Malaria

Introduction

caused by protozoan – probably the most important parasitic disease. Almost ½ of the world is at risk

US cases are related to immigration and soldiers returning home from endemic areas. Vectors are here!

1.5 –2.7 malaria deaths per year, more children (> 5 y/o) die of malaria than of any other single cause

Emerging Infection failure of eradication programs has lead to a resurgence. Outbreaks in areas previously under control is due to vector resistance to pesticides and parasite resistance to anti-malarial drugs

Distribution mainly tropical and sub tropical regions (Africa, Haiti, Dominican Republic, South America, Middle East)

caused by the parasite Plasmodia. The vectors are mosquitoes of the Anopheles persuasion

Life cycle of Malaria

summary: (in human) sporozyte Þ merizoite Þ trophozoite Þ schizont Þ gametocyte Þ (mosquito) Þ microgametes Þ macrogametes Þ ookinete Þ oocyst Þ sporocyte Þ (to human)

human stage

sporozoite injected into human with saliva of mosquito
sporozoites penetrate liver cells and replicates asexually in liver to produce merizoites

merizoites infect RBC's and form vacuoles that gobbles up hemoglobin – this blood stage is most important in disease

infected RBC’s become huge and lose normal cellular structure
"knobs" of parasitic proteins are added to the RBC membrane
these proteins enable the infected RBC to sequester itself (to avoid spleen)

merizoites eventually emerge from RBC's as uninucleate trophozoites

trophozoites divide asexually to form multinucleate schizont

schizont divides to form more merizoites (that reinfect RBC's) and gametocytes that are taken up into the mosquito

mosquito stage

gametocytes are taken up during the mosquito bite and become microgametes

microgametes form macrogametes that fuse to form a diploid zygote called an ookinete

the ookinete invades the mosquito midgut and develops into an oocyst

the oocyst ruptures and releases sporocytes that penetrate the mosquito salivary gland where they infect another human

The Disease – Blood Stage is most important in disease

Fevers occur during periods of RBC lysis

48 hours from infection to release

the parasites tend to be synchronized (they all got there at the same time) and thus cycle (fever, no fever, fever, no fever, etc.) with fever spikes corresponding to release (lysis) and invasion associated with fever-free period

Four species of plasmodia:

(1) P. falciparum – most common form; affects all RBC's regardless of age and causes very severe disease
(2) P. vivax – most common outside Africa; affects only young RBC's and causes moderately severe disease
(3) P. ovale – affects only young RBC's and causes moderately severe disease
(4) P. malariae – affects only old RBC's and causes mild disease
Sporozoites of P. vivax and P. ovale have a latent form. Relapses are due to the dormant liver forms of Vivax and ovale. P. malariea relapses are due to low grade parasitemia. No relapses with P. falciparum.

P. falciparum has a parasite load one log higher than the rest. It binds to microvasculature in an attempt to avoid the spleen, where damaged RBC’s are taken out of circulation.

Vector characteristics can impact the severity of the disease (what the Anopheles feeds on, how long it lives, etc)

Uncomplicated illness: Fever with asexual parasitemia, self-limiting, common in infants and children

Severe Illness

Cerebral Malaria: Encephalopathy – ½ of all Malarial deaths (Coma, rigidity, totally unresponsive Þ needs intubation and treatment. If not treated, microhemorrhages in the brain

Very Severe Anemia: Lysing lots of RBC’s - Also get suppression of the body’s ability to generate new RBC’s, Folate deficiency secondary to hemolysis

Tropical Splenomegaly Syndrome TSS: Big spleens, tend to get infarctions in the spleen

Blackwater Fever: Small blood vessels in the kidney get blocked Þ necrosis in the kidney

Children 1 – 5 y/o are not immune (maternal Ab’s are gone), most deaths in 3 month – 1 y/o group.

Acquired Immunity – to various stages of infection develops in endemic areas. Infected but not diseased. Immunity is transient Þ without continual exposure immunity wears off and individual is vulnerable again.

Malaria D_{X and}R_X – travel history and anti-malarial prophylaxis use are very important information

On blood smear see parasites in serum and merizoites in RBC’s (if suspected but normal labs repeat every 6 hr for 24 hrs)

Rapid institution of therapy, especially quinine, is life saving – do not use steroids