**6. Vaccination**

A vaccine that prevents the seeding of human livers by both active schizonts and dormant hypnozoites of *P. vivax* would provide a conspicuously useful tool in eliminating this species. Mass or routine vaccination now seems impractical with non-sterilizing vaccines of short-lived immunity needing 3 or 4 doses. These may improve in the future, but even now a malaria vaccine could be applied in geographically or demographically narrowed settings to potentially great impacts. For example, high-risk and hard-to-reach populations like migrant workers or soldiers having sterile immunity to malaria (even if for just a season or two) may not only protect those people from harm but also greatly slow importation of malaria into receptive areas where transmission has been interrupted. Likewise, people living in areas prone to reintroduction of endemic malaria by high volumes of immigration from high-risk areas may be immunized and protected against very dangerous outbreaks and epidemics [69].

systems offering protection against *P. vivax* would represent a quantum leap forward for vaccination against this species by effectively sidestepping the requirement for continuous labo-

Challenges in the Control and Elimination of *Plasmodium vivax* Malaria

http://dx.doi.org/10.5772/intechopen.77082

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The greatest challenge in eliminating vivax malaria—the hypnozoite reservoir—may also be the greatest opportunity to accomplish the task. If >80% of incident malaria cases indeed derive from hypnozoites, then surely attacking and shrinking that reservoir would deliver substantial reductions in the burden of morbidity and mortality. Despite the availability of PQ for over 65 years, sustained and systematic assault on that reservoir has not been accomplished in the endemic tropics—largely due to the unsolved clinical problem of its hemolytic

Eliminating *P. vivax* malaria will require accepting the inadequacy of conventional falciparum malaria-focused control strategy, tactics, and tools and committing to the optimizing and validating of interventions suited to this stubborn parasite. This effectively means striving to solve the wrenchingly difficult problem of the hemolytic toxicity of PQ in G6PD-deficient patients by almost any means. The obstacles presented in managing populations and individual patients carrying this infection emphasize the great advantage of preventing it in the first place with an effective vector control strategy. In this context, species sanitation has proven highly effective against endemic Asian malarias a century ago [54] and would probably do

Taking all these factors into considerations, we recommend the following measures for elimi-

**1.** Active case detection and early treatment are essential steps, fundamental to eliminating any endemic malaria; however, this measure alone will not lead to elimination—too many

**2.** Adoption of safe and universal access to radical cure for cases of vivax malaria along with universal access to alternative means of relapse prevention for people ineligible for therapy with 8-aminoquinolines would accelerate progress to elimination. Achieving that will likely also require better diagnostics for both the parasite and G6PD deficiency than are

**3.** Adoption of radical cure with an 8-aminoquinoline and ACT with diagnosis of any species of malaria where *P. vivax* also occurs as a means of targeting likely carriers of hypnozoites.

**4.** Reduce new vivax infections/seeding of the liver with hypnozoites by substantially reducing human contact with malaria vectors, effectively stranding extant parasites in all stages of human infection—latent, sub-patent, patent, and eventually vanishing without *Anopheles* contact and onward transmission. Interrupting transmission by species sanita-

tion measures may be the most durable and effective means of achieving this goal.

infections are latent, sub-patent, sequestered, and asymptomatic.

ratory cultivation for a live vaccine.

toxicity in G6PD-deficient patients.

nating endemic vivax malaria:

currently available.

so again.

**7. Challenges and recommendations**

Today, there is no vaccine available that can prevent infection by *P. vivax* with high levels of sterilizing immune protection. That is also true for all other plasmodial species. The half-century-long efforts to develop a vaccine against *P. falciparum*—greatly aided by the ability to cultivate this species in continuous laboratory cultures since the late 1970s culminated in the molecular subunit vaccine called RTS,S ASO1 (mimicking a proteincoating infectious sporozoites) [70] with the registered trademark name Mosquirix™ (GlaxoSmithKline). The vaccine did not prevent infection in the African infants and young children vaccinated but had the modest effects against higher parasitemias and signs of illness [67]. The modest efficacy combined with worrying and puzzling signals like increased risk of pneumococcal meningitis and significantly higher all-cause mortality among vaccinated females apparently explains the WHO position to withhold a favorable opinion on the vaccine until further studies involving targeted and limited rollout in several African nations are completed [71]. Molecular subunit vaccines targeting *P. vivax* molecules have not progressed beyond Phase 2a and show similar inability to achieve high levels of sterilizing protection [72].

Over the past decade, investigators applying live-attenuated sporozoites of *P. falciparum* have shown high levels of durable (~12 months) sterilizing protection in malaria-naïve adult volunteers in controlled human malaria infection (CHMI) experiments using a challenge strain homologous to the vaccine strain [73]. This approach relies on laboratory harvest of infectious sporozoites from laboratory-reared aseptic anopheline mosquitoes infected by *P. falciparum* maintained in the laboratory. Deriving live-attenuated sporozoites of *P. vivax* is possible [74] but exceedingly difficult, not strain-specific, and not sustainable as a source of vaccine. Nonetheless, immunization by irradiated sporozoites of the murine species *Plasmodium berghei* cross-protected against the murine species *Plasmodium yoelii* and *vice versa* in murine challenge models [75]. The possibility of sporozoites of *P. falciparum* cross-protecting against *P. vivax* challenge has not been examined directly, but proteomic analyses showed that these two human plasmodia species shared substantially more common probable T-cell epitopes than that between *P. berghei* and *P. yoelii*. A vaccine derived from laboratory-kept *P. falciparum*

systems offering protection against *P. vivax* would represent a quantum leap forward for vaccination against this species by effectively sidestepping the requirement for continuous laboratory cultivation for a live vaccine.
