section name header

Information

Microbiology and Epidemiology !!navigator!!

Six major species of Plasmodium cause nearly all cases of human disease: P. falciparum, P. vivax, two morphologically identical sympatric species of P. ovale, P. malariae, and P. knowlesi.

Pathogenesis !!navigator!!

After introduction of sporozoites into the bloodstream by female anopheline mosquitoes, the parasite travels to the liver and reproduces asexually to form merozoites that infect RBCs. The merozoites transform into trophozoites, feed on intracellular proteins (principally hemoglobin), multiply 6- to 20-fold every 48 h (P. knowlesi, 24 h; P. malariae, 72 h), and cause the RBCs to rupture, releasing daughter merozoites. The process then repeats.

  • Some parasites develop into long-lived sexual forms called gametocytes, whose uptake by another female anopheline mosquito allows transmission.
  • In P. vivax or P. ovale infection, dormant forms called hypnozoites remain in liver cells and may cause disease 3 weeks to >1 year later.
  • RBCs infected with P. falciparum may exhibit cytoadherence (attachment to venular and capillary endothelium), rosetting (adherence to uninfected RBCs), and agglutination (adherence to other infected RBCs). The result is sequestration of P. falciparum in vital organs, with consequent underestimation (through parasitemia determinations) of parasite numbers in the body. Sequestration is central to the pathogenesis of falciparum malaria but is not evident in the other human malarias.
  • In nonimmune individuals, infection triggers nonspecific host defense mechanisms such as increased splenic filtration.
    • - With repeated exposure to malaria, pts develop resistance to high-level parasitemia and disease but not to infection.
    • - Hemoglobinopathies (e.g., sickle cell disease, ovalocytosis, thalassemia) and G6PD deficiency are more common in endemic areas and protect against death from malaria.

Clinical Manifestations !!navigator!!

Pts initially develop nonspecific symptoms (e.g., headache, fatigue, myalgias) that are followed by fever.

  • Febrile paroxysms at regular intervals are unusual and suggest infection with P. vivax or P. ovale.
  • Splenomegaly, hepatomegaly, mild anemia, and jaundice may develop.
  • The diagnosis of severe falciparum malaria requires one or more of the following: impaired consciousness/coma, severe normocytic anemia, renal failure, pulmonary edema, ARDS, circulatory shock, DIC, spontaneous bleeding, acidosis, hemoglobinuria, jaundice, repeated generalized convulsions, and a parasitemia level of >5%.
    • - Cerebral malaria manifests as diffuse symmetric encephalopathy, typically without focal neurologic signs.
    • - Coma is an ominous sign associated with mortality rates of ~20%.
  • Pregnant women have unusually severe illness. Premature labor, fetal distress, stillbirth, and delivery of low-birth-weight infants are common.
  • Tropical splenomegaly (hyperreactive malarial splenomegaly) may result as a chronic complication of malaria and is characterized by massive splenomegaly, hepatomegaly, and an abnormal immunologic response to infection.

Diagnosis !!navigator!!

Although antibody-based diagnostic tests are being used with increasing frequency, demonstration of asexual forms of the parasite on peripheral-blood smears is required for diagnosis.

  • Thick and thin smears should be examined; thick smears and the less sensitive thin smears detect parasitemia levels as low as 0.001% and <0.05%, respectively.
  • If the level of clinical suspicion is high and smears are initially negative, they should be repeated q12-24h for 2 days.
  • Other laboratory findings generally include normochromic, normocytic anemia; elevated inflammatory markers; and thrombocytopenia (~105/µL).

Treatment: Malaria

  • See Table 108-1 for treatment regimens. IV artesunate is approved by the US Food and Drug Administration for emergency use against severe malaria through the Centers for Disease Control and Prevention (CDC) (Malaria Hotline: 855-856-4713; Emergency Operations Center [after hours]: 770-488-7100).
  • Pts receiving quinidine should undergo cardiac monitoring; a total plasma level of >8 µg/mL, increased QT intervals (>0.6 s), or QRS widening by >25% is an indication for slowing the infusion rate.
  • Exchange transfusions can be considered for severely ill pts, although indications for their use are not yet agreed upon.
  • All pts with severe malaria should receive a continuous infusion of dextrose. Unconscious pts should have blood glucose levels measured q4-6h.
  • Parasite counts and hematocrits for pts with severe malaria and pts with uncomplicated disease should be measured q6-12h and q24h, respectively.
  • Primaquine (0.5 mg of base/kg for 14 days) eradicates persistent liver stages and prevents relapse in P. vivax or P. ovale infection. G6PD deficiency must be ruled out before treatment.

Personal Protection Measures !!navigator!!

Measures that can protect persons against infection include avoidance of mosquito exposure, with particular caution at peak feeding times (dusk to dawn); use of insect repellents containing DEET (10-35%) or (if DEET is unacceptable) picaridin (7%); suitable clothing; and insecticide-impregnated bed nets.

Chemoprophylaxis !!navigator!!

  • See Table 108-2 for prophylaxis options.
  • Mefloquine is the only drug advised for pregnant women traveling to areas with drug-resistant malaria and is generally considered safe in the second and third trimesters; data regarding use in the first trimester, although limited, are reassuring.


Outline

Outline

Section 7. Infectious Diseases