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Keywords:

  • epidemiology;
  • public health;
  • Toxoplasma gondii;
  • toxoplasmosis;
  • uveitis

Abstract

  1. Top of page
  2. A
  3. Introduction
  4. Parasitology ofT. gondii
  5. Epidemiology of toxoplasmosis and ocular toxoplasmosis
  6. Public health considerations in toxoplasmosis
  7. Conclusion
  8. References

Ocular toxoplasmosis results from retinal infection with the protozoan, Toxoplasma gondii. This parasite, which exists as multiple clonal subpopulations and in three stages, is capable of replication in any nucleated cell of its primary feline or multiple paratenic hosts. Human seroprevalence of toxoplasmosis is high across the globe, but with geographic variation. While prevalence of ocular toxoplasmosis is not well documented, toxoplasmic retinochoroiditis is the commonest form of posterior uveitis in many countries. Correlation of parasite genotype with disease is an important area of new research. Ocular infection with T. gondii often follows ingestion of bradyzoites in undercooked infected meat. Oocysts may survive for an extended period in the environment, and water contaminated with oocysts is an important source in toxoplasmosis epidemics. Ocular toxoplasmosis is preventable by a combination of community activities and personal measures. Public health action is well justified by the considerable burden of congenital and postnatal infections.


Introduction

  1. Top of page
  2. A
  3. Introduction
  4. Parasitology ofT. gondii
  5. Epidemiology of toxoplasmosis and ocular toxoplasmosis
  6. Public health considerations in toxoplasmosis
  7. Conclusion
  8. References

Toxoplasmosis is an infectious disease caused by the apicomplexan parasite, Toxoplasma gondii. The most common clinical manifestation of this disease involves the eye in the form of retinochoroiditis.1 Seroprevalence of toxoplasmosis and prevalence of ocular toxoplasmosis vary across the globe, but both measures are substantial in many populations. Infection with T. gondii commonly follows oral ingestion of tissue cysts in raw meat, and epidemics have been attributed to contamination of water sources with oocysts. In this manuscript, we summarize the parasitology of T. gondii, review recent literature relating to the epidemiology of toxoplasmosis and ocular toxoplasmosis and discuss public health considerations relevant to the disease.

Parasitology ofT. gondii

  1. Top of page
  2. A
  3. Introduction
  4. Parasitology ofT. gondii
  5. Epidemiology of toxoplasmosis and ocular toxoplasmosis
  6. Public health considerations in toxoplasmosis
  7. Conclusion
  8. References

The protozoan, T. gondii, is a highly effective parasite. It infects any nucleated mammal cell and, in addition to humans, has been detected in a large spectrum of warm-blooded hosts, including birds2 and water dwellers,3 across many regions of the globe.4 Reasons for the wide host and geographic ranges of T. gondii are well summarized by Boothroyd5 and include both molecular mechanisms (e.g. independent motility, molecular mechanisms that allow the parasite to invade and reproduce within a cell irrespective of species and capacity to evade phagocytosis and to alter protein translation in the host cell) and infective behaviour (e.g. large-scale production of hardy and highly infectious oocyts by primary feline hosts, existence of multiple paratenic hosts and routes of transmission that include oral).

T. gondii is a member of the phylum, Apicomplexa, which also includes Cryptosporidium and Plasmodium species. The phylum name reflects the presence of a polar ‘apical complex’ that mediates attachment to the host cell membrane in this group of parasites.6T. gondii exists in three infectious forms (i.e. sporozoites, which are contained within oocysts, tachyzoites and bradyzoites, which reside in tissue cysts). The structure and biology of each stage was definitely reviewed by Dubey et al.7 and is briefly summarized in the following section.

Stages of T. gondii

Oocyst

Oocysts are produced solely in felines and require sexual reproduction of T. gondii. Each unsporulated oocyst measures approximately 10 microns in diameter and contains a zygote or sporont surrounded by a cell wall. With defecation by the feline, the immature oocysts are released into the environment, where sporulation occurs, yielding two sporocysts (each enclosing four sporozoites) from the sporont.

Tachyzoite

The tachyzoite is the fastest replicating form of T. gondii, and it is responsible for systemic dissemination and subsequent active tissue infection in intermediate hosts. Tachyzoites have a crescentic form and measure approximately 6 microns by 2 microns. One end, which has a pointed appearance, contains the apical complex. Host cell invasion and egress have been reviewed in detail by Black and Boothroyd.6 Invasion involves release of proteins from secretory granules, which are ejected through the tubular conoid organelle, all of which are housed within the apical complex. As it enters a host cell, the tachyzoite becomes enveloped in a parasitophorous vacuole, derived mostly from host cell membrane, in which it is able to survive and replicate. In addition to the apical complex and a complex cytoskeleton that allows independent motility, tachyzoites contain common organelles, including ribosomes, endoplasmic reticulum, Golgi apparatus and mitochondria. The apicoplast is an interesting organelle, which was first described in 1966,8 but only 30 years later identified as a plastid of algal origin.9 This organelle has a genome and is essential for parasite survival, and it presents an important target for drugs in use and antimicrobials in development for T. gondii infection.10,11

Bradyzoite

T. gondii bradyzoites are often referred to as the dormant form of the parasite, and this form is characteristic of chronic infection. Bradyzoites are found within tissue cysts that may persist in cells of various organs for the lifetime of the host. Young tissue cysts are small, but as a result of asexual replication, albeit slow, may grow to contain hundreds of parasites and reach 100 microns in length. Recent studies have surprised parasitologists by revealing an ability of individual bradyzoites to move from infected cell to uninfected cell, leaving the former intact.12 This observation may explain reports of dissemination during chronic infection.

Life cycle of T. gondii

The life cycle of T. gondii has been well described by Dubey et al.,7 and Black and Boothroyd.6 Replication occurs independently by one of two mechanisms, that is, sexual cycle (requiring feline intestinal epithelial cells) or asexual cycle (occurring in any nucleated cell subpopulation of an intermediate host).

Sexual cycle

After ingestion of a tissue cyst by a feline, digestive enzymes liberate bradyzoites, which invade the intestinal epithelium. The bradyzoites undergo replication and transformation, ultimately yielding microgametes, which fertilize macrogametes to produce zygotes. Each zygote or sporont is enclosed by a cell wall and discharged into the intestine as an unsporulated oocyst. Sporulation of the oocyst takes place ex vivo, within 5 days of passage from the host.7 The sporont undergoes several rounds of division and development ultimately resulting in an infective oocyst containing sporozoites. Tachyzoites or sporozoites may also be ingested, albeit less commonly, also leading in the generation of oocysts. Following bradyzoite ingestion, millions of oocysts may be released each day for a period of several weeks.13 Each sporulated oocyst has the potential to survive for 12 months or longer in soil14 or cold seawater.15 In the setting of immunocompromise, related to poor nutrition or concurrent infection, or if re-infection occurs years later, a feline may shed further rounds of oocysts.16

Asexual cycle

The asexual replication cycle is initiated when an intermediate host ingests an oocyst or tissue cyst. As occurs in the feline, these structures rupture in the gastrointestinal tract, releasing bradyzoites or sporozoites that invade and differentiate into tachyzoites in the intestinal epithelium. Tachyzoites disseminate throughout the body, primarily via the blood stream, and are capable of infecting nucleated cells in any tissue and being transmitted to the unborn child. The parasite's mode of transportation is not completely understood, but both free tachyzoites and infected leukocytes have been identified in blood of patients with toxoplasmosis.17 Following multiple rounds of asexual reproduction within a parasitophorous vacuole of a host cell, 64–128 daughter tachyzoites lyse the vacuole and subsequently the host cell, and propel themselves through the extracellular space to adjacent cells. In the tissue of an intermediate host, following a period of active replication, tachyzoites differentiate into bradyzoites. The location of cyst formation depends on the host species; in humans, the central nervous system, including retina, is the most common site of tissue cysts.18 Conversion from bradyzoite to tachyzoite may occur at a subsequent time.

Genetics of T. gondii

In 1995, Howe and Sibley19 studied the genotype of over 100 T. gondii isolates from human and animal hosts in Europe and North America by multi-locus restriction fragment length polymorphism analysis of six independent genetic loci. This work revealed just 15 different parasite genotypes, almost all of which could be classified into one of three genetic lineages. The investigators defined these groups as types I, II and III. Just 3.8% of the strains did not fit the pattern; subsequently such strains became referred to as ‘atypical’. Twelve years later, the same group performed a sophisticated phylogenetic analysis by multi-locus intron sequencing of 46 strains, including strains from South America, to demonstrate a more complex population genetic structure of T. gondii.4 This second study identified 11 parasite haplogroups, occupying distinct geographic regions (i.e. groups 1–3 [equivalent to types I–III]: North America and Europe; groups 4, 5 and 8–10: South America; group 6: North and South America and Europe) and allowed the classification of strains previously considered atypical. Recently, the same methodology was used to re-evaluate the genetics of North American parasite isolates, leading to identification of another haplogroup (i.e. haplogroup 12).20 This extensive body research has led the investigators to conclude, ‘the population structure of T. gondii consists of discrete lineages that tend to be highly clonal and that show strong geographic restriction’.4 Clearly, studies using isolates from other geographic regions may reveal additional haplogroups within the structure.

Epidemiology of toxoplasmosis and ocular toxoplasmosis

  1. Top of page
  2. A
  3. Introduction
  4. Parasitology ofT. gondii
  5. Epidemiology of toxoplasmosis and ocular toxoplasmosis
  6. Public health considerations in toxoplasmosis
  7. Conclusion
  8. References

In 2004, Montoya and Liesenfeld21 estimated that up to one-third of the human population was infected with T. gondii. However, seroprevalence of the infection, based on detection of serum antibody directed specifically against the parasite, varies significantly with geography.

Seroprevalence of toxoplasmosis

There is considerable variation in the reported seroprevalence of toxoplasmosis in different countries. This finding may be explained in part by the variations in study methodology. Geographic and socioeconomic environmental factors; host age, genetics and immune status; and parasite genotype, stage and load are other factors that may impact seroprevalence.22–24 However, taken together, current research in this area shows that a substantial proportion of many populations have been infected with T. gondii.

Africa

A few recent reports address the seroprevalence of toxoplasmosis in Africa. One study from Northeast Nigeria described a seroprevalence of 23.9% of 180 people aged 10 and older, who were tested by enzyme-linked immunosorbent assay (ELISA) for T. gondii-specific immunoglobulin (Ig) G.25 Another study of healthy people aged 14–84 years in rural Tanzania found IgG to T. gondii in 46% of 199 subjects by latex fixation test.26 Age was negatively correlated with seroprevalence, suggesting that exposure to T. gondii may be increasing in some populations.

Americas: North America

There is limited information on seroprevalence of toxoplasmosis in Canada. In 1995, the authors of Canada Communicable Diseases Report relating to a waterborne outbreak of toxoplasmosis in British Columbia commented that the prevalence of postnatally acquired toxoplasmosis in Canada was unknown.27 They cited one study conducted in region in 1977 that had documented antibodies in 28% of adults and reported that 10% of pregnant women participating in the local pregnancy screening programme tested positively for IgG. Surveying considerable data from the United States, Jones et al.28 tested 17 672 human blood samples, collected between 1999 and 2004, and compared these results with those obtained in a separate study of 17 658 samples collected between 1988 and 1994. Based on this comparison, investigators found a reduction from 14% to 9% in prevalence of serum T. gondii IgG among United States-born subjects aged 12–49 years. Much of this reduction was attributed to public health measures recently adopted by the meat industry.

Americas: Latin America

Studies performed in Brazil suggest that Latin America may have a particularly high seroprevalence of toxoplasmosis. In the late 1980s, one group of investigators found that 98% of 100 youth aged 10–15 years in a rural area of Southern Brazil carried serum antibodies against T. gondii.29 This appears to be the highest seroprevalence of toxoplasmosis reported in the medical literature. The same investigators followed 109 seronegative patients over a subsequent 7-year period and reported that approximately 20% developed specific serum antibodies.30 In another region of Brazil, Campos dos Goytacazes in Rio de Janeiro state, recent testing serum from 1436 residents by ELISA for T. gondii IgG revealed seroprevalence of toxoplasmosis that was extremely high among persons of low socioeconomic class (84%), in comparison with those of middle (62%) and high (23%) socioeconomic classes.31 Consumption of unfiltered water was a major risk factor for seropositivity. The seroprevalence of toxoplasmosis is high in Brazil's indigenous population, perhaps also related to consumption of untreated water. In a study of blood samples from just over 1000 indigenous Brazilians of three tribes, published in 2005, the seroprevalence of toxoplasmosis ranged from 55% to 80%, per ELISA for serum IgG.32

Several papers published over the past 15 years describe seroprevalence of toxoplasmosis in other countries of Latin America. In a poor neighbourhood of Maracaibo, Venezuela, 33% of 100 women aged between 10 and 45 years tested positively for T. gondii by ELISA.33 In Chile, a study of more than 75 000 blood samples from 13 regions of the country, examined by indirect hemagglutination test, revealed a toxoplasmosis seroprevalence of almost 37%.34 In Cali, Colombia, enzyme immunoassay detected specific IgG and/or IgM in 45.8% of 955 pregnant women.35 Consistent with several other reports, the authors found a correlation between lower economic status and seropositivity. One study undertaken in Northern Mexico between 2009 and 2010 was unusual in finding only 7.4% of subjects with IgG antibodies and 1.9% with IgM against T. gondii.36 The authors highlighted this finding of low seroprevalence in comparison with those in other parts of the Americas and considered differences in climate and population as possible explanations.

Asia

Seroprevalence for toxoplasmosis is quite variable across different Asian nations. At one end of the spectrum, a seroprevalence study in Jakarta, Indonesia, in 2003 that involved 1693 blood samples, recorded a prevalence of 70%.37 High seroprevalence in domestic cats was proposed as one potential explanation for this high percentage. In India, a nationwide study examined 23 094 peripheral blood samples taken in 2005 by ELISA.38 Although 24.8% were positive for IgG and/or IgM to T. gondii, there was an obvious geographic effect, with higher seroprevalence recorded in persons living in more southern cities. Because many Indians are vegetarian, the researchers responsible for this study suggested ingestion of contaminated water or vegetables was a major source of infection. A Chinese study of 2634 healthy individuals aged 15–65 years found 12.5% of persons were positive for IgG to T. gondii.39 Sera from 1265 patients at a Korean general hospital were assessed for IgG antibodies to T. gondii by latex agglutination test and ELISA, revealing a seroprevalence of approximately 7%.40 In study performed in three regions of Vietnam with a total of 650 subjects, investigators found a similarly low seroprevalence, varying from 1.09% to 6.36%.41

Europe

One large study from The Netherlands reviewed seroprevalence of toxoplasmosis using sera collected nationwide in 1995 and 1996 from 7521 people and a decade later from 5541 subjects.42 This study demonstrated a considerable decrease in seroprevalence, from 40.5% to 26.0%. Improvements in the preparation of meat for human consumption was suggested as a major reason for this decline, as in the United States.28 In a new survey from France, 47% of 273 subjects tested positively for IgG to T. gondii by ELISA.43 Surprisingly, seroprevalence was not associated with any factors related to meat consumption. A recent Spanish study compared the prevalence of T. gondii IgG in immigrant and non-immigrant female populations.44 This study of nearly 3000 women found a higher prevalence of IgG antibodies in immigrants (41%) versus non-immigrants (12%). Seroprevalence was highest in women from Eastern Europe (47%), Africa (43%) and Latin America (43%). A 2007 report from the Czech Republic described a 23% seroprevalence in 3250 military personnel who were tested by complement fixation and ELISA for specific IgG and IgM.45

Oceania

In New Zealand, a 2004 report of the immunological analysis of 500 blood samples from women undergoing standard antenatal screening described anti-T. gondii IgG in 33%.46 Another recent study conducted in New Zealand recorded a 42.9% seroprevalence in 140 presumed healthy blood donors from both rural and urban areas tested by latex agglutination test.47 Australian researchers evaluated 308 first-time attendees at an antenatal screening programme in 1998–1999 for T. gondii seroprevalence by enzyme immunoassay and found specific IgG antibodies in 23% of these women.48

T. gondii genotyping in human toxoplasmosis

Routine clinical testing for toxoplasmosis does not distinguish between different haplogroups of T. gondii, but current research is attempting to draw correlations between parasite genotype and occurrence and severity of disease.

Howe and Sibley's19 ground-breaking early genotypic study of T. gondii strains at six loci revealed a predominance of type II among isolates from 68 human samples and of type III in 34 animal specimens. These strains were obtained in North America or Europe, and the majority of human sources had acquired immunodeficiency syndrome (AIDS) or were congenitally infected. A subsequent work from the same group, using clinical samples from 68 North American patients, who had immunocompromising diseases or congenital toxoplasmosis, and genotyping based on polymorphism in the T. gondii SAG2 gene, yielded similar results.49 In contrast, a third study from this group that used four different genetic markers identified type I alleles in 75% of T. gondii DNA isolated from cerebrospinal fluid of eight patients with AIDS.50 However, an independent group in the United States also reported a bias towards type I strains or strain-containing alleles in vitreous samples from 12 patients with severe or atypical toxoplasmosis, including six who were immunocompetent.51

Research from Europe in this field has also delivered apparently conflicting results. A genetic analysis of SAG2 in 25 fluid and tissue samples, including aqueous, that were collected in Spain, revealed type II strains in 52% of samples from immunocompromised patients and type I strains in 75% of congenital toxoplasmosis.52 Determination of eight microsatellite markers in 86 T. gondii isolates from cases of congenital toxoplasmosis in four Western European countries showed a predominance of type II parasites.53 Researchers in France genotyped parasite DNA in aqueous and vitreous humour samples from 13 patients with atypical ocular toxoplasmosis for five microsatellite markers.54 The group included both immunocompetent and immunocompromised persons, who were either immigrants or French born. Ten of the 17 patients were infected with type II T. gondii. In one further study that was conducted in Poland, investigators sequenced single nucleotide polymorphisms in an untranscribed region of the T. gondii genome in blood samples from 59 otherwise healthy individuals with ocular toxoplasmosis, and in all cases, type I parasites were identified.55

In South America, the situation is also complicated. Investigators in Colombia analysed the SAG2 locus in non-ocular samples from immunocompromised individuals and cases of congenital toxoplasmosis, and found the majority of the 50 contained type I T. gondii.56 Approximately half of 72 blood and cerebrospinal fluid samples from AIDS patients in Brazil tested positively for type I alleles at four locations.57 Another Brazilian study of 11 globes with clinical evidence of ocular toxoplasmosis demonstrated that type I strains were responsible in all cases by analysis of the SAG2 gene.58 Khan et al.59 examined four different genetic loci in parasitic material obtained from a variety of samples from Brazil, which also included peripheral blood leukocytes of patients with ocular toxoplasmosis. These investigators reported that most of the clinical samples were infected with T. gondii strains that could not be neatly classified as I, II or III.

Clearly, the investigation of T. gondii genotypes in human disease is in its infancy. Although the studies conducted to date suggest genetic variation by geographic area and host immunological status, it is difficult to draw general conclusions at the present time. This difficulty relates to factors that include: variation in methodology between studies; a changing definition of the population structure of T. gondii; and the fact that most work has used human material from immunocompromised or congenitally infected patients, with relatively few samples from otherwise healthy persons.60

Prevalence of ocular toxoplasmosis

Research regarding the prevalence of ocular toxoplasmosis is scarce. On the other hand, multiple studies, conducted in diverse countries across the globe, have identified ocular toxoplasmosis as the most common form of posterior uveitis. Indeed, in some populations, ocular toxoplasmosis is the leading identifiable cause of all forms of uveitis.

Africa

Ocular toxoplasmosis is considered an important cause of uveitis in Africa, but there are a few studies describing the epidemiology of the disease on this continent. In Sierra Leone, West Africa, in 1992, ocular toxoplasmosis was the most common cause of non-onchocercal uveitis, accounting for 43% of all cases.61 The importance of the disease in this region had been suspected since 1967, when it was reported that immigrants from West Africa to Great Britain had a significantly higher prevalence of toxoplasmosis than white or immigrants from other regions of the world.62 In Cameroon, toxoplasmosis is also a major cause of uveitis, responsible for approximately one-third of total cases in the mid-1990s.63 Review of the clinical records of 472 Tunisian patients who presented consecutively at the Fattouma Bourguiba University Hospital Uveitis Clinic, Monastir, revealed that ocular toxoplasmosis was the second most common cause of uveitis (10.8%) and the most common cause of posterior uveitis (38.3%).64

Americas: North America

Jones and Holland65 estimated that in 2009, 1 075 242 persons became infected, resulting in 21 505 cases (i.e. 2% of the population) of ocular toxoplasmosis and 4839 (i.e. 0.45% of the population) symptomatic eye infections in the United States. Latino patients have been identified as a high-risk group for the diagnosis in this country.66 A particularly large retrospective study conducted at the Massachusetts Eye and Ear Infirmary, Harvard Medical School, identified ocular toxoplasmosis as the most common form of posterior uveitis in the 1990s.67 A recent survey of paediatric patients with uveitis treated at one of three tertiary referral clinics across the United States identified ocular toxoplasmosis as the most common form of posterior uveitis in children also.68

Americas: Latin America

Data from Colombia and Brazil suggest that ocular toxoplasmosis may be more common in South America than on any other continent. In Erechim in Southern Brazil, a population-based study of 1042 subjects undertaken in 1990 revealed a prevalence of toxoplasmic retinal lesions that was extraordinarily high, that is, 17.7%.69 In one study conducted in the Quindio region of Colombia in 2005, healthy university students and staff were screened for ocular toxoplasmosis.70 Six percent of these persons had retinal scars attributed to ocular toxoplasmosis. A separate, but concurrent, prospective study from the same region provided an incidence for clinically apparent, postnatally acquired cases of three per 100 000 inhabitants per year.71 This figure is considerably higher than results of similar measurements for North America65 and Europe.72 The retrospective chart review of 693 Colombian patients with uveitis, seen over a 10-year period ending in 2006, determined that ocular toxoplasmosis was the most common cause of uveitis, accounting for approximately 40% of cases.73

Asia

The current prevalence of ocular toxoplasmosis in Asian nations has not been specifically addressed, but several studies provide information regarding the contribution of the disease as a cause of uveitis. One retrospective chart review of 1233 patients presenting with uveitis in Northern India found ocular toxoplasmosis in just 1.7% of cases,74 although similar reviews conducted in northeastern75 and southern76 centres in India identified ocular toxoplasmosis as the most common specific cause of posterior uveitis, accounting for a total of 12% and 8% of cases, respectively. A retrospective survey of 1752 Chinese patients managed at an academic uveitis clinic in Guangzhou included only two cases of ocular toxoplasmosis.77 A nationwide survey of more than 3060 patients with uveitis at 41 university hospitals suggested that T. gondii infection also was not a leading cause of uveitis in Japan, being responsible for 1.1% of all cases.78 In contrast, a prospective study from Thailand describing 138 consecutive patients first presenting with non-human immunodeficiency virus associated uveitis found toxoplasmosis to be the main infectious cause of uveitis (8.7%).79

Europe

Taking a population-based active reporting approach in the United Kingdom, Gilbert et al.72 collected data that enabled them to conservatively place the incidence of symptomatic ocular toxoplasmosis at 0.8/100 000 persons per year, and the lifetime risk (to 60 years) at 18/100 000 liveborns. As might be expected from the seroprevalence data, these figures were significantly higher for Black persons than White persons. T. gondii infection was the main cause of posterior uveitis in 1064 consecutive patients at a national uveitis referral centre in Italy between 2002 and 2008, accounting for 6.9% of all uveitis.80 In Germany, a survey of 1916 patients seen in a similar setting and almost concurrently, also found ocular toxoplasmosis to be the most frequent diagnosis in patients with posterior uveitis and the cause of 4.2% of uveitis cases.81

Oceania

There are limited data relating to ocular toxoplasmosis in Oceania. In Australia, ocular toxoplasmosis accounted for 4.2% of 245 uveitis cases managed at the Sydney Eye Hospital tertiary referral clinic from 1980 to 1985.82 A very recent population-based study of uveitis in indigenous Australians found that ocular toxoplasmosis accounted for 82% of posterior uveitis, which had a prevalence of 0.59%.83

Congenital toxoplasmosis

Congenital toxoplasmosis deserves specific consideration in a discussion of the epidemiology of ocular toxoplasmosis. The incidence of congenital infection varies by world region, with more current estimates approximating 1 in 10 000 live births in the United States,84 1 in 10 000 to 1 in 1000 in different European nations,85 and 1 in 770 in Brazil.86 In neonates with congenital toxoplasmosis, the incidence of active or inactive retinochoroiditis varies in different studies, but may be as high as 74–95%.86–88 Studies that describe the prevalence of eye versus brain and/or systemic involvements in children suggest that ocular disease is the most common manifestation of congenital toxoplasmosis.88,89 In addition to the presence of clinically detectable ocular lesions at birth, new lesions typically appear over decades in approximately one-third of children who receive extended (i.e. 1-year duration) anti-microbial treatment postnatally90 and three-quarters of children who do not receive such treatment.91 One study that directly compared infected children, who were identified by prenatal or neonatal screening in Brazil or Western Europe, suggested that geography substantially impacts occurrence and severity of ocular involvement in congenital toxoplasmosis.92 In comparison to 281 European subjects, 30 children from Brazil had significantly higher risk of developing retinochoroiditis and suffering recurrent inflammation. For children with lesions, overall mean size was larger and more lesions were multiple in the Brazilian cohort.

Public health considerations in toxoplasmosis

  1. Top of page
  2. A
  3. Introduction
  4. Parasitology ofT. gondii
  5. Epidemiology of toxoplasmosis and ocular toxoplasmosis
  6. Public health considerations in toxoplasmosis
  7. Conclusion
  8. References

Burden of ocular toxoplasmosis

The burden of disease related to ocular toxoplasmosis is considerable. Havelaar et al.93 calculated the disability-adjusted life years (DALYs) – defined as the number of years of life lost because of mortality plus number of years lived with a disability, weighted for the severity of the disability94– for toxoplasmosis in The Netherlands. The results were sobering: the combined disease burden of congenital toxoplasmosis and postnatally acquired toxoplasmosis was 2400 DALYs, with each form of the disease accounting for 1200 DALYs. In congenital cases, retinochoroiditis accounted for 35% of the burden, second only to stillbirth. When disease was acquired after birth, retinochoroiditis accounted for almost the entire burden. The authors noted that the disease burden was double that of infection with Campylobacter species and roughly equivalent to that of tuberculosis. As they pointed out in a subsequent study, DALYs vary with the incidence of disease and the health-care system in any given country. Because the incidence in most industrialized nations, including The Netherlands, is 1–10 per 10 000 live births, their calculations should be roughly applicable across these nations, with that qualification.95

Transmission of T. gondii

In a majority of cases, ocular toxoplasmosis is contracted orally, by eating or handling raw meat that harbours tissue cysts, or by drinking water or consuming food contaminated with oocysts.21,96 Less commonly, tachyzoite passes vertically. In rare cases, infection may follow organ transplantation or occur as the result of an accident in the research setting.

Meat

Transmission of T. gondii in infected meat from different animals was comprehensively reviewed in 2008 by Dubey and Jones,96 and Kijlstra and Jongert.97 Although in theory, ingestion of contaminated meat from any warm-blooded animal can transmit toxoplasmosis; pork, chicken and lamb are more likely sources than beef. Cattle are susceptible to infection with oocysts, but parasite numbers in the tissues drop rapidly over time.98 The recent drop in T. gondii seroprevalence in the United States and some parts of Europe has been attributed to a switch from outdoor to indoor farming.99 In 2005, Dubey et al.100 tested samples from multiple meat retailers across the United States and detected no T. gondii in raw beef or chicken, and parasites in less than 1% of raw pork. Separately, Dubey et al.101 have described a high prevalence of toxoplasmosis in goat, which is being consumed with increasing popularity in the United States. Antibodies to T. gondii were present in 47.9% of heart samples from 234 goats that were slaughtered in northeastern states, and parasites were isolated from 12.4%.

Currently, there are strong movements worldwide towards organic farming of agricultural animals because of environmental, animal welfare and food quality concerns. Inherent to the organic approach is access to an outdoor environment, which has the potential to be soiled by felines. A study in The Netherlands sampled peripheral blood from almost 2000 pigs and found that although no pigs from indoor farms carried T. gondii, some pigs from outdoor farms had IgG against the parasite, albeit in relatively low numbers.102 Although the authors did not look for tissue cysts, they cited convincing work that correlated seropositivity and presence of tissue cysts in pigs.103 They appropriately cautioned that new farming strategies might result in increased prevalence of ocular toxoplasmosis if not combined with prevention strategies.

Water

Water reservoirs that become contaminated by faeces of infected cats may deliver T. gondii oocysts to many people in a short time interval.16 Such outbreaks of toxoplasmosis have been described in various world regions. In 1995, physicians in British Columbia, Canada, observed an outbreak of acute systemic and ocular toxoplasmosis that affected an estimated 2894–7718 persons.104 In one sample of infected persons, 19% developed retinitis. The geographic distribution of human infections fitted the distribution of a local water reservoir. An outbreak of toxoplasmosis was suspected in 2001 in Southern Brazil, after several hundred persons presented with consistent systemic symptoms.105 All citizens of the area were invited for serological screening, and 11.5% of those tested had specific IgM. T. gondii was isolated from one reservoir serving neighbourhoods where most infected persons resided. In Tamil Nadu, India, 248 patients were diagnosed with acute toxoplasmic retinitis in a 12-month period spanning 2004 and 2005, in comparison with only 47 recurrent cases in the previous 18 months.106 All tested cases had anti-T. gondii IgM. As most infected individuals use municipal water for consumption, contaminated water was the logical suspect for the source of infection, although this hypothesis could not be confirmed.

Vegetables and fruit

Several observations strongly suggest the possibility that vegetables or fruit contaminated with oocysts represent a source of T. gondii infection, although there are no reports of human disease that are definitively linked with this route of transmission. One laboratory study demonstrated that mice fed berries artificially coated with T. gondii oocysts developed toxoplasmosis.107 Recently, investigators in Poland were able to isolate parasite DNA from 9.7% of 219 vegetable and fruit items obtained in stores, marketplaces and farms.108

Congenital toxoplasmosis

Infection with T. gondii can be transmitted vertically from mother to child, although a minority of infected individuals worldwide acquire the parasite congenitally.109 Studies conducted in different countries in the Americas, Asia, Europe and Oceania over the past 40 years using varied methodologies present rates of primary infection during pregnancy that range from 1.0/1000 to 5.7/1000 pregnant women and do not suggest a temporal trend.110–119 The risk of vertical transmission increases as pregnancy progresses, but infection acquired in the early stages of pregnancy is more likely to result in clinical disease. Per estimates generated by Dunn et al.120 between 1987 and 1995 in France, the risk of vertical transmission is 6% at 13 weeks gestational age, 40% at 26 weeks and 72% at 36 weeks. On the other hand, the risk of clinical infection is 61% if T. gondii IgM is first detected in the mother at 13 weeks, 25% at 26 weeks and 9% at 36 weeks.120 Exceptionally rarely, an immunocompetent woman infected with T. gondii remote to the pregnancy has transmitted the parasite vertically, both in the context of active toxoplasmic retinochoroiditis and inactive disease.121,122 This unusual scenario has been blamed on depressed T cell-mediated immune responses during pregnancy123 or reinfection with a second strain of T. gondii.122

Risk factors for contracting toxoplasmosis

A large cross-sectional survey conducted in the United States by Jones et al.,23 using data generated in the Third National Health and Nutrition Examination Survey (1988–1994) revealed risk factors for T. gondii seropositivity that included: less than college level education; working in a soil-related occupation; and living in a crowded environment of at least one person per household room.23 Although cross-sectional surveys conducted within the last 5 years in Mexico did not link occupations that involved exposure to water or soil with infection, persons who sorted waste were at increased risk.124,125

In the mid-1990s, Cook et al.126 performed a case-control study of 252 pregnant subjects who had IgM to T. gondii and 858 control women, all living in one of six European cities, with the aim of defining risk factors associated with the infection. Eating undercooked meats, with the exception of pork; tasting meat while cooking; contact with soil; and travel outside Europe or North America were all significantly associated with toxoplasmosis. The most common identifiable risk factors related to contact with raw meat. In this study, the fact that consumption of undercooked pork was not associated with infection was attributed in part to the current preference for indoor farming of pigs.99 Another case-control study conducted on a similar scale in United States, from 2002 to 2007, consistently identified eating raw meats or cured, dried or smoked meats, and working with raw meat as risk factors for T. gondii seropositivity.127 Consumption of unpasteurized goat milk and eating raw filter feeder seafood were also associated with infection. In apparent contradiction to these reports, a case-control study conducted among Mexican butchers from 2009 to 2010 found no difference in seroprevalence of T. gondii IgG and IgM between the 124 subjects and 248 controls.128 Most meat handled by the butchers was beef, which may explain this unexpected observation, because cows are a poor host for T. gondii.98

Neither the cross-sectional study from Jones et al.23 from the United States nor the case-control study conducted in Europe by Cook et al.126 associated feline ownership with T. gondii infection. However, an independent North American case-control study that compared 148 infected subjects with 413 non-infected controls found that ownership of at least three cats was a strong risk factor for infection with the parasite.127

Prevention of T. gondii infection

Preventive measures of varying complexity limit T. gondii infection of animals bred for human consumption and, as a consequence, human infection via ingestion of tissue cysts. Apart from the obvious action of removing cats from meat-producing farms, other measures that have proven effective include vaccination of cats to prevent oocyst liberation129 and rodent control.130 To prevent T. gondii transmission from meat that harbour tissue cysts, cooking to 67°C rapidly kills cysts.131 Injecting meat with 2% sodium chloride or 1.4% sodium/potassium lactate and maintaining it at 4°C for at least 8 hours and freezing meat for a week also eliminate viable cysts.132

Because of the potential for water to carry and even sporulate oocysts, municipal water supplies should be appropriately treated, per the recommendations of Jones and Dubey.16 Notably, T. gondii oocysts are not destroyed by common chemical and physical means of water treatment, including ultraviolet light, chlorine and ozone, but should be removed by a filter with pores of 1-micron diameter. Consumption of untreated water from rivers or other natural sources should be avoided, but when this is necessary, boiling is an effective measure to kill oocysts.

Although all studies do not show a correlation between known risk factors and increased seroprevalence of toxoplasmosis, it is important to remain aware of routes by which disease may be contracted and to avoid the potential for infection of persons without immunity to T. gondii, especially immunocompromised patients and pregnant women. Recommendations from the National Center for Infectious Diseases, which were prepared in relation to congenital toxoplasmosis in the United States, but are broadly applicable, state that ‘Toxoplasma infection can be prevented in large part by …’: cooking meat at 67°C or hotter; peeling or washing fruits and vegetables; cleaning cooking utensils after contact with raw meat and seafood; gardening and changing cat litter with gloves, followed by hand washing; and feeding cats cooked meat and preventing their access to infected prey'.133 Clearly, public health campaigns and health practitioner education programmes continue to be a useful means for implementing these simple measures.

Conclusion

  1. Top of page
  2. A
  3. Introduction
  4. Parasitology ofT. gondii
  5. Epidemiology of toxoplasmosis and ocular toxoplasmosis
  6. Public health considerations in toxoplasmosis
  7. Conclusion
  8. References

Toxoplasmosis is associated with a substantial disease burden worldwide, mainly due to retinochoroiditis. Although not curable, infections with T. gondii are largely preventable by filtration of water for human consumption and simple personal behaviours relating to food preparation and ownership of domestic cats. Educational campaigns should particularly target persons who have not yet been exposed to T. gondii, especially immunocompromised individuals and pregnant women.

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  2. A
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  4. Parasitology ofT. gondii
  5. Epidemiology of toxoplasmosis and ocular toxoplasmosis
  6. Public health considerations in toxoplasmosis
  7. Conclusion
  8. References
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