Chagas disease is a growing problem in Arequipa, Peru. A previous study in the city uncovered micro-epidemics of transmission associated with high density of vectors, suggesting that targeting screening based on entomologic information could be an efficient means of detecting T. cruzi
infected individuals 
. In this prospective field trial, we uncovered important differences in the association between vector-parasite distribution and human Chagas disease infection, which merit consideration in the design of screening programs for Chagas in Arequipa and other urban settings.
There are numerous reasons why the vector-based targeted screening strategy designed for a previously studied community (Guadalupe), yielded fewer cases when applied elsewhere in the city. In Guadalupe, parasite infections in both humans and vectors were clustered, and the age-prevalence curves suggested established epidemics of T. cruzi
. The present study sites, much closer to the city center, also contained clusters of parasite-infected vectors, but these consisted of fewer households. These smaller clusters are likely indicative of a relatively short history of vectorial transmission, leading to few locally acquired cases.
In addition to epidemiology and ecology, social and demographic phenomena may also affect patterns of human Chagas disease 
. Frequent migratory movement between rural and metropolitan Arequipa may bring parasite into the city 
; the cases of infection we detected were most associated with a history of triatomine exposure and residence in rural areas, where Chagas disease is historically endemic 
. It is possible that the few clusters of parasite are due to introductions from outside that did not manage to spread beyond a handful of households in the new urban environment. That periurban time of residence did not significantly contribute to overall risk of infection in this study is another indication of minimal vectorial disease transmission in the study communities.
Interestingly, one of the 18 communities studied, Simón Bolívar, did display patterns of infection reminiscent of the micro-epidemic hotspots observed in Guadalupe. In Simón Bolivar, the 4 secondary cases detected within 15 meters of index cases may suggest significant rates of local vector-borne transmission at the time of insecticide application. The dissimilar migration history of the cases found in Simón Bolívar allow us to rule out that this clustering may be due to a group of infected migrants from the same sending community settling on the same city block, a phenomenon that has occurred in periurban settlements of Arequipa 
. Importantly, there was no obvious a priori
evidence in Simón Bolívar to expect transmission to differ from the other 17 communities considered. This study adds to growing evidence of an uneven distribution of T. cruzi
infection in the city of Arequipa 
, not uncommon to this parasitic disease 
. Other similar pockets of vector-borne transmission may exist in the city; the implementation of small pilot studies in infested areas followed by spatial adaptive sampling around human cases can help uncover them and determine the appropriate screening strategy for each setting. Where urban vectorial transmission is present, this adaptive strategy identifies secondary cases efficiently. When employed in an area without vectorial transmission, adaptive sampling should return few or no secondary cases, such that additional screening is curtailed and expenditures capped. Although harder to obtain, longitudinal entomological data, as opposed to the cross-sectional data utilized here, may be informative in locating these mini-epidemics. We are currently exploring community-based recognition and alert systems as a promising mechanism for obtaining this longitudinal vector data.
In addition, our disease screening activities took place between 5 months and 4 years after household insecticide application and collection of the entomologic data. It is not clear what the effect of this time lapse may be on the association between vector data and human infections detected. The strategies may work much better if these delays were eliminated. However, considering that exposure risk is greatly reduced by the elimination of vectors, we can reasonably expect that there were little new infections prior to our testing.
Another possible cause of error is the inability of migration histories to capture participants' short visits to endemic areas. While a potentially important source of exposure, there are methodological and recall challenges to documenting travel history at such a fine level. We found that screening based on personal risk assessment and residence-exposure history (ie, time lived in rural and/or infested areas) is advantageous for capturing high-risk individuals. Studies of blood donors in Canada and the US have found promising usefulness and operational feasibility of residence history questionnaires 
Our study consisted of operational research in a large heterogeneous city. In the wake of vector control campaigns, the target population was well-aware of their risk of Chagas disease. Residents of houses where no infestation was detected could have been at risk of vectorial transmission due to proximity to infested houses. However, during our fieldwork, it became clear that those who participated in this optional Chagas disease screening did so because they believed themselves to be at risk due to prior exposure. Participants from houses with no infestation detected often expressed concern about a previous infestation in their current or prior homes. In contrast, those who refused often reported being uninterested in testing because they did not consider themselves at risk, or because in their memory they had no contact with a vector. As a result, this study suffered from a self-selection bias according to perceived risk among participants living in vector-free houses at the time of the spray campaign. This bias likely caused an overestimate of the Chagas disease prevalence in houses with no infestation detected. Although not directly comparable, our observed overall prevalence of 2.28% is much higher than the 0.73% reported in a 2004–05 cross-sectional screening of pregnant women in Arequipa, which included populations from communities also studied here 
. In contrast, we believe the prevalence estimate of 2.60% among the infected vector group to be quite accurate for persons living in this risk category due to the 98% participation rate.
Factors affecting participation need to be taken into consideration to design an economically optimal algorithm for targeted screening of Chagas disease. The high refusal rate among houses with no infestation detected required double the number of household visits per participant recruited than for the infected-vector group, making it the most expensive strategy in our cost calculation. If similar entomologic data from vector control campaigns are used to guide a human Chagas disease case-finding strategy, minimizing costs for fieldwork while still detecting cases would be optimal. Targeting screening according to the presence of T. cruzi
-infected T. infestans
was less expensive and similarly effective compared to the other strategies. Further, coupling screening to ongoing vector control campaigns can improve participation 
with the added advantage of eliminating the time lapse between entomologic data and human testing that we experienced in some communities of this study.
In large cities like Arequipa, where T. cruzi
exposure is highly heterogeneous, a targeted screening program is necessary for the prompt diagnosis of indeterminate Chagas disease, the prevention of future transmission and the maximization of limited resources 
. A greater knowledge of the patterns of infection can be obtained by pilot studies, and would improve the design of screening strategies. Rural, urban and periurban places have different ecologies, and it is reasonable to expect different epidemiologies of Chagas disease in these settings 
. The flexibility to adapt to the epidemiology that emerges during pilot screenings is key to an efficient case detection intervention. Finally, this data can help develop a brief residence history questionnaire for referring to diagnostic testing those at greatest risk of Chagas disease. Self-assessment of risk and triatomine exposure time is a potentially useful tool for screening; volunteer screening programs at local health posts or fairs may be very effective ways to capture infections in heterogeneous periurban communities subsequent to informative vector control campaigns.