High Prevalence of Congenital Trypanosoma cruzi Infection and Family Clustering in Salta, Argentina

Objective. Trypanosoma cruzi, the causative agent of Chagas’ disease, is transmitted mainly by insect vectors, but congenital and transfusion-borne infections occasionally occur. The factors that are involved in transmission from mother to offspring are not well understood. The objective of this study was to study the presence of T cruzi infection in children who were born to infected mothers and in the children’s siblings to evaluate the epidemiologic risk factors associated with congenital transmission of Chagas’ disease. Methods. Congenital T cruzi infection was studied in 340 children who were born to chronically infected mothers in Salta, Argentina. Infection was detected in 31 children, who were selected for additional study as infected index cases (IIC). Of the 309 noninfected children, 31 were taken as noninfected index cases (NIIC). We compared the prevalence of congenital T cruzi transmission in the remaining siblings of the IIC and NIIC. Data and blood samples were collected in house-to-house visits. Diagnosis of infection was established mainly by serologic methods, indirect hemmagglutination, and enzymelinked immunosorbent assay. Results. The prevalence was 31.4% (32 of 102 children) for IIC siblings, whereas no infected siblings were found in families with NIIC (0 of 112). Clustering of congenital infection was found in 14 families, in which >1 child was infected. Second-generation congenital transmission (from grandmother to mother to newborn) was established in 4 families. The association among low weight at birth, prematurity, and congenital transmission was highly significant. An important observation was the absence of pathologic findings in a high proportion of infected children. The detection of asymptomatic infections was a consequence of population screening, as opposed to hospital-based diagnosis, for which symptomatic cases predominate. Congenital transmission was associated with the geographic origin of mothers: women from areas where insect vectors proliferate were less likely to give birth to infected offspring than women from areas under active vector control. Conclusions. Siblings of an infant infected with T cruzi are at high risk for infection themselves and, even in the absence of symptoms, should also be screened for infection. The findings of family clustering of infection and of second-generation congenital infection in vectorfree areas suggest that new modalities of transmission, other than classic vector-borne spread, may occur both in endemic and in nonendemic areas. Pediatrics 2005; 115:e668–e672. URL: www.pediatrics.org/cgi/doi/10.1542/ peds.2004-1732; Trypanosoma cruzi, Chagas’ disease, family clustering, congenital infection. ABBREVIATIONS. IC, index case; IIC, infected index case; NIIC, noninfected index case; Ag, antigen. Chagas’ disease (American trypanosomiasis) is a parasitic disease with considerable impact on public health. The main factor associated with transmission is the presence of triatomine insect vectors in human houses, so Chagas’ disease is most commonly associated with poor, rural dwellings. Vector control with insecticides has been successful to reduce the global seroprevalence in some countries.1 In the province of Salta, Argentina, the proportion of seropositive, 20-year-old soldiers dropped significantly during the 1980s.2 Socioeconomic factors that have prevailed in Latin America in the past 3 decades have produced largescale migrations from rural to periurban settlements. This has given rise to the epidemiologic phenomenon of “urbanization of parasitism,” meaning that Chagas’ disease is no longer found exclusively in the rural environment. As a consequence, new transmission modalities such as congenital and transfusional are occurring in the absence of insect vectors. A previous study in northwestern Argentina3 revealed that in 8.8% of the deliveries from Trypanosoma cruzi– infected mothers, congenital transmission occurs. Congenital T cruzi infection seems to be, on the basis of hospital records of clinically detected cases, a symptomatic condition that presents with fever, edema, lymphadenopathy, anemia, hepatosplenomegaly, and cardiomegaly.4,5 However, the true frequency of asymptomatic cases should be examined by active search studies, such as the present one. The standard diagnostic methods are the microhematocrit,6 which allows detection of parasites in blood during the first months after birth, and the serologic reactions.7 Indirect hemmagglutination and enzymelinked immunosorbent assay should be applied after the eighth month of age to avoid detection of passively acquired antibody. Treatment with 5 mg/kg per day benznidazole for 2 months is most often successful, as indicated by the progressive decline of antibody. Early detection and treatment become a relevant issue of public health, considering that early drug treatment is curative8–12 and up to 30% of inFrom the Instituto de Patologı́a Experimental, Facultad de Ciencias de la Salud, Universidad Nacional de Salta, Calle Buenos Aires, Salta, Argentina. Accepted for publication Dec 9, 2004. doi:10.1542/peds.2004-1732 No conflict of interest declared. Reprint requests to (O.S.N.) Laboratorio de Patologı́a Experimental, Facultad de Ciencias de la Salud, Universidad Nacional de Salta, Calle Buenos Aires 177, 4400 Salta, Argentina. E-mail: [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 2005 by the American Academy of Pediatrics. e668 PEDIATRICS Vol. 115 No. 6 June 2005 www.pediatrics.org/cgi/doi/10.1542/peds.2004-1732 by guest on April 10, 2017 Downloaded from fected, nontreated children irreversibly progress toward the chronic phase of Chagas’ disease.4,13 Risk factors for congenital T cruzi infection are poorly understood.14 No clear association of this mode of transmission with factors such as maternal age, number of previous deliveries, or geographic origin has been found.15 Most epidemiologic studies on congenital transmission simply state the number of studied cases and the number of positive diagnoses found, without analyzing their association with epidemiologic factors in mothers and newborns. Several reports have documented the transmission of T cruzi from one mother to 24,5,13,16 or several17,18 of her offspring, whereas other siblings are spared from infection.17–19 At least 2 cases of second-generation congenital infection have been published.13,20 The purpose of this work was to study the presence of T cruzi infection in children who were born to infected mothers and to evaluate epidemiologic risk factors associated with congenital transmission of Chagas’ disease.