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ABSTRACTThe global malaria agenda has undergone a reorientation from control of clinical cases to entirely eradicating malaria. For that purpose, a key objective is blocking transmission of malaria parasites from humans to mosquito vectors. The new antimalarial drug candidate NITD609 was evaluated for its transmission-reducing potential and compared to a few established antimalarials (lumefantrine, artemether, primaquine), using a suite of in vitroassays. By the use of a microscopic readout, NITD609 was found to inhibit the early and late development of Plasmodium falciparumgametocytes in vitroin a dose-dependent fashion over a range of 5 to 500 nM. In addition, using the standard membrane feeding assay, NITD609 was also found to be a very effective drug in reducing transmission to the Anopheles stephensimosquito vector. Collectively, our data suggest a strong transmission-reducing effect of NITD609 acting against different P. falciparumtransmission stages.

ABSTRACTUpon the invasion of the host by microorganisms, innate immunity is triggered through pathogen recognition by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are the best-studied class of PRRs, and they recognize specific pathogen-associated molecular patterns (PAMPs) from various microorganisms. A large number of studies have shown that genetic variation in TLRs may influence susceptibility to infections. We assessed the genetic variation of TLR2, which encodes one of the most important TLRs, in various populations around the globe and correlated it with changes in the function of the molecule. The three best-known nonsynonymous TLR2polymorphisms (1892C>A, 2029C>T, and 2258G>A) were assessed in different populations from the main continental masses: Romanians, Vlax-Roma, Dutch (European populations), Han Chinese (East Asia), Dogon, Fulani (Africa), and Trio Indians (America). The 2029C>T polymorphism was absent in both European and non-European populations, with the exception of the Vlax-Roma, suggesting that this polymorphism most likely arose in Indo-Aryan people after migration into South Asia. The 1892C>A polymorphism that was found exclusively in European populations, but not in Asian, African, or American volunteers, probably occurred in proto-Indo-Europeans. Interestingly, 2258G>A was present only in Europeans, including Vlax-Roma, but at a very low frequency. The differential pattern of the TLR2polymorphisms in various populations may explain some of the differences in susceptibility to infections between these populations.

Upon the invasion of the host by microorganisms, innate immunity is triggered through pathogen recognition by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are the best-studied class of PRRs, and they recognize specific pathogen-associated molecular patterns (PAMPs) from various microorganisms. A large number of studies have shown that genetic variation in TLRs may influence susceptibility to infections. We assessed the genetic variation of TLR2, which encodes one of the most important TLRs, in various populations around the globe and correlated it with changes in the function of the molecule. The three best-known nonsynonymous TLR2 polymorphisms (1892C>A, 2029C>T, and 2258G>A) were assessed in different populations from the main continental masses: Romanians, Vlax-Roma, Dutch (European populations), Han Chinese (East Asia), Dogon, Fulani (Africa), and Trio Indians (America). The 2029C>T polymorphism was absent in both European and non-European populations, with the exception of the Vlax-Roma, suggesting that this polymorphism most likely arose in Indo-Aryan people after migration into South Asia. The 1892C>A polymorphism that was found exclusively in European populations, but not in Asian, African, or American volunteers, probably occurred in proto-Indo-Europeans. Interestingly, 2258G>A was present only in Europeans, including Vlax-Roma, but at a very low frequency. The differential pattern of the TLR2 polymorphisms in various populations may explain some of the differences in susceptibility to infections between these populations.

ABSTRACTDuring asexual intraerythrocytic growth, Plasmodium falciparumutilizes hemoglobin obtained from the host red blood cell (RBC) as a nutrient source. Papain-like cysteine proteases, falcipains 2 and 3, have been reported to be involved in hemoglobin digestion and are targets of current antimalarial drug development efforts. However, their expression during gametocytogenesis, which is required for malaria parasite transmission, has not been studied. Many of the available antimalarials do not inhibit development of sexual stage parasites, and therefore, the persistence of gametocytes after drug treatment allows continued transmission of the disease. In the work reported here, incubation of stage V gametocytes with membrane-permeant cysteine protease inhibitor E64d significantly inhibited oocyst production (80 to 100%). The same conditions inhibited processing of gametocyte-surface antigen Pfs230 during gametogenesis but did not alter the morphology of the food vacuole in gametocytes, inhibit emergence, or block male exflagellation. E64d reduced the level of oocyst production more effectively than that reported previously for falcipain 1-knockout parasites, suggesting that falcipains 2 and 3 may also be involved in malaria parasite transmission. However, in this study only falcipain 3 and not falcipain 2 was found to be expressed in stage V gametocytes. Interestingly, during gametocytogenesis falcipain 3 was transported into the red blood cell and by stage V was localized in vesicles along the RBC surface, consistent with a role during gamete emergence. The ability of a membrane-permeant cysteine protease inhibitor to significantly reduce malaria parasite transmission suggests that future drug design should include evaluation of gametogenesis and sporogonic development.

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.

Roeffen, W., Teelen, K., van As, J., vd Vegte-Bolmer, M., Eling, W., and Sauerwein R. 2001. Plasmodium falciparum: Production and characterization of rat monoclonal antibodies specific for the sexual-stage Pfs48/45 antigen. Experimental Parasitology,97, 45–49.

Elastic electron deuteron scattering was measured at the Bonn 2.5 GeV Electron-Synchrotron using a two spectrometer coincidence technique. Data were taken at values of the four momentum transfer squaredQ2=0.50, 0.60, 0.78, 1.00, and 1.3 (GeV/c)2 at electron scattering angles ?e=77.5° to 139.0° in order to separate the magnetic dipole formfactorFM(Q2) from the electric formfactorFE(Q2). Experimental cross sections are compared to theoretical predictions and to measurements of other laboratories. The results indicate that contributions from meson exchange currents are not negligible in thisQ2 region.

Inclusive production cross sections for photons and p0's ine+e- annihilation at a center of mass energy of 29 GeV have been measured. The p0 production spectrum agrees with a corresponding measurement for p±. The ratio of the p0 inclusive rate to the average for p± is 0.92±0.14. The fractions of the total energy carried by photons and p0's are 0.244±0.016 and 0.217±0.033, respectively. The fraction of total energy carried by all stable hadrons, prompt leptons and photons is determined to be 0.938±0.045, leaving 0.062±0.045 for neutrinos.

We have measured the inclusive prompt electron cross section over a wide momentum range (P>0.5 GeV/c) with the PEP-4 TPC detector. The semielectronic branching fractions of thec andb quarks are (9.1±0.9 (stat.)±1.3 (syst.))% and (11.0±1.8±1.0)%, respectively. Theb quark fragmentation function peaks at highz with b>=0.74±0.05±0.03. The axial couplings to the neutral current areac=2.3±1.4±1.0 for thec quark andab=-2.0±1.9±0.5 for theb quark.

We report on measurements of the reactionep?enp+ in the region of theD13(1520) andF15(1688) resonances. At an invariant four-momentum transferq2=0.3 (GeV/c)2 the outgoing pion was detected in the forward and backward directions. The values of the helicity-1/2-partial wave amplitudesA2-(D13(1520)) andA3-(F15(1688)) are determined from these measurements. A comparison of the results with single quark transition models is made.

The clinical presentation of severe malaria shows a wide range of signs and symptoms, which have been defined by distinct WHO criteria, cerebral malaria being the most prominent syndrome. Sequestration and adherence of parasitized erythrocytes and blockage of the microvascular system is considered a hallmark in the pathogenesis of cerebral malaria. Whether this is the common pathogenic process in all manifestations of severe malaria is still under debate. We hypothesize that the strict cerebral form, being the next step in severity after non-severe disease, is due to sequestration and adherence of parasitized erythrocytes and synthesis of reactive nitrogen molecules that disturb the level of consciousness. No obvious anatomical damage is observed in the vascular integument. Through an additional activation of white blood cells, development of an uncontrolled inflammatory response and release of inflammatory mediators, this stage of the disease may rapidly progress to a condition with (multiple) organ failure. Reactive oxygen intermediates may be particularly important in the development of endothelial damage, vascular leakage and haemorrhages in the brain and other organs.

Mosquitoes are infected with Plasmodium falciparum by taking a blood meal from a gametocyte carrier. Since a mosquito takes a volume of 1 to 2 microl, a blood meal may contain 1 x 10(4) to 3 x 10(4) leukocytes (WBC). The majority of WBC are composed of neutrophils which may phagocytose and kill developing gametes inside the mosquito midgut. Phagocytosis was measured in vitro by a luminol-dependent chemiluminescence (CL) assay. In the presence of P. falciparum gametes, sera from areas of endemicity had an increased CL response compared to controls. In mosquito membrane feeding experiments some such sera showed a transmission reduction which was related to the presence of viable WBC. The results of this study suggest that phagocytosis of opsonized gametes inside the mosquito midgut occurs and can contribute to a reduction in the transmission of P. falciparum parasites.

The role of T-cells in development of experimental cerebral malaria was analysed in C57B1/6J and C57B1/10 mice infected with Plasmodium berghei K173 or Plasmodium berghei ANKA by treatment with anti-CD4 or anti-CD8 mAbs. Mice were protected against cerebral malaria (CM) when anti-CD4 or anti-CD8 mAbs were injected before or during infection. Even in mice in end-stage disease, i.e. with a body temperature below 35·5 °C, treatment with anti-CD4 or anti-CD8 antibodies or the combination protected against CM, whereas chloroquine treatment was completely ineffective in inhibiting further development of the cerebral syndrome.

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 in 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.

Elastic electron deuteron scattering has been measured at the Bonn 2.5 GeV electron-synchrotron using a tensor polarized ND3 target. The scattered electrons and deuterons were detected in coincidence by two magnetic spectrometers. Data were taken at an average value of four momentum transfer ofQ2=0.495 (GeV/c)2 in order to separate the electric monopole and quadrupole form factors of the deuteron. To have a sufficient control of systematic effects, both polarized and unpolarized cross sections were measured with an identical experimental set up. In the ratioREXP=dspol/dsunp systematic effects are expected to cancel. This ratioREXP is related to the theoretical polarized cross section d dsT where the spin quantization axis for the deuterons is orientated in the ed-scattering plane, perpendicular to the virtual photon direction. Our final result for the corresponding recoil tensor polarization ist20=-2.01±1.13.

We have extended the measurements ofK-andL-shell ionization cross sections by electron impact into the ultra relativistic energy region, 0.9≦E≦2.0 GeV, in order to search for a saturation of the cross section. This phenomenon, which is due to the polarization of the target medium, is called density effect. It is predicted to occur at several hundred MeV impact energy and preferentially for lowZ target elements. Theoretical calculations are presented, based on the one-photon-exchange approximation. The absolute measurements of theK-andL-shell cross sections for Ni(K), Cu(K), Ag(K, L) and Au(L) performed at the 2.5 GeV electron synchrotron of the Bonn University, however, exhibit that the cross sections show no saturation but are still increasing. Furthermore, from theK X-ray yields, obtained at 0.9 and 2.0 GeV by bombarding the lowZ elements S, Ca, Mn, Ni and Ge, we obtain for the corresponding cross section ratio σK(2GeV)/σK(0.9GeV)=1.08±0.01 on the average. TheK X-ray yield of a composite Ca — Mn target amounts to

The polarization of the recoil proton from the reactionγp→π0p has been measured for photon energies between 600 and 1,200 MeV and pion c.m. angles between 90° and 150°.

A method for determining the infectious reservoir of malaria (K) and vector survival rate (P) by measuring oocyst size and discriminating between the most recent and other infections is described. In the laboratory the mean diameter of 3 d oocysts in Anopheles gambiae, kept at 26 °C, was 11·5 µm and the mean diameter at day 5 was 24·5 µm. Oocyst sizes in wild caught mosquitoes from southern Tanzania, that had fed on the occupants of bed nets with holes in the sides, were more variable. 2060 A. gambiae s.l.and 1982 A. Funestuswere examined for oocysts 3 d after feeding; 796 and 654 oocysts from the 153 and 170 infected females, respectively, were measured. Because of misclassification errors, the use of a simple cut-off model, in which all oocysts less than 17.5 µm in diameter were considered to have arisen from the most recent feed, was thought to overestimate Kand underestimate P. A statistical model which allows for overlap in the oocyst size distributions is described. Estimates of the infectious reservoir derived from this model were 2.8% for A. gambiae s.l.and 4.2% for A. funestus, and the estimated survival rates per gonotrophic cycle were 65.5% and 52.9%, respectively. The utility of measuring oocyst size in naturally infected mosquitoes is discussed.

We investigated the development of exoerythrocytic forms (EEF) of Plasmodium berghei in livers of normal and macrophage-depleted Brown Norway rats. Macrophages were depleted by use of liposome-encapsulated dichloromethylene diphosphonate. Upon inoculation of sporozoites, macrophage-depleted rats had significantly larger numbers of EEF than untreated rats. We also investigated the effect of macrophage impairment by silica treatment on the development of EEF and confirmed that silica induces a significant reduction of EEF development. Intravenous administration of silica induced high levels of interleukin-6 in plasma within a few hours. The seemingly contradictory results for EEF development may be explained by our previous observation that interleukin-6 strongly inhibits sporozoite penetration and EEF development in vivo. We conclude that in experimental infections with sporozoites, Kupffer cells inhibit rather than enhance EEF development.

By use of the parental hybridoma cell line 63F2A2 that produces specific antibodies of immunoglobulin isotype G1 (IgG1; 63F2A2.1) against Pfs230, we attempted to enrich for the synthesis of the downstream switch variant IgG2b and IgG2a monoclonal antibodies (MAbs) of the hybridoma cell line (63F2A2.2b and 63F2A2.2a, respectively). The parental IgG1 did not reduce the Plasmodium falciparum transmission in a bioassay irrespective of the presence of complement. MAbs 63F2A2.2b and 63F2A2.2a were effective in reducing the infectivity of P. falciparum parasites to Anopheles gambiae mosquitoes in membrane-feeding experiments. A transmission reduction of 91% was accomplished by the 63F2A2.2b switch variant, and a reduction of greater than 99% was accomplished by the 63F2A2.2a switch variant, but only in the presence of active human complement. Subsequently, the transmission-reducing effect of MAb 63F2A2.2b or 63F2A2.2a was confirmed in vitro by the rapid lysis of newly formed macrogametes or zygotes in the presence of active complement. MAb 63F2A2.1 did not lyse the newly formed macrogametes or zygotes irrespective of the presence of complement.

By use of the parental hybridoma cell line 63F2A2 that produces specific antibodies of immunoglobulin isotype G1 (IgG1; 63F2A2.1) against Pfs230, we attempted to enrich for the synthesis of the downstream switch variant IgG2b and IgG2a monoclonal antibodies (MAbs) of the hybridoma cell line (63F2A2.2b and 63F2A2.2a, respectively). The parental IgG1 did not reduce the Plasmodium falciparum transmission in a bioassay irrespective of the presence of complement. MAbs 63F2A2.2b and 63F2A2.2a were effective in reducing the infectivity of P. falciparum parasites to Anopheles gambiae mosquitoes in membrane-feeding experiments. A transmission reduction of 91% was accomplished by the 63F2A2.2b switch variant, and a reduction of greater than 99% was accomplished by the 63F2A2.2a switch variant, but only in the presence of active human complement. Subsequently, the transmission-reducing effect of MAb 63F2A2.2b or 63F2A2.2a was confirmed in vitro by the rapid lysis of newly formed macrogametes or zygotes in the presence of active complement. MAb 63F2A2.1 did not lyse the newly formed macrogametes or zygotes irrespective of the presence of complement.

The in vitro production of interleukin-1beta (IL-1beta), IL-6, and the IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation with different bacterial strains was measured to study the possible relationship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Streptococcus pyogenes induced the cytokines IL-1beta, IL-6, and IL-1ra. Gram-negative bacteria induced significantly higher levels of proinflammatory cytokine production than gram-positive bacteria. These differences were less pronounced for the anti-inflammatory cytokine IL-1ra. In addition, blood was stimulated with E. coli killed by different antibiotics to study the effect of the antibiotics on the cytokine-inducing capacity of the bacterial culture. E. coli treated with cefuroxime and gentamicin induced higher levels of IL-1beta and IL-6 production but levels of IL-1ra production similar to that of heat-killed E. coli. In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killing showed a decreased or similar level of induction of cytokine production as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.

In cerebral malaria, pathological changes can be found in the brain of infected people and in the brain of Plasmodium berghei-infected mice. The pathogenesis of cerebral malaria in mice is believed to be due to an immunopathological reaction giving rise to an excessive production of cytokines such as interferon gamma (IFN-gamma) and tumor necrosis factor (TNF). We find that low doses of interleukin 1 (IL-1) protect mice against cerebral malaria; IL-1 also inhibits parasitemia. The IL-1 effect on parasitemia was not observed in nude mice and was at least partly reversed in mice treated with IL-1 in combination with antibody to IFN-gamma, indicating the involvement of T cells. Mice protected against development of cerebral malaria by IL-1 treatment developed the syndrome when TNF was given as observed in control infected mice or infected mice treated with inactivated IL-1.

Two monoclonal antibodies which can be used for the unambiguous identification by fluorescence microscopy of Encephalitozoon intestinalis spores in clinical specimens are described. Monoclonal antibody Si91 is specific for the extruded polar filament, and Si13 recognizes the surfaces of E. intestinalis spores. No cross-reaction with spores of Encephalitozoon hellem was observed. Immunogold electron microscopy confirmed the specific reactivities of both antibodies. Combined in an indirect immunofluorescence assay, these antibodies are used to identify spores in feces. Although there was some cross-reaction with fecal bacteria and fungi, the typical morphology of the extruded polar filaments enabled proper identification of the E. intestinalis spores. Parasites could also be demonstrated to be present in urine, nasal swabs, lung brush biopsy specimens, and bronchoalveolar lavage fluid from a patient with disseminated infection with E. intestinalis. The use of these monoclonal antibodies facilitates the detection and species determination of E. intestinalis in clinical specimens.

Three currently used fragmentation models are tested by studying the distribution of particles between jet axes in the 3-jet events ofe+e− annihilation, using data collected by the Time Projection Chamber at PEP. These three models — the Lund String model, the Webber Cluster model and an Independent Fragmentation model (IF) — each implement different Lorentz-frame structures for the fragmentation process of quarks and gluons into hadrons. The Lund model provides a good description of the data, while the IF model does not. The Webber model, which is untuned, does not describe the absolute particle densities between jets, but correctly predicts the ratios of those densities, which are less sensitive to the tuning.

We study long-range correlations between hadrons in opposite jets ine+e− annihilation events at =29 GeV. We use the data to measure differences between quark and antiquark fragmentation functions into charged hadrons, and to estimate the variation of fragmentation properties among quark flavors. We find large variations in longitudinal fragmentation functions, but universal mean transverse momenta of hadrons in jets.

The reactionep?enp+ has been studied in the invariant mass range of 1.44?W?1.83 GeV. The outgoing pion was detected in the backward direction (cos?p*?-0.94) with respect to the virtual photon at four-momentum transfers of 0.4?q2?0.7 (GeV/c)2. The values of the helicity-1/2-partial wave amplitudesA2-(D13(1520)) andA3-(F15(1688)) were determined by a phenomenological analysis and compared with single quark transition models (S.Q.T.M.).

Mosquitoes are infected with Plasmodium falciparum by taking a blood meal from a gametocyte carrier. Since a mosquito takes a volume of 1 to 2 microl, a blood meal may contain 1 x 10(4) to 3 x 10(4) leukocytes (WBC). The majority of WBC are composed of neutrophils which may phagocytose and kill developing gametes inside the mosquito midgut. Phagocytosis was measured in vitro by a luminol-dependent chemiluminescence (CL) assay. In the presence of P. falciparum gametes, sera from areas of endemicity had an increased CL response compared to controls. In mosquito membrane feeding experiments some such sera showed a transmission reduction which was related to the presence of viable WBC. The results of this study suggest that phagocytosis of opsonized gametes inside the mosquito midgut occurs and can contribute to a reduction in the transmission of P. falciparum parasites.

Lensen, A., Bril, A., van de Vegte, M., van Gemert, G. J., Eling, W., and Sauerwein, R. 1999.Plasmodium falciparum:Infectivity of cultured, synchronized gametocytes to mosquitoes.Experimental Parasitology91,101–103.

Summary In contrast to the situation in cattle, goat and sheep,Campylobacter fetus subspeciesfetus only rarely causes disease in humans. While a major inducer of septic abortion in animals, only a minority of clinical infections in humans are found during pregnancy. Eleven cases have so far been described in pregnant women. Clinical symptomatology is usually mild during gestation but often leads to premature labor. Here we present a multigravida with positive cultures forC. fetus who went into septic shock. She completely recovered after delivery of aC. fetus-infected fetus at 18 weeks' gestation and treatment with a combination of cephazolin and gentamicin.C. fetus infections should be suspected in patients with intensive contact with (infected) cattle or after intake of unpasteurized dairy products.

The standard laboratory test for reduction in malaria transmission is based on the measurement of oocyst numbers in mosquitoes fed on blood meals containing test and control sera. Interpretation of the results, however, is often hampered by the large variation in numbers of infected mosquitoes and oocysts. The objective of this study was to compare 3 measures for the assessment of transmission reduction (so-called R values) and to define the experimental criteria that allow interpretation of the results. To determine variability in R values of control sera, a replicate experiment was performed with 10 non-endemic sera of Dutch blood donors. Furthermore, 2 measures for calculation of transmission reduction were compared in a triplicate experiment using Plasmodium falciparum, Anopheles gambiaeand malaria endemic sera. Calculations using the geometric mean of Williams are currently used to identify blocking and non-blocking sera. However, calculations using log-transformed data could distinguish more gradual levels of transmission reduction activity by endemic sera—i.e. blocking, reducing and non-blocking activity. Grading of transmission reduction activity is important for epidemiological studies on transmission immunity and for validation of future transmission-blocking vaccines.

We regret that in the article by M. van der Kolk et al. in Parasitology (2005) Vol. 130 (1), 13–22, W. Sauerwein should have been given as R. W. Sauerwein.

Experimental cerebral malaria (ECM) can be induced in C57B1 mice by infection with Plasmodium berghei K173 parasites. Behavioral changes shortly before they die of ECM may reflect disturbance of the integrity of the blood-brain barrier (BBB). Folic acid elicits strong convulsive activity if the permeability of the BBB is increased. Administration of folic acid to mice during development of ECM induced convulsions. Interventions known to prevent fatal outcome from ECM, such as splenectomy or treatment with anti-CD4 or anti-CD8 monoclonal antibodies, also prevented sensitivity to folic acid—induced convulsions. In addition, infected mice with ECM and sensitive to folic acid—induced convulsions, recovered from this sensitivity after treatment with anti—T cell antibodies within 4 h. These data suggest that disturbance of the permeability of the BBB can be reversed and depends on the involvement of T cells.

Transmission of Plasmodium falciparum can be reduced by immune factors present in the mosquito blood meal. Specific antibodies and white blood cells (WBCs) can interact with the sexual stages of the parasite inside the mosquito midgut. The relative contribution of serum factors and WBCs on transmission reduction in gametocyte carriers from an endemic area in Cameroon and in travelers with a first malaria experience was studied. Blood from these gametocyte carriers was fed to mosquitoes through membrane feeders after serum replacement, WBC depletion, or both. In most imported malaria cases, serum factors, WBCs, or both showed a significant effect on transmission reduction, while infectiousness of gametocyte carriers from Cameroon was reduced by humoral plasma factors only. In addition, the infectivity of gametocytes from semiimmune carriers was significantly lower compared with that of nonimmune carriers, and infectivity was independent of gametocyte density and the presence of WBCs or plasma factors (or both) in the blood meal.