Fecal Immunoglobulin A Against a Sporozoite Antigen at 12 Months Is Associated With Delayed Time to Subsequent Cryptosporidiosis in Urban Bangladesh: A Prospective Cohort Study.

In this prospective cohort study of Bangladeshi children, greater fecal immunoglobulin A, but not plasma immunoglobulin G, directed against the Cryptosporidium sporozoite-expressed antigen Cp23 at 12 months of age was associated with delayed time to subsequent cryptosporidiosis. This finding suggests a protective role for mucosal antibody-mediated immunity in naturally exposed children.

Case-Control Study of Cryptosporidium Transmission in Bangladeshi Households.

BACKGROUND: Cryptosporidium is a leading contributor to diarrheal morbidity and mortality in under-5 children worldwide. As there is no vaccine and no effective drug therapy in young children for this infection, preventing infection is critical. We undertook a pilot case-control study to define the extent of person-to-person transmission of cryptosporidiosis within an urban and a rural community in Bangladesh. METHODS: We enrolled 48 case families with a Cryptosporidium-infected child aged 6-18 months. Controls were age- and sex-matched Cryptosporidium-negative children in 12 households. Children and household members were followed for 8 weeks with weekly illness survey and stool testing with quantitative polymerase chain reaction for Cryptosporidium. RESULTS: In the 24 urban case families, the secondary attack rate was 35.8% (19/53) vs 0% (0/11) in controls (P = .018, χ2 test). In contrast, in the 24 rural case families, the secondary attack rate was 7.8% (5/64) vs 0% (0/21) in controls (P = .19, χ2 test). Genotyping by gp60 demonstrated infection with the same subspecies in 5 families, and evidence of transmission in 2. Serologic response to Cryptosporidium infection was associated with younger age, longer duration of infection, and Cryptosporidium hominis gp60_IbA9G3R2 infection. CONCLUSIONS: In the urban site, the high rate of secondary infection and infection with the same subspecies within families suggests that person-to-person transmission is a major source of Cryptosporidium infection for young children living in this region. Molecular genotyping can be applied to determine transmission of Cryptosporidium in endemic regions. Further work is needed to understand the differences in parasite transmissibility and immunity to different genotypes.

Species of Cryptosporidia Causing Subclinical Infection Associated With Growth Faltering in Rural and Urban Bangladesh: A Birth Cohort Study.

Background: Cryptosporidiosis is a major cause of childhood diarrhea in low- and middle-income countries and has been linked to impairment of child growth. This study investigated the burden of cryptosporidiosis and its impact on child growth in both a rural and an urban site in Bangladesh. Methods: Pregnant women in the second trimester were identified at 2 sites in Bangladesh, 1 urban and 1 rural. Their offspring were enrolled at birth into the study (urban, n = 250; rural, n = 258). For 2 years, the children were actively monitored for diarrhea and anthropometric measurements were obtained every 3 months. Stool samples were collected monthly and during diarrheal episodes with Cryptosporidium infection and causative species determined by quantitative polymerase chain reaction assays. Results: Cryptosporidium infections were common at both sites and mostly subclinical. In the urban site, 161 (64%) children were infected and 65 (26%) had ≥2 infections. In the rural site, 114 (44%) were infected and 24 (9%) had multiple infections. Adjusted for potential confounders, cryptosporidiosis was associated with a significantly greater drop in the length-for-age z score (LAZ) at 24 months from LAZ at enrollment (Δ-LAZ), an effect greatest in the children with multiple episodes of cryptosporidiosis. The most common species in Mirpur was Cryptosporidium hominis, whereas Cryptosporidium meleagridis predominated in Mirzapur. Conclusions: Cryptosporidiosis is common in early childhood and associated with early growth faltering in Bangladeshi children. Predominant Cryptosporidium species differed between the 2 sites, suggesting different exposures or modes of transmission but similar consequences for child growth. Clinical Trials Registration: NCT02764918.

Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: a meta-analyses study.

BACKGROUND: The protozoan Cryptosporidium is a leading cause of diarrhoea morbidity and mortality in children younger than 5 years. However, the true global burden of Cryptosporidium infection in children younger than 5 years might have been underestimated in previous quantifications because it only took account of the acute effects of diarrhoea. We aimed to demonstrate whether there is a causal relation between Cryptosporidium and childhood growth and, if so, to quantify the associated additional burden. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2016 was a systematic and scientific effort to quantify the morbidity and mortality associated with more than 300 causes of death and disability, including diarrhoea caused by Cryptosporidium infection. We supplemented estimates on the burden of Cryptosporidium in GBD 2016 with findings from a systematic review of published and unpublished cohort studies and a meta-analysis of the effect of childhood diarrhoea caused by Cryptosporidium infection on physical growth. FINDINGS: In 2016, Cryptosporidium infection was the fifth leading diarrhoeal aetiology in children younger than 5 years, and acute infection caused more than 48 000 deaths (95% uncertainty interval [UI] 24 600-81 900) and more than 4·2 million disability-adjusted life-years lost (95% UI 2·2 million-7·2 million). We identified seven data sources from the scientific literature and six individual-level data sources describing the relation between Cryptosporidium and childhood growth. Each episode of diarrhoea caused by Cryptosporidium infection was associated with a decrease in height-for-age Z score (0·049, 95% CI 0·014-0·080), weight-for-age Z score (0·095, 0·055-0·134), and weight-for-height Z score (0·126, 0·057-0·194). We estimated that diarrhoea from Cryptosporidium infection caused an additional 7·85 million disability-adjusted life-years (95% UI 5·42 million-10·11 million) after we accounted for its effect on growth faltering-153% more than that estimated from acute effects alone. INTERPRETATION: Our findings show that the substantial short-term burden of diarrhoea from Cryptosporidium infection on childhood growth and wellbeing is an underestimate of the true burden. Interventions designed to prevent and effectively treat infection in children younger than 5 years will have enormous public health and social development impacts. FUNDING: The Bill & Melinda Gates Foundation.

Epidemiology and Risk Factors for Cryptosporidiosis in Children From 8 Low-income Sites: Results From the MAL-ED Study.

Background: Cryptosporidium species are enteric protozoa that cause significant morbidity and mortality in children worldwide. We characterized the epidemiology of Cryptosporidium in children from 8 resource-limited sites in Africa, Asia, and South America. Methods: Children were enrolled within 17 days of birth and followed twice weekly for 24 months. Diarrheal and monthly surveillance stool samples were tested for Cryptosporidium by enzyme-linked immunosorbent assay. Socioeconomic data were collected by survey, and anthropometry was measured monthly. Results: Sixty-five percent (962/1486) of children had a Cryptosporidium infection and 54% (802/1486) had at least 1 Cryptosporidium-associated diarrheal episode. Cryptosporidium diarrhea was more likely to be associated with dehydration (16.5% vs 8.3%, P < .01). Rates of Cryptosporidium diarrhea were highest in the Peru (10.9%) and Pakistan (9.2%) sites. In multivariable regression analysis, overcrowding at home was a significant risk factor for infection in the Bangladesh site (odds ratio, 2.3 [95% confidence interval {CI}, 1.2-4.6]). Multiple linear regression demonstrated a decreased length-for-age z score at 24 months in Cryptosporidium-positive children in the India (ß = -.26 [95% CI, -.51 to -.01]) and Bangladesh (ß = -.20 [95% CI, -.44 to .05]) sites. Conclusions: This multicountry cohort study confirmed the association of Cryptosporidium infection with stunting in 2 South Asian sites, highlighting the significance of cryptosporidiosis as a risk factor for poor growth. We observed that the rate, age of onset, and number of repeat infections varied per site; future interventions should be targeted per region to maximize success.

Natural History of Cryptosporidiosis in a Longitudinal Study of Slum-Dwelling Bangladeshi Children: Association with Severe Malnutrition.

BACKGROUND: Cryptosporidiosis is a common cause of infectious diarrhea in young children worldwide, and is a significant contributor to under-five mortality. Current treatment options are limited in young children. In this study, we describe the natural history of Cryptosporidium spp. infection in a birth cohort of children in Bangladesh and evaluate for association with malnutrition. METHODOLOGY/PRINCIPAL FINDINGS: This is a longitudinal birth cohort study of 392 slum-dwelling Bangladeshi children followed over the first two years of life from 2008 to 2014. Children were monitored for diarrheal disease, and stool was tested for intestinal protozoa. Anthropometric measurements were taken at 3-month intervals. A subset of Cryptosporidium positive stools were genotyped for species and revealed that C. hominis was isolated from over 90% of samples. In the first two years of life, 77% of children experienced at least one infection with Cryptosporidium spp. Non-diarrheal infection (67%) was more common than diarrheal infection (6.3%) although 27% of children had both types of infection. Extreme poverty was associated with higher rates of infection (chi-square, 49.7% vs 33.3%, p = 0.006). Malnutrition was common in this cohort, 56% of children had stunted growth by age two. Children with Cryptosporidium spp. infection had a greater than 2-fold increased risk of severe stunting at age two compared to uninfected children (odds ratio 2.69, 95% CI 1.17, 6.15, p = 0.019) independent of sex, income, maternal body-mass index, maternal education and weight for age adjusted z (WAZ) score at birth. CONCLUSIONS/SIGNIFICANCE: Cryptosporidium infection is common (77%) in this cohort of slum-dwelling Bangladeshi children, and both non-diarrheal and diarrheal infections are significantly associated with a child's growth at 2 years of age.

Calcified neurocysticercus, perilesional edema, and histologic inflammation.

Abstract. Here, we present the second report of the histopathology of a Taenia solium calcification giving rise to perilesional edema. This has important implications, because if perilesional edema lesions are inflammatory in character, immunosuppressive or anti-inflammatory medications, not just antiepileptic drugs alone, may be useful to prevent or treat recurring episodes in such patients.

REG1B as a predictor of childhood stunting in Bangladesh and Peru.

BACKGROUND: Undernutrition remains a significant problem worldwide, with environmental enteropathy implicated as a contributing factor. An understanding of the pathogenesis and identification of children at risk are critical to the design of more-effective interventions. OBJECTIVE: The stool regenerating gene 1ß (REG1B) protein, which is a putative measure of intestinal injury and repair, was tested as a noninvasive biomarker of future childhood stunting. DESIGN: A total of 222 children from Bangladesh and 97 children from Peru, who were from impoverished communities, were followed from birth through 24 mo of age with anthropometric measures obtained every 3 mo. Stool REG1B protein concentrations were obtained by using an REG1B polyclonal-polyclonal ELISA at 3 mo of age. We tested for the ability of REG1B to forecast future anthropometric shortfalls, independent of known predictors of undernutrition of family income and baseline height and weight. RESULTS: In the Bangladesh cohort of 222 children, higher REG1B concentrations at month 3 were significantly and independently associated with a growth shortfall in a linear regression analysis at months 9, 12, 18, 21, and 24 and, in the Peru cohort, at months 12, 15, 18, 21, and 24. With the use of a mixed model for repeated measurements, higher stool REG1B concentrations at 3 mo were also independently predictive of a lower future length-for-age z score through 24 mo of age (Bangladesh P = 0.006; Peru P = 0.058). CONCLUSION: The ability of fecal REG1B to predict growth shortfall in independent cohorts of impoverished children from the developing world offers promise as a malnutrition biomarker and supports a role for environmental enteropathy in the pathogenesis of growth shortfall.

Breast milk parasite-specific antibodies and protection from amebiasis and cryptosporidiosis in Bangladeshi infants: a prospective cohort study.

In this prospective cohort study, the presence of parasite-specific immunoglobulin A in breast milk was associated with protection of Bangladeshi infants from cryptosporidiosis and amebiasis. Our findings suggest that passive immunity could be harnessed for the prevention of Entamoeba histolytica and Cryptosporidium species infection in children living in endemic regions.

Evaluation of a rapid point-of-care fecal antigen detection test for Entamoeba histolytica.

Amebiasis is a major cause of morbidity and mortality in the developing world. A reliable point-of-care test would help to improve diagnosis and early treatment. We evaluated a novel rapid fecal antigen detection test for E. histolytica (E. HISTOLYTICA QUIK CHEK; TechLab, Inc., Blacksburg, VA), in a cohort of children in Bangladesh where amebiasis is endemic. This point-of-care test had a sensitivity of 100% and a specificity of 100% when compared with enzyme-linked immunosorbent assay antigen detection.

Environmental enteropathy: critical implications of a poorly understood condition.

Environmental enteropathy (also called tropical enteropathy) is a subclinical condition caused by constant fecal-oral contamination and resulting in blunting of intestinal villi and intestinal inflammation. Although these histological changes were discovered decades ago, the clinical impact of environmental enteropathy is just starting to be recognized. The failure of nutritional interventions and oral vaccines in the developing world may be attributed to environmental enteropathy, as the intestinal absorptive and immunologic functions are significantly deranged. Here we review the existing literature and examine potential mechanisms of pathogenesis for this poorly understood condition.