Cerebral malaria in inbred mice. I. A new model and its pathology

Plasmodium berghei ANKA was tested for its usefulness as a model for cerebral malaria in inbred mouse strains A, A2G, A/J, C57L, SJL/J and SWR. A suitable model was obtained in A or A/J strain mice. Mortality was 100% after five to eight days with brain haemorrhages occurring terminally. The histopathology is described. The model was stable after six blood passages at 5- to 7-day intervals. Chloroquine abolished the haemorrhages and no intercurrent viral or blood protozoal infections were detected.     

Epidemiological, clinical and therapeutic features of Bihar kala-azar (including post kala-azar dermal leishmaniasis)

This epidemic of kala-azar in Bihar, India, started from a small block and gradually spread to almost all of North Bihar. Vaishali was the district most affected, with the highest incidence rate of 5.9 per thousand in 1978. The epidemic spread more to the east than to the west. In 1977 there were 100,000 cases of kala-azar in Bihar and in Vaishali district the death rate was 28.7% of affected cases. It took five years to control the epidemic. 750 parasitologically confirmed cases of kala-azar were studied. The male:female ratio was 5.5:1. 63.4% of cases were aged 10 to 29 years. Clinical features were classical. Sodium stibogluconate, used as a first line drug, was effective in 92.6% of cases. By increasing the course of antimonial therapy from 10 to 20 days the relapse rate was reduced to 0.5% compared with 15% in the previous epidemic. Kala-azar patients who also had tuberculosis were treated with the antimonial and antituberculosis drugs concurrently and all cases recovered. 86 cases unresponsive to sodium stibogluconate were given pentamidine, which was effective in 93.4%. Side effects with sodium stibogluconate were minimal, but were common and serious with pentamidine. The need for a safer drug effective in cases which do not respond to antimony was very evident. 20 cases of post kala-azar dermal leishmaniasis (PKDL) were reviewed: two had no previous previous history of kala-azar. The relapse rate was higher in PKDL than in kala-azar.     

Smoking habits and blood carbon monoxide levels

The carboxyhemoglobin concentrations (COHb) of 97 meat porters, 77 office workers, and 200 pregnant women have been determined. Individuals were questioned on smoking habits including numbers normally smoked per day, numbers already smoked on day of sampling, and time since last cigarette. The number of cigarettes smoked per day appears to allow the best prediction of COHb concentration. Individuals whose occupation involved them in physical exertion (meat porters) accumulated less carbon monoxide (CO) for numbers of cigarettes smoked per day than individuals smoking whilst sedentary. Pregnant women were seen to accumulate CO in a similar way to the active meat porters. In all groups, smokers had significantly higher COHb concentrations than nonsmokers. The effects of activity on CO uptake and elimination are discussed in relation to cigarette smoking, and it is suggested that the effect of activity on COHb is related more to elimination in the nonsmoking periods rather than uptake in the smoking periods.     

First report of septicaemic melioidosis in Hong Kong

Septicaemia due to Pseudomonas pseudomallei was found in five patients; it complicated pneumonia in three. Four patients were old and had diabetes mellitus; the fifth patient, though young, was immunocompromised by steroid therapy. The clinical features were indistinguishable from those of other Gram-negative septicaemia. Four of the patients died. This was the first report of septicaemic melioidosis in Hong Kong where the disease might be endemic. Soil sampling and serological survey gave further supporting evidence. Early treatment using a bactericidal anti-Pseudomonal cephalosporin, such as ceftazidime, was suggested for this life-threatening infection.     

The general labour conflict in Sweden 1980: effects on the mortality in Stockholm County

For 2 weeks in spring 1980 Sweden was affected by a general labour conflict involving large sections of industry, commerce and public services. Certain parts of the health sector were affected and at some of the Stockholm hospitals all elective surgery was being withheld. The purpose of this study was to find out wether the labour conflict had any effects on the mortality in Stockholm County. The analysis was focused on possible effects of the reduced activity at some major hospitals.From the Stockholm County Medical Information System information on all deaths.as well as deaths occurring in hospitals, was obtained for the years 1979 an 1980. The death rate for eacht week in 1980 was compared with the corresponding week in 1979.During the second week of the conflict and week immediately following, the overall county mortality was remarkably low, and significantly lower than in 1979. The results of the analysis suggest a decrease in overall mortality by the time of the conflict. The decrease in mortality could, however, be explained neither by the withholding of elective surgery nor by the general reduction of hospital activity.     

Cardiovascular and cerebrovascular mortality among the elderly Finnish population 1960–79

Cardiovascular and cerebrovascular diseases are the leading cause of death among thepopulation 65 years and over. This retrospective study based on mortality statistics examined the deaths of Finns 65 years and over from these diseases during 1960–79. In the early 1960s, mortality was still relatively high, but since the mid-60s and throughout the 1970s death rates have continuously decreased. Female mortality began to drop earlier than male mortality, and the decrease in female mortality has also been more rapid. Both cerebrovascular mortality and mortality from ischaemic and arteriosclerotic heart diseases decreased in all 5-year age groups. Mortality from cerebrovascular diseases declined more sharply than mortality in ischaemic and arteriosclerotic heart diseases.     

Non-typhoidal Salmonella infection in Zambian infants

In the University Teaching Hospital, Lusaka, Zambia, 45 strains of various non-typhoidal Salmonella species were isolated from 2990 samples of stools, blood and C.S.F. About 93% of the 45 strains were isolated from infants less than two years old. S. heidelberg was the most common species isolated from stools and revealed a multi-drug resistant character. Only S. typhimurium and S. bovis-morbificans were isolated from blood and C.S.F.     

Road traffic mortality in Victoria: An exploratory investigation into successful strategies

Road traffic mortality data for the mainland states of Australia show that there have been the following changes between 1969–1970 and 1973–1974 in road traffic mortality:A reduction of approximately 16% in Victoria, but an increase of approximately 1% in New South Wales, an increase of approximately 12% in Queensland, an increase of approximately 18% in South Australia, and an increase of approximately 5% in Western Australia.A detailed comparison of mortality for New South Wales and Victoria for each of the years 1969–1974 is made. It is shown that, in the years immediately following the introduction of legislation requiring the compulsory use of seat belts, there was a reduction of about 18% in driver mortality and of about 12% in passenger mortality in both States. Since that time, there have been further reductions in mortality in Victoria so that driver, passenger, and pedestrian mortality have all been reduced by approximately 20%. These latter reductions have not been matched in New South Wales. It is therefore suggested that some factors, not yet identifiable, have operated in Victoria to produce this welcome additional reduction. Suggestions for further studies are offered.     

Sugar absorption by the mouse small intestine following infection with Schistosoma mansoni.

The effect of acute schistosomiasis on the structure and function of the mouse small intestine has been examined. Whole loops of small intestine from normal mice, and mice seven weeks post-infection were incubated in an in vitro perfusion apparatus. The transport of glucose, 3-0-methylglucose, sorbitol and fluid were all markedly impaired in loops from the infected animals. Kinetic analysis of the data for glucose transport indicated that schistosome infection brought about a reduction in the total number, but not the affinity, of the absorptive sites for glucose. Under the scanning electron microscope, villi from normal mice were tall and erect, with intact surfaces devoid of mucus, whereas the villi from the infected animals were partially covered with strands of mucus and appeared swollen and eroded, with lesions around their apices.     

Salmonella and Shigella in adult diarrhoea in Addis Ababa--prevalence and antibiograms

Ninety Shigella and 45 Salmonella strains were isolated from 1000 adult diarrhoeal out-patients from various hospitals and clinics in Addis Ababa. The Shigella species were isolated in the order of frequency of S. flexneri, S. dysenteriae, S. boydii and S. sonnei and the Salmonella in the order of Group C, Group B, S. typhi, other Group D and Groups A and E. Almost all Shigella isolates were sensitive to cephalothin, gentamicin, kanamycin, polymyxin B and trimethoprim-sulphamethoxazole. About 17% were sensitive to the 11 drugs tested. Multiple resistance was detected in 62%, the most common to six drugs (27%). All Salmonella isolates were sensitive to gentamicin, polymyxin B and trimethoprim-sulphamethoxazole. About 69% were sensitive to all drugs tested. 22% were multiply resistant and the most common was to eight drugs (18%).     

The susceptibility of chickens to Trypanosoma brucei subspecies

Chickens were susceptible to infection with three different stocks of the subgenus Trypanozoon: two of presumptive Trypanosoma b. brucei and one of T. b. rhodesiense. Two groups of chickens were used: the first hatched following inoculation with either T. b. brucei or T. b. rhodesiense during embryonic development, and the second were infected as adult birds. In both experimental groups, parasitaemia persisted for prolonged periods, but was mostly subpatent and detectable only by subinoculation of blood into mice. In chickens infected as embryos, parasitaemias were patent for five weeks after hatching, but subpatent thereafter (to weeks 13 to 17). Quantitative estimations of the parasitaemias of seven of the birds hatched from embryos inoculated with T. b. brucei revealed fluctuations in the number of circulating trypanosomes, with an initial peak between days 2 to 9 after hatching. Between weeks 13 to 17 after hatching the chickens appeared to have recovered spontaneously from the trypanosome infections. Homologous challenge at week 20 failed to produce a recrudescence of parasitaemia, indicative of a possible acquired immunity.The infections of ten chickens inoculated with either T. b. brucei or T. b. rhodesiense as adult birds were microscopically subpatent throughout the observation period of six weeks, but subinoculation of blood into mice showed the chickens were parasitaemic from week one and thereafter. Different aspects of infection of avian hosts by the Trypanozoon subspecies are discussed.     

Rate of metabolism of norethisterone in women from different populations.

The rate of metabolism of orally administered norethisterone was compared in fourteen centres by measuring plasma levels of the steroid by radioimmunoassay at varying times after oral administration of a 1 mg dose. The inter-centre differences were of the same order as the intra-centre differences. Variations in metabolism appeared not to be due to variations in body size.     

Pharmacokinetics of ethynyloestradiol in women from different populations

The pharmacokinetics of a dose of 50μg ethynyloestradiol administered orally was studied in fourteen centres. Absorption was rapid and the highest serum concentrations of total ethynyloestradiol were found in most subjects at 1 h and by 24 h concentrations were less than 250 pg/ml. Calculation of the half-lives for absorption, distribution and elimination showed wide variations between subjects, the half-life of elimination varying from 2.5 h to more than 30 h. Bioavailability as measured by the area under the serum ethynyloestradiol concentration-time curve also showed more than a ten-fold variation. Intra-centre differences in the various parameters measured were as large as the inter-centre differences.     

Hepatitis B virus (HBV) markers among patients with chronic liver disease in Kuwait

The prevalence of hepatitis B surface antigen (HBsAg), antibody to the hepatitis B core (anti-HBc) and to surface antigen (anti-HBs), was investigated, using sensitive radioimmunoassay (RIA) systems, among patients with different clinical entities of chronic liver disease in Kuwait, and compared to a control blood donor population. 81% of patients and 44% of the controls had at least one HBV marker. 24% of patients, but none of the controls had both HBsAg and a high titre of anti-HBc in the absence of anti-HBs, suggesting a chronic infection. 31% of our patients with hepatosplenic schistosomiasis, 20% with cryptogenic cirrhosis and chronic active liver disease and 60% with hepatocellular carcinoma had these two markers. HBV antigenaemia was significantly more prevalent among male than among female patients and was particularly high among those less than 35 years old. The high prevalence of the various HBV markers among our patients suggests that HBV is a major factor in the development of chronic liver disease in our area. Furthermore, in view of the high prevalence of antigenaemia in patients with hepatosplenic schistosomiasis, HBV infection must play a concomitant role in the development of a more serious form of chronic liver disease among such patients.     

Transfer of contraceptive steroids in milk of women using long-acting gestagens

Levels of norethisterone and medroxyprogesterone acetate were measured in serum and milk of women receiving the injectable contraceptive formulations Norigest and DepoProvera, respectively, throughout complete injection intervals. In 5 of 10 women receiving Norigest, serum norethisterone levels were undetectable by 8 weeks after injection and only 2 women had detectable levels of norethisterone in milk at this time. In contrast, 8 of 10 women receiving DepoProvera had detectable levels of medroxyprogesterone acetate in both serum and milk 12 weeks after injection. The ratio of the milk:serum concentrations of norethisterone varied from 0.12 to 0.92 (mean 0.34) and for medroxyprogesterone acetate from 0.12 to 2.60 (mean 0.88). It is unlikely that these differences between the two formulations are due entirely to differences between the binding of norethisterone and medroxyprogesterone acetate to serum proteins. The area under the curve of serum steroid concentrations plotted against time was only 50% higher for women injected with DepoPovera than for those injected with Norigest but the area under the curve for milk values was 400 times higher. Assuming the infant ingests 600 ml daily, the daily intake of steroids in the first week after injection would be 0.5 to 2.4 micrograms for norethisterone and 1 to 13 micrograms for medroxyprogesterone acetate. By 8 weeks after injection, the amount of norethisterone ingested would be small but that of medroxyprogesterone acetate would still be significant.     

A diagnostic "patch test" for onchocerciasis using topical diethylcarbamazine

There is great need for a simple, inexpensive, and sensitive diagnostic test for onchocerciasis, especially in endemic areas where trained personnel and laboratory facilities are limited. Diethylcarbamazine (DEC) was applied as a "patch test" to the skin of 45 patients with onchocerciasis in the Southern Sudan. 75 tests were done on these 45 patients, and 69 (92%) were positive. A positive reaction was a papular eruption beneath the patch. Histopathological studies of the skin beneath the patch revealed the microscopic features of a severe Mazzotti reaction, including degenerating microfilariae in the upper dermis and within epidermal eosinophilic abscesses.     

Pharmacokinetics of different doses of norethisterone oenanthate

Doses of norethisterone oenanthate of 300, 150, 100 and 50 mg were administered to four groups of subjects. Due to wide intersubject variations there were no statistically significant differences in the pharmacokinetic parameters for the different groups but there were significant correlations between the dose and the mean values for these parameters. There was little difference between the groups in the duration for which ovarian function was suppressed due to the inter-subject variation being greater than the inter-dose effect. The duration of the anti-fertility action of norethisterone oenanthate cannot be increased by increasing the dose above the standard 200 mg; however, with an injection interval of 60 to 70 days, it seems likely that the dose could be reduced to 150 mg.     

Pharmacokinetics of oral contraceptive steroids after morning or evening administration

An oral contraceptive containing ethynyloestradiol and norethisterone was administered to six women in the morning and in the evening using a cross-over design. Serum levels of ethynyloestradiol and norethisterone were measured at various times' after administration. There was no significant difference in a number of pharmacokinetic parameters between the two times of administration, suggesting that morning or evening administration of the contraceptive are equally effective.     

Hepatitis-B virus infection in children and adults in Northern Nigeria: a preliminary survey

Hepatitis-B surface antigen (HBsAg) and its corresponding antibody (anti-HBs) have been detected by radio-immunoassay in children and adults and in adult expatriates in Zaria, Northern Nigeria. The exposure rate to hepatitis-B virus (frequency of HBsAg and anti-Hbs) was found to vary from 59% in children under five years to 72·5% in adults over 30 years of age, while the frequency of HBsAg alone was 40% and 10% respectively. The anti-HBs prevalence rates rose progressively with age and reached a peak at 62·5% in adults. Five of 32 adult expatriates (15·6%) were positive for anti-HBs. The factors contributing to the high exposure rate in the indigenous population in this region require further study to enable judicious use to be made of preventive measures.