Transmission‐reducing immunity is inversely related to age in Plasmodium falciparum gametocyte carriers

Abstract

Immunity to the sexual stages of Plasmodium falciparum is induced during natural infections and can significantly reduce the transmission of parasites to mosquitoes (transmission reducing activity; TRA) but little is known about how these responses develop with increasing age/exposure to malaria. Routinely TRA is measured in the standard membrane feeding assay (SMFA). Sera were collected from a total of 199 gametocyte carriers (median age 4 years, quartiles 2 and 9 years) near Ifakara, Tanzania; 128 samples were tested in the SMFA and generated TRA data classified as a reduction of > 50% and > 90% of transmission. TRA of > 50% was highest in young children (aged 1-2) with a significant decline with age (chi(2) trend = 5.79, P = 0.016) and in logistic regression was associated with prevalence of antibodies to both Pfs230 and Pfs48/45 (OR 4.03, P = 0.011 and OR 2.43 P = 0.059, respectively). A TRA of > 90% reduction in transmission was not age related but was associated with antibodies to Pfs48/45 (OR 2.36, P = 0.055). Our data confirm that antibodies are an important component of naturally induced TRA. However, whilst a similar but small proportion of individuals at all ages have TRA > 90%, the gradual deterioration of TRA > 50% with age suggests decreased antibody concentration or affinity. This may be due to decreased exposure to gametocytes, probably as a result of increased asexual and/or gametocyte specific immunity.

Naturally Acquired Immune Responses to Plasmodium falciparum Sexual Stage Antigens Pfs48/45 and Pfs230 in an Area of Seasonal Transmission

“…Spearman's rank correlation test was used to assess association between antibody levels of tested antigens. The association between Pfs230 and Pfs48/45 antibody responses and functional transmission-reducing activity (TRA) in the standard membrane feeding assay (SMFA) in previous studies (9,11,18) was presented after categorization of TRA as Ͼ50% and Ͼ90% reduction (9,11,18) and calculating odds ratios (OR) with 95% confidence intervals (95% CI). The level of significance was set at a two-tailed P value of Ͻ0.05.…”

“…The volume of plasma that remained from this study was insufficient to study functional transmission-reducing activity in the standard membrane feeding assay (SMFA). To aid interpretation of the current results, paired ELISA-SMFA data from three studies (9,11,18) were combined and are presented in Table 4. Sexual stage antibody responses were determined using exactly the same ELISA methodology as used in the current study.…”

“…A proportion of gametocytes die in the human host without being passed on to a mosquito, thereby exposing sexual stage antigens to the human immune system. Sexual stage-specific antibodies may be elicited against these antigens (31) and may play a role in transmission-blocking immunity by preventing fertilization or the development of sporogonic stage parasites in mosquitos (4,7,18,20,21,42,44,49). These antibody responses may reduce the spread of malaria in human populations.…”

“…Pfs230 and Pfs48/45 are major gametocyte and gamete surface antigens that induce antibody responses in naturally exposed individuals (7,18,21,42,44) that are associated with functional transmission-reducing immunity (21,25,42,44).…”

Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

“…[1][2][3][4][5] A variety of determinants modulate transmission, including gametocyte quality, vector competence, and human innate and acquired immunity. Although host antibodies [6][7][8] have been shown to affect parasite infectivity for mosquitoes, transmission inefficiency is still observed in malaria hypoendemic regions where presence of antibody is thought to be low. 2,9 Previous work in Sri Lanka has suggested that humoral factors associated with the malarial paroxism reduces parasite infectivity for mosquitoes.…”