Malaria

Background

Distribution of malaria in the world (2010; see CDC website for current distribution): ♦ 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

Traveler Precautions

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

• 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

• Any one of the following:
  • Altered mental status/coma
  • Severe normocytic anemia [hemoglobin < 7]
  • Renal failure
  • ARDS
  • Hypotension
  • DIC
  • Spontaneous bleeding
  • Acidosis
  • Hemoglobinuria
  • Jaundice
  • Hepatomegaly
  • Splenomegaly
  • Repeated generalized seizures
  • Parasitemia >5%

Uncomplicated

• None of the above

Differential Diagnosis

Fever in traveler

• Normal causes of acute fever!
• Malaria
• Dengue
• Leptospirosis
• Typhoid fever
• Typhus
• Viral hemorrhagic fevers
  • Ebola virus disease
  • Marburg virus disease
  • Lassa fever
  • Crimean-Congo hemorrhagic fever
• Chikungunya
• Yellow fever
• Rift valley fever
• Q fever
• Amebiasis
• Zika virus

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
  • Normocytic anemia
  • Thrombocytopenia
  • ↑ ESR
  • ↑ LDH
  • LFT abnormalities (elevated indirect bilirubin)
  • ↑ Cr
  • Hyponatremia
  • Hypoglycemia
  • Low Haptoglobin
  • False positive VDRL

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)
• 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)
  • Quinine + clindamycin x 7 days
• 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

• Travel Medicine
• Parasitic Diseases

External Links

• IAMAT world map and country details
• https://www.cdc.gov/parasites/malaria/index.html