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.

Retracing micro-epidemics of Chagas disease using epicenter regression.

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1.

Patrones de coloración en la inmunofluorescencia indirecta y su utilidad en el diagnóstico de leishmaniasis tegumentaria y enfermedad de Chagas / Indirect immunofluorescence staining patterns and their use for diagnosing cutaneous leishmaniasis and Chagas' disease

Objetivo: Determinar el valor diagnóstico de la Inmunofluorescencia indirecta (IFI) en el diagnóstico de leishmaniasis y enfermedad de Chagas. Material y método: La inmunofluorescencia indirecta (IFI) fue aplicada para el diagnóstico de leishmaniasis y la enfermedad de Chagas utilizando como sustrato antigénico epimastigotos de Trypanosoma cruzi. Se descubrió un patrón de fluorescencia nuclear con los sueros de pacientes con leishmaniasis y un patrón periférico para con los de la enfermedad de Chagas. Luego, en un estudio ciego, se estimó el valor diagnóstico de la IFI en ambas enfermedades. Resultados: En el diagnóstico de Leishmaniasis se encontró: Sensibilidad: 84,2%, especificidad: 100%, valor predictivo positivo: 100%, valor predictivo negativo: 82,9% y exactitud: 91,0%. Conclusiones: la técnica de Inmunofluorescencia utilizando epimastigotos de Trypanosoma cruzi y considerando los patrones de coloración propuestos, tiene utilidad en el diagnóstico de leishmaniasis tegumentaria y también en el diagnóstico de la infección chagásica evitando la confusión dada por la reacción inmune cruzada de estas enfermedades.

Objective: To determine the value of indirect immunofluorescence (IFI) in the diagnosis of leishmaniasis and Chagas disease. Material and method: Indirect immunofluorescence (IFI) was employed for diagnosing leishmaniasis and Chagas disease using Trypanosoma cruzi epimastigota as substrate antigens. A nuclear fluorescence pattern was found in sera from patients with leishmaniasis, and a peripheral pattern was found in those with Chagas disease. Afterwards, we estimated the diagnostic value of IFI for both diseases in a blinded fashion. Results: For diagnosing leishmaniasis, IFI sensitivity was 84.2%, specificity, 100%, positive predictive value, 100%, negative predictive value 82.9%, and accuracy was 91.0%. Conclusions: The immunofluorescence technique using Trypanosoma cruzi epimastigota, considering the proposed color patterns, is useful for diagnosing cutaneous leishmaniasis and T. cruzi infection by avoiding confusion because of immune cross-reactivity between these conditions.

Spatial patterns in discordant diagnostic test results for Chagas disease: links to transmission hotspots.

Diagnosis of Chagas disease is hindered by discordance between screening and confirmatory test results for Trypanosoma cruzi infection. In periurban Arequipa, Peru, spatial analysis revealed that individuals with discordant test results are spatially clustered in hotspots of T. cruzi transmission, suggesting that discordant results likely represent true infections in this setting.

Impregnated netting slows infestation by Triatoma infestans.

We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13-0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.

Chagas disease transmission in periurban communities of Arequipa, Peru.

BACKGROUND: Chagas disease, caused by Trypanosoma cruzi infection, is an urban problem in Arequipa, Peru, and the epidemiology of Chagas disease is likely to be quite different in this area, compared with in rural zones. METHODS: We conducted a serosurvey of 1615 children <18 years old in periurban districts that included hillside shantytowns and slightly more affluent low-lying communities. In addition, 639 adult residents of 1 shantytown were surveyed to provide data across the age spectrum for this community. RESULTS: Of 1615 children, 75 (4.7%) were infected with Trypanosoma cruzi. Infection risk increased by 12% per year of age, and children living in hillside shantytowns were 2.5 times as likely to be infected as were those living in lower-lying communities. However, age-prevalence data from 1 shantytown demonstrated that adults were no more likely to be seropositive than were teenagers; the results of maximum likelihood modeling suggest that T. cruzi transmission began in this community <20 years ago. CONCLUSIONS: The problem of Chagas disease in periurban settings, such as those around Arequipa, must be addressed to achieve elimination of vector-borne T. cruzi transmission. Identification of infected children, vector-control efforts, and education to avoid modifiable risk factors are necessary to decrease the burden of Chagas disease.

Targeted screening strategies to detect Trypanosoma cruzi infection in children.

BACKGROUND: Millions of people are infected with Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Anti-trypanosomal drug therapy can cure infected individuals, but treatment efficacy is highest early in infection. Vector control campaigns disrupt transmission of T. cruzi, but without timely diagnosis, children infected prior to vector control often miss the window of opportunity for effective chemotherapy. METHODS AND FINDINGS: We performed a serological survey in children 2-18 years old living in a peri-urban community of Arequipa, Peru, and linked the results to entomologic, spatial and census data gathered during a vector control campaign. 23 of 433 (5.3% [95% CI 3.4-7.9]) children were confirmed seropositive for T. cruzi infection by two methods. Spatial analysis revealed that households with infected children were very tightly clustered within looser clusters of households with parasite-infected vectors. Bayesian hierarchical mixed models, which controlled for clustering of infection, showed that a child's risk of being seropositive increased by 20% per year of age and 4% per vector captured within the child's house. Receiver operator characteristic (ROC) plots of best-fit models suggest that more than 83% of infected children could be identified while testing only 22% of eligible children. CONCLUSIONS: We found evidence of spatially-focal vector-borne T. cruzi transmission in peri-urban Arequipa. Ongoing vector control campaigns, in addition to preventing further parasite transmission, facilitate the collection of data essential to identifying children at high risk of T. cruzi infection. Targeted screening strategies could make integration of diagnosis and treatment of children into Chagas disease control programs feasible in lower-resource settings.

Seroprevalencia de la infección por Trypanosoma cruzi y factores asociados en población adulta en una zona de alta endemicidad de Arequipa, Perú / Seroprevalence of infection by Trypanosoma cruzi and associated factors in the adult population in a highly endemic area of Arequipa, Perú

Objetivo: determinar la seroprevalencia de infección por T. cruzi en pobladores mayores de 15 años del valle de Vítor, describiendo características generales y presencia de factores asociados a la infección. Material y Métodos: se seleccionaron aleatoriamente a 499 personas mayores de 15 años de edad, mediante encuesta se obtuvo la respectiva información epidemiológica. El diagnóstico serológico de la enfermedad se realizó mediante ELISA e IFI. Resultados: la seroprevalencia fue de 10,22%. En mujeres 10,35% y varones 10,04%. La mediana de edad del paciente chagásico fue de 42±17,86 años el tiempo de residencia fue de 34±15,95 años. El 50,98% es natural del valle de Vítor. Según la ocupación de la población general, agricultor 41,18%, ama de casa 31,37%. El 50,98% tiene instrucción secundaria. El único factor asociado a la infección fue el material rústico de las vivienda. Conclusion: el valle de Vítor es zona chagásica endémica. La infección afecta tanto a hombres como a mujeres. El poblador infectado es natural del valle de Vítor, se dedica a la agricultura y tiene secundaria como grado de instrucción. El material rústico de las viviendas se asocia a la infección por T.cruzi al favorecer la presencia del vector.

Objective: determine the seroprevalence of infection by T. cruzi in the population above age 15 in the valley of Vítor, describing general characteristics and the presence of associated factors. Materials and Methods: 499 people above age 15 were randomly selected; epidemiological information was obtained through a survey. The diagnosis of the disease was made by ELISA and IIF. Results: the seroprevalence for Chagas reactivity was 10,2%, 10,35% in women and 10,0% in men. The median of age of the "typical" Chagas disease patient was 42±17,9, his/her time of residence in Vítor was 34±15,9 years; 51,0% had been born in the valley of Vítor. Agricultural workers made up 41,2%, of the general population, and 51,0% have a high school education. Rustic housing materials were associated with the infection. Conclusions: the valley of Vítor is an endemic area for Chagas disease. The infection equally affects men and women. The "typical" infected patient is native to the valley of Vítor, works in agriculture and has secondary level education. Rustic building materials is associated to the infection by T.cruzi because it favors the presence of the vector.

Periurban Trypanosoma cruzi-infected Triatoma infestans, Arequipa, Peru.

In Arequipa, Peru, vectorborne transmission of Chagas disease by Triatoma infestans has become an urban problem. We conducted an entomologic survey in a periurban community of Arequipa to identify risk factors for triatomine infestation and determinants of vector population densities. Of 374 households surveyed, triatomines were collected from 194 (52%), and Trypanosoma cruzi-carrying triatomines were collected from 72 (19.3%). Guinea pig pens were more likely than other animal enclosures to be infested and harbored 2.38x as many triatomines. Stacked brick and adobe enclosures were more likely to have triatomines, while wire mesh enclosures were protected against infestation. In human dwellings, only fully stuccoed rooms were protected against infestation. Spatially, households with triatomines were scattered, while households with T. cruzi-infected triatomines were clustered. Keeping small animals in wire mesh cages could facilitate control of T. infestans in this densely populated urban environment.

Seroprevalencia de la infección por Trypanosoma cruzi en escolares del valle de Vítor, Arequipa, Perú / Sero-prevalence of Trypanosoma cruzi infection in school age students in the valley of Vitor, Arequipa, Peru

En los últimos años ha existido una alta infestación por T. infestans en el valle de Vítor, sur del Perú; lo que ameritó un estudio de infección humana en población joven (escolares) y sus aspectos epidemiológicos. De un total de 886 escolares de 14 centros educativos de inicial a secundaria del valle de Vítor, se eligió aleatoriamente a 282. Se obtuvo una muestra de sangre venosa y datos epidemiológicos de la enfermedad de cada uno de ellos. Cada muestra se procesó mediante IFI y ELISA para detectar anticuerpos contra T. cruzi. En los escolares sero-reactivos se aplicó xenodiagnóstico. De los 282 alumnos, el 96,5 por ciento tuvo contacto visual con el T. infestans. 32 (11,3 por ciento) resultaron con serología reactiva a ambas pruebas, 13,3 por ciento en varones 9,1 por ciento en mujeres (p=0,26). 4 de 31 sero-reactivos (12,9 por ciento) presentaron xenodiagnóstico positivo. No se halló asociación estadísticamente significativa entre seropositividad y edad o sexo. Solamente se halló riesgo estadísticamente significativo de infección en aquellos que habitaban viviendas totalmente rústicas en relación a aquellos que lo hacían en viviendas construidas total o parcialmente con material noble. Concluimos que la enfermedad de Chagas continúa siendo un problema de salud muy importante en la población escolar de este valle del sur peruano.

[The prevalence of Chagas' disease in puerperal women and congenital transmission in an endemic area of Peru]. / Prevalencia de la enfermedad de Chagas en puérperas y transmisión congénita en una zona endémica del Perú

OBJECTIVES: To determine the prevalence of antibodies against Trypanosoma cruzi in puerperal women and to assess possible congenital transmission of Chagas' disease in the department of Arequipa, Peru, where the disease is endemic. METHODS: Women who had given birth between December 2001 and July 2002 in three hospitals (two urban and one rural) and four health centers (three rural and one urban) of the department of Arequipa, Peru, were studied. The serological study included screening all the puerperal women in order to detect antibodies against T. cruzi through indirect immunofluorescence (IIF), with confirmatory testing done with enzyme-linked immunosorbent assay (ELISA) testing and the titration of immunoglobulin G (IgG) antibodies by IIF. IIF tests to screen for immunoglobulin M (IgM) antibodies were done with the seropositive women and their newborns, and infection was evaluated through xenodiagnosis (evaluated at 30 and 60 days) and the direct micromethod of Freilij et al. The results were analyzed in terms of the presence of the vector and of cases of Chagas' disease in the places where the puerperal women had been born and where they were living. Two neonatologists clinically evaluated the newborns in order to detect abnormalities and signs of congenital Chagas' disease. RESULTS: The overall prevalence of Chagas' disease in the 3 000 puerperal women studied was 0.73%. Prevalence was highest in two health centers located in rural areas (2.2% in El Pedregal and 4.1% in La Joya) (P=0.018). The disease was associated with previous direct contact with the vector (P<0.05) and with having been born in an area considered endemic (P<0.01). Four (20%) of the 20 seropositive puerperal women were also positive by xenodiagnosis. However, none of the women was aware of her infectious carrier state, and none showed the characteristic symptoms or signs of acute or chronic Chagas' disease. IgM antibodies were not detected in any of the puerperal women. One neonate (whose mother did not have evidence of parasitemia) presented an IgM titer of 1/8, but in later controls neither IgM nor IgG antibodies were detected. Parasites were not detected in the blood of the neonates by either of the two testing methods used. Of the 20 neonates evaluated, one presented microcephaly and hepatosplenomegaly; although the child had specific IgG antibodies against T. cruzi at birth, the antibodies were not present at the age of two months. The growth and development of the other 19 newborns were normal. CONCLUSIONS: The prevalence of Chagas' disease in puerperal women of the department of Arequipa, Peru, is low. No cases of intrauterine congenital transmission were found. We recommend carrying out studies on prenatal detection that evaluate more mothers and in which women who give birth at home also participate.

Enfermedad de chagas en sujetos asintomáticos con y sin alteraciones electrocardiográficas en una zona endémica / Illness of Chagas in subject asintomáticos with and without alterations electrocardiográficas in an endemic area

Introducción: Este estudio fue realizado en el Hospital Toquepala División Medica Southern Perú Limited. Toquepala es un centro minero localizado a 3,100 m.s.n.m., en la región sur del Perú. La población pertenece a una zona endémica para enfermedad de Chagas. Discusión: Se seleccionaron dos grupos de pacientes (trabajadores), con rangos de edades iguales o mayores de 40 años. Los cuales fueron entrevistados después del examen médico anual. Ambos grupos fueron pacientes asintomáticos, pero fueron clasificados de acuerdo a la presencia o no de cambios electrocardiográficos en el EKG. Aquellos pacientes con alteraciones en el EKG compatibles con Enfermedad de Chagas fueron clasificados como grupo A (n=160) y aquellos sin alteraciones en el EKG fueron clasificados como grupo B (n=160), con el propósito de establecer la prevalencia de Infección Chagásica en ambas poblaciones y compararlas. Se utilizaron dos técnicas diagnósticas: IFI y ELISA. Un resultado fue considerado como positivo cuando ambas pruebas fueron positivas. Ambos grupos fueron similares en sus características demográficas y epidemiológicas. Resultados: La prevalencia de Infección Chagásica fue 13.8 por ciento en los individuos con EKG anormal y 4.8 por ciento en los individuos con EKG normal, con un p < 0.005 y un OR de 3.15 (1.28-7.97) en la prueba Chi Cuadrado con corrección de yates. Conclusiones: en zonas endémicas, todos los individuos con EKG anormal compatible con Cardiopatía Chagásica Crónica tiene 3.15 veces más chance de presentar Infección Chagásica que los individuos con EKG normal. Solamente 13.8 por ciento de los individuos con EKG anormal compatible con etiología chagásica, tiene serología positiva; lo que demuestra que un EKG anormal no puede considerarse como un marcador sensible de infección. En el grupo de pacientes con diagnóstico de Infección Chagásica, se encontró EKG anormal en un 73.3 por ciento; lo que sugiere que la Infección por Trypanosoma cruzi (enfermedad de Chagas) es un importante factor de riesgo para enfermedad cardiaca, por lo que sería recomendable un EKG a todos los pacientes con serología positiva para descartar Cardiopatía Chagásica Crónica.

Evaluación del enterotest modificado en el diagnóstico de la giardiasis / Evaluation of modified enterotest diagnosis of giardiasis

Durante 1991-92, aplicamos simultáneamente el enterotest modificado (cápsula preparada por uno de nosotros) y el examen de heces seriado (3 en 1) a 108 personas, de ambos sexos, entre 5 y 36 años de edad, procedentes del distrito de Hunter, vecino de la ciudad de Arequipa (2,340 metros de altitud). Mediante del enterotest diagnosticamos 53 (49%) personas con Giardia Lamblia y con el examen de heces, 17 (15.74%) (p<0.001). Hallamos coincidencia de resultados positivos por ambos métodos en 16 personas y de negativos en 54. El enterotest permitió diagnosticar 37 casos que no lo fueron al examen de heces; y el examen de heces un caso que no lo fue al enterotest. El enterotest fue aceptado favorablemente por los niños y los adultos.

During the 1991-92 period we compared the use of an enterotest technique as modified by us and serial stool examinations (3) for ova a parasites in 108 patients of both sexes between 5 and 36 years in age, from the neighbourdhood (district) of Hunter close to Arequipa, Perú, at 2.340 meters above sea level. The enterotest detected Giardia lamblia in 53 patients (49%), while the stool examinations revealed this parasite in only 17 patients (15.74%) )(p0.001). There was agreement between both tests in 16 cases and disagreement in 54. The enterotest was positive in 37 who patients failed to show the parasite on stool examination, while the latter was positive in only one case found negative by the enterotest. Enterotest is a procedure favorably accepted by both children and adults and we advise its use in the investigations of giardiasis.