Toxocara cati Infection in Cats (Felis catus): A Systematic Review and Meta-Analysis

Simple Summary Toxocariasis, caused by species of Toxocara, affects canines, felines, humans, and other vertebrates. The primary mode of infection is by ingesting embryonated eggs. It poses environmental, human, and animal health risks, especially in park soils. This study aimed to assess the global prevalence of Toxocara cati in cats (Felis catus), a neglected species compared to T. canis, via a systematic literature review across six databases. Significant prevalence was observed using coproparasitological methods, with Nepal displaying the highest rates. The findings highlight the imperative of preventive measures against toxocariasis due to its widespread occurrence. Recognising the interconnectedness of animal, environmental, and human health underscores the importance of deworming cats, promoting hygiene, and educating the public to mitigate the risks of this zoonotic condition. Protecting feline health benefits cats and reduces the likelihood of human transmission, creating a positive outcome for both. Abstract Introduction: Toxocariasis is an infection caused in canines, felines, humans, and other vertebrates by species of the genus Toxocara, such as T. canis and T. cati. The embryonated eggs of these parasites are the primary means of acquiring the infection for both definitive hosts, dogs and cats, respectively, and for intermediates, such as humans and other vertebrates. When deposited on park soils, environmental contamination becomes a risk to environmental, human, and animal health. Objective: To determine the global prevalence of Toxocara cati in cats (Felis catus). Methods: A systematic review of the literature was carried out in six databases (Scopus, PubMed, ScienceDirect, SciELO and Google Scholar) to evaluate the global prevalence of Toxocara cati in cats, defined by coproparasitological, histological, and molecular techniques. A meta-analysis was performed using a random effects model to calculate pooled prevalence and 95% confidence intervals (95% CI). A two-tailed 5% alpha level was used for hypothesis testing. Results: Two hundred and eighty-nine studies were included. The global pooled prevalence of Toxocara cati in cats using coproparasitological methods was 17.0% (95.0% CI: 16.2–17.8%). In the subgroup analysis according to country, Nepal had the highest prevalence of T. cati infection (94.4%; 95% CI 89.7–99.2%). The pooled prevalence of T. cati infection by PCR in four studies was 4.9% (95.0% CI: 1.9–7.9%). Conclusions: This systematic review underscores the need for preventive action against toxocariasis due to its widespread prevalence. The interplay between animal and human health should be emphasised, necessitating measures like deworming cats, hygiene practices, and public education to mitigate risks. Safeguarding feline health can also reduce human transmission, benefiting both species.


Introduction
Zoonoses are a group of infectious diseases transmissible between animals and humans [1], including conditions where the human is not a definitive host of the etiological agent [2].Pets such as dogs and cats are considered opportune hosts of various pathogenic agents of zoonotic incidence, such as gastrointestinal helminths of the Toxocara genus [3].Toxocariasis is a parasitic disease with worldwide distribution, and its etiological agents in dogs and cats are Toxocara canis and Toxocara cati, respectively [4].The parasite is transmitted vertically (transplacental and transmammary) and horizontally, addressing the ingestion of embryonated eggs in infected animals' soil and fur and through consuming contaminated food [5][6][7][8].The adult nematodes of T. canis and T. cati complete their reproductive cycle in the intestine of their definitive host (dogs and cats), reproducing and eliminating about 200,000 eggs per day, excreted in faeces into the environment [9].
In dogs and cats, T. canis and T. cati mainly affect young animals from birth, presenting clinical signs such as cachexia, emaciation, body weakness, rough coat, growth dekay, vomiting, cough, diarrhoea, and distended abdomen; the cough is due to larval migration to the lungs [10][11][12].The disease can affect adult cats and dogs, but they do not usually present clinical signs [13].Toxocara infection occurs accidentally in humans due to the ingestion of eggs in soil or contaminated food, including paratenic hosts, such as poultry, pork, and beef [14,15].Based on the clinical manifestations observed in humans, the disease can be classified into four primary syndromes: visceral larva migrans (VLM), ocular toxocariasis (OT), covert toxocariasis (TC), and neuro toxocariasis (NT) [16].
At a global level, both stray and domestic cats contribute to the dispersion and contamination of embryonated Toxocara eggs into the environment [17,18].The presence of eggs in public places represents a risk for animal health and even for humans, given that approximately 21% of public spaces worldwide are contaminated with Toxocara eggs [19].In Latin America, it is estimated that the prevalence of Toxocara in public parks is 50%, which means it can be considered a transmission route for people who attend these places, mainly children who might play on the ground [20].On the other hand, studies have reported that direct contact with the fur of cats infected with T. cati is a route of transmission since potentially infective embryonated eggs have been identified in perianal areas, extremities, and the lower part of the tail of cats [8,21].The global prevalence of T. cati in cats starts from 17%, with an average of 134 million cats worldwide contributing to the dispersal of eggs in the environment, generating a public health problem [11].
Diagnostic tests for Toxocara spp. in pets are fundamentally based on the microscopic examination of faeces to find eggs and analyse their morphology, using different coprodiagnostic techniques such as direct smear, Kato-Katz, MacMaster, and Faust (flotationsedimentation), among others [22].However, other diagnostic tests have greater sensitivity and specificity, such as serological tests, ELISA to detect anti-Toxocara IgG antibodies, and molecular techniques, such as polymerase chain reaction (PCR) and Western blot, that determine the larval TES antigen [23][24][25].

Protocol:
The protocol followed the recommendations established by the PRISMA statement.
Inclusion criteria: Peer-reviewed published articles were included in which infection with coproparasitological, histological, or molecular confirmation of Toxocara catis in cats (Felis catus) was reported.For parasitological tests, we considered egg detection for tests based on molecular biology and PCR.The article language limit was not set, and we included publications from 1 January 1950 to the date the search ended, 31 January 2024.Review articles, opinion articles, and letters that do not present original data were excluded from the study, as were studies that reported cases with incomplete information.
Information sources and search strategy: A systematic review was conducted using Medline/PubMed, Scopus, ScienceDirect, SciELO, and Google Scholar.The search terms used were the following: "Prevalence", "Toxocara", "Toxocara cati", and "cats".

Study selection:
Results from the initial search strategy were first selected by title and abstract.The full texts of relevant articles were examined for the inclusion and exclusion criteria.When an article provided duplicate information from the same subjects, the information from both reports was combined to obtain complementary data, counting as only one study.Observational studies reporting the prevalence of Toxocara cati in cats were included for quantitative synthesis (meta-analysis).
Data collection process and data elements: Two researchers independently completed data extraction forms, including information on publication type, publishing institution, country, year and date of publication, and number of infected animals evaluated by serological or molecular tests.A third researcher verified the list of articles and data extractions to ensure no duplicate articles or information from the same study were presented, and resolved any discrepancies regarding study inclusion.
Assessment of methodological quality and risk of bias: We used the IHE case series study quality assessment checklist and the critical appraisal tool to assess the quality of cross-sectional studies (AXIS) [26].Publication bias was assessed using a funnel plot.Given the varying degrees of data heterogeneity and the heterogeneity inherent in any systematic review of published literature studies, a random effects model was used to calculate the pooled prevalence and 95% confidence interval (95%CI).
Statistical approach: Unit discordance for variables was resolved by converting all units to a standard measurement for that variable.Percentages and means ± standard deviation (SD) were calculated to describe the distributions of categorical and continuous variables, respectively.Since individual case information was unavailable, we will report weighted means and SDs.Baseline data were analysed using Stata version 14.0, licensed.Meta-analyses were performed with Stata, the licensed Open Meta [Analyst], and Comprehensive Meta-Analysis ve.3.3 ® software.The pooled prevalences and their 95% confidence intervals (95% CI) were used to summarise the weighted effect size for each study pooling variable using the binary random effects model of the individual studies (weighting took into account sample sizes), except for median age, where a continuous random effects model was applied (DerSimonian-Laird procedure).A random effects meta-analysis model will imply the assumption that the effects estimated in the different studies are not identical but rather follow a particular distribution.For random effects analyses, the pooled estimate and 95% CIs refer to the centre of the pooled prevalence distribution but do not describe the width of the distribution.Often, the pooled estimate and its 95% CI are cited in isolation as an alternative estimate of the quantity evaluated in a fixed-effects meta-analysis, which is inappropriate.The 95% CI of a random effects meta-analysis describes the uncertainty in the location of the systematically different mean prevalence in different studies.Measures of heterogeneity, including Cochran's Q statistic, I 2 index, and squared tau test, were estimated and reported.We performed subgroup analyses using techniques, countries, subregions, and meta-analyses for each variable of interest.Publication bias was assessed using a funnel plot.A random effects model was used to calculate pooled prevalence and 95% CI, given the varying degrees of data heterogeneity and inherent heterogeneity in any systematic review of published literature studies.

Selection of Studies
Our search strategy yielded 16,266 records in the databases combined.After removing duplicates and screening for titles and abstracts, 329 articles underwent full-text review.Finally, 289 articles were included in the systemic review and meta-analysis  (Table 1).Figure 1 shows the PRISMA flow chart.

Risk of Bias Assessment
In the risk of bias assessment, twenty studies were at high risk of bias, while the remaining 269 were at low risk of bias.

Risk of Bias Assessment
In the risk of bias assessment, twenty studies were at high risk of bias, while the remaining 269 were at low risk of bias.

Discussion
Toxocariasis, a helminth parasitic disease, is widespread, particularly in low-and middle-income nations.Despite its significant clinical implications, including the potential for fatal outcomes in humans and animals, mainly domestic ones, such as dogs and cats, many countries, particularly those with limited resources, do not actively monitor this condition [312].There is a lack of epidemiological surveillance in many regions of the planet for toxocariasis in humans and animals.
This systematic review and meta-analysis, aimed at determining the pooled prevalence of Toxocara cati in cat populations worldwide using a comprehensive search approach across six databases, found a relevant prevalence.The findings underscore the considerable diversity in parasite prevalence across various countries and continents, as indicated by previous studies [20,313,314].Through an extensive exploration of studies published between 1973 and 2023 across diverse geographic regions, this study facilitated the execution of a meta-analysis to ascertain the global prevalence of T. cati.This broad temporal and geographical scope enabled a robust synthesis of data, based on more than 150,000 animals, to provide insights into the prevalence patterns of this parasite on a global scale.As expected, Toxocara cati, compared with T. canis, is more neglected [315], making it difficult to understand that this pathogen affects other domestic and non-domestic animals and humans [316][317][318][319]. Toxocariasis in humans is also neglected, especially in developing countries [320,321].Very few studies, and even more cases reported, can confirm T. cati infection specifically in humans, by serological or molecular methods, as compared with just toxocariasis or Toxocara spp infection in humans, mainly due to a lack of confirmation or a lack of specific tests to confirm species at diagnosis.It is also believed that there are no implications at all regarding the implicated Toxocara species [316,322].Recent studies suggest that no proteins from T. canis and T. cati exist that could be used as a diagnostic tool to enable differential serodiagnostics of these species in humans.In addition, a heterogenic protein pattern between individual hosts has been found, which was most pronounced in T. cati-infected pigs [322].
Most of the studies on toxocariasis in animals have traditionally focused on dogs and Toxocara canis [12,323,324].Comparatively, there have been a lack of studies on toxocariasis in cats, mainly due to T. cati.Cats are also relevant hosts of zoonotic diseases, specifically zoonotic parasites [325,326].In this systematic review, it was observed that coproparasitological methods are still the predominant means of establishing toxocariasis in cats, showing a relevant prevalence that seems to be higher during specific years and places, probably, as shown before, influenced by seasonal, environmental, and even climatic factors [327][328][329][330].For example, as expected, the country with the highest prevalence was Nepal, a country with a low Human Capital Index (0.5) and included in the group of lower-middle income economies (LMIE), according to the World Bank (https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups)(accessed on 1 February 2024).Higher prevalences were also observed in other LMIE, such as Bangladesh, Vietnam, and Myanmar, all of them in Asia, which

Discussion
Toxocariasis, a helminth parasitic disease, is widespread, particularly in low-and middle-income nations.Despite its significant clinical implications, including the potential for fatal outcomes in humans and animals, mainly domestic ones, such as dogs and cats, many countries, particularly those with limited resources, do not actively monitor this condition [312].There is a lack of epidemiological surveillance in many regions of the planet for toxocariasis in humans and animals.
This systematic review and meta-analysis, aimed at determining the pooled prevalence of Toxocara cati in cat populations worldwide using a comprehensive search approach across six databases, found a relevant prevalence.The findings underscore the considerable diversity in parasite prevalence across various countries and continents, as indicated by previous studies [20,313,314].Through an extensive exploration of studies published between 1973 and 2023 across diverse geographic regions, this study facilitated the execution of a meta-analysis to ascertain the global prevalence of T. cati.This broad temporal and geographical scope enabled a robust synthesis of data, based on more than 150,000 animals, to provide insights into the prevalence patterns of this parasite on a global scale.As expected, Toxocara cati, compared with T. canis, is more neglected [315], making it difficult to understand that this pathogen affects other domestic and non-domestic animals and humans [316][317][318][319]. Toxocariasis in humans is also neglected, especially in developing countries [320,321].Very few studies, and even more cases reported, can confirm T. cati infection specifically in humans, by serological or molecular methods, as compared with just toxocariasis or Toxocara spp infection in humans, mainly due to a lack of confirmation or a lack of specific tests to confirm species at diagnosis.It is also believed that there are no implications at all regarding the implicated Toxocara species [316,322].Recent studies suggest that no proteins from T. canis and T. cati exist that could be used as a diagnostic tool to enable differential serodiagnostics of these species in humans.In addition, a heterogenic protein pattern between individual hosts has been found, which was most pronounced in T. cati-infected pigs [322].
Most of the studies on toxocariasis in animals have traditionally focused on dogs and Toxocara canis [12,323,324].Comparatively, there have been a lack of studies on toxocariasis in cats, mainly due to T. cati.Cats are also relevant hosts of zoonotic diseases, specifically zoonotic parasites [325,326].In this systematic review, it was observed that coproparasitological methods are still the predominant means of establishing toxocariasis in cats, showing a relevant prevalence that seems to be higher during specific years and places, probably, as shown before, influenced by seasonal, environmental, and even climatic factors [327][328][329][330].For example, as expected, the country with the highest prevalence was Nepal, a country with a low Human Capital Index (0.5) and included in the group of lower-middle income economies (LMIE), according to the World Bank (https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups) (accessed on 1 February 2024).Higher prevalences were also observed in other LMIE, such as Bangladesh, Vietnam, and Myanmar, all of them in Asia, which resulted in it being the continent with the highest prevalence.Culturally, there is a high level of contact with and apparent care of cats by humans in many Asian and Middle Eastern countries, such as Turkey (17%), Egypt (30%), and China (11%), among others.A recent study showed that cats are more popular than dogs in 91 countries, and dogs are more prevalent in 76 countries (https://www.budgetdirect.com.au/pet-insurance/guides/cats-vs-dogs-which-doesthe-world-prefer.html)(accessed on 1 February 2024).However, the number of articles and the number of samples analysed per study for some countries would be insufficient to understand the relationships between prevalence and associated factors, despite the fact that the prevalence is weighted in the meta-analysis by the number of studies and the sample size.
The type of cat significantly influences the prevalence of toxocariasis in cats.Those living in wild, non-urban areas (feral) presented the highest prevalence (43%), while domestic cats (13%) and breed cats (3%) showed the lowest values.Other studies show that this is a risk factor for higher prevalences [326].In general, unattended cats without proper veterinary control and assessment are at risk of exposure and infection.
The main coproparasitological methods vary slightly regarding the prevalence of toxocariasis, from 10.5% to 26.1%, with the faecal direct smear method associated with the highest prevalence.
Many studies assessed infection in dead animals, reporting a high prevalence, even higher than those studies assessing infection by coproparasitological methods.The prevalence of Toxocara cati at necropsy was 30%.In contrast, PCR prevalence was only 5%.Then, this was less sensitive than coproparasitological methods (17%).Again, the number of articles and the number of samples analysed per study by molecular methods such as PCR, would be insufficient to understand the differences in the sensitivity and specificity of methods, despite the fact that the prevalence is weighted in the meta-analysis by the number of studies and the sample size.To understand the sensitivity of PCR, specific studies of diagnostic test comparison should be performed, which was clearly outside the objectives of this systematic review, which focused on the prevalence of T. cati in cats.
Indeed, the histological diagnosis of T. cati can be limited, which makes a differential diagnosis with T. canis impossible.An infection due to Toxocara in a cat is not necessarily due to T. cati, as an infection due to Toxocara in a dog is not necessarily due to T. canis.Both species may infect other hosts, and in some, these may serve as paratenic hosts, just serving for infection without the reproduction and development of adult forms, as occurs in humans that are exclusively paratenic hosts [331][332][333].More commercial tests and laboratories with standardised PCR for molecular diagnosis must be conducted.The molecular diagnosis of toxocariasis is only sometimes available for humans, where the primary tool is serological tests [312,333,334].There is an urgent need for a molecular diagnosis of toxocariasis, with possibilities of sequencing and identifying species [335,336].At the same time, better immunological tests are required, as ELISA and Western blot still need to be improved, mainly due to the antigen quality.Then, recombinant antigens-based tests are preferred and it is recommended that they are widely available [337][338][339].
Although dogs have been studied more, the present systematic review shows that infections due to Toxocara cati in cats may be even higher (17%) than those due to T. canis in dogs.A recent systematic review of T. canis in dogs found that the overall prevalence was 11.1% (95% CI, 10.6-11.7%)after studying more than 3 million dogs in 60 countries [12].The authors concluded that young (<1 year of age), stray, rural, and male dogs had a significantly higher prevalence of infection than older, pet, urban, or female dogs [12].Our results confirm the findings of a review from 2020, in which the prevalence of Toxocara infection in cats was 17.0% (16.1-17.8%),but there was a contrast regarding the continents, as this review found the highest prevalence in African countries (43.3%, 28.3-58).As mentioned earlier, we found this in Asia (28%).In Africa, we found 21.4 (7.1-35.6%).They found that the prevalence of Toxocara was higher in stray cats (28.6%, 25.1-32.1%)[11].Our review found 29.9% in stray cats (25.3-34.4%)but higher results in feral cats (42.6%).
As indicated, cats may also serve as a source of human infections due to Toxocara.Cats play a crucial role globally as primary hosts for Toxocara, releasing eggs into the environment and thereby heightening public health concerns.Health authorities and cat caregivers must prioritise efforts toward preventing and managing this zoonotic disease in feline populations.This is especially crucial in regions with elevated risk factors and prevalence rates, necessitating heightened vigilance and proactive measures [11].
Cats, as with other species, may also be infected with another member of the family Toxocaridae, as is the case of Toxascaris leonina; nevertheless, fewer studies about it are available [340,341].Regardless, studies and systematic reviews so far are lacking and needed [341].
This systematic review has certain limitations, including the fact that we were unable to assess the age or gender of cats, as this was not reported in most of the studies.This aspect could also be important in the prevalence and risk of T. cati infection, as has been suggested in T. canis [312].

Conclusions
The significance of toxocariasis in cats is its potential to infect humans, in addition to the damage that it may cause to felines.Humans can become accidental hosts by ingesting Toxocara cati eggs through contaminated soil, water, or food.Once ingested, the larvae can migrate to various tissues in the body, causing visceral larva migrans (VLM) or ocular larva migrans (OLM), which can result in serious health complications, including vision impairment, organ damage, and even neurological disorders.Preventive measures should be considered, given the high prevalence found in this systematic review and previous studies.The zoonotic aspect of toxocariasis in cats and dogs highlights the interconnectedness of animal and human health, including OneHealth, emphasising the importance of preventive measures such as deworming protocols for cats [311,[342][343][344], proper hygiene practices, and public education on the risks associated with exposure to contaminated environments.By addressing toxocariasis in cats, feline health can be safeguarded, and the potential transmission of this parasitic infection to humans and other animals can also be minimised, promoting the well-being of both animals and humans.Finally, in farming animals, toxocariasis can lead to reduced productivity.Infected animals may exhibit decreased weight gain, reduced milk production (in dairy cattle), decreased fertility, and lower overall performance.This can directly impact farm income by reducing the quantity and quality of products produced.

Figure 1 .
Figure 1.The 2020 PRISMA flow diagram.* All included databases, raw results.** At an initial quality screening, including lack of inclusion criteria.

Figure 1 .
Figure 1.The 2020 PRISMA flow diagram.* All included databases, raw results.** At an initial quality screening, including lack of inclusion criteria.

Figure 2 .
Figure 2. Prevalence of Toxocara cati in cats found using coproparasitological methods.Figure 2. Prevalence of Toxocara cati in cats found using coproparasitological methods.

Figure 2 .
Figure 2. Prevalence of Toxocara cati in cats found using coproparasitological methods.Figure 2. Prevalence of Toxocara cati in cats found using coproparasitological methods.

Figure 3 .
Figure 3. Prevalence of Toxocara cati in cats found using coproparasitological methods by years.

Figure 4 .
Figure 4. Prevalence of Toxocara cati in cats found using coproparasitological methods by countries.Error bars show the upper 95% CI value.

Figure 3 .
Figure 3. Prevalence of Toxocara cati in cats found using coproparasitological methods by years.

Figure 3 .
Figure 3. Prevalence of Toxocara cati in cats found using coproparasitological methods by years.

Figure 4 .
Figure 4. Prevalence of Toxocara cati in cats found using coproparasitological methods by countries.Error bars show the upper 95% CI value.

Figure 4 .
Figure 4. Prevalence of Toxocara cati in cats found using coproparasitological methods by countries.Error bars show the upper 95% CI value.

Figure 5 .
Figure 5. Prevalence of Toxocara cati in cats found using coproparasitological methods by continents.Error bars show the upper 95% CI value.

Figure 6 .
Figure 6.Prevalence of Toxocara cati in cats found using coproparasitological methods by cat type.Error bars show the upper 95% CI value.

Figure 5 . 39 Figure 5 .
Figure 5. Prevalence of Toxocara cati in cats found using coproparasitological methods by continents.Error bars show the upper 95% CI value.

Figure 6 .
Figure 6.Prevalence of Toxocara cati in cats found using coproparasitological methods by cat type.Error bars show the upper 95% CI value.

Figure 6 .
Figure 6.Prevalence of Toxocara cati in cats found using coproparasitological methods by cat type.Error bars show the upper 95% CI value.

Figure 7 .
Figure 7. Prevalence of Toxocara cati in cats found using different coproparasitological methods.Error bars show the upper 95% CI value.

Figure 7 .
Figure 7. Prevalence of Toxocara cati in cats found using different coproparasitological methods.Error bars show the upper 95% CI value.

Figure 9 .
Figure 9. Prevalence of Toxocara cati in cats found using PCR.

Author
Contributions: J.L.B.-A.: Conceptualisation, methodology, formal analysis, investigation, writing-original draft preparation, and writing-review and editing; A.C.E.-N.: Conceptualisation, formal analysis, investigation, writing-original draft preparation, and writing-review and editing; D.K.B.-A.: Conceptualisation, formal analysis, investigation, writing-original draft preparation, and writing-review and editing; A.J.R.-M.: Conceptualisation, investigation, writing-original draft preparation, and writing review and editing.All authors have read and agreed to the published version of the manuscript.

Funding:
Universidad Continental, Huancayo, Peru, covered the APC in this article.Institutional Review Board Statement: Not applicable.Informed Consent Statement: Not applicable.Data Availability Statement: Available upon reasonable request.