Worldwide Control and Management of Chagas Disease in a New Era of Globalization: a Close Look at Congenital Trypanosoma cruzi Infection

Abstract

Population movements have turned Chagas disease (CD) into a global public health problem. Despite the successful implementation of subregional initiatives to control vectorial and transfusional Trypanosoma cruzi transmission in Latin American settings where the disease is endemic, congenital CD (cCD) remains a significant challenge. In countries where the disease is not endemic, vertical transmission plays a key role in CD expansion and is the main focus of its control. Although several health organizations provide general protocols for cCD control, its management in each geopolitical region depends on local authorities, which has resulted in a multitude of approaches. The aims of this review are to (i) describe the current global situation in CD management, with emphasis on congenital infection, and (ii) summarize the spectrum of available strategies, both official and unofficial, for cCD prevention and control in countries of endemicity and nonendemicity. From an economic point of view, the early detection and treatment of cCD are cost-effective. However, in countries where the disease is not endemic, national health policies for cCD control are nonexistent, and official regional protocols are scarce and restricted to Europe. Countries of endemicity have more protocols in place, but the implementation of diagnostic methods is hampered by economic constraints. Moreover, most protocols in both countries where the disease is endemic and those where it is not endemic have yet to incorporate recently developed technologies. The wide methodological diversity in cCD diagnostic algorithms reflects the lack of a consensus. This review may represent a first step toward the development of a common strategy, which will require the collaboration of health organizations, governments, and experts in the field.

Keywords: Trypanosoma cruzi; congenital Chagas disease; diagnosis; endemic; health policies; nonendemic.

FIG 1

Latin American policies to control congenital Chagas disease (cCD). Countries in blue recommend antenatal screening, but their guides do not include a specific diagnostic algorithm. Countries in green have an official guide that includes a diagnostic algorithm for cCD. Diagnostic algorithms are detailed in Fig. 2. No data were found for countries in gray.

FIG 2

Timeline of the methodologies used in the algorithms for the diagnosis of congenital Chagas disease implemented in Latin America. Blue, parasitological tests; green, serological tests; orange, molecular diagnosis. MH, microhematocrit; S, Strout; F, fresh-blood observation; T, thin and/or thick blood smears; MS, microstrout; C, culture; m, months. ^aFor Argentina (233, 234), serological techniques that can be used are an enzyme-linked immunosorbent assay (ELISA), an indirect immunofluorescence (IIF) assay, an indirect hemagglutination assay (IHA), and particle agglutination. ^bFor Bolivia (235), umbilical cord blood can be used for parasitological testing. Serological techniques that can be used are an ELISA, an IIF assay, and an IHA. A positive result must be confirmed by an ELISA or IHA. In the case of a weak positive result when using the IHA, repeat testing should be performed 3 months later. ^cFor Brazil (236), parasitological analysis should be repeated 1 week after birth. Serological techniques that can be used are an ELISA, IIF, and IHA. Serological confirmation requires coincident positive results by two tests based on different principles. ^dFor Chile (237, 238), both parasitological testing and PCR should be carried out at birth. Two positive PCRs are needed to confirm the infection. In the case of a positive result by PCR at 2 months, a new sample should be requested immediately instead of waiting until 9 months. A positive PCR result at 9 months needs to be confirmed by a detectable level of antibodies by serology. Serological techniques that can be used are an ELISA, IIF, IHA, and Western blotting (WB). ^eFor Colombia (239), serological techniques that can be used are an ELISA, an IIF assay, an IHA, WB, and a chemiluminescence immunoassay (ChLIA). Serological confirmation requires coincident positive results by two tests based on different principles. ^fFor Costa Rica (240), it is not clear which is the serological technique (or techniques) of choice. A positive serological result at birth and/or at 3 months without a positive parasitological result requires serological and/or parasitological confirmation at 7 months. ^gFor El Salvador (242), serological techniques that can be used are an ELISA, IIF, IHA. ^hFor Guatemala (243), serological follow-up continues until 18 months of age. The ELISA is indicated as the serological technique of choice. ⁱFor Mexico (245), umbilical cord blood can be used for parasitological testing. According to the text, serological control should be conducted from 6 to 10 months of age, whereas the diagnostic algorithm in the same guide recommends serology at 12 months. Similarly, the text indicates the potential diagnostic use of PCR 1 month after birth, but it does not appear in the diagnostic algorithm. Serological techniques that can be used are an ELISA, IIF, and IHA. Serological confirmation requires coincident positive results by two tests based on different principles. ^jFor Nicaragua (246), a positive parasitological result at birth requires confirmation by a second parasitological test. Umbilical cord blood can be used for parasitological testing. Serological confirmation requires coincident positive results by two ELISAs: first, a conventional ELISA and, second, an ELISA based on recombinant antigens. ^kFor Panama (247), at birth, parasitological testing and/or PCR can be carried out. In the case of negative results at birth, repeat testing every week during 1 month should be performed. ^lFor Paraguay (249), at birth and 1 month afterward, parasitological testing and/or PCR can be carried out. Umbilical cord blood can be used for parasitological and molecular testing. It is not clear which is the serological technique (or techniques) of choice. Serological techniques that can be used are an ELISA, IHA, and ChLIA. ^mFor Peru (250), parasitological testing or PCR can be carried out at birth. Serological follow-up by an ELISA and an IIF assay is carried out only in cases of a positive result at birth in order to compare IgG titers. ⁿFor Uruguay (251), parasitological and serological tests that can be used are not specified. ^oFor Venezuela (252), parasitological testing and PCR (if possible) can be carried out at birth. Umbilical cord blood is used for parasitological testing. Serological testing by IgG and IgM determination can be performed. Serological techniques that can be used are an ELISA, IIF, IHA, and direct agglutination. Serological confirmation requires coincident positive results by two tests.

FIG 3

European regions with an official screening protocol including a specific algorithm to diagnose congenital Chagas disease. Diagnostic algorithms are included in Fig. 5.

FIG 4

Spanish policies to control congenital Chagas disease (cCD). Regions in blue recommend antenatal screening, but their guides do not include a specific diagnostic algorithm. Aragon follows the recommendations of the Spanish Society of Gynecology and Obstetrics (278). Regions in green have an official guide that includes a diagnostic algorithm for cCD. Regions in red have an unofficial initiative that includes a diagnostic algorithm for cCD. All diagnostic algorithms are detailed in Fig. 5. In the case of Extremadura, antenatal screening for CD is also officially recommended, but the technical document refers to a previously published algorithm (274). No data were found for regions in gray. In the case of Castile and Leon, antenatal screening for CD is recommended in the area of Salamanca (276).

FIG 5

Timeline of the methodologies used in the algorithms for the diagnosis of congenital Chagas disease implemented in Spain and the Italian region of Tuscany. Blue, parasitological tests; green, serological tests; orange, molecular diagnosis. Opt., optional; MH, microhematocrit; MS, microstrout; C, culture; T, thin and/or thick blood smears; ELISA, enzyme-linked immunosorbent assay; ChLIA, chemiluminescence immunoassay. ^aFor Catalonia (266), microhematocrit is optional and recommended only for centers with experience in the technique. In the case of a doubtful PCR result, repeat testing should be performed. In the case of a positive serological result, repeat testing with another technique based on a different principle should be performed. If the second test is negative or with a value close to the cutoff, repeat testing with the same technique 2 months afterward should be performed. ^bFor the Community of Madrid (267), both parasitological testing and PCR must be carried out at birth and 1 month afterward. A positive PCR result at birth in a sample of umbilical cord blood must be confirmed by another PCR in the peripheral blood of the newborn. Repeat serology should be performed at 12 months only in cases of a positive result at 9 months in order to compare IgG titers. It is not clear which is the serological technique (or techniques) of choice. ^cFor Extremadura (268), both parasitological testing and PCR must be carried out at birth and 1 month afterward. It is not clear which is the serological technique (or techniques) of choice. ^dFor Galicia (269), both parasitological testing and PCR must be carried out at birth and 1 month afterward. Repeat serology at 12 months should be performed only in the case of a positive result at 9 months in order to compare IgG titers. It is not clear which is the serological technique (or techniques) of choice. ^eFor the Valencian Community (272), both parasitological testing and PCR must be carried out at birth and 1 month afterward. Umbilical cord blood can be used for parasitological and molecular testing. Serological testing at birth is performed by IgG and IgM determination. Repeat serology at 12 months should be performed only in the case of a positive result at 7 to 9 months with a reduction of IgG titers compared to those at birth. An increase of IgG titers at 7 to 9 months compared to those at birth means congenital infection. Recommended serological techniques are an ELISA, an indirect immunofluorescence (IIF) assay, and an indirect hemagglutination assay (IHA). Serological confirmation requires coincident positive results by two tests. ^fFor Tuscany, Italy (273), both parasitological testing and PCR must be carried out at birth, and parasitological testing and/or PCR must be carried out 1 month after birth. Repeat serology should be performed at 12 months only in the case of a positive result at 9 months with a reduction of IgG titers compared to those at birth. An increase of IgG titers at 9 months compared to those at birth means congenital infection. It is not clear which is the serological technique (or techniques) of choice.