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The A.A. weight present criteria of choice in order to set right a correct and effective anti-malarial prophylaxis. In the last ten years, a progressive increase of tropical diseases has been observed. This is due to the considerable growth of intercontinental traffic and of the number of persons moving to or from tropical areas where such diseases are endemic. Among these, malaria represent the most alarming problem, both because of the incidence cases and the difficulties related to the efficacy of pharmacological remedies for the chemoprophylaxis. In particular, three are now various pharmacological possibilities for malarial prophylaxis. Undoubtedly Chloroquine is the most efficacious even if there are many Plasmodium falciparum species resistant to Chloroquine and to other available medicines (multi-resistance). Most authors recommend to associate Chloroquine to others pharmacological substances to avoid pharmaco-resistance phenomena. Among the most famous pharmacological products used elsewhere are Fansidar, Maloprim, Paludrine and Lapudrine, not all are available in Italy. In China, for the therapy of resistant forms of malaria, the Qinghaosu a "schizont-killer" acting on multiresistant plasmodium falciparum has been utilizing for years. The Qinghaosu is not responsible for the crossing-reactions with other anti-malarial medicines. Various substances with Ca-antagonist action (Verapamil) are being experimented. It is supposed that Verapamil associated with Chloroquine can stop the flow of chlorine from plasmodium cells. The same mechanism is expected to be valid also for Desipramine, an experimental tricyclic anti-depressive when associated to Chloroquine. To the people moving to endemic areas, the A.A., at the end, suggest a series of practical norms to prevent infection and, therefore, the incidence of imported cases, still increasing at the moment, due to the absence of efficacious vaccine.
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PMID:[A current problem: the prevention of malaria]. 248 2

Fifty-two Gambian children who had received fortnightly chemoprophylaxis with maloprim, (pyrimethamine and dapsone), and 45 receiving placebo, were studied. Cellular immune responses to malaria antigens, measured by lymphoproliferative responses and interferon production, were higher in children who had received prophylaxis than in controls, although the anti-malarial antibody levels were lower. During a one-year period after termination of prophylaxis, there was no increase in the frequency of clinical episodes of malaria in the children who had received Maloprim. These results suggest that chemoprophylaxis for 3 years may lower malaria antibody levels, but does not interfere with the development of protective immunity, perhaps by enhancing cell-mediated immune responses to malaria in protected children.
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PMID:Cellular immune responses to Plasmodium falciparum antigens in children receiving long term anti-malarial chemoprophylaxis. 251 34

The incidence of acute gastrointestinal and acute respiratory infections was measured in 2 groups of approximately 750 Gambian children aged 3-59 months during a 3-year period. One group of children was partially protected against malaria by fortnightly chemoprophylaxis with Maloprim whilst children in the other group were infected much more frequently. Mortality from acute gastroenteritis and from acute respiratory infections was similar in the 2 groups. The proportions of children in each group who complained of gastrointestinal or severe respiratory symptoms on morbidity surveillance were also similar. Thus, no evidence was found to suggest that malaria plays either a direct or indirect role in causing acute gastrointestinal or respiratory infections in young children in The Gambia.
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PMID:Lack of an association between acute gastroenteritis, acute respiratory infections and malaria in young Gambian children. 255 9

A trial of malaria chemoprophylaxis given by traditional birth attendants was undertaken in a rural area of The Gambia where access to antenatal clinics is difficult. Women received one or more doses of Maloprim or placebo from a traditional birth attendant during 1049 of 1208 pregnancies (87%) recorded in 16 villages over a 3-year period. Primigravidae who received Maloprim had a lower parasite rate and a significantly higher mean packed cell volume than primigravidae who received placebo, and their babies were significantly heavier (6% low birth weight vs 22%). In multigravidae chemoprophylaxis reduced malaria parasitaemia but it had no beneficial effect on haemoglobin level and much less effect on birth weight than was observed in primigravidae. However, the mean birth weight of babies born to grandemultigravidae who received chemoprophylaxis was significantly higher than that of babies born to grandemultigravidae who did not.
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PMID:The effects of malaria chemoprophylaxis given by traditional birth attendants on the course and outcome of pregnancy. 261 19

A comparison has been made of Lapudrine (chlorproguanil) and Maloprim (pyrimethamine +dapsone) as malaria chemoprophylactics when given every two weeks for 3 years to Gambian children under the age of 5 years. Both drugs produced falls in spleen and malaria parasite rates and an increase in packed cell volume. Maloprim, but not chlorproguanil, significantly reduced the incidence of episodes of fever accompanied by malaria parasitaemia. Children who received Maloprim, but not those who received chlorproguanil, grew better than children in the placebo group. This finding suggests that brief clinical episodes of malaria are more important in impairing growth than more prolonged periods of asymptomatic parasitaemia. No serious side-effect attributable to either drug was observed. After chemoprophylaxis had been given for 3 malaria transmission seasons the level of resistance of Plasmodium falciparum to pyrimethamine and to chlorproguanil was about 10%.
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PMID:A comparative study of Lapudrine (chlorproguanil) and Maloprim (pyrimethamine and dapsone) as chemoprophylactics against malaria in Gambian children. 269 27

The most recent acquisitions on chemotherapy and chemoprophylaxis of malaria are reviewed. With regard to chemotherapy, candidate antimalarial compounds have been divided into four groups, according to their stages of development. Mefloquine and the combination of mefloquine with sulfadoxine/pyrimethamine belong to the first group: they have completed clinical trials and have been registered in several countries for routine clinical use. The second group is characterized by chemical compounds which are in an advanced stage of development, including clinical trials. The compounds considered in this group are: a) the 9-phenanthrenemethanols, among which halofantrine is the most promising one; b) the sesquiterpene lactones such as Qinghaosu, artemether, artesunate, artesunic acid and arteether which must be further tested in order to find more effective drug regimens capable of eliminating recrudescences and for the completion of toxicity studies; c) pyronaridine, which appears to be a promising antimalarial, effective also against chloroquine-resistant P. falciparum, but still requiring further investigations on resistance and cross-resistance, as well as its pharmacokinetics, tolerability and bioavailability; d) enpiroline, another promising compound, which needs to be further studied in Phase II and Phase III investigations with naturally acquired malaria. The third group is composed of seven chemical classes of compounds that are in an advanced pre-clinical development, namely: the 4-aminoquinolines, such as dabechin, piperaquine, hydroxypiperaquine, tripiperaquine, dichlor-quinazine and the Mannich base compounds, the 8-aminoquinolines, the 4-quinolinemethanols, the quinolones, the naphthoquinones, the quinazolines and the dihydrotriazines. Among the many antimalarial compounds of interest, which can be considered at the moment as leads for further studies, only the acridandione derivatives such as floxacrine, the antibiotics, antifungal agents or their metabolites, plant substances such as Yingzhaosu A and quassinoids have been mentioned. Malaria chemoprophylaxis, especially in chloroquine-resistant P. falciparum areas, has become a real problem. The attempts to secure protection under these circumstances with the utilization of amodiaquine, the combination of sulfadoxine/pyrimethamine (Fansidar), sulfalene/pyrimethamine (Metakelfin), of pyrimethamine/dapsone (Maloprim), with or without chloroquine, had to be abandoned or to be used with caution in view of the severe complications following the weekly administration of these drugs. The combination of chloroquine with proguanil or chlorproguanil, which could be recommended on theoretical bases, did not meet the expectations when tested in the field. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recent acquisitions on chemotherapy and chemoprophylaxis of malaria. 269 8

A battalion of Royal Thai Marine militia was assigned to take either 50 mg or 100 mg of doxycycline daily or pyrimethamine/dapsone weekly for malaria prophylaxis on the Thai-Kampuchean border for a 17 week period. Attack rates for the groups expressed as cases/100 men were 34 for 50 mg doxycycline, 18 for 100 mg doxycycline, and 52 for pyrimethamine/dapsone. The relative efficacy of the two doxycycline regimens compared to Maloprim were 1.6 and 1.4. Compliance with the daily drug nearly equalled that of the weekly regimen. This suggests that 100 mg of doxycycline daily can be effectively used for malaria prophylaxis by soldiers under operational conditions on the Thai-Kampuchean border.
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PMID:Malaria prophylaxis with doxycycline in soldiers deployed to the Thai-Kampuchean border. 277 4

Two drug strategies for the control of malaria in children aged 3-59 months have been compared in a rural area of The Gambia--treatment of presumptive episodes of clinical malaria with chloroquine by village health workers, and treatment combined with fortnightly chemoprophylaxis with 'Maloprim' (pyrimethamine/dapsone) which was also given by village health workers. Treatment alone did not have any significant effect on mortality or morbidity from malaria. In contrast, treatment and chemoprophylaxis reduced overall mortality in children aged 1-4 years, mortality from probable malaria, and episodes of fever associated with malaria parasitaemia. A high level of compliance with chemoprophylaxis was obtained and no harmful consequences of chemoprophylaxis were observed.
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PMID:Comparison of two strategies for control of malaria within a primary health care programme in the Gambia. 289 57

A cohort of 48 Gambian children was protected against malaria by fortnightly administration of Maloprim (pyrimethamine and dapsone) for 2 years between their 3 and 5 birthdays. A matched cohort of 47 children received placebo. During the year following the termination of prophylaxis there was no increase in the frequency of clinical attacks of malaria in the protected children compared with the control children. Antibody levels to circumsporozoite protein were measured by a radioimmunoassay and that to blood-stage antigens by a variety of techniques including an ELISA to whole blood-stage Plasmodium falciparum antigen, immunofluorescent assays (IFAT) to acetone fixed, glutaraldehyde fixed and unfixed parasites, a merozoite inhibition test and an opsonizing assay. Antibody levels were, in general, lower in protected than in control children and several differences between the two groups were statistically significant. When antibody levels were measured by ELISA and IFAT at the end of the following rainy season, when malaria transmission was intense, those in protected children had increased to comparable levels to those found in control children. Our findings suggest that chemoprophylaxis given for 2 years lowers malaria antibody levels but that it does not interfere with the development of protective immunity.
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PMID:Immunity to malaria in young Gambian children after a two-year period of chemoprophylaxis. 305 50

The dapsone-pyrimethamine combination (100 mg of dapsone, 12.5 mg of pyrimethamine [Folaprim; Maloprim, one tablet a week) is considered to provide adequate prophylaxis for Plasmodium falciparum malaria, but to be inadequate for the prevention of P. vivax malaria. Field trials and case reports, however, have shown the comparable efficacy of this combination in the suppression of parasitaemias caused by both parasites. In Lae, Papua New Guinea, 12 patients with clinical signs of malaria had serum concentrations of dapsone-pyrimethamine which were consistent with appropriate weekly use of this combination. The fact that 10 of these patients had P. vivax malaria supports the hitherto unsubstantiated view that dapsone-pyrimethamine can be ineffective in suppressing parasitaemias caused by this parasite. In the two patients with P. falciparum malaria, host factors rather than parasite resistance to dapsone-pyrimethamine were implicated in the development of the parasitaemias.
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PMID:Inadequate prophylaxis of malaria with dapsone-pyrimethamine. 388 12


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