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

Plain Language Summary Plasmodium vivax malaria is the most common type of malaria in South and South-East Asia, the Eastern Mediterranean region, and South America. Following a mosquito bite, the P. vivax parasite enters the blood and travels to the liver. It may cause malaria immediately or lie dormant and reactivate to cause relapses, weeks, months, or even years later. In P. vivax endemic regions, population immunity develops over time with repeated exposure to the parasite. Children bear the burden of disease since they have not acquired clinical immunity. Repeated relapses can cause anemia and affect growth and development. Radical cure refers to treatment of parasites in the blood and dormant parasites in the liver to prevent relapse. Until recently, primaquine was the only medicine approved for radical cure. When a primaquine regimen (7-14 days, depending on dose) is not completed, it is less effective. Additionally, there is no pediatric formulation currently available. Recently, tafenoquine, prescribed as a single dose, was approved for radical cure in children. Before radical cure, testing patients for deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD) is necessary since patients with this deficiency may have rupturing or destruction of red blood cells. However, access to G6PD deficiency testing is limited, creating barriers to treatment. Eradication of P. vivax is challenging due to its ability to relapse, and the treatment challenges described above. It is imperative that future elimination efforts focus on improving access to curative treatments for infants and children who bear the burden of disease. 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.