Molecular Epidemiology of Human Cryptosporidiosis in Low- and Middle-Income Countries

Abstract

Cryptosporidiosis is one of the most important causes of moderate to severe diarrhea and diarrhea-related mortality in children under 2 years of age in low- and middle-income countries. In recent decades, genotyping and subtyping tools have been used in epidemiological studies of human cryptosporidiosis. Results of these studies suggest that higher genetic diversity of Cryptosporidium spp. is present in humans in these countries at both species and subtype levels and that anthroponotic transmission plays a major role in human cryptosporidiosis. Cryptosporidium hominis is the most common Cryptosporidium species in humans in almost all the low- and middle-income countries examined, with five subtype families (namely, Ia, Ib, Id, Ie, and If) being commonly found in most regions. In addition, most Cryptosporidium parvum infections in these areas are caused by the anthroponotic IIc subtype family rather than the zoonotic IIa subtype family. There is geographic segregation in Cryptosporidium hominis subtypes, as revealed by multilocus subtyping. Concurrent and sequential infections with different Cryptosporidium species and subtypes are common, as immunity against reinfection and cross protection against different Cryptosporidium species are partial. Differences in clinical presentations have been observed among Cryptosporidium species and C. hominis subtypes. These observations suggest that WASH (water, sanitation, and hygiene)-based interventions should be implemented to prevent and control human cryptosporidiosis in low- and middle-income countries.

Keywords: Cryptosporidium; WASH; anthroponotic transmission; low- and middle-income countries; molecular epidemiology.

FIG 1

Age pattern of pediatric cryptosporidiosis in Kenya and Ghana (30, 128). Numbers above the bars denote the number of Cryptosporidium-positive cases/total number of children studied in each age group (the first line) and the 95% confidence intervals of the infection rates (the second line).

FIG 2

Proportion (%) of Cryptosporidium parvum and Cryptosporidium hominis in different areas and socioeconomic conditions. Numbers above bars denote sample size (n). In the bars, “a” indicates a significant difference in proportion of C. hominis between industrialized nations and the group under comparison (P < 0.05 by chi-square test), while “b” indicates a significant difference in proportion of C. parvum between industrialized nations and the group under comparison (P < 0.05).

FIG 3

Distribution of common Cryptosporidium hominis subtype families among low- and middle-income countries in Asia, Africa, the Middle East, and the Americas. Numbers above bars denote sample size (n). In the bars, “a,” “b,” “c,” and “d” indicate a significant difference in distribution of Ia, Ib, Id, and Ie between Asia and the group under comparison (P < 0.05 by chi-square test), respectively.

FIG 4

Proportion (%) of common Cryptosporidium parvum subtype families in different areas and socioeconomic conditions. Numbers above bars denote sample size (n). In the bars, “a,” “b,” and “c” indicate a significant difference in proportion of IIa, IIc, and IId between industrialized nations and the group under comparison (P < 0.05 by chi-square test), respectively.

FIG 5

Distribution of Cryptosporidium parvum subtype families in humans in Asia, Africa, Europe, Oceania, the Middle East, South America, and North America. Numbers above bars denote sample size (n). In the bars, “a,” “b,” and “c” indicate a significant difference in distribution of IIa, IIc, and IId between Asia and the group under comparison (P < 0.05 by chi-square test), respectively.

FIG 6

Differences in transmission of major subtype families of Cryptosporidium parvum in humans between low- and middle-income countries and industrialized nations. The blue arrows indicate major directions of transmission, and the red plus symbols indicate their importance in cryptosporidiosis epidemiology. The relative distribution of the major subtype families is indicated in the pie chart.