Sexual-Stage Antibody Responses to P. falciparum in Endemic Populations

Abstract

Gametocytes and sporogonic stages are responsible for the spread of disease and drug resistance in the population. Sexual stage immunity affects the infectiousness of gametocytes to mosquitoes. Specific antibodies including anti-Pfs48/45 and anti-Pfs230 antibodies are found in individuals with limited prior exposure to malaria. Sexual stage antibodies are rapidly acquired after infection and are relatively prevalent in gametocytaemic individuals. Functional transmission reducing activity (TRA) is found after primary infections and in young children and appears to depend on recent rather than cumulative exposure to gametocytes. Exposure to gametocytes decreases with age most likely as a consequence of the acquisition of asexual-stage immunity that controls asexual parasite density and consequently gametocytaemia. This results in lower exposure to the antigenic load of gametocytes in semi-immune individuals. Since sexual stage immunity is probably short-lived in the absence of gametocytes, we hypothesize that sexual stage immunity will wane, resulting in low antibody and TRA prevalences in clinically semi-immune carriers.

Characterization of Plasmodium vivax Transmission-Blocking Activity in Low to Moderate Malaria Transmission Settings of the Colombian Pacific Coast

“…This is also in agreement with results from previous studies, where it was shown that sera with low levels of specific antimalarial antibodies rather than blocking induced transmission enhancing. 9 We could not conclusively state that the enhancing phenomenon is produced by antibodies but there is a direct correlation between a decrease in antibody titers and TB ( Figure 1 ). Antibody potency studies have indicated a rapid reduction of blocking activity at sera dilutions of 1:4 and 1:16.…”

“…9,10 Natural TB activity for Plasmodium falciparum infections has been demonstrated but less is known about TB immunity in P. vivax , the most common malaria parasite in Latin America, Asia, and other regions where 132-391 million malaria cases are reported yearly. 11 It has been found that in high P. vivax transmission areas of Sri Lanka only 22% of sera from infected patients living in endemic settings have TB activity, whereas 65% of sera from acute infected patients living in non-endemic areas are blockers.…”

“…The duration of the TB activity in the latter study was < 4 months, 10,12,13 and it was hypothesized that TB immunity depends on recent rather than on cumulative exposure to parasite. 9 In lowto-moderate malaria P. vivax transmissions setting of Latin America, only two studies have been reported, one in Mexico and another in Colombia. 14,15 Both studies indicated high TB activity in infected individuals at the time of malaria diagnosis, but neither addressed the question about duration.…”

Advances and challenges in malaria vaccine development

“…These vaccines could be important tools for malaria elimination and could protect against epidemics if P. falciparum parasites are reintroduced after a period of elimination. The feasibility of this approach is supported by the observation of transmission-blocking antibodies in individuals living in endemic areas (100,101). However, the vaccine would need to be used in the entire population to block transmission.…”

In vivo and in vitro gametocyte production of Plasmodium falciparum isolates from Northern Thailand

“…Gametocyte-specific acquired immunity may actually reduce with age, in contrast to that induced against asexual parasites, as a result of infections in adults producing fewer gametocytes; this phenomenon has been proposed to be a deliberate strategy by the parasite in order to limit the acquisition of transmission blocking immunity Bousema et al, 2006a). Interestingly, recent work has suggested that host genetic factors influence whether asymptomatic infections will produce gametocytes (Lawaly et al, 2010).…”