Plasmodium falciparum induces a Th1/Th2 disequilibrium, favoring the Th1-type pathway, in the human placenta.

During pregnancy, a local and systemic Th2 bias of maternal immunity favors Th1-dependent infections such as malaria. This study measured cytokines secreted in cultures of chorionic villi, placental blood cells (PBC), and serum in term placentas from 88 malaria-infected and -noninfected Cameroon women. Interleukin (IL)--2 and --4 were consistently low; IL-1 beta, IL-6, granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)--beta 2 were highest in villi cultures. Tumor necrosis factor (TNF)--alpha, interferon (IFN)--gamma, and IL-10 were highest in PBC cultures. Malaria placental infection increased Th1-type cytokines, whereas Th2-type cytokines and TGF-beta 2 were unchanged. Addition of lipopolysaccharide or infected erythrocytes to cultures increased TNF-alpha, IL-1 beta, IL-6, and IL-10 secretions but not those of IFN-gamma and IL-4. Overall, Plasmodium falciparum induced a placental immune response involving both Th1- and Th2-type cell activation. Although the Th1 pathway was favored, IL-10 secretion was also increased, and this increase should be effective in protecting the placenta by controlling the negative effects of Th1 cytokines on pregnancy.

Cytoadherence of Plasmodium falciparum-infected erythrocytes in the human placenta.

In Plasmodium falciparum-parasitized pregnant women, erythrocytes infected by mature stages of the parasite sequester into placental intervillous spaces. The presence of parasites in the placenta causes maternal anaemia and low birth weight of the infant. In-vitro studies suggest placental sequestration may involve the cytoadherence of infected erythrocytes to chondroitin sulphate A (CSA) and/or intercellular adhesion molecule 1 (ICAM-1) expressed by human placental syncytiotrophoblast. We identified P. falciparum receptors expressed on the surface of human syncytiotrophoblast using immunofluorescence of placental biopsies from Cameroon, a malaria-endemic area. In all placentas, a strongly positive staining was observed on the syncytiotrophoblast for CSA, but not for ICAM-1, vascular endothelium cell adhesion molecule-1, E-selectin, nor CD36. The cytoadherence ability of parasites from pregnant women and nonpregnant subjects was assessed on in-vitro cultured syncytiotrophoblast. Parasites from pregnant women bound to the trophoblast via CSA but not ICAM-1. Parasites from nonpregnant hosts either did not bind to the trophoblast culture or bound using ICAM-1. Our data support the idea that placental sequestration may result from cytoadherence to placental trophoblast and that pregnant women are parasitized by parasites that differ from parasites derived from nonpregnant host by their cytoadherence ability.

Binding properties of octaaminocryptands.

Complexation and protonation equilibria were studied in aqueous solution for a new range of aminocryptand ligands, N(CH2CH2NHCH2RCH2NHCH2CH2)3N, (R = m-xylyl, p-xylyl, 2,5-furan, 2,6-pyridine) and demonstrate that stability constants for first transition series ions Co2+ to Zn2+ are relatively high. X-ray crystallography shows that the cryptands are reasonably well preorganized for complexation. The furan-spaced cryptand L6.H2O crystallizes in the rhomobohedral space group R3 (no. 148) with a = 14.645(1), b = 14.645(1), and c = 25.530(4) A, whereas the m-xylyl-spaced cryptand L4 crystallizes in the triclinic space group P1 (no. 2) with a = 9.517(1), b = 15.584(2), and c = 23.617(4) A. The highest formation constant (log beta21 = 33.07) is observed for the dicopper cryptate of a pyridine-spaced cryptand, suggesting involvement in complexation of donors from the spacer link. This pyridine-spaced host also shows good selectivity for copper(II) over zinc(II), making it a possible candidate for treatment of copper-excess pathology.

Development of antibodies against chondroitin sulfate A-adherent Plasmodium falciparum in pregnant women.

In areas where Plasmodium falciparum is endemic, pregnant women are at increased risk for malaria, and this risk is greatest during the first pregnancy. The placenta sequesters parasites that are able to cytoadhere to chondroitin sulfate A (CSA), a molecule expressed by the placental syncytiotrophoblast, while parasites from a nonpregnant host do not bind to CSA. Cytoadherence is mediated by the expression of variants of the P. falciparum-erythrocyte membrane protein 1 family. Each member of this molecule family induces antibodies that specifically agglutinate infected erythrocytes and inhibit their cytoadherence ability. We investigated whether the higher susceptibility of primigravidae was related to the lack of immune response towards CSA-binding parasites. In a cross-sectional study, primigravidae delivering with a noninfected placenta were less likely to have antibodies agglutinating CSA-binding parasites than multigravidae (P < 0.01). In contrast, parasites from nonpregnant hosts were as likely to be recognized by the sera from women of various parities. In a longitudinal study, at 6 months of pregnancy, antibodies against CSA-binding parasites were present in 31.8% of primigravidae and in 76.9% of secundigravidae (P = 0.02). The antibodies against CSA-binding parasites inhibited the cytoadherence of a CSA-adherent parasite strain to the human placental trophoblast. Our data support the idea that the higher susceptibility of primiparae is related to a lack of a specific immune response to placental parasites.

Levofloxacin: serum bactericidal activity against methicillin-resistant Staphylococcus aureus isolates.

The aim of this study was to assess the serum bactericidal activity (SBA) of levofloxacin compared with that of ofloxacin against methicillin-resistant Staphylococcus aureus (MRSA) isolates. Serum from 10 healthy volunteers (seven females, three males) was collected after a single oral dose of either levofloxacin (500 mg) or ofloxacin (400 mg). Subjects were allocated randomly to treatment after at least a 1 week interval between antibiotic regimens. Three well-defined MRSA strains were tested, each susceptible to levofloxacin and ofloxacin, with different levels of resistance to methicillin (HBD 456, HBD 3 and HBD 2; class 1, 2 and 3 Tomasz heterogeneous resistance, respectively) together with a methicillin-susceptible (MSSA) reference strain (S. aureus ATCC 25,923). SBA was tested in vitro by a microtitration method 15 min before dosing and at 1, 4, 8 and 12 h after drug absorption. Levofloxacin was significantly more bactericidal than ofloxacin against all strains of S. aureus tested (SBA > or = 1:2). An SBA was recorded for only a short period with ofloxacin, and thereafter only bacteriostatic activity remained. This study, therefore, confirms the superior activity of levofloxacin over that of ofloxacin against MSSA and MRSA.

Plasmodium falciparum-isolates from Cameroonian pregnant women do not rosette.

The placenta of pregnant women is frequently parasitized by erythrocytes infected by mature stages of Plasmodium falciparum (IE), a phenomenon associated with low birth weight of the offspring. The cytoadherence phenotype of the parasites from pregnant women suggests that placental sequestration may result from cytoadherence to the syncytiotrophoblast. However, as anatomopathological studies report that cytoadherence in the placenta is a rare event, we investigated whether placental parasites may sequester by forming rosettes with uninfected erythrocytes, another possible sequestration mechanism. Parasites from placental blood as well as parasites from the peripheral blood of pregnant and non pregnant subjects were assessed for their ability to rosette. In non pregnant subjects, the rosetting capacity of parasites was as reported in literature while, except in one case, parasites from pregnant women did not rosette. We conclude that the lack of rosetting is a new feature of IEs from pregnant women and that rosetting cannot be involved in the placental sequestration of IEs.

An in vitro microassay to assess the ability of Plasmodium falciparum-infected erythrocytes to bind to the human syncytiotrophoblast.

PROBLEM: Erythrocytes parasitized by matures stages of Plasmodium falciparum are frequently sequestered in human placenta. The consequences of this sequestration have been well described, but little is known about the mechanisms used by the parasite to concentrate in the placenta. METHOD OF STUDY: We developed an in vitro assay to study their binding capacity to the human syncytiotrophoblast. Our cytoadherence test was scaled down, and each step of the assay was optimized to enhance the sensitivity of our model. RESULTS: Cytoadherence assays between P. falciparum-infected erythrocytes and human trophoblasts are easily performed using low numbers of trophoblast cells. The process can also be used to carry out immunofluorescence and immunostaining techniques. CONCLUSIONS: The test may be adapted to any kind of cell, is inexpensive, and allows the culture of virtually any kind of cell for several weeks.

Cytoadherence of Plasmodium falciparum to intercellular adhesion molecule 1 and chondroitin-4-sulfate expressed by the syncytiotrophoblast in the human placenta.

Late stages of Plasmodium falciparum-infected erythrocytes (IRBCs) frequently sequester in the placentas of pregnant women, a phenomenon associated with low birth weight of the offspring. To investigate the physiological mechanism of this sequestration, we developed an in vitro assay for studying the cytoadherence of IRBCs to cultured term human trophoblasts. The capacity for binding to the syncytiotrophoblast varied greatly among P. falciparum isolates and was mediated by intercellular adhesion molecule 1 (ICAM-1), as binding was totally inhibited by 84H10, a monoclonal antibody specific for ICAM-1. Binding of the P. falciparum line RP5 to the syncytiotrophoblast involves chondroitin-4-sulfate (CSA), as this binding was dramatically impaired by addition of free CSA to the binding medium or by preincubation of the syncytiotrophoblast with chondroitinase ABC. ICAM-1 and CSA were visualized on the syncytiotrophoblast by immunofluorescence, while CD36, E-selectin, and vascular cell adhesion molecule 1 were not expressed even on tumor necrosis factor alpha (TNF-alpha)-stimulated syncytiotrophoblast tissue, and monoclonal antibodies against these cell adhesion molecules did not inhibit cytoadherence. ICAM-1 expression and cytoadherence of wild isolates was upregulated by TNF-alpha, a cytokine that can be secreted by the numerous mononuclear phagocytes present in malaria-infected placentas. These results suggest that cytoadherence may be involved in the placental sequestration and broaden the understanding of the physiopathology of the malaria-infected placenta.

Malaria cellular immune responses in neonates from Cameroon.

T cell responses to leucoagglutinin, PPD, and seven Plasmodium falciparum blood stages antigens were investigated in 164 cord blood samples from Cameroonian neonates. In vitro T cell responses were measured by lymphocyte proliferation, and IL-2, IFN-gamma, and IL-4 release in the presence of crude schizont extract, purified Pf155/RESA protein, and synthetic peptides from Pf155/ RESA. Following culture in presence of leucoagglutinin or PPD, proliferation and cytokine production were very low, as compared to adults from the same area. Interestingly, following stimulation of cord blood lymphocytes by malaria antigens, the percentage of responders and the mean level of positive responses were of the same order than those observed in adults for IL-2 production, while proliferative and IL-4 responses were only marginally decreased. Conversely, IFN-gamma production was highly reduced, as compared to adults. Our results demonstrate that prenatal immune priming to malarial antigens is common in this area and that the fetal immune system is able to respond to antigenic stimuli, as cells proliferate and generate cytokines. As cord blood lymphocytes may be induced to differentiate into effector cells producing predominantly Th1 or Th2 cytokines, malaria during pregnancy might direct the functional capacity of fetal T cells to respond to further infection.

Malaria and pregnancy in Cameroonian primigravidae: humoral and cellular immune responses to Plasmodium falciparum blood-stage antigens.

To investigate the mechanisms underlying the increased susceptibility to malaria in pregnant women, we determined the level of malaria-specific immunity in primigravidae. Humoral and cellular in vitro responses to unpurified (a crude schizont extract and a gametocyte preparation) and purified (affinity-purified Pf155/ring-infected erythrocyte surface antigen [RESA]) Plasmodium falciparum proteins, an immunodominant 45/47-kilodalton antigen from Mycobacterium bovis, and leucoagglutinin were compared between 52 primigravidae and 52 nonpregnant women from a semirural area of Cameroon. In vitro cellular responses were investigated in terms of lymphocyte proliferation, as well as production of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and IL-4. Cells from primigravidae exhibited a reduced proliferative response to schizont and gametocyte antigens, as well as to the M. bovis antigen. Conversely, the IL-2 response to Pf155/RESA was reduced. Interleukin-4 and IFN-gamma production did not appear to be affected in primigravidae. Antibody levels were also similar between pregnant and nonpregnant women. Our results underline the importance of examining several parameters of T cell activation with different types of antigens for a correct evaluation of the ability of lymphocytes to respond to malaria.

Humoral and cellular immune responses to synthetic peptides from the Plasmodium falciparum blood-stage antigen, Pf155/RESA, in Cameroonian women.

T- and B-cell responses to the Plasmodium falciparum blood-stage antigen Pf155/RESA were investigated in 104 Cameroonian women, half of whom were pregnant. We used purified protein and six synthetic peptides representing T- and B-cell epitopes. In vitro T-cell responses were measured by proliferation and IL2, IFN-gamma, and IL4 release. B-cell responses were assessed by plasma antibodies. All peptides induced a cellular response in some individuals. A proliferative response was induced in 25% of the donors by Pf155/RESA, and in 7 to 11% by any peptide. Cytokine release occurred in 23 to 30% of the Pf155/RESA-stimulated cultures, and in 8 to 25% of the peptide-stimulated cultures. Overall, each peptide induced a cellular response (proliferation and/or cytokine release) in 44% of the donors. T-cells from 23% of the donors failed to respond to any peptide. Responding cells did not usually respond in all readouts, and proliferation and release of any of the three cytokines were not correlated. Similarly, antibody and T-cell responses were not related. Selected epitopes of Pf155/RESA, an important vaccine candidate, are well recognized in naturally exposed individuals and are able to activate T-cells to proliferate and to produce various lymphokines in numerous individuals from a malaria endemic area.

High prevalence of anti-hepatitis C virus antibodies in a Cameroon rural forest area.

Sera of 807 people living in a rural forest area in southern Cameroon were tested by enzyme-linked immunosorbent assay; 101 (12.5%) gave positive results and were confirmed by line immunoassay. There was a highly significant difference between subjects aged over 40 years and those under 40 years, with the former having a much higher prevalence of antibodies. There were also significant differences between antibody prevalences among subjects aged > 40 years in the 3 ethnic groups studied--Baka Pygmies (6%), Fangs (30%) and Boulous (44%). Further studies are necessary to determine the reasons for these differences.

[Management of sexually transmissible diseases in an urban environment in Cameroon in 1992]. / Prise en charge des maladies sexuellement transmissibles au Cameroun, en milieu urbain, en 1992.

During the progress, in 1989, of a programme of social marketing of condoms in Cameroon, it was obvious that this approach should be supplemented by a similar programme for the management of STD's. Nine surveys were carried out in 1992 in Yaounde and Douala in the sexually most active male population (in the general community, at the workplace and in the leisure environment) in order to collect the basic data necessary for its implementation. Treatment essentially consists of mono-chemotherapy with drugs which are generally inefficient against the two principal etiologies of urethritis: Neisseria gonorrhoeae and Chlamydia trachomatis. The cost of treatment is considered excessive and leads to poor follow-up of the complete prescription. Simultaneous treatment of partners should be developed. All these data have been taken into account for the elaboration of a pilot programme which should be implemented in 1993.

Avancee du front epidemique de l'infection a VIH1 en Afrique centrale

Pour limiter l'expansion de l'infection a VIH une etude socio-spaciale s'avere necessaire. En Afrique Centrale; la prevalence presente une situation contrastee; d'un cote l'expansion est rapide et lente de l'autre. Malgre une relative accalmie dans les grandes metropoles; on note une nette expansion dans les centres urbains secondaires

[Severe malaria attacks in adults in Cameroon: comparison of 2 therapeutic protocols using quinine via parenteral route]. / Accès palustre grave de l'adulte au Cameroun: comparaison de deux protocoles therapeutiques utilisant la quinine par voie parentérale.

Increasing frequency and severity of cerebral malaria have become a major problem in the area of Yaoundé (Cameroon, Central Africa). Based on recent findings in pharmacokinetic parameters in cerebral malaria, a quinine infusion regimen (8 mg of quinine base/kg of body weight over 1 h followed by 8 mg of base/kg over 7 h, then 8 mg/kg over 8 h 3 times daily for 3 days) was randomly allocated to 10 patients; 10 others received a more classical regimen currently used in Cameroon of 8 mg of base/kg over 8 h, 3 times daily for 3 days. In the loading dose group, there was a significant decrease in the duration of coma (48%), and the parasite clearance times were reduced by 33%. This regimen has been safe and effective: it is recommended in Yaoundé.

Specificite du card agglutination trypanosomiasis test (CATT) dans le diagnostic de la trypanosomiase humaine au Cameroun : approche du probleme

Cette etude a pour but de verifier si les parasitoses sanguicoles; filarioses et paludisme; interferent avec la trypanosomiase dans la positivite du test. Il a de ce fait ete decide de tester le card agglutination trypanosomiasis test dans une population indemne de trypanosomiase humaine africaine; par absence de vecteur; mais ou les taux de prevalence des filarioses sanguicoles pathogenes ou non pathogenes et de paludisme sont tres eleves. Il ressort de cette enquete que sur un total de 265 sujets; 80; soit 30;2 pour cent ont ete trouves porteurs d'au moins un parasite sanguicole. 4 sujets etaient positifs au CATT : aucun n'a ete trouve porteur de parasites

Interet de l'amodiaquine dans le traitement des acces palustres simples a plasmodium falciparum en zone de chloroquinoresistance

La resistance aux amino-4-quinoleines a ete constatee pour la premiere fois en 1985 au Sud du Cameroun; a Limbe. En 1987-1988; une etude realisee a Yaounde mettait en evidence un taux de 37 pour cent d'echec de l'amodiaquine a la posologie de 25 mg/kg sur trois jours. A celle de 35 mg/kg; toujours sur trois jours; ce taux d'echec a chute a 6 pour cent en 1989 et a 2 pour cent en 1990. En consequence l'amodiaquine; a la posologie de 35 mg/kg repartis sur trois jours; est proposee en traitement de premiere intention dans les formations sanitaires du Cameroun

Evaluation des taux d'infection par le VIH1 a Libreville; Gabon; en 1991 : evolution depuis 1986

Les auteurs rapportent les resultats d'une enquete de seroprevalence VIH1 effectuee en mars 1991 par le sondage en grappes dans la population generale de Libreville; Gabon. En populations standardisees; le taux de seroprevalence est de 2;8 pour cent; il etait de 1;6 pour cent en 1986 et de 2;0 pour cent en 1989. D'un point de vue methodologique; au lieu de realiser un passage transversal unique comme lors des enquetes precedentes; les enqueteurs sont repasses pour inclure dans l'echantillon les personnes absentes au premier passage. Si les resultats sont identiques pour le VIH1; les taux de serologie treponomique sont significativement superieurs chez les personnes absentes. Ceci suggere une possibilite de biais dans la representativite des echantillons realises pour ce type d'etude par passage transversal unique