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Biomedical subjects

P Ringwald

Publications and source records attributed to P Ringwald.

At least 91 records · Page 5Linked to original sources

[A study of the efficacy of the chemoprevention of malaria using chlorproguanil alone or in combination with chloroquine in French expatriates in Dar-es-Salaam, Tanzania].

Seventy-nine French residents in Dar-es-Salaam, Tanzania, on 3 chemoprophylactic regimens, were included in a prospective study for a mean time of 10.8 +/- 3 months. No malaria attack was observed in the group (n = 32) taking chlorproguanil and chloroquine for chemoprophylaxis. Two attacks were reported in the group (n = 29) using chlorproguanil alone and 5 attacks in the group (n = 20) that was not taking antimalarial chemoprophylaxis. The blood concentration of chlorproguanil and chlorcycloguanil, the active metabolite, were measured, 3 hours (II3), 3 days (D3), and 7 days (D7) after the weekly dose. The urine concentration was measured at D7. The prophylaxis failure with chlorproguanil can be explained either by irregular use of the drug, or insufficiently lasting plasma concentration of chlorcyloguanil, or existence of parasite resistance to dihydrofolate reductase inhibitors.

Adolescent↗

[Pulmonary tuberculosis and cutaneous anergy to tuberculin].

A negative tuberculin test in a bacilliferous subject is an apparently paradoxical situation, since the first penetration of tubercle bacilli into the human body is known to induce hypersensitivity to tuberculin and to enhance cellular immunity. These two facets of cutaneous reaction are most probably related to lymphocyte populations of two different phenotypes. The authors found that 21% of skin tests were negative in patients carrying tubercle bacilli, with a higher frequency in elderly people and in subjects with low serum albumin levels and/or biochemical hepatic alterations. Helped by the literature, they are wondering about the significance and possible mechanisms of this situation.

Adult↗

Chronotherapy of malaria: improved efficacy of timed chloroquine treatment of patients with Plasmodium falciparum infections.

The effect of routine treatment with chloroquine (10 mg/kg on days 1 and 2 and 5 mg/kg on day 3) on parasitaemia and parasitaemic profile of patients infected with Plasmodium falciparum was studied. As with P. vinckei petteri, the mid-term trophozoites of P. falciparum were the most susceptible stages to chloroquine treatment. It is suggested that, in order to diminish the frequency of drug administration and to lower the risks of chemoresistance developing, treatment should be diversified, using the drug which is most effective on the parasite stages present in the peripheral blood.

Animals↗

Immune response to Plasmodium falciparum liver stage antigen-1: geographical variations within Central Africa and their relationship with protection from clinical malaria.

Two populations of schoolchildren from Gabon and Cameroon were tested in 1995 for their immunological reactivity to synthetic peptides (LSA-Rep, LSA-J and LSA-CTL) from Plasmodium falciparum liver stage antigen-1 (LSA-1). The prevalence and levels of both cellular (lymphocyte proliferation, tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma), and interleukin-10 (IL-10)) and humoral (immunoglobulin G) responses were determined. Protection from clinical malaria, determined after a prospective 1 year study in both sites, was associated with elevated proliferative responses to LSA-Rep and LSA-CTL in the Gabonese children, as well as with higher antibody levels to both schizont extract and LSA-Rep. The prevalence of peptide-stimulated TNF-alpha secretion was higher in the Cameroonian group, but higher levels of antibodies to LSA-Rep and LSA-J were found in the Gabonese children. The immunological differences observed between children in the 2 study sites are discussed in the context of both epidemiological and individual host factors.

Animals↗

Point mutations in the Plasmodium falciparum cg2 gene, polymorphism of the kappa repeat region, and their relationship with chloroquine resistance.

Based on the available DNA sequence data of the Plasmodium falciparum cg2 gene, we have hypothesized that 3 amino-acid substitutions, His275Gln, Gly281Ala, and His299Gln, may represent the key mutations that confer resistance to chloroquine. The presence of 14 tandemly repeated hexamer units in the kappa region has also been suggested to be indicative of chloroquine resistance. These 2 hypotheses were tested by determining the sequence of DNA fragments containing all 3 codons and kappa repetitive region (approximately 450-basepairs) for 53 randomly selected clinical isolates (obtained in Cameroon in 1994-97) with known response in vivo and/or in vitro to chloroquine. The cg2 genotypes based on the 3 codons and the response in vitro to chloroquine, as well as the number of kappa repeat units and responses in vivo and in vitro to chloroquine, were associated (P < 0.05). cg2 gene mutations were more common in parasites from patients with failure in vivo. However, this difference did not achieve statistical significance (P = 0.055). The sensitivity and specificity of the 3 codons and kappa repeat region to predict the response in vitro to chloroquine ranged between 75% and 85%. The sensitivity and specificity of these genetic markers to predict the response in vivo to chloroquine were of lower values. The kappa repeat region of the clinical isolates is polymorphic but characterized by several conserved features.

Antimalarials↗

Amodiaquine remains effective for treating uncomplicated malaria in west and central Africa.

Many countries in Africa are now confronted with the dilemma of shifting drug policies for uncomplicated falciparum malaria from chloroquine, which has become largely ineffective, to a new first-line drug and amodiaquine is one of the possible options. A multicentre, open-label randomized controlled trial of amodiaquine 30 mg/kg vs chloroquine 25 mg/kg over 3 days was performed in Senegal, Cameroon, Gabon, and Burkina Faso between 1996 and 1998 and patients were followed-up for 14 days. Sensitivity of isolates in vitro and whole blood levels of chloroquine and amodiaquine were also measured. The primary efficacy parameter was parasitological clearance on day 14 (parasitological success). The secondary efficacy parameter was absence of signs/symptoms of malaria on day 14 (clinical success). Among the 364 patients randomized and receiving the assigned treatment (chloroquine n = 185, amodiaquine n = 179), 137 and 139, respectively, reached the primary endpoint. Amodiaquine proved significantly more effective than chloroquine. The summary odds ratio (95% CI) was 7.79 (4.54-13.35) for parasitological success, and 6.3 (3.4-11.68) for clinical success. Sensitivity in vitro and chloroquine blood levels were good predictors of chloroquine failure. Amodiaquine remains effective for treating uncomplicated falciparum malaria in areas of West and Central Africa where chloroquine resistance is prevalent. However, measures should be taken to protect the lifespan of amodiaquine where the drug is introduced for use.

Adolescent↗