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The Lancet. Global Health Dec 2020The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5-15 years is underappreciated and represents an important source of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5-15 years is underappreciated and represents an important source of human-to-mosquito transmission of Plasmodium falciparum. Additional interventions are needed to control and eliminate malaria. We aimed to assess whether preventive treatment of malaria might be an effective means of reducing P falciparum infection and anaemia in school-aged children and lowering parasite transmission.
METHODS
In this systematic review and two meta-analyses, we searched the online databases PubMed, Embase, Cochrane CENTRAL, and Clinicaltrials.gov for intervention studies published between Jan 1, 1990, and Dec 14, 2018. We included randomised studies that assessed the effect of antimalarial treatment among asymptomatic school-aged children aged 5-15 years in sub-Saharan Africa on prevalence of P falciparum infection and anaemia, clinical malaria, and cognitive function. We first extracted data for a study-level meta-analysis, then contacted research groups to request data for an individual participant data meta-analysis. Outcomes of interest included prevalence of P falciparum infection detected by microscopy, anaemia (study defined values or haemoglobin less than age-adjusted and sex-adjusted values), clinical malaria (infection and symptoms on the basis of study-specific definitions) during follow-up, and code transmission test scores. We assessed effects by treatment type and duration of time protected, and explored effect modification by transmission setting. For study-level meta-analysis, we calculated risk ratios for binary outcomes and standardised mean differences for continuous outcomes and pooled outcomes using fixed-effect and random-effects models. We used a hierarchical generalised linear model for meta-analysis of individual participant data. This study is registered with PROSPERO, CRD42016030197.
FINDINGS
Of 628 studies identified, 13 were eligible for the study-level meta-analysis (n=16 309). Researchers from 11 studies contributed data on at least one outcome (n=15 658) for an individual participant data meta-analysis. Interventions and study designs were highly heterogeneous; overall risk of bias was low. In the study-level meta-analysis, treatment was associated with reductions in P falciparum prevalence (risk ratio [RR] 0·27, 95% CI 0·17-0·44), anaemia (0·77, 0·65-0·91), and clinical malaria (0·40, 0·28-0·56); results for cognitive outcomes are not presented because data were only available for three trials. In our individual participant data meta-analysis, we found treatment significantly decreased P falciparum prevalence (adjusted RR [ARR] 0·46, 95% CI 0·40-0·53; p<0·0001; 15 648 individuals; 11 studies), anaemia (ARR 0·85, 0·77-0·92; p<0·0001; 15 026 individuals; 11 studies), and subsequent clinical malaria (ARR 0·50, 0·39-0·60; p<0·0001; 1815 individuals; four studies) across transmission settings. We detected a marginal effect on cognitive function in children older than 10 years (adjusted mean difference in standardised test scores 0·36, 0·01-0·71; p=0·044; 3962 individuals; five studies) although we found no significant effect when combined across all ages.
INTERPRETATION
Preventive treatment of malaria among school-aged children significantly decreases P falciparum prevalence, anaemia, and risk of subsequent clinical malaria across transmission settings. Policy makers and programme managers should consider preventive treatment of malaria to protect this age group and advance the goal of malaria elimination, while weighing these benefits against potential risks of chemoprevention.
FUNDING
US National Institutes of Health and Burroughs Wellcome Fund/ASTMH Fellowship.
Topics: Adolescent; Africa South of the Sahara; Antimalarials; Child; Child, Preschool; Humans; Malaria
PubMed: 33222799
DOI: 10.1016/S2214-109X(20)30325-9 -
Allergy Apr 2011The rate of increase in prevalence of allergic disease in some countries implies environmental exposures may be important etiological factors. Our aim was to undertake a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The rate of increase in prevalence of allergic disease in some countries implies environmental exposures may be important etiological factors. Our aim was to undertake a systematic review and meta-analysis of epidemiological studies to quantify the association between current intestinal parasite infection and the presence of atopy and to determine whether this relation is species specific.
METHODS
We searched MEDLINE, EMBASE, LILIACS and CAB Abstracts (to March 2009); reviews; and reference lists from publications. No language restrictions were applied. We included studies that measured current parasite infection using direct fecal microscopy and defined atopy as allergen skin sensitization or presence of specific IgE. We estimated pooled odds ratios (OR) and 95% confidence intervals (95% CI) using data extracted from published papers using random-effects model.
RESULTS
Twenty-one studies met our inclusion criteria. Current parasite infection was associated with a reduced risk of allergen skin sensitization OR 0.69 (95% CI 0.60-0.79; P < 0.01). When we restricted our analyses to current geohelminth infection, the size of effect remained similar OR 0.68 (95% CI 0.60-0.76; P < 0.01). In species-specific analysis, a consistent protective effect was found for infection with Ascaris lumbricoides, Tricuris trichuria, hookworm and Schistosomiasis. There were insufficient data to pool results for atopy defined by the presence of specific IgE.
CONCLUSION
Intestinal parasite infection appears to protect against allergic sensitization. Work should continue to identify the mechanisms of this effect and means of harnessing these to reduce the global burden of allergic disease.
Topics: Dermatitis, Atopic; Humans; Intestinal Diseases, Parasitic
PubMed: 21087217
DOI: 10.1111/j.1398-9995.2010.02512.x -
PloS One 2023Toxoplasma gondii, a ubiquitous parasitic protozoan, may be an important cause of neurological and psychiatric diseases. The present systematic review and meta-analysis,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Toxoplasma gondii, a ubiquitous parasitic protozoan, may be an important cause of neurological and psychiatric diseases. The present systematic review and meta-analysis, therefore, was conducted to investigate the scientific evidence regarding the potential association between T. gondii infection and psychiatric disorders in Iran.
METHODS
We systematically reviewed articles from world-wide databases, including PubMed, Scopus, Science Direct, Web of Science, Google Scholar, and Iranian national databases up to July 30th, 2021. The Newcastle Ottawa Scale (NOS) was used to assess the quality of included studies. The common odds ratio (OR) was estimated using inverse variance and a random-effects model. Heterogeneity was assessed using the χ2-based Cochrane test (Q) and the I2 index. Also, sensitivity analyses and publication bias were calculated. Moreover, subgroup analysis was performed based on the type of disorder and quality score of different eligible studies.
RESULTS
16 studies were included in this meta-analysis. Our meta-analyses found that the OR of the risk of anti- T. gondii IgG and IgM in psychiatric patients compared to the control group was 1.56 (95% CI; 1.23-1.99) and 1.76 (95% CI: 1.19-2.61), respectively. Subgroup analysis based on the type of disorder showed that the OR of the risk of anti- T. gondii IgG in Iranian schizophrenia patients and other psychiatric disorders compared to the control group were 1.50 (95% CI; 1.09-2.07) and 2.03 (95% CI: 1.14-3.60), respectively, which are statistically significant. Also, the OR of the risk of anti- T. gondii IgM in Iranian schizophrenia and depression patients compared to the control group was 1.54 (95% CI; 0.9-2.64) and 1.03 (95% CI: 0.2-5.24), respectively, which are not statistically significant. Additionally, subgroup analysis based on quality scores showed no significant influence on the results according to the moderate quality studies. However, this association was significant according to the high quality studies. The obtained results of Egger's test were 1.5 (95% CI; -0.62-3.73, P = 0.15) and 0.47 (95% CI; -0.82-1.76, P = 0.45), respectively, indicating publication bias. The significant results of the heterogeneity analysis confirmed a high level of heterogeneity in the IgG test (P = 0.000, I2 = 66.6%). However, no significant results from the test of heterogeneity were detected in the IgM test (P = 0.15, I2 = 27.5%). The results of the sensitivity analysis showed that the impact of each study on the meta-analysis was not significant on overall estimates.
CONCLUSIONS
Despite the limited number of studies, these outcomes supported a possible link between T. gondii infection and psychiatric disorders in Iran. However, more high-quality investigations are needed in the future.
Topics: Humans; Iran; Toxoplasmosis; Toxoplasma; Schizophrenia; Immunoglobulin G; Immunoglobulin M; Seroepidemiologic Studies
PubMed: 37552680
DOI: 10.1371/journal.pone.0284954 -
PLoS Neglected Tropical Diseases Apr 2021Intestinal parasitic infection are a major public health concern affecting both children and adolescents in Ethiopia. The aim of this systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Intestinal parasitic infection are a major public health concern affecting both children and adolescents in Ethiopia. The aim of this systematic review and meta-analysis was to determine pooled prevalence and associated factors of intestinal parasitic infection in this target group.
METHOD
We systematically retrieved available articles on the prevalence of intestinal parasitic infection following database searches using PubMed, Scopus, Cochrane Library, and Science Direct between March 1 and May 27, 2020. Two authors independently extracted all relevant data using a standardized Microsoft Excel data extraction form. Heterogeneity among included studies was assessed with the Higgins I2 tests. The pooled estimates and associated factors were assessed with a random-effects model using Stata/se Version 14.
RESULT
We retrieved 30 eligible articles with a pooled sample size of 14,445 primary school children with response rate of 97.8%. Entamoeba spp (16.11%), Ascaris lumbricoides (13.98%), hookworm (12.51%) and Giardia lamblia (9.98%) are the top causes of intestinal parasitic infection among primary school children in Ethiopia. The pooled prevalence for at least one intestinal parasitic infection was 46.09 (95% CI: 38.50, 53.68). Heterogeneity was assessed by doing subgroup analysis by study province/region. Thus, the highest prevalence of 66.6% (95% CI: 55.5, 77.7) occurred in Tigray region, which was followed by Southern Nations, Nationalities, and Peoples' Region at 50.8% (95% CI: 33.1, 68.5). No latrine availability (OR = 4.39: 2.50,7.73), no fingernail hygiene (OR = 2.37: 1.67, 3.35), open defecation (OR = 1.67:1.64,4.36), no formal maternal education (OR = 2.02: 1.18,3.47), rural residence (OR = 1.88: 1.46, 2.41), no habit of wearing shoes (OR = 2.66: 1.79, 3.96), non-pipe source of drinking water (OR = 1.99: 1.42,2.76), no regular hand washing practices (OR = 3.45:1.85,6.47), and no habit of washing fruits and vegetables (OR = 1.59:1.01,2.49) were associated with parasitic infection.
CONCLUSIONS
The prevalence of intestinal parasitic infection was high (46%). Attention should be given to promoting personal hygiene, latrine utilization, wearing shoes, avoiding eating raw food, creating awareness for those mothers who lack formal education. Moreover, future research ideally will expand on the topic by conducting research in regions which have no prior research.
Topics: Adolescent; Child; Ethiopia; Humans; Intestinal Diseases, Parasitic; Prevalence; Risk Factors; Schools; Students
PubMed: 33905414
DOI: 10.1371/journal.pntd.0009379 -
Parasites & Vectors Nov 2012Toxoplasmosis is a disease caused by Toxoplasma gondii and at least one-third of the world's population has detectable T. gondii antibodies. The seroprevalence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Toxoplasmosis is a disease caused by Toxoplasma gondii and at least one-third of the world's population has detectable T. gondii antibodies. The seroprevalence of T.gondii ranges from 15% to 50% among the Mexican general population. The aim of this work was to determine the mean prevalence and weighted mean prevalence of T. gondii infection, and to evaluate the epidemiological transition of infection in Mexico.
METHODS
Pub Med, Lilacs, Medline, Latindex, Google Scholar data bases were searched to retrieve reports from 1951 up to 2012 regarding prevalence data, diagnostic tests and risk factors of infection among the adult population. Data collection and criteria eligibility was established in order to determine the crude prevalence (proportion of positive cases) of each study, together with weighted population prevalence according to individual research group categories to limit the bias that may impose the heterogeneous nature of the reports. A Forest Plot chart and linear regression analysis were performed by plotting the prevalence of infection reported from each study over a period of sixty years.
RESULTS
A total of 132 studies were collected from 41 publications that included 70,123 individuals. The average mean prevalence was 27.97%, and weighted mean prevalence was 19.27%. Comparisons among different risk groups showed that the weighted prevalence was higher in women with miscarriages (36.03%), immunocompromised patients (28.54%), mentally-ill patients (38.52%) and other risk groups (35.13%). Toxoplasma infection among the Mexican population showed a downward trend of 0.1%/year over a period of sixty years that represents a 5.8% reduction in prevalence.
CONCLUSIONS
This analysis showed a downward trend of infection; however, there are individuals at high risk for infection such as immunocompromised patients, mentally-ill patients and pregnant women. Further research is required to provide better prevention strategies, effective diagnostic testing and medical management of patients. Educational efforts are required to avoid the transmission of infection in populations that cannot be controlled by drugs alone.
Topics: Abortion, Spontaneous; Antibodies, Protozoan; Databases, Factual; Female; Humans; Immunocompromised Host; Male; Mental Disorders; Mexico; Pregnancy; Pregnancy Complications, Parasitic; Prevalence; Risk Factors; Seroepidemiologic Studies; Toxoplasma; Toxoplasmosis
PubMed: 23181616
DOI: 10.1186/1756-3305-5-271 -
American Journal of Respiratory and... Sep 2006Epidemiologic studies suggest that intestinal parasite infections may protect against asthma. (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Epidemiologic studies suggest that intestinal parasite infections may protect against asthma.
OBJECTIVES
A systematic review and meta-analysis of epidemiologic studies to determine whether total or species-specific current parasite infection is associated with a reduced risk of asthma or wheeze.
METHODS
We searched MEDLINE, EMBASE, and CINAHL (up to January 2006); reviews; and reference lists from publications, with no language restrictions. We included studies that reported asthma or wheeze as an outcome measure and ascertained parasite infection by fecal examination. We estimated pooled odds ratios (OR) and 95% confidence intervals (CI) using data extracted from published papers, or where available, original data provided by authors, using random effect models.
MEASUREMENTS AND MAIN RESULTS
Thirty-three studies met the inclusion criteria. Infection with any parasite was associated with a small, nonsignificant increase in asthma risk (OR, 1.24; 95% CI, 0.98-1.57; 29 studies). In species-specific analysis, Ascaris lumbricoides was associated with significantly increased odds of asthma (OR, 1.34; 95% CI, 1.05-1.71; 20 studies), while hookworm infection was associated with a significantly strong reduction (OR, 0.50; 95% CI, 0.28-0.90; 9 studies) that was directly and significantly related to infection intensity (p < 0.001; OR for highest tertile of infection, 0.34; 95% CI, 0.19-0.62). Other species had no significant effects on asthma. Infection effects on wheeze were derived from smaller numbers, but revealed a broadly similar pattern of results.
CONCLUSIONS
Parasite infections do not in general protect against asthma, but infection with hookworm may reduce the risk of this disease.
Topics: Adult; Asthma; Child; Humans; Intestinal Diseases, Parasitic; Risk Assessment
PubMed: 16778161
DOI: 10.1164/rccm.200603-331OC -
The Lancet. Global Health Jul 2023Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD).
METHODS
For this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine-pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342.
FINDINGS
The search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0-55·9, 66 substudies) for submicroscopic and 8·0% (0·0-50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0-100); this proportion was highest in the Americas (73·3%, 0·0-100), followed by Asia (67·2%, 36·4-100) and Africa (56·5%, 20·5-97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02-1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45-5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection.
INTERPRETATION
During pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections.
FUNDING
Bill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.
Topics: Female; Humans; Pregnancy; Adult; Prevalence; Malaria; Antimalarials; Malaria, Falciparum; Risk Factors
PubMed: 37276878
DOI: 10.1016/S2214-109X(23)00194-8 -
Infectious Diseases of Poverty Oct 2023Clonorchis sinensis, one of the most important food-borne zoonotic trematodes, remains prevalent in China. Understanding its infection status in animals is crucial for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clonorchis sinensis, one of the most important food-borne zoonotic trematodes, remains prevalent in China. Understanding its infection status in animals is crucial for controlling human clonorchiasis. Here we conducted a systematic review and meta-analysis to focus on the spatio-temporal disparities of C. sinensis infection in animals in China.
METHODS
Data on C. sinensis prevalence in snails, the second intermediate hosts, or animal reservoirs in China were extracted from electronic databases including PubMed, Embase, Web of Science, Chinese Wanfang database, CNKI, VIP, and China Biomedical Literature database. A random-effects meta-analysis model was utilized to estimate the pooled prevalence in each of the above animal hosts. Subgroup analysis and multivariable meta-regression were performed to explore potential sources of heterogeneity across studies and compare the temporal disparity of infection rates between high and low epidemic areas. Scatter plots were used to depict the biogeographical characteristics of regions reporting C. sinensis infection in animals.
RESULTS
The overall pooled prevalence of C. sinensis was 0.9% (95% CI: 0.6-1.2%) in snails, 14.2% (12.7-15.7%) in the second intermediate host, and 14.3% (11.4-17.6%) in animal reservoirs. Prevalence in low epidemic areas (with human prevalence < 1%) decreased from 0.6% (0.2-1.2%) before 1990 to 0.0% (0.0-3.6%) after 2010 in snails (P = 0.0499), from 20.3% (15.6-25.3%) to 8.8% (5.6-12.6%) in the second intermediate hosts (P = 0.0002), and from 18.3% (12.7-24.7%) to 4.7% (1.0-10.4%) in animal reservoirs. However, no similar decrease in prevalence was observed in high epidemic areas (with human prevalence ≥ 1.0%). C. sinensis infections were predominantly reported in areas with altitudes below 2346 m and annual cumulative precipitation above 345 mm and were mostly concentrated in eastern China.
CONCLUSIONS
There are spatio-temporal disparities in the animal infections of C. sinensis in different areas of China. Animal infections are primarily concentrated in regions with low altitude and high precipitation. The results suggest that implementing One Health-based comprehensive measures targeting both humans and animals, especially in high epidemic areas, is essential for successful eradication of C. sinensis in China.
Topics: Animals; Humans; Clonorchiasis; Clonorchis sinensis; China; Prevalence; Snails
PubMed: 37845775
DOI: 10.1186/s40249-023-01146-4 -
Parasitology Research Jan 2015Toxoplasmosis, a cosmopolitan parasitic infection caused by Toxoplasma gondii, is frequently found in meat-producing animals and human beings. This review and... (Meta-Analysis)
Meta-Analysis Review
Toxoplasmosis, a cosmopolitan parasitic infection caused by Toxoplasma gondii, is frequently found in meat-producing animals and human beings. This review and meta-analysis study was performed to evaluate the overall prevalence of T. gondii infection among sheep and goats in Iran. Data were systematically collected from 1977 to 2012 in Iran on the following electronic databases: PubMed, Google Scholar, Science Direct, Scopus, Web of Science, Magiran, Irandoc, IranMedex, and Scientific Information Database (SID). Additionally, abstracts of national scientific congresses and dissertations were included. A total of 34 articles in field of sheep and 18 articles about goat toxoplasmosis, totalizing to the examination of 14,372 sheep and 3,120 goats, reporting prevalence of toxoplasmosis from different regions of Iran fulfilled our eligibility criteria. The overall prevalence rate of toxoplasmosis in Iran was estimated to be 31% (95% confidence interval (CI) = 0.259825 to 0.352382) in sheep and 27% (95% CI = 0.140097 to 0.424782) in goats, respectively. There was no significant difference in infection rate between males and females among sheep (odds ratio (OR) = 1.002, 95% CI = 0.59 to 1.696) and goats (OR = 1.027, 95% CI = 0.685 to 1.541). Analysis revealed that infection rate in sheep over than 1 year old was 2.4 times more than that in less than 1 year old (OR = 2.396, 95% CI = 1.050 to 5.467). This systematic review and meta-analysis study revealed that infection is widespread in Iran. Further studies are required to improve strategies for controlling infection among flocks and consequently in human population.
Topics: Animals; Female; Goat Diseases; Goats; Iran; Male; Prevalence; Sheep; Sheep Diseases; Toxoplasma; Toxoplasmosis, Animal
PubMed: 25378258
DOI: 10.1007/s00436-014-4176-2 -
PloS One 2017Zoonotic enteric parasites are ubiquitous and remain a public health threat to humans due to our close relationship with domestic animals and wildlife, inadequate water,... (Review)
Review
INTRODUCTION
Zoonotic enteric parasites are ubiquitous and remain a public health threat to humans due to our close relationship with domestic animals and wildlife, inadequate water, sanitation, and hygiene practices and diet. While most communities are now sedentary, nomadic and pastoral populations still exist and experience unique exposure risks for acquiring zoonotic enteric parasites. Through this systematic review we sought to summarize published research regarding pathogens present in nomadic populations and to identify the risk factors for their infection.
METHODS
Using systematic review guidelines set forth by PRISMA, research articles were identified, screened and summarized based on exclusion criteria for the documented presence of zoonotic enteric parasites within nomadic or pastoral human populations. A total of 54 articles published between 1956 and 2016 were reviewed to determine the pathogens and exposure risks associated with the global transhumance lifestyle.
RESULTS
The included articles reported more than twenty different zoonotic enteric parasite species and illustrated several risk factors for nomadic and pastoralist populations to acquire infection including; a) animal contact, b) food preparation and diet, and c) household characteristics. The most common parasite studied was Echinococcosis spp. and contact with dogs was recognized as a leading risk factor for zoonotic enteric parasites followed by contact with livestock and/or wildlife, water, sanitation, and hygiene barriers, home slaughter of animals, environmental water exposures, household member age and sex, and consumption of unwashed produce or raw, unprocessed, or undercooked milk or meat.
CONCLUSION
Nomadic and pastoral communities are at risk of infection with a variety of zoonotic enteric parasites due to their living environment, cultural and dietary traditions, and close relationship to animals. Global health efforts aimed at reducing the transmission of these animal-to-human pathogens must incorporate a One Health approach to support water, sanitation, and hygiene development, provide education on safe food handling and preparation, and improve the health of domestic animals associated with these groups, particularly dogs.
Topics: Animals; Humans; Intestinal Diseases, Parasitic; Risk Factors; Zoonoses
PubMed: 29190664
DOI: 10.1371/journal.pone.0188809