Performance of a Mobile Phone App-Based Participatory Syndromic Surveillance System for Acute Febrile Illness and Acute Gastroenteritis in Rural Guatemala.

BACKGROUND: With their increasing availability in resource-limited settings, mobile phones may provide an important tool for participatory syndromic surveillance, in which users provide symptom data directly into a centralized database. OBJECTIVE: We studied the performance of a mobile phone app-based participatory syndromic surveillance system for collecting syndromic data (acute febrile illness and acute gastroenteritis) to detect dengue virus and norovirus on a cohort of children living in a low-resource and rural area of Guatemala. METHODS: Randomized households were provided with a mobile phone and asked to submit weekly reports using a symptom diary app (Vigilant-e). Participants reporting acute febrile illness or acute gastroenteritis answered additional questions using a decision-tree algorithm and were subsequently visited at home by a study nurse who performed a second interview and collected samples for dengue virus if confirmed acute febrile illness and norovirus if acute gastroenteritis. We analyzed risk factors associated with decreased self-reporting of syndromic data using the Vigilant-e app and evaluated strategies to improve self-reporting. We also assessed agreement between self-report and nurse-collected data obtained during home visits. RESULTS: From April 2015 to June 2016, 469 children in 207 households provided 471 person-years of observation. Mean weekly symptom reporting rate was 78% (range 58%-89%). Households with a poor (<70%) weekly reporting rate using the Vigilant-e app during the first 25 weeks of observation (n=57) had a greater number of children (mean 2.8, SD 1.5 vs mean 2.5, SD 1.3; risk ratio [RR] 1.2, 95% CI 1.1-1.4), were less likely to have used mobile phones for text messaging at study enrollment (61%, 35/57 vs 76.7%, 115/150; RR 0.6, 95% CI 0.4-0.9), and were less likely to access care at the local public clinic (35%, 20/57 vs 67.3%, 101/150; RR 0.4, 95% CI 0.2-0.6). Parents of female enrolled participants were more likely to have low response rate (57.1%, 84/147 vs 43.8%, 141/322; RR 1.4, 95% CI 1.1-1.9). Several external factors (cellular tower collapse, contentious elections) were associated with periods of decreased reporting. Poor response rate (<70%) was associated with lower case reporting of acute gastroenteritis, norovirus-associated acute gastroenteritis, acute febrile illness, and dengue virus-associated acute febrile illness (P<.001). Parent-reported syndromic data on the Vigilant-e app demonstrated agreement with nurse-collected data for fever (kappa=.57, P<.001), vomiting (kappa=.63, P<.001), and diarrhea (kappa=.61, P<.001), with decreased agreement as the time interval between parental report and nurse home visit increased (<1 day: kappa=.65-.70; ≥2 days: kappa=.08-.29). CONCLUSIONS: In a resource-limited area of rural Guatemala, a mobile phone app-based participatory syndromic surveillance system demonstrated a high reporting rate and good agreement between parental reported data and nurse-reported data during home visits. Several household-level and external factors were associated with decreased syndromic reporting. Poor reporting rate was associated with decreased syndromic and pathogen-specific case ascertainment.

Repeated Rapid Active Sampling Surveys Demonstrated a Rapidly Changing Zika Seroprevalence among Children in a Rural Dengue-endemic Region in Southwest Guatemala during the Zika Epidemic (2015-2016).

Although Central America is largely dengue virus (DENV)-endemic, the 2015-2016 Zika virus (ZIKV) pandemic brought new urgency to develop surveillance approaches capable of characterizing the rapidly changing disease burden in resource-limited settings. We conducted a pediatric DENV surveillance study in rural Guatemala, including serial cross-sectional surveys from April through September 2015 (Survey 1), in October-November 2015 (Survey 2), and January-February 2016 (Survey 3). Serum underwent DENV IgM MAC ELISA and polymerase chain reaction testing. Using banked specimens from Surveys 2 and 3, we expanded testing to include DENV 1-4 and ZIKV microneutralization (MN50), DENV NS1 IgG ELISA, and ZIKV anti-NS1 antibody Blockage of Binding (BoB) ELISA testing. Demographic risk factors for ZIKV BoB positivity were explored using multivariable generalized linear regression models. Of Survey 2 and 3 samples available (N = 382), DENV seroprevalence slightly increased (+1%-10% depending on the assay) during the surveillance period and increased with age. In contrast, ZIKV seroprevalence consistently increased over the 3-month period, including from 6% to 34% (P < 0.0001) and 10%-37% (P < 0.0001) using the MN50 ≥100 and BoB ELISA assays, respectively. Independent risk factors for ZIKV seropositivity included older age (prevalence ratio (PR)/year = 1.12, 95% confidence interval (CI) = 1.07-1.17) and primary caregiver literacy (PR = 2.80, CI = 1.30-6.06). Rapid active surveillance (RAS) surveys demonstrated a nearly 30% increase in ZIKV prevalence and a slight (≤ 10%) increase in DENV seroprevalence from October to November 2015 to January to February 2016 in rural southwest Guatemala, regardless of serologic assay used. RAS surveys may be a useful "off-the-shelf" tool to characterize arboviruses and other emerging pathogens rapidly in resource-limited settings.

Identification of Enteropathogens by Multiplex PCR among Rural and Urban Guatemalan Children with Acute Diarrhea.

Multiplex polymerase chain reaction (PCR) platforms have enhanced understanding of intestinal pathogens in low- and middle-income countries (LMICs). However, few such studies have been performed in Latin America, where poverty, poor sanitation, and undernutrition persist. Multiplex PCR (BioFire, Salt Lake City, UT) was used to identify viral, bacterial, and parasitic pathogens in stool collected on day 1 and 31 from children aged 6 to 35 months with acute, non-bloody diarrhea in two locations (rural and urban) in Guatemala. We analyzed correlation between pathogens and clinical, demographic, and socioeconomic variables; described patterns of pathogen acquisition, persistence, and clearance over the 30-day period; and calculated population attributable fractions (PAFs) for diarrheal causation for individual pathogens. We analyzed 316 subjects (144 urban; 172 rural) enrolled between March 2015 and January 2016. Rural subjects had significantly more malnutrition, animal exposure, and unimproved water/sanitation infrastructure. The majority of subjects had multiple pathogens/sample (4.8 rural and 2.7 urban). Few meaningful correlates were identified between individual pathogens and clinical, demographic, or environmental variables. Escherichia coli pathotypes, Shigella, Campylobacter, and Giardia had high rates of persistence between initial and 30-day follow-up. Statistically significant adjusted PAFs were identified for Campylobacter (14.9%, 95% CI: 3.2-23.1), norovirus (10.2%, 95% CI: 0.4-17.1), sapovirus (7.6%, 95% CI: 2.3-10.9), and adenovirus 40/41 (5.6%, 95% CI: 0.3-8.7). These observations further characterize the diversity and complexity of enteric pathogens in children in LMICs. Patterns of chronic symptomatic and asymptomatic infection among Latin American children are similar to those observed in other LMIC regions. Findings have direct implications for practitioners treating individuals with acute infectious diarrhea and should inform regional public health strategies.

Rapid Active Sampling Surveys as a Tool to Evaluate Factors Associated with Acute Gastroenteritis and Norovirus Infection among Children in Rural Guatemala.

We examined burden and factors associated with norovirus (NoV) acute gastroenteritis (AGE) among children in rural Guatemala. Children age 6 weeks to 17 years were enrolled into three AGE surveillance groups, using two-stage cluster sampling: a prospective participatory syndromic surveillance (PSS) cohort and two cross-sectional rapid active sampling (RAS) surveys, conducted from April 2015 to February 2016. Epidemiologic and NoV testing data were used to identify factors associated with NoV infection, AGE, and NoV+ AGE. The three cross-sectional surveys (PSS enrollment visit, RAS Survey 1, and RAS Survey 2) enrolled 1,239 children, who reported 134 (11%) AGE cases, with 20% of AGE and 11% of non-AGE samples positive for NoV. Adjusted analyses identified several modifiable factors associated with AGE and NoV infection. The cross-sectional RAS surveys were practical and cost-effective in identifying population-level risk factors for AGE and NoV, supporting their use as a tool to direct limited public health resources toward high-risk populations.

A Rapid Epidemiological Tool to Measure the Burden of Norovirus Infection and Disease in Resource-Limited Settings.

BACKGROUND: Rapid, cost-effective tools are needed to estimate the disease burden of acute gastroenteritis (AGE) and norovirus (NoV) in resource-limited settings. METHODS: Households with children (6 weeks-17 years) in rural Guatemala were randomly enrolled into 2 parallel AGE surveillance systems: (1) a prospective cohort, which included an enrollment visit followed by 1 year of prospective observation using a smartphone-based weekly symptom diary; and (2) 2 sequential cross-sectional rapid active sampling (RAS) surveys. Norovirus testing was performed during enrollment (all subjects) and for prospective AGE episodes (prospective cohort only). RESULTS: The prospective cohort enrolled 207 households (469 children) from April to September 2015 followed by 471 person-years of observation; RAS survey 1 enrolled 210 households (402 children) during October to November 2015, and RAS survey 2 enrolled 210 separate households (368 children) during January to February 2016. The prospective cohort detected a NoV+ AGE prevalence of 11% and a population-attributable fraction (PAF) of -1.6% at enrollment, followed by an incidence of 1.4 episodes/100 person-years. Rapid active sampling surveys 1 and 2 identified a NoV+ AGE prevalence of 14%-21% and a PAF of 3.2%-12.4%. CONCLUSIONS: Rapid active sampling surveys were practical and identified more cases of NoV infection and disease compared with a parallel prospective cohort in rural Guatemala.