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Contains fulltext : 53397.pdf (publisher's version ) (Open Access), This study investigated the significance of serum complement on transmission-reducing activity (TRA) of field sera from 24 infected Plasmodium falciparum gametocyte carriers (from Cameroon) against cultured NF54 P. falciparum. Laboratory-reared Anopheles stephensi were given infectious blood meals prepared either with sera from naive Dutch donor (AB type) or pair-matched field serum samples, both with and without active complement. TRA of serum factors and host complement on mosquito infection rate and oocyst intensity were divided into the various components involved in the early stages of sporogony. The majority (>80%) of sera tested showed positive antibody titres to Pfs230, the relevant complement-dependent target of transmission-reducing mechanisms. Regardless of the presence of active complement, bloodmeals with field sera exhibited significantly lower infection rates and oocyst intensity than the control group. Serological reactivity in Capture-ELISA against Pfs230 was significantly correlated with the reduction of parasite infectivity. Contrary to our expectation, the presence of active complement in the mosquito bloodmeal did not increase parasite losses and therefore the magnitude of transmission reduction by individual immune sera. Our findings on P. falciparum are consistent with previous studies on animal hosts of Plasmodium, indicating that early P. falciparum sporogonic stages may be insensitive to the antibody-dependent pathways of complement in human serum.

Contains fulltext : 57970.pdf (publisher's version ) (Closed access), Summary 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.

Item does not contain fulltext, Epidemiological studies on the infectivity of Plasmodium falciparum gametocyte carriers to mosquitoes are important to estimate the human reservoir in malaria endemic areas and to evaluate the impact of conatrol measures aiming at reduction of malaria transmission. Muirhead Thomson (1957) investigated infectivity through direct feeding of batches of Anopheles gambiae on human subjects. Recent field studies used a similar approach (Gamage-Mendis et al. 1991; Githeka et al. 1992), but for ethical and practical reasons preference is often given to membrane feeding with blood from gametocyte carriers.

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Contains fulltext : 22984___.PDF (publisher's version ) (Open Access)

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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.

We have characterized a glutamate rich Plasmodium falciparum antigen, GLURP, which by immunoassays appears to be present in both the pre-erythrocytic and erythrocytic stages of the vertebrate life cycle. The gene, which is located on chromosome 10, encodes a polypeptide of 1271 residues with a predicted molecular mass of 145 kDa. Rabbit antiserum against a fusion protein expressing the C-terminal end of the molecule detects a protein with a molecular mass of 220 kDa. The sequence includes two hydrophobic regions: one consisting of 23 residues and located by the N-terminus which may act as signal peptide, and the second located at the C-terminus consisting of 33 predominantly hydrophobic residues. Except for these hydrophobic regions the protein is hydrophilic and highly charged. The sequence has two tandem repeats designated as R1 and R2. These regions were found to be conserved in isolates from different geographical areas. High levels of anti-GLURP antibodies have been shown to correlate with low parasite density. The indication of GLURP being present in all stages of the parasite in the human host raises significantly the prospects of the potential of this molecule.

Two seroepidemiological studies were performed in an area of Burkina Faso hyperendemic for malaria to estimate the protective role of immunoglobulin M (IgM) antibodies. Six cross-sectional surveys were carried out on children (ages, <16 years) in the village of Karankasso. The evolution of antibodies to crude extracts of Plasmodium falciparum (IgG or IgM antisomatic and IgG antiexoantigens) were tested by IFI or enzyme-linked immunosorbent assay and were followed up according to the fluctuations of the parasite densities. Specific IgG antibodies had the same evolution as parasite densities. By contrast, specific IgM antibodies increased when IgG and parasite densities began to decrease (despite a high inoculation rate). A longitudinal survey of 77 children and adults was conducted in another village (Dafinso). In that study, clinical follow-up of the selected individuals allowed us to define three groups in the population. Children in group 1 were considered nonimmune (children with one or more malaria attacks). Group 2 was composed of semiimmune children who did not present with any malarial attack during the survey but who had high levels of parasitemia during the transmission period. Group 3 was composed of immunoprotected adults. Specific IgM and IgG antibodies to crude extracts or a recombinant antigen (glutamate-rich protein) of P. falciparum were tested. Specific IgM antibodies were lower in group 1 (nonimmune) than in groups 2 (semiimmune) and 3 (immunoprotected). Furthermore, there was a negative correlation between parasite densities and the levels of specific IgM antibodies. We discuss the possible role of IgM antibodies in the acquisition of immunity to malaria.