Mefloquine resistant malaria in cameroon and correlation with resistance quinine

Based on the results of in vitro sensitivity of Plasmodium falciparum to chloroquine, quinine and mefloquine, and evaluation of drug consumption conducted in 1987-1988 in four areas in the noth and south-west of Cameron, two opposite situations were encountered in this country. In northern Cameron where mefloquine resistance is prevalent a close correlation was found between the responses of P. falciparum to mefloquine and to quinine, but not between mefloquine and chloroquine. In the south, where chloroquine resistance is highly prevalent, no correlation was found neither between mefloquine and chloroquine nor mefloquine and quinine, but the responses to quinine and chloroquine appear partly correlated. These lead to formulate the hypothesis of a "southern" type of P. falciparum submitted to a high chloroquine drug pressure inducing a secondary cross resistance, whilst a "northern"type submitted to a relatively high and abortive quinine drug pressure inducing a primary quinine resistance and a secondary cross resistance with mefloquine.

A study on the pathogenesis of human cerebral malaria and cerebral babesiosis

Cerebral complications are important, but poorly understood pathological features of infections caused by some species of Plasmodium and Babesia. Patients dying from P. falciparum were classified as cerebral or non-cerebral cases according to the cerebral malaria coma scale. Light microscopy revealed that cerebral microvessels of cerebral malaria patients were field with a mixture of parazited and unparazited erythrocytes, with 94% of the vessels showing parasitized red blood cell (PRBC) sequestration. Some degree of PRBC sequestration was also found in non-cerebral malaria patients, but the percentage of microvessls with sequestered PRBC was only 13% Electron microscopy demonstrated knobs on the membrane of PRBC that formed focal junctions with the capillary endothelium. A number of host cell molecules such as CD36, thrombospondim (TSP) and intracellular adhesion molecule I (ICAM-1) may function as endothelial cell surfacereports for P. falciparum-infected erythrocytes. Affinity labeling of CD36 and TSP to the PRBC surface showed these molecules specifically bind to the knobs. Babesia bovis infected erythrocytes procedure projections of the erythrocyte membrane that are similar to knobs. When brain tissue from B. bovis-infected cattle was examined, cerebral capillaries were packed with PRBC. Infected erythrocytes formed focal attachments with cerebral endothelial cells at the site of these knob-like projections. These findings indicate that cerebral pathology caused by B. bovis is similar to human cerebral malaria. A search for cytoadherence proteins in the endothelial cells may lead to a better understanding of the pathogenisis of cerebral babesiosis.

Variation in the cytoadherence characteristics of malaria parasites: is this a true virulence factor?

The sequestration of Plasmodium falciparum-infected erythrocytes to the endothelial cells of brain capillaries is believed to represent one of the determining factors in the pathogenesis of cerebral malaria. In vitro studies of cytoadherence provide an experimental approach to understand the mechanism of sequestration and the respective roles played by parasite and host components in this interaction. This paper critically reviews current studies on cytoadherence, with particular emphasis on the nature of the information provided by such studies and their limitations. The paper also describes how cytoadherence studies using the patient's own monocytes can provide original information on the level of receptor up-regulation in the course of malarial infection.

Cytokines and dysregulation of the immune response in human malaria

The dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. In spite of the important role interleukin-I (IL-1) in malaria are lacking. We found that only 2 out of 35 subjectswith acute malaria showed increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL-1 could interfere with T- lymphocyte responses, blood mononuclear cells from patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were cultured with phytohemagglutinin, and lymphocyte proliferation measured 72h later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses are depressed both in P. falciparum (10,500 ñ 2,900) and P. vivax malaria (13,000 ñ 3,300), as compared to that of healthy individuals (27,000 ñ 3,000). Addition of IL-1 partially reserved depression of malaria lymphocytes, but had no effect on normal cells. On the other hand, T-lymphocytes from malaria infected-subjects presented a minimal decrease in proliferation, when cultured in the presence of exogenous PGE2. These data indicate the occurrence of two defects of immunoregulation in malaria: a deficiency of IL-1 production by monocytes/macrophages, and an increased resistance of lymphocytes to the antiproliferative effect of PGE2.

Efficacy of insecticide impregnated bed-nets to control malaria in a rural forested area in Southern Cameron

Due to current spreading of chemoresistant strains of Plasmodium falciparum malaria control must incorporate vector control programmes. Due to well known constraints house sprayings cannot be performed as before. Personal protection can be developed and a large scale use of insecticide treated bed-nets appeared to be very useful to reduce man-vector contact in Asia, South America and West and East Africa. No trial has done is forest Central Africa where transmission is permanent. We performed such a trial in the southern part of Cameroon (using deltamethrin, at 25mg/m*) and obtained similar data to those observed in the Gambia Burkina Faso and Tanzania with a noteworthy reduction of both transmission and high parasitaemia of P. falciparum (respectively 78% and 75%) meaning a drop of malaria morbidity.

Vector incrimination and effects of antimalarial drugs on malaria transmission and control in the Amazon Basin of Brazil

World ecosystems differ significantly and a multidisciplinary malaria control approach must be adjusted to meet these requirements. These include a comprehensive understanding of the malaria vectors, their behavior, seasonal distribution and abundance, susceptibility to insecticides (physiological and behavioral), methods to reduce the numbers of human gametocyte carriers through effective health care systems and antimalarial drug treatment, urban malaria transmission versus rural or forest malaria transmission, and the impact of vaccine development. Many malaria vectors are members of species complexes and individual relationship to malaria transmission, seasonal distribution, bitting behavior, etc. is poorly understood. Additionaly, malaria patients are not examined for circulating gametocytes and both falciparum and vivax malaria patients may be highly infective to mosquitoes after treatment with currently used antimalarial drugs. Studies on the physiological and behavioral effects of DDT and other insecticides are inconclusive and need to be evalusted.

South American monkeys in the development and testing of malarial vaccines - a review

South American Aoutus an d Saimiri monkeys, which are susceptible to infection with human malarias, have been used to develop models for the testing of huma malaria vaccines. Studies indicate that blood-stage and sporozoite vaccines can be tested in these monkeys using appropriate strains of parasites.

Direct analysis of peptide binding to cell-associated MHC class I molecules.

Exogenously added synthetic peptides can mimic endogenously produced antigenic peptides recognized on target cells by MHC class I-restricted cytolytic T lymphocytes. While it is assumed that exogenous peptides associate with class I molecules on the target cell surface, direct binding of peptides to cell-associated class I molecules has been difficult to demonstrate. Using a newly developed binding assay based on photoaffinity labeling, we have investigated the interaction of two antigenic peptides, known to be recognized in the context of H-2Kd or H-2Db, respectively, with 20 distinct class I alleles on living cells. None of the class I alleles tested, with the exception of H-2Kd or H-2Db, bound either of the peptides, thus demonstrating the exquisite specificity of peptide binding to class I molecules. Moreover, peptide binding to cell-associated H-2Kd was drastically reduced when metabolic energy, de novo protein synthesis or protein egress from the endoplasmic reticulum was inhibited. It is thus likely that exogenously added peptides do not associate with the bulk of class I molecules expressed at the cell surface, but rather bind to short-lived molecules devoid of endogenous peptides.

Interrelationship between Schistosomiasis and concomitant diseases

The biological literature contains many examples of mutual influences between different species of parasites, especially with respect to concomitant helminth infections. Several situations are known in wich the association of infection by Shistosoma mansoni with other pathogens in the same host results in a type of disease wich differs from the simple summation of the individual effects of each infection. The present study concerns concomitant infections involving S. mansoni and enterobacteriaceae; S. mansoni and other helmints such as Ascaris lumbricoides, Ancylostomids, Toxocara canis and species of the genus Hymenolepis; S. mansoni and different protozoa such as Trypanosoma cruzi, T. brucei, Toxoplasma gondii and Plasmodium berghei. The interaction between hepatitis B virus and S. mansoni, leading to prolonged viremia and worsening of liver damage, is also discussed. The paper also treats the simultaneous occurrence of schistosomiasis and other aggravating factors such as malnutrition and neoplasias wich may alter the host's response to the trematode.

Modern immunological approaches to assess malaria transmission and immunity and to diagnose plasmodial infection

The present paper reviews our recent data concerning the use of immunological methods employing monoclonal antibodies and synthetic peptides to study malaria transmission and immunity and to diagnose plasmodial infection. As concerns malaria transmission, we studied the main vectors of human malaria and the plasmodial species transmitted in endemic areas of Rondônia state, Brazil. The natural infection on anopheline was evaluated by immunoradiometric assay (IRMA) using monoclonal antibodies to an immunodominant sporozoite surface antigen (CS protein) demonstrated to be species specific. Our results showed that among six species of Anopheles found infected, An. darlingi was the main vector transmitting Plasmodium falciparum and P. vivax malaria in the immediate vicinity of houses. In order to assess the level of anti-CS antibodies we studied, by IRMA using the synthetic peptide corresponding to the repetitive epitope of the sporozoite CS protein, sera of individuals living in the same areas where the entomological survey has been performed. In this assay the prevalence of anti-CS antibodies was very low and did not reflect the malaria transmission rate in the studied areas. In relation to malaria diagnosis, a monoclonal antibody specific to an epitope of a 50 kDa exoantigen, the major component of supernatant collected at the time of schizont rupture, was used as a probe for the detection of P. falciparum antigens. This assay seemed to be more sensitive than parasitological examination for malaria diagnosis since it was able to detect plasmodial antigens in both symptomatic and asymtomatic individuals with negative thick blood smear at different intervals after a last parasitologically confirmed confirmed attack of malaria.

Virulence and the immune response in malaria

Many factors determine the virulence of a malaria infection. These include host innate resistance mechanisms and, with Plasmodium falciparum, the ability to cytoadhere to endothelial cells, form rosetts, and induce release of cytokines. The effect on virulence of acquired immune responses can be determined by Class I and Class II MHC-antigens; levels of immunological responsiveness may be determined too in other ways. The structure of parasite surface antigens and their great diversity modulate the immune response and influence parasite survival and hence virulence, and transmission to the vector.

Observations on some Avian Coccidia (Apicomplexa: Eimeriidae) in Amazonian Brazil

Oocysts of Eimeria porphyrulae n. sp. are described in faeces of Porphyrula martinica (Aves: Gruiformes: Rallidae). They are ellipsoidal to oval, 22.4 x 17.7 (20.0-23.7 x 16.2-18.7) µm, shape-index (length/width) 1.3. Oocyst wall about 1.25 µm thick, colourless, with two layers: inner one prominently striated. Micropyle and sub-micropylar granule present: no oocyst residuum. Sporocysts 17.5 x 9.0 (17.0-19.0 x 8.0-10.0) µm, shape-index 1.9, with inconspicuous Stieda/sub-Stieda bodies. Sporocyst residuum of scattered granules, sometimes a compact mass: sporozoites with two refractile bodies. Eimeria crypturelli n. sp. is described in faeces of Crypturellus soiu (Tinamiformes: Tinamidae). Oocysts ellipsoidal-oval, 20.75 x 14.5 (17.5-25.0 x 11.25-21.25) µm, shape-index 1.4. Oocysts wall about 1.25 µm thick and bi-layered: inner layer faintly striated. Micropyle present, with oocyst residuum immediately below: single polar body rarely present. Sporocysts 13.0 x 7.5 (12.5-13.75 x 7,5-8.1) µm, shape-index 1.7, with a Stieda body but seemingly no sub-Stieda. Sporocyst residuum compact: sporozoites with two refractile bodies. Isospora cacici n. sp. is recorded from faeces of Cacicus cela cela (Passeriformes: Icteridae). Oocysts subspherical-spherical, 26.5 x 23.7 (22.5-27.5 x 20.0-26.2) µm, shape-index 1.1. Wall a single, colourless layer about 1.5 µm thick. No micropyle or oocyst residuum: 1-2 polar bodies. Sporocysts ellipsoidal, 17.7 x 12.5 (17.5-18.75 x 11.25-13.75) µm, shape-index 1.4, with pronounced Stieda/sub-Stieda bodies: residuum compact and sporozoites with two refractile bodies. Isospora thraupis n. sp. is described from faeces of Thraupis palmarum melanoptera (Passeriformes: Thraupidae). Oocysts subspherial-spherical, 19.9 x 19.0 (18.7-21.2 x 18.75-20.0) µm, shape-index 1.0. Wall about 0.6 µm thick, smooth, colourless and a single layer: no micropyle, oocyst residuum or polar bodies. Sporocysts 14.2 x 9.2 (13.7-16.2 x 8.7-10.0) µm, shape-index 1.5: Stied/sub-Stieda bodies inconspicuous. Residuum compact: sporozoites with two refractile bodies.

IL-13 induces expression of CD36 in human monocytes through PPARgamma activation.

The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)gamma pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPARgamma pathway was demonstrated using transfection of a PPARgamma expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARgamma, and in peritoneal macrophages from PPARgamma-conditional null mice. We also show that CD36 induction by IL-13 via PPARgamma is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-Delta12,14-prostaglandin J2, an endogenous PPARgamma ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARgamma are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARgamma in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARgamma ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.

Tyzzeria boae n. sp., (Apicomplexa: Eimeriidae), a New Coccidium from the Kidney of the snake Boa constrictor constrictor (Serpentes: Boidae)

A new species of Tyzzeria is described from the kidney of the snake Boa constrictor constrictor Linnaeus, from the State of Pará, north Brazil. Oocysts from the coacal contents matured in eight days, at approximately 24°C. They measured 19.0 x 18.0 (15.0 x 15.0 - 22.5 x 21.5) µm, shape-index (length/width) 1.0 (1.0 - 1.1). The oocyst wall is of an extremely delicate single, colourless layer, with no micropyle. Division of the oocyst contents into the 8 naked sporozoites leaves a bulky, spherical oocyst residuum averaging 15.5 x 14.8 (13.5 x 13.5 - 18.5 x 17.5) µm; the sporozoites measure an average of 11.0 x 1.8 (8.5 x 1.25 - 12.5 x 2.0) µm, and possess both anterior and posterior refractile bodies. Tyzzeria boae n.sp. is unique among the recorded species of the genus by virtue of its development in the epithelial cells of the distal convoluted tubules and collecting tubules of the kidney: stages in the merogony and gametogony of the parasite are described and figured.

Transmission blocking immunity as observed in a feeder system and serological reactivity to Pfs 48/45 and Pfs230 in field sera

Monoclonal antibodies (mAbs) and human sera from gametocyte carriers were applied in the bio-assay to test for their transmission-blocking capacity. Competition ELISA's have been developed for the detection of natural transmission blocking antibodies. Approximately 55 of the sera blocking in the bio-assay gave positive results in these competition ELISA's.