Date Published: November 20, 2015
Publisher: Public Library of Science
Author(s): Rosalind E. Howes, Robert C. Reiner Jr., Katherine E. Battle, Joshua Longbottom, Bonnie Mappin, Dariya Ordanovich, Andrew J. Tatem, Chris Drakeley, Peter W. Gething, Peter A. Zimmerman, David L. Smith, Simon I. Hay, Hernando A del Portillo. http://doi.org/10.1371/journal.pntd.0004222
Abstract: Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv) transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health significance of Pv, as well as the other neglected non-Pf parasites, which are currently invisible to most public health authorities in Africa, but which can cause severe clinical illness and require specific control interventions.
Partial Text: Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). The identification of the Duffy antigen as the obligate trans-membrane receptor for P. vivax (Pv) infection of red blood cells by Miller et al. during the 1970s [1,2] stalled research into the epidemiology of Pv in Africa as indigenous populations on this continent were known to rarely express the Duffy antigen (and therefore be resistant to infection) and the dogma of “Pv absence from Africa” became entrenched [3,4]. However, against a backdrop of increasing appreciation for the clinical severity of Pv infection [5–7], multiple sources of evidence suggest that Pv may be more prevalent on this continent than commonly perceived [3,8–10]. The absence of any thorough effort to unify these sporadic reports, however, precludes appraisal of their significance, and assessment of the public health significance of Pv in sub-Saharan Africa.
The broad aims of this study were to evaluate what, if any, evidence existed of Pv transmission in Africa, and to explore whether the small subset of known susceptible individuals (i.e. Duffy positives) could be sustaining the observed prevalence levels reported from community surveys. Here, details are given about (i) the evidence base assembly, (ii) the unified framework weighting the evidence, (iii) quantification of the Duffy positive population at risk of infection (PvPAR), (iv) the prevalence data analysis in relation to PvPAR, and (v) reports of Pv infections in Duffy negative hosts.
It is evident that Pv is not absent from Africa. There is robust evidence from a variety of corroborating sources of Pv transmission across all sub-regions, with direct evidence from 21 of the 47 countries considered, and 42 countries are attributed with infection of visiting travellers. Overall, there was moderate to conclusive evidence of Pv transmission from within 18 countries. The remaining countries either had only weak evidence of transmission or no evidence could be found at all. These observations of widespread Pv infection should not be surprising: a suitable environment, competent vectors and susceptible human hosts make it unlikely that the parasite would not be present. The implications of the present Pv-specific study apply to all non-Pf species: without adequate diagnosis and reporting, their true public health burden cannot be determined. While Po and Pm are more widely acknowledged to be endemic to parts of Africa, Pf-specific diagnostics will not diagnose the low-level parasitaemia and non-specific symptoms that the non-Pf malarias present as, and radical cure is not available for either of the relapsing species, Pv or Po.