PubMed Health⌕ Search

Biomedical subjects

E Onori

Publications and source records attributed to E Onori.

At least 19 recordsLinked to original sources
PubMed1989

Recent acquisitions on chemotherapy and chemoprophylaxis of malaria.

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)

Antimalarials↗
PubMed1987

Double-blind study to assess the efficacy of chlorproguanil given alone or in combination with chloroquine for malaria chemoprophylaxis in an area with Plasmodium falciparum resistance to chloroquine, pyrimethamine and cycloguanil.

In this study the efficacy of chlorproguanil (20 mg base weekly) was compared in schoolchildren with that of chloroquine (200 mg base weekly) and that of both drugs combined (20 mg base + 200 mg base weekly). The double blind trial was performed in the rice field area of the Ruzizi valley in Burundi, where Plasmodium falciparum is widely resistant to chloroquine, and where pyrimethamine resistance with cycloguanil cross-resistance had been demonstrated. After 17 weeks, when the trial was ended, 60% breakthroughs had been observed among the children taking chloroquine, 72% among those under chlorproguanil and 61% among those under chlorproguanil and chloroquine. In children weighing between 15 and 24 kg, the failure rate was significantly higher in those treated with chlorproguanil than in the group treated with chloroquine. No difference in efficacy was observed in children weighing 25 to 39 kg. There was no significant increase of efficacy when chlorproguanil was given in association with chloroquine. The mean titre of fluorescent antibodies was the same in each treated group on week 5 and week 15. The comparison of these data with the infection rates in non-protected children suggests that malaria could not be prevented with any of the drug regimens utilized in the study.

Adolescent↗
PubMed1984

The problem of Plasmodium falciparum drug resistance in Africa south of the Sahara.

The resistance of P. falciparum malaria to dihydrofolate reductase inhibitors, to the 4-aminoquinolines (in particular, chloroquine), and to the combination sulfadoxine-pyrimethamine is reviewed in the light of past and the most recent findings. Considering the gravity of the situation following the recent discovery of resistance of P. falciparum to chloroquine among the semi-immune populations of Africa south of the Sahara, a few suggestions are made for a realistic and rational approach to the drug resistance problem. Some questions that may be worthy of applied field research are briefly mentioned and governments are invited to take the necessary action to ensure better control of the procurement, distribution, and use of antimalarials.

Africa, Central↗
PubMed1982

Incipient resistance of Plasmodium falciparum to chloroquine among a semi-immune population of the United Republic of Tanzania. 2. The impact of chloroquine used as a chemosuppressant on the immune status of the population.

Decreased sensitivity and incipient resistance of Plasmodium falciparum strains to chloroquine have been reported from Mto-wa-Mbu, in the north-east of the United Republic of Tanzania. In this locality the population had been exposed to chloroquine pressure for about two decades, in the form of medicated salt and through easy availability of the drug itself. In an attempt to find out whether such chemosuppression had influenced the immune response of the population, two seroepidemiological surveys were carried out in March 1981 and March 1982; the second survey was performed to confirm the results obtained in the first one. The humoral immunological response was measured by the immunofluorescent antibody technique. In the absence of information on the immunological profile that existed in the area prior to the introduction of chloroquine in 1960, the results of the present surveys were compared with those obtained in another locality in the north-east of the United Republic of Tanzania in 1967, and in the West Kiang district of Gambia in 1965. The two areas used for comparison exhibited a malaria endemicity similar to that prevailing in Mto-wa-Mbu prior to the introduction of the medicated salt. The results from Mto-wa-Mbu showed a significantly lower proportion of subjects with positive titres and a lower geometric mean titre in all age groups.A reduction in the humoral immunological response might be explained by the drug pressure that has been exerted in the area for many years. The depressed immune response found at Mto-wa-Mbu, however, was so marked that other factors may have contributed to its establishment.In view of the importance of these findings, it is recommended that further, longitudinal serological studies be conducted in the field to assess the effects of chemosuppression on the immune response of the protected populations.

Anopheles↗
PubMed1982

Incipient resistance of Plasmodium falciparum to chloroquine among a semi-immune population of the United Republic of Tanzania. 1. Results of in vivo and in vitro studies and of an ophthalmological survey.

The sensitivity of Plasmodium falciparum strains to chloroquine was tested in one locality in the north-east of the United Republic of Tanzania, where a chloroquine-medicated salt project has been implemented for chemosuppression for many years, and where large amounts of the drug have been available during the last decade for the treatment of malaria infections.Single doses of chloroquine (5 or 10 mg of base/kg of body weight) failed to clear P. falciparum trophozoites in asymptomatic parasite carriers selected from the school population. In comparison, clearance had been obtained easily ten years previously with 5 mg of base/kg of body weight in several localities in the area.A total dose of 25 mg of base/kg of body weight given over a 3-day period succeeded in clearing asexual parasites from the peripheral blood by day 3 in all instances. Asexual parasites were not found again during the nine days following administration of the drug.All the schoolchildren who had received 5 or 10 mg of base/kg of body weight at the beginning of the trial were treated with a further 20 mg of base/kg of body weight at the end of the 7-day observation period. Asexual parasites reappeared in the blood of some of these children 7-10 days after the second administration of the drug.Using the in vitro microtechnique, incomplete schizont inhibition was observed in 3 out of 21 cases at a chloroquine concentration of 1.14 mumol/litre of blood, which is the discriminating dosage for resistance at RI level.No cases of retinopathy related to the prolonged use of chloroquine were detected among the 221 residents who had spent more than 16 consecutive years in the locality.

Adolescent↗
PubMed1981

[Resistance of Plasmodium falciparum to antimalarials: practical implications and control prospects].

The author reviews the present knowledge on the resistance of P. falciciparum to various antimalarials, such as the inhibitors of the dehydrofolate reductase (proguanil, pyrimethamine, cycloguanil embonate and trimethoprim), the 4-aminoquinolines, quinine and the combination of sulfadoxine-pyrimethamine and combinations of other antimalarials and outlines the geographical distribution of P. falciparum chloroquine-resistant strains. The genetic peculiarities of resistance to antimalarials and their possible relation to the actions exerted by the drugs in some biological processes of the parasite are described in the light of present knowledge. The classification of the response of P. falciparum to 4-aminoquinolines, proposed by a working group of the World Health Organization (sensitivity, resistance at R I, R II and R III levels) and the methods at present available to define the different responses (in vivo and in vitro methods) are described in detail. Attention is then drawn to the practical implications resulting from the continuous spreading of the phenomenon of drug-resistance, both in countries already affected by the problem and in those which are exposed to the risk of the importation of drug-resistant strains. Practical advice is given: (i) for the treatment of chloroquine- or poly-resistant P. falciparum strains with a brief description of the therapeutic potentialities of new antimalarials still at the experimental stage, especially mefloquine and (ii) on the measures to be taken to prevent the spreading and to control the phenomenon of drug-resistance. The future prospects for an efficacious control of the disease and of drug-resistance are viewed with some pessimism, due to the recent discovery of chloroquine-resistant P. falciparum strains in Africa and to the scarcity of the financial resources required to implement adequate control programmes.

Antimalarials↗
PubMed1980

Indicators for the forecasting of malaria epidemics.

The entomological inoculation rate is presented as a comprehensive indicator of malaria transmission level, its relative changes reflecting the risk of potential epidemic development. This rate is a known function of several epidemiological direct factors and is particularly sensitive to the survival rate and the sporogonic cycle of the vector. Although not yet fully quantifiable, relationships exist between direct factors responsible for the transmission of infection and certain meteorological and environmental indirect factors like air temperature, relative humidity, or importation of malaria parasites.The establishment of a two-stage monitoring system is suggested: the first stage would involve setting up a warning system based on the surveillance of the relevant indirect factors; at the appropriate time, this would trigger the second stage monitoring of the epidemiological direct factors having a definite bearing on the development of malaria outbreaks. It is recognized that the gain in reliability of the proposed approach depends largely on the progress still to be achieved in the quantification of the complex system of relations connecting the main direct factors with single or combined indirect factors. It is also noted that the proposed monitoring system should, in due course, provide the decision-makers with the epidemiological information required for the selection and implementation of intervention measures designed to prevent epidemic resurgences.

Climate↗
PubMed1980

Quantitative estimates of the evolution of a malaria epidemic in Turkey if remedial measures had not been applied.

In 1978, public health authorities, by means of large-scale control operations, succeeded in containing a severe malaria epidemic that had reached alarming proportions in the Cukurova and Amikova plains of southern Turkey. The benefits derived from this intervention are indirectly quantified in this article by estimating the number of cases that would have ocurred in the area if remedial measures had not been applied.For this purpose a simple mathematical model was fitted to both the number of cases in January (seasonal minimum) and the number of cases in July/August (seasonal maximum) that were recorded during the years 1976, 1977, and the beginning of 1978; the incidence trend from 1978 onwards was then determined by projection. By this method, it was possible to estimate that in the absence of intervention the projected annual parasite incidence would have been 75.4 per 1000 in 1978 instead of the observed incidence of 24.5 per 1000. According to the forecast, this incidence would have reached 100.9 per 1000 in 1979, 115.1 per 1000 in 1980, to arrive at a final stable level of 129.4 per 1000, if intervention measures had not been applied.Comparison of the number of malaria cases actually detected in 1978 (70 468) with the number projected in the absence of intervention (226 252) seems to indicate that about 2/3 of the expected cases were prevented in 1978 by the remedial measures applied.

Disease Outbreaks↗
PubMed1979

A histological investigation of skin lesions in onchocerciasis patients from Southern Togo.

Specimens from unselected populations in an area of hyperendemic onchocerciasis were used to describe and quantify histological changes in the upper layers of the dermis and the findings were compared with the macroscopical lesions observed. 553 persons, the inhabitants of two villages in Southern Togo, were examined. 502 biopsies were processed histologically. Onchocerciasis prevalence was over 75% and macroscopical skin lesions were evident in 30--40% of the population examined. Histological changes typical for the infection existed in the dermis in 68.5%. A cellular infiltration was seen in 49%, changes in the elastic or collagenous fibrils in 28.9% of the specimen. The observations are described in detail. Signs of inflammatory as well as primary degenerative changes were seen in biopsies from all age-groups. When microscopic and macroscopic findings are compared, it can be noticed that atrophy may start at an early age without preceeding dermatitis and that inflammatory reactions may occur at all ages. After submersion in saline for 24 hours not all microfilariae had emerged from the skin snips as evidenced by the histological examination. In 12.1% of those that otherwise would have been diagnosed as negative, microfilariae were identified in the sections.

Adolescent↗
PubMed1975

An epidemiological assessment of the residual effect of DDT on Anopheles hyrcanus sensulato and A. pulcherrimus (Theobold) in the North eastern region of Afghanistan.

In the irrigated zones of North-eastern region of Afghanistan malaria transmission is sustained by A. pulcherrimus and A. hyrcanus despite many years of DDT spraying. A. hyrcanus is an exophilic and exophagic mosquito, strongly resistant to DDT. A. pulcherrimus is still largely susceptible to the insecticide but seems to be deterred from entering houses when these are sprayed with DDT. Entomological and parasitological studies in an area of the province of Kunduz where DDT has not been applied for 2 consecutive years have clearly indicated that the insecticide still plays an important role in reducing malaria transmission in the area though, as expected, it cannot interrupt transmission. A deterioration of the epidemiological situation in the area can be expected if the insecticide is withdrawn. The technical problems now existing in the irrigated zones of the North-eastern region of Afghanistan cannot be solved by routine attack measures. Malaria in the area can be eradicated only with the introduction of new attack measures which are very expensive and for which, at present, the necessary funds are not available.

Afghanistan↗