Malaria

Aka: Malaria, Plasmodium falciparum, Plasmodium malariae

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II. Etiology

  1. Plasmodium vivax
  2. Plasmodium ovale
  3. Plasmodium falciparum
  4. Plasmodium malariae

III. Pathophysiology

  1. See Vector-Borne Infection
  2. Transmitted by bite of anopheline (or anopheles) Mosquito
    1. Usually bites between dusk and dawn
    2. Injects Malaria protozoa from Salivary Glands
  3. Species of Malaria
    1. Plasmodium falciparum (most common and most life threatening)
      1. Fulminant Malaria associated with high Parasitemia and intravascular congestion
    2. Plasmodium vivax
    3. Plasmodium malariae
    4. Plasmodium ovale
    5. Plasmodium knowlesi
      1. Emerging pathogen in those exposed to macque monkeys
      2. Similar in appearance to p. Malariae
  4. Life cycle of Malaria
    1. Injected from Mosquito as sporozoite
    2. Sporozoites invade hepatocytes in human liver
      1. Develop into merozoites after weeks to months of development within hepatocytes
      2. Merozoites released into blood stream
      3. Sporozoites may lie dormant in liver (hypnozoites)
        1. Occurs with Plasmodium vivax and Plasmodium ovale
        2. Symptoms recur when reactivates in months to years
    3. Merozoites invade erythrocytes and circulate freely
      1. P. Malariae may remain in Red Blood Cells without lysis, latent for months to years
      2. Typically results in Red Blood Cell lysis within 48-72 hours of erythrocyte invasion
      3. Hemolysis is associated with fever spikes
        1. Fever spikes typically occur randomly, but may occur with RBC lysis in a pattern
        2. May cause tertian fever (recurring every third day)
        3. May cause quartan fever (recurring every fourth day)
    4. Circulating merozoites differentiate into Gametocytes
      1. Gametocytes are the sexual form of plasmodium
      2. Mosquito ingests gametocytes from infected host
      3. Protozoa develop within the Mosquito over a 10-21 day course
      4. Mosquito infects next human host with bite

IV. Epidemiology

  1. Incidence
    1. Most common life threatening disease for travelers
    2. Mosquito population is expected to as much as double with global warming (0.4 C) by 2020
    3. European, North American traveler cases: 30,000/year
    4. Cases reported to CDC per year: 1500 (out of 18 million U.S. travelers to Malaria endemic areas)
    5. Worldwide Infections: 300 million per year
    6. Worldwide Mortality: 1-3 million deaths per year
      1. Malaria is among the top three infectious causes of death in the world (along with HIV Infection and Tuberculosis)
  2. Timing
    1. Majority of Malaria outbreaks occur between May and December
    2. Highest risk is during and after the rainy season
      1. River beds and stagnant pools of water are most common breading grounds
  3. Regions
    1. Endemic to tropical and subtropical world (106 countries as of 2010)
    2. Highest Risk
      1. Sub-Saharan Africa
      2. Papua New Guinea
      3. Solomon Islands
      4. Vanuatu
    3. Intermediate Risk
      1. Haiti
      2. Indian subcontinent
    4. Low Risk
      1. Southeast Asia
      2. Latin America

V. Symptoms

  1. Timing
    1. Presentation within the first month of return from travel to endemic region
    2. Delayed presentation beyond 2 months may occur with the use of chemoprophylaxis
  2. Initial prodrome
    1. Headache
    2. Malaise
  3. Next
    1. Fever (>50% of patients)
    2. Shaking chills
  4. Next
    1. Drowsiness
    2. Lethargy
    3. Fatigue
  5. Other symptoms
    1. Myalgias
    2. Arthralgias
    3. Back pain
    4. Nausea
    5. Vomiting
    6. Diarrhea
    7. Abdominal Pain

VI. Signs

  1. Fever for 1-8 hours
  2. Fever recurs
    1. Plasmodium vivax: 48 hours
    2. Plasmodium malariae: 72 hours
    3. Plasmodium falciparum: Variable
  3. Gastrointestinal findings (in <35-40% of cases)
    1. Tender Splenomegaly
  4. Severe falciparum Malaria
    1. Hypotension and shock
    2. Multisystem failure
      1. Pulmonary edema
      2. Acute Respiratory Distress Syndrome
      3. Renal Failure (1% of cases)
      4. Jaundice and liver failure (associated with poor prognosis)
    3. Cerebral Malaria
      1. Altered Mental Status to unresponsive
      2. Seizures
      3. Meningism

VII. Labs

  1. Blood Glucose
    1. Hypoglycemia may occur (esp. children)
  2. Complete Blood Count (CBC) with differential
    1. Especially consider Malaria with Leukopenia and Left Shift, Thrombocytopenia
    2. Hemoglobin or Hematocrit consistent with Anemia (29%)
    3. Leukopenia with White Blood Cell Count <5000/mm3 (26%)
    4. Thrombocytopenia (45%)
    5. Bandemia (85%)
  3. Urinalysis
    1. Urobilinogen positive
    2. Hemoglobinuria (rare, may occur with Plasmodium falciparum)

VIII. Diagnosis

  1. Peripheral Blood Smear
    1. Gold standard for diagnosis
    2. Stains
      1. Giemsa stain (standard stain for Malaria evaluation with thick and thin smears)
        1. Thin blood smear (first-line Malaria evaluation)
          1. Giemsa stain of blood fixed with Alcohol to prevent Red Blood Cell lysis
        2. Thick blood smear (perform if thin blood smear negative)
          1. Giemsa stain of blood allowed to dry on slide (allowing cell lysis)
      2. Wright stain (standard stain for most Complete Blood Count associated manual differentials)
        1. Test Sensitivity approaches that of Giemsa stain
    3. Protocol
      1. Stat blood smear with direct communication with reading pathologist
      2. Examine new smear every 12-24 hours for 3 days (low Parasitemia may require additional smears)
      3. Sample is best obtained when patient is febrile
    4. Image
      1. HemeoncFalciparum.jpg
  2. Rapid blood dipstick testing (when smear not available)
    1. Tests
      1. HRP-2 detection (only detects P. falciparum)
      2. LDH detection (detects all 4 Malaria types)
    2. Precautions
      1. Decreased Test Sensitivity with low levels of Parasitemia (e.g. patients who took chemoprophylaxis, or prior exposure)
      2. Negative rapid tests should be confirmed with blood smears
  3. Malaria PCR
    1. Detects low levels of parsites in blood (<5 Parasites/ul)
    2. Distinguishes between plasmodium species
    3. May be used to monitor response to treatment at 5-8 days (however false positives may occur)

IX. Management: Chemoprophylaxis

  1. See Malaria Chemoprophylaxis

X. Precautions

  1. Fever in a returning traveler from Malaria endemic area is Malaria until proven otherwise
  2. Up to 50% of Malaria cases are misdiagnosed on the first visit
  3. Malaria is an emergent evaluation

XI. Management: Non-falciparum Malaria treatment

  1. Uncomplicated non-falciparum Malaria
    1. Step 1: Chloroquine
      1. Dose: 600 mg load, then 300 mg in 6-8 hours, then 300 mg daily for 2 days
      2. Obtain baseline EKG for QT Prolongation and monitor as needed
    2. Step 2: Primaquine (if G6PD Deficiency negative)
      1. Used to eliminate hypnozoites (liver stage) of vivax and ovale species
      2. Dose: 30 mg daily for 2 weeks after Chloroquine course
      3. Decrease dose if Tinnitus or hyperexcitability occur
      4. Use Chloroquine weekly for 6 months if patient G6PD Deficiency positive
  2. Severe Non-falciparum Malaria
    1. Replace Chloroquine with Quinine, Quinidine or Artesunate
    2. Follow course with Primaquine if without G6PD Deficiency (as above)

XII. Management: Falciparum Malaria treatment

  1. Admit all cases to hospital (high mortality in first 48 hours)
    1. Also admit all undiferentiated cases where species of Malaria cannot be discerned
  2. Combination antiparasitic agents (2 agents)
    1. Agent 1: Artemisinin (or dihydroartemisinin, artemether, or artesunate)
    2. Agent 2: Chloroquine, Sulfadoxine-pyrimethamine (Fansidar) or Mefloquine
  3. Specific complication management
    1. Shock
      1. Intravenous hydration (including fluid boluses)
      2. Obtain Blood Cultures and add third generation Cephalosporin to regimen until cultures back (risk of comorbid Bacterial Sepsis)
    2. Cerebral Malaria (18% of cases)
      1. Seizures
      2. Supportive care including intubation may be needed
      3. Meningism (uncommon but carries 23% mortality)
    3. Bleeding
      1. Coagulopathy reversal
      2. Blood Transfusion

XIII. Prevention

  1. See Malaria Chemoprophylaxis
    1. Critical and not taken adequately in as much as 75% of U.S. travelers
  2. See Prevention of Vector-borne Infection
  3. Malaria Vaccine (investigational in 2012)
  4. Stay in air conditioned or well screened rooms
  5. Reduce nighttime outdoor activity (Dusk until dawn)
  6. Apply an effective Insect repellent
    1. DEET 30% to skin every 3-4 hours or
    2. p-Menthane-3,8-diol (PMD)
  7. Spray clothing and bed nets with Permethrin
  8. Wear long sleeve shirt and pants
  9. Use Insecticide aerosols at dusk in living areas
  10. Use a strong fan at bedside
  11. Use Mosquito bed netting even in hotel rooms
    1. Mosquito net pre-treated with Permethrin
    2. Reapply Permethrin every 6 months

XIV. Prognosis

  1. Plasmodium falciparum Mortality: 4% (20% severe cases)

XV. Resources

  1. See Travel Resources
  2. CDC Malaria hotline (physicians)
    1. Phone: 855-856-4713
  3. CDC Malaria
    1. http://www.cdc.gov/malaria
  4. Malaria Foundation International
    1. http://www.malaria.org

XVI. References

  1. Anderson (2014) Crit Dec Emerg Med 28(7): 11-9
  2. Baird (1999) Med Clin North Am 83(4):923-44 [PubMed]
  3. Croft (2000) BMJ 321(7254):154-60 [PubMed]
  4. Feder (2013) Am Fam Physician 88(8): 524-30 [PubMed]
  5. Johnson (2012) Am Fam Physician 85(10): 973-7 [PubMed]
  6. Lo Re (2003) Am Fam Physician 68(3):509-16 [PubMed]

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Ontology: Malaria (C0024530)

Definition (MSHCZE) Onemocnění zapříčiněné u lidí čtyřmi druhy prvoka rodu PLASMODIUM: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE a PLASMODIUM MALARIAE. Je šířené kousnutím nakaženého samičího komára rodu ANOPHELES. Malárie se vyskytuje v částech Asie, Afriky, střední a jižní Ameriky, Oceánie a v některých částech karibských ostrovů. Charakterizuje ji značné vyčerpání spojené s návaly vysoké horečky, pocení, třesavkou, a chudokrevností. Malárie u zvířat je způsobena jinými druhy plasmódií.
Definition (MEDLINEPLUS)

Malaria is a serious disease caused by a parasite. You get it when an infected mosquito bites you. Malaria is a major cause of death worldwide, but it is almost wiped out in the United States. The disease is mostly a problem in developing countries with warm climates. If you travel to these countries, you are at risk. There are four different types of malaria caused by four related parasites. The most deadly type occurs in Africa south of the Sahara Desert.

Malaria symptoms include chills, flu-like symptoms, fever, vomiting, diarrhea, and jaundice. A blood test can diagnose it. It can be life-threatening. However, you can treat malaria with drugs. The type of drug depends on which kind of malaria you have and where you were infected.

Malaria can be prevented. When traveling to malaria-prone regions

  • See your doctor for medicines that protect you
  • Wear insect repellent with DEET
  • Cover up
  • Sleep under mosquito netting

Centers for Disease Control and Prevention
Definition (NCI) A protozoan infection caused by the genus Plasmodium. There are four species of Plasmodium that can infect humans: Plasmodium falciparum, vivax, ovale, and malariae. It is transmitted to humans by infected mosquitoes. Signs and symptoms include paroxysmal high fever, sweating, chills, and anemia.
Definition (CSP) protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum, P. vivax, P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles; malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands; characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia; malaria in animals is caused by other species of plasmodia.
Definition (MSH) A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.
Concepts Disease or Syndrome (T047)
MSH D008288
ICD9 084.6, 084
ICD10 B54
SnomedCT 187510004, 154374002, 186797008, 61462000, 248437004, 105649009
LNC LA10488-7
English Infection, Plasmodium, Infections, Plasmodium, Plasmodium Infection, Plasmodium Infections, MALARIA, Malaria, unspecified, Unspecified malaria, [X]Unspecified malaria, PLASMODIUM INFECT, INFECT PLASMODIUM, malaria (diagnosis), malaria, Plasmodia infections, Malaria NOS, Malaria [Disease/Finding], malarial fever, malarias, paludism, fever malaria, malaria fever, [X]Unspecified malaria (disorder), Plasmodium infection, Unspecified malaria (disorder), Plasmodiosis, Malarial fever, Disease due to Plasmodiidae (disorder), Disease due to Plasmodiidae, Malaria (disorder), Malarial fever (finding), corsican; fever, fever; Cameroon, fever; corsican, fever; jungle fever, fever; jungle, fever; paludal, jungle fever; fever, jungle; fever, marsh fever, Cameroon fever, Cameroon; fever, paludal; fever, Corsican fever, Malaria, NOS, Paludism, Malaria, Malaria fever NOS, Fever, Marsh, Fever, Remittent, Marsh Fever, Remittent Fever
French PALUDISME, Infection à Plasmodium, Paludisme, non précisé, Paludisme SAI, Paludisme, Malaria, Infections à Plasmodium
Portuguese MALARIA, Malária NE, Infecção por Plasmodium, Febre Malárica, Impaludismo, Doença Malárica, Fiebre Remitente na Malária, Infecção Malárica, Febre da Malária, Maleita, Paludismo, Infecções por plasmódios, Infecções por Plasmodium, Malária, Febre Remitente Paludosa, Febre do Mangue
German MALARIA, Plasmodium Infektion, Malaria, unspezifisch, Malaria NNB, Paludismus, Malaria, nicht naeher bezeichnet, Plasmodien-Infektionen, Malaria, Plasmodium-Infektionen
Italian Infezioni da Plasmodi, Malaria NAS, Malaria non specificata, Infezione da Plasmodium, Paludismo, Malaria
Dutch malaria NAO, malaria, niet-gespecificeerd, paludisme, Corsica; koorts, Kameroen; koorts, fever; jungle, jungle fever; koorts, jungle; fever, koorts; Corsica, koorts; Kameroen, koorts; jungle fever, koorts; moeras, moeras; koorts, Niet gespecificeerde malaria, Plasmodia-infecties, malaria, Malaria, Plasmodium-infectie
Spanish Paludismo NEOM, Paludismo no especificado, Infección por plasmodium, paludismo no especificado, [X]paludismo no especificado, [X]paludismo no especificado (trastorno), malaria no especificada, paludismo no especificado (trastorno), Paludismo, Fiebre Malárica, enfermedad causada por Plasmodiidae (trastorno), enfermedad causada por Plasmodiidae, fiebre palúdica (hallazgo), fiebre palúdica, malaria (trastorno), malaria, paludismo (trastorno), paludismo, plasmodiosis, Infecciones por plasmodium, Infecciones por Plasmodium, Malaria, Fiebre Remitente, Fiebre de los Marjales
Japanese マラリアＮＯＳ, マラリア原虫感染, マラリア、詳細不明, ﾏﾗﾘｱNOS, ﾏﾗﾘｱｼｮｳｻｲﾌﾒｲ, ﾏﾗﾘｱ, ﾏﾗﾘｱｹﾞﾝﾁｭｳｶﾝｾﾝ, Plasmodium属感染症, マラリア, マラリア原虫感染症
Swedish Malaria
Czech Plasmodium - infekce, zimnice bahenní, malárie, Paludismus, Malárie, Malárie NOS, Infekce způsobená plasmodiemi, Malárie, blíže neurčená, Plasmodiové infekce, střídavka
Finnish Malaria
Russian PLASMODIUM-INFEKTSII, MALIARIIA, PLASMODIUM-ИНФЕКЦИИ, МАЛЯРИЯ
Korean 상세불명의 말라리아
Croatian MALARIJA
Polish Malaria, Zarażenie Plazmodium, Zimnica
Hungarian Paludismus, Plasmodium fertőzések, malaria k.m.n., Malaria, nem meghatározott, Plasmodium fertőzés, malaria
Norwegian Malaria
Derived from the NIH UMLS (Unified Medical Language System)

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