Page 95 - Journal of Special Operations Medicine - Fall 2017

Anopheles salivary duct into human skin is termed the sporo- classic signs and symptoms of benign (a.k.a., uncomplicated)
zoite. An infective Anopheles bite inoculates the human with malaria: fever, chills, dizziness, diarrhea, body pains, dyspnea,
around 8 to 15 (sometimes up to 100) sporozoites, 12p1206 which splenomegaly, anemia, thrombocytopenia, and increased bili-
travel via the circulatory system to the liver within 30 minutes. rubin in the urine. 7p702 The often-cited malaria fever-spike in-
Once inside the liver, sporozoites invade liver cells (hepato- tervals (every 48 hours in P. vivax) occur only if the timing of
cytes) and begin the creation of virtual Plasmodium factories erythrocytic schizont ruptures is synchronized. 12p1210 Early in
within those cells. These infected liver cells are termed hepatic the time course of malaria, blood schizont ruptures tend to be
schizonts, with each schizont manufacturing between 10,000 asynchronous (and may never attain synchronicity); therefore,
and 30,000 copies of the next stage of Plasmodium: the mer- fever regularity should not be depended on as a means of rul-
ozoite. Maturation times of the hepatic schizonts vary ac- ing in or out malaria in the febrile patient.
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cording to the Plasmodium species. In P. vivax, the hepatic
schizonts rupture after 6 to 8 days, unleashing a storm of Any of the Plasmodium species may cause severe (a.k.a., com-
RBC-seeking merozoites into the bloodstream. 7p700 plicated) malaria with P. falciparum as the biggest offender in
this category. 7pp704,712 Severe malaria may manifest with some
In cases of P. vivax and P. ovale, some of the hepatic schizonts or all of the signs seen in benign malaria, with the addition of
do not rupture with their fellows but instead lie dormant for any of the following signs: metabolic acidosis, decreased level
weeks, months, or years before releasing their cache of mero- of consciousness, hypoglycemia, prostration, convulsions,
zoites. This dormant liver schizont is known as a hypnozoite, shock, jaundice, elevated serum lactate levels, hematuria, renal
and the onset of illness following the rupture of hypnozoites impairment, and pulmonary edema. 7pp704-705
is called relapsing malaria. 12p1226 Hypnozoites add layers of
complexity to the management of P. vivax by virtue of be- The risk of severe malaria in P. vivax is low—exactly how low
ing diagnostically undetectable, invisible to the host’s immune remains an elusive statistic as the total number of P. vivax cases
system, and impervious to standard malaria treatments. Note is virtually impossible to pin down, due to a high prevalence of
that these liver stages—the hepatic schizont and hypnozoite— seropositive patients who do not manifest signs and symptoms
produce no signs or symptoms in the patient; the infection at of infection. One study showed that the median case-fatality
5
this stage is termed the prepatent period, that is, the time be- rate (CFR) among inpatients with severe P. vivax malaria was
tween inoculation of sporozoites and appearance of parasit- 3.1%, while the CFR for severe P. falciparum cases was 11.6%. 5
emia (parasites in the blood). 7p698
A fundamental tenet of medical practice in the tropics is to
From the hepatic schizonts erupt tens of thousands of mero- reserve a high index of suspicion for malaria in any febrile
zoite-stage parasites into the bloodstream, which promptly in- patient. 6p203 Medics working in malaria-endemic settings should
vade RBCs to initiate a process similar to what occurred in the use bedside rapid diagnostic tests (RDTs) and/or microscopy
liver, minus the possibility of liver reinfection or hypnozoite to confirm the diagnosis of malaria, when indicated. Note
formation (only sporozoites are capable of infecting the liver). that cerebral malaria (caused by capillary sequestration of P.
Each invaded RBC develops into an erythrocytic schizont—a falciparum or P. knowlesi blood schizonts) typically produces
smaller-scale merozoite factory than its hepatic predecessor— visible changes in the patient’s retina. Fundoscopic signs of ce-
which, in the case of P. vivax, rupture roughly every 48 hours, rebral malaria may include vessel color changes, macular or
releasing from 12 to 24 newly minted merozoites into the extramacular whitening, or white-centered hemorrhages. 7p708
bloodstream. It is worth noting that P. vivax merozoites tar-
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get reticulocytes (immature erythrocytes that constitute about Due to growing drug resistance and a high degree of regional
1% of all RBCs) 7p698 ; this preference for reticulocytes is what variability, Medics should consult current WHO guidelines,
constrains P. vivax from rising to critical levels of parasitemia. journal articles, and/or reputable tropical medicine texts when
P. falciparum, on the other hand, is an equal-opportunity in- prescribing both malaria prophylaxis and treatment regimens.
vader of RBCs of all ages and can lead to a parasitemia of Modern malaria chemoprophylaxis consists of a daily regi-
50% or more. 12p1209 men of either atovaquone/proguanil (Malarone ) or doxycy-
®
cline (dosing details are listed in Part 3). Mefloquine (Lariam )
®
As the erythrocytic cycle of malaria continues, some of the is a widely used prophylactic drug that has been removed
parasitized RBCs do not mature into schizonts but instead from the U.S. military formulary due to its neuropsychiatric
develop into gametocytes, the sexual forms of the Plasmo- reactions. 12p1253 If the potential exists for hypnozoite formation
dium parasite. The male and female gametocytes do not pair due to the presence of either P. vivax or P. ovale in the deploy-
within the human but await uptake by a feeding Anopheles ment area, then primaquine is administered at the conclusion of
mosquito. Once inside the stomach of the mosquito, gameto- exposure to the malarious region as a postexposure prophylaxis
cytes mature into gametes, which merge into motile zygotes (provided the patient is not severely G6PD deficient). 12p1256 In
called ookinetes. The ookinete bores into the stomach lining cases of mild-to-moderate G6PD deficiency, primaquine may be
and lodges there, transforming into an oocyst. Within a single administered at lower doses over a longer time course.
oocyst spawn several thousand sporozoites, which migrate to
the mosquito’s salivary glands and ducts, awaiting the next Part 2: The Inherent Challenges of
blood meal and the chance to infect a new human host. 12p1208 Diagnosing and Treating P. vivax
This completes the Plasmodium life cycle.
Owing to the marked curtailment of P. falciparum in recent
Symptomatic malaria manifests at the moment of erythro- years, the pervasive P. vivax parasite is emerging as the next-
cytic schizont rupture (not the rupture of hepatic schizonts) in-line target in the war on malaria. While P. vivax is less lethal
as the parasitized RBCs release fresh merozoites into the than P. falciparum and infrequently encountered in Africa, it
bloodstream. This erythrocyte destruction is the trigger for the is responsible for widespread disease and morbidity outside

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