Cumulative Febrile, Respiratory, and Gastrointestinal Illness Among Infants in Rural Guatemala and Association With Neurodevelopmental and Growth Outcomes.

BACKGROUND: Infectious disease exposures in early life are increasingly recognized as a risk factor for poor subsequent growth and neurodevelopment. We aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants. METHODS: From June 2017 to July 2018, infants 0-3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and underwent weekly at-home surveillance for caregiver-reported cough, fever, and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, 6 months, and 1 year. RESULTS: Of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12-15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score < -2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] < -2 SD). In multivariable analysis, greater cumulative instances of reported cough illness (beta = -0.08/illness-week, P = 0.06) and febrile illness (beta = -0.36/illness-week, P < 0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12-15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; P = 0.27) or with cumulative instances of diarrheal/vomiting illness alone ( P = 0.66). No association was shown between cumulative instances of illness and stunting or microcephaly at 12-15 months. CONCLUSIONS: These findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore pathogen-specific illnesses, host response associated with these syndromic illnesses, and their association with neurodevelopment.

COVID-19 Attitudes and Vaccine Hesitancy among an Agricultural Community in Southwest Guatemala: A Cross-Sectional Survey.

Despite offering free-of-charge COVID-19 vaccines starting July 2021, Guatemala has one of the lowest vaccination rates in Latin America. From 28 September 2021 to 11 April 2022, we conducted a cross-sectional survey of community members, adapting a CDC questionnaire to evaluate COVID-19 vaccine access and hesitancy. Of 233 participants ≥ 12 years, 127 (55%) received ≥1 dose of COVID-19 and 4 (2%) reported prior COVID-19 illness. Persons ≥ 12 years old who were unvaccinated (n = 106) were more likely to be female (73% vs. 41%, p < 0.001) and homemakers (69% vs. 24%, p < 0.01) compared with vaccinated participants (n = 127). Among those ≥18 years, the main reported motivation for vaccination among vaccinated participants was to protect the health of family/friends (101/117, 86%); on the other hand, 40 (55%) unvaccinated persons reported little/no confidence in public health institutions recommending COVID-19 vaccination. Community- and/or home-based vaccination programs, including vaccination of families through the workplace, may better reach female homemakers and reduce inequities and hesitancy.

Anthropometric proxies for child neurodevelopment in low-resource settings: length- or height-for-age, head circumference or both?

Stunting (<-2 SD of length- or height-for-age on WHO growth curves) is the most used predictor of child neurodevelopmental (ND) risk. Occipitofrontal head circumference (OFC) may be an equally feasible, but more direct and robust predictor. We explored association of the two measurements with ND outcome, separately and combined, and examined if cutoffs are more efficacious than continuous measures in predicting ND risk. Infants and young children in rural Guatemala (n = 642; age range = 0.1-35.9 months) were enrolled in a prospective natural history study, and their ND was tested using the Mullen Scales of Early Learning (MSEL) longitudinally. Length- or height-for-age and OFC-for-age were calculated. We performed age-adjusted multivariable regression analyses to explore the association between 1) length or height and ND, 2) OFC and ND, and 3) both length or height and OFC combined, with ND; concurrently, predictively, and longitudinally, as continuous variables and using WHO z-score cutoffs. Continuous length- or height-for-age and OFC z-scores were more strongly associated with MSEL than the traditional -2 SD WHO cutoff. The combination of height-for-age z-score and OFC z-score was consistently, strongly associated with the MSEL Early Learning Composite concurrently (p-values 0.0004-0.11), predictively (p-value 0.001-0.07), with the exception of the 18-24 months age group which had very few records, and in the longitudinal model (p-value <0.0001-0.004). The combination of continuous length- or height-for-age and OFC shows additional utility in estimating ND risk in infants and young children. Measurement of OFC may improve precision of prediction of ND risk in infants and young children.

Clinical and Economic Impact of COVID-19 on Agricultural Workers, Guatemala1.

We evaluated clinical and socioeconomic burdens of respiratory disease in banana farm workers in Guatemala. We offered all eligible workers enrollment during June 15-December 30, 2020, and annually, then tracked them for influenza-like illnesses (ILI) through self-reporting to study nurses, sentinel surveillance at health posts, and absenteeism. Workers who had ILI submitted nasopharyngeal swab specimens for testing for influenza virus, respiratory syncytial virus, and SARS-CoV-2, then completed surveys at days 0, 7, and 28. Through October 10, 2021, a total of 1,833 workers reported 169 ILIs (12.0 cases/100 person-years), and 43 (25.4%) were laboratory-confirmed infections with SARS-CoV-2 (3.1 cases/100 person-years). Workers who had SARS-CoV-2‒positive ILIs reported more frequent anosmia, dysgeusia, difficulty concentrating, and irritability and worse clinical and well-being severity scores than workers who had test result‒negative ILIs. Workers who had positive results also had greater absenteeism and lost income. These results support prioritization of farm workers in Guatemala for COVID-19 vaccination.

Challenges and lessons learned from the rapid operationalization of a prospective cohort to study the natural history and neurodevelopmental outcomes of postnatal Zika virus infection among infants and children in rural Guatemala.

During the course of the 2015-2017 outbreak of Zika virus (ZIKV) in the Americas, the emerging virus was recognized as a congenital infection that could damage the developing brain. As the Latin American ZIKV outbreak advanced, the scientific and public health community questioned if this newly recognized neurotropic flavivirus could affect the developing brain of infants and young children infected after birth. We report here the study design, methods and the challenges and lessons learned from the rapid operationalization of a prospective natural history cohort study aimed at evaluating the potential neurological and neurodevelopmental effects of postnatal ZIKV infection in infants and young children, which had become epidemic in Central America. This study enrolled a cohort of 500 mothers and their infants, along with nearly 400 children 1.5-3.5 years of age who were born during the initial phase of the ZIKV epidemic in a rural area of Guatemala. Our solutions and lessons learned while tackling real-life challenges may serve as a guide to other researchers carrying out studies of emerging infectious diseases of public health priority in resource-constrained settings.

High SARS-CoV-2 Seroprevalence and Rapid Neutralizing Antibody Decline among Agricultural Workers in Rural Guatemala, June 2020-March 2021.

Essential agricultural workers work under occupational conditions that may increase the risk of SARS-CoV-2 exposure and transmission. Data from an agricultural worker cohort in Guatemala, and anti-SARS-CoV-2 nucleocapsid IgG (anti-N IgG) testing were used to estimate past infections and analyze risk factors associated with seropositivity at enrollment and association with SARS-CoV-2 infection. The stability of neutralizing antibody (NAb) responses were assessed in a subset of participants. The adjusted relative risk (aRR) for seroprevalence at enrollment was estimated accounting for correlations within worksites. At enrollment, 616 (46.2%) of 1334 (93.2%) participants had anti-N IgG results indicating prior SARS-CoV-2 infection. A cough ≤ 10 days prior to enrollment (aRR = 1.28, 95% CI: 1.13−1.46) and working as a packer (aRR = 2.00, 95% CI: 1.67−2.38) or packing manager within the plants (aRR = 1.82, 95% CI: 1.36−2.43) were associated with increased risk of seropositivity. COVID-19 incidence density among seronegative workers was 2.3/100 Person-Years (P-Y), higher than seropositive workers (0.4/100 P-Y). Most workers with follow-up NAb testing (65/77, 84%) exhibited a 95% average decrease in NAb titers in <6 months. While participants seropositive at baseline were less likely to experience a symptomatic SARS-CoV-2 infection during follow-up, NAb titers rapidly waned, underscoring the need for multipronged COVID-19 prevention strategies in the workplace, including vaccination.

A prospective cohort study of head circumference and its association with neurodevelopmental outcomes in infants and young children in rural Guatemala.

Microcephaly, an anthropometric marker of reduced brain volume and predictor of developmental disability, is rare in high-income countries. Recent reports show the prevalence of microcephaly to be much higher in lower resource settings. We calculated the prevalence of microcephaly in infants and young children (n = 642; age range = 0.1-35.9 months), examined trends in occipitofrontal circumference (OFC) growth in the year after birth and evaluated the relationship between OFC and performance on the Mullen Scales of Early Learning (MSEL) in rural Guatemala. Multivariable regression analyses adjusted for age were performed: (1) a model comparing concurrent MSEL performance and OFC at all visits per child, (2) concurrent OFC and MSEL performance by age group, and (3) OFC at enrollment and MSEL at final visit by age group. Prevalence of microcephaly ranged from 10.1% to 25.0%. OFC z-score decreased for most infants throughout the first year after birth. A significant positive association between continuous OFC measurement and MSEL score suggested that children with smaller OFC may do worse on ND tests conducted both concurrently and ∼1 year later. Results were variable when analyzed by OFC cutoff scores and stratified by 6-month age groups. OFC should be considered for inclusion in developmental screening assessments at the individual and population level, especially when performance-based testing is not feasible.

Clinical and Economic Impact of COVID-19 on Plantation Workers: Preliminary Results from the Guatemala Agricultural Workers and Respiratory Illness Impact (AGRI) Study.

We evaluated the clinical and socioeconomic burdens of respiratory disease in a cohort of Guatemalan banana plantation workers. All eligible workers were offered enrollment from June 15-December 30, 2020, and annually, then followed for influenza-like illnesses (ILI) through: 1) self-reporting to study nurses, 2) sentinel surveillance at health posts, and 3) absenteeism. Workers with ILI submitted nasopharyngeal swabs for influenza, RSV, and SARS-CoV-2 testing, then completed surveys at days 0, 7, and 28. Through October 10, 2021, 1,833 workers developed 169 ILIs (12.0/100 person-years) and 43 (25.4%) of these ILIs were laboratory-confirmed SARS-CoV-2 (3.1/100 person-years). Workers with SARS-CoV-2-positive ILI reported more anosmia (p<0.01), dysgeusia (p<0.01), difficulty concentrating (p=0.01), and irritability (p=0.01), and greater clinical and well-being severity scores (Flu-iiQ) than test-negative ILIs; they also had greater absenteeism (p<0.01) and lost income (median US$127.1, p<0.01). These results support the prioritization of Guatemalan farm workers for COVID-19 vaccination.

Caregiver rating of early childhood development: Reliability and validity of the ASQ-3 in rural Guatemala.

BACKGROUND: Although performance-based assessment of early childhood development is preferred, there are a number of limitations to this methodology in low resource settings (LRSs). Hence, clinicians and researchers often rely on caregiver report screening tools. The Ages and Stages Questionnaire 3 (ASQ) is one of the most widely used caregiver report measures globally. Adequate psychometric properties have been demonstrated in high income settings, especially when used in older children, high- risk children, or those with severe neurodevelopmental delays. However, its utility is more variable within very young children and for use in LRSs. METHODS: The reliability and validity of the ASQ was determined for children ages 0-5 years living in rural Guatemala. Internal consistency and test-retest reliability were assessed, as well as concurrent and predictive validity. Sensitivity, specificity, positive and negative predictive values related to performance-based developmental assessment (Mullen Scales of Early Learning; MSEL) and growth status (i.e. stunting) were also calculated. RESULTS: Internal consistency reliability for the ASQ was adequate, except when results were limited by small sample size. Test-retest reliability ranged from low to moderate (r = 0.08-0.43; p < 0.05-0.01). However, there was significant variability in mean scores over time across ASQ domain scores. In terms of validity, the ASQ did not discriminate adequately between children who performed within or below age-expectations on performance-based developmental testing or those with and without stunting. CONCLUSIONS: The ASQ did not demonstrate adequate psychometric properties in rural Guatemala, consistent with concerns documented in other LRSs. These results indicate that existing caregiver report screening measures of early childhood development should be utilized with caution in LRSs, and alternative methods for assessment or in the development and utilization of caregiver report measures should be considered.

Parent Report of Health Related Quality of Life in Young Children in Rural Guatemala: Implementation, Reliability, and Validity of the PedsQL in Stunting and Wasting.

In this study, we review the implementation, reliability, and validity of the Pediatric Quality of Life Inventory (PedsQL), a measure of health-related quality of life, in young children in rural Guatemala. Mothers of 842 children (age range = 1-60 months) completed the PedsQL Generic Core Scales 4.0 serially for 1 year. Low (Pearson's r = 0.28, P < .0001) to moderate (Pearson's r = 0.65, P < .0001) consistency in responding over time was shown. The PedsQL did not discriminate reliably between healthy children and those with stunting or wasting. PedsQL scores were not lower during the time of an acute illness. While we found low to moderate evidence for the reliability of the PedsQL in healthy children, it did not discriminate between healthy children and those with stunting, wasting or other acute illness.

Gouverneur' syndrome in a young Hispanic patient: A case report of a rare presentation of a rectal adenocarcinoma tumor.

This is an unusual case report of 32-year-old Hispanic male who presented with an early-onset advanced stage colorectal cancer with an enterovesical fistula. A 32-year-old man presented to our institution referring suprapubic pain, urinary frequency, dysuria and tenesmus for several weeks suggesting Gouverneur's syndrome. Patient had been treated with oral antibiotics for his recurrent urinary tract infections without resolution. Associated unintentional weight loss, decreased appetite and suprapubic pain raised concern for occult malignancy. Abdominopelvic computed tomography scan revealed a rectal mass with invasion to bladder. Colonoscopy biopsy confirmed diagnosis of moderately differentiated rectal adenocarcinoma. This report provides vital information about clinical presentations of enterovesical fistula in an imposed rectal adenocarcinoma in a young Hispanic adult with no previous family or medical history. A thorough clinical assessment must be taken to ensure accurate diagnosis and early detection of colorectal cancer in the young Hispanic population.

Reliability and Validity of an Adapted and Translated Version of the Mullen Scales of Early Learning (AT-MSEL) in Rural Guatemala.

BACKGROUND: A growing literature base supports the use of tests developed in high-income countries to assess children in low resource settings when carefully translated, adapted, and applied. Evaluation of psychometric properties of adapted and translated measures within populations is necessary. The current project sought to evaluate the reliability and validity of an adapted and translated version of the Mullen Scales of Early Learning (AT-MSEL) in rural Guatelama. METHODS: The reliability and validity of the AT-MSEL in rural Guatemala were analyzed for children ages 0-5 years. RESULTS: Interrater reliability coefficients (ICC = 0.99-1.0) and internal consistency (Cronbach's alpha = 0.91-0.93) were excellent for all subscales. General linear models utilizing paired data showed consistency between standard scores (p < 0.0001). Mean raw scores increased with chronological age, as expected. Across age groups, subscales were significantly, positively correlated with one another (p < 0.05 - < 0.001) with one exception, visual reception and expressive language at the 0-10 month age range (p = 0.43). CONCLUSIONS: The AT- MSEL showed strong psychometric properties in a sample of young children in rural Guatemala. Findings demonstrate that the AT-MSEL can be used validly and reliably within this specific population of children. This work supports the concept that tests developed in high-income countries can be used to assess children in low resource settings when carefully translated, adapted and applied.

Receptive language skills among young children in rural Guatemala: The relationship between the Test de Vocabulario en Imagenes Peabody and a translated and adapted version of the Mullen Scales of Early Learning.

BACKGROUND: Children in low- and lower middle income countries (LMICs) often have poorer language skills compared with children from high-income countries. Limited availability of culturally and linguistically appropriate assessment measures in LMICs, especially for young children, can hinder early identification and prevention efforts. Here, we describe receptive language (RL) skills among young children in rural Guatemala and report on the validity of a translated and culturally adapted developmental measure of RL. METHODS: Children (n = 157; m = 53.6 months, range = 42-68 months) enrolled in a prospective cohort study of postnatally acquired Zika virus infection were administered the Test de Vocabulario en Imagenes Peabody (TVIP) and the RL scale from a translated and adapted version of the Mullen Scales of Early Learning (MSEL). Performance on the TVIP was compared with the Latin American normative sample. Correlational analysis examined the relationship between performance on the TVIP and the MSEL-RL. RESULTS: Mean scores were significantly below the normative sample mean on the TVIP, t(126) = -11.04, p < .001; d = 1.00. Performance on the TVIP among children who passed the practice items (n = 127) was significantly positively associated with performance on the MSEL-RL (r = .50, p < .001), but not significantly associated with age or gender. Older age (p < .0001) and female gender (p = .018) were associated with passing the TVIP practice items. CONCLUSIONS: Delays in RL vocabulary were identified among young children in rural Guatemala on the TVIP. The association between scores on the TVIP and the RL scale of the MSEL provides preliminary support for the construct validity of this translated and adapted version of the MSEL.

The global school-based student health survey as a tool to guide adolescent health interventions in rural Guatemala.

BACKGROUND: Adolescents from rural areas in low-middle income countries face increasing physical and mental health challenges that are not well characterized or addressed due to resource limitations. We used the Global School-based Student Health Survey (GSHS) to describe adolescent health behaviors, and to inform prioritization of health promotion efforts in a resource-limited, rural, agricultural region in Guatemala. METHODS: In July 2015, a group of volunteers administered the GSHS to students from seven schools in four communities in the southwest Trifinio region of Guatemala. Prevalence and predictors of nutritional, mental, and sexual health behaviors were calculated from survey responses, and summarized in region- and school-level reports. Facilitated discussion of survey results with local leadership in January 2016 led to the identification of priorities for school-based health interventions. RESULTS: Five hundred fifty-four out of 620 (87%) students aged 12-18 years completed the survey. Prevalence of unhealthy dietary behaviors and body size was high: 61% reported high current soft drink intake, 18% were overweight, and 31% were moderate-severely stunted. In multivariable regression models, being food insecure was marginally associated with being underweight/stunted (OR = 1.95, 95%CI = 0.95-4.0). Boys were more likely than girls to report being sexually active (25% versus 6.4%, p < 0.001). Local school leadership identified food insecurity and sexual education as priority areas for intervention, and made plans for providing breakfast in schools, sexual education curriculum development and teacher training, and continued adolescent health reporting and evaluation. CONCLUSIONS: The GSHS is a rapid, cost-efficient, useful tool for surveillance of adolescent health behaviors in vulnerable, resource-limited populations. Results of a locally-administered GSHS informed school-based interventions to decrease food insecurity, early sexual initiation, and teen pregnancy in a rural Guatemalan region.

Trends in the Mode of Delivery of Pregnant Women in Rural Guatemala from a Quality Improvement Database.

Purpose To evaluate trends and factors associated with mode of delivery in the rural Southwest Trifinio region of Guatemala. Description We conducted a retrospective analysis of self-reported antepartum factors and postpartum outcomes recorded in a quality improvement database among 430 women enrolled in a home-based maternal healthcare program between June 1, 2015 and August 1, 2017. Assessment Over the study period, the rates of cesarean delivery (CD) increased (from 30 to 45%) and rates of vaginal delivery (VD) decreased (70-55%) while facility-based delivery attendance remained stable around 70%. Younger age (23.5 years for VD vs. 21.6 years for CD, p < 0.001), nulliparity (25.1% for VD vs. 45.0% for CD, p < 0.001), prolonged/obstructed labor (2.4% for VD vs. 55.6% for CD, p < 0.001), and fetal malpresentation (0% for VD vs. 16.3% CD, p < 0.001) significantly influenced mode of delivery in univariate analysis. The leading indications for CD were labor dysfunction (47.5%), malpresentation (14.5%), and prior cesarean delivery (19.8%). The CD rate among the subpopulation of term, nulliparous women with singleton pregnancies in vertex presentation also increased from 20% of all CD in 2015, to 38% in 2017. Conclusion Among low-income women from rural Guatemala, the CD rate has increased above the World Health Organization (WHO) recommendations in a period of 3 years. Additional research on the factors affecting this trend are essential to guide interventions that might improve the appropriateness of CD, and to determine if reducing or stabilizing rates is necessary.

Responding to the Zika Epidemic: Preparation of a Neurodevelopmental Testing Protocol to Evaluate Young Children in Rural Guatemala.

The ongoing Zika virus (ZIKV) epidemic in Latin America presented a unique opportunity to develop a neurodevelopmental assessment protocol for children in a lower middle-income country. Although studies of neurodevelopment in young children have taken place in many diverse global settings, we are not aware of any study that has provided a high level of detail about how a measure was selected and then specifically translated and adapted in a low-resource setting. Here, we describe considerations in measurement selection and then the process of translation and adaptation to assess neurodevelopmental outcomes of infants and young children with postnatal exposure to ZIKV in rural Guatemala. We provide a framework to other research teams seeking to develop similar assessment models across the globe.

Are Physician Assistants Needed in Guatemala? A Survey of Potential Urban and Rural Users.

PURPOSE: The shortage of trained health care personnel has been increasing worldwide. With the physician assistant (PA) profession, created in the United States in the 1960s, expanding globally, this study sought to ascertain whether PAs can be an innovative solution to this crisis. METHODS: We conducted a convenience sample survey to assess the need for and acceptability of future PA professionals in Guatemala. Eighty-nine doctors, nurses, and community members from rural and urban areas of Guatemala participated in the survey. RESULTS: More urban (70%) than rural (58%) respondents found it difficult to access a doctor, with cost being the major reason (34%). Access in rural areas was reportedly limited by lack of doctors and inaccessible office hours. CONCLUSIONS: Most survey respondents considered PAs to be suitable and potentially helpful providers for Guatemala, with a preference for competencies in the diagnosis of serious illnesses, drug prescription, labor and delivery attendance, and care for injuries and fractures, especially in rural locations. Belonging to the community was deemed very important for a PA who would practice in the country.

The association of DNA Repair with breast cancer risk in women. A comparative observational study.

BACKGROUND: Previous studies have found a link between a low DNA repair capacity (DRC) level and increased cancer risk. Our aim was to assess the statistical association of DRC level and breast cancer (BC) using a case-control epidemiological study in a Hispanic community. METHODS: We conducted a comparative observational study to assess the validity of DRC in detecting BC in 824 women throughout Puerto Rico. Over a 6-year period, we compared 285 women newly diagnosed with BC to 539 without BC. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. We assessed the sensitivity, specificity, and association using the receiver operating characteristic curve analysis. Multiple logistic regression-adjusted odds ratios were estimated with 95% confidence level to measure the strength of the association of DRC and BC after adjusting for all confounders simultaneously. RESULTS: Compared to women without cancer, women with BC showed an average decrease of 60% in their DRC levels (p < 0.001). Validity of the association of DRC as a measure of BC risk showed a sensitivity of 83.2% and specificity of 77.6% (p < 0.0001). CONCLUSIONS: Our results support the usefulness of DRC level as a measure of BC risk. Additional studies in other populations are needed to further verify its usefulness.

Non-specific symptomatogy presenting in a patient with Gaucher's disease creating a challenging diagnosis: a case report.

Gaucher's disease is the most common of the lysosomal storage diseases; however, with a current worldwide incidence of 1/75,000, it is still a rare occurrence. We present a case of Gaucher's disease type 1 in a Hispanic patient, the first incidence of this specific subtype of Gaucher's disease to be reported in Puerto Rico. Due to the patient's uncharacteristic presentation of negative initial bone marrow biopsy followed by the findings of Gaucher cells on splenic tissue examination, we investigate the specificity and sensitivity of various diagnostic methods to the disease as evidenced in the current literature. Physician awareness of an effective diagnostic approach as illustrated by this report is critical for the early diagnosis of Gaucher's disease so as to prevent disease progression and increased patient morbidity.