Risk Factors for Acquiring Scrub Typhus among Children in Deoria and Gorakhpur Districts, Uttar Pradesh, India, 2017

Scrub typhus is associated with outbreaks of acute encephalitis syndrome in Uttar Pradesh, India. A case-control study indicated that children residing, playing, or visiting fields; living with firewood stored indoors; handling cattle fodder; and practicing open defecation were at increased risk for scrub typhus. Communication messages should focus on changing these behaviors.


The Study
We conducted AFI surveillance in public health facilities in Deoria (n = 5) and Gorakhpur (n = 3) districts during October 3-November 11, 2017, a period coinciding with AES outbreaks in Gorakhpur district.We enrolled children 2-15 years of age with a >3-day history of fever, from whom we collected 2 mL of blood after obtaining written informed consent from parents and assent from children 7-15 years of age.We screened serum samples for IgM and IgG against O. tsutugamushi by using ELISA kits (Scrub Typhus Detect; InBios International Inc., Seattle, WA, USA).For our study, an optical density value >0.5 indicated IgM positivity.This cutoff has 93% sensitivity and 91% specificity for ST diagnosis (12).An optical density value <0.5 indicated IgM and IgG negativity.
Febrile children who were positive for O. tsutugamushi IgM were considered case-patients, whereas patients who were seronegative for IgM and IgG were considered controls.Case-patients and controls and their parents or guardians were interviewed in their houses by using a pretested structured questionnaire to collect information on sociodemographics, household characteristics, behaviors, and environmental exposures during the 2 weeks before fever onset.Interviewers were blinded to the case-patient or control status of children except during the first week of study.
We calculated crude odds ratios (ORs) and 95% CIs associated with different exposures.We included variables with p value <0.2 in univariate analysis in a stepwise backward elimination model to identify variables for inclusion in the final unconditional multiple logistic regression model by using Stata 13 (StataCorp LLC, College Station, TX, USA).
Aside from fever, clinical signs and symptoms among patients varied (online Technical Appendix Table 2).Five ST patients, who did not receive doxycycline/azithromycin, had onset of neurologic manifestations and required hospitalization; they recovered after administration of azithromycin.
Univariate analysis showed that ST patients were more likely than controls to live in houses located within or adjoining fields, houses with unpaved surroundings with mud or unkempt grass, and mud-floored houses (Table 2).In addition, a higher proportion of case-patients lived in households that used wood or cow dung for cooking and stored this fuel indoors.Compared with controls, children with ST were more likely to have played in agricultural fields, defecated in agricultural fields, bathed in a river or stream, carried grass bundles on their heads, handled fodder for cattle, or visited or accompanied parents to an agricultural field during the 2 weeks before fever onset (Table 2).

Conclusions
In Gorakhpur and Deoria districts, recent exposure to the outdoor environment, either while defecating or playing in agricultural fields, as well as visiting agricultural fields, storing firewood indoors, and handling fodder for cattle were associated with higher risk for acquiring ST among children.Of these risk factors, defecation in the agricultural field was the most common exposure at the population level.The observed association of ST and defecation in fields is consistent with the findings from an ST outbreak in Manipur, India, where persons who defecated or urinated in the jungle or bushy areas were found to be at higher risk for ST (11).In Gorakhpur and Deoria districts, about one third of the study population had toilets, a finding consistent with the 2015 national level survey, which indicated that 29.5% of the households in rural Uttar Pradesh had sanitary toilets and 27.3% of households that had access to toilets were using them (http:// www.mdws.gov.in/sites/default/files/Swachh%20Survek-shan%20Report%20Eng.PDF).Efforts to prevent ST in the region therefore also need to focus on constructing household and community toilets, as well as behavior change communication about avoiding open defecation in the fields.In addition, storing firewood and fodder indoors attracts rodents that can harbor mites.Mites present on the firewood and fodder collected from fields might expose children to mite bites during storage or handling of the cattle fodder.Our study had limitations.First, although OT IgM is detectable as early as 4 days after fever onset (13), some ST patients in our study might have been negative for IgM and hence misclassified as controls.However, such nondifferential misclassification is likely to underestimate the actual association.Further, the median duration of fever was 7 days (interquartile range 4.5-10.0days) among casepatients and 5 days (interquartile range 4-8 days) among controls (Table 1), indicating minimal possibility of such misclassification.Some controls might have been misclassified as case-patients because of persistence of IgM from previous infection (14).However, this possibility is less likely considering that IgM peaks by 4 weeks of infection and declines rapidly thereafter (15).Second, our controlpatients were AFI patients from healthcare facilities and not healthy children from the general population.Nevertheless, the behaviors of children visiting healthcare facilities before their febrile illness and children from the general population are less likely to be different.
For prevention of ST among children in Gorakhpur and Deoria districts, communication messages should focus on changing behaviors such as defecating or playing

Table 1 .
Sociodemographic details of cases and controls, Deoria and Gorakhpur districts, Uttar Pradesh, 2017 *Values are percentages unless otherwise indicated.IQR, interquartile range.

Table 2 .
Risk factors associated with scrub typhus, Gorakhpur and Deoria districts, Uttar Pradesh, 2017* agricultural fields and unnecessary visits to agricultural fields.Onset of central nervous system manifestations among untreated ST patients underscores the importance of early administration of doxycycline/azithromycin to ST patients in Gorakhpur and Deoria districts to prevent progression to AES.
*aOR, adjusted odds ratio; OR, odds ratio. in

Table 1 .
Details of AFI patients enrolled, tested for IgM and IgG antibodies against O. tustsugamushi (OT),

Table 2 .
Clinical features of cases and controls, Gorakhpur and Deoria districts, 2017