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Biomedical subjects

H M Gilles

Publications and source records attributed to H M Gilles.

At least 19 recordsLinked to original sources

Surveillance of wild polioviruses in patients with acute flaccid paralysis in Malta during 1998 and 1999.

Certification of global poliomyelitis eradication can only be accomplished when all countries have been certified as having achieved wild poliovirus eradication. In order to achieve certification of eradication of poliomyelitis in Malta an active acute flaccid paralysis (AFP) surveillance system comprising the whole population was set up. Surveillance became effective in January 1998. During 1998, there were nine reported cases of AFP (non-polio AFP rate: 2.38 per 100,000 population) two of whom were children under 15 years of age (non-polio AFP rate: 2.52 per 100,000 for the population aged <15 years). In 1999 five cases of AFP were reported (non-polio AFP rate: 1.32 per 100,000 population). One case occurred in a child under 15 years (non-polio AFP rate: 1.28 per 100,000 for population aged <15 years). Virological investigation did not detect any wild or Sabin-like polioviruses.

Adolescent↗

Tropical medicine: 100 years of progress.

Over the past century, tropical medicine has passed through several overlapping phases. Initially, the picture was of endemic and epidemic diseases that wreaked havoc on people living in warm climates and visitors to these areas. High morbidity and mortality associated with these diseases reflected the poor state of knowledge about their causes and epidemiology and the lack of effective technologies for their control. At this stage, tropical medicine was dominated by parasitic and infectious diseases that had affinity for warm climates and some specific nutritional disorders. The next phase involved the steady accumulation of knowledge about the aetiological agents and, in the case of parasitic and infectious diseases, identification of reservoirs and vectors. The development of new and improved technologies for the control of tropical diseases characterised the third phase. The new products included drugs, diagnostic tools, vector control measures and vaccines. In the fourth phase, the new technologies are being deployed in programmes aimed at achieving disease control and, where feasible, total elimination of the problem. In the course of these operations, many useful lessons have been learnt from both the successes and failures of major schemes. In particular, experience has shown the important role of research not only in providing new technologies but also in optimising their effectiveness when applied in control programmes. The role of social and behavioural factors in the epidemiology and control of tropical diseases has drawn attention to the value of a multidisciplinary approach in designing and implementing control programmes. There is a sense of cautious optimism that, if the lessons learnt over the past century are carefully applied, further gains can be made in controlling and eliminating the classical problems that characterised tropical medicine at the beginning of this century.

Disease Outbreaks↗

The conquest of 'river blindness'.

Studies carried out at the WHO/OCP Onchocerciasis Chemotherapeutic Centre in Tamale, Ghana, are reported, culminating in the clinical trials of ivermectin (Mectizan), which has revolutionized our approach to the treatment of the disease. It is concluded that the conquest of 'river blindness' is an eminently achievable goal.

Clinical Trials as Topic↗

The chemotherapy of onchocerciasis. XV. Studies with albendazole.

Ninety-two males, infected with Onchocerca volvulus, from an area of on-going transmission in the forest zone of southern Ghana were treated with albendazole. 31 patients received 800 mg daily x 3, 31 received 1200 mg daily x 3 and 30 others received 800 mg daily x 7. Albendazole was given as a single daily dose with a fatty breakfast. Detailed systemic, ocular and laboratory examinations were performed pretreatment and at intervals over one year. Nodules were extirpated on days 30 and 60 and examined by histopathology. All the dose regimes were well tolerated but were neither microfilaricidal nor macrofilaricidal. The main effect was embryotoxicity affecting all intra-uterine stages. The most encouraging results were obtained in the 800 mg daily x 3 group in which a prolonged suppression of skin microfilarial counts occurred. Controlled studies in combination with ivermectin are recommended to determine whether an additive effect of the two drugs would result in permanent sterilisation of the adult worms.

Adult↗

Malaria--an overview.

The epidemiology, clinical features, diagnosis, prognosis, management, chemotherapy and chemoprophylaxis of malaria are reviewed.

Animals↗

Inter-subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man.

1. The metabolism of proguanil to the active metabolite cycloguanil has been evaluated in 135 British Troops and 26 Kenyan schoolchildren. 2. Large inter-subject variability was observed in both plasma and urinary concentrations of proguanil and cycloguanil after standard doses of drug. 3. Based on the ratio of proguanil to cycloguanil (P/C) in urine the British troops formed a non-normal distribution. 90% of the population formed a discrete distribution with P/C ranging from 0.5 to 9.0 while the remaining 10% were scattered throughout the distribution to an extreme value of 39. A similar pattern of variability was observed using P/C from a 6 h plasma sample. 4. This variability was due to differences in the ability of individuals to metabolise proguanil to cycloguanil. 5. Thirteen schoolchildren who had experienced malaria during prophylaxis with proguanil and thirteen matched controls each received proguanil (100 mg). We could not discriminate between the two groups based on P/C ratio in either a 6 h plasma or 0-6 h urine sample.

Adolescent↗

The chemotherapy of onchocerciasis. XIII. Studies with ivermectin in onchocerciasis patients in northern Ghana, a region with long lasting vector control.

One hundred and ninety eight patients with moderate to heavy infections with Onchocerca volvulus were randomly assigned to receive single doses of 100, 150 or 200 mcg/kg of ivermectin or matching placebo capsules. Detailed systemic, ocular and parasitological examinations were carried out at intervals over a period of one year. Nodules were excised twelve months after treatment to evaluate the effect of the treatment with ivermectin in adult O. volvulus. The three ivermectin-treated groups produced massive reductions in skin microfilariae (over 97%) with low levels being maintained over one year. The 150 and 200 mcg/kg doses were however superior to the 100 mcg/kg dose in achieving a greater reduction in skin microfilarial counts initially and in maintaining significant lower levels throughout the period of observation. There was no difference between the 150 and 200 mcg/kg doses at anytime. The three ivermectin doses were equally effective in the clearance of ocular microfilariae. The proportion of dead adult worms was very high in all treatment groups, which is effected by the successful ten years lasting vector control in northern Ghana. In spite of this superannuation of the worm population, an impact of the treatment with ivermectin on the reproductivity of the parasite could be shown. Systemic total clinical reaction was mild and was similar in the ivermectin treated groups. However, severe symptomatic postural hypotension (SSPH) was limited to patients treated with 150 or 200 mcg/kg of ivermectin. Ocular reactions were mild in all patients and no ocular deficiency occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Efficacy of multiple-dose halofantrine in treatment of chloroquine-resistant falciparum malaria in children in Kenya.

Halofantrine hydrochloride given to 46 Kenyan children with falciparum malaria at 10 mg/kg for two doses, and to 60 other children at 8 mg/kg for three doses, resulted in rapid parasite clearance, mean parasite clearance times being 45.4 h and 54.8 h, respectively. In-vitro chemosensitivity tests showed that most infections were due to chloroquine-resistant parasites, and that parasite maturation was inhibited by considerably lower concentrations of halofantrine than of chloroquine.

Administration, Oral↗

Clinical trials with halofantrine hydrochloride in Malawi.

Two clinical trials of the phenanthrene methanol compound halofantrine in the treatment of Plasmodium falciparum were conducted in Malawi, in areas where the parasite was known to be chloroquine resistant. In the first trial all 46 patients had symptoms of malaria and parasite densities ranging from 2500/microliter to 212,000/microliter. They were given a single dose of halofantrine hydrochloride, 16 mg/kg body weight. The recrudescence rate on day 14 of follow up was unacceptably high (38%). In the second trial the dose given was 8 mg/kg 6 hourly for three doses. Of the 49 children followed up for 14 days, 47 became aparasitaemic--ie, the cure rate was 96%. In both trials the drug was very well tolerated. Halofantrine hydrochloride seems to be effective against P falciparum chloroquine sensitive and resistant strains in Africa.

Administration, Oral↗

Inadequacy of chlorproguanil 20 mg per week as chemoprophylaxis for falciparum malaria in Kenya.

After treatment with chloroquine and pyrimethamine/sulfadoxine, 118 school children aged 6 to 10 years living near the Kenyan coast were enrolled in a malaria chemoprophylaxis study and followed up for 20 weeks. Children were randomly assigned to receive either chlorproguanil 20 mg weekly (n = 78) or placebo (n = 37). The attack rate of Plasmodium falciparum infection was 42% in chlorproguanil recipients (39.8 episodes per 1000 person-weeks of prophylaxis) and 73% in placebo recipients (69.2 episodes per 1000 person-weeks, p less than 0.02). Sensitivity tests on 36 isolates successfully cultured in vitro showed that all 21 isolates from chloroproguanil recipients were resistant to dihydrofolate-reductase inhibitors, whereas only 3 of 15 isolates from the placebo group were resistant (p less than 10(-6)). Chlorproguanil in a weekly adult dose of 40 mg does not provide adequate prophylaxis against P falciparum in Kenya, probably because drug levels between doses fall below those required to suppress parasites resistant to dihydrofolate-reductase inhibitors.

Adolescent↗

Ocular findings in a double-blind study of ivermectin versus diethylcarbamazine versus placebo in the treatment of onchocerciasis.

The effect of ivermectin, a new microfilaricide, was assessed in a double blind trial against diethylcarbamazine citrate (DEC) and placebo. Fifty-nine adult males with moderate to heavy infection with Onchocerca volvulus and with eye involvement were recruited from an area under Onchocerciasis Control Programme (OCP) vector control in Northern Ghana. They were randomly assigned to an eight-day treatment with ivermectin as a single dose of 12 mg on day 1 followed by placebo for the remaining seven days, or DEC, total dose 1.3 g, or placebo, and ophthalmological review was undertaken over a period of one year. DEC acted quickly to eliminate microfilariae from the eye and was associated with reactive ocular changes and in a few cases functional deficit. Ivermectin eliminated microfilariae slowly from the anterior chamber of the eye over a period of six months. The ocular inflammatory reaction was minimal and no functional deficit occurred. It is postulated that the observed slow action of ivermectin on the eye may be attributed in part to its instability to cross the blood-aqueous humour barrier because of its molecular size as a macrocyclic lactone causing microfilariae to leave the eye gradually along a newly created gradient. Ivermectin is an effective microfilaricide with minimal ocular adverse effect and could therefore be suitable for widespread application without strict supervision.

Adolescent↗

The chemotherapy of onchocerciasis. XII. The prediction of microfilarial loads in patients with onchocerciasis after treatment with diethylcarbamazine in northern Ghana.

This paper presents some statistical problems of analysing changes in patterns of microfilarial loads in onchocerciasis patients after chemotherapeutic treatment. Analyses are made of a pooled set of data from ten separate studies of diethylcarbamazine (DEC) conducted at the Onchocerciasis Chemotherapeutic Research Centre, Tamale, between 1978 and 1983. Regression models of microfilarial load at different intervals post-treatment are fitted with initial microfilarial load, total dose of DEC, duration of treatment and age of the patient as the independent variables. Appropriate transformations of the variables are chosen by examination of plots of residuals for violations of the assumptions underlying the regression models. A dose response curve for DEC is produced.

Adult↗

The chemotherapy of onchocerciasis. XI. A double-blind comparative study of ivermectin, diethylcarbamazine and placebo in human onchocerciasis in northern Ghana.

Fifty-nine onchocerciasis patients with ocular involvement were randomly assigned to receive either 12 mg of ivermectin in a single dose or 1300 mg of diethylcarbamazine over eight days or matching placebo capsules. Detailed standardized follow-up examination was carried out for one year. Both ivermectin and diethylcarbamazine rapidly reduced skin microfilarial counts to a similar extent over six months, after which counts increased significantly more with diethylcarbamazine. Diethylcarbamazine rapidly eliminated microfilariae from the eye, while ivermectin did so over six months. Reactions to treatment were more severe with diethylcarbamazine, which also produced clinical ocular deficiency in two patients. Ivermectin produced intra-uterine sequestration and degeneration of microfilariae in adult worms, which may account for its ability to produce prolonged suppression of skin microfilariae. Ivermectin proved superior to diethylcarbamazine in safety, tolerance and efficacy, but further work is needed to assess fully its effects in patients with heavy intraocular microfilarial loads.

Adolescent↗

The immune response to vaccination in undernourished and well-nourished Nigerian children.

The immune response of young Nigerian children to a full course of infant immunizations was studied in relation to their nutritional state at the time of vaccination. No significant correlations were found between anthropometric measurements made at the time of vaccination and the antibody response to triple, polio, measles, meningococcal and typhoid vaccines. Significant correlations were found between serum pre-albumin levels and the response to group A meningococcal polysaccharide vaccine and between serum albumin levels and the response to group C meningococcal polysaccharide vaccine. These correlations may reflect the depressive effect of malaria both on serum albumin and pre-albumin levels and on immune responsiveness to meningococcal polysaccharides. No significant correlations were found between nutritional state at the time of BCG vaccination and the development of a positive tuberculin reaction five weeks later. We conclude that under-nutrition has little or no effect on the immune response to vaccines used in routine infant immunization programmes.

Antibody Formation↗

Malumfashi Endemic Diseases Research Project XXI. Some aspects of the collection of demographic data.

This paper considers some of the procedures used and problems encountered in the collection of demographic data for a large-scale medical project: the Endemic Diseases Research Project at Malumfashi in northern Nigeria, 1974-1979. 43,216 people were enumerated and a subset of 26,100 were visited monthly for one year for the purpose of registration of vital events. The majority of problems encountered are relevant to similar studies in developing countries. Some difficulties cannot be avoided, but it is considered helpful to identify them. Other situations, however, deserve particular attention, such as the development of adequate on-site data-checking mechanisms, as these are areas in which future programmes could benefit from the experience of the demographic studies in Malumfashi. More effort still needs to be put into the improvement of data collection methods themselves.

Attitude to Health↗