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      Cryptosporidium Prevalence and Risk Factors among Mothers and Infants 0 to 6 Months in Rural and Semi-Rural Northwest Tanzania: A Prospective Cohort Study

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          Abstract

          Background

          Cryptosporidium epidemiology is poorly understood, but infection is suspected of contributing to childhood malnutrition and diarrhea-related mortality worldwide.

          Methods/Findings

          A prospective cohort of 108 women and their infants in rural/semi-rural Tanzania were followed from delivery through six months. Cryptosporidium infection was determined in feces using modified Ziehl-Neelsen staining. Breastfeeding/infant feeding practices were queried and anthropometry measured. Maternal Cryptosporidium infection remained high throughout the study (monthly proportion = 44 to 63%). Infection did not differ during lactation or by HIV-serostatus, except that a greater proportion of HIV-positive mothers were infected at Month 1. Infant Cryptosporidium infection remained undetected until Month 2 and uncommon through Month 3 however, by Month 6, 33% of infants were infected. There were no differences in infant infection by HIV-exposure. Overall, exclusive breastfeeding (EBF) was limited, but as the proportion of infants exclusively breastfed declined from 32% at Month 1 to 4% at Month 6, infant infection increased from 0% at Month 1 to 33% at Month 6. Maternal Cryptosporidium infection was associated with increased odds of infant infection (unadjusted OR = 3.18, 95% CI 1.01 to 9.99), while maternal hand washing prior to infant feeding was counterintuitively also associated with increased odds of infant infection (adjusted OR = 5.02, 95% CI = 1.11 to 22.78).

          Conclusions

          Both mothers and infants living in this setting suffer a high burden of Cryptosporidium infection, and the timing of first infant infection coincides with changes in breastfeeding practices. It is unknown whether this is due to breastfeeding practices reducing pathogen exposure through avoidance of contaminated food/water consumption; and/or breast milk providing important protective immune factors. Without a Cryptosporidium vaccine, and facing considerable diagnostic challenges and ineffective treatment in young infants, minimizing the overall environmental burden (e.g. contaminated water) and particularly, maternal Cryptosporidium infection burden as a means to protect against early infant infection needs prioritization.

          Author Summary

          Early infancy and childhood Cryptosporidium infection is associated with poor nutritional status, stunted growth, and cognitive deficits, yet minimal research is available regarding the burden and risk factors worldwide. Since there is no vaccine available, and because diagnostic challenges exist and treatment for children younger than one year is ineffective, prevention of early infancy infection through a better understanding of basic epidemiology is critical. This study was designed to investigate symptomatic and clinically silent infection amongst HIV-seropositive and HIV-seronegative mothers and their infants in a longitudinal cohort, and to indentify potential risk factors. Findings indicate that infants are living in a Cryptosporidium environment as demonstrated by the chronically high level of maternal infection throughout the 6-month post-partum period. Despite this, infant infection prevalence remains low until six months of age when it dramatically rises. The increase in infant infection corresponds to a reduction in exclusive breastfeeding. As expected, maternal infection is associated with increased infant infection, but unexpectedly, so is maternal hand washing prior to infant feeding. Since prevention may indeed be the “best medicine” for infants, investigation of beneficial breastfeeding practices, protective correlates in breast milk, and ways to reduce the maternal and environmental Cryptosporidium burden are needed.

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          Most cited references21

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          Cryptosporidium: a water-borne zoonotic parasite.

          Of 155 species of mammals reported to be infected with Cryptosporidium parvum or C. parvum-like organisms most animals are found in the Orders Artiodactyla, Primates, and Rodentia. Because Cryptosporidium from most of these animals have been identified by oocyst morphology alone with little or no host specificity and/or molecular data to support identification it is not known how many of the reported isolates are actually C. parvum or other species. Cryptosporidiosis is a cause of morbidity and mortality in animals and humans, resulting primarily in diarrhea, and resulting in the most severe infections in immune-compromised individuals. Of 15 named species of Cryptosporidium infectious for nonhuman vertebrate hosts C. baileyi, C. canis, C. felis, C. hominis, C. meleagridis, C. muris, and C. parvum have been reported to also infect humans. Humans are the primary hosts for C. hominis, and except for C. parvum, which is widespread amongst nonhuman hosts and is the most frequently reported zoonotic species, the remaining species have been reported primarily in immunocompromised humans. The oocyst stage can remain infective under cool, moist conditions for many months, especially where water temperatures in rivers, lakes, and ponds remain low but above freezing. Surveys of surface water, groundwater, estuaries, and seawater have dispelled the assumption that Cryptosporidium oocysts are present infrequently and in geographically isolated locations. Numerous reports of outbreaks of cryptosporidiosis related to drinking water in North America, the UK, and Japan, where detection methods are in place, indicate that water is a major vehicle for transmission of cryptosporidiosis.
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            Effects of Cryptosporidium parvum infection in Peruvian children: growth faltering and subsequent catch-up growth.

            The authors conducted a 2-year (1989-1991) community-based longitudinal study in a shantytown in Lima, Peru, to examine the effect of Cryptosporidium parvum infection on child growth during the year following the onset of infection. A cohort of children, aged 0-3 months at recruitment, was followed monthly for anthropometrics, weekly for stool samples, and daily for diarrheal status. Data from 185 children in the cohort permitted a comparison of growth in C. parvum-infected and noninfected children. The analyses fitted smooth, flexible curves with a linear random-effects model to estimate growth differences between C. parvum-infected and noninfected children. Children infected with C. parvum experienced growth faltering, both in weight and in height, for several months after the onset of infection, followed by a period of catch-up growth. Younger children took longer to catch up in weight than did older children. Catch-up growth, however, did not occur in children infected between ages 0 and 5 months. These children did not catch up in height, and one year after infection they exhibited an average deficit of 0.95 cm (95% confidence interval (CI) 0.38-1.53) relative to noninfected children of similar age. Stunted children who became infected also did not catch up in either weight or height, and one year after infection they exhibited a height deficit of 1.05 cm (95% CI 0.46-1.66) relative to noninfected, stunted children of similar age. These results indicate that Cryptosporidium parvum has a lasting adverse effect on linear (height) growth, especially when acquired during infancy and when children are stunted before they become infected.
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              High dose prolonged treatment with nitazoxanide is not effective for cryptosporidiosis in HIV positive Zambian children: a randomised controlled trial

              Background Treatment of cryptosporidiosis in HIV infected children has proved difficult and unsatisfactory with no drugs having demonstrable efficacy in controlled trials except nitazoxanide. We hypothesised that a prolonged course of treatment with high dose nitazoxanide would be effective in treating cryptosporidiosis in HIV positive Zambian children. Methods We performed a double-blind, randomised, placebo controlled trial in paediatric patients in the UTH in Lusaka. The study included HIV positive children between one and eleven years of age if 2 out of 3 stool samples were positive for oocysts of Cryptosporidium spp. Children were given nitazoxanide suspension in a dose of 200 mg twice daily (bid) for 28 days (if 1-3 years old) or 400 mg bid for 28 days (if 4-11 years old), or matching placebo. Results Sixty children were randomised and 52 were fully evaluated. Only five children were 4 years of age or over and received the higher dose. In the primary efficacy analysis, 11 out of 26 (42%) in the active treatment group achieved a 'Well' clinical response compared to 8 out of 26 (35%) in the placebo group. Parasitological response was declared as 'Eradicated' in 27% in the active group and 35% in the placebo group. Mortality (16/52, 31%) did not differ by treatment allocation. Conclusion We found no significant benefit in children with cryptosporidiosis despite high dose and longer treatment duration. This is the second randomised controlled trial to suggest that in Zambian children with HIV-related immunosuppression nitazoxanide does not eradicate this infection nor provide clinical symptom reduction. Trial Registration The trial was registered as ISRCTN41089957.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                October 2014
                2 October 2014
                : 8
                : 10
                : e3072
                Affiliations
                [1 ]Division of Nutritional Sciences, Cornell University, Ithaca, New York, United States of America
                [2 ]Mwanza Intervention Trials Unit, London School of Hygiene and Tropical Medicine, Mwanza, Tanzania
                [3 ]Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [4 ]National Institute for Medical Research, Mwanza, Tanzania
                [5 ]Department of Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
                Ege University, Turkey
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JMM ALW SHP. Performed the experiments: SHP DCW. Analyzed the data: JMM SHP. Contributed reagents/materials/analysis tools: JMM AA SMK MU DMM JT JC. Wrote the paper: SHP JMM.

                Article
                PNTD-D-14-00354
                10.1371/journal.pntd.0003072
                4183438
                25275519
                392452a7-9aad-4407-9b6a-0494377610d1
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 28 February 2014
                : 23 June 2014
                Page count
                Pages: 9
                Funding
                The sponsors (Cornell University, National Science Foundation) were not involved in the design or oversight of the study. Members of the writing team had full access to the study data. The authors had final responsibility for the decision to submit for publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Nutrition
                Parasitology
                Intestinal Parasites
                Medicine and health sciences
                Epidemiology
                Health Care
                Environmental Health
                Sanitation
                Infectious diseases
                Viral diseases
                HIV infections
                Parasitic Diseases
                Cryptosporidiosis
                Pediatrics
                Neonatology
                Breast Feeding
                Women's Health
                Maternal Health
                People and Places
                Geographical Locations
                Africa
                Tanzania
                Population Groupings
                Age Groups
                Infants

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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