Plasmodium vivax in Children: Hidden Burden and Conspicuous Challenges, a Narrative Review

Abstract

There has been progress towards decreasing malaria prevalence globally; however, Plasmodium vivax has been less responsive to elimination efforts compared with Plasmodium falciparum . P. vivax malaria remains a serious public health concern in regions where it is the dominant species (South and South-East Asia, the Eastern Mediterranean region, and South America) and is increasingly recognized for its contribution to overall morbidity and mortality worldwide. The incidence of P. vivax decreases with increasing age owing to rapidly acquired clinical immunity and there is a disproportionate burden of P. vivax in infants and children, who remain highly vulnerable to severe disease, recurrence, and anemia with associated developmental impacts. Diagnosis is sometimes difficult owing to the sensitivity of diagnostic tests to detect low levels of parasitemia. Additionally, the propensity of P. vivax to relapse following reactivation of dormant hypnozoites in the liver contributes to disease recurrence in infants and children, and potentiates morbidity and transmission. The 8-aminoquinolines, primaquine and tafenoquine, provide radical cure (relapse prevention). However, the risk of hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency necessitates testing prior to administration of 8-aminoquinolines, which has limited their uptake. Additional challenges include lack of availability of pediatric dose formulations and problems with adherence to primaquine owing to the length of treatment recommended. A paucity of data and studies specific to pediatric P. vivax malaria impacts the ability to deliver targeted interventions. It is imperative that P. vivax in infants and children be the focus of future research, control initiatives, and anti-malarial drug development. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-022-00713-w.

Expression, Purification, and Characterization of Plasmodium vivax Lactate Dehydrogenase from Bacteria without Codon Optimization

“…Second, it can be used for the development of bioreceptors such monoclonal antibodies and aptamers for the diagnosis of P. vivax -specific malaria [ 32 , 55 ]. As mentioned above, since the life cycle of P. vivax in the human host is different that of P. falciparum [ 13 , 14 , 15 , 16 , 17 , 18 ], the parasite must be distinguished. Finally, it can be used as a useful tool for basic research related to identification of the metabolic pathway of parasites involved in PvLDH.…”

“…P. vivax forms a hypnozoite (dormant form) in the liver, which unless completely eliminated, can get re-activated and cause recurrence of malarial infection [ 9 , 10 , 11 , 12 , 13 ]. In addition, recent studies have revealed that P. vivax evades the host immune system [ 14 ], is fatal to infants and children [ 15 ], and invades the reticulocytes (called young red blood cells) [ 16 , 17 , 18 ]. Therefore, measures for eliminating P. vivax are completely warranted.…”

Modelling the within-host dynamics ofPlasmodium vivaxhypnozoite activation: an analysis of the SPf66 vaccine trial

“…Plasmodium vivax is now the predominant malaria parasite species in most of endemic Asia and Latin America. It is an important cause of morbidity and developmental delay in children, and in high transmission settings it contributes to childhood mortality via severe anaemia [45]. The main barrier to P. vivax elimination is relapse.…”

Optimal balance of benefit versus risk for tafenoquine in the treatment of Plasmodium vivax malaria

“…Therefore, relapse prevention through adequate 8-aminoquinoline anti-hypnozoite activity must be balanced with the need to avoid clinical haemolysis due to widespread erythrocyte loss associated with G6PD deficiency [ 20 , 22 ]. To minimize risk, the WHO recommends G6PD testing for all individuals before the administration of curative doses of 8-aminoquinolines, where feasible [ 8 , 23 ].…”