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The advances in the study of Afrotropical malaria vectors outlined in this report were obtained with the support of the EC-STD2 program by a network led by a research team of the Istituto di Parassitologia, University of Rome "La Sapienza" and including various collaborators based in different African countries. A list of authors and collaborating laboratories is given in the acknowledgements. The main results obtained are as follows. 1) Discovery of new chromosomally recognized taxa of the An. gambiae complex in Mali. One of them, the Mopti chromosomal form, is specifically adapted to breeding during the dry season and replaces other members of the complex in irrigated areas also in Burkina Faso and Northern Benin. 2) Evidence for increasing potential for P. falciparum transmission in the area of Cotonou (Benin) where highly anthropophilic An. gambiae (fresh water breeder) replaces the less effective vector An. melas (salt water breeder) when lagoon pile-dwelling traditional villages are converted into unplanned urban settlements. 3) Analysis of the vector system responsible for the P. falciparum epidemics on the Madagascar plateau showing the absence of An. gambiae, the secondary role of An. arabiensis (characterized by zoophilic and exophilic behaviour) and the primary role of An. funestus which is characterized by a peculiar focal distribution presumably depending on larval overwintering. 4) Evidence for a role for An. pharoensis (or at least of one of the taxa of this complex) in the transmission of P. falciparum malaria in the Senegal river delta. 5) Evidence for bionomical differences between An. gambiae and An. arabiensis and for intraspecific heterogeneities in both taxa associated with paracentric inversion polymorphisms.
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PMID:Advances in the study of Afrotropical malaria vectors. 823 6

To compare the efficacy and side effects of intramuscular (i.m.) and intravenous (i.v.) quinine, children in Mozambique with severe and complicated malaria between 6 months and 7 years were randomized to treatment with i.m. or i.v. quinine, both in a dosage of quinine dihydrochloride 20 mg/kg followed by 10 mg/kg every 8 h. Of 57 children treated with i.m. quinine, 4 died, 3 had neurological sequelae and 2 had sterile intramuscular abscesses. Of 47 children treated with i.v. quinine, 6 died and 1 had neurological sequelae. The mean parasite clearance time was 58.6 h in the i.m. group and 59.3 h in the i.v. group. Mean temperature clearance times were 56.1 and 51.8 h, and mean coma clearance times 40.4 and 38.7 h, respectively. None of these differences was statistically significant. Mean trough and peak concentrations of quinine were almost identical in the 2 groups, ranging from 10.5 to 12.6 mg/L, which is in the therapeutic non-toxic range. It is concluded that i.m. quinine is as effective as quinine by i.v. infusion in children with severe and complicated malaria; that minor local side effects can probably be avoided by using diluted quinine for i.m. injection; and that the optimal dose regimen for children with severe and complicated malaria in Africa at present is probably quinine salt 20 mg/kg followed by 10 mg/kg every 12 h.
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PMID:Comparison of intramuscular and intravenous quinine for the treatment of severe and complicated malaria in children. 823 98

As part of the Combatting Childhood Communicable Diseases (CCCD) project funded by the US Agency for International Development (USAID), the Zairian CCCD programme conducted surveys in the rural health zones of Kingandu and Pai-Kongila, Zaire, in 1984-1985 and 1988-1989 to determine whether a strategy of selective primary health care would affect childhood mortality. This paper describes the changes in the medical care infrastructure and the increasing coverage of selected services. The strategies evaluated were vaccination, oral rehydration therapy, and treatment of febrile episodes with antimalarial drugs for children; and tetanus vaccination and malaria prophylaxis for pregnant women. The health infrastructure in the Kingandu and Pai-Kongila Health Zones expanded considerably from 1984 to 1989, with health centres increasing from 7 to 18. During this period, economic conditions deteriorated moderately, with the nation experiencing nearly 700% inflation. Medical care costs remained stable because of external subsidies. Use of health services was assessed in 1984, 1988, and 1989. Between 1984 and 1989, the proportion of children aged 12-23 months vaccinated against measles increased from 22% to 71%. Coverage with other vaccine antigens increased similarly. Women's knowledge of the correct recipe for the preparation of sugar-salt solution increased from 0% to 61%. Reported treatment at home with sugar-salt or oral rehydration solution increased from 6% to 53%. The proportion of children with febrile episodes who were treated presumptively for malaria with chloroquine remained unchanged (47% in 1984; 44% in 1988). We conclude that, despite a moderate deterioration in economic conditions, Kingandu and Pai-Kongila Health Zones achieved remarkable increases in use of selected health services between 1984 and 1989, especially in vaccination coverage.
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PMID:Changes in use of health services in a rural health zone in Zaire. 830 72

As part of an evaluation of child survival programmes in 13 African countries, cluster surveys were carried out in two Liberian counties in 1984 and 1988 to measure use of three primary health care services: immunization of infants, antimalarial treatment of children with fever, and oral rehydration of childhood diarrhoea. Immunization rates increased (30-53% for DPT-1 and 13-33% for measles), treatment of malaria with drugs available in the home increased from 5 to 35%, and home use of sugar-salt solution to prevent dehydration remained essentially unchanged, 5.9% in 1984 and 3.8% in 1988.
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PMID:Immunization, oral rehydration therapy and malaria chemotherapy among children under 5 in Bomi and Grand Cape Mount counties, Liberia, 1984 and 1988. 830 75

It has been suggested that sulfadoxine-pyrimethamine (SD/PM) may be useful in the treatment of severe malaria since it could enhance the killing of parasites by quinine (QN) and it can be given as a single intramuscular injection. Eighty Kenyan children with severe malaria were allocated at random to receive either intramuscular QN alone (quinine dihydrochloride 20 mg salt/kg as a loading dose, followed by 10 mg salt/kg 12 hourly for a total of 6 doses) or the same QN regimen plus one intramuscular injection of SD/PM (sulfadoxine 25 mg/kg, pyrimethamine 1.25 mg/kg). There was no difference in time to defervescence, aparasitaemia, or 50% reduction in parasitaemia, parasite elimination half-life, or mortality between the 2 groups. In addition, the concentrations of SD and PM were measured in 14 children and of QN in 8 of these children. Concentrations needed to achieve synergy against PM-resistant strains of Plasmodium falciparum were achieved in all of the children with severe malaria within the first hour and maintained for more than 72 h. SD/PM did not perturb the pharmacokinetics of QN.
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PMID:A single dose of intramuscular sulfadoxine-pyrimethamine as an adjunct to quinine in the treatment of severe malaria: pharmacokinetics and efficacy. 833 31

1. The pharmacokinetics of rac-primaquine (45 mg base) and its principal plasma metabolite, carboxyprimaquine have been investigated in healthy Thai adults prior to and following a single oral dose of mefloquine (10 mg kg-1). 2. Primaquine was rapidly absorbed, attaining peak plasma concentrations (median and range) of 167 (113-532) micrograms l-1 in 2 (1-4) h. Thereafter, concentrations declined rapidly with an apparent terminal half-life of 6.1 (1.7-16.1) h and an oral clearance (CLpo) of 33.1 (17.6-49.3) l h-1. Administration of mefloquine had no effect on the values of any of these parameters at the 5% level of significance [Cmax 229 (114-503) micrograms l-1; tmax 3 (2-4) h; t1/2,z 3.9 (1.7-13.5) h; CLpo 34.0 (21.7-49.0) l h-1]. 3. The carboxylic acid metabolite of primaquine achieved maximum concentrations (median and range) of 890 (553-3634) micrograms l-1 at 6 (3-16) h. Thereafter, plasma concentrations of carboxyprimaquine declined to 346 (99-918) micrograms l-1 at 24 h. AUC (0,24 h) was 12737 (6837-27388) micrograms l-1 h. Administration of mefloquine had no effect on the plasma concentrations of this metabolite [Cmax 1035 (174-3015) micrograms l-1; tmax 8 (2-24) h; AUC(0,24) 13471 (2132-17863) micrograms l-1 h]. 4. The effect of falciparum malaria and treatment with quinine (10 mg salt kg-1 p.o.) on the pharmacokinetics of primaquine (45 mg base p.o.) has been investigated in adult Thai patients during and after infection with falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions among primaquine, malaria infection and other antimalarials in Thai subjects. 844 39

The efficacy and toxicity of oral quinine combined with oral chloroquine were studied in 50 Thai men with uncomplicated falciparum malaria. All were treated for 7 days with quinine sulphate (10 mg salt/kg every 8 h). Twenty-five of the patients, selected at random, were also given oral tetracycline (4 mg/kg four times daily) over the same period and the remainder were given chloroquine (25 mg base/kg over the first 3 days). There were no serious adverse effects. Overall fever-clearance times (FCT) and parasite-clearance times (PCT) in the chloroquine and tetracycline groups were not significantly different, with mean (S.D.) values of 51 (33) and 41 (27) h for FCT and 80 (25) and 83 (21) h for PCT, respectively. Most of the patients (18 in each group) were followed for > or = 2 months. Recrudescence rates (R1) were significantly higher in the chloroquine group than in the tetracycline group (39% v. 6%; P = 0.02), all recrudescences occurring within 4 weeks (18-25 days) of starting treatment. Subsequent parasitaemia with Plasmodium vivax, however, occurred less frequently in the chloroquine group (11%) than in the tetracycline group (33%) (P = 0.11) and took longer to develop in the chloroquine group [51 or 59 days compared with a mean (S.D.) value of 29 (10) days in the tetracycline group; P = 0.01]. Within the chloroquine group, FCT and PCT were both shorter in those with cure than in those with R1 resistance, with mean (S.D.) values of 41 (25) and 70 (33) h for FCT (P = 0.09) and 72 (20) and 100 (18) h for PCT (P = 0.01), respectively. Chloroquine does not potentiate the clinical response to quinine against resistant strains of uncomplicated falciparum malaria, nor does it convey any useful antipyretic effect.
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PMID:Therapeutic effects of chloroquine in combination with quinine in uncomplicated falciparum malaria. 875 41

A 3 d shortened course of the quinine-quinidine-cinchonin association Quinimax was compared to the usual 7 d regimen for routinely treating 462 acute uncomplicated Plasmodium falciparum malaria attacks in 72 children under the age of 10 years in Dielmo, a holoendemic village in Senegal. 25 mg/kg Quinimax salt daily, given in 3 equal doses, improved clinical status in 99.6% of the patients receiving the course and in all of those treated for 7 d. Even if the 3 d course did not systematically eliminate parasitaemia, reducing oral Quinimax treatment of uncomplicated malaria from 7 to 3 d did not increase the recurrence of attacks, even among the youngest children. Both the quinine sensitivity of the Senegalese strains of P. falciparum and the partial acquired immunity of the children were probably responsible for the absence of any difference between the courses. Oral Quinimax for 3 d is a possible alternative regimen to chloroquine and sulfadoxine-pyrimethamine for treating uncomplicated malaria in highly endemic areas of Africa where clinical resistance to these drugs exists.
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PMID:Reducing the oral quinine-quinidine-cinchonin (Quinimax) treatment of uncomplicated malaria to three days does not increase the recurrence of attacks among children living in a highly endemic area of Senegal. 876 82

In a longitudinal study we have observed the fluctuation in density of two Anopheles populations responsible for malaria transmission in a village built on a brackish lake. The two A. gambiae complex species are A. melas and A. gambiae s.s. The former is the most abundant (88%). The brackish lake ecosystem gives to both species possibilities of adaptation. The salt water species of the A. gambiae complex, A. melas, was found to be tolerant to waters with very low salinity. On the other hand, A. gambiae s.s. was found to support relatively high salinity rates. Both specimens live together the whole year round but their frequencies vary with the inundation of the lake. During inundation the salt rate decreases and A. melas eventually disappears. Transmission is low, seasonal and short on the lake. It is perceptible between March and August. The inoculation rate (11 infected bites per man/year) is lower than what we have observed in other lagoon areas of Benin, or even in the city of Cotonou (33 infected bites per man/year). The low malaria transmission on the lake is probably due to the presence of an important population of A. melas with low infection rates and the widespread use of bed nets.
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PMID:[Entomological study on the malaria transmission in coastal and lagoon areas: the case of a village built on a brackish lake]. 884 99

The effect of tryptophan-N-formylated gramicidin (NFG) on the growth of Plasmodium berghei in mice was tested in three different experiments. NFG was shown to be capable of inhibiting the growth of the parasite in a dose-dependent way, although its action did not result in elimination of the parasite and was only temporary, preventing mice from early death, presumably due to cerebral malaria, but not from fatal generalized malaria. Intriguingly, a similar observation was made with two other drugs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, an inhibitor of viral and eukaryotic DNA polymerases, and the presumed topoisomerase II inhibitor, a bisquaternary quinolinium salt. A rise in the level of parasitemia after 8 days, despite continued treatment, was not due to parasite-induced reticulocytosis, as demonstrated in experiments in which this condition was induced artificially. NFG was added in the form of lipid vesicles in which the peptide had been incorporated. The inhibitory action of NFG was not modulated by the lipid composition of the vesicles. Control experiments did not demonstrate any toxicity of NFG when it was administered in lipid vesicles. The main observation is that NFG is able to inhibit the growth of a malaria parasite in vivo at concentrations that are well tolerated by the host.
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PMID:Effect of tryptophan-N-formylated gramicidin on growth of Plasmodium berghei in mice. 925 60


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