Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia

Abstract INTRODUCTION: Trypanosoma cruzi (Tc) infection is usually acquired in childhood in endemic areas, leading to Chagas disease, which progresses to Chagas cardiomyopathy in 20-30% of infected individuals over decades. The pathogenesis of Chagas cardiomyopathy involves the host inflammatory response to T. cruzi, in which upstream caspase-1 activation prompts the cascade of inflammatory chemokines/cytokines, cardiac remodeling, and myocardial dysfunction. The aim of the present study was to examine the association of two caspase-1 single nucleotide polymorphisms (SNPs) with cardiomyopathy. METHODS: We recruited infected (Tc+, n = 149) and uninfected (Tc−, n = 87) participants in a hospital in Santa Cruz, Bolivia. Cardiac status was classified (I, II, III, IV) based on Chagas cardiomyopathy-associated electrocardiogram findings and ejection fractions on echocardiogram. Genotypes were determined using Taqman probes via reverse transcription-polymerase chain reaction of peripheral blood DNA. Genotype frequencies were analyzed according to three inheritance patterns (dominant, recessive, additive) using logistic regression adjusted for age and sex. RESULTS: The AA allele for the caspase-1 SNP rs501192 was more frequent in Tc+ cardiomyopathy (classes II, III, IV) patients compared to those with a normal cardiac status (class I) [odds ratio (OR) = −2.18, p = 0.117]. This trend approached statistical significant considering only Tc+ patients in class I and II (OR = −2.64, p = 0.064). CONCLUSIONS: Caspase-1 polymorphisms may play a role in Chagas cardiomyopathy development and could serve as markers to identify individuals at higher risk for priority treatment.

Temporal differences in blood meal detection from the midguts of Triatoma infestans / Diferencias temporales en la detección de fuentes de alimentación en el contenido intestinal de Triatoma infestans

We used genus/species specific PCRs to determine the temporal persistence of host DNA in Triatoma infestans experimentally fed on blood from six common vertebrate species: humans, domestic dogs, guinea pigs, chickens, mice, and pigs. Twenty third or fourth instar nymphs per animal group were allowed to feed to engorgement, followed by fasting-maintenance in the insectary. At 7, 14, 21, or 28 days post-feeding, the midgut contents from five triatomines per group were tested with the respective PCR assay. DNA from all vertebrate species was detected in at least four of five study nymphs at seven and 14 days post-feeding. DNA of humans, domestic dogs, guinea pigs, pigs, and chickens were more successfully detected (80-100%) through day 21, and less successfully (20-100%) at day 28. Findings demonstrate that species-specific PCRs can consistently identify feeding sources of T. infestans within two weeks, a biologically relevant time interval.

Se utilizó pruebas PCR género o especie específicas para determinar la persistencia temporal de ADN del hospedero en el contenido intestinal de Triatoma infestans que fueron alimentados experimentalmente con sangre de seis vertebrados muy frecuentemente asociados a enfermedad de Chagas: humano, perro, cobayo, pollo, ratón, y cerdo. Se emplearon 20 ninfas de tercer y cuarto estadio por cada especie de hospedero. Fueron alimentados a saciedad y mantenidas en el insectario sin alimentación posterior. Se obtuvo el contenido intestinal de cinco triatominos por cada grupo a los 7, 14, 21 y 28 días post - alimentación, que fueron evaluados con los respectivos PCRs específicos. El ADN de todos los vertebrados fue detectado en al menos 4 de 5 ninfas evaluadas a los 7 y 14 días post - alimentación. El ADN de humano, perro, cobayo, cerdo y pollo fue detectado exitosamente (80-100%) hasta el día 21 y con menos éxito (20-100%) en el día 28. Estos resultados demuestran que PCRs específicos para cada especie de hospedero pueden identificar consistentemente la fuente de alimentación de T. infestans dentro de las dos semanas post - alimentación, siendo un intervalo de tiempo biológicamente relevante.

Risk factors for anemia in Vietnam.

Anemia is a significant public health problem in Vietnam, but representative national data and comprehensive risk factors analysis are lacking. The objectives of this study were to: 1) determine the distribution and severity of anemia in Vietnam, and 2) to assess potential risk factors for anemia. Nine thousand five hundred fifty households in 53 provinces were covered using a stratified two-stage cluster survey carried out in 1995. Selected household members were interviewed; intestinal helminthes were tested in non-pregnant women by Kato-Katz technique; hemoglobin concentrations were measured with Hemocue. Data were weighted and analyzed by survey procedures using SAS 9.0. Overall, 60% of children under 2 years old, 53% of pregnant women, 40% of non-pregnant women and 15.6% of men were anemic. Hookworm infection was the strongest factor associated with anemia (OR = 1.7; 2.9 and 4.5 for 11,999, 2,000-3,999 and > or = 4,000 hookworm egg counts, respectively) and accounted for 22% of anemia. Hookworm intensity was significantly associated with hemoglobin level; for each 1,000 egg increase, hemoglobin was reduced by 2.4 g/l. Living in different ecological zones, eating < 1 serving of meat/ week, and farming were significantly associated with anemia in women and children. Other risk factors in women included having > 3 children and having a child < 24 months old. In men, no variables were found significantly associated with anemia.

Intestinal helminth infections among reproductive age women in Vietnam: prevalence, co-infection and risk factors.

Intestinal helminth infections are a significant public health problem for Vietnamese women, but prevalence and risk factor data are scarce. The objectives of this paper were to (1) determine the prevalence of helminth infections among women; (2) investigate interactions among intestinal helminth species in individuals and (3) identify risk factors that contribute to intestinal helminth infections. In a nationwide survey conducted in 1995, 9550 households in 53 provinces were covered using a stratified two-stage cluster survey. Stool specimens were examined by Kato-Katz technique. Of 5,127 women, 76% were infected with one or more helminth species, 36% with hookworm, 59% with Ascaris lumbricoides and 28% with Trichuris trichiura. A. lumbricoides and T. trichiura were more likely to be concurrent than expected by chance. There was significant interaction between prevalence and intensity of infection in all three species. All three helminth species were more common in certain ecologic zones than others. Hookworm infection was associated with farming [Odd ratio (OR) = 2.1] and lack of a closed latrine (OR = 2.0), A. lumbricoides with use of untreated feces as fertilizer (OR = 1.2) and coinfection with T. trichiura (OR = 2.1) and T trichiura with A. lumbricoides co-infection (OR = 2.1). Our findings suggest that reproductive-age women, especially rural farmers, should be included among the high priority groups for helminth control programs through mass chemotherapy and improving sanitation.

The epidemiology of visceral leishmaniasis in Bangladesh: prospects for improved control.

The parasitic disease kala-azar (visceral leishmaniasis, VL) was first described in 1824 in Jessore district, Bengal (now Bangladesh). Epidemic peaks were recorded in Bengal in the 1820s, 1860s, 1920s, and 1940s. After achieving good control of the disease during the intensive vector control efforts for malaria in the 1950s-1960s, Bangladesh experienced a VL resurgence that has lasted to the present. Surveillance data show an increasing trend in incidence since 1995. Research in recent years has demonstrated the utility of non-invasive diagnostic modalities such as the direct agglutination test and rapid tests based on the immune response to the rK39 antigen. In common with its neighbours India and Nepal, VL in Bangladesh is anthroponotic. Living in proximity to a kala-azar case is the strongest risk factor for disease, while consistent use of bed nets in the summer months and the presence of cattle are protective. Shortages of first-line antileishmanial drugs and insecticide for indoor spraying programmes have hindered VL treatment and vector control efforts. Effective control of VL will require activities to improve availability and access to diagnostic testing and antileishmanial drugs, enhanced surveillance for kala-azar, post-kala-azar dermal leishmaniasis and VL treatment failures, and increased coverage and efficacy of vector control programmes.