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Toxoplasmosis
Infection Toxoplasma Gondii
Toxoplasmosis is an infectious disease caused by the protozoan Toxoplasma gondii. In an immunocompetent host, infection is generally asymptomatic, but toxoplasmosis in pregnancy can cause birth defects.

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WIKIDATA, Public Domain
WIKIDATA, CC BY-SA 3.0

Presentation

Asymptomatic lymphadenopathy is the most usual presentation. The main lymph nodes involved are cervical and suboccipital. Fever, malaise and generalised rash will also be present. The clinical picture is very similar to infectious mononucleosis.

Neurological symptoms include neck stiffness and headache. Maculopapular rashes are also present. An acute febrile illness with maculopapular rash and hepatosplenomegaly, uveitis, chorioretinitis and myocarditis may also present.

In an immunosuppressed individual, febrile and neurological symptoms [7] are very prominent. In all AIDS cases, disease occurs in the CNS where tachyzoites causes necrosis, vasculitis, haemorrhage, oedema and inflammation. Patients are often drowsy, disoriented, confused and may have fever. Seizures may occur [8].

Congenital toxoplasmosis exhibits signs and symptoms which are indicative of CNS involvement. The characteristic syndrome of Savin which includes internal hydrocephalus, chorioretinitis and convulsions is common. Tremors, nystagmus, microopthalmia and pneumonitis may also be present. Complications in infants can manifest as mental retardation, spastic paraplegia or epilepsy [9].

Immune System

  • Cervical Lymphadenopathy

    Primary infection is usually subclinical but in some patients cervical lymphadenopathy or ocular disease can be present. Infection acquired during pregnancy may cause severe damage to the fetus. [ncbi.nlm.nih.gov]

    Clinical signs include: Fever, Skin eruption, Malaise, Myalgia and arthralgia, Cervical lymphadenopathy, Pneumonia, Myocarditis, Meningoencephalitis, Chorioretinitis Post-mortem findings In cattle, multiple, proliferative necrotic granulomas in the lungs [lrd.spc.int]

    Table 1: Toxoplasma serostatus and risk of toxoplasmosis in transplant recipients Click here to view In immunocompetent individuals, in more than 80% of cases, there is an asymptomatic infection. [22] In the remaining cases, fever, cervical lymphadenopathy [doi.org]

    Ivanova et al. [86] described a case of 46-year-old male patient with acute toxoplasma lymphadenitis, similar to malignant cervical lymphadenopathy. [intechopen.com]

  • Generalized Lymphadenopathy

    When present, clinical manifestations at birth are maculopapular rash, jaundice, generalized lymphadenopathy, organomegaly, central nervous system anomalies and hyperbilirubinemia, anemia, and thrombocytopenia. [orpha.net]

    The most common sign is generalized lymphadenopathy, which occurs in up to 20% of patients.149 Symptomatic CNS toxoplasmosis rarely develops during primary infection in normal hosts, but unusual cases of CNS involvement in immunocompetent patients can [epilepsy.com]

Entire Body System

  • Fever

    Congenitally affected calves show fever, dyspnoea, coughing, sneezing and neurological signs. If the disease occurs in adults, symptoms include fever, dyspnoea, and nervous signs, followed by lethargy. [lrd.spc.int]

    After some time, the baby presented fever and cervical lymphadenitis. [ncbi.nlm.nih.gov]

    Those which survive may show show lack of appetite, fever, dyspnea, and jaundice. Causes Cats become infected through contact with the T. gondii parasite, which may be acquired from rooting in infected soil or from ingesting cat feces. [petmd.com]

    Fatigue Fever Swollen lymph nodes Sometimes there are no symptoms at all How common is toxoplasmosis? Toxoplasmosis is most common in areas with warm, moist climates. [americanpregnancy.org]

    These symptoms include: Confusion Fever Headache Blurred vision Seizures What Do I Do? Most people with toxoplasmosis don't need treatment. [foodsafety.gov]

  • Hunting

    Cats get infected by hunting and eating prey, eating raw food diets, or by inadvertently licking oocysts during grooming. [veterinarypartner.com]

    Most responsible pet owners keep their domestic cats indoors and restrict their hunting activities, minimising the risk of infection. But feral cats need to hunt and kill to survive. [web.archive.org]

    Cats most often become carriers of toxoplasmosis by killing and eating wild animals who have been infected-a good reason not to let your cat outside to hunt! [pets.webmd.com]

    Discourage pet cats from hunting. Since eating rodents and birds infects cats, pet cats that do not hunt will not be exposed and do not pose a risk to their owners. [sahealth.sa.gov.au]

  • Lymphadenopathy

    A lower increase was observed for patients with lymphadenopathy of ≥3 months’ duration (P = 0.01). [cvi.asm.org]

    After having obtained an insufficient evidence from the fine-needle biopsy, the patient finally received an excisional biopsy which highly indicated the possibility of lymphadenopathy consistent with toxoplasmosis. [ncbi.nlm.nih.gov]

    In some casejust a lymphadenopathy. Congenitally affected calves show fever, dyspnoea, coughing, sneezing and neurological signs. If the disease occurs in adults, symptoms include fever, dyspnoea, and nervous signs, followed by lethargy. [lrd.spc.int]

  • Malaise

    Symptoms may occur following an incubation period of one to two weeks after exposure and include mild fever, swollen glands, malaise, muscle and/or joint pain, headache, sore throat, and skin rash. [aapos.org]

    A symptomatic infection most often produces swollen glands in the neck and armpits (which may result in the mistaken diagnosis of infectious mononucleosis); other symptoms may include fatigue, malaise, muscle pain and a fluctuating low fever. [web.archive.org]

    Fever, malaise and generalised rash will also be present. The clinical picture is very similar to infectious mononucleosis. Neurological symptoms include neck stiffness and headache. Maculopapular rashes are also present. [symptoma.com]

    Clinical signs include: Fever, Skin eruption, Malaise, Myalgia and arthralgia, Cervical lymphadenopathy, Pneumonia, Myocarditis, Meningoencephalitis, Chorioretinitis Post-mortem findings In cattle, multiple, proliferative necrotic granulomas in the lungs [lrd.spc.int]

    The illness may mimic glandular fever, with other symptoms of muscle pain, intermittent fever and malaise. Dormant infection persists for life and can reactivate in the immunosuppressed person. [www2.health.vic.gov.au]

  • Fatigue

    Fatigue Fever Swollen lymph nodes Sometimes there are no symptoms at all How common is toxoplasmosis? Toxoplasmosis is most common in areas with warm, moist climates. [americanpregnancy.org]

    Some people, however, develop signs and symptoms similar to those of the flu, including: Body aches Swollen lymph nodes Headache Fever Fatigue In people with weakened immune systems If you have HIV/AIDS, are receiving chemotherapy or have recently had [web.archive.org]

    She said that the symptoms of toxoplasmosis are vague, but include fatigue, headache, sore throat, aching muscles and sometimes fever. [irishhealth.com]

    However, immunodeficient individuals may experience body aches, swollen lymph nodes, head ache, fever, or fatigue. Babies of pregnant mothers are usually the most potent victims as congenital toxoplasmosis can result to fetal death. [news.abs-cbn.com]

    Symptoms appear around 2/3 weeks after you have been exposed to the infection and include headaches, aches and pains, fatigue and flu-like symptoms. [mummypages.ie]

Gastrointestinal

  • Diarrhea

    Signs of infection include fever, diarrhea, cough, difficulty breathing, jaundice, seizures, and death. Adult animals with weakened immune systems are extremely susceptible to developing sudden, generalized toxoplasmosis. [merckvetmanual.com]

    Such symptoms include: Lethargy Depression Fever Weight loss Respiratory problems, like shortness of breath Uncoordinated gait Seizures Tremors Muscular weakness Partial or complete paralysis Vomiting Diarrhea Abdominal Pain Jaundice Loss of appetite [petmd.com]

    It is believed that toxoplasmosis may trigger transient diarrhea in some cats. Very rarely, Toxoplasma may spread widely throughout the cat's body, leading to neurological problems or death. [drbarchas.com]

    When the cat gets infected, the early stages involve an intestinal form where the contagious oocysts are shed in feces but the cat may or may not have any diarrhea. [veterinarypartner.com]

    A smaller number of cats might develop diarrhea, or respiratory problems, or even problems with their eyes. The majority of cats, though, will be permanently infected with the parasite and show no outward signs of illness. [petsandparasites.org]

  • Abdominal Pain

    Such symptoms include: Lethargy Depression Fever Weight loss Respiratory problems, like shortness of breath Uncoordinated gait Seizures Tremors Muscular weakness Partial or complete paralysis Vomiting Diarrhea Abdominal Pain Jaundice Loss of appetite [petmd.com]

    pain, rash or neurological symptoms. [drugs.com]

    Symptoms of toxoplasmosis in cats can include: ( 8 ) lethargy or depression weight loss fever breathing problems seizures or tremors uncoordinated gait muscular weakness partial or complete paralysis vomiting diarrhea abdominal pain jaundice loss of appetite [draxe.com]

    In immune competent adults during the acute stage, mild and non-specific flu-like symptoms occur, such as fever, myalgia, enlarged lymph nodes, sore throat, and abdominal pain ( Anand et al., 2012 ). [waterpathogens.org]

Liver, Gall & Pancreas

  • Hepatomegaly

    […] infection can be accompanied by a plethora of symptoms, ranging from the most common encephalomyelitis, retinochoroiditis, intracranial calcification and hydrocephalus to the non-specific symptoms of acute infection such as convulsion, splenomegaly, hepatomegaly [fao.org]

    Intracranial calcifications, micro- or macrocephaly, ventricular dilatation and hydrocephalus, hepatomegaly, splenomegaly, cardiomegaly, ascites and intrauterine growth retardation can be observed in infected fetuses. [orpha.net]

    There may be ventriculomegaly, CNS calcifications, placental changes, hepatomegaly, splenomegaly, ascites and pericardial or pleural effusion [ 3 ]. [patient.info]

Eyes

  • Blurred Vision

    The signs and symptoms of severe toxoplasmosis — blurred vision, confusion, loss of coordination — require immediate medical care, particularly if your immune system has been weakened. [web.archive.org]

    A 68-year-old patient with normal immunity was complained about blurred vision and black shadow in the right eye for 1 week. [ncbi.nlm.nih.gov]

    Eye symptoms vary, but may include blurred vision or floaters during active disease. The diagnosis can be confirmed by detecting antibodies to Toxoplasma in the blood. [aapos.org]

Musculoskeletal

  • Myalgia

    Pulmonary toxoplasmosis is a serious pulmonary condition caused by the protozoan Toxoplasma gondii It typically affects immunocompromised patients presenting acutely with cough, fever, myalgias, arthralgias and lymphadenopathy, and chronically with persistent [ncbi.nlm.nih.gov]

    Clinical signs include: Fever, Skin eruption, Malaise, Myalgia and arthralgia, Cervical lymphadenopathy, Pneumonia, Myocarditis, Meningoencephalitis, Chorioretinitis Post-mortem findings In cattle, multiple, proliferative necrotic granulomas in the lungs [lrd.spc.int]

    A few of these also have a mild flu-like syndrome of fever, malaise, myalgia, hepatosplenomegaly, and less commonly, pharyngitis, which can mimic infectious mononucleosis and include lymphadenitis. [merckmanuals.com]

    As cysts (filled with bradyzoites) have predilection for neural, ocular and muscle cells, reactivation (tachyzoites) will often present as chorioretinitis, myalgias and cerebral toxoplasmosis, which is usually fatal if left untreated. II. [clinicaladvisor.com]

Face, Head & Neck

  • Neck Swelling

    Here we describe a 50-year-old woman presented with a progressive, painful, submental and left neck swelling for 1 month. [ncbi.nlm.nih.gov]

Neurologic

  • Headache

    These symptoms include: Confusion Fever Headache Blurred vision Seizures What Do I Do? Most people with toxoplasmosis don't need treatment. [foodsafety.gov]

    Some people, however, develop signs and symptoms similar to those of the flu, including: Body aches Swollen lymph nodes Headache Fever Fatigue In people with weakened immune systems If you have HIV/AIDS, are receiving chemotherapy or have recently had [web.archive.org]

    Confusion Fever Headache Blurred vision due to inflammation of the retina Seizures People without symptoms usually do not need treatment. [medlineplus.gov]

    […] toxoplasmosis (except in immunocompromised patients) in alterations of behavioral parameters and also its role in the etiology of schizophrenia and depressive disorders, obsessive-compulsive disorder, Alzheimer's diseases and Parkinson's disease, epilepsy, headache [ncbi.nlm.nih.gov]

Workup

Many cases of toxoplasmosis go undetected as the patient exhibits no signs and symptoms; it may be an incidental finding. Serological tests are the mainstay of diagnosis for acquired infections [10].

Physical examination findings will reveal mainly lymphadenopathy, cervical and suboccipital. Enlargement of suboccipital lymph nodes in particular should raise a high suspicion of toxoplasmosis. The lymph nodes are generally firm, discrete and are usually multiple. Enlarged spleen or liver may be palpable. Patient may be febrile and may appear weak.

Laboratory tests are non-specific. Lymhocytosis and atypical lymphocytes are seen. An elevation of transaminases to non-hepatic levels may be detected. The CSF is under pressure and the levels of proteins are elevated.

Diagnosis is based on a rise in antibodies of IgM class. Serological testing is the only practical method of diagnosing toxoplasmosis. Following an acute infection, the toxoplasma IgG antibodies become positive within two weeks peak at two months and then settle down to lower levels. It remains positive at these lower levels lifetime. IgM antibodies are essentially of use in diagnosing acute infection in healthy indiviuals. Raised antibody levels are common in general population and only raising antibody titres are highly indicative of toxoplasmosis. The IgM- immunofluorescent [11] antibody (IgM-IFA) test is very ueful.

T. gondii can be isolated by injecting the peritoneum of mice with tissue extracts from bone marrow and body fluids. This is of no practical value.

MRIs are done to observe the brain lesions in neurological involvement. The typical multiple ring lesions are seen.

Ultrasound

  • Enlargement of the Liver

    About 10% to 20% of people will develop swollen glands and some of these people will develop symptoms that are similar to the flu or infectious mononucleosis (e.g., low-grade fever, muscle aches, sore throat, an enlarged spleen and liver, and sometimes [medbroadcast.com]

    When it does occur, it may look similar to infectious mononucleosis and include: Fever Swollen lymph glands, particularly in the region of the neck Headache Muscle aches and pains Sore throat Enlargement of the liver and spleen General feelings of being [healthychildren.org]

    Most affected newborns are symptom -free at birth; however in 10% there is chorioretinitis with blindness and in 20% there is more generalised disease (such as fever, anaemia, jaundice, and enlargement of the liver and spleen) or neurological symptoms [dermnetnz.org]

    Enlargement of suboccipital lymph nodes in particular should raise a high suspicion of toxoplasmosis. The lymph nodes are generally firm, discrete and are usually multiple. Enlarged spleen or liver may be palpable. [symptoma.com]

Treatment

Most of the cases do not require treatment as the disease is self-limiting provided the immunity is good. In case of persistence of symptoms more than 2 weeks, or any complication, treatment should be offered.

Pyrimthamine and sulphadiazine are given together as they are synergisitic. Therapy should be continued minimum for a month. Folinic acid should be given to prevent pancytopenia which results due to this therapy. Spiramycin is a useful alternative for treatment during pregnancy [12].

Tests should be done again to judge response to treatment. Dosage should be reduced and continued for longer periods as relapse rates are high. Steroids may be useful in ocular toxoplasmosis.

Prognosis

The prognosis is excellent with full recovery in immunocompetent indiviuals. 80-90% of the cases have complete recovery with no residual complications.

The outcome in infants with toxoplasmosis is variable. It depends upon the month in which the fetus gets infected and the severity of the infection. Disease progress and response to treatment also determine the prognosis. Infants affected in the first trimester have a bad prognosis with physical and mental malformations that may lead to death.

Immunosuppressed patients respond to treatment with prompt diagnosis which helps in a better recovery rate. The treatment has to be maintained throughout life.

Etiology

The causative agent of this infectious disease is an intracellular parasite called as Toxoplasmosis gondii. Infection within the cat is the principal infection and takes place when these feline species ingest material which is infected with cysts in tissue (bradyzoite forms) and these undergo sexual reproduction in the gut of the cat [2].

Humans get infected with these tissue cysts when they come in contact with cat faeces or contaminated food or water. These tissue cysts enter the human body and can invade almost any part of the body but affect mainly heart, brain, muscles, eyes and lungs. Important factors which help in the etiology of this disease:

  • Contact with cat faeces: Commonly, domestic felines do not harbour the infection. It is mainly the wild cats who hunt that are invaded with the T. gondii cysts. Accidental contact can occur when gardening or digging the soil.
  • Eating raw meat mainly pork and lamb which are most likely to be infested with T. gondii cysts result in the spread. In certain places it is common to eat raw pork or lamb. Dairy products which are not pasteurised can also transmit this infection.
  • Consumption of fruits and vegetables, raw and unwashed, can be infected with this parasite.
  • Hand to mouth contact also occurs with individuals handling raw meat or using kitchen utensils contaminated with the cysts.
  • Transplacental transmission can occur to the fetus when the pregnant woman is severely infected with the parasite resulting in congenital toxoplasmosis.

The exact route of transmission of Toxoplasmosis is not yet certain [3].

Epidemiology

Toxoplasmosis occurs mainly in warm blooded animals worldwide. Human infection is common but remains asymptomatic. Toxoplasmosis is common in tropical countries with a hot and humid weather [4].

About 25-30% of human population have been infected with toxoplasmosis, though it cannot be demonstrated as most of the times there are no clinical manifestations.

The main routes of transmission are foodborne, animal to human and mother to child. The prevalence varies amongst different countries and communities.

Since this infection can transmit via placenta to fetus, extra importance is given to its prevalence among childbearing women between 15-44 years of age. About 15-20% of women have known to be infected with this parasite during pregnancy.

Pathophysiology

The feline species are the definite hosts of this intracellular parasite. The cat primarily gets infected after ingestion of material that contains cysts (bradyzoites) which are released within the gut to undergo sexual reproduction in the uroepithelial cells of the cat gut.

Sexual reproduction by fusion of gametes produces zygotes which are excreted out in cat faeces as unsporulated oocysts. After exposure to proper weather conditions, these oocysts sporulate to form infectious sporozites.

These can be ingested by human when they come in contact with cat litter directly or indirectly. Cats give out millions of oocysts for roundabout 3 weeks, that can remain infective for minimum a year.

Once in human stomach, these bradyzoites and sporozoites invade intestinal epithelial cells where they form vacuoles [5] and tachyzoites which rapidly multiply causing cells to rupture. These tachyzoites spread all over the body but in particular have an affinity for the lymphatic system, central nervous system and the eyes.

Transplacental transmission takes place at this stage. Cell-mediated and humoral immunity can result in total destruction of these tachyzoites, but inactive cysts remain dormant in the human body maturing and rupturing later on.

Histologically, there is an acute inflammatory response which surrounds a point of cell necrosis. Mononuclear infiltrate is present. Tachyzoites are never visualised and inactive cysts never cause an inflammation. In lymph nodes, there is characteristic hyperplasia of follicles which are surrounded by numerous macrophages. In the eyes, multifocal granulomatous lesions with chorioretinitis and iridocyclitis [6] will be observed.

In the central nervous system, there will be diffuse meningoencephalitic changes with infiltrates in a perivascular distribution mainly of mononuclear cells with random neutrophillic exudate.

Prevention

There are few guidelines laid down for prevention of this infectious disease. Prevention mainly includes reducing the chances of ingesting the parasite. Hygiene should be maintained, especially after handling raw uncooked meat, hands should be washed. Fruits and vegetables should be thoroughly washed prior to consumption.

Domesticated cats should be given packaged food. Avoid contact with wild cats. All dairy products should be properly pasteeurised. Pregnant women should take extra precautions to avoid contact with cat litter.

Pregnant women infected with this parasite should start treatment immediately so as to minimise risk to fetus. No vaccine is available presently for prevention.

Summary

Toxoplasmosis is an infectious disease caused by Toxoplasma gondii, an intracellular protozoon which requires for completion of its lifecycle, a definite host e.g. a cat, sheep or pig and an intermediate host which are humans.

Infections in humans occur either congenitally or by ingestion of foodstuffs contaminated by cat faeces or raw meat contaminated with T. gondii cysts. Toxoplasmosis produces a clinical picture similar to infectious mononucleosis with an abnormal liver biochemistry [1].

Clinical manifestations occur only in certain settings, mainly in immunosuppressed conditions. Toxoplasmosis acquired at an early age may remain asymptomatic throughout life and might only be an incidental detection.

Toxoplasmosis produces a flu like clinical picture mainly in pregnant women, infants and immunocompromised individuals.
Treatment may not be required if the individual is healthy with good immunity. Since it is an infectious disease, the best approach is prevention.

Patient Information

Toxoplasmosis is an infection caused by a parasite called Toxoplasma gondii. This is one of the most common parasitic infections in the world. It is acquired when there is contact with cat faeces or consumption of raw uncooked meat which harbours this parasite. This infection may have no symptoms and is usually self-limiting unless the individual immunity is compromised. A pregnant woman who contracts this infection just before or during pregnancy can transmit this infection to her baby which can cause severe complications.

Cat faeces are the main source of these parasites which can spread to other animals as well. Contact with cat faeces or raw uncooked meat is the main source of infection.

The main symptoms are mild flu like signs which are not very severe other symptoms include tiredness and weakness. There may be swollen glands in the neck or underarm. In case of severely immune compromised individuals, they may show more severe signs like a swollen liver or spleen. Pregnant women should immediately consult a medical provider in case of suspected contact with parasite.

Blood tests will be done to detect antibodies in relation to the parasite. Depending upon the severity of the infection, treatment will be started. Due to relapse the treatment should be maintained in spite of improvement.

The best approach to this infection is prevention. Raw uncooked meat should be avoided. Hands should be washed carefully after handling raw meat. All fruits and vegetables should be carefully washed before consumption. Contact with wild cats should be avoided especially by pregnant women. Pregnant women should take all preventive measures as it can affect the unborn baby. Presently, there is no vaccine for this infection, thus, prevention is the best method.

With accurate treatment recovery is complete unless the immunity of the patient is supressed. The outlook of this infection is good with no residual complications.

References

  1. Lindsay DS, Dubey JP. Toxoplasma gondii: the changing paradigm of congenital toxoplasmosis. Parasitology. 2011 Dec;138(14):1829-31.
  2. Montoya JG, Remington JS. Toxoplasmicchorioretinitis in the setting of acute acquired toxoplasmosis. Clin Infect Dis. 1996 Aug;23(2):277-82.
  3. Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet. 2004 Jun 12;363(9425):1965-76
  4. Jones JL, Kruszon-Moran D, Sanders-Lewis K, Wilson M. Toxoplasma gondii infection in the United States, 1999 2004, decline from the prior decade. Am J Trop Med Hyg. 2007 Sep;77(3):405-10.
  5. Martin AM, Liu T, Lynn BC, Sinai AP. The Toxoplasma gondiiparasitophorous vacuole membrane: transactions across the border. J Eukaryot Microbiol. 2007 Jan-Feb;54(1):25-8.
  6. Phan L, Kasza K, Jalbrzikowski J, Noble AG, et al. Longitudinal study of new eye lesions in children with toxoplasmosis who were not treated during the first year of life. Am J Ophthalmol. 2008 Sep;146(3):375-384.
  7. Luft BJ, Remington JS. Toxoplasmic encephalitis in AIDS. Clin Infect Dis. 1992 Aug;15(2):211-22.
  8. Porter SB, Sande MA. Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome. N Engl J Med. 1992 Dec 3;327(23):1643-8.
  9. Henriquez SA, Brett R, Alexander J, Pratt J, Roberts CW. Neuropsychiatric disease and Toxoplasma gondii infection. Neuroimmunomodulation. 2009;16(2):122-33.
  10. Frenkel JK. Toxoplasmosis. Pediatr Clin North Am. 1985 Aug;32(4):917-32
  11. Pinon JM, Chemla C, Villena I, et al. Early neonatal diagnosis of congenital toxoplasmosis: value of comparative enzyme-linked immunofiltration assay immunological profiles and anti-Toxoplasma gondii immunoglobulin M (IgM) or IgA immunocapture and implications for postnatal therapeutic strategies. J Clin Microbiol. 1996 Mar;34(3):579-83.
  12. Paquet C, Yudin MH. Toxoplasmosis in pregnancy: prevention, screening, and treatment. J Obstet Gynaecol Can. 2013 Jan;35(1):78-9. .
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