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Toxoplasmosis as a travel risk
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Travel Medicine and Infectious Disease (2014) xx, 1e10
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
REVIEW
Toxoplasmosis as a travel risk Q10
´mez-Marin c, ´lveda-Arias a,b,*, Jorge E. Go Juan C. Sepu d, Carlos A. Naranjo-Galvis a,e, Branko Bobic -Djakovic b,d Olgica Djurkovic a
Facultad de Ciencias de la Salud, Departamento de Ciencias Ba´sicas, Grupo Infeccio´n e Inmunidad,
Q2 Universidad Tecnolo ´gica de Pereira, Pereira, Colombia Q3 b Zoonoses of the International Society for Chemotherapy
(ISC), Colombia Facultad de Ciencias de la Salud, Grupo GEPAMOL, Centro de Investigaciones Biome´dicas, Universidad del Quindio, Armenia, Colombia d National Reference Laboratory for Toxoplasmosis, Institute for Medical Research, University of Belgrade, Dr. Subotica 4, P.O. Box 102, 11129 Belgrade, Serbia e Facultad de Salud, Universidad Auto´noma de Manizales, Manizales, Colombia c
Q4
Received 18 February 2014; received in revised form 22 April 2014; accepted 23 May 2014
KEYWORDS
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Toxoplasmosis; Travelers; Clinical presentation; Treatment; Diagnosis; Strain genotypes; Prevention
Summary Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects more than one third of the global population. Primary infection in immunocompetent individuals is usually asymptomatic; however, different organs can be affected in immunocompromised individuals leading to the development of encephalitis, myocarditis or pneumonitis. The prevalence of infection with Toxoplasma as well as its genetic structure varies geographically and for that reason travel may be considered as a risk factor to acquire the infection. As toxoplasmosis is a foodborne disease, health care providers should give health education on prevention measures to all prospective travelers in order to decrease the risk of infection in endemic areas. This review presents an overview of the infection with T. gondii with some considerations for travelers to and from endemic zones. ª 2014 Published by Elsevier Ltd.
1. Introduction Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii which has the capacity to infect all warm-blooded animals. This parasite is responsible for
the most common parasitic zoonosis worldwide. The infection can be acquired by oral ingestion of infectious oocysts from the environment (water, soil, vegetables and fruits), by oral ingestion of tissue cysts contained in raw or undercooked meat, or by transplacental transmission of
* Corresponding author. Departamento de Ciencias Ba ´sicas, Facultad de Ciencias de la Salud, Universidad Tecnolo ´gica de Pereira, Pereira, Risaralda, Colombia. Tel.: þ57 6 3137127; fax: þ57 6 3216252. E-mail addresses: [email protected] (J.C. Sepu ´mez-Marin), [email protected] ´lveda-Arias), [email protected] (J.E. Go (B. Bobi c), [email protected] (C.A. Naranjo-Galvis), [email protected] (O. Djurkovic-Djakovic). http://dx.doi.org/10.1016/j.tmaid.2014.05.007 1477-8939/ª 2014 Published by Elsevier Ltd.
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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2 tachyzoites (Fig. 1). By tachyzoites, Toxoplasma may also be transmitted by blood transfusion, organ transplantation or by consumption of unpasteurized goat milk [1e3]. Seroprevalence estimates for human populations vary greatly among countries (Fig. 2) and even among regions within a country [4]. Differences are huge, for instance, between North and South America where the seroprevalence is as low as 6.1% in Mexico whereas in some areas of Brazil it reaches 77.5% [5,6]. Seroprevalence in Europe also ranges widely, from 8.2% in Switzerland, to 57.6% in
J.C. Sepu ´lveda-Arias et al. Romania, but a common characteristic is a decrease over the past decades [7]. A most marked decrease has been shown in France, where the prevalence has decreased, from 83% in 1965 to 54% in 1995 and 44% in 2003, to 37% in 2010 [8]. Similarly, a decrease has been registered in SouthEast Europe, and currently does not surpass 50% across the region, ranging from 20% in Greece to 49% in Albania [7]. Variations in prevalence are observed in other regions of the world and the highest prevalence (83.5%) has been reported in Madagascar [9]. These variations can be
Fig. 1 Lyfe cycle of T. gondii (From http://www.dpd.cdc.gov/dpdx). Members of the cat family (Felidae) are the only known definitive hosts for the sexual stages of T. gondii and thus are the main reservoirs of infection. Cats become infected with T. gondii by carnivorism . After tissue cysts or oocysts are ingested by the cat, viable organisms are released and invade epithelial cells of the small intestine where they undergo an asexual followed by a sexual cycle and then form oocysts, which are excreted. The unsporulated oocyst takes 1e5 days after excretion to sporulate (become infective). Although cats shed oocysts for only 1e2 weeks, large numbers may be shed. Oocysts can survive in the environment for several months and are remarkably resistant to disinfectants, freezing, and drying, but are killed by heating to 70 C for 10 min. Human infection may be acquired in several ways: A) ingestion of undercooked infected meat containing Toxoplasma cysts ; B) ingestion of the oocyst from fecally contaminated hands or food ; C) organ transplantation or blood transfusion; D) transplacental transmission; E) accidental inoculation of tachyzoites. The parasites form tissue cysts, most commonly in skeletal muscle, myocardium, and brain; these cysts may remain throughout the life of the host.
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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Toxoplasmosis as a travel risk
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Fig. 2 World map of global seroprevalence for T. gondii. Dark red equals prevalence above 60%, light red equals 40e60%, yellow 20e40%, blue 10e20% and green equals prevalence <10%. White equals absence of data (reproduced from Pappas G, et al. Int J Parasitol 2009; 39:1385e94, with permission from Elsevier). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
attributed to factors associated with the parasite strain (and genotype), geographic location and climatic conditions, cultural practices and ethnic group. Primary infection with Toxoplasma in immunocompetent individuals is usually asymptomatic, however, about 10% of the patients develop lymphadenitis or a mild flu-like syndrome or a mononucleosis-like illness [10]. Also, immunocompetent individuals may develop ocular toxoplasmosis (chorioretinitis) as a manifestation of primary infection [11,12]. Infection in immunocompromised individuals in most cases results from reactivation of a preexisting latent Toxoplasma infection. This reactivation can be lifethreatening, as it most often involves the central nervous system (SNC) and symptoms may include those of meningoencephalitis or mass lesion such as headache, confusion, fever, lethargy, seizures and focal neurological signs. Classically, congenital toxoplasmosis results from primary infection during pregnancy and the clinical presentation of the disease depends on numerous factors including gestational age, size of the inoculum, infecting form of the parasite, maternal treatment and genetic factors of the host and the parasite. Fetal infections may result in intrauterine death and spontaneous abortion, or in manifestations including hydrocephalus, microcephaly, macrocephaly, encephalitis, seizures, calcifications, chorioretinitis and blindness. Most importantly, clinical symptomatology is often absent at birth but untreated children develop late sequelae (chorioretinitis, neurological or cognitive disorders) [10]. The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) have recently established toxoplasmosis as a foodborne parasite infection of global concern [13]. Travelers (independent of previous contact with the parasite) may be at risk of infection with different parasite strains. In this review we present an overview of the infection by
Toxoplasma with some considerations for travelers to and from endemic zones.
2. Clinical presentation Acquired Toxoplasma infection in immunocompetent subjects is considered to be symptomatic only in 10e20% of the cases [14]. Indeed, no data exist on the percent of symptomatic people from longitudinal studies looking for symptoms in populations naturally exposed to this protozoan. The proportion of symptomatic people after a primary infection has been obtained from reports of outbreaks [15e18], but this information is influenced by high inocula, specificity of infection source and events that led to the infection [15e19]. Acute toxoplasmosis may resemble the clinical presentation of a cytomegalovirus or EpsteineBarr virus infection (infectious mononucleosis-like syndrome). This syndrome is characterized by the presence of fever, pharyngitis, lymphadenopathy and lymphomonocytosis [20e22]. And indeed, clinical series have shown that the most frequently observed clinical symptoms in acquired toxoplasmosis are non-tender and non-suppurative lymphadenopathies [19,23], of cervical (72,5%) (Fig. 3), axillary (20%) or occipital (7.5%) localization [23,24]. In a cohort report, 88% of cases presented more than one group of affected lymph nodes, usually located in the neck [24]. The associated clinical symptoms included asthenia and fever in 69e81% and 45e81% of cases, respectively, and sore throat in 15e20% of cases, as well as myalgia, arthralgia, splenomegaly and hepatomegaly [18,19,23,24]. Ocular involvement secondary to acquired toxoplasmosis has been reported to appear in 2e19% of cases [15e17,19]. Ocular symptoms appeared 14e87 days after infection in the Vancouver’s outbreak [15], two months after exposure to
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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J.C. Sepu ´lveda-Arias et al.
Fig. 4 Retinal exudative lesion in acquired ocular toxoplasmosis. (Source: Dr. Jorge Enrique Go ´mez-Marin, Centro de Investigaciones Biome ´dicas, Armenia, Quindı´o, Colombia).
Fig. 3 Cervical lymphadenopathy in a patient after three months of untreated primary toxoplasmosis (Source: Dr. Jorge Enrique Go ´mez-Marin, Centro de Investigaciones Biome ´dicas, Armenia, Quindı´o, Colombia).
rare meat in Korea [16], and 120 days after a family outbreak in New York [19]. We observed the case of a tourist from Bogota ´ that visited a Caribbean region in the North of Colombia, who first developed glandular toxoplasmosis and ocular toxoplasmosis one month later (Go ´mez-Marin JE, unpublished observation), and another one of a tourist from Serbia who developed chorioretinitis simultaneously with generalized lymphadenopathy two weeks after returning from a vacation in the African island of Mauritius (Djurkovic-Djakovic O, unpublished observation). The ophthalmological examination usually reveals a focal necrotizing chorioretinitis accompanied by vitreous inflammatory reaction (Fig. 4). The main clinical presentations of toxoplasmosis are shown in Table 1. Severe forms of toxoplasmosis have been reported for infections acquired in the South American jungle, leading to respiratory and cardiac complications requiring hospitalizations in intensive care units to provide cardiac and respiratory support [25,26]. These severe forms were also reported in European people consuming meat originating from Brazil [27,28]. A recent study on the immune response in South American patients showed results consistent with the hypothesis that some South American strains may cause severe ocular toxoplasmosis due to an inhibition of the protective effect of IFN-g [29].
3. Diagnosis The specific diagnosis of Toxoplasma infection in humans is based on the use of various laboratory methodologies, including serology, histologic demonstration of the parasite
and/or its antigens, isolation of the organism (by bioassay or in cell culture), or the detection of its DNA, by amplification of specific nucleic acid sequences (polymerase chain reaction (PCR)-based techniques) [30]. Serological tests are the primary method of diagnosis and in general, a combination of tests is usually required to establish if the infection was acquired recently or in the past. The detection of specific IgG antibodies gives information about previous contact with Toxoplasma, which is important to evaluate in pregnant women and in immunocompromised patients (due to the risk of reactivation of a latent infection). IgG antibodies appear within 1e2 weeks of acquisition of the infection, peak within 1e2 months and then decline to levels that persist for the life of the individual [31]. Several serological test have been used to detect antigen-specific IgG antibodies, such as the SabinFeldman dye test (nowadays used in very few laboratories), the immunofluorescent antibody test, enzymelinked immunosorbent assay (ELISA) and direct agglutination. Determination of specific IgM antibodies may be useful to detect acute infection, but the interpretation of an IgM result is complicated by the fact that IgM antibodies can be detected long after acute infection [32]. Therefore the clinical history of the patient is important to help in the interpretation of the results. A useful complementary method is the measurement of Toxoplasma-specific IgG avidity, which is based on the increasing avidity of IgG antibodies for the antigen with the length of time that has elapsed since initial infection. A high avidity finding generally rules out infection within the last four months [33e35]. Specific IgA antibodies may be detected in acute infection, but their shorter duration [36] has been disputed [37]. Secretory IgA antibodies in tears have been suggested as a reliable marker of acute ocular toxoplasmosis [38]. However, direct detection of the parasite is required for the confirmation of the diagnosis in clinical situations such as fetal infection and diagnosis of reactivated toxoplasmosis.
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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Toxoplasmosis as a travel risk Table 1
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Main clinical presentations of toxoplasmosis.
Host immune status
Clinical presentation
Signs and symptoms
Percentagea [ref]
Immunocompetent
Asymptomatic Infectious mononucleosislike syndrome
None Cervical adenopathies Asthenia Fever Sore throat Chorioretinitis Ocular lesions Intracranial lesios Any clinical manifestation Chorioretinitis Focal signs Headache Motor-sensory defects Seizures Other neurological signs
80e90% [14e18] 75% [23,24] 69-81% [18,19,24] 45-81% [18,19,23] 15-20% [18,19,23] 2-19% [15e17,19] 18% [85] 13% [85] 24% [85] 1-21% [86] 70% [87] 55% [87] 49% [87] 22% [87] 8% [87]
Ocular toxoplasmosis Congenital toxoplasmosis
Immunocompromised
a
Ocular toxoplasmosis Toxoplasmic Encephalitis
Percentage of each sign or symptom with regard to clinical presentation. [ref] Reference.
For the isolation of the organism, the bioassay of suspected biological materials into laboratory mice is the “gold standard”. This assay is sensitive for virulent and avirulent strains and detects only viable parasites [39]. A number of PCR tests targeting different gene sequences of Toxoplasma have been developed to amplify parasite DNA [40e42] and to detect it in body fluids or other clinical samples. The PCR is recommended as a part of diagnostic procedure of fetal infection in the second trimester of pregnancy with high sensitivity and specificity [43e45].
4. Treatment Treatment of symptomatic toxoplasmosis in immunocompetent patients that acquire the infection in Europe or North America may only include alleviation of symptoms and decision on whether to treat with specific antibiotics is made on a case by case basis, whereas for infections acquired in South America, due to the presence of more virulent parasites and the possibility of ocular involvement, the use of specific antibiotics (in the absence of controlled studies) is recommended. A 1-month course of cotrimoxazole treatment (40 mg sulfamethoxazole/8 mg trimethoprim per kg of body weight) twice a day has been reported to be effective in a double-blind randomized trial [46]. Classical therapy for toxoplasmosis consists of pyrimethamine, sulfadiazine and folinic acid (Table 2A). In ocular toxoplasmosis oral prednisolone (1 mg/kg daily) is given from the third day of therapy and tapered over 2e6 weeks when there are macular lesions or neuritis [47]. A good response with resolution of inflammation and appearance of the characteristic lesion hyperpigmentation can be observed after 4e6 weeks of treatment. Folinic acid should be also administered to protect against anemia and leukopenia [47]. Corticosteroid therapy without the concomitant use of antimicrobial agents, even in immunocompetent patients, can lead to severe tissue destruction [48]. Fulminant Toxoplasma retinochoroiditis has also been
observed in patients treated with intravitreal steroids alone [49]. The use of systemic steroids without antibiotics and subconjunctival injection of steroids were identified as the main factors related to recurrence in a group of patients [50]. Therefore, the use of steroids alone to treat ocular toxoplasmosis can be harmful. Alternative therapies in case of toxicity, allergic reactions or unavailability of the first line antibiotics are shown in Table 2B.
5. Toxoplasmosis in travelers Since Toxoplasma is a ubiquitous parasite, exposure exists in any geographical area of the world and Toxoplasma infection has indeed been detected virtually worldwide, resulting in one third of the global population being infected [2]. However, the degree of exposure to different sources of infection varies significantly among geographic areas. The oocyst survives better in warm and moist areas than in cold and arid ones, and at lower altitudes. The proportion of infections caused by oocysts has been reported to be 78% in the United States [51] and 43% in Chile [52], as determined by a specific test that detects anti-oocyst antibodies. Consequently, 22% and 57% of all infections in the United States and Chile, respectively, may be attributed to cystcontaining meat. The range of seroprevalence in food animals varies as widely, from 1 to 99% [1,3,53]. The cat, however, seems to be necessary for the transmission to go on, since areas devoid of cats seem to be infection-free [54]. A cultural factor contributing to infection is human nutritional habits, which may differ even in geographically close areas, such as consumption of raw or rare meat in France as opposed to well-cooking in the neighboring Germany. In many countries, traditional cured meat (particularly pork) products have been associated with Toxoplasma infection [53,55]. As a result of all these factors, certain areas are characterized by more frequent Toxoplasma infection than others. Central America, South America and Africa are viewed by some as endemic areas for
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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J.C. Sepu ´lveda-Arias et al. Table 2
Recommended dose of antibiotics for toxoplasmosis. A. First line antibiotics. B. Second line antibiotics.
A. First line antibiotics
B. Second line antibiotics
Drug
Adult dose
Pediatric dose
Pyrimethamine
200 mg oral first day followed by 75 mg once a day.
Sulfadiazine
4 g/day.
Folinic acid TMP-SMX
15 mg/day. TMP (160 mg)/SMX (800 mg) every 12 h. Or 2 pills TMP (80 mg/SMX (400 mg) every 12 h, for 6 weeks. 500 mg/day for 5 weeks. 1 mg intravitreal clindamycin and 400 mg dexamethasone.
2 mg/kg first dose and then 1 mg/kg day during one year (congenital form) or 4e5 weeks in acquired infections. 50 mg/kg twice daily (100 mg/kg/ dı´a) during one year in congenital infection or for 4e5 weeks in acquired forms. 7.5 mg/day. No reports for use in children with congenital forms.
Azithromycin Intravitreal clindamycin plus dexamethasonea
10 mg/kg/day during two months. Not reported.
Trimethoprim (TMP), Sulfamethoxazole (SMX). a In refractory cases to first and second line antibiotics in ocular toxoplasmosis.
toxoplasmosis. A report about Toxoplasma infection in Canadian travelers described 14 immunocompetent patients that returned with symptomatic primary toxoplasmosis from regions including Central America, South America, Africa and France [56]. In some areas of Brazil, the prevalence of ocular toxoplasmosis is 17% [57]. Although Toxoplasma was initially described as clonal, with three major lineages designated as types I, II and III, these are, with an emphasis on type II, only predominant in Europe and North America [58]. In South America and Africa, a higher frequency of non-clonal, highly polymorphic strains referred to as atypical has been revealed [59]. Moreover, specific African non-clonal genotypes, termed Africa 1, 2 and 3, have been identified [60,61]. But the picture is currently being complicated in the Western World as well, since a fourth clonal lineage (autochtonous haplogroup 12) has been recently described in North America [62]. In Europe, most data on human isolates originate from France, showing an overwhelming predominance (>90%) of type II [63,64]. This seems true of the rest of Europe as well, as virtually all typed isolates from cases of congenital toxoplasmosis (nine in Poland; one in Serbia and Romania each) [65e67] were type II. European immunosuppressed patients also predominantly reactivate type II strains [68]. Type II is also vastly predominant in animals in Europe, including wildlife [59]. The recent finding of the Africa 1 genotype in two human isolates from Turkey was associated with the geographical position of Turkey between Asia, Europe and Africa [69]. Similarly, the isolation of a non-clonal Toxoplasma strain in a hematopoietic stem cell transplant recipient in Serbia may indicate phylogenetic ties among Asian, African and European Toxoplasma populations [70]. Significant differences have been shown in the strains isolated from patients with ocular toxoplasmosis in France and Colombia [29,71]. Moreover, severe ocular inflammation
in Colombia was recently associated with infection by strains harboring the ROP18 type I allele [72]. The clinical severity of toxoplasmosis in South America is further illustrated by cases of fatal primary toxoplasmosis documented in immunocompetent adults in French Guiana and Surinam [17,25]. Furthermore, severe forms of myocarditis and pneumonitis have been reported in military personnel operating in the Colombian jungle [26]. This has been associated with differing patterns of the Toxoplasma population genetic structure in the (sub) tropical regions. Also, in the few cases of birth of a congenitally infected infant to a mother with serological evidence of past infection, re-infection with a strain of a different genotype has been discussed as the underlying reason [73]. In consequence, in the light of both the widely varying geographically-dependent prevalence of infection and the new knowledge on the geographic differences in the Toxoplasma population structure, travel may be a risk factor for Toxoplasma infection. Indeed, a European multicenter caseecontrol study of risk factors identified travel outside Europe, the United States and Canada as a strong predictor of acute infection in pregnant women [55]. Unimmunized travelers from areas of low to areas of high Toxoplasma prevalence may be at increased risk of infection. Furthermore, unimmunized travelers, and even those immunized, from Europe and North America, to Africa, Asia and South America, may be at risk of severe clinical entities caused by toxoplasmosis including ocular disease, pneumonia, and even life-threatening toxoplasmosis. Also, if pregnant women travel to tropical and subtropical areas, they may be at risk of (re)infection with atypical strains. Conversely, women born in the tropics, even if immunized against atypical Toxoplasma strains, could be at risk of re-infection by a type II strain if they travel to Europe or North America [73]. In the returning traveler, the presence of fever is challenging for the physician because of the broad differential
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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Toxoplasmosis as a travel risk diagnosis of this symptom [20]. Although malaria and dengue are the most common etiologies of fever in travelers [74,75], cosmopolitan infections such as toxoplasmosis, should be considered in the differential diagnosis of fever. Some case reports suggest that toxoplasmosis should be considered in the differential diagnosis of travelers with non-specific symptoms such as fatigue, fever, headache and lymphadenopathy [20,56,76]. In 72 prospectively studied travelers with the mononucleosis-like syndrome, toxoplasmosis was the cause in 22% and it was clinically indistinguishable of other causes [20].
6. Prevention Despite continuous efforts, there is yet no antitoxoplasmic vaccine for humans. The global spread of Toxoplasma infection, with a consequent worldwide risk of exposure to infection, and typically benign course of infection, do not provide justification for using chemoprophylaxis. Therefore, the only possible approach to prevent infection is health education. Question is ¿who should this target? Conventionally, pregnant women are the target population. However, new information on ocular toxoplasmosis calls for expanding the indications for implementation of preventive measures for toxoplasmosis from pregnant women and immunocompromised individuals to almost the whole population, especially under the age of 30 [77]. As the routes of infection are well established, measures for the prevention of primary Toxoplasma infection have long been well-known [1,3,53], and involve reduction of environmental risk and reduction of the risk of toxoplasmosis as a food/water-borne infection. Main measures to reduce the environmental risk include those to reduce environmental contamination (feeding cats only with commercial food or well-cooked meats, disinfecting the cat-litter box daily with boiling water for 5 min before refilling) [1] and those to reduce transmission to people, such as avoiding direct handling of stray cats, especially kittens, and avoiding contact with soil. While the measures to avoid environmental contamination are irrelevant to travelers, those to reduce the risk of transmission to individuals, particularly after exposure to cats or soil, are simple regular hands washing with soap and if possible, with warm water, most often feasible during travel [1]. The measures to reduce the risk of toxoplasmosis as a food/water-borne infection, including consumption of previously frozen meat; cooking with treated water [78]; careful washing of cutting boards, dishes, counters, utensils, and hands with hot soapy water after contact with raw meat, poultry, seafood, or unwashed fruits or vegetables; are not implementable by travelers, who by definition eat out of home and therefore have no control over food preparation [79]. However, the measures that travelers can abide with include avoiding to eat meat still pink in the center or undercooked poultry, smoked or dried meat [55,80,81], or fresh seafood [1,82]; peeling or thorough washing of fresh fruits and salads before eating; and drinking treated, preferably bottled, water [83,84]. New culinary experiences are part of the pleasure of traveling, which people cannot be expected to willingly deny themselves of. Therefore, given the potential food
7 hazards, health care providers should provide health education to all prospective travelers and insist on adherence to prevention measures in order to decrease the risk of infection in endemic areas. In returning travelers who present as patients, health care providers should consider toxoplasmosis, and in view of the increasing insight into the diverse clinical spectrum of toxoplasmosis, atypical presentations (such as pneumonitis or ocular toxoplasmosis) should be kept in mind. In pregnant women, diagnosis of acute toxoplasmosis should require appropriate treatment as a measure of secondary prevention i.e. prevention of vertical transmission.
Conflict of interest
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The authors declare that they have no conflict of interest.
Acknowledgments The authors gratefully acknowledge financial support from Universidad Tecnolo ´gica de Pereira, Colombia (Project 514-1), COLCIENCIAS, Colombia (Project 111056934589, Contrato 469-2013) and grant III 42019 from the Ministry of Education, Science and Technological Development of Serbia. The authors declare that they have no conflict of interest.
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References [1] Dubey JP. Toxoplasmosis of animals and humans. 2nd ed. CRC Press, Taylor and Francis Group; 2010. [2] Robert-Gangneux F, Darde ML. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 2012; 25:264e96. [3] Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol 2000;30:1217e58. [4] Pappas G, Roussos N, Falagas ME. Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol 2009;39:1385e94. [5] Alvarado-Esquivel C, Sifuentes-Alvarez A, Narro-Duarte SG, Estrada-Martinez S, Diaz-Garcia JH, Liesenfeld O, et al. Seroepidemiology of Toxoplasma gondii infection in pregnant women in a public hospital in northern Mexico. BMC Infect Dis 2006;6:113. [6] Porto AM, Amorim MM, Coelho IC, Santos LC. Serologic profile of toxoplasmosis in pregnant women attended at a teachinghospital in Recife. Rev Assoc Med Bras 2008;54:242e8. [7] Bobic B, Nikolic A, Klun I, Djurkovic-Djakovic O. Kinetics of Toxoplasma infection in the Balkans. Wien Klin Wochenschr 2011;123:2e6. [8] Nogareda F, LE Strat Y, Villena I, DE Valk H, Goulet V. Incidence and prevalence of Toxoplasma gondii infection in women in France, 1980e2020: model-based estimation. Q8 Epidemiol Infect 2013;14:1e10. [9] Lelong B, Rahelimino B, Candolfi E, Ravelojaona BJ, Villard O, Rasamindrakotroka AJ, et al. Prevalence of toxoplasmosis in a population of pregnant women in Antananarivo (Madagascar). Bull Soc Pathol Exot 1995;88:46e9. [10] Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004;363: 1965e76. [11] Delair E, Monnet D, Grabar S, Dupouy-Camet J, Yera H, Brezin AP. Respective roles of acquired and congenital in-
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23] [24]
[25]
[26]
[27]
[28]
[29]
[30]
J.C. Sepu ´lveda-Arias et al. fections in presumed ocular toxoplasmosis. Am J Ophthalmol 2008;146:851e5. Montoya JG, Remington JS. Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis. Clin Infect Dis 1996; 23:277e82. Robertson LJ, van der Giessen JW, Batz MB, Kojima M, Cahill S. Have foodborne parasites finally become a global concern? Trends Parasitol 2013;29:101e3. Go ´mez-Marin JE. Protozoologia me ´dica: Protozoos para ´sitos en el contexto latinoamericano. 1st ed. 2010. Editorial Manual Moderno. Bowie WR, King AS, Werker DH, Isaac-Renton JL, Bell A, Eng SB, et al. Outbreak of toxoplasmosis associated with municipal drinking water. The BC Toxoplasma Investigation Team. Lancet 1997;350:173e7. Choi WY, Nam HW, Kwak NH, Huh W, Kim YR, Kang MW, et al. Foodborne outbreaks of human toxoplasmosis. J Infect Dis 1997;175:1280e2. Demar M, Ajzenberg D, Maubon D, Djossou F, Panchoe D, Punwasi W, et al. Fatal outbreak of human toxoplasmosis along the Maroni River: epidemiological, clinical, and parasitological aspects. Clin Infect Dis 2007;45:88e95. Ekman CC, Chiossi MF, Meireles LR, Andrade Jr HF, Figueiredo WM, Marciano MA, et al. Caseecontrol study of an outbreak of acute toxoplasmosis in an industrial plant in the state of Sao Paulo, Brazil. Rev Inst Med Trop Sao Paulo 2012; 54:239e44. Masur H, Jones TC, Lempert JA, Cherubini TD. Outbreak of toxoplasmosis in a family and documentation of acquired retinochoroiditis. Am J Med 1978;64:396e402. Bottieau E, Clerinx J, Van den Enden E, Van Esbroeck M, Colebunders R, Van Gompel A, et al. Infectious mononucleosis-like syndromes in febrile travelers returning from the tropics. J Travel Med 2006;13:191e7. Klemola E, Von Essen R, Henle G, Henle W. Infectiousmononucleosis-like disease with negative heterophil agglutination test. Clinical features in relation to EpsteineBarr virus and cytomegalovirus antibodies. J Infect Dis 1970;121: 608e14. Lajo A, Borque C, Del Castillo F, Martin-Ancel A. Mononucleosis caused by EpsteineBarr virus and cytomegalovirus in children: a comparative study of 124 cases. Pediatr Infect Dis J 1994;13:56e60. Montoya JG, Remington JS. Studies on the serodiagnosis of toxoplasmic lymphadenitis. Clin Infect Dis 1995;20:781e9. Durlach RA, Kaufer F, Carral L, Hirt J. Toxoplasmic lymphadenitiseclinical and serologic profile. Clin Microbiol Infect 2003;9:625e31. Carme B, Demar M, Ajzenberg D, Darde ML. Severe acquired toxoplasmosis caused by wild cycle of Toxoplasma gondii, French Guiana. Emerg Infect Dis 2009;15:656e8. Pino LE, Salinas JE, Lo ´pez MC. Descripcio ´n de un brote epide ´mico de toxoplasmosis aguda en pacientes inmunocompetentes miembros de las fuerzas militares de Colombia durante operaciones de selva. Infectio 2009;13:83e91. Sobanski V, Ajzenberg D, Delhaes L, Bautin N, Just N. Severe toxoplasmosis in immunocompetent hosts: be aware of atypical strains. Am J Respir Crit Care Med 2013;187:1143e5. Pomares C, Ajzenberg D, Bornard L, Bernardin G, Hasseine L, Darde ML, et al. Toxoplasmosis and horse meat, France. Emerg Infect Dis 2011;17:1327e8. de-la-Torre A, Sauer A, Pfaff AW, Bourcier T, Brunet J, SpeegSchatz C, et al. Severe South American ocular toxoplasmosis is associated with decreased IFN-gamma/IL-17a and increased IL-6/IL-13 intraocular levels. PLoS Negl Trop Dis 2013;7:e2541. Remington J, Mcleod R, Thulliez P, Desmonts G. Toxoplasmosis. In: Remington JSKJ, editor. Infectious diseases of the
[31]
[32]
[33]
[34]
[35] [36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
fetus and newborn infant. 5th ed. Philadelphia: WB Saunders; 2001. pp. 205e346. Montoya JG. Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis. J Infect Dis 2002;1l85(Suppl. 1): S73e82. Bobic B, Sibalic D, Djurkovic- Djakovic O. High levels of IgM antibodies specific for Toxoplasma gondii in pregnancy 12 years after primary Toxoplasma infection. Case report. Gynecol Obstet Invest 1991;31:182e4. Auer H, Vander-Mose A, Picher O, Walochnik J, Aspock H. Clinical and diagnostic relevance of the Toxoplasma IgG avidity test in the serological surveillance of pregnant women in Austria. Parasitol Res 2000;86:965e70. Liesenfeld O, Montoya JG, Kinney S, Press C, Remington JS. Effect of testing for IgG avidity in the diagnosis of Toxoplasma gondii infection in pregnant women: experience in a US reference laboratory. J Infect Dis 2001;183:1248e53. Hazell SL. Clinical utility of avidity assays. Expert Opin Med Diagn 2007;1:511e9. Decoster A, Gontier P, Dehecq E, Demory JL, Duhamel M. Detection of anti-Toxoplasma immunoglobulin A antibodies by Platelia-Toxo IgA directed against P30 and by IMx Toxo IgA for diagnosis of acquired and congenital toxoplasmosis. J Clin Microbiol 1995;33:2206e8. Nascimento FS, Suzuki LA, Rossi CL. Assessment of the value of detecting specific IgA antibodies for the diagnosis of a recently acquired primary Toxoplasma infection. Prenat Diagn 2008;28:749e52. Lynch LF, Lynch MI, Ferreira RS, Vasconcelos MS, Melo N, Ferreira S, et al. Ocular toxoplasmosis: evaluation of lacrimal-specific secretory IgA levels in both patients with active and inactive phases of the disease. Mem Inst Oswaldo Cruz 2011;106:625e8. James GS, Sintchenko VG, Dickeson DJ, Gilbert GL. Comparison of cell culture, mouse inoculation, and PCR for detection of Toxoplasma gondii: effects of storage conditions on sensitivity. J Clin Microbiol 1996;34:1572e5. Burg JL, Grover CM, Pouletty P, Boothroyd JC. Direct and sensitive detection of a pathogenic protozoan, Toxoplasma gondii, by polymerase chain reaction. J Clin Microbiol 1989; 27:1787e92. Homan WL, Vercammen M, De Braekeleer J, Verschueren H. Identification of a 200- to 300-fold repetitive 529 bp DNA fragment in Toxoplasma gondii, and its use for diagnostic and quantitative PCR. Int J Parasitol 2000;30:69e75. van de Ven E, Melchers W, Galama J, Camps W, Meuwissen J. Identification of Toxoplasma gondii infections by BI gene amplification. J Clin Microbiol 1991;29:2120e4. Robert-Gangneux F, Gavinet MF, Ancelle T, Raymond J, Tourte-Schaefer C, Dupouy-Camet J. Value of prenatal diagnosis and early postnatal diagnosis of congenital toxoplasmosis: retrospective study of 110 cases. J Clin Microbiol 1999;37:2893e8. Romand S, Wallon M, Franck J, Thulliez P, Peyron F, Dumon H. Prenatal diagnosis using polymerase chain reaction on amniotic fluid for congenital toxoplasmosis. Obstet Gynecol 2001;97:296e300. Thalib L, Gras L, Romand S, Prusa A, Bessieres MH, Petersen E, et al. Prediction of congenital toxoplasmosis by polymerase chain reaction analysis of amniotic fluid. BJOG: Int J Obstetrics Gynaecol 2005;112:567e74. Alavi SM, Alavi L. Treatment of toxoplasmic lymphadenitis with co-trimoxazole: double-blind, randomized clinical trial. Int J Infect Dis 2010;14(Suppl. 3):67e9. de-la-Torre A, Stanford M, Curi A, Jaffe GJ, Gomez-Marin JE. Therapy for ocular toxoplasmosis. Ocul Immunol Inflamm 2011;19:314e20.
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Toxoplasmosis as a travel risk [48] O’Connor GR, Frenkel JK. Editorial: dangers of steroid treatment in toxoplasmosis. Periocular injections and systemic therapy. Arch Ophthalmol 1976;94:213. [49] Sabates R, Pruett RC, Brockhurst RJ. Fulminant ocular toxoplasmosis. Am J Ophthalmol 1981;92:497e503. [50] de-la-Torre A, Rios-Cadavid AC, Cardozo-Garcia CM, GomezMarin JE. Frequency and factors associated with recurrences of ocular toxoplasmosis in a referral centre in Colombia. Br J Ophthalmol 2009;93:1001e4. [51] Boyer K, Hill D, Mui E, Wroblewski K, Karrison T, Dubey JP, et al. Unrecognized ingestion of Toxoplasma gondii oocysts leads to congenital toxoplasmosis and causes epidemics in North America. Clin Infect Dis 2011;53:1081e9. [52] Munoz-Zanzi CA, Fry P, Lesina B, Hill D. Toxoplasma gondii oocyst-specific antibodies and source of infection. Emerg Infect Dis 2010;16:1591e3. [53] Klun I, Djurkovi c-Djakovic O, Katic-Radivojevic S, Nikolic A. Cross-sectional survey on Toxoplasma gondii infection in cattle, sheep and pigs in Serbia: seroprevalence and risk factors. Vet Parasitol 2006;135:121e31. [54] Dubey JP, Su C. Population biology of Toxoplasma gondii: what’s out and where did they come from. Mem Inst Oswaldo Cruz 2009;104:190e5. [55] Cook AJ, Gilbert RE, Buffolano W, Zufferey J, Petersen E, Jenum PA, et al. Sources of Toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis. Br Med J 2000;321:142e7. [56] Anand R, Jones CW, Ricks JH, Sofarelli TA, Hale DC. Acute primary toxoplasmosis in travelers returning from endemic countries. J Travel Med 2012;19:57e60. [57] Jones JL, Muccioli C, Belfort Jr R, Holland GN, Roberts JM, Silveira C. Recently acquired Toxoplasma gondii infection. Braz Emerg Infect Dis 2006;12:582e7. [58] Howe DK, Sibley LD. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 1995;172:1561e6. [59] Sibley LD, Khan A, Ajioka JW, Rosenthal BM. Genetic diversity of Toxoplasma gondii in animals and humans. Philos Trans R Soc Lond B Biol Sci 2009;364:2749e61. [60] Ajzenberg D, Banuls AL, Su C, Dumetre A, Demar M, Carme B, et al. Genetic diversity, clonality and sexuality in Toxoplasma gondii. Int J Parasitol 2004;34:1185e96. [61] Mercier A, Devillard S, Ngoubangoye B, Bonnabau H, Banuls AL, Durand P, et al. Additional haplogroups of Toxoplasma gondii out of Africa: population structure and mousevirulence of strains from Gabon. PLoS Negl Trop Dis 2010;4: e876. [62] Khan A, Dubey JP, Su C, Ajioka JW, Rosenthal BM, Sibley LD. Genetic analyses of atypical Toxoplasma gondii strains reveal a fourth clonal lineage in North America. Int J Parasitol 2011; 41:645e55. [63] Ajzenberg D, Cogne N, Paris L, Bessieres MH, Thulliez P, Filisetti D, et al. Genotype of 86 Toxoplasma gondii isolates associated with human congenital toxoplasmosis, and correlation with clinical findings. J Infect Dis 2002;186:684e9. [64] Ajzenberg D, Yera H, Marty P, Paris L, Dalle F, Menotti J, et al. Genotype of 88 Toxoplasma gondii isolates associated with toxoplasmosis in immunocompromised patients and correlation with clinical findings. J Infect Dis 2009;199: 1155e67. [65] Nowakowska D, Colon I, Remington JS, Grigg M, Golab E, Wilczynski J, et al. Genotyping of Toxoplasma gondii by multiplex PCR and peptide-based serological testing of samples from infants in Poland diagnosed with congenital toxoplasmosis. J Clin Microbiol 2006;44:1382e9. [66] Djurkovi c-Djakovic O, Klun I, Khan A, Nikolic A, KnezevicUsaj S, Bobi c B, et al. A human origin type II strain of
9
[67]
[68] [69]
[70]
[71]
[72]
[73]
[74]
[75]
[76]
[77]
[78]
[79]
[80]
[81]
[82]
[83]
[84]
Toxoplasma gondii causing severe encephalitis in mice. Microbes Infect 2006;8:2206e12. Costache CA, Colosi HA, Blaga L, Gyorke A, Pastiu AI, Colosi IA, et al. First isolation and genetic characterization of a Toxoplasma gondii strain from a symptomatic human case of congenital toxoplasmosis in Romania. Parasite 2013;20:11. Ajzenberg D. Type I strains in human toxoplasmosis: myth or reality? Future Microbiol 2010;5:841e3. Doskaya M, Caner A, Ajzenberg D, Degirmenci A, Darde ML, Can H, et al. Isolation of Toxoplasma gondii strains similar to Africa 1 genotype in Turkey. Parasitol Int 2013;62:471e4. Stajner T, Vasiljevic Z, Vujic D, Markovic M, Ristic G, Micic D, et al. Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency. J Clin Microbiol 2013;51:2686e90. Peyron F, Lobry JR, Musset K, Ferrandiz J, Gomez-Marin JE, Petersen E, et al. Serotyping of Toxoplasma gondii in chronically infected pregnant women: predominance of type II in Europe and types I and III in Colombia (South America). Microbes Infect 2006;8:2333e40. Sanchez V, de-la-Torre A, Gomez-Marin JE. Characterization of ROP18 alleles in human toxoplasmosis. Parasitol Int 2014; 63:463e9. Elbez-Rubinstein A, Ajzenberg D, Darde ML, Cohen R, Dumetre A, Yera H, et al. Congenital toxoplasmosis and reinfection during pregnancy: case report, strain characterization, experimental model of reinfection, and review. J Infect Dis 2009;199:280e5. Demeester RP, Bottieau E, Pini A, Visser LG, TorrusTendero D, Wetsteyn JC, et al. Prospective multicenter evaluation of the expert system “KABISA TRAVEL” in diagnosing febrile illnesses occurring after a stay in the tropics. J Travel Med 2011;18:386e94. Wilson ME, Weld LH, Boggild A, Keystone JS, Kain KC, von Sonnenburg F, et al. Fever in returned travelers: results from the GeoSentinel Surveillance Network. Clin Infect Dis 2007; 44:1560e8. Abhilash KP, Roshine MK, Vandana K, Varghese GM. A probable case of acquired toxoplasmosis presenting as pyrexia of unknown origin in an immunocompetent individual. Int J Infect Dis 2013;17:e1067e8. Garweg JG, Scherrer JN, Halberstadt M. Recurrence characteristics in European patients with ocular toxoplasmosis. Br J Ophthalmol 2008;92:1253e6. de Moura L, Bahia-Oliveira LM, Wada MY, Jones JL, Tuboi SH, Carmo EH, et al. Waterborne toxoplasmosis, Brazil, from field to gene. Emerg Infect Dis 2006;12:326e9. Baril L, Ancelle T, Goulet V, Thulliez P, Tirard-Fleury V, Carme B. Risk factors for Toxoplasma infection in pregnancy: a case-control study in France. Scand J Infect Dis 1999;31: 305e9. Bobic B, Jevremovic I, Marinkovic J, Sibalic D, DjurkovicDjakovic O. Risk factors for Toxoplasma infection in a reproductive age female population in the area of Belgrade, Yugoslavia. Eur J Epidemiol 1998;14:605e10. Jones JL, Dargelas V, Roberts J, Press C, Remington JS, Montoya JG. Risk factors for Toxoplasma gondii infection in the United States. Clin Infect Dis 2009;49:878e84. Miller MA. Tissue cyst-forming coccidia of marine mammals. In: Fowler M, Miller R, editors. Zoo and wild animal medicine. Saunders Elsevier; 2008. pp. 319e40. Bahia-Oliveira LM, Jones JL, Azevedo-Silva J, Alves CC, Orefice F, Addiss DG. Highly endemic, waterborne toxoplasmosis in North Rio de Janeiro State, Brazil. Emerg Infect Dis 2003;9:55e62. Kapperud G, Jenum PA, Stray-Pedersen B, Melby KK, Eskild A, Eng J. Risk factors for Toxoplasma gondii infection in
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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10 pregnancy. Results of a prospective caseecontrol study in Norway. Am J Epidemiol 1996;144:405e12. [85] Thiebaut R, Leproust S, Chene G, Gilbert R. Effectiveness of prenatal treatment for congenital toxoplasmosis: a metaanalysis of individual patients’ data. Lancet 2007;369: 115e22.
J.C. Sepu ´lveda-Arias et al. [86] Rodgers CA, Harris JR. Ocular toxoplasmosis in HIV infection. Int J STD AIDS 1996;7:307e9. [87] Raffi F, Aboulker JP, Michelet C, Reliquet V, Pelloux H, Huart A, et al. A prospective study of criteria for the diagnosis of toxoplasmic encephalitis in 186 AIDS patients. The BIOTOXO Study Group. AIDS 1997;11:177e84.
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Travel Medicine and Infectious Disease (2014) xx, 1e10
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevierhealth.com/journals/tmid
REVIEW
Toxoplasmosis as a travel risk Q10
´mez-Marin c, ´lveda-Arias a,b,*, Jorge E. Go Juan C. Sepu d, Carlos A. Naranjo-Galvis a,e, Branko Bobic -Djakovic b,d Olgica Djurkovic a
Facultad de Ciencias de la Salud, Departamento de Ciencias Ba´sicas, Grupo Infeccio´n e Inmunidad,
Q2 Universidad Tecnolo ´gica de Pereira, Pereira, Colombia Q3 b Zoonoses of the International Society for Chemotherapy
(ISC), Colombia Facultad de Ciencias de la Salud, Grupo GEPAMOL, Centro de Investigaciones Biome´dicas, Universidad del Quindio, Armenia, Colombia d National Reference Laboratory for Toxoplasmosis, Institute for Medical Research, University of Belgrade, Dr. Subotica 4, P.O. Box 102, 11129 Belgrade, Serbia e Facultad de Salud, Universidad Auto´noma de Manizales, Manizales, Colombia c
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Received 18 February 2014; received in revised form 22 April 2014; accepted 23 May 2014
KEYWORDS
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Toxoplasmosis; Travelers; Clinical presentation; Treatment; Diagnosis; Strain genotypes; Prevention
Summary Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects more than one third of the global population. Primary infection in immunocompetent individuals is usually asymptomatic; however, different organs can be affected in immunocompromised individuals leading to the development of encephalitis, myocarditis or pneumonitis. The prevalence of infection with Toxoplasma as well as its genetic structure varies geographically and for that reason travel may be considered as a risk factor to acquire the infection. As toxoplasmosis is a foodborne disease, health care providers should give health education on prevention measures to all prospective travelers in order to decrease the risk of infection in endemic areas. This review presents an overview of the infection with T. gondii with some considerations for travelers to and from endemic zones. ª 2014 Published by Elsevier Ltd.
1. Introduction Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii which has the capacity to infect all warm-blooded animals. This parasite is responsible for
the most common parasitic zoonosis worldwide. The infection can be acquired by oral ingestion of infectious oocysts from the environment (water, soil, vegetables and fruits), by oral ingestion of tissue cysts contained in raw or undercooked meat, or by transplacental transmission of
* Corresponding author. Departamento de Ciencias Ba ´sicas, Facultad de Ciencias de la Salud, Universidad Tecnolo ´gica de Pereira, Pereira, Risaralda, Colombia. Tel.: þ57 6 3137127; fax: þ57 6 3216252. E-mail addresses: [email protected] (J.C. Sepu ´mez-Marin), [email protected] ´lveda-Arias), [email protected] (J.E. Go (B. Bobi c), [email protected] (C.A. Naranjo-Galvis), [email protected] (O. Djurkovic-Djakovic). http://dx.doi.org/10.1016/j.tmaid.2014.05.007 1477-8939/ª 2014 Published by Elsevier Ltd.
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2 tachyzoites (Fig. 1). By tachyzoites, Toxoplasma may also be transmitted by blood transfusion, organ transplantation or by consumption of unpasteurized goat milk [1e3]. Seroprevalence estimates for human populations vary greatly among countries (Fig. 2) and even among regions within a country [4]. Differences are huge, for instance, between North and South America where the seroprevalence is as low as 6.1% in Mexico whereas in some areas of Brazil it reaches 77.5% [5,6]. Seroprevalence in Europe also ranges widely, from 8.2% in Switzerland, to 57.6% in
J.C. Sepu ´lveda-Arias et al. Romania, but a common characteristic is a decrease over the past decades [7]. A most marked decrease has been shown in France, where the prevalence has decreased, from 83% in 1965 to 54% in 1995 and 44% in 2003, to 37% in 2010 [8]. Similarly, a decrease has been registered in SouthEast Europe, and currently does not surpass 50% across the region, ranging from 20% in Greece to 49% in Albania [7]. Variations in prevalence are observed in other regions of the world and the highest prevalence (83.5%) has been reported in Madagascar [9]. These variations can be
Fig. 1 Lyfe cycle of T. gondii (From http://www.dpd.cdc.gov/dpdx). Members of the cat family (Felidae) are the only known definitive hosts for the sexual stages of T. gondii and thus are the main reservoirs of infection. Cats become infected with T. gondii by carnivorism . After tissue cysts or oocysts are ingested by the cat, viable organisms are released and invade epithelial cells of the small intestine where they undergo an asexual followed by a sexual cycle and then form oocysts, which are excreted. The unsporulated oocyst takes 1e5 days after excretion to sporulate (become infective). Although cats shed oocysts for only 1e2 weeks, large numbers may be shed. Oocysts can survive in the environment for several months and are remarkably resistant to disinfectants, freezing, and drying, but are killed by heating to 70 C for 10 min. Human infection may be acquired in several ways: A) ingestion of undercooked infected meat containing Toxoplasma cysts ; B) ingestion of the oocyst from fecally contaminated hands or food ; C) organ transplantation or blood transfusion; D) transplacental transmission; E) accidental inoculation of tachyzoites. The parasites form tissue cysts, most commonly in skeletal muscle, myocardium, and brain; these cysts may remain throughout the life of the host.
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Toxoplasmosis as a travel risk
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Fig. 2 World map of global seroprevalence for T. gondii. Dark red equals prevalence above 60%, light red equals 40e60%, yellow 20e40%, blue 10e20% and green equals prevalence <10%. White equals absence of data (reproduced from Pappas G, et al. Int J Parasitol 2009; 39:1385e94, with permission from Elsevier). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
attributed to factors associated with the parasite strain (and genotype), geographic location and climatic conditions, cultural practices and ethnic group. Primary infection with Toxoplasma in immunocompetent individuals is usually asymptomatic, however, about 10% of the patients develop lymphadenitis or a mild flu-like syndrome or a mononucleosis-like illness [10]. Also, immunocompetent individuals may develop ocular toxoplasmosis (chorioretinitis) as a manifestation of primary infection [11,12]. Infection in immunocompromised individuals in most cases results from reactivation of a preexisting latent Toxoplasma infection. This reactivation can be lifethreatening, as it most often involves the central nervous system (SNC) and symptoms may include those of meningoencephalitis or mass lesion such as headache, confusion, fever, lethargy, seizures and focal neurological signs. Classically, congenital toxoplasmosis results from primary infection during pregnancy and the clinical presentation of the disease depends on numerous factors including gestational age, size of the inoculum, infecting form of the parasite, maternal treatment and genetic factors of the host and the parasite. Fetal infections may result in intrauterine death and spontaneous abortion, or in manifestations including hydrocephalus, microcephaly, macrocephaly, encephalitis, seizures, calcifications, chorioretinitis and blindness. Most importantly, clinical symptomatology is often absent at birth but untreated children develop late sequelae (chorioretinitis, neurological or cognitive disorders) [10]. The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) have recently established toxoplasmosis as a foodborne parasite infection of global concern [13]. Travelers (independent of previous contact with the parasite) may be at risk of infection with different parasite strains. In this review we present an overview of the infection by
Toxoplasma with some considerations for travelers to and from endemic zones.
2. Clinical presentation Acquired Toxoplasma infection in immunocompetent subjects is considered to be symptomatic only in 10e20% of the cases [14]. Indeed, no data exist on the percent of symptomatic people from longitudinal studies looking for symptoms in populations naturally exposed to this protozoan. The proportion of symptomatic people after a primary infection has been obtained from reports of outbreaks [15e18], but this information is influenced by high inocula, specificity of infection source and events that led to the infection [15e19]. Acute toxoplasmosis may resemble the clinical presentation of a cytomegalovirus or EpsteineBarr virus infection (infectious mononucleosis-like syndrome). This syndrome is characterized by the presence of fever, pharyngitis, lymphadenopathy and lymphomonocytosis [20e22]. And indeed, clinical series have shown that the most frequently observed clinical symptoms in acquired toxoplasmosis are non-tender and non-suppurative lymphadenopathies [19,23], of cervical (72,5%) (Fig. 3), axillary (20%) or occipital (7.5%) localization [23,24]. In a cohort report, 88% of cases presented more than one group of affected lymph nodes, usually located in the neck [24]. The associated clinical symptoms included asthenia and fever in 69e81% and 45e81% of cases, respectively, and sore throat in 15e20% of cases, as well as myalgia, arthralgia, splenomegaly and hepatomegaly [18,19,23,24]. Ocular involvement secondary to acquired toxoplasmosis has been reported to appear in 2e19% of cases [15e17,19]. Ocular symptoms appeared 14e87 days after infection in the Vancouver’s outbreak [15], two months after exposure to
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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Fig. 4 Retinal exudative lesion in acquired ocular toxoplasmosis. (Source: Dr. Jorge Enrique Go ´mez-Marin, Centro de Investigaciones Biome ´dicas, Armenia, Quindı´o, Colombia).
Fig. 3 Cervical lymphadenopathy in a patient after three months of untreated primary toxoplasmosis (Source: Dr. Jorge Enrique Go ´mez-Marin, Centro de Investigaciones Biome ´dicas, Armenia, Quindı´o, Colombia).
rare meat in Korea [16], and 120 days after a family outbreak in New York [19]. We observed the case of a tourist from Bogota ´ that visited a Caribbean region in the North of Colombia, who first developed glandular toxoplasmosis and ocular toxoplasmosis one month later (Go ´mez-Marin JE, unpublished observation), and another one of a tourist from Serbia who developed chorioretinitis simultaneously with generalized lymphadenopathy two weeks after returning from a vacation in the African island of Mauritius (Djurkovic-Djakovic O, unpublished observation). The ophthalmological examination usually reveals a focal necrotizing chorioretinitis accompanied by vitreous inflammatory reaction (Fig. 4). The main clinical presentations of toxoplasmosis are shown in Table 1. Severe forms of toxoplasmosis have been reported for infections acquired in the South American jungle, leading to respiratory and cardiac complications requiring hospitalizations in intensive care units to provide cardiac and respiratory support [25,26]. These severe forms were also reported in European people consuming meat originating from Brazil [27,28]. A recent study on the immune response in South American patients showed results consistent with the hypothesis that some South American strains may cause severe ocular toxoplasmosis due to an inhibition of the protective effect of IFN-g [29].
3. Diagnosis The specific diagnosis of Toxoplasma infection in humans is based on the use of various laboratory methodologies, including serology, histologic demonstration of the parasite
and/or its antigens, isolation of the organism (by bioassay or in cell culture), or the detection of its DNA, by amplification of specific nucleic acid sequences (polymerase chain reaction (PCR)-based techniques) [30]. Serological tests are the primary method of diagnosis and in general, a combination of tests is usually required to establish if the infection was acquired recently or in the past. The detection of specific IgG antibodies gives information about previous contact with Toxoplasma, which is important to evaluate in pregnant women and in immunocompromised patients (due to the risk of reactivation of a latent infection). IgG antibodies appear within 1e2 weeks of acquisition of the infection, peak within 1e2 months and then decline to levels that persist for the life of the individual [31]. Several serological test have been used to detect antigen-specific IgG antibodies, such as the SabinFeldman dye test (nowadays used in very few laboratories), the immunofluorescent antibody test, enzymelinked immunosorbent assay (ELISA) and direct agglutination. Determination of specific IgM antibodies may be useful to detect acute infection, but the interpretation of an IgM result is complicated by the fact that IgM antibodies can be detected long after acute infection [32]. Therefore the clinical history of the patient is important to help in the interpretation of the results. A useful complementary method is the measurement of Toxoplasma-specific IgG avidity, which is based on the increasing avidity of IgG antibodies for the antigen with the length of time that has elapsed since initial infection. A high avidity finding generally rules out infection within the last four months [33e35]. Specific IgA antibodies may be detected in acute infection, but their shorter duration [36] has been disputed [37]. Secretory IgA antibodies in tears have been suggested as a reliable marker of acute ocular toxoplasmosis [38]. However, direct detection of the parasite is required for the confirmation of the diagnosis in clinical situations such as fetal infection and diagnosis of reactivated toxoplasmosis.
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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Toxoplasmosis as a travel risk Table 1
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Main clinical presentations of toxoplasmosis.
Host immune status
Clinical presentation
Signs and symptoms
Percentagea [ref]
Immunocompetent
Asymptomatic Infectious mononucleosislike syndrome
None Cervical adenopathies Asthenia Fever Sore throat Chorioretinitis Ocular lesions Intracranial lesios Any clinical manifestation Chorioretinitis Focal signs Headache Motor-sensory defects Seizures Other neurological signs
80e90% [14e18] 75% [23,24] 69-81% [18,19,24] 45-81% [18,19,23] 15-20% [18,19,23] 2-19% [15e17,19] 18% [85] 13% [85] 24% [85] 1-21% [86] 70% [87] 55% [87] 49% [87] 22% [87] 8% [87]
Ocular toxoplasmosis Congenital toxoplasmosis
Immunocompromised
a
Ocular toxoplasmosis Toxoplasmic Encephalitis
Percentage of each sign or symptom with regard to clinical presentation. [ref] Reference.
For the isolation of the organism, the bioassay of suspected biological materials into laboratory mice is the “gold standard”. This assay is sensitive for virulent and avirulent strains and detects only viable parasites [39]. A number of PCR tests targeting different gene sequences of Toxoplasma have been developed to amplify parasite DNA [40e42] and to detect it in body fluids or other clinical samples. The PCR is recommended as a part of diagnostic procedure of fetal infection in the second trimester of pregnancy with high sensitivity and specificity [43e45].
4. Treatment Treatment of symptomatic toxoplasmosis in immunocompetent patients that acquire the infection in Europe or North America may only include alleviation of symptoms and decision on whether to treat with specific antibiotics is made on a case by case basis, whereas for infections acquired in South America, due to the presence of more virulent parasites and the possibility of ocular involvement, the use of specific antibiotics (in the absence of controlled studies) is recommended. A 1-month course of cotrimoxazole treatment (40 mg sulfamethoxazole/8 mg trimethoprim per kg of body weight) twice a day has been reported to be effective in a double-blind randomized trial [46]. Classical therapy for toxoplasmosis consists of pyrimethamine, sulfadiazine and folinic acid (Table 2A). In ocular toxoplasmosis oral prednisolone (1 mg/kg daily) is given from the third day of therapy and tapered over 2e6 weeks when there are macular lesions or neuritis [47]. A good response with resolution of inflammation and appearance of the characteristic lesion hyperpigmentation can be observed after 4e6 weeks of treatment. Folinic acid should be also administered to protect against anemia and leukopenia [47]. Corticosteroid therapy without the concomitant use of antimicrobial agents, even in immunocompetent patients, can lead to severe tissue destruction [48]. Fulminant Toxoplasma retinochoroiditis has also been
observed in patients treated with intravitreal steroids alone [49]. The use of systemic steroids without antibiotics and subconjunctival injection of steroids were identified as the main factors related to recurrence in a group of patients [50]. Therefore, the use of steroids alone to treat ocular toxoplasmosis can be harmful. Alternative therapies in case of toxicity, allergic reactions or unavailability of the first line antibiotics are shown in Table 2B.
5. Toxoplasmosis in travelers Since Toxoplasma is a ubiquitous parasite, exposure exists in any geographical area of the world and Toxoplasma infection has indeed been detected virtually worldwide, resulting in one third of the global population being infected [2]. However, the degree of exposure to different sources of infection varies significantly among geographic areas. The oocyst survives better in warm and moist areas than in cold and arid ones, and at lower altitudes. The proportion of infections caused by oocysts has been reported to be 78% in the United States [51] and 43% in Chile [52], as determined by a specific test that detects anti-oocyst antibodies. Consequently, 22% and 57% of all infections in the United States and Chile, respectively, may be attributed to cystcontaining meat. The range of seroprevalence in food animals varies as widely, from 1 to 99% [1,3,53]. The cat, however, seems to be necessary for the transmission to go on, since areas devoid of cats seem to be infection-free [54]. A cultural factor contributing to infection is human nutritional habits, which may differ even in geographically close areas, such as consumption of raw or rare meat in France as opposed to well-cooking in the neighboring Germany. In many countries, traditional cured meat (particularly pork) products have been associated with Toxoplasma infection [53,55]. As a result of all these factors, certain areas are characterized by more frequent Toxoplasma infection than others. Central America, South America and Africa are viewed by some as endemic areas for
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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Recommended dose of antibiotics for toxoplasmosis. A. First line antibiotics. B. Second line antibiotics.
A. First line antibiotics
B. Second line antibiotics
Drug
Adult dose
Pediatric dose
Pyrimethamine
200 mg oral first day followed by 75 mg once a day.
Sulfadiazine
4 g/day.
Folinic acid TMP-SMX
15 mg/day. TMP (160 mg)/SMX (800 mg) every 12 h. Or 2 pills TMP (80 mg/SMX (400 mg) every 12 h, for 6 weeks. 500 mg/day for 5 weeks. 1 mg intravitreal clindamycin and 400 mg dexamethasone.
2 mg/kg first dose and then 1 mg/kg day during one year (congenital form) or 4e5 weeks in acquired infections. 50 mg/kg twice daily (100 mg/kg/ dı´a) during one year in congenital infection or for 4e5 weeks in acquired forms. 7.5 mg/day. No reports for use in children with congenital forms.
Azithromycin Intravitreal clindamycin plus dexamethasonea
10 mg/kg/day during two months. Not reported.
Trimethoprim (TMP), Sulfamethoxazole (SMX). a In refractory cases to first and second line antibiotics in ocular toxoplasmosis.
toxoplasmosis. A report about Toxoplasma infection in Canadian travelers described 14 immunocompetent patients that returned with symptomatic primary toxoplasmosis from regions including Central America, South America, Africa and France [56]. In some areas of Brazil, the prevalence of ocular toxoplasmosis is 17% [57]. Although Toxoplasma was initially described as clonal, with three major lineages designated as types I, II and III, these are, with an emphasis on type II, only predominant in Europe and North America [58]. In South America and Africa, a higher frequency of non-clonal, highly polymorphic strains referred to as atypical has been revealed [59]. Moreover, specific African non-clonal genotypes, termed Africa 1, 2 and 3, have been identified [60,61]. But the picture is currently being complicated in the Western World as well, since a fourth clonal lineage (autochtonous haplogroup 12) has been recently described in North America [62]. In Europe, most data on human isolates originate from France, showing an overwhelming predominance (>90%) of type II [63,64]. This seems true of the rest of Europe as well, as virtually all typed isolates from cases of congenital toxoplasmosis (nine in Poland; one in Serbia and Romania each) [65e67] were type II. European immunosuppressed patients also predominantly reactivate type II strains [68]. Type II is also vastly predominant in animals in Europe, including wildlife [59]. The recent finding of the Africa 1 genotype in two human isolates from Turkey was associated with the geographical position of Turkey between Asia, Europe and Africa [69]. Similarly, the isolation of a non-clonal Toxoplasma strain in a hematopoietic stem cell transplant recipient in Serbia may indicate phylogenetic ties among Asian, African and European Toxoplasma populations [70]. Significant differences have been shown in the strains isolated from patients with ocular toxoplasmosis in France and Colombia [29,71]. Moreover, severe ocular inflammation
in Colombia was recently associated with infection by strains harboring the ROP18 type I allele [72]. The clinical severity of toxoplasmosis in South America is further illustrated by cases of fatal primary toxoplasmosis documented in immunocompetent adults in French Guiana and Surinam [17,25]. Furthermore, severe forms of myocarditis and pneumonitis have been reported in military personnel operating in the Colombian jungle [26]. This has been associated with differing patterns of the Toxoplasma population genetic structure in the (sub) tropical regions. Also, in the few cases of birth of a congenitally infected infant to a mother with serological evidence of past infection, re-infection with a strain of a different genotype has been discussed as the underlying reason [73]. In consequence, in the light of both the widely varying geographically-dependent prevalence of infection and the new knowledge on the geographic differences in the Toxoplasma population structure, travel may be a risk factor for Toxoplasma infection. Indeed, a European multicenter caseecontrol study of risk factors identified travel outside Europe, the United States and Canada as a strong predictor of acute infection in pregnant women [55]. Unimmunized travelers from areas of low to areas of high Toxoplasma prevalence may be at increased risk of infection. Furthermore, unimmunized travelers, and even those immunized, from Europe and North America, to Africa, Asia and South America, may be at risk of severe clinical entities caused by toxoplasmosis including ocular disease, pneumonia, and even life-threatening toxoplasmosis. Also, if pregnant women travel to tropical and subtropical areas, they may be at risk of (re)infection with atypical strains. Conversely, women born in the tropics, even if immunized against atypical Toxoplasma strains, could be at risk of re-infection by a type II strain if they travel to Europe or North America [73]. In the returning traveler, the presence of fever is challenging for the physician because of the broad differential
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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Toxoplasmosis as a travel risk diagnosis of this symptom [20]. Although malaria and dengue are the most common etiologies of fever in travelers [74,75], cosmopolitan infections such as toxoplasmosis, should be considered in the differential diagnosis of fever. Some case reports suggest that toxoplasmosis should be considered in the differential diagnosis of travelers with non-specific symptoms such as fatigue, fever, headache and lymphadenopathy [20,56,76]. In 72 prospectively studied travelers with the mononucleosis-like syndrome, toxoplasmosis was the cause in 22% and it was clinically indistinguishable of other causes [20].
6. Prevention Despite continuous efforts, there is yet no antitoxoplasmic vaccine for humans. The global spread of Toxoplasma infection, with a consequent worldwide risk of exposure to infection, and typically benign course of infection, do not provide justification for using chemoprophylaxis. Therefore, the only possible approach to prevent infection is health education. Question is ¿who should this target? Conventionally, pregnant women are the target population. However, new information on ocular toxoplasmosis calls for expanding the indications for implementation of preventive measures for toxoplasmosis from pregnant women and immunocompromised individuals to almost the whole population, especially under the age of 30 [77]. As the routes of infection are well established, measures for the prevention of primary Toxoplasma infection have long been well-known [1,3,53], and involve reduction of environmental risk and reduction of the risk of toxoplasmosis as a food/water-borne infection. Main measures to reduce the environmental risk include those to reduce environmental contamination (feeding cats only with commercial food or well-cooked meats, disinfecting the cat-litter box daily with boiling water for 5 min before refilling) [1] and those to reduce transmission to people, such as avoiding direct handling of stray cats, especially kittens, and avoiding contact with soil. While the measures to avoid environmental contamination are irrelevant to travelers, those to reduce the risk of transmission to individuals, particularly after exposure to cats or soil, are simple regular hands washing with soap and if possible, with warm water, most often feasible during travel [1]. The measures to reduce the risk of toxoplasmosis as a food/water-borne infection, including consumption of previously frozen meat; cooking with treated water [78]; careful washing of cutting boards, dishes, counters, utensils, and hands with hot soapy water after contact with raw meat, poultry, seafood, or unwashed fruits or vegetables; are not implementable by travelers, who by definition eat out of home and therefore have no control over food preparation [79]. However, the measures that travelers can abide with include avoiding to eat meat still pink in the center or undercooked poultry, smoked or dried meat [55,80,81], or fresh seafood [1,82]; peeling or thorough washing of fresh fruits and salads before eating; and drinking treated, preferably bottled, water [83,84]. New culinary experiences are part of the pleasure of traveling, which people cannot be expected to willingly deny themselves of. Therefore, given the potential food
7 hazards, health care providers should provide health education to all prospective travelers and insist on adherence to prevention measures in order to decrease the risk of infection in endemic areas. In returning travelers who present as patients, health care providers should consider toxoplasmosis, and in view of the increasing insight into the diverse clinical spectrum of toxoplasmosis, atypical presentations (such as pneumonitis or ocular toxoplasmosis) should be kept in mind. In pregnant women, diagnosis of acute toxoplasmosis should require appropriate treatment as a measure of secondary prevention i.e. prevention of vertical transmission.
Conflict of interest
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The authors declare that they have no conflict of interest.
Acknowledgments The authors gratefully acknowledge financial support from Universidad Tecnolo ´gica de Pereira, Colombia (Project 514-1), COLCIENCIAS, Colombia (Project 111056934589, Contrato 469-2013) and grant III 42019 from the Ministry of Education, Science and Technological Development of Serbia. The authors declare that they have no conflict of interest.
Q7
References [1] Dubey JP. Toxoplasmosis of animals and humans. 2nd ed. CRC Press, Taylor and Francis Group; 2010. [2] Robert-Gangneux F, Darde ML. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 2012; 25:264e96. [3] Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol 2000;30:1217e58. [4] Pappas G, Roussos N, Falagas ME. Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int J Parasitol 2009;39:1385e94. [5] Alvarado-Esquivel C, Sifuentes-Alvarez A, Narro-Duarte SG, Estrada-Martinez S, Diaz-Garcia JH, Liesenfeld O, et al. Seroepidemiology of Toxoplasma gondii infection in pregnant women in a public hospital in northern Mexico. BMC Infect Dis 2006;6:113. [6] Porto AM, Amorim MM, Coelho IC, Santos LC. Serologic profile of toxoplasmosis in pregnant women attended at a teachinghospital in Recife. Rev Assoc Med Bras 2008;54:242e8. [7] Bobic B, Nikolic A, Klun I, Djurkovic-Djakovic O. Kinetics of Toxoplasma infection in the Balkans. Wien Klin Wochenschr 2011;123:2e6. [8] Nogareda F, LE Strat Y, Villena I, DE Valk H, Goulet V. Incidence and prevalence of Toxoplasma gondii infection in women in France, 1980e2020: model-based estimation. Q8 Epidemiol Infect 2013;14:1e10. [9] Lelong B, Rahelimino B, Candolfi E, Ravelojaona BJ, Villard O, Rasamindrakotroka AJ, et al. Prevalence of toxoplasmosis in a population of pregnant women in Antananarivo (Madagascar). Bull Soc Pathol Exot 1995;88:46e9. [10] Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004;363: 1965e76. [11] Delair E, Monnet D, Grabar S, Dupouy-Camet J, Yera H, Brezin AP. Respective roles of acquired and congenital in-
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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8
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23] [24]
[25]
[26]
[27]
[28]
[29]
[30]
J.C. Sepu ´lveda-Arias et al. fections in presumed ocular toxoplasmosis. Am J Ophthalmol 2008;146:851e5. Montoya JG, Remington JS. Toxoplasmic chorioretinitis in the setting of acute acquired toxoplasmosis. Clin Infect Dis 1996; 23:277e82. Robertson LJ, van der Giessen JW, Batz MB, Kojima M, Cahill S. Have foodborne parasites finally become a global concern? Trends Parasitol 2013;29:101e3. Go ´mez-Marin JE. Protozoologia me ´dica: Protozoos para ´sitos en el contexto latinoamericano. 1st ed. 2010. Editorial Manual Moderno. Bowie WR, King AS, Werker DH, Isaac-Renton JL, Bell A, Eng SB, et al. Outbreak of toxoplasmosis associated with municipal drinking water. The BC Toxoplasma Investigation Team. Lancet 1997;350:173e7. Choi WY, Nam HW, Kwak NH, Huh W, Kim YR, Kang MW, et al. Foodborne outbreaks of human toxoplasmosis. J Infect Dis 1997;175:1280e2. Demar M, Ajzenberg D, Maubon D, Djossou F, Panchoe D, Punwasi W, et al. Fatal outbreak of human toxoplasmosis along the Maroni River: epidemiological, clinical, and parasitological aspects. Clin Infect Dis 2007;45:88e95. Ekman CC, Chiossi MF, Meireles LR, Andrade Jr HF, Figueiredo WM, Marciano MA, et al. Caseecontrol study of an outbreak of acute toxoplasmosis in an industrial plant in the state of Sao Paulo, Brazil. Rev Inst Med Trop Sao Paulo 2012; 54:239e44. Masur H, Jones TC, Lempert JA, Cherubini TD. Outbreak of toxoplasmosis in a family and documentation of acquired retinochoroiditis. Am J Med 1978;64:396e402. Bottieau E, Clerinx J, Van den Enden E, Van Esbroeck M, Colebunders R, Van Gompel A, et al. Infectious mononucleosis-like syndromes in febrile travelers returning from the tropics. J Travel Med 2006;13:191e7. Klemola E, Von Essen R, Henle G, Henle W. Infectiousmononucleosis-like disease with negative heterophil agglutination test. Clinical features in relation to EpsteineBarr virus and cytomegalovirus antibodies. J Infect Dis 1970;121: 608e14. Lajo A, Borque C, Del Castillo F, Martin-Ancel A. Mononucleosis caused by EpsteineBarr virus and cytomegalovirus in children: a comparative study of 124 cases. Pediatr Infect Dis J 1994;13:56e60. Montoya JG, Remington JS. Studies on the serodiagnosis of toxoplasmic lymphadenitis. Clin Infect Dis 1995;20:781e9. Durlach RA, Kaufer F, Carral L, Hirt J. Toxoplasmic lymphadenitiseclinical and serologic profile. Clin Microbiol Infect 2003;9:625e31. Carme B, Demar M, Ajzenberg D, Darde ML. Severe acquired toxoplasmosis caused by wild cycle of Toxoplasma gondii, French Guiana. Emerg Infect Dis 2009;15:656e8. Pino LE, Salinas JE, Lo ´pez MC. Descripcio ´n de un brote epide ´mico de toxoplasmosis aguda en pacientes inmunocompetentes miembros de las fuerzas militares de Colombia durante operaciones de selva. Infectio 2009;13:83e91. Sobanski V, Ajzenberg D, Delhaes L, Bautin N, Just N. Severe toxoplasmosis in immunocompetent hosts: be aware of atypical strains. Am J Respir Crit Care Med 2013;187:1143e5. Pomares C, Ajzenberg D, Bornard L, Bernardin G, Hasseine L, Darde ML, et al. Toxoplasmosis and horse meat, France. Emerg Infect Dis 2011;17:1327e8. de-la-Torre A, Sauer A, Pfaff AW, Bourcier T, Brunet J, SpeegSchatz C, et al. Severe South American ocular toxoplasmosis is associated with decreased IFN-gamma/IL-17a and increased IL-6/IL-13 intraocular levels. PLoS Negl Trop Dis 2013;7:e2541. Remington J, Mcleod R, Thulliez P, Desmonts G. Toxoplasmosis. In: Remington JSKJ, editor. Infectious diseases of the
[31]
[32]
[33]
[34]
[35] [36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
fetus and newborn infant. 5th ed. Philadelphia: WB Saunders; 2001. pp. 205e346. Montoya JG. Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis. J Infect Dis 2002;1l85(Suppl. 1): S73e82. Bobic B, Sibalic D, Djurkovic- Djakovic O. High levels of IgM antibodies specific for Toxoplasma gondii in pregnancy 12 years after primary Toxoplasma infection. Case report. Gynecol Obstet Invest 1991;31:182e4. Auer H, Vander-Mose A, Picher O, Walochnik J, Aspock H. Clinical and diagnostic relevance of the Toxoplasma IgG avidity test in the serological surveillance of pregnant women in Austria. Parasitol Res 2000;86:965e70. Liesenfeld O, Montoya JG, Kinney S, Press C, Remington JS. Effect of testing for IgG avidity in the diagnosis of Toxoplasma gondii infection in pregnant women: experience in a US reference laboratory. J Infect Dis 2001;183:1248e53. Hazell SL. Clinical utility of avidity assays. Expert Opin Med Diagn 2007;1:511e9. Decoster A, Gontier P, Dehecq E, Demory JL, Duhamel M. Detection of anti-Toxoplasma immunoglobulin A antibodies by Platelia-Toxo IgA directed against P30 and by IMx Toxo IgA for diagnosis of acquired and congenital toxoplasmosis. J Clin Microbiol 1995;33:2206e8. Nascimento FS, Suzuki LA, Rossi CL. Assessment of the value of detecting specific IgA antibodies for the diagnosis of a recently acquired primary Toxoplasma infection. Prenat Diagn 2008;28:749e52. Lynch LF, Lynch MI, Ferreira RS, Vasconcelos MS, Melo N, Ferreira S, et al. Ocular toxoplasmosis: evaluation of lacrimal-specific secretory IgA levels in both patients with active and inactive phases of the disease. Mem Inst Oswaldo Cruz 2011;106:625e8. James GS, Sintchenko VG, Dickeson DJ, Gilbert GL. Comparison of cell culture, mouse inoculation, and PCR for detection of Toxoplasma gondii: effects of storage conditions on sensitivity. J Clin Microbiol 1996;34:1572e5. Burg JL, Grover CM, Pouletty P, Boothroyd JC. Direct and sensitive detection of a pathogenic protozoan, Toxoplasma gondii, by polymerase chain reaction. J Clin Microbiol 1989; 27:1787e92. Homan WL, Vercammen M, De Braekeleer J, Verschueren H. Identification of a 200- to 300-fold repetitive 529 bp DNA fragment in Toxoplasma gondii, and its use for diagnostic and quantitative PCR. Int J Parasitol 2000;30:69e75. van de Ven E, Melchers W, Galama J, Camps W, Meuwissen J. Identification of Toxoplasma gondii infections by BI gene amplification. J Clin Microbiol 1991;29:2120e4. Robert-Gangneux F, Gavinet MF, Ancelle T, Raymond J, Tourte-Schaefer C, Dupouy-Camet J. Value of prenatal diagnosis and early postnatal diagnosis of congenital toxoplasmosis: retrospective study of 110 cases. J Clin Microbiol 1999;37:2893e8. Romand S, Wallon M, Franck J, Thulliez P, Peyron F, Dumon H. Prenatal diagnosis using polymerase chain reaction on amniotic fluid for congenital toxoplasmosis. Obstet Gynecol 2001;97:296e300. Thalib L, Gras L, Romand S, Prusa A, Bessieres MH, Petersen E, et al. Prediction of congenital toxoplasmosis by polymerase chain reaction analysis of amniotic fluid. BJOG: Int J Obstetrics Gynaecol 2005;112:567e74. Alavi SM, Alavi L. Treatment of toxoplasmic lymphadenitis with co-trimoxazole: double-blind, randomized clinical trial. Int J Infect Dis 2010;14(Suppl. 3):67e9. de-la-Torre A, Stanford M, Curi A, Jaffe GJ, Gomez-Marin JE. Therapy for ocular toxoplasmosis. Ocul Immunol Inflamm 2011;19:314e20.
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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Toxoplasmosis as a travel risk [48] O’Connor GR, Frenkel JK. Editorial: dangers of steroid treatment in toxoplasmosis. Periocular injections and systemic therapy. Arch Ophthalmol 1976;94:213. [49] Sabates R, Pruett RC, Brockhurst RJ. Fulminant ocular toxoplasmosis. Am J Ophthalmol 1981;92:497e503. [50] de-la-Torre A, Rios-Cadavid AC, Cardozo-Garcia CM, GomezMarin JE. Frequency and factors associated with recurrences of ocular toxoplasmosis in a referral centre in Colombia. Br J Ophthalmol 2009;93:1001e4. [51] Boyer K, Hill D, Mui E, Wroblewski K, Karrison T, Dubey JP, et al. Unrecognized ingestion of Toxoplasma gondii oocysts leads to congenital toxoplasmosis and causes epidemics in North America. Clin Infect Dis 2011;53:1081e9. [52] Munoz-Zanzi CA, Fry P, Lesina B, Hill D. Toxoplasma gondii oocyst-specific antibodies and source of infection. Emerg Infect Dis 2010;16:1591e3. [53] Klun I, Djurkovi c-Djakovic O, Katic-Radivojevic S, Nikolic A. Cross-sectional survey on Toxoplasma gondii infection in cattle, sheep and pigs in Serbia: seroprevalence and risk factors. Vet Parasitol 2006;135:121e31. [54] Dubey JP, Su C. Population biology of Toxoplasma gondii: what’s out and where did they come from. Mem Inst Oswaldo Cruz 2009;104:190e5. [55] Cook AJ, Gilbert RE, Buffolano W, Zufferey J, Petersen E, Jenum PA, et al. Sources of Toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis. Br Med J 2000;321:142e7. [56] Anand R, Jones CW, Ricks JH, Sofarelli TA, Hale DC. Acute primary toxoplasmosis in travelers returning from endemic countries. J Travel Med 2012;19:57e60. [57] Jones JL, Muccioli C, Belfort Jr R, Holland GN, Roberts JM, Silveira C. Recently acquired Toxoplasma gondii infection. Braz Emerg Infect Dis 2006;12:582e7. [58] Howe DK, Sibley LD. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 1995;172:1561e6. [59] Sibley LD, Khan A, Ajioka JW, Rosenthal BM. Genetic diversity of Toxoplasma gondii in animals and humans. Philos Trans R Soc Lond B Biol Sci 2009;364:2749e61. [60] Ajzenberg D, Banuls AL, Su C, Dumetre A, Demar M, Carme B, et al. Genetic diversity, clonality and sexuality in Toxoplasma gondii. Int J Parasitol 2004;34:1185e96. [61] Mercier A, Devillard S, Ngoubangoye B, Bonnabau H, Banuls AL, Durand P, et al. Additional haplogroups of Toxoplasma gondii out of Africa: population structure and mousevirulence of strains from Gabon. PLoS Negl Trop Dis 2010;4: e876. [62] Khan A, Dubey JP, Su C, Ajioka JW, Rosenthal BM, Sibley LD. Genetic analyses of atypical Toxoplasma gondii strains reveal a fourth clonal lineage in North America. Int J Parasitol 2011; 41:645e55. [63] Ajzenberg D, Cogne N, Paris L, Bessieres MH, Thulliez P, Filisetti D, et al. Genotype of 86 Toxoplasma gondii isolates associated with human congenital toxoplasmosis, and correlation with clinical findings. J Infect Dis 2002;186:684e9. [64] Ajzenberg D, Yera H, Marty P, Paris L, Dalle F, Menotti J, et al. Genotype of 88 Toxoplasma gondii isolates associated with toxoplasmosis in immunocompromised patients and correlation with clinical findings. J Infect Dis 2009;199: 1155e67. [65] Nowakowska D, Colon I, Remington JS, Grigg M, Golab E, Wilczynski J, et al. Genotyping of Toxoplasma gondii by multiplex PCR and peptide-based serological testing of samples from infants in Poland diagnosed with congenital toxoplasmosis. J Clin Microbiol 2006;44:1382e9. [66] Djurkovi c-Djakovic O, Klun I, Khan A, Nikolic A, KnezevicUsaj S, Bobi c B, et al. A human origin type II strain of
9
[67]
[68] [69]
[70]
[71]
[72]
[73]
[74]
[75]
[76]
[77]
[78]
[79]
[80]
[81]
[82]
[83]
[84]
Toxoplasma gondii causing severe encephalitis in mice. Microbes Infect 2006;8:2206e12. Costache CA, Colosi HA, Blaga L, Gyorke A, Pastiu AI, Colosi IA, et al. First isolation and genetic characterization of a Toxoplasma gondii strain from a symptomatic human case of congenital toxoplasmosis in Romania. Parasite 2013;20:11. Ajzenberg D. Type I strains in human toxoplasmosis: myth or reality? Future Microbiol 2010;5:841e3. Doskaya M, Caner A, Ajzenberg D, Degirmenci A, Darde ML, Can H, et al. Isolation of Toxoplasma gondii strains similar to Africa 1 genotype in Turkey. Parasitol Int 2013;62:471e4. Stajner T, Vasiljevic Z, Vujic D, Markovic M, Ristic G, Micic D, et al. Atypical strain of Toxoplasma gondii causing fatal reactivation after hematopoietic stem cell transplantion in a patient with an underlying immunological deficiency. J Clin Microbiol 2013;51:2686e90. Peyron F, Lobry JR, Musset K, Ferrandiz J, Gomez-Marin JE, Petersen E, et al. Serotyping of Toxoplasma gondii in chronically infected pregnant women: predominance of type II in Europe and types I and III in Colombia (South America). Microbes Infect 2006;8:2333e40. Sanchez V, de-la-Torre A, Gomez-Marin JE. Characterization of ROP18 alleles in human toxoplasmosis. Parasitol Int 2014; 63:463e9. Elbez-Rubinstein A, Ajzenberg D, Darde ML, Cohen R, Dumetre A, Yera H, et al. Congenital toxoplasmosis and reinfection during pregnancy: case report, strain characterization, experimental model of reinfection, and review. J Infect Dis 2009;199:280e5. Demeester RP, Bottieau E, Pini A, Visser LG, TorrusTendero D, Wetsteyn JC, et al. Prospective multicenter evaluation of the expert system “KABISA TRAVEL” in diagnosing febrile illnesses occurring after a stay in the tropics. J Travel Med 2011;18:386e94. Wilson ME, Weld LH, Boggild A, Keystone JS, Kain KC, von Sonnenburg F, et al. Fever in returned travelers: results from the GeoSentinel Surveillance Network. Clin Infect Dis 2007; 44:1560e8. Abhilash KP, Roshine MK, Vandana K, Varghese GM. A probable case of acquired toxoplasmosis presenting as pyrexia of unknown origin in an immunocompetent individual. Int J Infect Dis 2013;17:e1067e8. Garweg JG, Scherrer JN, Halberstadt M. Recurrence characteristics in European patients with ocular toxoplasmosis. Br J Ophthalmol 2008;92:1253e6. de Moura L, Bahia-Oliveira LM, Wada MY, Jones JL, Tuboi SH, Carmo EH, et al. Waterborne toxoplasmosis, Brazil, from field to gene. Emerg Infect Dis 2006;12:326e9. Baril L, Ancelle T, Goulet V, Thulliez P, Tirard-Fleury V, Carme B. Risk factors for Toxoplasma infection in pregnancy: a case-control study in France. Scand J Infect Dis 1999;31: 305e9. Bobic B, Jevremovic I, Marinkovic J, Sibalic D, DjurkovicDjakovic O. Risk factors for Toxoplasma infection in a reproductive age female population in the area of Belgrade, Yugoslavia. Eur J Epidemiol 1998;14:605e10. Jones JL, Dargelas V, Roberts J, Press C, Remington JS, Montoya JG. Risk factors for Toxoplasma gondii infection in the United States. Clin Infect Dis 2009;49:878e84. Miller MA. Tissue cyst-forming coccidia of marine mammals. In: Fowler M, Miller R, editors. Zoo and wild animal medicine. Saunders Elsevier; 2008. pp. 319e40. Bahia-Oliveira LM, Jones JL, Azevedo-Silva J, Alves CC, Orefice F, Addiss DG. Highly endemic, waterborne toxoplasmosis in North Rio de Janeiro State, Brazil. Emerg Infect Dis 2003;9:55e62. Kapperud G, Jenum PA, Stray-Pedersen B, Melby KK, Eskild A, Eng J. Risk factors for Toxoplasma gondii infection in
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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TMAID748_proof ■ 10 June 2014 ■ 10/10
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10 pregnancy. Results of a prospective caseecontrol study in Norway. Am J Epidemiol 1996;144:405e12. [85] Thiebaut R, Leproust S, Chene G, Gilbert R. Effectiveness of prenatal treatment for congenital toxoplasmosis: a metaanalysis of individual patients’ data. Lancet 2007;369: 115e22.
J.C. Sepu ´lveda-Arias et al. [86] Rodgers CA, Harris JR. Ocular toxoplasmosis in HIV infection. Int J STD AIDS 1996;7:307e9. [87] Raffi F, Aboulker JP, Michelet C, Reliquet V, Pelloux H, Huart A, et al. A prospective study of criteria for the diagnosis of toxoplasmic encephalitis in 186 AIDS patients. The BIOTOXO Study Group. AIDS 1997;11:177e84.
Please cite this article in press as: Sepu ´lveda-Arias JC, et al., Toxoplasmosis as a travel risk, Travel Medicine and Infectious Disease (2014), http://dx.doi.org/10.1016/j.tmaid.2014.05.007
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