Daniel Camus

Atovaquone-proguanil versus chloroquine-proguanil for malaria prophylaxis in non-immune travellers: a randomised, double-blind study

BACKGROUND Chloroquine plus proguanil is widely used for malaria chemoprophylaxis despite low effectiveness in areas where multidrug-resistant malaria occurs. Studies have shown that atovaquone and proguanil hydrochloride is safe and effective for prevention of falciparum malaria in lifelong residents of malaria-endemic countries, but little is known about non-immune travellers. METHODS In a double-blind equivalence trial, 1083 participants travelling to a malaria-endemic area were randomly assigned to two treatment groups: atovaquone-proguanil plus placebos for chloroquine and proguanil, or chloroquine, proguanil, and placebo for atovaquone-proguanil. Follow-up was by telephone 7 and 60 days after travel and at a clinic at 28 days. Serum samples were tested for antibodies to a malaria circumsporozoite protein. Blood and serum samples of participants with a potential malaria diagnosis were tested in a reference laboratory. FINDINGS 7 days after travel, at least one adverse event was reported by 311 (61%) of 511 participants who received atovaquone-proguanil and 329 (64%) of 511 who received chloroquine-proguanil. People receiving atovaquone-proguanil had a lower frequency of treatment-related gastrointestinal adverse events (59 [12%] vs 100 [20%], p=0.001), and of treatment-related adverse events of moderate or severe intensity (37 [7%] vs 56 [11%], p=0.05). There were fewer treatment-related adverse events that caused prophylaxis to be discontinued in the atovaquone-proguanil group than in the chloroquine-proguanil group (one [0.2%] vs ten [2%], p=0.015). INTERPRETATION Overall the two preparations were similarly tolerated. However, significantly fewer adverse gastrointestinal events were observed in the atovaquone-proguanil group in than in the chloroquine-proguanil group.

Immunocompetent Hosts as a Reservoir of Pneumocystis Organisms: Histological and RT-PCR Data Demonstrate Active Replication

Abstract The present study was conducted to further examine recent data suggesting that pneumocystosis could be transmitted between patients and healthcare workers in the hospital environment, as has been proven with Pneumocystis-infected SCID mice and immunocompetent Balb/c mice. Using an experimental design (i.e., SCID–Balb/c mouse airborne transmission system), the present work found that healthy host-to-healthy host transmission of Pneumocystis organisms can occur, and that ‘second’ healthy contacts are able to transmit the infectious organisms to immunocompromised hosts. Further tests designed to explore the behavior of Pneumocystis organisms in the lungs of immunocompetent hosts were performed using histological and molecular approaches (e.g. testing the expression of both cyclin-dependent serine-threonine kinase and heat-shock 70 protein in Pneumocystis). The results showed Pneumocystis organisms were able to replicate in the lungs of immunocompetent hosts, which indicates these hosts are a reservoir for Pneumocystis spp.

Atovaquone-Proguanil versus Chloroquine-Proguanil for Malaria Prophylaxis in Nonimmune Pediatric Travelers: Results of an International, Randomized, Open-Label Study

Atovaquone-proguanil has been shown to be effective and well tolerated for malaria prophylaxis in residents of countries of endemicity and in nonimmune adult travelers, but data about traveling children are limited. In a randomized, open-label, multicenter prophylaxis trial, 221 nonimmune pediatric travelers (age, 2-17 years) received either atovaquone-proguanil or chloroquine-proguanil. Safety and clinical outcome were evaluated 7, 28, and 60 days after travel. By posttravel day 7, a total of 39 (35%) of 110 atovaquone-proguanil and 41 (37%) of 111 chloroquine-proguanil recipients reported > or =1 adverse event. The data indicate that, over the course of treatment, fewer atovaquone-proguanil recipients had treatment-related adverse events (8% vs. 14%), including gastrointestinal complaints (5% vs. 10%). Two subjects discontinued prophylaxis because of drug-related adverse events; both had received chloroquine-proguanil. Observed compliance with prophylaxis was similar before and during travel, but it was higher for atovaquone-proguanil in the posttravel period. No study participant developed malaria. Atovaquone-proguanil was well tolerated and is an important addition to the limited arsenal of prophylactic agents available to children.

Cryptosporidium Population Genetics: Evidence of Clonality in Isolates from France and Haiti

TRAMY NGOUANESAVANH, KARINE GUYOT, GABRIELA CERTAD, YVES LE FICHOUX, CHRISTOPHE CHARTIER, ROSE-IRENE VERDIER, JEAN-CHARLES CAILLIEZ, DANIEL CAMUS, EDUARDO DEI-CAS and ANNE-LAURE BAÑULS Ecologie du Parasitisme (EA 3609), IFR 142, Institut Pasteur de Lille, 1 rue du Professeur Calmette-BP245, 59019 Lille Cedex, France, and Cátedra de Parasitologı́a, Escuela de Medicina ‘‘José Marı́a Vargas’’, Universidad Central de Venezuela, Caracas, Venezuela, and Parasitologie-Mycologie, Centre Hospitalier Universitaire de Nice, France, and AFSSA Laboratoire d’études et de recherches caprines, Niort, France, and Centre GHESKIO, Port au Prince, Haı̈ti, and Laboratoire Environnement et Santé, Université Catholique de Lille, France, and Parasitologie-Mycologie, Centre Hospitalier Régional et Universitaire de Lille, France, and Génétique et Evolution des Maladies Infectieuses, IRD, Montpellier, France

Immunoregulation by Parasite Extracts

The mechanisms of parasite survival in the immune host have recently appeared as an essential feature in host-parasite relationships. It is generally agreed that parasites (helminths or protozoa), may use various clever mechanisms to escape the host immune response: antigenic variation is observed among trypanosomes, Plasmodium, and Babesia [5]; schistosomes may acquire host antigens either glycolipids of erythrocyte origin or glycoproteins endogeneously synthetized [3, 45]. Schistosomes have also recently been shown to acquire gene products of the major histocompatibility complex [44] and to possess receptors for the Fc fragment of immunoglobulin G and s 2 microglobulin [47]. For parasites in intracystic location, anatomic immune seclusion may represent another potent escape mechanism [14]. All these possibilities are expressed at the parasite level and may be regarded as protective weapons against effector mechanisms of immunity.

In vitro and in vivo inhibition of mast cell degranulation by a factor from Schistosoma mansoni.

Schistosome incubation product (SIP) obtained from Schistosoma mansoni was tested on mast cell degranulation in vitro or in vivo elicited by chemical compounds or anaphylactic reactions. Normal mast cells from Wistar rats were labeled with 3H-serotonin and incubated with the SIP. Serotonin release normally induced by the chemical compounds 48/80, polymyxin B or an anaphylactic system (ovalbumin-antiovalbumin) was inhibited when mast cells were preincubated with the SIP. Cutaneous reactions elicited by the compound 48/80 or polymyxin B and passive or active cutaneous anaphylactic reactions, were inhibited by the intradermal injection of the SIP before the challenge. The anaphylactic shock by ovalbumin was also inhibited in guinea pigs by a previous intraperitoneal injection of the SIP. This inhibitor appeared dialysable, heat resistant and soluble in trichloroacetic acid (TCA). The inhibitory activity was found in the fraction eluted from an antischistosome immunosorbent. However, no inhibition of cutaneous reactions was observed with the circulating (TCA-soluble, thermostable) M antigen previously described and purified from schistosomes. No effect of the SIP was observed on the growth of HeLa cells or the J 111 human monocytic cell line. The increase of intracellular cAMP levels in mast cells incubated with the SIP suggests that modulation of cAMP is involved in the mechanism of inhibition. The SIP inhibited also the mast cell-dependent eosinophil cytotoxicity for schistosomula sensitized with IgG2a antibody. The SIP appeared to act selectively on mast cell degranulation without effect on eosinophils or the mast cell mediators. This inhibitor, denominated schistosome-derived inhibitory factor, released by the parasite, which acts on mast cells could partly explain the low incidence of clinical allergic manifestations observed in parasitic diseases and might represent an escape mechanism of the parasite to the antibody-dependent eosinophil cytotoxicity mechanism.

Vaccination in older adults: development of an educational tool, Vaxisenior, in France.

The benefits of vaccination in older adults are well documented yet there is poor uptake of such preventive measures, and one of the main reasons in France is a lack of recommendation and support from healthcare professionals. To address this issue a multidisciplinary group of experts has developed an educational tool, Vaxisenior, to assist in the training of physicians/healthcare workers who can act as advocates for immunization programs. The tool comprises of eight sections (general introduction; immunosenescence; diphtheria–tetanus–poliomyelitis; influenza; pneumococcus; pertussis; herpes zoster; and vaccines for travelers). In addition, it includes national immunization schedules and recommendations, practical information regarding opportunities to expand vaccine coverage that is convenient to the patient and a questions and answers section covering topics relating to particular usage and responsibilities. Implementation of vaccination policies for older adults is a major issue and will require extensive promotional campaigns, as well as active support from healthcare and public health professionals to improve overall vaccine coverage.

Immunoregulation by Schistosoma mansoni

Schistosoma mansoni is known to release an inhibitory factor of lymphocyte proliferation elicited in vitro. The effect of this dialyzable schistosome incubation product (DSIP) was tested in vivo on different aspects of the cell-mediated immune response. First, the DSIP injected into C57B1/6 mice markedly inhibited the delayed type hypersensitivity to sheep red blood cells (SRBC). Furthermore, the DSIP injected into S. mansoni infected Fisher rats at the beginning of the infection induced an inhibition of the specific lymphocyte response to S. mansoni antigen and of the spleen cell response to concanavalin A (Con A). The DSIP injected into uninfected rats also inhibited the spleen cell response to Con A. In uninfected as in infected rats injected with the DSIP, the lymphocyte response to Con A was restored after purification of the spleen cells on a nylon wool column. Moreover spleen cells from rats injected wtih the DSIP reduced the proliferative response of normal syngeneic spleen cells induced by Con A. This inhibition was not observed when cells from DSIP-injected rats were previously passed through a nylon wool column. In contrast, nylon wool depletion of spleen cells from infected rats injected with the DSIP did not restore the lymphocyte response to S. mansoni antigen. It seems tht DSIP could partly explain the modulation of the cellular immune responses observed during S. mansoni infection and could represent one of the mechanisms of this parasites survival in the immunized host.

Educational vaccine tools: the French initiative

Prevention is an important but neglected issue in geriatric medicine. Vaccination plays a major role in prevention of infectious diseases, but its implementation in clinical practice is far from perfect. To improve practice, a group of French experts composed of geriatricians and infectious disease specialists prepared a set of educational material about vaccination for older subjects. The tool has been designed to be used by medical teachers to help them teach this topic to other physicians, nursing staff and students. The group first defined teaching objectives and reviewed the scientific literature on the efficacy and use of various vaccines in the elderly. Results were recorded in 217 slides. These slides were grouped to allow their use for short presentations: the immune system in the elderly and general information about vaccination; universal vaccines, influenza vaccines, pneumococcal vaccines, Herpes zoster vaccine, pertussis vaccine, vaccines for old travellers. Written comments were added to most slides to help presenters teach the topics. The content and design of the slides were analyzed and discussed by the whole group. The set was collected in a CD with ready-to-use files for oral presentations. This educational tool was presented and given to French teachers in geriatrics. It has been used for educational sessions in geriatric hospital wards, for continuous medical education for general practitioners and for courses for physicians learning geriatrics. It has also been proposed to physicians in charge of medical coordination of nursing homes and is available on a web site.