Pharmacokinetics and pharmacodynamics of a new ACT formulation: Artesunate/Amodiaquine (TRIMALACT) following oral administration in African malaria patients.

A new fixed-dose combination of artesunate (AS) plus amodiaquine (AQ) (TRIMALACT) was recently developed for the treatment of uncomplicated falciparum malaria. The originality of this combination lies in its galenic formulation which consists of a three-layer tablet with two layers containing each of the active ingredients, i.e. AS and AQ, and these are separated by a middle layer containing an antioxidant compound. To evaluate the efficacy and tolerability of this combination, adults with uncomplicated malaria received three administrations of two tablets (100:300 mg AS/AQ) in a 24-h interval, in Democratic Republic of Congo. Parasitemia and fever were measured and the plasma levels of parent compounds and metabolites [dihydroartemisinin (DHA) and monodesethylamodiaquine (MdAQ)] were determined by high-performance liquid chromatography. In addition, we determined the prevalence of molecular markers of resistance to chloroquine (CQ) and sulfadoxine/pyrimethamine (SP). The AS/AQ combination TRIMALACT demonstrated a good efficacy resulting in an excellent clinical and parasitological response rate of 100% after correction for PCR results. Treatment regimen was well tolerated. The main disposition parameters to AS+AQ were: for DHA, AUC = 632 +/- 475 ng h/ml and Cmax = 432 +/- 325 ng/ml, and for MdAQ = 14268 +/- 4114 ng h/ml and Cmax = 336 +/- 225 ng/ml (mean +/- standard deviation). Parasite genotyping show high frequencies of molecular SP- and CQ-resistance markers with more 80% of the samples showing more than three mutations linked to SP resistance and 93.48% carrying parasite with the CQ-resistant haplotype. This study shows that the AS/AQ combination TRIMALACT is safe and effective in the treatment of highly drug-resistant falciparum malaria.

Evaluation of the application of national malaria treatment guidelines in private pharmacies in a rural area in the Democratic Republic of Congo.

In the Democratic Republic of the Congo, the first recourse in case of suspected malaria in the health system is the private pharmacy sector. This study was therefore designed to assess private provider adherence to national case management guidelines in Kimpese, a rural area of Central Kongo province. A descriptive cross-sectional survey of 103 pharmacies took place in March 2016. The study included 97 pharmacies. The artemether-lumefantrine combination recommended as the first-line treatment for uncomplicated P. falciparum malaria was available in 100% of pharmacies but only 3% stocked quality-assured medicines. The sulfadoxine-pyrimethamine recommended for intermittent preventive treatment of malaria in pregnant women and quinine, which is no longer part of national policy, were widely available (>97.0% of pharmacies). Among providers, fewer than 20% were aware of the national malaria treatment guidelines. The main reasons for non-adherence to national guidelines among private dispensers was the high cost (up to 10 times more expensive than sulfadoxine-pyrimethamine treatment) and adverse effects of artemisinin-based combination therapies. Governmental interventions to improve private sector engagement in implementation of the national guidelines and to prevent the spread of ineffective and non-quality assured antimalarial medicines must be intensified.

Access to artemisinin-based combination therapies and other anti-malarial drugs in Kinshasa.

OBJECTIVE: Artemisinin-based combination therapies have been available since 2005 in the Democratic Republic of the Congo to treat malaria and to overcome the challenge of anti-malarial drug resistance as well as to improve access to effective treatments. The private sector is the primary distribution source for anti-malarial drugs and thus, has a key position among the supply chain actors for a rational and proper use of anti-malarial drugs. We aimed to assess access to nationally recommended anti-malarial drugs in private sector pharmacies of the capital-city of Kinshasa. METHOD: We performed a cross-sectional survey of 404 pharmacies. RESULTS: Anti-malarial drugs were stocked in all surveyed pharmacies. Non-artemisinin-based anti-malarial therapies such as quinine or sulfadoxine-pyrimethamine, were the most frequently stocked drugs (93.8% of pharmacies). Artemisinin-based combination therapies were stocked in 88% of pharmacies. Artemether-lumefantrine combinations were the most frequently dispensed drugs (93% of pharmacies), but less than 3% were quality-assured products. Other non-officially recommended artemisinin-based therapies including oral monotherapies were widely available. CONCLUSION: Artemisinin-based combination therapies were widely available in the private pharmacies of Kinshasa. However, the private sector does not guarantee the use of nationally recommended anti-malarial drugs nor does it give priority to quality-assured anti-malarial drugs. These practices contribute to the risk of emergence and spread of resistance to anti-malarial drugs and to increasing treatment costs.

[Chemosusceptibility analysis of Plasmodium falciparum imported from Comoros to Marseilles, France in 2001-2003]. / Chimiosensibilité de Plasmodium falciparum importé des Comores à Marseille en 2002-2003.

OBJECTIVES: The aim of this work was to study the chemosensitivity of Plasmodium falciparum strains isolated from patients presenting with malaria after having returned from Comoros Islands in 2002-2003, and hospitalized at the North University Hospital, in Marseilles, France. MATERIALS AND METHODS: In vitro drug susceptibility (for strains maintained in culture) and mutation-specific polymerase chain reaction (PCR) assays (for all strains) were performed. RESULTS: Out of 23 strains kept in culture, 50% were shown to be resistant in vitro to chloroquine, 50% were resistant to pyrimethamine, 40% to cycloguanil, 25% to atovaquone, and 7% to mefloquine. However all these strains were susceptible to quinine, halofantrine, and artemether. Moreover, 48 strains were tested by molecular methods. As a result, 69% were shown to have the Asp108 mutation in the dihydrofolate reductase gene (Pfdhfr), the basic mutation associated with antifolate resistance, and 54% had additional mutations Ile51 plus Arg59, associated with a high level of resistance. Furthermore, 90% of the 20 strains tested in 2003 were shown to have the point mutation Pfcrt76 in the P. falciparum chloroquine resistance transporter (Pfcrt) gene recently proposed as a molecular marker of chloroquine-resistance. CONCLUSION: Obtaining plasmodium strains from Comoros to be tested in Marseilles, where all laboratory facilities are available, is a unique opportunity to establish a surveillance of falciparum drug resistance in the Comoros islands.

[Imported malaria at the Marseilles Hôpital-Nord, France: a prospective study on 352 cases between 2001 and 2003]. / Le paludisme d'importation à l'Hôpital-Nord de Marseille en 2001-2003: étude prospective de 352 cas.

OBJECTIVE: The authors had for aim to study epidemiological, clinical, and parasitological characteristics, as well as regimen received, of imported malaria cases hospitalised at the North University Hospital, in Marseilles, France. DESIGN: The patients presenting with imported malaria included in this study were hospitalised in the infectious and tropical diseases unit and in the pediatrics unit at the North University Hospital, from January 1, 2001 to December 31, 2003. Variables were prospectively collected and recorded. RESULTS: 352 patients including 240 adults and 112 children were included. Most of them (67% of the adults and 92% of the children) were contaminated during a trip to the Comoros Islands. Plasmodium falciparum was the most common species identified. 97.5% of adult and 98% of child patients back from Comoros did not take any chemoprophylaxis against malaria or took inadequate regimens. Halofantrin was the most commonly used drug for children to treat uncomplicated P. falciparum malaria. In adults, atovaquone-proguanil was used as a first line drug in the absence of vomiting, and a 3-day intravenous regimen of quinine-clindamycin in case of vomiting. CONCLUSION: The specificity of imported malaria in Marseilles is the high proportion of Comorian patients who go back home periodically to visit friends and relatives. A better education of the Comorian population in Marseilles, regarding malaria risks and prophylaxis, needs to be implemented.

A MAP kinase homologue from the human malaria parasite, Plasmodium falciparum.

Pfmap-1, a gene encoding a novel protein kinase, has been identified in the human malaria parasite Plasmodium falciparum, using the polymerase chain reaction with degenerate oligodeoxyribonucleotides designed to hybridise to conserved regions of cdc2-related kinases. Computer comparison with other protein kinases strongly suggests that the protein encoded by this gene is closely related to mitogen-activated protein (MAP) kinases, which play important roles in eukaryotic adaptative response and signal transduction. In addition to the conserved MAP kinase catalytic domain, Pfmap-1 contains a highly charged C-terminal extension that includes two sets of repeated amino acid motifs. Pfmap-1 is located on chromosome 14 of P.falciparum, and its mRNA has a size of 3.7 kb.

A Plasmodium falciparum novel gene encoding a coronin-like protein which associates with actin filaments.

Plasmodium falciparum, the major causative agent of human malaria, is an Apicomplexa protozoan parasite which invades in its intermediate host hepatocytes and erythrocytes. The driving force underlying internalization into the host cell is thought to involve both polymerization of parasite actin, as entry is inhibited by the cytochalasins, and an actin motor-associated protein. In the related Apicomplexa parasite, Toxoplasma gondii, the involvement of parasite actin during both processes of motility and host cell entry has been genetically established. In a search for molecules that can regulate actin dynamics within Apicomplexa parasites, we have identified a P. falciparum homologue of the actin associated protein called coronin originally described in the amoeba Dictyostelium discoideum. The single copy gene displays a strong homology with the amoeba sequence and with the bovine and human coronin homologues recently cloned. This homology lies not only within the N-terminus containing the five WD repeats that characterize coronin but also extends in the C-terminal part. Furthermore, using an affinity-purified mouse monoclonal antibody against D. discoideum coronin, we have detected in extracts of P. falciparum young and mature schizonts a 42-kDa polypeptide which binds this antibody and is present in a Triton insoluble fraction that also contains parasite actin filaments. In addition, the recombinant protein encoded by the homologue nucleotidic sequence of P. falciparum coronin is indeed recognized by the antibody against D. discoideum coronin. Finally, the cross-reactive polypeptide displays the ability to cosediment with exogenous F-actin, a property which fits with its involvement in actin dynamics.

Recombinant human thrombomodulin(csa+): a tool for analyzing Plasmodium falciparum adhesion to chondroitin-4-sulfate.

The proteoglycan thrombomodulin has been shown to be involved, via its chondroitin-sulfate moiety, in the cytoadhesion of chondroitin-4-sulfate-binding-Plasmodium falciparum-infected erythrocytes to endothelial cells and syncytiotrophoblasts. We cloned and expressed in CHO and COS-7 cells a gene encoding soluble human recombinant thrombomodulin, with a chondroitin-4-sulfate moiety. This system is complementary to the in vitro cell models currently used to study the chondroitin-4-sulfate-binding phenotype. It also provides a means of overcoming the lack of specificity observed in interactions of infected erythrocytes with modified chondroitin-4-sulfate. This thrombomodulin displayed normal activity in coagulation, indicating that it was in a functional conformation. The recombinant protein, whether produced in CHO or COS-7 cells, inhibited cytoadhesion to Saimiri brain microvascular endothelial cells 1D infected with Palo-Alto(FUP)1 parasites selected for chondroitin-4-sulfate receptor preference. Thus, the recombinant protein was produced with a chondroitin-sulfate moiety, identified as a chondroitin-4-sulfate, in both cell types. In both cases, the recombinant protein bound to the chondroitin-4-sulfate phenotype, but not to CD36- and ICAM-1-binding parasites. The chondroitin-4-sulfate was 36 kDa in size for CHO and 17.5 kDa for COS-7 cells. There was, however, no difference in the capacities of the recombinant proteins produced by the two cell types to inhibit the cytoadhesion of infected erythrocytes. Thrombomodulin immobilized on plastic or coupled to Dynabeads was used to purify specifically the infected erythrocytes that bind to chondroitin-4-sulfate. These infected erythrocytes were cultured to establish parasite lines of this phenotype. We then showed that the thrombomodulin, labeled with FITC, could be used to detect this phenotype in blood samples. Finally, the direct binding of infected erythrocytes to immobilized thrombomodulin was used to screen for anti-chondroitin-4-sulfate-binding antibodies.

Characterisation of the chondroitin sulphate of Saimiri brain microvascular endothelial cells involved in Plasmodium falciparum cytoadhesion.

Cytoadhesion of Plasmodium falciparum-infected erythrocytes (IRBC) to chondroitin-4-sulphate (CSA) is inhibited by soluble CSA in vitro on Saimiri brain microvascular endothelial cells (SBEC) and in vivo in P. falciparum-infected Saimiri monkeys. We tested whether the SBEC model was appropriate for studying CSA-binding IRBC using four cell lines. All SBEC expressed a chondroitin sulphate (CS), with a composition of CSA. The mean sizes of these CSA were 20.5, 22, 23, 32.5 and 36 kDa for SBEC 3A and C2, CHO, SBEC 1D and 17, respectively. We found that cytoadhesion of the Palo-Alto (FUP)1 CSA-binding phenotype, selected by panning on SBEC 17, was specifically inhibited in a dose-dependent manner by all the purified CSA. The extent of inhibition depended on the cellular origin of the tested CSA. SBEC 17 CSA was 33 times more efficient than CHO-CSA and 21 times more efficient than the 50 kDa commercial bovine trachaea CSA. Dynabeads coated with a total extract of SBEC 1D CS-proteoglycans interacted with CSA- but not with CD36- or ICAM-1-binding IRBC. These Dynabeads also interacted specifically with the PfEMP1 DBL-3 domain, on the surface of CHO transfectants, but not with the CIDR-1 domain. Thrombomodulin was involved in IRBC adhesion to all SBEC whereas CD44 was only expressed by SBEC 1D and 17. These two CSA-proteoglycans have also been detected at the surface of human endothelial cells. Thus, the two homologous models, SBEC/Saimiri sciureus, are useful and reliable tools for the evaluation of new anti-CSA adhesion treatments and anti-disease vaccines for pregnant women.

Conserved organization of genes in trypanosomatids.

Trypanosomatids are unicellular protozoan parasites which constitute some of the most primitive eukaryotes. Leishmania spp, Trypanosoma cruzi and members of the Trypanosoma brucei group, which cause human diseases, are the most studied representatives of this large family. Here we report a comparative analysis of a large genomic region containing glucose transporter genes in three Salivarian trypanosomes (T. brucei, T. congolense and T. vivax), T. cruzi and Leishmania donovani. In T. brucei, the 8 kb (upstream) and 14 kb (downstream) regions flanking the glucose transporter genes cluster contain two and six new genes, respectively, six of them encoding proteins homologous to known eukaryotic proteins (phosphatidylinositol 3 kinase, ribosomal protein S12, DNAJ and three small G-proteins--Rab1, YPT6 and ARL3). This gene organization is identical in T. brucei, T. congolense and T. vivax suggesting that Salivarian trypanosomes have a high level of conservation in gene organization. In T. cruzi and Leishmania, the overall organization of this cluster is conserved, with insertion of additional genes when compared with T. brucei. Phylogenetic reconstitution based on glucose transporters is in accord with the monophyly of the genus Trypanosoma and the early separation of T. vivax within Salivarian trypanosomes. On the basis of gene organization, biochemical characteristics of isoforms and phylogeny, we discuss the genesis of the glucose transporter multigene family in Salivarian trypanosomes.

Experimental infection of human erythrocytes from alcoholic patients with Bartonella quintana.

Bartonella spp. are found in the erythrocytes of their specific natural hosts and B. quintana bacteremia is associated epidemiologically with lice, alcoholism, and homelessness. The aim of our study was to compare the growth and the number of bacteria per erythrocyte in vitro in laboratory-infected red blood cells from alcoholic patients versus normal blood donor erythrocytes. Enumeration of bacteria was performed either with plate counting or with a real-time PCR quantitative assay. Number of bacteria per cell was determined using immunofluorescence assay and laser confocal microscopy. Although the number of bacteria after 4 days of incubation was similar in the two groups of erythrocytes, we found that the distribution of bacteria per erythrocyte in the two groups was different. Erythrocytes from alcoholics contain significantly more bacteria per cell than erythrocytes from blood donors. Our results suggest that there is a link between alcoholism and infections of B. quintana that may be due to the macrocytosis of erythrocytes.

Proguanil resistance in Plasmodium falciparum African isolates: assessment by mutation-specific polymerase chain reaction and in vitro susceptibility testing.

The antifolate proguanil is commonly used in the prophylaxis and treatment of Plasmodium falciparum malaria. A series of point mutations in the dihydrofolate reductase (DHFR) gene has been linked to differential susceptibility of varied P. falciparum clones or isolates to this drug. To survey the efficiency of proguanil prophylaxis in an African endemic region, and to evaluate the level of proguanil resistance in the corresponding parasite population, we performed drug susceptibility assays with P. falciparum isolates from Senegal, Kenya, and Niger. In parallel, we developed a mutation-specific polymerase chain reaction assay that enabled us to characterize mutations in the DHFR gene of the same isolates without in vitro parasite cultivation. We confirm previously available data showing that parasites harboring a point mutation from Ser108 to Asn present a decrease in susceptibility to cycloguanil (the active metabolite of proguanil), and we show that mutations in codons 51 and 59 appear to modulate the level of resistance to cycloguanil. No mutations in codons 16 and 164 were detected in resistant parasites, in contrast with results from some previous studies.

In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine.

The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug susceptibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC50) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confidence interval [CI] = 2.1-3.9). Pyronaridine was less potent against chloroquine-resistant isolates than chloroquine-susceptible isolates but more potent than chloroquine against chloroquine-resistant parasites. The cut-off value for in vitro reduced susceptibility to pyronaridine was an IC50 > 15 nM. Two isolates (3%) showed an IC50 > 15 nM. A significant positive correlation was found between the activities of pyronaridine and chloroquine (r2 = 0.26, P < 0.001), pyronaridine and quinine (r2 = 0.36, P < 0.001), pyronaridine and amodiaquine (r2 = 0.55, P < 0.001), and pyronaridine and halofantrine (r2 = 0.50, P < 0.001). This correlation suggests in vitro cross-resistance or at least in vitro cross-susceptibility, which is not necessarily predictive of cross-resistance in vivo. The present in vitro findings require comparison with those of clinical studies.

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71-50% inhibitory concentration (IC50) values for doxycycline ranged from 0.7 to 108.0 microM and the geometric mean IC50 for the 71 isolates was 11.3 microM (95% confidence interval = 9.5-13.4 microM). The activity of doxycycline did not differ significantly (P = 0.0858) between the chloroquine-susceptible isolates and the chloroquine-resistant isolates. There was no in vitro correlation between the responses to doxycycline and those to artemether, chloroquine, quinine, amodiaquine, pyrimethamine, and cycloguanil, suggesting no in vitro cross-resistance among these drugs. Potency was increased by prolonged exposure. In 96-hr incubations, the activity of doxycycline was 4-5-fold more increased than in 48-hr incubations. The in vitro activity of doxycycline against intraerythrocytic stages of multidrug-resistant P. falciparum, its action against the preerythrocytic forms, the lack of correlation between the responses in vitro of P. falciparum to doxycycline and the other antimalarial drugs, and its original potential site of action are factors that favor its use as antimalarial drug.

Assay of fipronil efficacy to prevent canine monocytic ehrlichiosis in endemic areas.

Our objective was to evaluate the efficacy of fipronil for the prevention of Ehrlichia canis transmission to dogs by Rhipicephalus sanguineus in two endemic areas situated in Africa (Dakar and Djibouti). We carried out controlled trials in kennels for 1 year on 248 dogs, mainly police dogs and military working dogs. Eight groups were studied in a multi-centre study. Fifty five fipronil treated dogs were located in two separated kennels (G3, 37 dogs in Djibouti and G8, 18 dogs in Dakar). G1 (66 dogs) and G2 (60 dogs) were untreated control groups located in Djibouti, whereas G4 (32 dogs), G5 (13 dogs), G6 (18 dogs) and G7 (4 dogs) were the control groups located in Dakar. The epidemiological status of each group is known. G1 and G2 dogs were not kept in kennels, whereas G3, G4, G5, G6, G7, G8 dogs were housed in equivalent kennels. Tick infestation, clinical status and Ehrlichia seroprevalence were assessed during 1 year (duration of the study). Dog treated with fipronil showed neither canine monocytic ehrlichiosis (CME) nor tick infestations. In all groups of untreated control animals, R. sanguineus tick infestations were frequent, particularly in kennels (G5, G6 and G7) as well as morbidity and mortality due to CME. E. canis infection rates were low for fipronil treated animals: 2.7% (1/37) for G3 and 5.5% (1/18) for G8 group. Among control animals, seroprevalence was maximum (100%) in dogs kept in kennels (G5, G6 and G7 groups) and high among native dogs in Djibouti (G1 group): 69.7% (46/66) and in Dakar (G4 group): 50% (16/32). Dogs belonging to expatriate citizens (G2 group) were less likely to be infected: 21.7% (13/60). The comparison of serological results among French army dogs and French citizen dogs that were introduced in Djibouti for an average of 10 months shows a statistically significant (P<0.001) difference. Among fipronil treated animals (G3 group), 2 dogs out of 55 seroconverted (3.6%) compared to 13 out of 60 dogs (21.7%) in the control G2 group. The results of our study indicate the preventative efficacy of a fipronil monthly treatment to avoid CME in endemic areas. Epidemiological data concerning animals that live in the same endemic areas are an example of the serious consequences (in terms of mortality and morbidity) that are related to the absence of efficient methods for tick-control. In order to protect dogs that are in transit in endemic areas against tick-transmitted diseases, the use of an adapted acaricide product is recommended.

[Resistance to chloroquine and cycloguanil of Plasmodium falciparum in patients arriving in France after travel in Africa without chemoprophylaxis]. / Résistance à la chloroquine et au cycloguanil de Plasmodium falciparum chez des patients arrivant en France après un voyage en Afrique sans chimioprophylaxie.

The in vitro susceptibility of chloroquine and the genomic profile of dihydrofolate reductase (DHFR) codon 108 was determined against african isolates of P. falciparum (Pf) from imported malaria cases without previous drug intake by an isotopic microtest or PCR + RFLP. Pf resistance to chloroquine or to the DHFR inhibitor was present in 49% and 46% of isolates, respectively. Pf drug resistance was more frequent in permanent than in seasonal malarial transmission areas and chloroquine plus DHFR resistance reached 28% in years 1995-97. Updating the guidelines for the prevention of malaria in travellers to Africa is necessary.

[In vitro sensitivity of Plasmodium falciparum isolates from Gabon to chloroquine and cycloguanil]. / Sensibilité in vitro d'isolats gabonais de Plasmodium falciparum vis-à-vis de la chloroquine et du cycloguanil.

The in vitro susceptibility of 91 Plasmodium falciparum isolates obtained from malaria-infected children living near Libreville (Gabon) was evaluated against chloroquine and cycloguanil (biologically active metabolite of proguanil), using an isotopic micro-drug susceptibility test. In vitro resistance to chloroquine and cycloguanil was observed in 83% (35/42) and in 38% (30/78) of the patients, respectively. Our data showed that 41% (16/39) of Gabonese field isolates were resistant both to chloroquine and cycloguanil. These findings are of great importance because they might indicate imminent chloroquine-proguanil failure, and there are not many affordable antimalarial drugs to replace chloroquine-proguanil combination.

[Considering disparities in resistance of Plasmodium falciparum in Africa in chemoprevention decisions]. / Prise en compte des disparités de résistance de Plasmodium falciparum en Afrique dans la décision chimioprophylactique.

OBJECTIVES: Assess the efficacy of preventive and curative treatments of imported malaria. METHODS: The in vitro drug susceptibility of mefloquine, chloroquine and cycloguanil was determined against African isolates of Plasmodium falciparum from imported malaria cases by an isotopic in vitro test or a genomic approach. RESULTS: Plasmodium falciparum resistance to mefloquine, chloroquine or to the dihydrofolate reductase inhibitor was present in 5.2%, 46% and 42% of isolates respectively. Plasmodium falciparum drug resistance to chloroquine or antifolinics was more frequent in permanent than in seasonal malarial transmission areas. Simultaneous resistance to chloroquine and antifolinics was observed in 17% of isolates between 1991 and 1994 and in 28% between 1995 and 1997.

[Diarrhea and acquired immunodeficiency syndrome in the tropics (tropical AIDS). The place of digestive endoscopic examinations in diagnosing opportunistic infections]. / Diarrhée et syndrome d'immunodepression acquise sous les tropiques (S.I.D.A. tropical). La place des explorations endoscopiques digestives dans la recherche d'infections opportunistes.

A.I.D.S. has revealed some parasitic, microbiotic, mycotic or viral diseases causing diarrhea or has given a revival of interest to them. So are Cryptosporidium, Isospora belli, Salmonella typhi murium, Cytomegalovirus. Some easy techniques lead to the diagnosis of some pathogenic agents, such as parasitologic diagnosis of Cryptosporidium. Some other pathogenic agents call for a biopsy in view of an histopathology test: it is the case of Cytomegalovirus of which the diagnosis is stated positively by the histological picture with virus intranuclear inclusions. Then, it is necessary to make clear the actual indications of digestive endoscopic scanning when confronted by a diarrhea of tropical A.I.D.S.

[Canine ehrlichiosis in Senegal: human and canine seroepidemiological survey in Dakar]. / L'ehrlichiose canine au Sénégal: enquête séroépidemiologique humaine et canine à Dakar.

Since 1986, several cases of human ehrlichiosis due to Ehrlichia canis have been reported in the U.S.A. Suspecting a pathology transmissible from dog to man the authors conducted an epidemiologic survey in an ehrlichiosis zone in Senegal on a population of 42 men and 66 dogs. In 1987, this rickettsiosis accounted for the deaths of a good half of the military dogs stationed in Dakar. Yet two years after implementing a prophylactic policy the seroprevalence rate in the kennel dropped from 53% to 13%. Among the dog population of the Gendarmerie Nationale Sénégalaise, the seroprevalence rate is very high (78%) and in the sample of civil, native dogs, seroprevalence was 37%. The fact that no positive human serology was observed among the working-dog handlers in permanent contact with the infected dogs leads the authors to conclude that man is not receptive to Ehrlichia canis.