Possible prognostic significance of a brief rise in parasitaemia following quinine treatment of severe Plasmodium falciparum malaria.

An increase in parasitaemia is not uncommon after initiation of treatment for Plasmodium falciparum malaria, but its exact significance is unknown. The time-course of parasitaemia was assessed retrospectively in 33 patients with severe imported malaria. In 19 patients (group 1) mean parasitaemia (+/- SEM) fell promptly after starting quinine treatment, from 24.9 +/- 4.1% on day 0 to 9.7 +/- 2.3% on day 1 and 1.8 +/- 0.7% on day 2. In 14 other patients (group 2), parasitaemia did not change significantly or increased, with mean parasitaemia (+/- SEM) of 9.5 +/- 2.1% on day 0, 17.2 +/- 2.6% on day 1, and 3.7 +/- 1.8% on day 2. Simplified acute physiology scores on admission (mean +/- SEM) were 17.4 +/- 1.4 in group 1 and 11.7 +/- 1.0 in group 2 (P = 0.006). The mean number of complications of malaria per patient (+/- SEM) was 2.9 +/- 0.5 in group 1 and 1.6 +/- 0.3 in group 2 (P = 0.046). Two group 1 patients died. Initially, more than 95% of peripheral blood parasites were tiny and small rings in both groups, and this distribution was unchanged on day 1, suggesting that the parasitaemia increase in group 2 was not due to release of sequestered mature parasites. In severe falciparum malaria, a rise in parasitaemia after treatment initiation may be of favourable prognostic significance and should not lead to aggressive therapeutic approaches such as exchange transfusion.

[Chemical resistance of Plasmodium falciparum in Africa. Current situation, implications for chemoprophylaxis]. / Chimio-résistance de Plasmodium falciparum en Afrique. Situation actuelle, implications pour la chimioprophylaxie.

Resistance of Plasmodium falciparum to antimalarial drugs is a growing worldwide problem in endemic areas. This is particularly obvious with chloroquine resistance which has been spreading throughout Africa since 1978. Initially localized on the Eastern coast of the continent, it has recently reached the Atlantic coast although Western Africa is as yet unaffected. This resistance has most probably arisen in the autochtonous population under the selective pressure of insufficient curative treatments as a result of self medication. It is most prevalent in children of urban areas but is often revealed in non immune expatriates. In addition, moderately resistant parasites in expatriates under chemoprophylaxis may lead to an insidious clinical form with a low or even negative parasitemia which raises diagnostic problems. Prophylactic and therapeutic schemes must take this new situation into account.

[Reserve treatment for malaria: pros and cons]. / Le traitement de réserve du paludisme: le pour et le contre.

Any discussion of stand-by treatment will raise several questions: to whom should it be prescribed? which drugs are advised for stand-by treatment, according to the expected sensitivity of the parasites, the chemoprophylaxis and the possible side effects of the drugs chosen? what information should be given to a potential user? under what circumstances should stand-by treatment be used? how can the use of stand-by treatment and its efficacy be evaluated? are there any data for the stand-by treatment in literature? what are the pros and cons for the use of stand-by treatment? what is the place for stand-by treatment in today's array of antimalarial treatment? All of these questions were discussed at a round table stating that while stand-by treatment is an important element in malarial prevention for travellers, it must not become synonymous with self-treatment. An initial prescription of stand-by treatment is essential with the physician informing the user of the conditions for its use and its risks. The use of stand-by treatment does not exempt the traveller from rigourously carrying out the extensive recommended preventive measures. If, in spite of these precautions, a traveller does come down with a presumed malarial fever, the use of stand-by treatment should not prevent him from consulting a physician. A physician is in the best position to indicate an available stand-by treatment which should be considered as a back-up treatment. Self-treatment should only be considered as a last resort given its limitations. In all cases, it is indispensable to consult a physician.

[Bacterial and viral epidemics of zoonotic origin; the role of hunting and cutting up wild animals]. / Epidémies bactériennes et virales d'origine zoonotique. Rôle de la chasse et du dépeçage d'animaux sauvages.

Since the Prehistoric times hunting has been a vital activity for man. However, this may account for the contamination of the hunter, his family and relatives. Infections may occur by direct contact with blood or tissues of infected animal during handling and cutting up preys and when preparing or eating meat, or also when bitten by injured animal. Apes and antelopes hunting in sub-Saharan Africa proves to be particularly important since it has been well established that the recent or previous emergence of some viral zoonosis (Ebola, Aids, T lymphotropic viruses and Monkeypox) resulted from hunting and poaching. Moreover predation among different species of non human primates such as that practised by chimpanzees against monkeys, has led to the construction of recombinant simian Lentiviruses, such as SIV cpz able to infect man and then spread over the entire mankind as it was the case with HIV-1. SARS is another possible example of the zoonotic risks represented by the sale, handling and cutting up Chinese wild animals such as Himalayan civets for culinary purposes.

[The geography of infection with the human immunodeficiency virus (HIV) in black Africa: determination of epidemiological and regional factors]. / La géographie de l'infection par les virus de l'immunodéficience humaine (VIH) en Afrique noire: mise en évidence de facteurs d'épidémisation et de régionalisation.

In Africa, the continent most affected by HIV, the geography of the epidemic shows major contrasts. Strong regionalization differentiates both central-east Africa from west Africa and, within the countries, the urban zones from rural ones. Spatial and population factors are important when mapping the geography of the infection. An analysis of the evolution of movements--merchandise as well as populations--of the landlocked countries of the Great Lakes region of Africa leads the author to formulate a hypothesis involving regional considerations.

[Hemolytic anemia associated with minor salmonellosis in an HIV positive, G6PD deficient Congolese woman]. / Anémie hémolytique associée a une salmonellose mineure chez une congolaise VIH positive déficitaire en G6PD.

Haemolytic anaemia in G6PD-deficient patients with thyphoid fever is well known, but there is only one case-report associated with non-typhic salmonella fever. We report here a case observed in a black african young woman whose HIV infection has been discovered on this occasion. Because of the high prevalence of HIV infection, salmonellosis and G6PD deficiency in sub-saharian Africa, an increasing number of such haemolytic anaemias should be expected in this geographic area.

[Contribution of molecular genetics to the understanding of chemoresistance of Plasmodium falciparum]. / Apport de la génétique moléculaire à la compréhension des chimio-résistances de Plasmodium falciparum.

Resistance to pyrimethamine and proguanil is due to a single point mutation in the gene that codes for dihydrofolate reductase. A single mutation gives rise to resistance to only one of the drugs. Resistance to both drugs results from several mutations. Chloroquine resistance phenotype is due to a rapid efflux of the drug from the parasite's digestive vacuole. This efflux is associated with a transmembrane permeability glycoprotein, or P-gp, which is similar to the protein implicated in the multidrug resistant phenotype of some cancer cells. However, one or several other poorly understood major gene(s) may be involved. Drugs which can inhibit the supposed affinity of P-gp for chloroquine are under study.

[Effects of chloroquine on the replication of a murine retrovirus]. / Effets de la chloroquine sur la réplication d'un rétrovirus murin.

The wide use of chloroquine (Cq) for prophylaxis and chemotherapy of malaria in Africa, and the increased spread of AIDS in areas of this continent where malaria is endemic, raised the question of a possible interaction between chloroquine intake and HIV infection. Indeed, hydroxychloroquine and chloroquine itself have been shown to inhibit HIV-1 replication in vitro, hydroxychloroquine being proposed as a potential useful adjunctive therapy in the treatment of HIV-1 infection. On the other hand, chloroquine has been reported to enhance the replication of Semliki forest and encephalomyocarditis viruses in a mouse model. In an attempt to elucidate Cq effect on retroviral replication, we have studied the effect of various concentrations of chloroquine in vitro (0.1 nmol/l to 25 mumol/l) on Friend retrovirus (FV)-infected fibroblasts of mice and in vivo (2 to 30 mg/kg) on FV-infected mice. No reduction in the number of virus foci was found in chloroquine-treated fibroblasts cultures. In chloroquine treated-infected mice, no differences were observed in the spleen weights, except an increase at 10 mg/kg. A decrease in splenocyte virus titer was only observed at 10 and 30 mg/kg. No differences in the median survival time was observed up to 30 mg/kg. The authors concluded that chloroquine seemed to have variable effects on viral replication in vivo depending on the dosage, but has no influence on the course of FV-induced disease.

[Prophylaxis of malaria]. / Prophylaxie du paludisme.

Malaria prevention involves vector control, individual protection against mosquito bites and chemoprophylaxis. Chemoprophylaxis has become more difficult in recent years owing to the spread of chloroquine-resistant P. falciparum strains. Current possibilities are chloroquine and mefloquine (with relatively poor tolerance and a few resistant strains), or the chloroquine-proguanil combination (well tolerated with some failures). Prophylaxis should not be discontinued unless transmission remains at a low level. Among inhabitants of endemic areas, prophylaxis is generally restricted to pregnant women.

[Plasmodium falciparum malaria attacks with low or negative parasitemia on returning from areas of endemic resistance to 4-aminoquinolines]. / Accès palustres à Plasmodium falciparum à parasitémie faible ou nulle au retour de régions d'endémie de résistance aux amino-4-quinoléines.

Twelve recent cases of Plasmodium falciparum malaria presented with unusual clinical and laboratory features. All patients had regularly been taking adequate doses of amino-4-quinolines as prophylaxis. In most cases the symptoms were mild as compared with those in a group of 20 control patients with typical malaria. More surprisingly, parasitaemia was either negative or very weakly positive (less than 1000 infested erythrocytes per mm3). All cases occurred in people returning from areas in which resistance of P. falciparum to these drugs is endemic. Diagnostic problems could be solved in most patients by new immunological techniques relying on the detection of parasitized erythrocytes and plasmodium antigens using a battery of monoclonal antibodies. A physiopathological model explaining why parasitaemia is negative in such cases is suggested.

[Resistance to P. falciparum malaria in tropical Africa: congenital and genetic factors. General review (author's transl)]. / Facteurs congénitaux et facteurs génétiques dans la résistance au paludisme. A P. falciparum en Afrique tropiciale. Revue générale.

During the first months of life, maternal antibodies and foetal haemoglobine reduce the parasitical multiplication and allow the development of an effective immunological defense. In addition, the foetal defense structures receive a useful information from the malarial antigens passing in through the placenta. Genetic erythrocytic factors also, operate in some individuals, who, as a rule, are homozygotic. Various genes control the development of a premunition-type immunization giving an almost perfect balance between host and parasite, in individuals as well as for populations as a whole. It is likely that selective mutation has increased the frequency of favourable genes.

[Drug resistance of Plasmodium falciparum. Analysis of factors in its appearance and spread]. / La chimio-resistance chez Plasmodium falciparum. Analyse des facteurs d'apparition et d'extension.

After recalling the biochemical and genetic mechanisms of P. falciparum chemo-resistance, the authors report on an analytic study of the factors ruling the apparition and diffusion of resistant strains. The phenomenon is of chromosomic origin. The repetitive and high doses of drugs exert a pressure on the strains which is the main factor for revealing the selecting resistant mutants. Other facilitating factors may operate such as a lack of immunity of the considered population, a possible particular efficiency of some anopheles (more specially A. balabacencis) in the transmission of chloroquino-resistant strains, transfers of population acting either by a massive arrival of persons receptive or carrying resistant plasmodia. The most serious concern is the recent apparition of polyresistant cases in the Indochina Peninsula. The geographical distribution of chloroquino-resistance suggests the existence of two distinct stocks of P. falciparum: one indigenous to Africa and the Atlantic skirt of the American continent, the other to south-est Asia and deep tropical America. Prophylactif consequences, though difficult to apply, are proposed.

[Treatment of Plasmodium falciparum malaria in Africa (except cerebral malaria)]. / Le traitement du paludisme à Plasmodium falciparum en Afrique (à l'exception des formes pernicieuses).

Chloroquine is currently the drug of choice for treatment of acute attacks of Plasmodium falciparum malaria in chloroquine-sensitive areas. In areas of low level resistance, this drug may still be used (25 mg/kg of body weight in three days) in semi-immune patients. In case of failure, or in areas of high level resistance, quinine (25 mg/kg/day for 3 to 5 days) or, in spite of increasing resistance, Fansidar should be prescribed. Mefloquine, Fansimef and Halofantrine ought to be strictly prescribed to delay occurrence of resistance. Severe attacks require quinine by continuous intravenous infusion. Spleen enlargement does not usually require specific treatment unless poor tolerance is observed. Blood transfusions present a considerable risk of HIV transmission. Appropriate malaria treatment may avoid blood transfusions thus preventing HIV dissemination in Africa.

[Geographical survey of drepanocytemia: causes of its distribution in Africa south of Sahara (author's transl)]. / Géographie de la drépanocytose: les causes de sa répartition dans l'Afrique au sud du Sahara.

In Africa South of Sahara, HbS is distributed in east-west oriented belts, its frequency decreasing from equator to tropics. This singular feature results from interaction of various and complex phenomenons: apparition and diffusion of the mutation, role of malaria, climatic conditions.

[Acquired immunodeficiency syndrome in the adult. Its value in tropical medicine]. / Le syndrome d'immuno-dépression acquise de l'adulte. Interêt en médecine tropicale.

In the temperate climate countries, AIDS is defined as the occurrence of opportunistic infections and/or Kaposi's sarcoma in adults, mostly homosexuals. It can be preceded by a related state of asthenia, loss of weight, adenopathies, diarrhoea, but which is far from always developing into AIDS. The immune syndrome is specified by cutaneous anergy , lymphopenia with an elective decrease of OKT4. The etiology is not known and, if one often refers to retro-viruses (specific disease), the role of multiple and repeated infections ( plurifactorial syndrome) can not be discarded. Cases of AIDS exist in Haiti and possibly in Equatorial Africa, the latter may be different from the occidental cases. The planning for a survey in Africa is suggested.

[Treatment of amibiasis with short-term secnidazole therapy]. / Le traitement de l'amibiase par le secnidazole en cure courte.

The authors have treated: a) 48 cases of E. histolytica histolytica intestinal amoebiasis by a single dose of 35 mg/kg of secnidazole with 98 p. 100 of parasitological success; b) 122 cases of E. histolytica minuta with several procedures: a unique dose of 25 mg/kg gives no success in 16.6 p. 100 of the cases, but the same single dose during three days gets only 2 p. 100 of failure; c) 22 cases of hepatic amoebiasis by a daily dose of 25 to 33 mg/kg during 5 days with success in every cases. Tolerance has been excellent. These short cures, facilitated by the long half-life of secnidazole are particularly easy to apply in developing countries.

[HIV infection and malaria]. / Infection à VIH et paludisme.

In sub-Saharian Africa, most HIV seropositive subjects carry either haematozoa (especially children) or antimalarial antibodies. Despite a transient decrease in cell-mediated immunity during malarial paroxysms, Plasmodium falciparum malaria does not seem to influence the course of the HIV infection. Paroxysms may be slightly more frequent or slightly more severe in HIV seropositive subjects, but they raise no diagnostic or therapeutic problem. Some cases of HIV contamination have been attributed to the blood transfusions required by malaria-induced anaemia. Prophylactic measures include early chemotherapy of malaria and detection of dangerous blood donors, if necessary by quick tests. Modern HIV tests avoid most of the false-positive reactions sometimes observed during malaria.

[Treatment of bilharziasis]. / Le traitement des bilharzioses.

Specific treatment of bilharziosis is obviously simplified by praziquantel which, unfortunately, is not easily available in endemic areas. Nevertheless, the major problem is an early treatment before the occurrence of severe sequellae. Mass chemoprophylaxis remains needed and, if possible, with praziquantel. For economic purposes, we have often to use either oxamniquine or niridazole-metrifonate combination.

[Human transmission and plasmodium resistance]. / Transmission humaine et résistance des plasmodies.

There is no longer malaria transmission in Europe and North America, while the transmission decreases in sub-tropical areas and increases in tropical countries. Most of malarias are now due to Plasmodium falciparum and happen in Africa. In the regions where the transmission is high, malaria is stable, baby mortality is high, and protective immunity is achieved in early childhood. Falciparum resistant malaria originates from mutations on drug target decreasing affinity to antifols, or mutations preventing accumulation of chloroquine in parasitized red blood cells. Resistance is a rapid event following large use of antifols, even associated, while falciparum chloroquine resistance is now widespread. Resistance to quinine, mefloquine and halofantrine is still at low levels out of Thailand, as their use remains through medical hands. Non resistance was observed yet with artemisinin derivatives.