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Decrease in Incidence of Diarrhea Due to Cryptosporidium in Bangladeshi Children Is Associated With an Increase in
Carol A Gilchrist1, William A O Petri1, Biplob Hossain2
1Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Insights
Repeated Cryptosporidium infections in children lead to increased antibody avidity, reducing diarrheal illness but not subclinical infections. This suggests an adaptive immune response develops over time.
Area of Science:
- Immunology
- Infectious Diseases
- Pediatrics
Background:
- Cryptosporidium causes significant infant morbidity and mortality in low- and middle-income countries.
- Diarrhea is a major health concern for young children globally.
Purpose of the Study:
- To investigate the development of adaptive immunity to Cryptosporidium in children.
- To understand the relationship between repeated infections and clinical outcomes.
Main Methods:
- Longitudinal cohort study in Bangladesh.
- Analysis of diarrheal and subclinical Cryptosporidium infections.
- Measurement of parasite burden and antibody avidity.
Main Results:
- Cryptosporidiosis episodes decreased with age (from 0.19 to 0.05 per child).
- Parasite burden and infection duration decreased with repeated infections.
- Anti-Cryptosporidium antibody avidity increased with age and fewer diarrheal episodes.
Conclusions:
- Results support the development of an adaptive immune response to Cryptosporidium.
- Increased antibody avidity correlates with reduced symptomatic cryptosporidiosis.
- Subclinical infections were not affected by the developing immune response.
Background:
Cryptosporidium is a cause of diarrhea morbidity and mortality in infants in low- and middle-income countries.
Methods:
A cohort of children was followed longitudinally in a high-transmission-intensity community in Bangladesh.
Results:
Diarrhea attributed to Cryptosporidium (cryptosporidiosis) decreased from a peak of 0.19 episodes per child at 1-2 years to 0.05 episodes per child at 3-4 years of age (P = .0064). Notably, the decrease in cryptosporidiosis was not accompanied by a decline in subclinical infections. Using an episode-based analysis confirmed that the parasite burden declined with repeated infections (P < .0001 from the mixed-effects model included data from all infection frequencies; Cq value of the first and fourth infections (last reinfection with >10 cases): Cq 28.65 ± 5.533 versus 32.42 ± 4.046). There was also a decrease in the time required to clear a parasitic infection: longer infections (>1 month) occurred in 43% of the first infections compared to 24% in the fourth infections (P = .00017 from the mixed-effects model). The avidity of anti-Cp23 and anti-Cp17 plasma IgG increased in older children who had fewer diarrheal infections (ratio of the avidity index after the first infection versus that in the older repeatedly infected children: 1.81 ± 1.02 for anti-Cp23 IgG P > .0001 and 1.14 ± 0.35 anti-Cp17 IgG P = .0056).
Conclusions:
Our results are consistent with the development of an anti-Cryptosporidium adaptive immune response over repeated infections (average number of previous infections at 4 years, 2.42 ± 1.24) characterized by an increase in anti-Cryptosporidium antibody avidity that is associated with a decrease in cryptosporidiosis but not in subclinical Cryptosporidium infections. Clinical Trials Registration. NCT02764918.
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