[Benefits and indications of rehabilitation for coronary heart diseases]. / Intérêt et indications de la réadaptation chez le malade coronarien.

Cardiac rehabilitation (CR) is an essential element in the treatment of coronary artery disease. It can be conducted on an inpatient or ambulatory basis in cardiac rehabilitation units and includes complementary exercise training and a therapeutic patient education (TPE) program. Rehabilitation can reduce the occurrence of serious cardiac events and provide better control of cardiovascular risk factors. All epidemiological surveys show that this approach is beneficial: multidisciplinary care reduces mortality after myocardial infarction and improves cardiac patients' lifestyles. Rehabilitation centers are the only structures able to conduct 3- to 4-week program of cardiac training and TPE. Unfortunately, the number of patients who participate in such programs is still too low, and cardiac rehabilitation centers are underutilized (32 % in the French cohort of the EUROASPIRE III study and about 15 % of all coronary patients). This situation is regrettable, as all registers and epidemiological surveys have confirmed the capacity of CR to improve exercise tolerance, the ischemic threshold, and secondary prevention.

[Training in tropical medicine in France]. / La formation en médecine tropicale en France.

Tropical medicine was a key element of the medical structures provided by France to our former colonies and, later; to countries within the scope of our international cooperation. hI recent decades, France has drastically reduced its bilateral commitments to countries in the tropics, and especially in sub-Saharan Africa. At the same time, the teaching of tropical medicine, which was highly regarded even beyond our borders, has lost a good deal of its expertise. Initially available in a few large French centers, and ensured by teachers with extensive field experience, training in tropical medicine is now offered in many universities. However; their programs and educational objectives, focusing mainly on infectious and parasitic diseases, no longer meet the healthcare priorities of southern countries, which are facing an epidemiological transition and the rise of non communicable diseases. Few teachers now have recognized expertise in tropical medicine. These changes have had negative consequences for research programs in tropical medicine and for the image of French assistance to developing countries. In this context, the followving perspectives should be considered: 1) training in tropical medicine should be enhanced by the creation of a national diploma recognized by international bodies. 2) The creation of a doctoral course in tropical medicine is a prerequisite for achieving this goal, and the future diploma must include a significant research component. 3) Teaching in tropical medicine must become more practical and be ensured by teachers with extensive field experience. 4) Training in tropical medicine should be part of a bilateral relationship with countries in the tropics, each party contributing its expertise while respecting that of its partners. 5) Training in tropical medicine should be backed uip by high-level scientific research based on enhanced synergy of our current networks (Institute for Research and Development, Network of overseas Pasteur Institutes, universities, etc.). 6) Teaching of tropical medicine should be coordinated by a supra-university structure whose mission is to ensure coherence. 7) Success in all these objectives will require strong political commitment. This is the only way to restore the enviable position which France occupied in the recent past.

[Cardiovascular disease and aircraft transportation: specificities and issues]. / Maladie cardiovasculaire et voyage aérien : particularités et enjeux.

With the development of air transport and travel to distant destinations, the number of passengers and elderly passengers on board increases each year. In this population, cardiovascular events are a major concern. Among medical incidents occurring in-flight they are second-ranked (10%) behind gastrointestinal disorders (25%). Their occurrence may involve life-threatening events and require resuscitation, difficult to perform during flight or in a precarious health environment. Coronary heart disease and pulmonary thromboembolic disease are the most serious manifestations. They are the leading cause of hospitalization in a foreign country and sudden cardiac death occurring during or subsequent to the flight. Their occurrence is explained on aircraft by hypoxia, hypobaria and decreased humidity caused by cabin pressurization and upon arrival by a different environmental context (extreme climates, tropical diseases). Moreover, the occurrence of a cardiovascular event during flight can represent for the air carrier a major economic and logistic problem when diversion occurred. Furthermore, the liability of the practitioner passenger could be involved according to airlines or to the country in which the aircraft is registered. In this context, cardiovascular events during aircraft transportation can be easily prevented by identifying high risk patients, respect of cardiovascular indications to travel, the implementation of simple preventive measures and optimization of medical equipment in commercial flights.

[Particularities and management of arterial hypertension in sub-saharan Africa]. / Particularités et modalités de la prise en charge de l'hypertension artérielle dans les pays d'Afrique sub- saharienne.

More than 25% of adults worldwide have high blood pressure, and this proportion is expected to rise in coming years. In sub-Saharan Africa, it is estimated that 150 million persons will be hypertensive by 2025. This increase appears to be related to the growth and aging of the population, as well as to the growing number of overweight and obese persons. The association with type-2 diabetes is frequent and deleterious. These trends are associated with urbanization and lifestyle westernization. Hypertension presents several etiopathogenic particularities in sub-Saharan Africa, especially with respect to sodium sensitivity and low renin activity. Target organ damage is more common, due to delayed and inadequate therapeutic management and to a likely genetic predisposition. Heart failure, stroke and renal failure often occur in young people. The mainstay of treatment is the use of thiazide diuretics and calcium channel blockers, combined with lifestyle and dietary measures (especially sodium restriction). Because of logistic and economic difficulties, recommendations issued by international societies may not be applicable at the community level.

Doxycycline-chloroquine vs. doxycycline-placebo for malaria prophylaxis in nonimmune soldiers: a double-blind randomized field trial in sub-Saharan Africa.

Failures of malaria chemoprophylaxis have been related to a lack of compliance with doxycycline due to its short elimination half-life. Adding a molecule with a long half-life to doxycycline could be useful to take over from this drug in case of occasional missed doses. A double-blind, placebo-controlled randomized field trial was designed to compare the tolerability of a doxycycline-chloroquine combination vs. doxycycline as malaria prophylaxis among French soldiers deployed in Africa. Data from 936 volunteers were analyzed. In both groups, the proportion of volunteers who reported at least one adverse effect was about 57%. Tolerability was similar in the groups except for a higher proportion of nausea or vomiting in the doxycycline-chloroquine group. The reported compliance rate was 86.6% and was similar in the two groups. Eight Plasmodium falciparum malaria cases were diagnosed in the doxycycline group and seven in the doxycycline-chloroquine group. The efficacy of the two chemoprophylaxis regimens was similar. Our study was the first randomized field trial to assess a doxycycline-chloroquine combination as malaria prophylaxis and showed no significant decrease of overall tolerability of the combination compared with doxycycline alone. Our results showed that a doxycycline-chloroquine combination could be a safe combination for malaria chemoprophylaxis.

Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base.

BACKGROUND: Halofantrine (HF) was considered an effective and safe treatment for multi-drug resistant falciparum malaria until 1993, when the first case of drug-associated death was reported. Since then, numerous studies have confirmed cardiac arrythmias, possibly fatal, in both adults and children. The aim of the study was to review fatal HF related cardiotoxicity. METHODS: In addition, to a systematic review of the literature, the authors have had access to the global safety database on possible HF related cardiotoxicity provided by GlaxoSmithKline. RESULTS: Thirty-five cases of fatal cardiotoxicity related to HF, including five children, were identified. Females (70%) and patients from developing countries (71%) were over-represented in this series. Seventy-four percent of the fatal events occurred within 24 hours of initial exposure to HF. Twenty six patients (74%) had at least one predisposing factor for severe cardiotoxicity, e.g., underlying cardiac disease, higher than recommended doses, or presence of a concomitant QT-lengthening drug. All (100%) of the paediatric cases had either a contraindication to HF or an improper dose was given. In six cases there was no malaria. CONCLUSION: A distinction should be made between common but asymptomatic QT-interval prolongation and the much less common ventricular arrhythmias, such as torsades de pointes, which can be fatal and seem to occur in a very limited number of patients. The majority of reported cardiac events occurred either in patients with predisposing factors or with an improper dose.Therefore, in the rare situations in which HF is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females.

[French military medicine]. / Le Service de santé des armées, passé et avenir.

Since its creation in 1708, the French Health Army Service has contributed significantly to colonisation and war campaigns, and has also contributed greatly to improvements in medical technology. Its activity is currently oriented towards peace-keeping operations across the globe, often in association with the public hospital network. Its teaching activities are being adapted to current reforms.

[Current situation and future perspectives for malaria prophylaxis among travellers and military personnel]. / Situation actuelle et perspectives de la prophylaxie du paludisme chez le voyageur et dans les forces armées.

Malaria remains a major public health problem, both for travellers and for the 40,000 French soldiers deployed each year to endemic areas. Epidemiological data show that imported malaria (IM) is on the increase, and that migrants account for more than 60% of malaria cases notified each year in France. The increase in IM among French military personnel is explained by prematurely terminated chemoprophylaxis on return, repeated short missions, and more cases of P. vivax and P. ovale infection. The choice of chemoprophylaxis depends mainly on the level of chloroquine resistance in the country visited. The atovaquone-proguanil combination is well tolerated and only requires 7 days of intake on return from the endemic area. Doxycycline monohydrate is cheaper and better-tolerated than mefloquine, and is thus preferred for French military personnel. However, its short half-life necessitates very good compliance. Chemoprophylaxis should be combined with vector control measures and with personal protection (impregnated bednets, protective clothing, repellents, and indoor insecticide spraying). The need for these measures should be clearly explained before departure, during the stay, and after return.

[Healthcare response to bioterrorism]. / La réponse sanitaire au risque biologique terroriste.

Bioterrorists seek to use highly virulent pathogens to cause social and economic disruption. Historical agents such as anthrax, Yersinia pestis and botulinum toxin can easily be produced, whereas others such as hemorragic fever virus require much more sophisticated infrastructure and government-scale resources. In the near future, with the spread of new biotechnologies, bioterrorists may produce new transgenic pathogens. Epidemiological surveillance and diagnostic capacities should thus be more reactive. Real-time epidemiological surveillance together with a network of high-security laboratories would enable us to cope effectively with new infectious diseases that emerge naturally or through human manipulation. Clinical and research skills should be merged in infection-control centers, bringing a new dynamic to microbiology.

[Effects of antimalarial drugs and cardiomyocytes. Pathogenic approach and new therapeutic recommendations]. / L'impact des antipaludiques sur la cellule myocardique. Approche pathogénique et nouvelles recommandations thérapeutiques.

The cardiotoxicity of halofantrine was a major concern during the past decade. Other old antimalarials (quinine, mefloquine, etc.) and more recent drugs may carry a similar risk. Studies of ventricular repolarization and myocardial cells can throw light on these adverse effects. Studies of QT dispersion measured on the surface electrocardiogram and of QT dynamicity and variability (QT/RR slope) during long-term Holter recording help to identify patients at risk of drug-induced ventricular arrhythmia. Such electrocardiographic investigations have shown that quinine, mefloquine and artemisinin derivatives do not alter ventricular repolarization. In contrast, halofantrine significantly increases QT dispersion and the QT regression slope. At the cellular level, most major antimalarial drugs inhibit potassium channels, which are regulated by the LQT1 and HERG genes responsible for the congenital long-QT syndrome. We propose new recommendations for the use of these drugs in the treatment and prevention of malaria.

Urban malaria in Dakar, Senegal: chemosusceptibility and genetic diversity of Plasmodium falciparum isolates.

The chemosusceptibility and genetic polymorphism of Plasmodium falciparum populations from 48 patients hospitalized for malaria at the Hospital Principal in Dakar, Senegal were investigated during the 2002 malaria transmission season. Sixty-two percent of the isolates collected were from patients with severe malaria and 38% were from patients with mild malaria. In vitro activities of chloroquine, quinine, cycloguanil, atovaquone, mefloquine, halofantrine, and artesunate were evaluated. The prevalence of mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) and dihyropteroate synthetase (dhps) genes and the P. falciparum chloroquine resistance transporter (Pfcrt) gene associated with cycloguanil, pyrimethamine, sulfadoxine, and chloroquine resistance were estimated. The genetic polymorphism of the parasite populations was evaluated by analysis of the highly polymorphic regions of merozoite surface protein 1 (msp1) block 2 and msp2. Seventy percent of the isolates were assessed by an in vitro assay. Fifty-two percent of the isolates were chloroquine resistant, 45% were cycloguanil resistant, and 24% were atovaquone resistant. Four percent had low susceptibility to quinine. The Pfcrt and dhfr mutations were associated with in vitro chloroquine- and antimetabolic drug-resistant isolates, respectively. Approximately 70% of the isolates contained two or more clones. Genetic diversity of P. falciparum was high. The prevalence of allelic family K1 of msp1 was 68%. Isolates of P. falciparum were highly resistant to chloroquine, cycloguanil and atovaquone. The transmission rate of malaria in Dakar is low but a high degree of genetic polymorphism can increase severe malaria, as shown by persons coming to Dakar from areas highly endemic for malaria. Areas with urban malaria should use vector control measures and efficient chemoprophylaxis for non-immune populations.

[New concepts in epidemiological surveillance in French army]. / Les nouveaux concepts de la surveillance épidémiologique dans l'armée française.

Epidemiological surveillance within the French Armed Forces has had to take into account various changes in infectious diseases in recent years. The French Armed Forces are encountering new hazards, such as the spread of HIV infection, Plasmodium falciparum chemoresistance, and outbreaks of emerging diseases. Bioterrorism, industrial and occupational hazards are added concerns. For these reasons, the French Military Medical Service has introduced a new concept based on permanent epidemiological surveillance of communicable diseases. This is completed by a real-time spatial surveillance designed to detect very rapidly potential communicable diseases or new emerging diseases. This epidemiological system, based on data modeling, enhances the medical information available to staff commands before deployment to new areas.