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Toxoplasmosis, Emergency Medicine

Basics

Description

- Toxoplasma gondii " ”intracellular protozoan parasite: - 3 forms: - Tachyzoite: Asexual invasive form - Tissue cyst: Persists in tissues of infected hosts during chronic phase - Oocyst: Contains sporozoites and produced during sexual cycle in cat intestine

- Transmission: - Ingesting tissue cysts or oocysts: - Ingesting undercooked meat - Vegetables contaminated with oocysts - Contact with cat feces, through cat or soil

- Transplacental - Blood product - Organ transplantation

- Pulmonary: - Pneumonitis - Prolonged febrile illness - Nonproductive cough - Dyspnea

- Results from an asymptomatic acute infection during pregnancy - 1st trimester: - Spontaneous abortion - Stillbirth - Severe disease up to 25% of the time

- Diagnose via: - Isolation of organism: - Blood - CSF for encephalitis - Bronchoalveolar lavage for pneumonitis - Amniotic fluid - Aqueous humor

- Detection of tachyzoites in tissues or body fluids - Demonstrating characteristic lymph node pathology

- LDH >600/UL associated with toxoplasmosis - CBC: - ABG/pulse oximetry for pulmonary symptoms - IgG antibodies: - High number of false-positive and false-negative results - Common tests: - Sabin " “Feldman dye test - Indirect fluorescent antibody - Agglutination - Enzyme-linked immunosorbent assay test

- Immunoglobulin M (IgM) antibodies: - Absence excludes diagnosis in immunocompetent host - Reference labs may be helpful, such as Remington (650-853-4828 Toxoplasma Serology Laboratory) (www.pamf.org/serology) - Diagnoses acute infection - Appear in 5 days - Disappear in weeks to months - Neonatal testing differentiates from maternal infection

  • Toxoplasma gondii " ”intracellular protozoan parasite:3 forms:Tachyzoite: Asexual invasive formTissue cyst: Persists in tissues of infected hosts during chronic phaseOocyst: Contains sporozoites and produced during sexual cycle in cat intestine
  • Transmission:Ingesting tissue cysts or oocysts:Ingesting undercooked meatVegetables contaminated with oocystsContact with cat feces, through cat or soilTransplacentalBlood productOrgan transplantation

Etiology

  • 70% of adults seropositive
  • Asymptomatic in most immunocompetent patients
  • Worldwide; cats are the common host
  • Incubation is 7 days with a range of 4 " “21 days

Diagnosis

Signs and Symptoms

4 types of infection ‚

Immunocompromised Host ‚

  • CNS:Subacute presentation (90%)EncephalitisHeadacheAltered mental statusFeverSeizuresCranial nerve palsiesSpinal cord lesionsCerebellar signsMeningitis-like symptomsMovement disordersNeuropsychological symptoms:PsychosisParanoiaDementiaAnxietyAgitation
  • Pulmonary:PneumonitisProlonged febrile illnessNonproductive coughDyspnea

Immunocompetent Host ‚

  • 90% are asymptomatic
  • Lymphadenopathy, usually cervical
  • Fever
  • Malaise
  • Mononucleosis-like syndrome with macular rash and hepatosplenomegaly
  • Headache
  • Sore throat
  • Night sweats
  • Maculopapular rash
  • Urticaria
  • Usually, self-limited process; resolves in 2 " “12 mo
  • Rarely presents with pneumonitis or encephalitis

Ocular Toxoplasmosis ‚

  • Blurred vision
  • Scotoma
  • Pain
  • Photophobia
  • Retina:Small clusters of yellow-white cotton-like patchesChorioretinitis; affects 85% of young adults with untreated congenital infection

Congenital Toxoplasmosis ‚

  • Results from an asymptomatic acute infection during pregnancy
  • 1st trimester:Spontaneous abortionStillbirthSevere disease up to 25% of the time
  • 2nd or 3rd trimester:50 " “60% chance of acquiring congenital toxoplasmosis2% fatal
  • Most asymptomatic at birth
  • Delayed onset. 70 " “90% asymptomatic at birth:CNS diseaseOcular disease (blindness months to years later)LymphadenopathyHepatosplenomegalyAt birth, may have maculopapular rash, lymphadenopathy, hepatomegaly, splenomegaly, jaundice, thrombocytopenia

Essential Workup

  • Diagnose via:Isolation of organism:BloodCSF for encephalitisBronchoalveolar lavage for pneumonitisAmniotic fluidAqueous humorDetection of tachyzoites in tissues or body fluidsDemonstrating characteristic lymph node pathology
  • Thorough ocular exam:Retinal examVisual acuity

Diagnosis Tests & Interpretation

Lab

  • LDH >600/UL associated with toxoplasmosis
  • CBC:
  • ABG/pulse oximetry for pulmonary symptoms
  • IgG antibodies:High number of false-positive and false-negative resultsCommon tests:Sabin " “Feldman dye testIndirect fluorescent antibodyAgglutinationEnzyme-linked immunosorbent assay test
  • Immunoglobulin M (IgM) antibodies:Absence excludes diagnosis in immunocompetent hostReference labs may be helpful, such as Remington (650-853-4828 Toxoplasma Serology Laboratory) (www.pamf.org/serology)Diagnoses acute infectionAppear in 5 daysDisappear in weeks to monthsNeonatal testing differentiates from maternal infection

Imaging

  • Chest radiograph for pulmonary symptoms:Pneumonitis associated with reticulonodular pattern
  • CT head with contrast:Multiple bilateral hypodense ring-enhancing lesions
  • MRI brain:High signal abnormalities on T2-weighted images
  • Serial fetal ultrasonography can be useful in exploring congenital infection of the CNS or other signs.

Diagnostic Procedures/Surgery

Brain biopsy for encephalitis " ”definitive diagnosis ‚

Differential Diagnosis

  • Cryptococcal meningitis
  • CNS lymphoma
  • Pneumocystis carinii pneumonia
  • Cytomegalovirus retinitis
  • Mycobacterial infection

Treatment

Initial Stabilization/Therapy

  • Treat seizures in standard fashion with diazepam and phenytoin.
  • Initiate oxygen if hypoxia due to pneumonitis.

Ed Treatment/Procedures

Immunocompetent

Toxoplasmic lymphadenitis: ‚

  • No antibiotics unless symptoms severe and persistent
  • Treat symptomatic patients with pyrimethamine and folinic acid plus sulfadiazine or clindamycin for 3 " “4 wk
  • Clindamycin may be a useful alternative to sulfadiazine because of the side effects of the latter and in those who are hypersensitive to sulfa
  • Pyrimethamine and sulfadiazine (Eon Labs 800-526-0225) is available as a combination drug.
  • Corticosteroids may be useful for ocular complications and CNS disease.
  • Reassess to determine if longer therapy needed.

Immunocompromised

  • Confirmed acute infection by serology/symptoms:Treat with pyrimethamine and folinic acid + sulfadiazine or clindamycin for 4 " “6 wk after resolution of symptoms.Alternative medications:Trimethoprim " “sulfamethoxazolePyrimethamine and folinic acid + dapsone
  • CNS symptoms + a lesion on CT or MRI:Treat empirically with pyrimethamine and folinic acid + sulfadiazine or clindamycin.Brain biopsy or CSF to confirm diagnosisAdminister anticonvulsants only if confirmed prior seizures:Poorer outcome for patients on anticonvulsants
  • Chronic asymptomatic infection:No therapy requiredProphylaxis options for toxoplasmosis in AIDS and immunosuppressed patients:Trimethoprim " “sulfamethoxazole; lifelong prophylaxis should be considered in HIV patients after consultation.Pyrimethamine (75 mg/wk) and dapsone (200 mg/wk) and leucovorin 10 " “25 mg with each dose pyrimethamine

Ocular

  • Treat with pyrimethamine and sulfadiazine for 1 mo.
  • May add clindamycin
  • Administer systemic steroids with macular or optic nerve involvement.

Acute Acquired Infection in Pregnancy

  • Initially treat with spiramycin pending confirmatory tests and consultation (FDA, Division of Special Pathograns and Transplant Drug Products 301-796-1600 or CDC at 404-718-4745).
  • After the infection is documented, initiate treatment after consultation:Spiramycin in the 1st 17 wkPyrimethamine and sulfadiazine after 17 wk
  • Spiramycin may reduce congenital transmission but does not treat fetus if infection is in placenta; maternal therapy may decrease severity of congenital disease.
  • Treat congenital infection with sulfadiazine, pyrimethamine, and folinic acid for 12 mo.
  • Prevention of exposure in seronegative pregnant women is important when contacting cats or their excrement.

Medication

  • Clindamycin:600 mg (peds: 20 " “40 mg/kg/24 h) IV q6h300 mg (peds: 8 " “20 mg/kg/24 h) PO q6hUseful if patient hypersensitive to sulfa
  • Dapsone: 50 mg PO per day or 200 mg PO per week (child >1 mo: 2 mg/kg PO per day)
  • Folinic acid: 5 " “25 mg PO daily in conjunction with pyrimethamine therapy
  • Pyrimethamine: 100 mg BID on 1st day loading dose, then 25 " “50 mg PO per day
  • Spiramycin: FDA authorization required
  • Sulfadiazine: 500 mg " “2 g (peds: 100 " “200 mg/kg/24 h div. BID) PO q6h
  • Trimethoprim " “sulfamethoxazole: 5 mg/kg of trimethoprim component IV or PO q12h

Follow-Up

Disposition

Admission Criteria

  • Acute infection with severe systemic symptoms
  • Immunocompromised patients with:Toxoplasmosis encephalitisPneumonitisSepsis

Discharge Criteria

  • Immunocompetent patients with:
  • Maternal/congenital infection with mild symptoms

Issues for Referral

Infectious disease consultant ‚

Additional Reading

  • American Academy of Pediatrics. Red Book 2012 Report of the Committee on Infectious Diseases. Elk Grove, IL: AAP; 2012.
  • Centers for Disease Control and Prevention. Guidelines for prevention and treatment of opportunistic infections in HIV infected adults and adolescents. MMWR. 2009;58:1 " “207. http://www.cdc.gov/mmwr/pdf/rr/rr58e324.pdf.
  • Jones ‚ JL, Dargelas ‚ V, Roberts ‚ J, et al. Risk factors for Toxoplasma gondii infection in the United States. Clin Infect Dis. 2009;49:878 " “884.
  • Kaplan ‚ JE, Benson ‚ C, Holmes ‚ KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58:1 " “207.
  • Sciammarella ‚ J. Toxoplasmosis. Available at http://www.emedicine.com/emerg/topic601.htm. Accessed on July 6, 2002.

Codes

ICD9

  • 130.0 Meningoencephalitis due to toxoplasmosis
  • 130.4 Pneumonitis due to toxoplasmosis
  • 130.9 Toxoplasmosis, unspecified
  • 130.1 Conjunctivitis due to toxoplasmosis
  • 130.2 Chorioretinitis due to toxoplasmosis
  • 130.7 Toxoplasmosis of other specified sites
  • 771.2 Other congenital infections specific to the perinatal period

ICD10

  • B58.2 Toxoplasma meningoencephalitis
  • B58.3 Pulmonary toxoplasmosis
  • B58.9 Toxoplasmosis, unspecified
  • B58.00 Toxoplasma oculopathy, unspecified
  • B58.89 Toxoplasmosis with other organ involvement
  • P37.1 Congenital toxoplasmosis

SNOMED

  • 187192000 Toxoplasmosis (disorder)
  • 192701001 Toxoplasma encephalitis (disorder)
  • 187196002 Toxoplasma pneumonitis (disorder)
  • 416481006 Ocular toxoplasmosis
  • 73893000 Congenital toxoplasmosis (disorder)