Page 96 - Journal of Special Operations Medicine - Fall 2017

that continent. Once inaccurately classified as one of the three 7. As with patients who have suffered multiple bouts of P.
“benign malarias,” untreated P. vivax infection may become falciparum, it is not uncommon for those infected with P.
as severe an illness as P. falciparum infection. 15 vivax to enter into a state of partial immunity, in which
the patient is infected yet asymptomatic, thus becoming
SOF Medics deploying to the tropics must be aware of the fol- an unsuspecting Plasmodium reservoir whose parasites
lowing characteristics of P. vivax: can be spread to others via mosquito bite, needle stick,
or blood transfusion. This state of asymptomatic parasit-
1. The life cycle of P. vivax includes the latent hypnozoite emia is referred to as premunition. 12p1204 In one study, up
stage in the liver—a stage that is impervious to typical an- to 97% of microscopically diagnosed P. vivax cases were
timalarial drug regimens (as well as diagnostic detection) asymptomatic. 7
and typically causes relapsing malaria weeks or months 8. The blood stage of P. vivax forms gametocytes very early (3
after the initial infection. Whenever P. vivax or P. ovale is days into the erythrocytic time course), which means that
suspected or confirmed, the liver should be cleared of po- these patients have possibly passed the infection along to
tential hypnozoites with primaquine, provided the patient’s Anopheles mosquitoes before feeling ill and seeking medi-
G6PD enzyme status is known. cal treatment. 7p700,15
2. In any given malaria-endemic region, from 1% to 30% 9. There are marked genetic differences in the global popula-
(average 8%) of the population is G6PD deficient. G6PD tion with respect to CYP2D6 (a phase 1 drug metabolizing
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deficiency—along with sickle cell trait, ovalocytosis, and enzyme). Accordingly, any given patient may be catego-
19
other RBC mutations—confers limited protection against rized as a nonresponder, poor responder, normal responder,
Plasmodium infection and is believed to have developed in or increased responder to certain drugs—including prima-
response to the evolutionary pressures of malaria. Prima- quine. This means that CYP2D6 nonresponders or poor
16
quine—the only drug approved to treat P. vivax hypnozo- responders may continue to harbor hypnozoites despite
ites—necessitates a 14-day regimen due to its short half-life undergoing primaquine therapy. 17p43 If a patient with un-
and presents unique challenges of its own, as described known CYP2D6 status is given primaquine as a therapy
later. Tafenoquine is an alternative drug under advanced (or postexposure prophylaxis) for P. vivax or P. ovale, that
development with a much longer half-life and commensu- patient should be carefully monitored for relapsing malaria
rate shorter dosing regimen. Due to risk of hemolysis, the due to the potential failure to metabolize primaquine.
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conscientious Medic must ascertain whether a particular
patient is G6PD deficient before administering primaquine. Part 3: Malaria Prevention and Treatment
3. Large subsets of the general population are ineligible for
primaquine therapy. These include pregnant women, young A lengthy (76-page) description of malaria chemoprophylaxis
infants, those deficient in the G6PD enzyme, and patients and treatment is available from the WHO, the full details
whose G6PD status is unknown. 15p2 As mentioned in Part of which are beyond the scope of this article. SOF Medics
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1, patients with mild-to-moderate levels of G6PD defi- charged with the health and welfare of indigenous populations
ciency may receive primaquine at reduced doses. should refer to the WHO’s current Guidelines for the Treat-
4. At the time of this writing, point-of-care G6PD tests are ment of Malaria in these cases.
both novel and rarely seen in the field, which only serves
to increase the number of indigenous patients who are For SOF Medics not tasked with the medical care of indigenous
ineligible for primaquine therapy. The CareStart G6PD populations, a synopsis of the WHO 2015 Guidelines for the
®
de vice 17p37 shows promise for field use, although it is insen- Treatment of Malaria—synthesized with the guidelines found in
sitive to mild deficiencies and certain female phenotypes. the Oxford Handbook of Tropical Medicine—should suffice for
Note also that G6PD testing may yield unreliable results in the chemoprophylaxis and treatment of their otherwise healthy
profoundly anemic patients. teammates (all doses listed here are for adults) (Tables 1 and
5. Both benign and severe cases of P. vivax may go undetected 2). 20,21 For patients with severe malaria, Medics should be pre-
on microscopy; this apparent absence of parasites is due to pared to manage comorbidities such as anemia, hypoglycemia,
a tendency of the bulk of P. vivax blood-stage schizonts to acidosis, shock, pulmonary edema, bacterial coinfections, and
sequester themselves in bone marrow and the spleen. 15p2 altered mental status and seizures secondary to cerebral malaria.
6. P. vivax infections may occur simultaneously with P. fal-
ciparum in the same host—with P. falciparum’s much According to the WHO, Anopheles mosquitoes living in ar-
higher parasitemia, a Medic could possibly miss the pres- eas where P. vivax is endemic tend to bite people outdoors
ence of P. vivax and fail to administer primaquine. In re- early in the evening—in which case the primary bite avoidance
gions saddled with both P. falciparum and P. vivax, RDTs strategy is covering exposed skin and application of mosquito
used should be capable of distinguishing between the two repellant during this period. 1pvi
species. Table 5 of the WHO report on product testing of
RDTs, round 6 (see pages 40–41 of the full pdf at http:// If the Medic is unsure as to whether the malaria-positive pa-
www.who.int/malaria/publications/atoz/9789241510035 tient he or she is dealing with should be classified as benign or
/en/) may be useful when choosing dual-species RDTs. 18 severe, a useful ad hoc gauge is the ability or inability of the
In some regions, P. falciparum is not detectable using patient to swallow a pill. 7p709
RDTs based on histidine-rich protein 2 (HRP2), which is
the most common target antigen in P. falciparum RDTs. Chloroquine, a long-time mainstay of malaria therapy, is
These regions include most of South America, the China- proving to be less effective over the years as resistance to the
Burma border, central Africa, and the Indian subcontinent. drug steadily increases. Despite the decline of chloroquine ef-
Medics deployed to these areas should consider using RDTs fectiveness, the WHO still recommends chloroquine (or an
that detect non-HRP2 antigens. 4pp32-33 ACT) as a remedy in cases of chloroquine-sensitive P. vivax.

92 | JSOM Volume 17, Edition 3/Fall 2017