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Quantitatively assessing the impact of naturally occurring transmission-blocking (TB) immunity on malaria parasite sporogonic development may provide a useful interpretation of the underlying mechanisms. Here, we compare the effects of plasma derived from 23 naturally infected gametocyte carriers (OWN) with plasma from donors without previous malaria exposure (AB) on the early sporogonic development of Plasmodium falciparum in Anopheles gambiae. Reduced parasite development efficiency was associated with mosquitoes taking a blood meal mixed with the gametocyte carriers' own plasma, whereas replacing autologous plasma with non-immune resulted in the highest level of parasite survival. Seven days after an infective blood meal, 39.1% of the gametocyte carriers' plasma tested showed TB activity as only a few macrogametocytes ingested along with immune plasma ended up as ookinetes but subsequent development was blocked in the presence of immune plasma. In other experiments (60.9%), the effective number of parasites declined dramatically from one developmental stage to the next, and resulted in an infection rate that was two-fold lower in OWN than in AB infection group. These findings are in agreement with those in other reports and go further by quantitatively examining at which transition stages TB immunity exerts its action. The transitions from macrogametocytes to gamete/zygote and from gamete/zygote to ookinete were identified as main targets. However, the net contribution of host plasma factors to these interstage parasite reductions was low (5–20%), suggesting that irrespective of the host plasma factors, mosquito factors might also lower the survival level of parasites during the early sporogonic development. [ABSTRACT FROM AUTHOR]

Transmission Blocking Immunity (Tbi) Was Studied In Relation To Age, Gametocyte Density And Transmission Intensity. Subjects With High Gametocytaemias Were Selected In A Hypo-endemic Urban District And A Hyper-endemic Rural Area In South Cameroon. Tbi Was Determined In Blood From Gametocyte Carriers In A Bioassay (Direct Membrane Feeding Assay), With Either Autologous Plasma (Own) Or Control Serum (Ab). Mosquito Infection Rates (Ir) Were Compared. Infection Rates Correlated Positively With Gametocyte And Oocyst Densities. Three Tbi Indicators Were Analysed: The Proportion Of Transmission Reducers (Irab > Irown, P  < 0·01), The Mean Intensity Of Tbi (Irab – Irown), And The Contribution Of Tbi To Total Inhibition [(Irab – Irown)/(100 −irown)]. We Could Not Discriminate Between Areas With Regard To Either The Proportion Of Transmission Reducers (Urban 15% And Rural 29%) Or The Mean Levels Of Tbi (Urban 10% And Rural 9%), Or Contribution Of Tbi To Total Inhibition (Urban 10% And Rural 13%). There Was No Relationship Between Tbi Indicators And Age, But A Trend Of Increasing Values Was Observed With Rising Gametocytaemia, Which Was Considered As A Confusing Factor. A Multivariable Analysis Showed That The Probability Of Being A Reducer Was 4·6 Fold Higher In The Rural Area Than In The Urban District. [ABSTRACT FROM AUTHOR]

Malaria transmission from humans to mosquitoes was assessed in two neighbouring villages in a rural area near Yaoundé, Cameroon during high and low transmission seasons during 1998–2000, using several indices previously evaluated in different areas endemic for malaria but never directly compared. These indices were estimated from human parasitological data and mosquito infection rates and, for each individual, thick blood films were prepared at the same time as experimental infection of laboratory-bred mosquitoes. Among the 685 volunteers examined, the prevalence of Plasmodium falciparum gametocyte carriers was 16%, and 8% of individuals were able to infect mosquitoes. The percentage of mosquitoes that became infected by feeding on the infectious individuals was 21 %. Children aged < 10 years contributed to about 75% of the infectious reservoir, although they constituted only 35% of the total population. Differences were found between the transmission seasons and the villages, and varied according to the index examined. Although there were more infectious individuals in one of the two villages, they were less infectious than those in the other village during the high transmission season. Comparative analysis of the transmission indices suggests the existence of functioning transmission-blocking immunity in one of the villages, which until now has been only hypothetically considered to play a role in malaria transmission in a natural setting. The epidemiological value of all the indices used and their accuracy in estimating the human infectious reservoir and its natural or induced variations are discussed. [Copyright &y& Elsevier]

We conducted parasitological and entomological malaria surveys among the population of Mengang district in southern Cameroon to analyse the relationship between malaria transmission intensity and malaria morbidity. We investigated two adjacent areas which differ 10-fold in transmission intensity [annual entomological inoculation rate (EIR) 17 vs. 170], but have very similar Plasmodium falciparum malariometric profiles with parasite prevalences of 58 vs. 64%, high parasitaemia prevalences (> 1000 parasites/microl) of 15 vs. 16% and the same morbidity of 0.17-0.5 attacks/person/year. Plasmodium malariae prevalence was 14 vs. 16%. One possible explanation is that the similarity of the duration of the short and high transmission seasons in both areas is equally, if not more, significant for parasitological and clinical profiles as the annual EIR. We discuss the relationships between variations in transmission levels, parasitaemia and clinical incidence, and draw parallels to similar situations elsewhere. [ABSTRACT FROM AUTHOR]

Background: Individuals may be homozygous (SS) or heterozygous (AS) sickle cell gene carriers or have normal adult haemoglobin (AA). Haemoglobin S could have a protective role against malaria but evidence is sparse and the operating mechanisms are poorly known.Methods: We followed two cohorts of children. The first was enrolled at birth (156 newborn babies) and the second at 24-36 months old (84 children). Both cohorts were followed for 30 months; monthly for parasitological data and half yearly for immunological data.Results: In the first cohort, 22%, and in the second 13% of children were AS. Whatever their age parasite prevalence rates were similar in AA and AS individuals. Mean parasite densities increased less rapidly with age in AS than in AA children, and were significantly lower in AS than in AA children >48 months old. The AA children tended to be more often admitted to hospital than AS children (22% versus 11%, NS). Both anti-Plasmodium falciparum and anti-Pfl55/RESA antibody rates increased more rapidly in AA than in AS children. Conversely, the prevalence rate of cellular responders to the Pfl55/RESA antigen was similar in AA and AS children during the first 2 years of life, then it was higher in AS than in AA children.Conclusions: Sickle cell trait related antimalarial protection varies with age. The role of the modifications of the specific immune response to P. falciparum in explaining the protection of AS children against malaria is discussed. [ABSTRACT FROM AUTHOR]

In malaria-endemic areas, protective immunity is acquired gradually. Some authors have proposed that different stages can be distinguished during development. To test this hypothesis, several in vitro assays of the host immune response to P. falciparum were performed in three groups of individuals: 'unprotected' children with clinical attacks, 'semi-immune' children, without clinical attacks but with transient high parasitaemias during the transmission period, and 'protected' adults with low residual parasitaemias. By comparison of immune responses in these groups and multifactorial analyses, discriminant factors and potential protective mechanisms were identified. Anti-RESA antibody levels were lower in 'unprotected' than in 'semi-immune' children, while specific cellular responses, TNF levels and percentage of activated T lymphocytes were higher. Low humoral immunity and high cellular activation in children were followed by high humoral immunity and low cellular activation in adults. Therefore, protective immunity seems to pass through different stages and to result from the association of different immune mechanisms according to the level and duration of the individual experience of malaria. [ABSTRACT FROM AUTHOR]

This study investigated the successive losses in the parasite densities of Plasmodium falciparum stages during the early sporogony in laboratory-reared Anopheles gambiae infected by membrane feeding with blood from naturally infected gametocyte carriers (>50 gametocytes/mm3). The developmental stages of P. falciparum in the mosquito were studied from zygote to oocyst, by immunofluorescent method using monoclonal antibodies against the Pfs25 protein present on the surface of newly formed gametes. This method allows for assessment of the various sporogonic stages before, during and after passage of the midgut wall. Parasite densities were determined within the entire blood meal at 3 h (zygotes and macrogametes) and 24 h (ookinetes) post-infection. At 48 h after the mosquito blood meal, midguts were checked for the presence of early oocysts. For the mid-size oocysts count, classic microscopy examination was used at day 7 postinfection. The parasite efficacy was estimated by following successive losses in parasite densities between different early stages of the sporogonic cycle in A. gambiae. Thirty-seven experimental infections were realized with high gametocyte densities, ranging from 64 to 2392 gametocytes/mm3. All gametocyte carriers showed infection with round forms 100%; ookinetes were found in 91.9%. The prevalences of infections with oocysts were 48.6% at day 2 (young oocyst) and 37.8% at day 7 (mid-size oocyst). The mean densities per mosquito for each parasite stage were 12.6 round forms, 5.5 ookinetes, 1.8 young oocyst and 2 mid-size oocysts. Significant correlations were found between two consecutive parasite stages (round forms/ookinetes, ookinetes/young oocysts, young oocysts/mid-size oocysts) and between round forms and mid-size oocysts. The mean parasite density significantly decreased between round forms and ookinetes (yield Y1 = 41.6%) and between ookinetes and young oocysts (Y2 = 61.4%). By contrast, no significant decrease was observed between young oocysts and mid-size oocysts (Y3 = 91.2%). The overall yield of the early sporogonic cycle (from round form to oocyst at day 7) was equal to 25.7%, indicating that almost 3/4 of the total parasites were lost during the early step of the sporogonic cycle, from 3 h post-infection to day 7. [ABSTRACT FROM AUTHOR]

A study involving 169 schoolchildren (5-14 years old) living in Manarintsoa near Antananarivo (Madagascar, East Africa) was performed during the seasonal malaria transmission period. For the whole population examined, the prevalence of Plasmodium falciparum and the rates of spleen enlargement and of circulating stable antigen (S-Ag) were found to be 60.9%, 71.7%, and 46,8%, respectively. The prevalence of IgG antibody to RESA (ring-infected erythrocyte surface antigen) was 42.7% and that of IgG and IgM antibodies to E-Ag (exoantigens) was 44.9% and 2.9%, respectively. The positive rates for IgG and IgM antibodies to Som-Ag (somatic antigen) were 48.5% and 5.9%, respectively. Concerning S−Ag, no significant relationship was observed for parasitemia, spleen size, age, or IgM antibody responses to exoantigens (E-Ag) or to somatic antigen (Som-Ag). Levels of S−Ag were found to be related to IgG antibodies to E-Ag. Our results suggest that S−Ag at low levels may participate in the mechanisms involved in the development of the IgG antibody responses to E-Ag and to Som-Ag, whereas at a comparative population level, higher quantities of S−Ag down-regulate antibody responses to P. falciparum. The data we obtained were compared with those gathered in another malaria mesoendemic area (Bobo-Dioulasso, Burkina Faso, West Africa), where lower levels of S−Ag were found. [ABSTRACT FROM AUTHOR]