The authors have declared that no competing interests exist.
Conceived and designed the experiments: PJC MC. Performed the experiments: CS NB IG. Analyzed the data: SKM AR PJC. Wrote the paper: SKM PJC AR.
Soil-transmitted helminths (STH) infect more than 2 billion humans worldwide, causing significant morbidity in children. There are few data on the epidemiology and risk factors for infection in pre-school children. To investigate risk factors for infection in early childhood, we analysed data prospectively collected in the ECUAVIDA birth cohort in Ecuador.
Children were recruited at birth and followed up to 3 years of age with periodic collection of stool samples that were examined microscopically for STH parasites. Data on social, demographic, and environmental risk factors were collected from the mother at time of enrolment. Associations between exposures and detection of STH infections were analysed by multivariable logistic regression. Data were analysed from 1,697 children for whom a stool sample was obtained at 3 years. 42.3% had at least one STH infection in the first 3 years of life and the most common infections were caused by
Our data show high rates of infection with STH parasites during the first 3 years of life in an Ecuadorian birth cohort, an observation that was strongly associated with maternal STH infections during pregnancy. The targeted treatment of women of childbearing age, in particular before pregnancy, with anthelmintic drugs could offer a novel approach to the prevention of STH infections in pre-school children.
Soil-transmitted helminths (STH) are intestinal worms that cause significant morbidity in school age and pre-school children in developing countries. Infections are associated with poverty, particularly through lack of access to sanitation and clean drinking water. Current control strategies rely on periodic anthelmintic treatment of schoolchildren but new strategies are required for STH control in young children. There are few data on modifiable risk factors in pre-school children. We investigated environmental and socioeconomic risk factors for STH infection in the first 3 years of life in a birth cohort from an STH-endemic region of Latin America. Our data provide evidence that maternal STH infections documented during pregnancy are an important risk factor for infection in young children, raising the possibility of a novel intervention for the prevention of STH-associated morbidity in early childhood through the deworming of women of childbearing age, in particular before pregnancy.
Soil-transmitted helminths (STH), including
Morbidity due to STH infections has primarily been associated with anaemia, malnutrition
Current strategies for the control of STH infections are primarily based upon periodic treatment of schoolchildren with anthelmintic drugs, and secondarily on education and improvements in sanitation. Treatment-based control strategies aim to control morbidity through reductions in the community transmission of STH infections
Previous studies have shown that the main risk factors for STH infection are rural residency, low socioeconomic status and poor sanitation
There are few data on the epidemiology of STH infections and risk factors for infection in pre-school children. Such data are relevant to the control of STH infections because pre-school children constitute an important reservoir of infection and are at risk of morbidity. To investigate the epidemiology of STH infections in early childhood and to identify risk factors for infection, we analysed data collected prospectively during the first 3 years of life in the ECUAVIDA birth cohort in tropical Ecuador.
Details of the design and methodology for the ECUAVIDA birth cohort study, an investigator-driven study, are provided elsewhere
All children recruited to the ECUAVIDA birth cohort study were eligible for inclusion in this analysis. Children were actively followed from birth to 3 years of age with collection of stool samples at 3, 7, 13, 18, 24, 30 and 36 months. Sample collection took place between November 2005 and December 2012 covering the period of cohort recruitment and the period to 3 years of age of the whole cohort. Stools at 3, 18, and 30 months were collected passively (mothers were asked to provide a sample at the next time point during the previous follow-up), while mothers were actively requested for stool samples at the respective ages for the remaining time points. Household members were also asked to provide one stool sample around the time that the mother was enrolled into the study. Data on risk factors and potential confounders were collected by a questionnaire that was administered to the child's mother by a trained member of the study team around the time of birth of the child. Categories included in the questionnaire were; maternal and paternal data (age, ethnicity, education, occupation, and number of live children [mother only]), urban versus rural location, socio-economic data (monthly income, number of material goods [household electrical appliances including refrigerator, television, Hi-Fi, and radio], a household electrical connection, household construction materials, sources of drinking water, and type of bathroom [for disposal of faeces]), number of sleeping rooms and number of people living in the household, and data on exposure to household pets, farming and farm animals. Household overcrowding was defined as number of people living in the household per bedroom. Data on number of anthelmintic treatments during the first 3 years of life was obtained from a questionnaire administered to the mother when the child was 7, 13, 24, and 36 months.
Single stool samples were collected and analysed for STH eggs and larvae by direct saline wet mounts (for detection of all STH eggs including
A sample size of 1,697 individuals included in this analysis was estimated to provide over 80% power at P<0.05 to detect exposure effects on risk of any STH prevalence with effect sizes of or less than 0.56 (10% exposure prevalence), 0.68 (20%), 0.72 (30%, and 0.74 (40%). Any STH infection was defined by the presence of at least one STH ovum or larva in any stool sample. Potential risk factors evaluated included parental factors, child factors (gender, gestational age, and birth order), socioeconomic status and factors relating to the environment in which the child was living. A socio-economic status (SES) index was created using principal components analysis for categorical data by combining the socioeconomic variables. The first component that accounted for 30.0% of variation was divided into tertiles to represent low, middle, and high SES. The primary outcome was infection with any STH infection during the first 3 years of life. Secondary outcomes were age of first STH infection and any infection with
The study protocol was approved by the ethics committee of the Hospital Pedro Vicente Maldonado, Universidad San Francisco de Quito, and Pontificia Universidad Catolica del Ecuador, Ecuador. The study is registered as an observational study (ISRCTN41239086). Informed written consent was obtained from the child's mother and from household members for the collection of stool samples. Children with positive stools for STH infections were treated with a single dose of 400 mg albendazole if aged 2 years or greater and with pyrantel pamoate (11 mg/kg) if aged less than 2 years, according to Ecuadorian Ministry of Public Health recommendations
Of 2,404 newborns recruited, 1,697 (70.6%) of children had a stool sample examined at 3 years of age and these were the children included in the present analysis. Follow-up to 3 years of age for stool sampling for the whole cohort is illustrated in
The children included in the present analysis were those for whom a stool sample was collected at 3 years of age.
Of the 1,697 children analysed here, 718 (42.3%) were infected with at least one STH infection during the first 3 years of life. The most frequent STH infection was
Prevalence of STH infections in children is shown at regular age intervals during the first 3 years of life. The maternal stool sample was collected during the 3rd trimester of pregnancy and from other household members soon after the child's birth.
Infection intensities were estimated using the Kato-Katz method in eggs per gramme of stool and intensity groups were categorized using WHO guidelines
Characteristic | Uninfected (n = 979) (N, %) | Infected (n = 718) (N, %) | P value | ||
Child Factors | |||||
Sex | |||||
Male | 497 | 50.8% | 357 | 49.7% | 0.671 |
Gestational age (weeks) [Mean/SD] | 39 | 2 | 39 | 2 | 0.791 |
Birth order | |||||
1–2 | 517 | 52.8% | 306 | 42.6% | |
3–4 | 311 | 31.8% | 235 | 32.7% | |
>5 | 151 | 15.4% | 177 | 24.7% | <0.001 |
Maternal Factors | |||||
Age [Mean/SD] | 26 | 6 | 25 | 6 | 0.048 |
Ethnicity | |||||
Afro-Ecuadorian | 187 | 19.1% | 259 | 36.1% | <0.001 |
Other | 792 | 80.9% | 459 | 63.9% | |
Educational level | |||||
Illiterate | 103 | 10.5% | 155 | 21.6% | |
Complete primary | 562 | 57.4% | 448 | 62.4% | |
Complete secondary | 314 | 32.1% | 115 | 16.0% | <0.001 |
Paternal Factors | |||||
Age [Mean/SD] | 30 | 8 | 30 | 9 | 0.516 |
Ethnicity | |||||
Afro-Ecuadorian | 175 | 18.3% | 204 | 29.4% | <0.001 |
Other | 779 | 81.6% | 491 | 70.6% | |
Educational level | |||||
Illiterate | 114 | 12.4% | 133 | 20.9% | |
Complete primary | 486 | 52.8% | 354 | 55.7% | |
Complete secondary | 321 | 34.9% | 149 | 23.4% | <0.001 |
Socioeconomic status | |||||
Low | 328 | 33.5% | 312 | 43.5% | |
Medium | 303 | 30.9% | 230 | 32% | |
High | 348 | 35.5% | 176 | 24.5% | <0.001 |
Environmental Factors | |||||
Area of residence | |||||
Urban | 652 | 66.6% | 528 | 73.5% | 0.002 |
Household overcrowding | |||||
≥3 people | 511 | 65.0% | 490 | 80.7% | <0.001 |
Maternal STH Infections | |||||
Any STH infection | |||||
Yes | 346 | 35.5% | 425 | 59.5% | <0.001 |
Yes | 184 | 18.9% | 273 | 38.2% | <0.001 |
Negative | 790 | 81.1% | 441 | 61.7% | |
Light | 174 | 17.9% | 200 | 28.0% | |
Moderate | 10 | 1.0% | 67 | 9.4 | |
Heavy | 0 | 0% | 6 | 0.8% | <0.001 |
Yes | 197 | 20.2% | 279 | 39.1% | <0.001 |
Negative | 777 | 79.8% | 438 | 61.2% | |
Light | 180 | 18.5% | 224 | 31.4% | |
Moderate | 17 | 1.7% | 47 | 6.6% | |
Heavy | 0 | 0% | 6 | 0.8% | <0.001 |
Hookworm | |||||
Yes | 41 | 4.2% | 63 | 8.8% | <0.001 |
Paternal STH infection | |||||
Yes | 82 | 23.9% | 104 | 40.9% | <0.001 |
Other household member with STH | |||||
Yes | 408 | 41.7% | 428 | 59.6% | <0.001 |
Number of stool samples from child | |||||
1–4 | 442 | 45.1% | 288 | 40.1% | |
≥5 | 537 | 54.9% | 430 | 59.9% | 0.022 |
Number of anthelmintic treatments |
|||||
Received by child | |||||
0 | 250 | 25.5% | 164 | 22.8% | |
1 | 451 | 46.1% | 323 | 45% | |
≥2 | 278 | 28.4% | 231 | 32.2% | 0.191 |
P values were calculated using Chi-squared or Student's t tests, as appropriate. Ethnicity ‘other’ represents: mothers; 1,245 Mestizo/6 Indigenous; fathers 1264 Mestizo/6 Indigenous. Socioeconomic status represents tertiles of z scores obtained using a factor analysis. Overcrowding is defined as the number of people living in the household per sleeping room. STH infections were detected using direct saline, Kato-Katz and formol-ether concentration methods. SD – standard deviation. Infection intensities were estimated using the Kato-Katz method. STH infection intensity categories were:
*Treatments with any of: albendazole, mebendazole, oxantel/pyrantel, piperazine, nitazoxanide, and flubendazole. Numbers of missing values (brackets) were: gestational age (312), maternal ethnicity (6), paternal ethnicity (54), paternal educational level (140), household overcrowding (304), maternal STH infection (9), and paternal STH infection (1100).
The distributions of covariates between children with any documented STH infection and those without a documented infection are shown in
Variable | Univariate | Multivariable | ||
OR (95% CI) | P value | OR (95% CI) | P value | |
Child Factors | ||||
Sex: Male vs. Female | 0.96 (0.79–1.16) | 0.671 | ||
Gestational age: <39 vs. ≥39 weeks | 0.95 (0.76–1.19) | 0.639 | ||
Birth Order: ≥5th vs. <5thh | 1.79 (1.41–2.29) | <0.001 | 1.85 (1.31–2.60) | 0.001 |
Maternal Factors | ||||
Age: <26 vs. ≥26 years | 1.19 (0.98–1.44) | 0.082 | 1.52 (1.15–2.01) | 0.003 |
Ethnicity: Afro vs. Other | 2.38 (1.91–2.97) | <0.001 | 2.11 (1.61–2.75) | <0.001 |
Educational level | ||||
Primary vs. Illiterate | 0.53 (0.40–0.70) | <0.001 | ||
Secondary vs. Illiterate | 0.24 (0.18–0.34) | <0.001 | ||
Paternal Factors | ||||
Age: <30 vs. ≥30 years | 0.88 (0.73–1.07) | 0.197 | ||
Ethnicity: Afro vs. Other | 1.84 (1.46–2.31) | <0.002 | ||
Educational level | ||||
Primary vs. Illiterate | 0.62 (0.47–0.83) | 0.001 | ||
Secondary vs. Illiterate | 0.40 (0.29–0.55) | <0.001 | ||
Socioeconomic status | ||||
Medium vs. Low | 0.80 (0.63–1.01) | 0.056 | 0.79 (0.60–1.06) | 0.118 |
High vs. Low | 0.53 (0.42–0.68) | <0.001 | 0.54 (0.40–0.74) | <0.001 |
Environmental Factors | ||||
Area of residence: Urban vs. Rural | 1.39 (1.13–1.72) | 0.002 | <0.001 | |
Household overcrowding: ≥3 vs. <3 | 2.25 (1.76–2.89) | <0.001 | <0.001 | |
Maternal STH Infections | ||||
Any geohelminth: Yes vs. No | 2.67 (2.19–3.26) | <0.001 | ||
2.66 (2.13–3.31) | <0.001 | |||
Light vs. Negative | 2.07 (1.63–2.62) | <0.001 | 1.50 (1.13–1.99) | 0.005 |
Moderate/heavy vs. Negative | 13.1 (6.7–25.6) | <0.001 | ||
2.53 (2.04–3.14) | <0.001 | |||
Light vs. Negative | 2.21 (1.76–2.77) | <0.001 | ||
Moderate/heavy vs. Negative | 5.53 (3.16–9.67) | <0.001 | ||
Hookworm: Yes vs. No | 2.20 (1.47–3.30) | <0.001 | ||
Paternal STH infection: Yes vs. No | 1.83 (1.35–2.49) | <0.001 | ||
Household member with STH infection: Yes vs. No | 2.07 (1.70–2.51) | <0.001 | ||
Number of stool samples from child | ||||
≥5 vs. 1–4 | 1.23 (91.01–1.49) | 0.039 | ||
Number of anthelmintic treatments | ||||
1 vs. 0 | 1.09 (0.86–1.39) | 0.48 | ||
≥2 vs. 0 | 1.27 (0.97–1.65) | 0.078 |
Multivariable analyses included data from 1,381 children for whom complete data were available. Paternal STH infection was excluded from the multivariate model because of missing data. Odds ratios (ORs), 95% confidence intervals (95% CI) were estimated using logistic regression. STH were detected using all 3 microscopic detection methods. Overcrowding was defined as number of household members per sleeping room. SES (socioeconomic) index shows tertiles of Z scores calculated using principal components analysis. Paternal and maternal age, overcrowding, and gestational age used the mean as cut-off. STH infection intensity categories were:
Most STH infections during the first 3 years of life were caused by
Multivariable analyses showed that maternal infections with either
Variable | Univariate | Multivariable | ||||
First year* | Second year | Third year | First year | Second year | Third year | |
OR (95% CI) P value | OR (95% CI) P value | OR (95% CI) P value | OR (95% CI) P value | OR (95% CI) P value | OR (95% CI) P value | |
Birth Order ≥5 vs. <5 | 3.0 (2.13–4.20) <0.001 | 1.59 (1.15–2.19) 0.005 | 1.29 (0.88–1.90) 0.196 | 2.04(1.36–3.07) 0.001 | 1.24(0.85–1.80) 0.261 | 0.87(0.55–1.36) 0.537 |
Maternal Ethnicity Afro-Ecuadorian vs. Other | 2.31 (1.66–3.21) <0.001 | 2.14 (1.61–2.83) <0.001 | 2.06 (1.49–2.86) <0.001 | 1.82(1.25–2.65) 0.002 | 1.92(1.40–2.63) <0.001 | 1.92(1.34–2.75) <0.001 |
Maternal Educational Level ≥Primary vs. Illiterate | 0.31(0.214–0.449) <0.001 | 0.53 (0.37–0.75) <0.001 | 0.50 (0.34–0.74) 0.001 | 0.52(0.33–0.81) 0.004 | 0.73(0.48–1.11) 0.138 | 0.60(0.38–0.96) 0.031 |
Paternal Ethnicity Afro-Ecuadorian vs. Other | 1.71 (1.20–2.44) 0.003 | 1.83 (1.36–2.47) <0.001 | 1.74 (1.23–2.39) 0.001 | |||
Paternal Educational level ≥Primary vs. Illiterate | 0.43 (0.29–0.63) <0.001 | 0.55 (0.39–0.79) <0.001 | 0.70(0.46–1.08) 0.106 | |||
SES Index Medium/High vs. Low | 0.54(0.40–0.74) <0.001 | 0.70(0.53–0.91) 0.008 | 0.64(0.47–0.87) 0.004 | |||
Area of residence Urban vs. Rural | 1.16(0.83–1.62) 0.385 | 1.33(1.0–1.78) 0.520 | 1.43(1.02–2.02) 0.038 | |||
Household overcrowding ≥3 vs. <3 | 2.02 (1.46–2.80) <0.001 | 2.05 (1.55–2.70) <0.001 | 1.93 (1.40–2.64) <0.001 | 1.21(0.84–1.76) 0.303 | 1.82(1.34–2.48) <0.001 | 1.82(1.28–2.58) <0.001 |
Maternal STH Infection Yes vs. No | 4.58 (3.26–6.43) <0.001 | 2.25 (1.72–2.93) <0.001 | 1.93 (1.43–2.61) <0.001 | |||
4.10(2.97–5.66) <0.001 | 2.34(1.76–3.11) <0.001 | 1.90(1.36–2.66) <0.001 | 2.34(1.61–3.40) <0.001 | 1.74(1.25–2.42) 0.001 | 1.39(0.95–2.04) 0.090 | |
T. trichiura Yes vs. No | 3.73(2.71–5.14) <0.001 | 2.07(1.56–2.75) <0.001 | 1.98(1.43–2.74) <0.001 | 2.57(1.77–3.73) <0.001 | 1.51(1.08–2.11) 0.015 | 1.46(1.0–2.13) 0.049 |
Hookworm Yes vs. No | 2.67(1.55–4.62) <0.001 | 1.88(1.12–3.18) <0.001 | 2.02(1.13–3.61) 0.019 | |||
Yes vs. No | <0.001 | <0.001 | 0.019 | |||
Household member with STH infection Yes vs. No | 2.71(1.97–3.74) <0.001 | 1.87(1.44–2.44) <0.001 | 1.76(1.30–2.38) <0.001 | 1.59(1.08–2.33) 0.019 | 1.25(0.92–1.70) 0.162 | 1.26(0.89–1.79) 0.193 |
Multivariable analyses included data from 1,381 children for whom we had complete data. Associations between risk factors and age at first infection were compared to children without any infection in the first 3 years of life using univariate and multivariable multinomial logistic regression. STH were detected using all 3 microscopic detection methods. Variables with more than 2 groups in
In the present analysis, we investigated the epidemiology of and risk factors for STH infection during the first 3 years of life in a birth cohort from a largely rural District in tropical Ecuador. Over 40% of children had at least one STH infection documented during the first 3 years of life. Almost all infections (96.9%) were caused by
Potential limitations to the present study include losses to follow-up – we collected a stool sample from 70% of the original cohort at 3 years of age. Such losses could lead to selection bias. However, baseline variables were generally similar between those included and excluded from the analysis indicating that selection bias is probably not an important issue. Although we attempted to control for potential confounders, we cannot exclude confounding by uncontrolled factors or by highly correlated exposures as an alternative explanation for our findings. Approximately 76% of children were reported by mothers to have received at least one anthelmintic treatment during the first 3 years of life. This proportion did not vary significantly between infected and uninfected children indicating that mothers of children who did not receive anthelmintic treatment for their child for a positive stool examination were extremely likely to obtain anthelmintic drugs through other sources irrespective of a negative stool examination and concurs with our own experience that a lot of illness in children is attributed by mothers to the presence of ‘parasites’ and that self-medication is extremely common. Although 30% of all children had received 2 or more doses of anthelmintic drugs, number of treatments was not associated with risk of STH infections, an observation that might be explained by misclassification of this variable (number of anthelmintic treatments) or by high rates of reinfection over the year following treatment. The use of questionnaires to collect data on exposures is subject to reporting biases although these are unlikely to be systematic. Because data on risk factors was collected around the time of birth and before the measurement of outcomes, observation biases would seem unlikely to be important. Our findings are likely to be relevant to young children living in poor rural Districts of tropical Latin America and other similar regions elsewhere. Strengths of the study are the longitudinal nature of the study allowing repeated sampling of the same children over time and a large sample size. The study was originally designed and powered to examine the effects of maternal and early childhood infections with STH parasites on the development of atopy and allergic diseases
Most STH infections are unable to replicate within the human host and the acquisition of increasing parasite burdens is time and exposure-dependent. Unsurprisingly STH infection prevalence increased with age in the cohort with the highest prevalence of 24.9% observed at 36 months. This is within the 19.6–35.5% estimate by PAHO-WHO of STH prevalence in Ecuadorian pre-school children
The strongest and most consistent risk factor for infection with STH in the first 3 years of life was maternal STH infections, particularly among children whose mothers harboured moderate to high parasite burdens with
The association between STH infections in mothers and infections of children has two possible explanations. 1) STH infections of the mother during pregnancy may increase susceptibility to infection in offspring through tolerization to parasite antigens -
Maternal STH infections were a common risk factor - approximately 46% of mothers were infected with STH in their third trimester of pregnancy, with an estimated attributable fraction of 27.9%. Our observations, therefore, have identified a potentially modifiable exposure - maternal STH infections - that could be evaluated in an intervention programme using currently available and highly efficacious anthelmintic treatments. An intervention in which anthelmintic drugs are given before pregnancy for women planning to have a family, during pregnancy or soon after birth or even periodically to women of child-bearing age could substantially reduce the risk of infection and potential morbidity during early childhood. Development of immune tolerance begins after 14 weeks gestation
A model illustrating risk factors for childhood STH infections in our study with potential interventions is provided in
The model shows potential effects of environmental and socioeconomic risk factors on risk of STH infections in early childhood and morbidity. Potential interventions to reduce risk of infection are illustrated with red crosses.
In conclusion, our study identified risk factors for STH infection during the first 3 years of life in a birth cohort conducted in a rural District in coastal Ecuador. Over 40% of children were infected at least once with STH parasites during the first 3 years of life and risk factors for infections were those associated with poverty. We identified maternal STH infections as an important and potentially modifiable risk factor that could be evaluated in future intervention studies for the control of STH infections in pre-school children.
STROBE Checklist.
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Comparison of covariables between children included (N = 1,697) and excluded (N = 707) from the analysis of the 2,404 newborns initially recruited.
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Risk factors for any infection with
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We thank the ECUAVIDA study team for their dedicated work and the cohort mothers and children for their enthusiastic participation. We acknowledge the support of the Ecuadorian Ministry of Public Health and the Director and Staff of the Hospital “Padre Alberto Buffoni”, Quinindé, Esmeraldas Province.