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Biomedical subjects

K S Warren

Publications and source records attributed to K S Warren.

At least 73 records · Page 4Linked to original sources

Selective primary health care: an interim strategy for disease control in developing countries.

Priorities among the infectious diseases affecting the three billion people in the less developed world have been based on prevalence, morbidity, mortality and feasibility of control. With these priorities in mind a program of selective primary health care is compared with other approaches and suggested as the most cost-effective form of medical intervention in the least developed countries. A flexible program delivered by either fixed or mobile units might include measles and diphtheria-pertussis-tetanus vaccination, treatment for febrile malaria and oral rehydration for diarrhea in children, and tetanus toxoid and encouragement of breast feeding in mothers. Other interventions might be added on the basis of regional needs and new developments. For major diseases for which control measures are inadequate, research is an inexpensive approach on the basis of cost per infected person per year.

Animals↗

Brugia malayi microfilaraemia in mice: a model for the study of the host response to microfilariae.

Microfilariae of Brugia malayi were obtained from the peritoneal cavities of infected gerbils and were then injected intravenously into mice. A sub-periodic, nocturnal microfilaraemia was produced. The level of microfilaraemia was proportional to the number of parasites injected, with approximately 1-3% of microfilariae being found in the peripheral circulation. The duration of microfilaraemia was proportional to the number of parasites injected; it subsided by 30 days after injection of 104 microfilariae but was still present at a low level 120 days after injection of 2 x 105 microfilariae. A transient splenomegaly developed after injection of microfilariae. Histopathological examination revealed large numbers of microfilariae free in the lumens of pulmonary small blood vessels and without any accompanying inflammatory reaction. Lesser numbers of microfilariae were seen in the cardiac blood and hepatic and renal blood vessels for the first few days after injection. There was cellular proliferation in the splenic white pulp and vascular congestion of the red pulp. Microfilariae labelled with 51Cr were injected intravenously; 57% of radioactivity was found in the lungs, 8.5% in the liver and 2.9% in the spleen. Mice developed immediate hypersensitivity reactions to B. malayi antigen by 4 weeks after injection, but Arthus and delayed hypersensitivity reactions were not seen at any time. when mice which had been injected 5 months previously were challenged with a 2nd injection of microfilariae, there was an accelerated clearance of parasites over 2 weeks and a marked peripheral blood eosinophilia developed. In contrast with natural infections, in which the continuous production of microfilariae complicates assessment, this model provides a system in which factors controlling the circulation of microfilariae in the bloodstream can be studied independently.

Animals↗

Control of schistosomiasis: report of a workshop.

Nineteen scientists, field workers, and representatives of funding agencies active in schistosomiasis research and control met in Bellagio, Italy in October 1977 to attempt to evaluate the effectiveness of current control methods and what might be accomplished with available technology. The deliberations included summaries of knowledge on the biology, transmission, and control of schistosomiasis and assessment of major control programs and methodologies. The groups concluded that in the major endemic areas considerable gains in control of schistosomiasis could be made with current technology. However, maintenance of control in most countries, and establishment of serious control programs in countries in which schistosomiasis is a less severe public health problem, would require development of less expensive modalities which would need little monitoring and possibly have benefits extending beyond schistosomiasis control.

Agriculture↗

Liver collagen synthesis in schistosomiasis mansoni.

We determined collagen synthetic rates and utilization of key amino acid precursors of collagen in slices of wedge liver biopsy specimens obtained at required surgery from 9 patients with hepatosplenic schistosomiasis and from 4 control patients. The liver specimens from the patients with schistosomiasis showed advanced fibrosis, with histologic evidence of schistosomiasis alone in four, and both schistosomiasis and chronic active hepatitis in five cases. Liver slices were incubated with radioactive proline, arginine and glutamine, using quantitative assay conditions validated earlier for murine schistosomiasis. Collagen peptide synthesis in slices from all nine fibrotic liver specimens was 4- to 25-fold greater than normal and correlated positively with liver collagen content, which was 2- to 5-fold greater than normal. Free proline, an amino acid that may contribute to regulation of collagen peptide synthesis, was increased in six of the nine fibrotic liver specimens, and proline was actively formed from arginine in liver slices from all specimens. These measurements of the initial steps of collagen biosynthesis in fibrotic human liver are quantitatively similar to those previously made of the same processes in experimental animals.

Adolescent↗

Schistosomiasis haematobia in coast province Kenya. Relationship between egg output and morbidity.

Several studies of schistosomiasis haematobia in Africa have revealed a correlation between intensity of infection as measured by urine egg counts and severity of disease as determined by intravenous pyelography. The present study consisted of a survey of 390 school children in the coastal area of Kenya involving a single egg count, and intravenous pyelograms in a stratified random sample of 69 children; the results showed a greater prevalence of urinary tract disease in those with higher intensities of infection. This survey was then followed by a more detailed study in which nine consecutive daily egg counts were done on 121 children; 17 of these children, subdivided into three groups with different intensities in infection, were given intravenous pyelograms. The results were similar in the 11 children with minimal and moderate counts (averaging, respectively, less than 1 egg and 167 eggs/10 ml urine daily), with approximately 30% having bladder or renal abnormalities. In comparison, all of the six children with heavy counts (averaging 1,288 eggs/10 ml urine daily) had bladder lesions and five of them had renal lesions.

Adolescent↗

The pathology, pathobiology and pathogenesis of schistosomiasis.

Although the general pathology of schistosomiasis has been well understood for more than 70 years, it is only recently that it has been possible to analyse the disease at the molecular level and to understand the relationship between the number of parasites in an infected individual and the appearance of overt disease.

Animals↗

Hycanthone dose-response in Schistosoma mansoni infection in Kenya.

The recommended doses of the drugs now used to cure schistosomiasis mansoni may be associated with toxic side-effects. Since Schistosoma mansoni does not multiply in the human host and the disease seems to be closely associated with the intensity of infection, it may not be necessary to use 100% lethal antischistosomal doses, particularly in endemic areas. A dose-response to the antischistosomal drug, hycanthone was established for three different doses in 169 patients with heavy S. mansoni infections in the Machakos district of Kenya. The highest dose used (1.5 mg/kg or half the recommended package-insert dose) resulted in a 96% decrease in egg output (equivalent ot death of the worms); 0.75 mg/kg in an 85% decrease; and 0.375 mg/kg in an 11% decrease one month after treatment. In contrast to the vomiting common with the package-insert dose (3.0 mg/kg), there were no side-effects with any of the lower doses.

Adolescent↗

Conditions for bacille Calmette-Guérin-induced resistance to infection with Schistosoma mansoni in mice.

Intravenous administration of a lyphilized preparation of bacille Calmette-Guérin (BCG-Tice) into mice significantly protected these animals from infection with Schistosoma mansoni. The protective effect depended on the dose of BCG and required the administration of at least 2 X 10(7) viable organisms. The route of administration of BCG was also crucial, as only intravenous inoculation produced significant protection. The BCG-induced resistance was found to last for eight weeks. Significant inflammation of the lungs was observed in mice receiving either viable or heat-killed BCG; however, protection followed only the administration of viable bacilli. Expression of BCG-induced protection was dependent on the presence of significant numbers of viable organisms and may have been associated with pulmonary inflammation at the time of passage of the schistosomula through the lungs.

Animals↗

Quantification of infection with Schistosoma haematobium in relation to epidemiology and selective population chemotherapy. I. Minimal number of daily egg counts in urine necessary to establish intensity of infection.

The intensity of infection with Schistosoma haematobium (worm burden) can be approximated by quantifying the number of parasite eggs excreted in the urine. A new method of egg counting has been developed in which urine samples are passed through transparent Nuclepore filters (Nuclepore Corp., Pleasanton, Calif.). The method requires no staining, is rapid, and can be performed in the field. It has previously been reported, however, that there is a significant daily fluctuation in output of eggs in the urine of patients with schistosomiasis haematobia. In the present study, daily urine samples were obtained on each of the 10 school days during a 12-day period from 121 schoolchildren in Coast Province, Kenya (total, 10 samples per child). In terms of detecting infection, it was of interest that egg counts of 0 were very rarely recorded for subjects whose mean egg counts were greater than 20/10 ml of urine. When the patients were classified into one of four groups, according to egg count (less than 1, 1--100, 101--400, greater than 400), the proportion correctly classified based on a single urine specimen was 75%; this proportion rose to 78% when the classification was based on two specimens and to 83% with three specimens. Most of the urine specimens that were misclassified belonged in an adjacent group.

Adolescent↗

Quantification of infection with Schistosoma haematobium in relation to epidemiology and selective population chemotherapy. II. Mass treatment with a single oral dose of metrifonate.

Determination of the efficacy of mass treatment of schistosomiasis is usually based on the rate of cure. However, schistosomes do not multiply in the human host, disease tends to cluster in the small proportion of individuals with heavy infections, and reinfection continually occurs in endemic areas. Thus drastic reduction in worm burdens can be a reasonable goal for mass treatment campaigns. The standard dose and regimen of metrifonate for the treatment of schistosomiasis haematobia is 7.5 mg/kg administered in three doses two weeks apart. This treatment results in a cure rate of approximately 50% and a reduction in egg output of 94.5%. In the present study, 72 infected children with egg counts before treatment that averaged from 0.1 to 2,334/10 ml of urine were treated with a single oral dose of 10 mg of metrifonate/kg: the cure rate was 22%, and the reduction in egg output was 96.5%. No side effects were recorded.

Administration, Oral↗

Hepatosplenic schistosomiasis: a great neglected disease of the liver.

Schistosomiasis mansoni and japonica, helminth infections involving the livers of 100 million people, are among the 'great neglected diseases of mankind' on the basis both of their prevalence and the relative lack of interest shown in them by clinicians and biomedical investigators. Schistosomiasis is not only an interesting disease in itself but has the added advantage of providing unique human and animal models of hepatic pathophysiology, immunopathogenesis, and collagen metabolism.

Collagen↗