Prevalence of Plasmodium falciparum transmission reducing immunity among primary school children in a malaria moderate transmission region in Zimbabwe

Abstract

Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide. Antigens in the various life cycle stages of malaria parasites are presented to the immune system during natural infection and it is widely recognized that after repeated malaria exposure, adults develop partially protective immunity. Specific antigens of natural immunity represent among the most important targets for the development of malaria vaccines. Immunity against the transmission stages of the malaria parasite represents an important approach to reduce malaria transmission and is believed to become an important tool for gradual elimination of malaria. Development of immunity against Plasmodium falciparum sexual stages was evaluated in primary school children aged 6–16 years in Makoni district of Zimbabwe, an area of low to modest malaria transmission. Malaria infection was screened by microscopy, rapid diagnostic tests and finally using nested PCR. Plasma samples were tested for antibodies against recombinant Pfs48/45 and Pfs47 by ELISA. Corresponding serum samples were used to test for P. falciparum transmission reducing activity in Anopheles stephensi and An. gambiae mosquitoes using the membrane feeding assay. The prevalence of malaria diagnosed by rapid diagnostic test kit (Paracheck)™ was 1.7 %. However, of the randomly tested blood samples, 66% were positive by nested PCR. ELISA revealed prevalence (64% positivity at 1:500 dilution, in randomly selected 66 plasma samples) of antibodies against recombinant Pfs48/45 (mean A405nm = 0.53, CI=0 .46 to 0.60) and Pfs47 (mean A405nm= 0.91, CI=0.80to 1.02); antigens specific to the sexual stages. The mosquito membrane feeding assay demonstrated measurable transmission reducing ability of the samples that were positive for Pfs48/45 antibodies by ELISA. Interestingly, 3 plasma samples revealed enhancement of infectivity of P. falciparum in An. stephensi mosquitoes. These studies revealed the presence of antibodies with transmission reducing immunity in school age children from a moderate transmission area of malaria, and provide further support to exploit target antigens such as Pfs48/45 for further development of a malaria transmission blocking vaccine.

The Relative Effects of Artemether-lumefantrine and Non-artemisinin Antimalarials on Gametocyte Carriage and Transmission of Plasmodium falciparum: A Systematic Review and Meta-analysis

“…Surprisingly, field trials suggest gametocyte carriage may persist longer in older than younger children [49]. Immune-mediated clearance of gametocytes remains incompletely characterized, and age-related immunity appears to differ in regard to clearance of gametocytes and that of asexual parasites [49][50][51].…”

Plasmodium P47 : a key gene for malaria transmission by mosquito vectors

“…The human immune system is another possible selective force on Pfs47 , as gametocytes not ingested by mosquitoes can elicit immunity [52,53], and antibodies following immunization with recombinant P. vivax Pvs47 have transmission-blocking activity [54]. This has led us to re-evaluate Pfs47 as a potential transmission-blocking vaccine target.…”

Immune Responses to Gametocyte Antigens in a Malaria Endemic Population—The African falciparum Context: A Systematic Review and Meta-Analysis

“…A total of 9 studies carried out over 14 study sites measured immune responses to Pfs48/45. The range of seroprevalence estimates reported was 0% from Stone et al's study sites in Burkina Faso (20) to 64% reported by Paul et al from their study in the Makoni district in Zimbabwe (43). As with Pfs230, there was significant heterogeneity between the studies, I 2 = 96% (95% CI: 95–97%), and hence no pooled estimate was calculated (Figure 3).…”