results suggest a pattern of differential gene flow and drift in western vs. eastern South America, supporting previous mtDNA and Y chromosome investigations.     

A review of trachoma history in China: research,prevention, and control

Trachoma is one of the most widespread blinding eye diseases, which is harmful to human visual health. The efforts to prevent and control trachoma in China can be divided into three periods, i.e., highly epidemic period, research on pathogenesis and control of trachoma, and blinding trachoma elimination and epidemiological evaluation. In 1956, Prof. Feifan Tang and Xiaolou Zhang first discovered and isolated Chlamydia trachomatis, which clarified the cause of trachoma, and kick-started a fresh chapter in trachoma research, prevention, and control around the world. Although, the prevalence of trachoma differed in different areas, the average prevalence once exceeded 50% and was as high as 90% in some areas before and at early liberation of China. Therefore, the government-led efforts were made to comprehensively prevent and control trachoma, including development of National Plan for the Prevention and Control of Trachoma, nationwide screening and treatment of trachoma, implementation of National Patriotic Health Campaign and improvement of water supply and lavatories. After decades of effort, China reached the goal of eliminating blinding trachoma in 2015. China has gained remarkable achievements in the prevention and treatment of trachoma, making outstanding contributions toward the goal of eliminating trachoma worldwide. The research, prevention, and control of trachoma in China were reviewed in this paper.     

A field trial of alternative targeted screening strategies for Chagas disease in Arequipa, Peru

Background

Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa, population ∼860,000. It is unclear how to implement cost-effective screening programs across a large urban and periurban environment.

Methods

We compared four alternative screening strategies in 18 periurban communities, testing individuals in houses with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Vector data were obtained from routine Ministry of Health insecticide application campaigns. We performed ring case detection (radius of 15 m) around seropositive individuals, and collected data on costs of implementation for each strategy.

Results

Infection was detected in 21 of 923 (2.28%) participants. Cases had lived more time on average in rural places than non-cases (7.20 years versus 3.31 years, respectively). Significant risk factors on univariate logistic regression for infection were age (OR 1.02; p = 0.041), time lived in a rural location (OR 1.04; p = 0.022), and time lived in an infested area (OR 1.04; p = 0.008). No multivariate model with these variables fit the data better than a simple model including only the time lived in an area with triatomine bugs. There was no significant difference in prevalence across the screening strategies; however a self-assessment of disease risk may have biased participation, inflating prevalence among residents of houses where no infestation was detected. Testing houses with infected-vectors was least expensive. Ring case detection yielded four secondary cases in only one community, possibly due to vector-borne transmission in this community, apparently absent in the others.

Conclusions

Targeted screening for urban Chagas disease is promising in areas with ongoing vector-borne transmission; however, these pockets of epidemic transmission remain difficult to detect a priori. The flexibility to adapt to the epidemiology that emerges during screening is key to an efficient case detection intervention. In heterogeneous urban environments, self-assessments of risk and simple residence history questionnaires may be useful to identify those at highest risk for Chagas disease to guide diagnostic efforts.     

Population dynamics and feeding behavior of Triatoma brasiliensis and Triatoma pseudomaculata, main vectors of chagas disease in Northeastern Brazil

Biological parameters of Triatoma brasiliensis and T. pseudomaculata that could influence the epidemiological importance of these insects as vectors of Trypanosoma cruzi were compared. The parameters studied were incubation period, interval between hatching or moulting and first feeding, number of blood meals, development time, mortality, net reproductive rate, instantaneous daily reproductive rate, time-lapse before starting feeding, duration of feeding, blood ingestion capacity, occurrence of defecation and blood ingestion velocity. Most aspects of feeding were similar for the two species, although T. pseudomaculata had a longer life cycle than T. brasiliensis producing one and two generations per year, respectively. The two species had similar instantaneous daily rates of population growth.     

Evolution and pathology in chagas disease--a review

Trypanosoma cruzi acute infections often go unperceived, but one third of chronically infected individuals die of Chagas disease, showing diverse manifestations affecting the heart, intestines, and nervous systems. A common denominator of pathology in Chagas disease is the minimal rejection unit, whereby parasite-free target host cells are destroyed by immune system mononuclear effectors cells infiltrates. Another key feature stemming from T. cruzi infection is the integration of kDNA minicircles into the vertebrate host genome; horizontal transfer of the parasite DNA can undergo vertical transmission to the progeny of mammals and birds. kDNA integration-induced mutations can enter multiple loci in diverse chromosomes, generating new genes, pseudo genes and knock-outs, and resulting in genomic shuffling and remodeling over time. As a result of the juxtaposition of kDNA insertions with host open reading frames, novel chimeric products may be generated. Germ line transmission of kDNA-mutations determined the appearance of lesions in birds that are indistinguishable from those seen in Chagas disease patients. The production of tissue lesions showing typical minimal rejection units in birds' refractory to T. cruzi infection is consistent with the hypothesis that autoimmunity, likely triggered by integration-induced phenotypic alterations, plays a major role in the pathogenesis of Chagas disease.     

A peculiar climbing Megalonychidae from the Pleistocene of Peru and its implication for sloth history

The Xenarthra, particularly the Tardigrada, are with the Notoungulata and Marsupialia among the most diversified South American mammals. Lujanian South American Land Mammal Age localities from the coastal Piedra Escrita site and Andean Casa del Diablo Cave, Peru, have yielded three specimens of the Megalonychidae Diabolotherium nordenskioldi gen. nov. This singular fossil sloth exhibits a peculiar mosaic of cranial and postcranial characters. Some are considered convergent with those of other sloths (e.g. 5/4 quadrangular teeth, characteristic of Megatheriidae), whereas others clearly indicate climbing capabilities distinct from the suspensory mode of extant sloths. The arboreal mode of life of D. nordenskioldi is suggested by considerable mobility of the elbow, hip, and ankle joints, a posteriorly convex ulna with an olecranon shorter than in fossorial taxa, a radial notch that faces more anteriorly than in other fossil sloths and forms an obtuse angle with the coronoid process (which increases the range of pronation–supination), a proximodistally compressed scaphoid, and a wide range of digital flexion. D. nordenskioldi underscores the great adaptability of Tardigrada: an arboreally adapted form is now added to the already known terrestrial, subarboreal, and aquatic (marine and freshwater) fossil sloths. A preliminary phylogenetic analysis of the Tardigrada confirmed the monophyly of Megatherioidea, Nothrotheriidae, Megatheriidae, and Megalonychidae, in which Diabolotherium is strongly nested.  © 2007 The Linnean Society of London, Zoological Journal of the Linnean Society , 2007, 149 , 179–235.     

A new method for forensic DNA analysis of the blood meal in chagas disease vectors demonstrated using Triatoma infestans from Chuquisaca, Bolivia

Background

Feeding patterns of the vector are important in the epidemiology of Chagas disease, the leading cause of heart disease in Latin America. Chagas disease is caused by the parasite, Trypanasoma cruzi, which is transmitted by blood feeding insects. Historically, feeding behaviours of haematophagous insects have been investigated using serological reactions, which have detection limits in terms of both taxonomic resolution, and quantity and quality of the blood meal. They are labor intensive, require technical expertise, need fresh or frozen samples and antibodies often are either not available commercially or the resources for synthesis and purification are not available. We describe an assay to identify vertebrate blood meal sources, and the parasite T. cruzi using species-specific PCR assays from insect vectors and use the method to provide information regarding three questions: (1) Do domestic and peri-domestic (chicken coop and animal corral) habitats vary in the blood meals detected in the vectors? (2) What is the pattern of multiple blood meals? (3) Does the rate of T. cruzi infection vary among habitats and is it associated with specific blood meal types?

Methodology/Principal Findings

Assays based on the polymerase chain reaction were evaluated for identification of the blood meal source in the heamatophagous Chagas disease vector Triatoma infestans. We evaluate a technique to identify 11 potential vertebrate food sources from the complex mixture extracted from the vector''s abdomen. We tested the assay on 81 T. infestans specimens collected from the Andean highlands in the department of Chuquisaca, located in central Bolivia, one of the regions in South America where sylvatic T. infestans have been reported. This area is suggested to be the geographic origin of T. infestans and has very high human infection rates that may be related to sylvatic vector populations.

Conclusion/Significance

The results of the assays revealed that a high percentage of insects collected in human dwellings had fed on peri-domestic animals. In contrast, one insect from a chicken coop but no bugs from corrals tested positive for human blood. Forty-eight percent of insects tested positive for more than one vertebrate species. T. cruzi infection was detected in 42% of the specimens. From the epidemiological point of view, the results reveal an overall pattern of movement from peri-domestic structures to human habitations for T. infestans in this region of Bolivia as well as the important role of pigs, dogs, chickens and guinea pigs in the dynamics of T. cruzi infection.     

Yellow-tailed woolly monkey (Lagothrix flavicauda) proximal spacing and forest strata use in La Esperanza,Peru

Inter-individual spacing of primates and their use of forest strata depend on temporal and spatial changes in the environment and on predator avoidance, group demography, and social conditions. Greater proximity also increases the chances of agonistic and affinitive contact between individuals. I collected behavioral data for three groups of yellow-tailed woolly monkeys (Lagothrix flavicauda) by instantaneous sampling of focal animals for 15 months in La Esperanza, northeastern Peru. By use of combined data for all groups I examined the effects of season, activity, and age/sex class on nearest-neighbor distances and forest strata use. Small differences were observed for nearest-neighbor distances, forest strata use by different age/sex classes, and activity. Adult males had the lowest contact index scores. Contact index scores were low for juvenile females, for which nearest-neighbor distances were largest. Very little aggressive behavior was observed. Focal animals preferred upper levels of the forest with little difference in height for different activities. Lagothrix flavicauda have very cohesive groups with little seasonal or activity-dependent difference between nearest-neighbor distances or proximity. These results suggest that this species has less variable social organization and greater group cohesion than other Atelini. However, more studies are needed on other populations of L. flavicauda to better determine the species’ social organization. Studies are also required to determine the extent to which dispersal times and kinship affect proximity, nearest-neighbor distances, and aggression.