Abstract:BackgroundA total dose of chloroquine of 25 mg/kg is recommended by the World Health Organization (WHO) to treat malaria by Plasmodium vivax. In several endemic areas, including the Brazilian Amazon basin, anti-malarial drugs are dispensed in small plastic bags at a dosing regimen based on age. This practice can lead to suboptimal dosing of the drug, which can impact treatment outcomes. The aim of the present study was to estimate the extent of sub-dosing of chloroquine in children and adolescents with vivax m… Show more
“…The use of suboptimal chloroquine dosing also increases the risk of recurrent P. vivax [49]. In a meta-analysis of individual pooled patient data, increasing the total dose of chloroquine from 25 mg/kg to 30 mg/kg, was predicted to reduce the number of recurrent infections by 41% in young children [50].…”
Plasmodium vivax is an important cause of malaria, associated with a significant public health burden. Whilst enhanced malaria-control activities have successfully reduced the incidence of Plasmodium falciparum malaria in many areas, there has been a consistent increase in the proportion of malaria due to P. vivax in regions where both parasites coexist. This article reviews the epidemiology and biology of P. vivax, how the parasite differs from P. falciparum, and the key features that render it more difficult to control and eliminate. Since transmission of the parasite is driven largely by relapses from dormant liver stages, its timely elimination will require widespread access to safe and effective radical cure.
Extent and Burden of Plasmodium vivaxOf the five Plasmodium species that cause human malaria, Plasmodium vivax is the most geographically widespread. The parasite is capable of surviving quiescent for prolonged periods when conditions are not conducive to its ongoing transmission. A century ago P. vivax was prevalent in almost all countries; even though the vivax endemic world has shrunk considerably, over four billion people remain at risk of infection [1]. In 2017, transmission was reported from 49 countries across Central and South America, the Horn of Africa, Asia, and the Pacific islands (Figure 1). In almost two-thirds of coendemic countries P. vivax is the predominant species of malaria (Figure 2), the proportion of malaria attributable to the parasite being greatest in areas where the prevalence of malaria is low (Figure 3) [2,3].Until recently the global burden of P. vivax malaria was derived from estimates of P. falciparum, the most prevalent species causing human malaria. However, a growing awareness of the public health importance of P. vivax has led to the strengthening of surveillance systems and better reporting practices of all of the Plasmodium species. The World Health Organization (WHO) first included P. vivax case estimates in its World Malaria Report (WMR) in 2013, documenting between 11.9 and 22 million P. vivax clinical cases per year [4]. Recent estimates, incorporating national surveillance data, prevalence surveys, and geospatial mapping, have revised the global burden to between 13.7 and 15 million cases in 2017 [1]. An estimated 82% (11.7 million cases) of the global vivax burden comes from four high-burden countries: India, Pakistan, Ethiopia, and Sudan.In sub-Saharan Africa, where the burden of malaria is overwhelmingly attributable to P. falciparum (Figure 1), the low prevalence of P. vivax is attributed to a high proportion of the population having a Duffy-negative blood group. The Duffy antigen is an important molecule for the erythrocytic invasion of P. vivax, and the lack of the receptor on red blood cells reduces the risk of infection [5]. However, a recent review of clinical and vector data has shown that P. vivax is present across almost all malaria-endemic regions of Africa [6].Biological Differences between P. falciparum and P. vivaxThe control and elimination of ...
“…The use of suboptimal chloroquine dosing also increases the risk of recurrent P. vivax [49]. In a meta-analysis of individual pooled patient data, increasing the total dose of chloroquine from 25 mg/kg to 30 mg/kg, was predicted to reduce the number of recurrent infections by 41% in young children [50].…”
Plasmodium vivax is an important cause of malaria, associated with a significant public health burden. Whilst enhanced malaria-control activities have successfully reduced the incidence of Plasmodium falciparum malaria in many areas, there has been a consistent increase in the proportion of malaria due to P. vivax in regions where both parasites coexist. This article reviews the epidemiology and biology of P. vivax, how the parasite differs from P. falciparum, and the key features that render it more difficult to control and eliminate. Since transmission of the parasite is driven largely by relapses from dormant liver stages, its timely elimination will require widespread access to safe and effective radical cure.
Extent and Burden of Plasmodium vivaxOf the five Plasmodium species that cause human malaria, Plasmodium vivax is the most geographically widespread. The parasite is capable of surviving quiescent for prolonged periods when conditions are not conducive to its ongoing transmission. A century ago P. vivax was prevalent in almost all countries; even though the vivax endemic world has shrunk considerably, over four billion people remain at risk of infection [1]. In 2017, transmission was reported from 49 countries across Central and South America, the Horn of Africa, Asia, and the Pacific islands (Figure 1). In almost two-thirds of coendemic countries P. vivax is the predominant species of malaria (Figure 2), the proportion of malaria attributable to the parasite being greatest in areas where the prevalence of malaria is low (Figure 3) [2,3].Until recently the global burden of P. vivax malaria was derived from estimates of P. falciparum, the most prevalent species causing human malaria. However, a growing awareness of the public health importance of P. vivax has led to the strengthening of surveillance systems and better reporting practices of all of the Plasmodium species. The World Health Organization (WHO) first included P. vivax case estimates in its World Malaria Report (WMR) in 2013, documenting between 11.9 and 22 million P. vivax clinical cases per year [4]. Recent estimates, incorporating national surveillance data, prevalence surveys, and geospatial mapping, have revised the global burden to between 13.7 and 15 million cases in 2017 [1]. An estimated 82% (11.7 million cases) of the global vivax burden comes from four high-burden countries: India, Pakistan, Ethiopia, and Sudan.In sub-Saharan Africa, where the burden of malaria is overwhelmingly attributable to P. falciparum (Figure 1), the low prevalence of P. vivax is attributed to a high proportion of the population having a Duffy-negative blood group. The Duffy antigen is an important molecule for the erythrocytic invasion of P. vivax, and the lack of the receptor on red blood cells reduces the risk of infection [5]. However, a recent review of clinical and vector data has shown that P. vivax is present across almost all malaria-endemic regions of Africa [6].Biological Differences between P. falciparum and P. vivaxThe control and elimination of ...
“…2529 patients were excluded, resulting in 6879 patients from 23 studies (one unpublished) and 16 countries in the final analysis ( figure 1 ; appendix pp 10–17 ). 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 In the post-hoc systematic review in Scopus, we did not identify additional eligible studies. Figure 1 Study selection *Includes all patients from four studies excluded on patient-level factors ( appendix p 13 ) and individual patients from additional studies.…”
“…Underdosing is a concern with both CQ and ACTs, potentially leading to inadequate clinical and parasitic responses [ 113 , 118 ]. The total recommended dose of chloroquine in children is 25 mg/kg over 3 days; however, owing to the unavailability of scales to weigh patients in many endemic regions, chloroquine is sometimes dispensed based on age, a practice which may lead to suboptimal dosing [ 115 , 119 ]. Additionally, to achieve clinical cure, prevent relapse, and limit transmission, dormant hypnozoites must be treated [ 81 , 120 ].…”
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.
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