Malaria

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Background

Distribution of malaria in the world (2010; see CDC website for current distribution):[1]  Elevated occurrence of chloroquine- or multi-resistant malaria
 Occurrence of chloroquine-resistant malaria
 No Plasmodium falciparum or chloroquine-resistance
 No malaria
Malaria vector: Anopheles stephensi mosquito.
The life cycle of malaria parasites.
  • Caused by parasitic protozoa species of the genus Plasmodium (P ovale, P vivax, P malariae, P knowlesi, and P falciparum) carried by the Anopheles mosquito
    • P falciparum most severe
    • Sickle Cell Trait (HbAS) is protective against severe P falciparum malaria
  • Failure to consider for febrile illness following travel, even if seemingly temporally remote, can result in significant morbidity or mortality, especially in children and pregnant or immunocompromised patients
  • Chemoprophylaxsis does not guarantee protection
  • CDC Malaria Hotline: 770-488-7788
  • Malaria is a US nationally notifiable disease and all cases should be reported
  • Malaria vaccine with ~30% efficacy will be piloted in African countries in 2018, study to assess pediatric mortality[2]

Traveler Precautions

The CDC recommends travelers to malaria-endemic regions take the following precautions:[3]

  • Use of insecticide-treated bed nets
  • Use of DEET-containing insect repellents
  • Wear long-sleeve shirts and pants
  • Chemoprophylaxis
Drug Regimen Dosage Side Effects Recommended Geography

Chloroquine Begin weekly dosing 1-2 weeks before exposure and continue until 4 weeks after returning 500mg weekly Headache, itching, bitter taste. Rare serious dermatologic and ocular effects First line in Central America, Mexico, Argentina, Paraguay, Hispaniola, Eastern Europe, Northern Africa, China, and parts of the Middle East
Atovaquone-proguanil (Malarone) Begin daily dosing 1-2 days before exposure and continue until 7 days after returning One pill (250mg/150mg) daily Headache, nausea, abdominal pain, LFT increase. Avoid with renal dysfunction. Second line agent; First line in areas of chloroquine resistance: Most of South America, sub-Saharan Africa, most of Asia, Oceania, and parts of Saudia Arabia, Yemen, Iran, and Oman
Mefloquine Begin weekly dosing 1-2 weeks before exposure and continue until 4 weeks after returning 250mg weekly Headache, Nausea, Diarrhea, Dizziness, Sleep Disturbance. Avoid with psychiatric disorders or arrhythmias Second line agent; First line in areas of chloroquine resistance: Most of South America, sub-Saharan Africa, most of Asia (except Thailand, Myanmar, and Cambodia), Oceania, and parts of Saudia Arabia, Yemen, Iran, and Oman
Doxycycline Begin daily dosing 1-2 days before exposure and continue until 4 weeks after returning 100mg daily Photosensitivity, Nausea Second line agent; First line in areas of chloroquine resistance: Most of South America, sub-Saharan Africa, most of Asia, Oceania, and parts of Saudia Arabia, Yemen, Iran, and Oman
Hydroxychloroquine Begin weekly dosing 1-2 weeks before exposure and continue until 4 weeks after returning 200mg weekly Headache, itching, bitter taste. Rare serious dermatologic and ocular effects Second line agent
Primaquine Begin daily dosing 1-2 days before exposure and continue until 2 days after returning 30mg daily Nausea, Diarrhea. Avoid with G-6-PD. Second line agent

Clinical Features

Different fever patterns observed in Plasmodium infections.
Child with malaria.
  • Fever + exposure to endemic country
    • Cyclic fever only after chronic infection
  • Headache, cough, GI symptoms

Classification

Severe

Uncomplicated

  • None of the above

Differential Diagnosis

Fever in traveler

Evaluation

Ring-forms and gametocytes of Plasmodium falciparum in human blood
  • First smear positive in >90% of cases (thick and thin Giemsa stain)
    • If initial negative, must be repeated BID x 2-3 days for proper exclusion of malaria
    • Determines degree of parasitemia and type (e.g. P. falciparum)
  • Additional lab findings

Management

  • Mixed infections involving more than one species of Plasmodium may occur in areas of high endemicity (have a low threshold for including treatment for P falciparum)[4]
  • Hyponatremia in the setting of hypovolemia does not require treatment beyond rehydration
  • Treat hypoglycemia
  • Check HIV status (coinfection can lead to worse clinical outcomes)
  • Exchange transfusion for patients with:
    • P falciparum malaria with a parasitemia greater than 10%
    • Life-threatening complications (ie, coma, respiratory failure, coagulopathy, fulminant kidney failure)
For specific dosing see the CDC Recommendations or call the Malaria CDC Hotline(855) 856-4713

Uncomplicated Malaria

  • Uncomplicated:
    • No evidence of organ dysfunction
    • Parasitemia <5%
    • Able to tolerate PO
  • Hospitalize:
    • Severe clinical manifestations in non-immune host for P. falciparum or P. knowlesi
  • Report to state health department
  • For non-pregnant patients (3 day course)
    • Artemether + lumefantrine
    • Artesunate + amodiaquine
    • Artesunate + mefloquine
    • Dihydroartemisinin + piperaquine
    • Artesunate + sulfadoxine–pyrimethamine (SP)
  • For pregnant (1st trimester)
  • Additional considerations
    • Avoid artesunate + SP in HIV/AIDS patients taking co-trimoxazole
    • Avoid artesunate + amodiaquine in HIV/AIDS patients taking efavirenz or zidovudine
    • P. vivax and P. ovale have dormant hypnozoites in the liver which require treatment with primaquine phosphate for complete eradication

Severe Malaria

  • Do not delay treatment in the unstable patient if strong suspicion for malaria as initial smear may be falsely negative
  • Treatment (IV for ≥24 hours then 3 days PO course)
    • Artesunate (IV)
      • Clears malaria faster than quinine
      • Distributed only through CDC
    • Quinidine (IV) also appropriate choice; more available in US

Cerebral Malaria

  • Insufficient evidence for or against giving antiepileptics
  • For severe cerebral edema, mannitol and steroids have not shown a demonstrable benefit

Disposition

Admit for

  • Patients with suspected or confirmed P falciparum or P knowlesi infection
  • Young children
  • Pregnant women
  • Immunocompromised patients

Admit to ICU for

  • Severe complications (e.g.coagulopathy or end-organ failure)
  • Cerebral malaria (e.g. altered mental status, repeated seizures, coma)
  • Parasitemia
    • >2% in non-immune (i.e. travelers)
    • >5% in semi-immune (i.e. locals)

See Also

External Links

References

  1. "Malaria". US Centers for Disease Control and Prevention. April 15, 2010. Archived from the original on April 16, 2012. Retrieved 2012-05-02.
  2. WHO. Ghana, Kenya and Malawi to take part in WHO malaria vaccine pilot programme. 24 April 2017. http://www.afro.who.int/en/media-centre/pressreleases/item/9533-ghana-kenya-and-malawi-to-take-part-in-who-malaria-vaccine-pilot-programme.html
  3. WHO Malaria Policy Advisory Committee and Secretariat. Malaria Policy Advisory Committee to the WHO: conlusionsions and recommendations of September 2013 meeting. Malar J. 2013;12(1):456
  4. World Health Organization. Guidelines for the treatment of malaria, 3rd ed, WHO, Geneva 2015. http://www.who.int/malaria/publications/atoz/9789241549127/en/