The largest meta-analysis on the global prevalence of microsporidia in mammals, avian and water provides insights into the epidemic features of these ubiquitous pathogens

Abstract

Background: Microsporidia are obligate intracellular parasites that can infect nearly all invertebrates and vertebrates, posing a threat to public health and causing large economic losses to animal industries such as those of honeybees, silkworms and shrimp. However, the global epidemiology of these pathogens is far from illuminated.

Methods: Publications on microsporidian infections were obtained from PubMed, Science Direct and Web of Science and filtered according to the Newcastle-Ottawa Quality Assessment Scale. Infection data about pathogens, hosts, geography and sampling dates were manually retrieved from the publications and screened for high quality. Prevalence rates and risk factors for different pathogens and hosts were analyzed by conducting a meta-analysis. The geographic distribution and seasonal prevalence of microsporidian infections were drawn and summarized according to sampling locations and date, respectively.

Results: Altogether, 287 out of 4129 publications up to 31 January 2020 were obtained and met the requirements, from which 385 epidemiological data records were retrieved and effective. The overall prevalence rates in humans, pigs, dogs, cats, cattle, sheep, nonhuman primates and fowl were 10.2% [2429/30,354; 95% confidence interval (CI) 9.2-11.2%], 39.3% (2709/5105; 95% CI 28.5-50.1%), 8.8% (228/2890; 95% CI 5.1-10.1%), 8.1% (112/1226; 95% CI 5.5-10.8%), 16.6% (2216/12,175; 95% CI 13.5-19.8%), 24.9% (1142/5967; 95% CI 18.6-31.1%), 18.5% (1388/7009; 95% CI 13.1-23.8%) and 7.8% (725/9243; 95% CI 6.4-9.2%), respectively. The higher prevalence in pigs suggests that routine detection of microsporidia in animals should be given more attention, considering their potential roles in zoonotic disease. The highest rate was detected in water, 58.5% (869/1351; 95% CI 41.6-75.5%), indicating that water is an important source of infections. Univariate regression analysis showed that CD4+ T cell counts and the living environment are significant risk factors for humans and nonhuman primates, respectively. Geographically, microsporidia have been widely found in 92 countries, among which Northern Europe and South Africa have the highest prevalence. In terms of seasonality, the most prevalent taxa, Enterocytozoon bieneusi and Encephalitozoon, display different prevalence trends, but no significant difference between seasons was observed. In addition to having a high prevalence, microsporidia are extremely divergent because 728 genotypes have been identified in 7 species. Although less investigated, microsporidia coinfections are more common with human immunodeficiency virus and Cryptosporidium than with other pathogens.

Conclusions: This study provides the largest-scale meta-analysis to date on microsporidia prevalence in mammals, birds and water worldwide. The results suggest that microsporidia are highly divergent, widespread and prevalent in some animals and water and should be further investigated to better understand their epidemic features.

Keywords: Epidemiology; Global prevalence; Meta-analysis; Microsporidia; Microsporidiosis.

Fig. 1

Flowchart for fetching and processing epidemiological data. Epidemiological publications on microsporidia were searched from databases and selected and scored according to the given criteria

Fig. 2

Forest plot diagram showing the prevalence of microsporidian infections in humans. The red items indicate the prevalence rate in different individuals and the 95% confidence interval (CI) in the considered studies based on the random effects model. The midpoint of each line shows the estimation of the prevalence, and the length of the line indicates the 95% CI of each study. The rhombic sign shows the combinational prevalence rate in corresponding studies

Fig. 3

Forest plot diagram showing the prevalence of E. bieneusi infection in humans. The red item indicates the prevalence rate of E. bieneusi and the 95% confidence interval (CI) in the considered studies based on the random effects model. The midpoint of each line shows the estimation of the prevalence, and the length of the line indicates the 95% CI of each study. The rhombic sign shows the combinational prevalence rate in corresponding studies

Fig. 4

Summary of global microsporidia prevalence. a Microsporidian species reported and recorded in the GenBank nucleotide database. b Prevalence and distribution of microsporidia in humans under different physical conditions. The Y-axis represents the prevalence rate of microsporidia. The X-axis represents the type of physical conditions. GD gastrointestinal disorders, OTR organ transplant recipients, HIV HIV-positive patients, CP cancer patients, OP patients with other diseases, NI normal immunity individuals. The number on the pie charts represents the number of positive samples of microsporidia detected. The pie chart shows the pathogen compositions, where red indicates the number of E. bieneusi-positive individuals tested, blue indicates the number of microsporidia-positive individuals, and gray indicates the number of Encephalitozoon-positive individuals. c The prevalence and species of microsporidia in animal hosts and water. The pie chart shows pathogen composition. d Seasonal distribution of E. bieneusi and Encephalitozoon infections

Fig. 5

The global geographic prevalence of microsporidia. The overall prevalence of microsporidia in countries worldwide is indicated by color depth on a world map. The outer and inner pie charts show the overall infected hosts and hosts infected by different microsporidia in each country, respectively. The number on the outer and inner pie charts represents the number of positive samples of microsporidia detected in different hosts and pathogens.