Electrocardiographic Abnormalities and Treatment with Benznidazole among Children with Chronic Infection by Trypanosoma cruzi: A Retrospective Cohort Study.

BACKGROUND: Chronic infection by Trypanosoma cruzi could cause heart conduction disturbances. We sought to analyze electrocardiographic abnormalities among children with chronic T. cruzi infection with and without trypanocidal treatment with benznidazole. METHODOLOGY/PRINCIPAL FINDINGS: We studied 111 children 6-16 years of age with asymptomatic chronic T. cruzi infection who were recruited in 1991-1992 in Salta, Argentina. Most children were randomly assigned to benznidazole 5 mg/Kg/day (n = 47) or matching placebo (n = 48) for 60 days. Remaining children (n = 16) received treatment with benznidazole 5 mg/Kg/day open-label. Electrocardiograms were obtained at baseline and in 1995-1996, 1998, 2000 and 2005, and were analyzed using the Buenos Aires method. Among the 94 children with an electrocardiogram at baseline, 8 (8.5%) had electrocardiographic abnormalities, including 4 (4.7%) children with right bundle branch block. Proportion of abnormal electrocardiograms in the full population (n = 111) remained constant over time (media follow-up 8.6 years). Multivariable adjusted prevalence ratios (95% confidence interval [95%CI]) for electrocardiographic abnormalities in 1995-1996, 1998, 2000 and 2005 comparing children treated with benznidazole versus those not treated were 2.76 (0.66, 11.60), 2.33 (0.44, 12.31), 3.06 (0.48, 19.56), and 1.94 (0.33, 11.25), respectively. Among the 86 children with a normal electrocardiogram at baseline, 16 (18.6%) developed electrocardiographic abnormalities during follow-up. The multivariable adjusted hazard ratio for incident electrocardiographic abnormalities comparing children treated with benznidazole versus those not treated was 0.68 (95%CI: 0.25, 1.88). CONCLUSIONS/SIGNIFICANCE: Electrocardiographic abnormalities are frequent among children with chronic T. cruzi infection. Treatment with benznidazole for 60 days may not be associated with less electrocardiographic abnormalities.

Fine-scale genetic structure in populations of the Chagas' disease vector Triatoma infestans (Hemiptera, Reduvidae).

Fine scale patterns of genetic structure and dispersal in Triatoma infestans populations from Argentina was analysed. A total of 314 insects from 22 domestic and peridomestic sites from the locality of San Martín (Capayán department, Catamarca province) were typed for 10 polymorphic microsatellite loci. The results confirm subdivision of T. infestans populations with restricted dispersal among sampling sites and suggest inbreeding and/or stratification within the different domestic and peridomestic structures. Spatial correlation analysis showed that the scale of structuring is approximately of 400 m, indicating that active dispersal would occur within this distance range. It was detected difference in scale of structuring among sexes, with females dispersing over greater distances than males. This study suggests that insecticide treatment and surveillance should be extended within a radius of 400 m around the infested area, which would help to reduce the probability of reinfestation by covering an area of active dispersal. The inferences made from fine-scale spatial genetic structure analyses of T. infestans populations has demonstrated to be important for community-wide control programs, providing a complementary approach to help improve vector control strategies.

Macrogeographic and microgeographic genetic structure of the Chagas' disease vector Triatoma infestans (Hemiptera: Reduviidae) from Catamarca, Argentina.

The genetic structure in populations of the Chagas' disease vector Triatoma infestans from six localities belonging to areas under the same insecticide treatment conditions of Catamarca province (Argentina) was examined at macrogeographical and microgeographical scales. A total of 238 insects were typed for 10 polymorphic microsatellite loci. The average observed and expected heterozygosities ranged from 0.319 to 0.549 and from 0.389 to 0.689, respectively. The present results confirm that populations of T. infestans are highly structured. Spatial genetic structure was detectable at macrogeographical and microgeographical levels. Comparisons of the levels of genetic variability between two temporal samples were carried out to assess the impact of the insecticide treatment. The genetic diversity of the population was not significantly affected after insecticide use since different genetic parameters (allele number, observed and expected heterozygosities) remained stable. However, loss of low frequency alleles and not previously found alleles were detected. The effective population size (N(e)) estimated was substantially lower in the second temporal sample than in the first; nevertheless, it is possible that the size of the remnant population after insecticide treatment was still large enough to retain the genetic diversity. Very few individuals did not belong to the local T. infestans populations as determined by assignment analyses, suggesting a low level of immigration in the population. The results of the assignment and first-generation migrant tests suggest male-biased dispersal at microgeographical level.

Sustainable vector control and management of Chagas disease in the Gran Chaco, Argentina.

Chagas disease remains a serious obstacle to health and economic development in Latin America, especially for the rural poor. We report the long-term effects of interventions in rural villages in northern Argentina during 1984-2006. Two community-wide campaigns of residual insecticide spraying immediately and strongly reduced domestic infestation and infection with Trypanosoma cruzi in Triatoma infestans bugs and dogs and more gradually reduced the seroprevalence of children <15 years of age. Because no effective surveillance and control actions followed the first campaign in 1985, transmission resurged in 2-3 years. Renewed interventions in 1992 followed by sustained, supervised, community-based vector control largely suppressed the reestablishment of domestic bug colonies and finally led to the interruption of local human T. cruzi transmission. Human incidence of infection was nearly an order of magnitude higher in peripheral rural areas under pulsed, unsupervised, community-based interventions, where human transmission became apparent in 2000. The sustained, supervised, community-based strategy nearly interrupted domestic transmission to dogs but did not eliminate T. infestans despite the absence of pyrethroid-insecticide resistance. T. infestans persisted in part because of the lack of major changes in housing construction and quality. Sustained community participation grew out of establishing a trusted relationship with the affected communities and the local schools. The process included health promotion and community mobilization, motivation, and supervision in close cooperation with locally nominated leaders.

Microsatellite analysis of genetic structure in natural Triatoma infestans (Hemiptera: Reduviidae) populations from Argentina: its implication in assessing the effectiveness of Chagas' disease vector control programmes.

The genetic structure in populations of the Chagas' disease vector Triatoma infestans was examined. Comparisons of the levels of genetic variability in populations of this species from areas with different periods since last insecticide treatment and from areas that never received treatment were also carried out. A total of 598 insects from 19 populations were typed for 10 polymorphic microsatellite loci. The average observed and expected heterozygosities ranged from 0.186 to 0.625 and from 0.173 to 0.787, respectively. Genetic drift and limited gene flow appear to have generated a substantial degree of genetic differentiation among the populations of T. infestans. Departures from Hardy-Weinberg expectations due to an excess of homozygotes suggested the presence of null alleles and population subdivision. Microgeographical analysis supports the existence of subdivision in T. infestans populations. Levels of genetic diversity in the majority of the populations of T. infestans from insecticide-treated localities were similar or higher than those detected in populations from areas without treatment. Since the populations of T. infestans are subdivided, a population bottleneck would result in independent genetic drift effects that could randomly preserve different combinations of alleles in each subpopulation. These events followed by a rapid population growth could have preserved high levels of genetic diversity. This study supports the hypothesis of vector population recovery from survivors of the insecticide-treated areas and therefore highlights the value of population genetic analyses in assessing the effectiveness of Chagas' disease vector control programmes.

Spatial pattern of reinfestation by Triatoma infestans in Chancanif, Argentina.

We examined the environmental correlates and the spatial pattern of infestation by Triatoma infestans, a vector of Chagas disease, in a rural area of Argentina five years following an insecticidal campaign. Patterns of infestation were identified in an entomological survey, as mapped with high-resolution satellite imagery and analyzed in a geographic information system. Logistic regression was used to relate infestation to observed household characteristics as well as the location and density of households. Location was the most significant predictor of infestation for domiciles. For peridomestic structures surrounding the domiciles, the combination of location and the presence/absence of goat pens was most significant. In considering any infestation, whether domiciliary or peridomestic, the combination of location, presence/absence of animal pens, and the type of household construction were found to be most significant. Using these statistical relationships to back-classify the field data resulted in accuracies between 85% and 87%. A map of infestation probability for the town of Chancaní was developed from the logistic regression.

[Epidemiology of Chagas disease in the state of Veracruz]. / Epidemiología de la enfermedad de Chagas en el estado de Veracruz.

OBJECTIVE: To assess the seroprevalence, household risk factors, and entomological indicators, in order to frame control measures in 11 Sanitary Jurisdictions of the state. MATERIAL AND METHODS: This study included 281 towns, 2 526 households, and 9782 individuals. Data were collected using a questionnaire. Blood was obtained in filter paper and a search for triatomines was conducted inside of and around dwellings. Prevalence rates were used to quantify exposure to risk factors and seropositivity. Odds ratios with 95% confidence intervals and Mantel-Haenszel chi-squared tests were obtained. Multivariate analysis was performed with unconditional logistic regression,variables included in the model were those that had a p-value up to 0.20 in the bivariate analysis. The etiologic fraction in the exposed was also obtained. RESULTS: The prevalence of Chagas disease was between 0 and 2.8%. Jurisdictions at a higher risk wereTuxpan, Panuco and Cordoba; Orizaba showed no risk. The main household risk factors were palma/zacate (palm-tree, grass leaves) roof and walls, dirt floor, the presence of the vector, and ventilation. CONCLUSIONS: Epidemiological surveillance should emphasize health education, housing improvement, and use of insecticides.

Incidence of trypanosoma cruzi infection among children following domestic reinfestation after insecticide spraying in rural northwestern Argentina.

Following increasing reinfestation with Triatoma infestans after insecticide spraying, the household incidence of infection with Trypanosoma cruzi in children was positively related to the domestic abundance of infected T. infestans and the presence or proportion of infected dogs or cats in Amamá, a rural village in northwestern Argentina. Seven (12.1%) children seronegative for antibodies to T. cruzi at baseline, with no history of travel or blood transfusion, seroconverted after three years. Six incident cases lived in houses heavily infested with T. infestans, with high proportions of bugs infected with T. cruzi and having fed on humans or dogs. The remaining incident case occurred under a very light domestic infestation detected only at the endpoint, and most bugs had fed on humans. Dogs had a 17 times greater force of infection than children (4.3% per year). Sustained vector surveillance is crucially needed in high-risk areas for Chagas disease such as the Gran Chaco.

Distribution and pathogenicity of Trypanosoma cruzi isolated from peridomestic populations of Triatoma infestans and Triatoma guasayana from rural Western Argentina.

We assessed the distribution of Trypanosoma cruzi infection in peridomestic triatomines collected manually at a district-wide scale in rural villages around Olta, Western Argentina, and typed the isolated strains according to their pathogenicity to laboratory mice. Of 1623 triatomines examined, only 14 (0.9%) were infected with T. cruzi based on microscopical examination of feces. The prevalence of T. cruzi infection was 0.8% in Triatoma infestans, 2.3% in T. guasayana, and nil in T. garciabesi, T. platensis, and T. eratyrusiformis. Local transmission occurred in kitchens, store-rooms and goat corrals or nearby, though at very low levels. T. cruzi was detected by at least one parasitological method in 11 (79%) of 14 microscope-positive bugs. Hemoculture was the most sensitive method (67%) followed by culture of organ homogenates, histopathology or xenodiagnosis of inoculated suckling mice (55-58%), and culture of microscope-positive bug feces (46%). The evidence suggests that most of the isolated T. cruzi strains would be myotropic type III. Our study establishes for the first time that peridomestic, microscope-positive T. guasayana nymphs were actually infected with T. cruzi, and may be implicated as a putative secondary vector of T. cruzi in domestic or peridomestic sites.

Epidemiología de la enfermedad de Chagas en el estado de Veracruz / Epidemiology of Chagas disease in the state of Veracruz

OBJETIVO: Identificar la seroprevalencia de enfermedad de Chagas, los factores de riesgo de la vivienda e índices entomológicos, para proponer medidas de control en 11 jurisdicciones sanitarias del estado de Veracruz. MATERIAL Y MÉTODOS: Entre 1997 y 2001 se hizo un estudio transversal cuya muestra quedó integrada por 281 localidades, 2 526 viviendas y 9 782 individuos. Se aplicó un cuestionario sobre factores de riesgo, se tomó sangre en papel filtro y se buscaron triatominos en el intra y peridomicilio. Se obtuvo la prevalencia de exposición a factores de riesgo y de seropositividad para la enfermedad. Se hizo análisis bivariado mediante la razón de momios, ji de Mantel y Haenszel e intervalo de confianza a 95 por ciento como prueba de significancia estadística. El análisis multivariado se hizo mediante la regresión logística no condicional y se incluyeron las variables que durante el análisis bivariado mostraron un valor de p hasta de 0.20. El impacto potencial se estimó con base en la fracción etiológica en expuestos. RESULTADOS: La prevalencia de enfermedad de Chagas fluctuó entre 0 y 2.8 por ciento. Las jurisdicciones con mayor riesgo fueron Tuxpan, Pánuco y Córdoba, y sin riesgo, Orizaba. Los principales factores de riesgo de la vivienda fueron el techo y muro de palma/zacate y piso de tierra, así como la presencia del vector y la ventilación. CONCLUSIONES: Es necesario realizar vigilancia epidemiológica basada en educación para la salud, mejoramiento de la vivienda y uso de insecticidas.

Distribution and pathogenicity of Trypanosoma cruzi isolated from peridomestic populations of Triatoma infestans and Triatoma guasayana from rural Western Argentina

We assessed the distribution of Trypanosoma cruzi infection in peridomestic triatomines collected manually at a district-wide scale in rural villages around Olta, Western Argentina, and typed the isolated strains according to their pathogenicity to laboratory mice. Of 1623 triatomines examined, only 14 (0.9 percent) were infected with T. cruzi based on microscopical examination of feces. The prevalence of T. cruzi infection was 0.8 percent in Triatoma infestans, 2.3 percent in T. guasayana, and nil in T. garciabesi, T. platensis, and T. eratyrusiformis. Local transmission occurred in kitchens, store-rooms and goat corrals or nearby, though at very low levels. T. cruzi was detected by at least one parasitological method in 11 (79 percent) of 14 microscope-positive bugs. Hemoculture was the most sensitive method (67 percent) followed by culture of organ homogenates, histopathology or xenodiagnosis of inoculated suckling mice (55-58 percent), and culture of microscope-positive bug feces (46 percent). The evidence suggests that most of the isolated T. cruzi strains would be myotropic type III. Our study establishes for the first time that peridomestic, microscope-positive T. guasayana nymphs were actually infected with T. cruzi, and may be implicated as a putative secondary vector of T. cruzi in domestic or peridomestic sites.

Effectiveness of residual spraying of peridomestic ecotopes with deltamethrin and permethrin on Triatoma infestans in rural western Argentina: a district-wide randomized trial.

OBJECTIVE: To compare the effectiveness of a single residual spraying of pyrethroids on the occurrence and abundance of Triatoma infestans in peridomestic ecotopes in rural La Rioja. METHODS: A total of 667 (32.8%) peridomestic sites positive for T. infestans in May 1999 were randomly assigned to treatment within each village, sprayed in December 1999, and reinspected in December 2000. Treatments included 2.5% suspension concentrate (SC) deltamethrin in water at 25 mg active ingredient (a.i.)/m(2) applied with: (a) manual compression sprayers (standard treatment) or (b) power sprayers; (c) 1.5% emulsifiable concentrate (EC) deltamethrin at 25 mg a.i./m(2); and (d) 10% EC cis-permethrin at 170 mg a.i./m(2). EC pyrethroids were diluted in soybean oil and applied with power sprayers. All habitations were sprayed with the standard treatment. FINDINGS: The prevalence of T. infestans 1-year post-spraying was significantly lower in sites treated with SC deltamethrin applied with manual (24%) or power sprayers (31%) than in sites treated with EC deltamethrin (40%) or EC permethrin (53%). The relative odds of infestation and catch of T. infestans 1-year post-spraying significantly increased with the use of EC pyrethroids, the abundance of bugs per site before spraying, total surface, and host numbers. All insecticides had poor residual effects on wooden posts. CONCLUSION: Most of the infestations probably originated from triatomines that survived exposure to insecticides at each site. Despite the standard treatment proving to be the most effective, the current tactics and procedures fail to eliminate peridomestic populations of T. infestans in semiarid rural areas and need to be revised.

[Treatment of Chagas disease with benznidazole and thioctic acid]. / Tratamiento de la enfermedad de Chagas con benznidazol y ácido tióctico.

A multicenter, randomized, triple blind and controlled trial was designed to determine whether the combination with thioctic acid (TA), an antioxidant agent, can reduce the intolerance rate to Benznidazol (BZ) in patients infected with Trypanosoma cruzi. Four regimens were assigned randomly for 3 age intervals, administrating placebo or TA orally at daily doses of 50 to 100 mg in association with BZ at a dose of 5 mg/k/day for 30 days. In some, medication was given during a run-in period. Safety controls were carried out on days 10, 20, 37 and 52 days after therapy initiation. A total of 249 patients between 15 and 44 years old were enrolled. At the end of the trial, 70.3% of the patients had completed the treatment, while 17.7% required its suspension due to BZ related adverse reactions. The proportion of individuals affected with at least one side effect ranged from 54.8% to 58%; however, none were serious. Reported side effects included: cutaneous maculopapular rush (28%), pruritus (13.6%), headache (8%), epigastralgia (6.2%), fever (6.2%), fatigue (4.3%), nausea (4%), myalgias (4.3%), others (21.5%). The incidence of these reactions did not differ significantly among the 4 therapeutic regimens, nor even among the age intervals considered. It can be concluded that the association with TA did not prevent the occurrence of adverse reactions related to BZ administration. However, a single month cycle of this parasiticide permitted a high compliance rate to therapy among infected outpatients.

Tratamiento de la enfermedad de Chagas con benznidazol y acido tioctico / Treatment of chagas disease with benznidazole and thioctic acid

Se realizó un ensayo clínico controlado, multicéntrico, a triple ciego, para evaluar si el tratamiento oral combinado del ácido tióctico (AT), reduce la incidencia de los efectos secundarios asociados al tratamiento con benznidazol (BZ) en pacientes infectados con Trypanosoma cruzi. Cuatro esquemas fueron asignados al azar pareados por edad, administrando placebo o AT por vía oral a razón de 50-100 mg día a dosis e intervalos variables (con y sin período pre-inducción) en combinación con BZ a dosis de 5 mg/kg/día por 30 días. Se realizaron evaluaciones en los días 10, 20, 37 y 52 de iniciado el tratamiento. Fueron enrolados 249 pacientes con edades entre 15 y 44 años. El 70.3% de los pacientes completó el tratamiento y el 17.7% restante debió suspender la medicación por causas relacionadas al BZ. La proporción de personas afectadas por al menos un efecto adverso, fue semejante entre los 4 grupos: entre 54.8 y 58%, aunque en ninguno de ellos resultó de carácter grave. Las manifestaciones clínicas adversas fueron: exantema morbiliforme (28%); prurito (13.6%); cefalea (8%); epigastralgia (6.2%); fiebre (6.2%); astenia (4.3%); náuseas (4.0%); mialgias (4.3%); vómitos (3.2%); otros (21.5%). La incidencia de experiencias adversas no difirió significativamente entre los 4 esquemas terapéuticos, ni entre los diferentes intervalos de edad de los pacientes. La asociación con ácido tióctico no demostró prevenir las manifestaciones de intolerancia a este agente. No obstante, la administración de BZ en un ciclo mensual único a pacientes infectados logró una elevada tasa de adherencia al tratamiento ambulatorio.

Short report: variation in mitochondrial 12S and 16S ribosomal DNA sequences in natural populations of Triatoma infestans (Hemiptera: Reduviidae).

Mitochondrial DNA sequences of the 12S and 16S ribosomal RNA genes were analyzed in five natural populations of the Chagas' disease vector Triatoma infestans from Argentina. DNA sequence comparisons of 878 basepairs (12S plus 16S) revealed 13 haplotypes. A total of 10 private haplotypes were found in four of the populations analyzed, suggesting low current levels of genetic exchange. The levels of genetic differentiation between the population of Chancaní (Córdoba) and other two of the populations analyzed indicated significant deviation from a pattern of unrestricted gene flow. The haplotypic diversity and the private haplotypes found in the geographically closest localities of Chancaní and El Jardín (La Rioja) suggest that the reduction in the population size by insecticide treatment did not avoid the recovery of the populations apparently from survivors of the same area.

Congenital transmission of Trypanosoma cruzi infection in Argentina.

Trypanosoma cruzi, the causative agent of Chagas disease, infects 10-18 million people and may be transmitted to the newborn. Using various data sources, we estimated that nearly 850 congenital cases occurred in Argentina in 1993, or 6.3 expected cases per each reported case in 1994 and in 1994-2001. The congenital transmission of T. cruzi constitutes a sizeable public health problem in the region.

[Hantavirus in human and rodent population in an endemic area for hantavirus pulmonary syndrome in Argentina]. / Hantavirus en población humana y de roedores de un área endémica para el síndrome pulmonar por Hantavirus en la Argentina.

This paper analyzed the prevalence and distribution of serological reactivity to hantavirus (antibody against ANDES virus) of human population exposed to hantavirus and rodents trapped in the studied area. This study was developed in Salta (Orán and San Martín Departments), area with the highest incidence for Hantavirus Pulmonary Syndrome (HPS) in Argentina. In December 1997, 453 healthy people were studied by serology and 39 rodents by serology and PCR. The studied individuals were distributed as: 145 farm inhabitants (FI), 212 people living in the same dwelling with healthy individuals (controls) (Cco), 87 people living in the same dwelling with persons undergoing SPH in 1997 (cases) (Cca). Moreover, 19 physicians and nurses who cared for patients with SPH in 1997 were also studied. The prevalence of hantavirus infection among the studied population was 6.3%. The prevalence was 10.3% among FI, 6.9% among Cca and 3.3% among Cco (p < 0.02). There was no serological reactivity among PS. The prevalence in 39 trapped rodents was 10.2%, with infection only for Oligoryzomys chacoensis, O. flavescens and Akodon varius species. The prevalence of human cases with asymptomatic infection in Salta is higher than in other regions of the country, and we are presenting a hypothesis to explain these differences. The analyzed data suggest that in this region up to the time this study was performed, there would not have been person to person transmission of hantavirus. The transmission would be from rodent contact exclusively and mainly in ongoing deforestation areas and domestic habitat surrounding rural dwellings.

Hantavirus en poblacion humana y de roedores de un area endemica para el hantavirus pulmonary syndrome in Argentina / Hantavirus in human and rodent population in an endemic area for hantavirus pulmonary syndrome in Argentina

This paper analyzed the prevalence and distribution of serological reactivity to hantavirus (antibody against ANDES virus) of human population exposed to hantavirus and rodents trapped in the studied area. This study was developed in Salta (Oran and San Martin Departments), area with the highest incidence for Hantavirus Pulmonary Syndrome (HPS) in Argentina. In December 1997, 453 healthy people were studied by serology and 39 rodents by serology and PCR. The studied individuals were distributed as: 145 farm inhabitants (FI), 212 people living in the same dwelling with healthy individuals (controls) (Cco), 87 people living in the same dwelling with persons undergoing SPH in 1997 (cases) (Cca). Moreover, 19 physicians and nurses who cared for patients with SPH in 1997 were also studied. The prevalence of hantavirus infection among the studied population was 6.3 percent. The prevalence was 10.3 percent among FI, 6.9 percent among Cca and 3.3 percent among Cco (p < 0.02). There was no serological reactivity among PS. The prevalence in 39 trapped rodents was 10.2 percent, with infection only for Oligoryzomys chacoensis, O. flavescens and Akodon varius species.The prevalence of human cases with asymptomatic infection in Salta is higher than in other regions of the country, and we are presenting a hypothesis to explain these differences. The analyzed data suggest that in this region up to the time this study was performed, there would not have been person to person transmission of hantavirus. The transmission would be from rodent contact exclusively and mainly in ongoing deforestation areas and domestic habitat surrounding rural dwellings.