Malaria is a critical infectious disease of public health importance that provokes considerable mortality in all endemic countries. The tremendous gains seen in cases and mortality reduction is as a result of deliberate intervention strategies [1]. However, the observed benefit has seen a plateau in the last two years especially in Africa where the greatest burden of disease is mostly impacted. In sub-Saharan Africa (sSA), majority (99%) of the infections is thought to be due to Plasmodium falciparum and rarely by P. ovale, P. malariae, with P. vivax not even being considered in the picture as one of the players [1] of malaria infection. With the availability of tools that are more sensitive, the detection of non-falciparum and even vivax human malaria parasites has gained more attention in sSA [2–6].
Historically, P. vivax prevails in Asia, [7, 8], South America [9, 10] and has some scanty presence in the Horns of Africa such as in Djibouti [11], Eritrea [12], Somalia [13, 14], Ethiopia [15–18] and Sudan [19, 20]. Thus P. vivax has a much wider geographical distribution unlike falciparum malaria which in a more specific term, can be said to have a much focal distribution in Africa.
Hence, the former notion is that, P. vivax originates from Asia and South America and gradually finds its way into Africa through the trade-route corridor. However, there are some current evidences supporting the hypothesis that, P. vivax could have originally evolved from a vivax-like strain detected in non-human primates in Africa [21, 22] and from there, dispersed to other continents during the period of human migration. Although, both hypotheses (whether from Africa to Asia or, Asia to Africa) require further validation. However, it seems likely that there might be an interplay of both hypothesis, in which case, simultaneous occurrence takes place and selective adaptation of the Duffy negative allele in sSA might have resulted in the absence of vivax malaria in the region. Nonetheless, later re-introduced when individuals expressing the Duffy null allele travels between continents and countries.
The Duffy (gp-FY; CD234) gene is the fourth red blood cell (RBC) gene after thalassemia, sickle cell anaemia and glucose-6-phosphate dehydrogenase (G6PD) associated with resistance to Plasmodium species [23] with particular protection against vivax malaria. Also known as the Duffy antigen receptor for chemokines (DARC), it is a variable receptor usually expressed on the surface of the red blood cell (RBC) and employed by P. vivax merozoites in gaining access in the RBCs and establishing its erythrocytic infection [24]. The DARC, located on chromosome 1 has two exons, and a single nucleotide substitution from a thymine (T) to a cytosine (C), upstream in the promoter region nullifies the expression of this gene on the RBCs, resulting in the FYO* allele [25]. This FYO* null allele predominates amongst sSA inhabitants as with African-Americans but has a very sparse representation in individuals of other ancestry [26]. Thus, the FYO* null allele has been validated to confer protection against P. vivax infection in this sub-region. Nevertheless, 11 countries in this region (Oboh et al unpublished data) have reported the occurrence of P. vivax, making it more real that vivax malaria might be gradually finding its way into sSA, thus it can be postulated that hidden transmission is occurring in this region. In some of these studies, such as in those conducted in Angola, Cameroon, Kenya, Madagascar, Mali and Mauritania, the Duffy status of the infected individuals was characterized and they were found to be mostly Duffy negative [3, 4, 27–30]. In others, however, the investigators were concerned with the identification of P. vivax without stating the Duffy status of the infected individuals [5, 31–33]. Interestingly, all studies were carried out amongst indigenous individuals with little or no travel history to vivax endemic areas, thus ruling out the possibility of imported infection.
In Nigeria, P. falciparum is responsible for > 95% of malaria infection, with P. malariae and P. ovale contributing a meagre < 5% of infection [1, 34]. Data implicating P. vivax infection in Nigeria includes its detection in a visiting pregnant female [35], two cases detected by microscopy [36, 37], both of which were not confirmed by any molecular technique and our previous study [6] which detected five Duffy negative individuals to be infected with P. vivax isolates and were subsequently confirmed by capillary sequencing.
Thus, as a follow-up to our previous study, we have collected samples from two sites – Oredo and Kosofe in Edo and Lagos state respectively and used the classical PCR method, to confirm additional P. vivax isolates (both single and mixed infection) by sequencing, as well as determined the Duffy status of the individuals. The importance of such genomic epidemiological studies cannot be undermined in this era of malaria elimination, as attention also needs to be given to non-falciparum infection, if the ambitious albeit, achievable 2030 elimination goal is to be reached.