Risk factors for sporadic toxoplasmosis: A systematic review and meta-analysis

https://doi.org/10.1016/j.mran.2020.100133Get rights and content

Highlights

  • Meat, vegetables, shellfish and raw milk are identified as risk factors.

  • The role of the cooking of meat and washing of produce are highlighted.

  • The role of hygiene practices during the preparation of food is underlined.

  • Contact with soil and animals, and in particular cats, are significant risk factors.

  • Contaminated drinking water can also be a risk factor.

Abstract

Toxoplasmosis is considered as the most prevalent parasitic zoonotic infection worldwide. The parasitic cycle is mostly known, but the relative contribution of different sources and pathways of transmission was not previously studied by a meta-analysis. A systematic review and a meta-analysis of case-control, cohort, and cross-sectional studies were performed to determine the main risk factors associated with sporadic Toxoplasma infection. Suitable scientific articles were identified through a systematic literature search and subjected to a methodological quality assessment. Mixed-effects meta-analysis models were adjusted by population type – children, mixed population, and pregnant women – to appropriate data partitions. 187 primary studies passed the quality assessment stage, investigating risk factors for sporadic infection with Toxoplasma gondii conducted between 1983 and 2016. Cases were defined by serology.

The meta-analysis of Toxoplasma sporadic infections revealed the significance of transmission by environmental factors such as contact with soil and contact with animals, in particular cats. The consumption of raw or undercooked meat and unwashed vegetables significantly increased the odds of acquiring the disease. Shellfish and raw milk were identified as significant sources of toxoplasmosis. Almost all meat categories were identified as risk factors: pork, poultry, beef, processed meat, lamb, and game meat. Contaminated drinking water may play a role in the acquisition of infection. Moreover, the lack of hygiene in preparing food was identified as a risk factor. A significant risk factor for pregnant women is traveling abroad. Lastly, blood transfusion (in pregnant women) and immunocompromised conditions were found associated with positive serology. The broad definition of exposures and the use of serology for the case definition are the main limitations for the interpretation of the results of this meta-analysis. The transmission pathways require further investigations using longitudinal studies and subtyping approaches.

Introduction

Toxoplasma gondii, an obligate protozoan parasite of the Apicomplexa phylum, is a worldwide parasite that can infect humans and a large range of warm-blooded vertebrates. Three major clonal lineages (type I to III) differ in pathogenicity and prevalence around the world, with genotype II dominating in congenital toxoplasmosis cases in Europe and the USA (Hosseini et al., 2019). The disease is generally benign, but some severe or life-threatening effects can occur in children (Dunn et al., 1999), when the transmission is congenital, and in immunocompromised patients (Robert-Gangneux and Darde, 2012). Since the conventional designation assumed this clonal population structure, other genotypes have been identified worldwide and termed as “atypical” or “exotic” (Dardé et al., 2014). Among these, highly virulent strains circulating mainly in South America have been responsible for severe cases in immunocompetent people (Carme et al., 2009). Approximately 30% of the human population is considered infected (Montoya and Liesenfeld, 2004). Serological tests are usually used to detect the infection, with detection of anti-T gondii specific IgG and/or IgM antibodies (Montoya, 2002). T. gondii is globally distributed and results in a high public health impact. The Global Disease Burden 2015 Study estimated that foodborne toxoplasmosis was responsible for 10.3 million (95% UI 7.40–14.9 million) cases in 2010, and 825,000 DALYs (95% UI 561,000–1.26 million) DALYs (Torgerson et al., 2015).

The parasitic cycle of toxoplasmosis is complex. During its primary infection, the cat (or other felines), the definitive host, excretes parasites (oocyst form) in its stool. Excretion in cats is limited in time (about two to three weeks) until immunity is established. Oocysts can contaminate the environment: the soil, water, and therefore shellfish that filter water and plant products directly or via irrigation water. Excreted oocysts are not infectious and become infective after sporulation, after few days in the environment depending on climate conditions, and become infectious with long resistance in environmental conditions (oocysts can survive for long periods, up to years, in a favorable environment). The remarkable resistance of the oocyst wall enables the dissemination of T. gondii through watersheds and ecosystems, and long-term persistence in diverse foods such as shellfish and fresh produce (Shapiro et al., 2019). Humans and all warm-blooded mammals are infected through the environment or food. Parasites encyst in all tissues, especially striated muscles and the brain. These cysts persist throughout life and can be a source of contamination of new hosts through meat ingestion (carnivorism) (Tenter et al., 2000).

T. gondii exposure to humans may have multiple origins, and the prevalence is high (and protective for pregnant women). So, numerous epidemiological studies investigate the main transmission pathways of sporadic T. gondii infection by serological studies. A systematic review of outbreaks was recently published (Meireles et al., 2015), still a systematic review and a meta-analysis of case-control, cohort, and cross-sectional studies have to be performed to determine the main risk factors associated with sporadic T. gondii infection. Characterization of risk factors of T. gondii could contribute to identify recommendations for susceptible populations such as pregnant women or immunocompromised patients. The objective of this meta-analysis is to summarize the evidence on risk factors for sporadic T. gondii infection regardless of the country of origin from relevant scientific information contained in epidemiological case-control/cohort/cross-sectional studies.

Section snippets

Material and methods

The protocol of the systematic review and the meta-analysis model are described in depth in the methodological paper of this issue (Gonzales–Barron et al., 2019).

Descriptive statistics

The quality assessment stage was passed by 213 primary studies investigating risk factors for sporadic infection with T. gondii, which were conducted between 1983 and 2016 (80.5% after 2000). Excluding susceptible populations other than pregnant women, and some risk factors (see above), 187 publications were retained for meta-analysis (Fig. 1 and Appendix 1). Primary studies investigated risk factors in different types of population, namely children (16 studies), mixed population (98 studies),

Discussion

The measurement of seroprevalence is an indicator of T. gondii infection, but it does not provide information on the time of infection. Besides, there may be a significant lapse of time between contamination and the collection of information on the exposures of infected persons (most often identified by serological research of IgG) during studies. Consequently, the results are conditioned on the absence of any change in the respondents' exposures over time. Cases could have been identified

Conclusion

The risk factors identified in this meta-analysis could complement those already established in future sporadic case-control studies quantifying the attributable risk fraction: mollusks (regarding the species), raw milk (goat/cows), vegetables (including the type of vegetable and the preparation i.e., washing), game meat and drinking water. Furthermore, the development of sensitive methods for the detection and isolation of T. gondii in these matrices is needed to confirm the causal association

CRediT authorship contribution statement

Anne Thebault: Methodology, Formal analysis, Writing - original draft, Writing - review & editing. Pauline Kooh: Methodology, Project administration, Writing - original draft, Writing - review & editing. Vasco Cadavez: Methodology, Investigation, Formal analysis. Ursula Gonzales-Barron: Methodology, Investigation, Formal analysis, Writing - review & editing. Isabelle Villena: Supervision, Writing - original draft, Writing - review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors would like to thank ANSES staff and the members of the ANSES Working Group on Source Attribution of Foodborne Diseases: Moez Sanaa, Laurence Watier, Jean Christophe Augustin, Frédéric Carlin, Julie David, Philippe Fravalo, Laurent Guillier, Nathalie Jourdan-Da Silva, Alexandre Leclercq, Lapo Mughini-Gras, Nicole Pavio. U. Gonzales-Barron and V. Cadavez are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER under Programme PT2020 for the financial support

References (55)

  • A.M. Tenter et al.

    Toxoplasma gondii: from animals to humans

    Int. J. Parasitol.

    (2000)
  • A. Adesiyun et al.

    Frequency of detection of immunoglobulins of Toxoplasma gondii, Leptospira spp., and Brucella abortus in livestock/farm and abattoir workers in Trinidad

    J. Agromed.

    (2011)
  • C. Alvarado-Esquivel et al.

    Seroepidemiology of infection with toxoplasma gondii in waste pickers and waste workers in Durango, Mexico

    Zoonoses Public Health

    (2008)
  • C. Alvarado-Esquivel et al.

    Seroepidemiology of infection with toxoplasma gondii in workers occupationally exposed to water, sewage, and soil in Durango, Mexico

    J. Parasitol.

    (2010)
  • C. Alvarado-Esquivel et al.

    Toxoplasma gondii infection in workers occupationally exposed to raw meat

    Occup. Med. Oxf.

    (2011)
  • C. Alvarado-Esquivel et al.

    Seroepidemiology of infection with Toxoplasma gondii in migrant agricultural workers living in poverty in Durango, Mexico

    Parasites Vectors

    (2013)
  • C. Alvarado-Esquivel et al.

    High seroprevalence of Toxoplasma gondii infection in inmates: a case control study in Durango city, Mexico

    Eur. J. Microbiol. Immunol.

    (2014)
  • C. Alvarado-Esquivel et al.

    Lack of association between Toxoplasma gondii infection and occupational exposure to animals

    Eur. J. Microbiolo. Immunol.

    (2014)
  • D. Aubert et al.

    Detection of Toxoplasma gondii oocysts in water: proposition of a strategy and evaluation in Champagne-Ardenne Region, France

    Mem. Inst. Oswaldo Cruz

    (2009)
  • L.M. Bahia-Oliveira et al.

    Highly endemic, waterborne toxoplasmosis in north Rio de Janeiro state, Brazil

    Emerg. Infect. Dis.

    (2003)
  • L. Bahia-Oliveira et al.

    Toxoplasma gondii

  • S. Belluco et al.

    Toxoplasma gondii infection and food consumption: a systematic review and meta-analysis of case-controlled studies

    Crit. Rev. Food Sci. Nutr.

    (2018)
  • R. Blaga et al.

    Toxoplasma gondii in beef consumed in France: regional variation in seroprevalence and parasite isolation

    Parasite

    (2019)
  • S. Boughattas

    Toxoplasma infection and milk consumption: meta-analysis of assumptions and evidences

    Crit. Rev. Food Sci. Nutr.

    (2017)
  • G.J. Brandon-Mong et al.

    Seroepidemiology of toxoplasmosis among people having close contact with animals

    Front. Immunol.

    (2015)
  • B. Carme et al.

    Severe acquired toxoplasmosis caused by wild cycle of Toxoplasma gondii, French Guiana

    Emerg. Infect. Dis.

    (2009)
  • G. Cavalcante et al.

    Seroprevalence of Toxoplasma gondii antibodies in humans from rural Western Amazon, Brazil

    J. Parasitol.

    (2006)
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