Falciparum Gametocyte Carriage Research Articles

Plasmodium falciparum gametocyte dynamics in areas of different malaria endemicity

BackgroundThe aim of this study was to identify and compare factors associated with Plasmodium falciparum gametocyte carriage in three regions of differing malaria endemicity.MethodsRetrospective data from Thailand, The Gambia and Tanzania were used. The data came from large prospective field-based clinical trials, which investigated gametocyte carriage after different anti-malarial drug treatments.ResultsGametocytaemia was detected during the observation period in 12% of patients (931 out of 7548) in Thailand, 34% (683 out of 2020) in The Gambia, and 31% (430 out of 1400) in Tanzania (p < 0.001). Approximately one third (33%, 680/2044) of the patients with gametocytaemia during the observation period, already had patent gametocytaemia at enrolment (day 0 or day 1): 35% (318/931) in Thailand, 37% (250/683) in The Gambia, 26% (112/430) in Tanzania. Maximum gametocytaemia was usually observed on or before the seventh day after starting treatment (93% in Thailand, 70% in Tanzania and 78% in The Gambia). Lowest gametocyte carriage rates were observed following treatment with artemisinin derivatives, while sulphadoxine-pyrimethamine (SP) was associated with significantly greater development of gametocytaemia than other drug treatments (p < 0.001). The duration of gametocyte carriage was shorter in Thailand by 86% and Tanzania by 65% than in The Gambia. Gametocyte carriage was 27% longer among people presenting with anaemia, and was shorter in duration among patients who received artemisinin derivatives, by 27% in Thailand and by 71% in Tanzania and The Gambia.ConclusionThis study confirms the independent association of gametocytaemia with anaemia, and the significantly lower prevalence and duration of gametocyte carriage following treatment with an artemisinin derivative. The large differences in gametocyte carriage rates between regions with different levels of malaria transmission suggest that drug interventions to prevent transmission will have different effects in different places.

Evaluation and optimization of membrane feeding compared to direct feeding as an assay for infectivity

BackgroundMalaria parasite infectivity to mosquitoes has been measured in a variety of ways and setting, includind direct feeds of and/or membrane feeding blood collected from randomly selected or gametocytemic volunteers. Anopheles gambiae s.l is the main vector responsible of Plasmodium falciparum transmission in Bancoumana and represents about 90% of the laboratory findings, whereas Plasmodium malariae and Plasmodium ovale together represent only 10%.Materials and methodsBetween August 1996 and December 1998, direct and membrane feeding methods were compared for the infectivity of children and adolescent gametocyte carriers to anopheline mosquitoes in the village of Bancoumana in Mali. Gametocyte carriers were recruited twice a month through a screening of members of 30 families using Giemsa-stained thick blood smears. F1 generation mosquitoes issued from individual female wild mosquitoes from Bancoumana were reared in a controlled insectary conditions and fed 5% sugar solution in the laboratory in Bamako, until the feeding day when they are starved 12 hours before the feeding experiment. These F1 generation mosquitoes were divided in two groups, one group fed directly on gametocyte carriers and the other fed using membrane feeding method.ResultsResults from 372 Plasmodium falciparum gametocyte carriers showed that children aged 4–9 years were more infectious than adolescents (p = 0.039), especially during the rainy season. Data from 35 carriers showed that mosquitoes which were used for direct feeding were about 1.5 times more likely to feed (p < 0.001) and two times more likely to become infected, if they fed (p < 0.001), than were those which were used for membrane feeding. Overall, infectivity was about three-times higher for direct feeding than for membrane feeding (p < 0.001).ConclusionAlthough intensity of infectivity was lower for membrane feeding, it could be a surrogate to direct feeding for evaluating transmission-blocking activity of candidate malaria vaccines. An optimization of the method for future trials would involve using about three-times more mosquitoes than would be used for direct feeding.

A Randomized Open-Label Trial of Artesunate- Sulfadoxine-Pyrimethamine with or without Primaquine for Elimination of Sub-Microscopic P. falciparum Parasitaemia and Gametocyte Carriage in Eastern Sudan

BackgroundIn areas of seasonal malaria transmission, treatment of asymptomatic carriers of malaria parasites, whose parasitaemia persists at low densities throughout the dry season, could be a useful strategy for malaria control. We carried out a randomized trial to compare two drug regimens for clearance of parasitaemia in order to identify the optimum regimen for use in mass drug administration in the dry season.Methodology and Principal FindingsA two-arm open-label randomized controlled trial was conducted during the dry season in an area of distinct seasonal malaria in two villages in Gedarif State in eastern Sudan. Participants were asymptomatic adults and children aged over 6 months, with low-density P. falciparum infection detected by PCR. Participants were randomized to receive artesunate/sulfadoxine-pyrimethamine (AS+SP) combination for three days with or without a dose of primaquine (PQ) on the fourth day. Parasitaemia detected by PCR on days 3, 7 and 14 after the start of treatment and gametocytes detected by RT-PCR on days 7 and 14 were then recorded. 104 individuals who had low density parasitaemia at screening were randomized and treated during the dry season. On day 7, 8.3% were positive by PCR in the AS+SP+PQ group and 6.5% in the AS+SP group (risk difference 1.8%, 95%CI −10.3% to +13.8%). At enrolment, 12% (12/100) were carrying gametocytes. This was reduced to 6.4% and 4.4% by day 14 (Risk difference 1.9% (95%CI −9.3% to +13.2%) in AS+SP+PQ and AS+SP groups, respectively.ConclusionAddition of primaquine to artemisinin combination treatment did not improve elimination of parasitaemia and prevention of gametocyte carriage in carriers with low-density parasitaemia in the dry season.Trial RegistrationClinicalTrials.gov NCT00330902

Role of heat-labile serum factor or host complement in the inhibition ofPlasmodium falciparumsporogonic stages inAnopheles stephensiby gametocyte carriers' serological factors

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 naïve 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.

Space-time clustering of childhood malaria at the household level: a dynamic cohort in a Mali village.

BackgroundSpatial and temporal heterogeneities in the risk of malaria have led the WHO to recommend fine-scale stratification of the epidemiological situation, making it possible to set up actions and clinical or basic researches targeting high-risk zones. Before initiating such studies it is necessary to define local patterns of malaria transmission and infection (in time and in space) in order to facilitate selection of the appropriate study population and the intervention allocation. The aim of this study was to identify, spatially and temporally, high-risk zones of malaria, at the household level (resolution of 1 to 3 m).MethodsThis study took place in a Malian village with hyperendemic seasonal transmission as part of Mali-Tulane Tropical Medicine Research Center (NIAID/NIH). The study design was a dynamic cohort (22 surveys, from June 1996 to June 2001) on about 1300 children (<12 years) distributed between 173 households localized by GPS. We used the computed parasitological data to analyzed levels of Plasmodium falciparum, P. malariae and P. ovale infection and P. falciparum gametocyte carriage by means of time series and Kulldorff's scan statistic for space-time cluster detection.ResultsThe time series analysis determined that malaria parasitemia (primarily P. falciparum) was persistently present throughout the population with the expected seasonal variability pattern and a downward temporal trend. We identified six high-risk clusters of P. falciparum infection, some of which persisted despite an overall tendency towards a decrease in risk. The first high-risk cluster of P. falciparum infection (rate ratio = 14.161) was detected from September 1996 to October 1996, in the north of the village.ConclusionThis study showed that, although infection proportions tended to decrease, high-risk zones persisted in the village particularly near temporal backwaters. Analysis of this heterogeneity at the household scale by GIS methods lead to target preventive actions more accurately on the high-risk zones identified. This mapping of malaria risk makes it possible to orient control programs, treating the high-risk zones identified as a matter of priority, and to improve the planning of intervention trials or research studies on malaria.

Parasite infectivity and immunity to Plasmodium falciparum gametocytes in Gambian children.

Immunity to the sexual stages of Plasmodium falciparum can be induced during natural infections. Characterization of this immunity may facilitate the design of a transmission-blocking vaccine (TBV). This study aimed to assess the prevalence and serological correlates of functional transmission-blocking immunity in Gambian children (aged 1-4 years old) who were P. falciparum gametocyte carriers. Serological assays showed 100% response to fixed, whole parasites but only 42% to live gametes. Responses to the antigens Pfs230 and Pfs48/45 were 54.1% and 37.3%, respectively, in an IgG1 ELISA. 14/55 sera were capable of reducing the infectivity of laboratory isolate NF54 in a standard membrane-feeding assay (SMFA). This activity was strongly correlated with IgG1 responses to Pfs48/45 (r = 0.49, P < 0.001) and to a serological reaction with epitopes of the same molecule (r = 0.38, P = 0.003). A weaker correlation was observed with IgG1 to Pfs230 (r = 0.29, P = 0.03). In direct membrane feeding assays (DMFA) with autologous isolates, sera from 4/29 children showed transmission-blocking activity. There was no correlation with serological assays and the DMFA or between the SMFA and DMFA. This may be caused by variation in sexual stage antigens and/or alternative modes of transmission-blocking immunity, both of which have implications for vaccine implementation.

Plasmodium falciparum malaria disease manifestations in humans and transmission to Anopheles gambiae: a field study in Western Kenya.

Transmission of the malaria parasite Plasmodium is influenced by many different host, vector and parasite factors. Here we conducted a field study at Mbita, an area of endemic malaria in Western Kenya, to test whether parasite transmission to mosquitoes is influenced by the severity of malaria infection in its human host at the time when gametocytes, the transmission forms, are present in the peripheral blood. We examined the infectivity of 81 Plasmodium falciparum gametocyte carriers to mosquitoes. Of these, 21 were patients with fever and other malaria-related symptoms, and 60 were recruited among apparently healthy volunteers. Laboratory-reared Anopheles gambiae s.s. (local strain) were experimentally infected with blood from these gametocyte carriers by membrane-feeding. The severity of the clinical symptoms was greater in febrile patients. These symptomatic patients had higher asexual parasitaemia and lower gametocyte densities (P = 0.05) than healthy volunteers. Ookinete development occurred in only 6 out of the 21 symptomatic patients, of which only 33.3% successfully yielded oocysts. The oocyst prevalence was only 0.6% in the 546 mosquitoes that were fed on blood from this symptomatic group, with mean oocyst intensity of 0.2 (range 0-2) oocysts per mosquito. In contrast, a higher proportion (76.7%) of healthy gametocyte carriers yielded ookinetes, generating an oocyst rate of 12% in the 1332 mosquitoes that fed on them (mean intensity of 6.3, range: 1-105 oocysts per mosquito). Statistical analysis indicated that the increased infectivity of asymptomatic gametocyte carriers was not simply due to their greater gametocyte abundance, but also to the higher level of infectivity of their gametocytes, possibly due to lower parasite mortality within mosquitoes fed on blood from healthy hosts. These results suggest that blood factors and/or conditions correlated with illness reduce P. falciparum gametocyte infectivity.

Plasmodium falciparum gametocyte carriage in asymptomatic children in western Kenya

BackgroundStudies on Plasmodium falciparum gametocyte development and dynamics have almost exclusively focused on patients treated with antimalarial drugs, while the majority of parasite carriers in endemic areas are asymptomatic. This study identified factors that influence gametocytaemia in asymptomatic children in the absence and presence of pyrimethamine-sulphadoxine (SP) antimalarial treatment.MethodsA cohort of 526 children (6 months – 16 years) from western Kenya was screened for asexual parasites and gametocytes and followed weekly up to four weeks. Children with an estimated parasitaemia of ≥1,000 parasites/μl were treated with SP according to national guidelines. Factors associated with gametocyte development and persistence were determined in untreated and SP-treated children with P. falciparum mono-infection.ResultsGametocyte prevalence at enrolment was 33.8% in children below five years of age and decreased with age. In the absence of treatment 18.6% of the children developed gametocytaemia during follow-up; in SP-treated children this proportion was 29.8%. Age, high asexual parasite density and gametocyte presence at enrolment were predictive factors for gametocytaemia. The estimated mean duration of gametocytaemia for children below five, children from five to nine and children ten years and above was 9.4, 7.8 and 4.1 days, respectively.ConclusionThis study shows that a large proportion of asymptomatic untreated children develop gametocytaemia. Gametocytaemia was particularly common in children below five years who harbor gametocytes for a longer period of time. The age-dependent duration of gametocytaemia has not been previously shown and could increase the importance of this age group for the infectious reservoir.

Estimation of malaria transmission from humans to mosquitoes in two neighbouring villages in south Cameroon: evaluation and comparison of several indices

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.

Decreased Hemoglobin Concentrations, Hyperparasitemia, and Severe Malaria Are Associated with Increased Plasmodium falciparum Gametocyte Carriage

Decreased Hemoglobin Concentrations, Hyperparasitemia, and Severe Malaria Are Associated with Increased Plasmodium falciparum Gametocyte Carriage

Malaria and mosquito gene expression

It has long been known that sexual development of Plasmodium falciparum occurs in the hindgut of the Anopheles gambiae mosquito. However, knowledge regarding the molecular basis of midgut–parasite interaction has been lacking. The identification of genes expressed during invasion and development of the sexual stage could shed light on host–parasite interactions. Furthermore, an understanding of the interactions between parasite and mosquito might also lead to the development of new strategies to interrupt malaria transmission.To this end, a recent study by Bonnet and colleagues1xTranscripts of the malaria vector Anopheles gambiae that are differentially regulated in the midgut upon exposure to invasive stages of Plasmodium falciparum. Bonnet, S. et al. Cell. Microbiol. 2001; 3: 449–458Crossref | PubMed | Scopus (25)See all References1 used differential display to identify mosquito genes expressed during the ingestion of a blood meal. As the in vitro production of gametocytes of P. falciparum is difficult, infection of mosquitoes was carried out in an endemic area of Cameroon, Africa, by experimental feeding on the blood of volunteers known to be infected with P. falciparum. The study focused specifically on the identification of genes differentially expressed in the midgut of mosquitoes fed on either parasite-free blood or on blood of P. falciparum gametocyte or asexual carriers. Five transcripts were identified: four corresponded to genes selectively upregulated by the presence of gametocyte-stage parasites, and one corresponded to a gene overexpressed in the presence of both gametocyte and asexual stages of P. falciparum. Seven additional transcripts were identified in the midgut of An. gambiae after a blood meal containing P. falciparum. Identified transcripts included rRNA genes, trypsin1xTranscripts of the malaria vector Anopheles gambiae that are differentially regulated in the midgut upon exposure to invasive stages of Plasmodium falciparum. Bonnet, S. et al. Cell. Microbiol. 2001; 3: 449–458Crossref | PubMed | Scopus (25)See all References1 and a profilin homolog. Analysis of the other transcripts revealed no known homology to other proteins. This is the first demonstration that ingestion of gametocyte-stage parasites of P. falciparum affects expression of An. gambiae midgut genes in a developmental-stage-dependent manner. The identification of mosquito genes involved in digestion of the blood meal or sexual development of malaria parasites might lead to the development of transgenic mosquitoes that are refractory to these parasites, possibly reducing the transmission of malaria.

Comparison of artificial membrane feeding with direct skin feeding to estimate infectiousness of Plasmodium falciparum gametocyte carriers to mosquitoes

Human infectiousness to mosquitoes can be estimated by 2 tests: direct feeding on the skin and membrane feeding on venous blood. To validate the membrane feeding assay, the infectiousness of Plasmodium falciparum gametocyte carriers to Anopheles gambiae was estimated by these 2 methods in the same individuals in a rural area of Cameroon. Results from 37 experiments showed that direct feeding gave significantly higher infection rates than membrane feeding. We observed an average of 19·4% infected mosquitoes by direct feeding compared with 12·1% by membrane feeding, and a mean oocyst load of 5·63 by direct feeding compared with 2·65 by membrane feeding. However, there was a very good concordance between the 2 tests: 84·3% with the Kappa test on percentages of infected mosquitoes and 98·7% with the interclass correlation coefficient on oocyst loads. In addition, we found a good linear correlation between the 2 methods.

The Use of Anti-Pfs 25 Monoclonal Antibody for Early Determination of Plasmodium falciparum Oocyst Infections in Anopheles gambiae: Comparison with the Current Technique of Direct Microscopic Diagnosis

Gouagna, L. C., Bonnet, S., Gounoue, R., Tchuinkam, T., Safeukui, I., Verhave, J.-P., Eling, W., and Boudin, C. 1999. The use of anti-Pfs 25 monoclonal antibody for early determination of Plasmodium falciparum oocyst infections in Anopheles gambiae: Comparison with the current technique of direct microscopic diagnosis. Experimental Parasitology92, 209–214. Experimental infections of laboratory-reared anopheline mosquitoes were carried out with 57 Plasmodium falciparum gametocyte carriers from Cameroon. Prevalence of infected mosquitoes and oocyst intensity were determined by two independent methods. Young P. falciparum oocysts were detected on day 2 after feeding using an immunofluorescent assay, and the results were compared with direct microscopic examination of midgut oocysts on day 7 postinfection. The immunofluorescent assay was based on a FITC-labeled anti-25-kDa monoclonal antibody, while the direct microscopy was performed on midguts stained with 2% mercurochrome. Young oocysts were easily detected by their typical and bright green-fluorescing Pfs25 positive coat and their characteristic pattern of pigment granules under transmitted white light examination. The agreement between the results of the two methods was assessed using the Kappa coefficient on prevalences of positive infections and the interclass correlation coefficient on arithmetic mean oocyst load per infected midgut. The results indicated a low agreement between the two methods for the comparison of prevalences of infected mosquitoes. However, this agreement was near perfect for the comparison of mean oocyst intensities. Prevalences of positive infections and the overall number of parasites per positive gut were significantly correlated for both methods. Thus, the immunofluorescent test could be an appropriate tool for early determination of malaria infection in mosquitoes, particularly under laboratory conditions. The possible applications of this immuno-fluorescent technique are discussed.

Plasmodium falciparum: Membrane Feeding Assays and Competition ELISAs for the Measurement of Transmission Reduction in Sera from Cameroon

Mulder, B., Lensen, T., Tchuinkam, T., Roeffen, W., Verhave, J. P., Boudin, C., and Sauerwein, R. 1999.Plasmodium falciparum: Membrane feeding assays and competition ELISAs for the measurement of transmission reduction in sera from Cameroon.Experimental Parasitology92,81–86. The effect of natural malaria transmission-blocking factors in the blood ofPlasmodium falciparumgametocyte carriers was assessed in two types of functional bioassays. In the direct membrane feeding assay (DMFA), a comparison is made between the infectivity of gametocytes from a naturally infected gametocyte carrier in the presence of autologous plasma and the infectivity in the presence of replacement plasma from nonimmune donors. In the standard membrane feeder assay (SMFA), cultured NF54 gametocytes are used to measure the capacity of endemic sera to block transmission. In the DMFA, 18 out of 48 sera (37.5%) from Cameroonian gametocyte carriers reduced transmission significantly, while in the SMFA 22 out of 48 sera (45.8%) produced transmission reduction. There was a positive correlation between both assays (r+ 0.41,P< 0.05). Antibodies against epitopes of transmission-blocking target antigens Pfs48/45 and Pfs230 were measured in competition ELISAs and compared with the results of DMFA and SMFA. Serological reactivity in competition ELISAs against three epitopes of Pfs48/45 was significantly higher in the group of transmission-reducing sera in both the DMFA and the SMFA, especially for epitope III. No significant difference was found for Pfs230 antibodies (epitope I). Sensitivity of the serological assays was approximately 60%, with a specificity of around 70%. Serological tests cannot replace the functional bioassay in field situations as yet, but can contribute in the selection of sera for SMFA evaluation.

Transmission-blocking effects of sera from malaria-exposed individuals on Plasmodium falciparum isolates from gametocyte carriers.

Sera from donors exposed to malaria were tested for their ability to block the transmission of isolates from Cameroonian Plasmodium falciparum gametocyte carriers. Sera were selected from amongst Cameroonian and Gambian donors who had positive antibody reactivity against the surface of activated gametes and against epitopes of Pfs 48/45 (a potential transmission-blocking vaccine candidate antigen). Aliquots of washed blood from gametocyte carriers were resuspended in test and control sera and fed to An. gambiae mosquitoes via a membrane feeder. Comparisons of the prevalence and intensity of infections is dissected mosquitoes showed variations in the ability of sera to block the transmission of the different isolates. Sera were identified that had little or no blocking effect on the transmission of isolates unless the isolate was poorly infectious. Some sera completely blocked the transmission of some isolates whilst having little or no effect on others. The observed variation in transmission-modulating activity may have implications for the development of a transmission-blocking vaccine.

Effects of artemisinin derivatives on malaria transmissibility

Summary Background On the western border of Thailand the efficacy of mefloquine in the treatment of falciparum malaria has declined while gametocyte carriage rates have increased, which suggests increased transmissibility of these resistant infections. We compared the following antimalarial drugs in relation to subsequent Plasmodium falciparum gametocyte carriage: mefloquine, halofantrine, quinine, and the artemisinin derivatives. Methods Between 1990 and 1995 we assessed gametocytaemia in a series of prospective studies of antimalarial drug treatment in 5193 adults and children with acute uncomplicated falciparum malaria in an area of malarious hill forest on the western border of Thailand. Weekly parasite counts from thick and thin blood films were done during the 4-week (1990-93) or 9-week (1993-95) follow-up period. Gametocyte positivity rates and person gametocyte week (PGW) rates were calculated to measure gametocyte carriage and transmission potential. Findings In primary P falciparum infections the gametocyte carriage rate was significantly higher after treatment with mefloquine than after treatment with the artemisinin derivatives (PGW 34·1 [95% Cl 25·2-42·9] vs 3·9 [1·9-5·9] per 1000 person weeks; relative risk 8·0 [4·1-15·6]; p<0·0001). Recrudescent infections were associated with increased gametocyte carrier rates (relative risk 2·2 [1·6-3·0]; p<0·0001), but retreatment with artemisinin derivatives reduced subsequent gametocyte carriage 18·5 fold [3·5-98] compared with mefloquine retreatment and 6·8 fold (3·1-15·1) compared with quinine retreatment (p<0·001). The introduction of the artemisinin derivatives in routine treatment at this study site in mid 1994 was associated with a reduction in the subsequent incidence of falciparum malaria of 47 (25-69)%. Interpretation Although environmental changes affect vector numbers, and hence malaria incidence, artemisinin derivatives were found to reduce the transmission potential of falciparum malaria. Widespread introduction of artemisinin derivatives in the treatment of falciparum malaria may prevent the spread of multidrug resistance.

Anti-Pfs25 monoclonal antibody 32F81 blocks transmission from Plasmodium falciparum gametocyte carriers in Cameroon

Anti-Pfs25 monoclonal antibody 32F81 blocks transmission from Plasmodium falciparum gametocyte carriers in Cameroon

Malaria transmission-blocking activity in experimental infections of Anopheles gambiae from naturally infected Plasmodium falciparum gametocyte carriers

Experimental infections of anopheline mosquitoes were carried out with Plasmodium falciparum gametocytes from 65 naturally infected patients in Cameroon. A comparison was made between infections with blood containing autologous plasma and blood in which the plasma was replaced with plasma from a donor without previous malaria exposure. A lower infection rate was observed in 50 of 65 autologous plasma samples. Transmission was significantly blocked in 3 infections. This indicates that, in a population living in an area endemic for malaria, blood plasma factor(s) can reduce the transmission capacity of gametocyte carriers to mosquitoes.

Human antibody responses to epitopes on the Plasmodium falciparum gametocyte antigen PFS 48/45 and their relationship to infectivity of gametocyte carriers.

Antibodies in human sera recognizing epitopes I, IIa, III, and IV on the Plasmodium falciparum gametocyte antigen Pfs 48/45 have been investigated by competitive enzyme-linked immunosorbent assay. More than one-third of the residents of three villages in Madang, Papua New Guinea responded to epitopes I, IIa and III, with little variation by village or with time. There was a bimodal distribution of positive sera by age, with the highest proportion of responders in the 5-9- and greater than 20-year-old age groups. The data suggest a lower prevalence of antibodies against epitopes IIa and III in P. falciparum gametocyte carriers than in non-carriers. Enhancement of binding of monoclonal antibodies to epitopes IIa and III was also observed more frequently with sera from gametocyte carriers. Sera from gametocyte carriers in Papua New Guinea and Thailand, whose infectivity to mosquitoes had been tested, were used to examine the relationship between recognition of particular epitopes and infectivity. There was a significant association between lack of infectivity of P. falciparum gametocyte carriers and recognition of epitope IIa on Pfs 48/45 by antibodies in their sera.

Studies on the use of a membrane feeding technique for infecting Anopheles gambiae with Plasmodium falciparum

An investigation was made of the optimum feeding time when using stirred membrane feeders for infecting Anopheles gambiae s.s. with Plasmodium falciparum. The aim was to simulate the natural situation of direct feeding on a host and so enable the malaria susceptibility of different populations of A. gambiae to be assessed. 45 feeds were carried out on blood donated by P. falciparum gametocyte carriers. The results show that only patients with at least 300 gametocytes/mm 3 are likely to produce a high infection in mosquitoes. There was a marked decline in infectivity over a 35-min period after bleeding and 10-min feeds gave the highest proportion f mosquitoes infected. The decline in infectivity ould not be attributed solely to the fact that the gametocytes had become activated before ingestion by the mosquito, since the rate of activation in a feeder was found to be lower than the rate of loss of infectivity to mosquitoes. The possible applications of the technique are discussed.