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Background Despite safe and effective childhood immunizations, decreased acceptance of vaccines has become an emerging global problem. The WHO SAGE Working Group on Vaccine Hesitancy developed a common diagnostic tool, the Vaccine Hesitancy Scale (VHS), to identify and compare hesitancy in different global settings. We field tested the VHS in rural and urban Guatemala. Methods We analyzed data from the enrollment visit of a study conducted at four public health clinics in Guatemala. Infants ages 6 weeks-6 months presenting for their first wellness visit were enrolled March-November 2016. Parents completed a demographic survey that included the 10 dichotomous and 10 Likert scale VHS questions. Chi-square or Fisher’s exact for categorical and ANOVA test for continuous variables were used to assess significance levels in survey differences. We conducted a factor analysis to assess the Likert scale questions. Results Of 1088 families screened, 871 were eligible and 720 (82.7%) participated. No parent had ever refused a vaccination, and only eight parents (1.1%) had been reluctant or hesitated to get a vaccination for their children. However, only 40.8% (n = 294) of parents said that they think most parents like them have their children vaccinated with all the recommended vaccines. Factor analysis identified two underlying constructs that had eigenvalues of 1.0 or greater and a substantive lack of variability in response across the Likert scale. There were consistent differences between how study clinics responded to the ordinal scaling. Conclusion Our results suggest problems with interpretation of the VHS, especially in the presence of vaccine shortages and using a Likert scale that does not resonate across diverse cultural settings. Our factor analysis suggests that the Likert scale items are more one-dimensional and do not represent the multiple constructs of vaccine hesitancy. We suggest more work is needed to refine this survey for improved reliability and validity. Clinical Trial Registry: NCT02567006 .

Vaccine hesitancy is a continuum of behaviors ranging from delay in receipt to vaccination refusal. Prior studies have typically focused on high-income countries, where vaccine hesitancy is particularly prevalent in more affluent groups, but the relationship between socioeconomic status and vaccine hesitancy in Low- and Middle-Income Countries (LMICs) is less clear. The aim of this study was to describe vaccine hesitancy in five LMICs. Mothers of children in Sirajganj, Bangladesh (n = 60), Shanghai, China (n = 788), Addis Ababa, Ethiopia (n = 341), Guatemala City and Quetzaltenango, Guatemala (n = 767), and Chandigarh, India (n = 309), completed a survey between 2016 and 2018 using the WHO&rsquo, s 10-item Vaccine Hesitancy Scale. The scores of different constructs were compared across countries and by the mother&rsquo, s education level using linear regression models with generalized estimating equations. Compared to mothers in China, mothers in Bangladesh perceived less vaccination benefit (&beta, 0.56, P = 0.0001), however, mothers in Ethiopia (&beta, &minus, 0.54, P &lt, 0.0001) and Guatemala (&beta, 0.74, P = 0.0004) perceived greater benefit. Education level was not significantly linked with vaccine hesitancy. Local circumstances are important to consider when developing programs to promote vaccines. We did not find consistent associations between education and vaccine hesitancy. More research is needed to understand socio-cultural influences on vaccine decision-making.

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.

Objective Millions of infants worldwide remain under-immunized and at risk for unnecessary morbidity and mortality. Text messaging may offer a low-cost solution. We aimed to evaluate text message reminders to improve infant immunization in Guatemala. Methods A randomized clinical trial was conducted at four public health clinics in rural and urban Guatemala. Infants ages six weeks to six months presenting for the first visit of the primary immunization series were randomly and equally allocated to an intervention or usual care group. Intervention participants were sent three text reminders before the second and third vaccine visits. The main outcome was timeliness of the second and third visits of the primary immunization series. Results Of 1088 families approached for enrollment between March to November 2016, 871 were eligible and 720 (82.7%) participated; only 54 families did not own a cell phone. Due to country-wide vaccine shortages, visit completion was used as a proxy for overall immunization coverage. In intention to treat analysis, both intervention and usual care groups had high rates of visit completion, but intervention participants presented on the scheduled date more often (151 [42.2%] of 358 intervention vs. 111 [30.7%] of 362 usual care participants for visit 2, p = 0.001, and 112 [34.0%] of 329 intervention vs. 90 [27.0%] of 333 usual care participants for visit 3, p = 0.05). Intervention caregivers were significantly more likely to want to receive future text message reminders for vaccines and other appointments and were more willing to pay for these reminders. Conclusion Caregivers who were sent text message reminders in urban and rural Guatemala were less delayed for their child’s immunization visits and reported high user satisfaction. Text message reminders may be an effective tool to increase infant vaccination coverage in low-income settings by reminding parents to vaccinate. Trial Registration: NCT02567006 at clinicaltrials.gov .

Highlights • A novel SMS vaccine reminder platform was created in a LMIC. • SMS vaccine reminders were proven feasible to implement in a LMIC. • SMS vaccine reminders were acceptable to use in a LMIC with high user satisfaction. • SMS vaccine reminders have the potential for widespread scalability at low cost., Background Patient reminder systems are an evidence-based way to improve childhood vaccination rates but are difficult to implement in low- and middle-income countries (LMICs). Short Message Service (SMS) texts may offer a potential low-cost solution, especially in LMICs where mobile phones are becoming more ubiquitous. Objective To determine if an SMS-based vaccination reminder system aimed at improving completion of the infant primary immunization series is feasible and acceptable in Guatemala. Methods A pilot randomized controlled trial was conducted at two public health clinics in Guatemala City. Infants aged 8–14 weeks presenting for the first dose of the primary immunization series were enrolled in March–April 2013. Participants randomized into the intervention received three SMS reminders one week before the second and third dose. A follow-up acceptability survey was administered to both groups. Results The participation rate was 86.8% (321/370); 8 did not own a cell phone and 12 could not use SMS. 96.9% of intervention parents were sent at least one SMS reminder prior to visit 2 and 96.3% prior to visit 3. Both intervention and usual care participants had high rates of vaccine and visit completion, with a non-statistically significant higher percentage of children in the intervention completing both visit 2 (95.0% vs. 90.1%, p = .12) and visit 3 (84.4% vs. 80.7%, p = .69). More intervention vs. usual care parents agreed that SMS reminders would be helpful for remembering appointments (p

Background Treatments for paediatric diarrhoeal disease are limited. We assessed the impact of a bovine colostrum and egg-based treatment designed to reduce diarrhoea duration through non-specific and pathogen-directed mechanisms in children. Methods Randomised, double-blind, placebo-controlled trial of PTM202, derived from bovine colostrum and hyperimmune hen’s egg on the duration of acute diarrhoeal disease in Guatemalan children. PTM202 contains specific immunoglobulins that target rotavirus, enterotoxigenic Escherichia coli , Shiga toxin-producing E. coli and Salmonella. Children aged 6–35 months presenting to three sites (one rural and two urban) with acute non-bloody diarrhoea were computer randomised to receive three daily doses of PTM202 or placebo. The primary outcome was the post-treatment duration of diarrhoea assessed in the per protocol population. Diarrhoeal pathogens were identified in stool by multiplex PCR (FilmArray Gastrointestinal-Panel, BioFire, Salt Lake City, Utah, USA). Key secondary outcomes included postdiarrhoeal weight gain and impact on diarrhoeal duration stratified by study site and presence of PTM202-targeted organisms in stool at enrolment. Safety was assessed in all participants. Results From 9 March 2015 to 25 January 2016, 325 children were enrolled, and 301 (154 intervention and 147 placebo) were analysed for the primary outcome. No difference in diarrhoea duration was observed between intervention and placebo in the total population, but a significant reduction was observed in the treatment group among children with at least one targeted pathogen in stool (HR=1.46, P=0.02), an effect most pronounced in urban subjects (HR 2.20, P=0.007) who had fewer stool pathogens and better nutritional status. No impact on 2-week or 4-week weight gain was noted. No adverse events attributed to PTM202 occurred. Conclusion Results demonstrate the potential to target specific pathogens occurring in children with acute non-bloody diarrhoea and shorten illness duration using a novel, safe, nutrition-based intervention. PTM202 may represent a new tool to ameliorate the effects of acute diarrhoeal disease in low/middle-income populations. Trial registration number NCT02385773; Results.

Background Little is known about the epidemiology and risk factors for Clostridium difficile infection (CDI) among children in low and middle-income countries (LMICs). We sought to characterize the clinical, demographic, and environmental factors associated with C.difficile acquisition and persistence over time, and assess the relationship between CDI and additional diarrheal pathogens among rural and urban Guatemalan children. Methods Children 6–35 months old with acute nonbloody diarrhea ( Results CDI was present in 26 of 298 subjects at baseline; 13 (50%) had persistence at 30 days and 13 (50%) cleared. New acquisition at day 30 occurred in 23 subjects. In multivariable analysis adjusted for age, recent hospitalization was marginally significantly associated with C. difficile presence in stool at baseline (prevalence ratio [PR] 2.65, P = 0.07). In subjects with either new C. difficile acquisition or persistence between baseline and day 30, residence in the rural site (PR 0.33, P = 0.003)) and presence of E. coli pathotypes: enteropathogenic (EPEC), enteroaggregative (EAEC), and enterotoxigenic (ETEC) (PR 0.43, P = 0.01)) were associated with reduced risk of CDI. Conclusion In an LMIC pediatric population, the presence of E. coli pathotypes appeared protective against C. difficile persistence/new acquisition. These findings add to our current understanding that CDI occurs in part as a result of competition within the intestinal microbiota, which may be independent of the potential pathogenicity of competing microbes. We hypothesize that this phenomenon could be suppressing the C. difficile burden among children in LMICs. Disclosures All authors: No reported disclosures.

Objective Combination vaccines have improved the efficiency of delivery of new vaccines in low and middle-income countries. Post-authorization monitoring of adverse events (AEs) after vaccination with a liquid pentavalent DTwP-HepB-Hib combination vaccine was conducted in Guatemalan infants. Methods A prospective observational safety study of the incidence of medical attended events (MAEs) and serious adverse events (SAEs) in children who received pentavalent and oral polio vaccines at 2, 4 and 6 months of age was conducted in two clinics at the Institute of Guatemala. Parents were contacted by telephone after each dose. All outpatient, emergency department visits, and hospitalizations were monitored. A self-controlled analysis was conducted to determine if there was evidence of increased risk of MAEs or SAEs following vaccines as compared to control time windows. Results Of 3000 recruited infants, 2812 (93.7%) completed the third dose and 2805 (93.5%) completed follow-up. Ten AEs in eight infants, of which four SAEs in four infants, were classified as related to the vaccine. Thirteen deaths were reported due to common illnesses of infancy, and none were judged to be related to the vaccine. The mortality rate (4.4 per 1000) was lower than expected for the population. The incidence-rate-ratio for healthcare visits was lower in post-vaccination time windows than for control windows; after the first vaccine dose, the rate ratios for the risk periods of 0–1, 2–6, and 7–30 days post-vaccination were 0.3, 0.5, and 0.7, respectively (all statistically significantly different from the reference value of 1.0 for the 31–60 day control period). Conclusion The liquid pentavalent vaccine was associated with lower rates of health care visits and not associated with increases in SAEs or hospitalizations. Systems can be set up in low to middle income countries to capture all health care visits to monitor the safety of new vaccines.

Background Concerns remain about lower effectiveness and waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both the monovalent (RV1; 2-dose series) and pentavalent (RV5; 3-dose series) vaccines were introduced in 2010. Methods A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth date and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness ([1 - odds ratio of vaccination] × 100%) was computed using logistic regression models. Results We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2-3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval [CI], 58%-84%) with hospital controls, and 52% (95% CI, 26%-69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6-11 months (74% [95% CI, 18%-92%]) and children ≥12 months of age (71% [95% CI, 44%-85%]) (P= .85), nor between complete courses of RV1 (63% [95% CI, 23%-82%]) and RV5 (69% [95% CI, 29%-87%]) (P= .96). An uncommon G12P[8] strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. Conclusions RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur.

Background: Despite efforts to promote vaccination in low- and middle-income countries (LMICs), over 20 million infants remain under-immunized and at risk for unnecessary morbidity and mortality. Mobile health technologies, such as Short Message Service (SMS) texts, have tremendous and untapped potential for disease management. Patient reminder systems are an important mechanism for improving childhood vaccination coverage and can be easily adapted to SMS platforms. However, current research lacks an understanding of the barriers and facilitators to mHealth program design, implementation, and scale in LMICs. Methods: We analyzed survey data collected March–November 2016 at the enrollment visit from a randomized controlled trial conducted at public health clinics in urban and rural Guatemala. Participants included eligible infants 6 weeks to 6 months of age receiving the first dose of the primary immunization series. At least one parent needed to own a mobile phone and be capable of deciphering SMS. Chi-square or Fisher’s exact and Student’s t-test were used to assess significance levels in demographic differences to describe factors that contribute to the feasibility of using an SMS-based vaccination reminder system. Results: Of 1,088 families approached for enrollment, 871 were eligible and 720 (82.7%) participated with equal numbers of urban and rural children enrolled; 54 parents did not own a mobile phone with SMS capability and three parents could not use SMS. There was no significant difference between urban and rural maternal mobile phone ownership (94.4% vs . 93.3%, P=0.53), but more urban fathers owned mobile phones (72.8% vs . 47.1%, P vs . 61.1%, P vs . 15.6%, P vs . 25.3%, P vs . 18.6%, P Conclusions: Our study results provide important insight into mobile phone access, usage, and preferences for voice and text communication across rural and urban populations of an LMIC that can be used to inform future mHealth interventions. Our findings suggest that offering a combination of more traditional communication methods with newer, modern technologies may be more effective at reminding families about vaccination visits, particularly for our rural population, and that targeting mothers for mobile phone interventions may provide the greatest benefits. Overall, our study suggests that using SMS reminders in LMICs can be a feasible tool for public health interventions.

Background Determination of the cause of childhood diarrhea in low- and middle-income countries is complicated by the presence of multiple potential pathogens in stool at the time of illness. Serial multiplex PCR may offer a method to characterize pathogens more likely to clear over time (suggesting a higher likelihood of causality) vs. those that are more typically persistent (suggesting higher likelihood of nonpathogenic colonization). Such determination may have both clinical and epidemiologic utility. Methods Children 6–35 months old with acute non-bloody diarrhea (duration

Background Diarrhea is a leading cause of morbidity and mortality in children in low and middle income countries (LMICs). Assessing diarrhea etiology in LMICs is of great importance in order to better develop both therapeutic and public health strategies, but is hampered by the complexity of potential diarrheal pathogens, and diverse methodology needed for pathogen identification Methods Subjects 6 to 35 months old with acute, moderate severity, non-bloody diarrhea were enrolled in a diarrheal treatment trial, conducted at one rural (N = 172) and two urban sites (N = 144) in Guatemala. Diarrheal pathogens were determined in stool by multiplex PCR (FilmArray GI® Biofire) which allows simultaneous identification of 23 bacterial, viral, parasitic pathogens. Descriptive statistics on demographics, pathogen load, and differences in pathogen occurrence by site were performed; differences were assessed with t-test and chi2 test Results Nearly all (96.8%) subjects had pathogens identified, and most had multiple potential pathogens identified (mean pathogen count: 2.7 urban and 4.8 rural; P < 0.001 (Figure 1). Notable pathogen differences were observed between rural and urban populations. Bacteria (particularly E.coli pathotypes and Campylobacter) and protozoa (particularly giardia) were more common in the rural population (Figure2). Viral pathogens were either similar or more common (norovirus; P = 0.04) in the urban population; rotavirus was uncommon in both sites (10 rural and 12 urban cases). A similar pattern of pathogen evolution with patient age was noted in both settings, with a decrease in the relative number of viral and increase in parasitic pathogens (Figure 3). Important demographic and socioeconomic differences between rural and urban were noted: rural subjects had poorer nutritional status, underdeveloped water and sanitation facilities and more domestic animal exposure Conclusion Acute diarrheal episodes in Guatemalan children were associated with a complex spectrum of pathogens when determined by multiplex PCR, with distinct patterns in rural and urban populations. Future studies to precisely determine diarrheal etiologies in LMICs will need to incorporate controls to sort causative organisms from those colonizing the intestine. Disclosures All authors: No reported disclosures.