Plasmodium vivax Thematic Review EPIDEMIOLOGY - Oxford

Plasmodium vivax Thematic Review EPIDEMIOLOGY Thematic evidence review submitted to the Writing Committee for the development of the Global Strategic Plan on Plasmodium vivax Control and Elimination

Rosalind E. Howes Katherine E. Battle Nick Golding Simon I. Hay Malaria Atlas Project Spatial Ecology and Epidemiology Group Department of Zoology University of Oxford

P. vivax thematic review – Epidemiology

Acknowledgments The authors would like to thank Richard Cibulskis and Erin Shutes for guidance on the structure and contents of the report, and sharing WHO case data for the ratio trend analysis. We also thank Nick Anstey and Kevin Baird for comments on an early version of the section: “Severe and lethal P. vivax”. We acknowledge Dave Smith for sharing unpublished results on the age distribution of P. vivax infection and Ivo Mueller for unpublished data which fuelled this analysis. We also acknowledge Andy Tatem for unpublished data on the proportions of Plasmodium species among returning travellers and Kamini Mendis for unpublished data regarding temporal trends in P. falciparum to P. vivax case ratios. Finally we thank Antoinette Wiebe, Kirsten Duda and Maria Devine for proof‐reading.

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Contents

Section 1: The distribution of P. vivax infection

Part 1. Geography………………………………………………………………………………………………..…..4

Part 2. Relapse………………………………………………………………………………………………………..28 Part 3. Temporal trends P. falciparum / P. vivax ratios…………………………………….………39

Section 2: Cases Part 1. Primary risk groups……………………………………………………………………..………..…….49 Part 2. Asymptomatic infections……………………………………………………………………………..60 Part 3. Estimates of P. vivax cases in 2010……………………………………………………………...66

Section 3: Severe and lethal P. vivax ……………………………………….………………….…74

Section 4: Chloroquine resistant P. vivax…………………..…………………………………82

Annex: Maps of uncertainty associated with predictions of P. vivax endemicity……….………...92

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Section 1: The distribution of P. vivax infection Part 1. Geography I.

Introduction to the geography of P. vivax

Plasmodium vivax is epidemiologically and biologically different to P. falciparum, and it is not, therefore, advisable to assume that control methods developed for falciparum malaria will prove transferable to vivax malaria with satisfactory results [1‐4]. Assessment of geographic variations in the level of endemicity of each parasite species is essential to estimate the burden of the disease, measure the impact of control and assess the feasibility and strategy of elimination [5, 6]. Biological features of P. vivax that distinguish it from P. falciparum present unique challenges to the control of the parasite [7‐9]; in elimination settings, P. vivax is often the ‘last parasite standing’ [5, 6, 10‐12]. Plasmodium vivax gametocytes are present earlier in the progression of a primary or recrudescent infection than P. falciparum [7, 13], such that the majority of patients have sufficient gametocytaemia to allow onward transmission even before the host becomes ill and seeks diagnosis and treatment [14‐16]. Plasmodium vivax gametocytes are transmitted more efficiently to Anopheles mosquito vectors [17, 18] than those of P. falciparum and are transmissible at lower parasite densities [8]. Within the mosquito, vivax sporozoites develop faster than P. falciparum and with slightly wider temperature range tolerances. Finally, P. vivax places dormant stage parasites in the liver of the human host, and these forms offer a safe haven during long, mosquito‐free cold seasons in frigid temperate climes. All of these factors conspire in creating a much wider geographical distribution [19], as shown in Figure 1.1. To accurately illustrate P. vivax endemicity, it is necessary to consider the distribution of the Duffy‐ negative phenotype. The varying prevalence of Duffy negativity in populations throughout the world is a significant determinant of the distribution of P. vivax [20]. Duffy‐negative individuals have historically been considered wholly refractory to P. vivax infection. The phenotype is found at highest frequencies in Africa, whereas it is relatively rare elsewhere [21]. The influence of Duffy negativity on P. vivax transmission reinforces the need to differentiate strategies employed to generate and interpret maps of P. vivax endemicity from those used for P. falciparum [22, 23]. Recent studies demonstrating P. vivax in Duffy negative patients raise concerns regarding a potential Duffy‐independent invasion mechanism, but this remains poorly understood, requiring further investigation[24]; nevertheless, this emphasizes the importance of mapping the parasite and Duffy phenotype/genotype. Global estimates of the frequencies of Duffy negativity [21] are incorporated into the figures in this chapter. Modelled spatial data on P. vivax transmission and prevalence [25, 26] are presented here as maps and estimates of geographic limits of transmission, endemicity, and populations at risk for each WHO region. 4


A

B

Figure 1.1. The spatial distribution of Plasmodium falciparum malaria endemicity compared to Plasmodium vivax. Panel A shows the limits and endemicity of P. falciparum and panel B, P. vivax. Both map the 2010 spatial limits of parasite‐specific malaria risk defined by annual parasite incidence (PvAPI) with further medical intelligence, temperature and aridity masks. Areas were defined as stable, unstable (dark grey areas, where PvAPI 70%. Plasmodium vivax (B) estimates of the parasite rate standardized to 1 to 99 year olds (PvPR1–99) range from 0% to 7% and are also shown as a spectrum of blue to red. Areas in which Duffy negativity gene frequency is predicted to exceed 90% [21] are shown in hatching for additional context in panel B.

II.

Distribution of P. vivax infections and limits of transmission

Table 1.1 shows our estimates of the population at risk (PAR) of infection by WHO region. These values were generated by combining maps of the limits of transmission with 1 km × 1 km resolution gridded population surfaces for 2010 projected from the Global Rural‐Urban Mapping Project (GRUMP) year 2000 beta version population counts [27, 28]. Fine‐scale population data were used to ensure the detailed variations in risk level described in our limits maps are appropriately assigned to the underlying population. 5

P. vivax thematic review – Epidemiology Table 1.1. Areas and populations at risk* of Plasmodium vivax malaria in 2010 by WHO region. Area (million km2) Population (million) Unstable Stable Any risk Unstable Stable Any risk African Region 17.36 1.47 18.83 19.23 36.80 56.02 Region of the Americas 1.38 8.08 9.46 87.66 49.79 137.45 Eastern Mediterranean Region 4.24 0.60 4.84 176.11 47.37 223.48 European Region 0.40 0.02 0.42 15.72 1.40 17.12 South‐East Asia Region 2.11 3.88 5.99 691.71 748.38 1440.09 Western Pacific Region 3.06 1.30 4.36 533.04 81.16 614.20 World 28.55 15.35 43.90 1523.47 964.90 2488.37 *Risk is stratified into unstable risk (PvAPI 7% prevalence). The methods used to generate these figures are described in detail elsewhere [25, 26, 29]. Throughout the world, endemicity was predicted within a relatively narrow range, with the point estimate of the P. vivax PR age‐standardised to the 1–99 year age range (PvPR1–99) rarely exceeding 7%.

Figure 1.2. Plasmodium vivax endemic countries by WHO region. The WHO regions are shown by colour: the African Region (AFRO) in green, the Region of the Americas (AMRO) in orange, the Eastern Mediterranean Region (EMRO) in blue, the European Region (EURO) in burgundy, the South‐East Asian Region (SEARO) in purple and the Western Pacific Region (WPRO) in dark green. The countries in each region that are not endemic for P. vivax are slightly greyed‐out and shaded a lighter colour. Those countries that are endemic only with P. vivax malaria are outlined in red.

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A

B

Figure 1.3. The global spatial distribution of Plasmodium vivax malaria endemicity. Panel A shows the 2010 spatial limits of P. vivax malaria risk defined by Plasmodium vivax annual parasite incidence (PvAPI) with further medical intelligence, temperature and aridity masks. Areas were defined as stable (dark grey areas, where PvAPI ≥ 0.1 per 1000 per annum), unstable (medium grey areas, where PvAPI