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

Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances. Copyright © 2015 Elsevier Ltd. All rights reserved.

Infections, no matter how mild, have adverse effects on nutritional status. The significance of these effects depends on the previous nutritional status of the individual, the nature and duration of the infection, and the diet during the recovery period. Conversely, almost any nutrient deficiency, if sufficiently severe, will impair resistance to infection. Iron deficiency and protein-energy malnutrition, both highly prevalent, have the greatest public health importance in this regard. Remarkable advances in immunology of recent decades have increased insights into the mechanisms responsible for the effects of infection. These include impaired antibody formation; loss of delayed cutaneous hypersensitivity; reduced immunoglobulin concentrations; decreased thymic and splenic lymphocytes; reduced complement formation, secretory immunoglobulin A, and interferon; and lower T cells and T cells subsets (helper, suppressor-cytotoxic, and natural killer cells) and interleukin 2 receptors. The effects observed with single or multiple nutrient deficiencies are due to some combination of these responses. In general, cell-mediated and nonspecific immunity are more sensitive than humoral immunity.

Highly prevalent conditions with multiple and complex underlying etiologies are a challenge to public health. Undernutrition, for example, affects 20% of children in the developing world. The cause and consequence of poor nutrition are multifaceted. Undernutrition has been associated with half of all deaths worldwide in children aged <5 years; in addition, its pernicious long-term effects in early childhood have been associated with cognitive and physical growth deficits across multiple generations and have been thought to suppress immunity to further infections and to reduce the efficacy of childhood vaccines. The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Study, led by the Fogarty International Center of the National Institutes of Health and the Foundation for the National Institutes of Health, has been established at sites in 8 countries with historically high incidence of diarrheal disease and undernutrition. Central to the study is the hypothesis that enteropathogen infection contributes to undernutrition by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. It is further postulated that this leads to growth faltering and deficits in cognitive development. The effects of repeated enteric infection and undernutrition on the immune response to childhood vaccines is also being examined in the study. MAL-ED uses a prospective longitudinal design that offers a unique opportunity to directly address a complex system of exposures and health outcomes in the community-rather than the relatively rarer circumstances that lead to hospitalization-during the critical period of development of the first 2 years of life. Among the factors being evaluated are enteric infections (with or without diarrhea) and other illness indicators, micronutrient levels, diet, socioeconomic status, gut function, and the environment. MAL-ED aims to describe these factors, their interrelationships, and their overall impact on health outcomes in unprecedented detail, and to make individual, site-specific, and generalized recommendations regarding the nature and timing of possible interventions aimed at improving child health and development in these resource-poor settings.