Performance and operational feasibility of two diagnostic tests for cryptosporidiosis in children (CRYPTO-POC): a clinical, prospective, diagnostic accuracy study

Johansen, Øystein Haarklau; Abdissa, Alemseged; Zangenberg, Mike; Mekonnen, Zeleke; Eshetu, Beza; Bjørang, Ola; Alemu, Yonas; Sharew, Bizuwarek; Langeland, Nina; Robertson, Lucy J.; Hanevik, Kurt

doi:10.1016/s1473-3099(20)30556-9

Cited by 22 publications

(28 citation statements)

References 27 publications

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“…Evidence from a multisite clinical trial is forthcoming about the role of azithromycin in treating watery diarrhea [ 22 ] which may help further direct the value of point-of-care identification of bacterial enteropathogens in the absence of dysentery. Point-of-care diagnostics [ 23 ] and novel therapeutics [ 24 ] for Cryptosporidium are areas of active areas of investigation and on the basis of these findings should be prioritized.…”

Section: Discussionmentioning

confidence: 99%

Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger

Platts-Mills

Houpt

Liu

et al. 2021

Journal of the Pediatric Infectious Diseases Society

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Background High-resolution data on the etiology of childhood diarrhea in countries with the highest burden and mortality remain sparse and are needed to inform burden estimates and prioritize interventions. Methods We tested stool specimens collected between October 2014 and December 2017 from children under 2 years of age from the per-protocol population of a placebo-controlled clinical trial of a bovine rotavirus pentavalent vaccine (Rotasiil) in Niger. We tested 1729 episodes of moderate-to-severe diarrhea (Vesikari score ≥ 7) using quantitative PCR and estimated pathogen-specific burdens by age, season, severity, and trial intervention arm. Results The 4 pathogens with the highest attributable incidence of diarrhea were Shigella (7.2 attributable episodes per 100 child-years; 95% confidence interval: 5.2, 9.7), Cryptosporidium (6.5; 5.8, 7.2), rotavirus (6.4; 5.9, 6.7), and heat-stabile toxin-producing enterotoxigenic Escherichia coli (ST-ETEC) (6.2; 3.1, 7.7). Cryptosporidium was the leading etiology of severe diarrhea (Vesikari score ≥ 11) and diarrhea requiring hospitalization. Shigella was the leading etiology of diarrhea in children 12-23 months of age but also had a substantial burden in the first year of life, with 60.5% of episodes of severe shigellosis occurring in infants. Shigella, Cryptosporidium, and ST-ETEC incidence peaked during the warmer and wetter period and coincided with peak all-cause diarrhea incidence. Conclusions In this high-burden setting, the leading diarrheal pathogens were Shigella, Cryptosporidium, rotavirus, and ST-ETEC, and each was disproportionately seen in infants. Vaccine development should target these pathogens, and the impact of vaccine schedule on diarrhea burden in the youngest children will need to be considered.

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Section: Discussionmentioning

confidence: 99%

Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger

Platts-Mills

Houpt

Liu

et al. 2021

Journal of the Pediatric Infectious Diseases Society

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“…Molecular methods are usually not a routine diagnostic in resource-poor settings, but sensitive and specific diagnostic methods are important everywhere, particularly when positive findings result in appropriate interventions such as improved hygiene and better farm management, both of which can be essential for disease control and prevention in both goats and humans. A recently published study indicated that auramine-phenol staining has high sensitivity and specificity for cryptosporidiosis and can be easily integrated with existing laboratory infrastructures in low-resource settings (36). Targeted sampling and preparation before diagnostics, along with dual application of staining and molecular techniques may provide the best possible results in terms of prevalence and epidemiology investigations.…”

Section: Diagnostic Methodsmentioning

confidence: 99%

Global Goat! Is the Expanding Goat Population an Important Reservoir of Cryptosporidium?

et al. 2021

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Goats are a primary or additional income source for many families in resource-poor areas. Although often considered inferior to other livestock, the resilience of goats and their ability to thrive in a range of environments means that that they are of particular value. Furthermore, goats emit less methane than other livestock species. In these same areas, it is well-documented that cryptosporidiosis has a substantial impact on infant morbidity and mortality, as well as reducing child growth and development. As Cryptosporidium also causes diarrheal disease in goats, the question arises whether goats may represent a reservoir of infection to humans. Epidemiological studies regarding the potential for transmission of Cryptosporidium between goats and humans have largely concluded that Cryptosporidium species infecting goats are not zoonotic. However, these studies are mostly from developed countries, where goat husbandry is smaller, management routines differ greatly from those of developing countries, contact between goats and their owners is more limited, and cryptosporidiosis has less impact on human health. In this article, background information on goat husbandry in different countries is provided, along with information on Cryptosporidium prevalence among goats, at both the species and sub-species levels, and the potential for zoonotic transmission. The intention is to indicate data gaps that should be filled and to increase awareness of the role of goats as providers for low-income families, often living in areas where cryptosporidiosis is endemic and where appropriate baseline interventions could have a positive impact, regardless of species of goat or parasite.

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“…To minimize the risk of confounding and overadjustment, while maintaining a pragmatic focus on cryptosporidiosis, we used three epidemiological tools that are well established, but that have not, to our knowledge, been previously combined in a risk-factor analysis for childhood diarrhoea: 1) hierarchical conceptual frameworks, where risk factors are organized in levels of a hierarchy [ 23 , 24 ], 2) improved case ascertainment, using a reference standard that includes quantitative cutoffs, allowing us to distinguish between incidental infection and cryptosporidiosis [ 20 , 21 , 25 , 26 ], and 3) a case-case-control design, an approach originally developed to study risk factors for multidrug-resistant bacterial infections [ 27 , 28 ], in order to distinguish between those risk factors unique to cryptosporidiosis, and those common with non-cryptosporidiosis diarrhoea.…”

Section: Methodsmentioning

confidence: 99%

A comparison of risk factors for cryptosporidiosis and non-cryptosporidiosis diarrhoea: A case-case-control study in Ethiopian children

et al. 2022

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Background Cryptosporidiosis is a major cause of diarrhoea in young children in low-and-middle-income countries. New interventions should be informed by evidence pertaining to risk factors and their relative importance. Inconsistencies in the literature may to some extent be explained by choice of methodology, furthermore, most previous risk factor studies compared cryptosporidiosis cases to diarrhoea cases of other aetiologies rather than with controls without diarrhoea. Methodology/Principal findings We investigated a broad set of factors in under-2-year-olds presenting with diarrhoea to a hospital and a health center in southwestern Ethiopia. We applied quantitative cut-offs to distinguish between cryptosporidiosis and incidental Cryptosporidium infection or carriage, a hierarchical causal framework to minimize confounding and overadjustment, and a case-case-control design, to describe risk factors for both cryptosporidiosis and non-cryptosporidiosis diarrhoea. Moderate and severe acute malnutrition were strongly associated with both cryptosporidiosis and non-cryptosporidiosis diarrhoea. Previous healthcare attendance and low maternal education were only associated with cryptosporidiosis, whereas unsafe child stool disposal, prematurity and early cessation of exclusive breastfeeding were significantly associated with non-cryptosporidiosis diarrhoea only. By estimation of population attributable fractions, socioeconomic factors—specifically low maternal education—and public tap water use, were apparently more important risk factors for cryptosporidiosis than for non-cryptosporidiosis diarrhoea. Conclusions/Significance Nutritional management of moderate acute malnutrition may be an effective intervention against cryptosporidiosis, particularly if combined with targeted therapy for cryptosporidiosis which, again, may mitigate nutritional insult. Focused caregiver education in healthcare settings and follow-up of children with acute malnutrition may prevent or improve outcomes of future episodes of cryptosporidiosis.

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Performance and operational feasibility of two diagnostic tests for cryptosporidiosis in children (CRYPTO-POC): a clinical, prospective, diagnostic accuracy study

Cited by 22 publications

References 27 publications

Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger

Etiology and Incidence of Moderate-to-Severe Diarrhea in Young Children in Niger

Global Goat! Is the Expanding Goat Population an Important Reservoir of Cryptosporidium?

A comparison of risk factors for cryptosporidiosis and non-cryptosporidiosis diarrhoea: A case-case-control study in Ethiopian children

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