ELISA method for detecting Plasmodium falciparum circumsporozoite antibody.

An enzyme-linked immunosorbent assay (ELISA) for circulating IgG mouse antibody to Plasmodium falciparum circumsporozoite (CS) protein was modified for use with human sera collected in an area of northern Zambia that was endemic for malaria and from individuals never exposed to malaria. Optimum sensitivity was achieved using Immulon 2 microtitration plates, boiled casein-Tween 20 blocking buffer, and by adding a solution of boiled casein (4 micrograms/ml) to the capture antigen diluent. The results for the detection of anti-CS IgG correlated well with those of sporozoite immunofluorescence antibody assays. Modification of the ELISA method permitted the simultaneous detection of anti-CS IgG and IgM antibody on a single serum sample in the same well of the microtitration plate and the detection of anti-CS IgG antibody in Kenyan dried whole-blood samples collected on filter-paper. The assay has been used to monitor human antibody levels in a phase-I malaria vaccine trial and in longitudinal studies of malaria transmission in Thailand and Kenya.

ELISA method for detecting Plasmodium falciparum circumsporozoite antibody

An enzyme-linked immunosorbent assay (ELISA) for circulating IgG mouse antibody to Plasmodium falciparum circumsporozoite (CS) protein was modified for use with human sera collected in an area of northern Zambia that was endemic for malaria and from individuals never exposed to malaria. Optimum sensitivity was achieved using Immulon 2 microtitration plates, boiled casein-Tween 20 blocking buffer, and by adding a solution of boiled casein (4 ug/ml) to the capture antigen diluent. The results for the detection of anti-CS IgG correlated well with those of sporozoite immunofluorescence antibody assays. Modification of the ELISA method permitted the simultaneous detection of anti-CS IgG and IgM antibody on a single serum sample in the same well of the microtitration plate and the detection of anti-CS IgG antibody in Kenyan dried whole-blood samples collected on filter-paper. The assay has been used to monitor human antibody levels in a phase-I malaria vaccine trial and in longitudinal studies of malaria transmission in Thailand and Kenya(AU)

Parenteral chloroquine for treating falciparum malaria.

There is no information and therefore no consensus on how chloroquine should be administered to persons with severe malaria. Although widely considered dangerous, parenteral chloroquine is extensively used. We studied the acute disposition and toxicity of intravenous (iv), intramuscular (im), subcutaneous (sc), and oral chloroquine in 60 adult Zambian patients hospitalized with falciparum malaria. Plasma concentration profiles after parenteral administration were characterized by wide fluctuations between peak and trough values. Absorption of im and sc chloroquine was rapid, with a median time to peak concentration of 30 min and a peak plasma concentration five times higher than after oral administration. The pharmacokinetic data suggest that the acute toxicity of parenteral chloroquine is related to transiently high concentrations in blood and result from incomplete distribution out of a relatively small central compartment. Parenteral chloroquine may be administered safely by simply giving smaller, more-frequent doses than are currently used or, in the case of iv administration, by using continuous infusion.

Evidence for heterosexual transmission and clinical manifestations of human immunodeficiency virus infection and related conditions in Lusaka, Zambia.

In a hospital-based survey in Lusaka, Zambia, 189 (17.5%) of 1078 subjects had antibodies against the human immunodeficiency virus (HIV). The prevalence of antibodies was low in subjects aged less than 20 or greater than 60 years; in men the peak prevalence (32.9%) occurred in those aged 30-35 years, and in women (24.4%) it occurred in the 20-25 year age-group. There was no significant difference in prevalence by sex after adjusting for age. High educational level was independently associated with HIV seropositivity; the antibody against HIV was found in 18.4% of blood donors and in 19.0% of hospital workers. Among patients the antibody prevalence ranged from 8.7% in antenatal women and 9.3% in orthopaedic patients to 29.2% in those attending sexually transmitted disease (STD) clinics (the prevalence being 37.3% in previous attenders and 22.8% in first-time attenders). Seropositivity rates were higher in patients with an infectious problem (23.4%) than in those without (11.4%, p = 0.0002). Herpes zoster, oral thrush, diarrhoea, tuberculosis, and weight loss were independently correlated with seropositivity. The data strongly suggest that HIV infection is prevalent in Africa and is transmitted heterosexually. The restricted distribution of seropositivity to the sexually active age-groups indicates that the epidemic, at least in this part of Africa, is newly introduced; this has substantial implications for prevention.

PIP: In a hospital-based survey conducted in Lusaka, Zambia, 189 (17.5%) of 1078 patients, blood donors, and health workers had antibodies against human immunodeficiency virus (HIV). The prevalence of antibodies (seropositivity) was low in study subjects under age 20 and over age 60. Seropositivity was highest among men age 30-35 (32.9%) and among women age 20-25 (24.4%). There was no significant difference in prevalence by sex, after adjusting for age. Increasing years of education was highly correlated with seropositivity, even after adjustment for age, sex, and marital status. This association presumably reflects the greater opportunities for travel and social interaction--and thus HIV exposure--among the better educated. The antibody against HIV was detected in 18.4% of blood donors and 19.0% of hospital workers. Among clinic patients, antibody prevalence was lowest among pregnant women (8.7%) and orthopedic patients (9.3%) and highest among those attending the dermatology (26.8%) and sexually transmitted disease (29.2%) clinics. Moreover, patients who had attended the sexually transmitted disease clinic more than once were more likely to be seropositive (37.3%) than first-time attendees (22.8%). Finally, patients with infectious conditions had significantly higher seropositivity rates (23.4%) than those with noninfectious problems (11.4%). Herpes zoster, oral thrush, diarrhea, tuberculosis, and weight loss were independently associated with seropositivity. These findings strongly suggest that HIV infection is prevalent in Africa and is transmitted heterosexually. The concentration of seropositivity in the sexually active age groups indicates that the epidemic is newly introduced, at least in this part of Africa.

Adult cerebral malaria in Zambia: preliminary report of clinical findings and treatment response.

Fifty-six adult patients diagnosed as having 'cerebral malaria' were admitted and treated over a 4 month period. The presenting symptoms were similar to those of control patients with malaria without cerebral manifestations except that vomiting and convulsions were significantly more frequent and joint pains were less frequent in the cases than in the controls. Physical examination revealed significantly more frequent occurrence of nuchal rigidity, positive Kernig's sign, confusion, muteness, pallor and jaundice in the cases than controls, while splenomegaly was significantly more common in controls than cases. Laboratory data showed that cerebral malaria cases had significantly lower haemoglobin and significantly higher reticulocyte count and erythrocyte sedimentation rate than controls. There was no significant difference in the parasite density between the cases and controls. All patients were treated with 200 mg base of intravenous chloroquine in 250 ml of isotonic saline infused over 2 h and repeated 12 hourly till oral therapy was possible. This proved to be efficacious and the recovery rate was over 90%. Five patients died and the diagnosis was confirmed in three in whom autopsy was permitted. A simple staging system is proposed which retrospectively seems to have prognostic value. It is recommended that the validity of this system be tested prospectively.

A double-blind clinical trial of a combination of mefloquine, sulfadoxine and pyrimethamine in symptomatic falciparum malaria.

Fansimef is a combination of 250 mg of mefloquine, 500 mg of sulfadoxine, and 25 mg of pyrimethamine per tablet. A total of 150 adult male Zambian patients who had symptomatic Plasmodium falciparum parasitaemia were treated in a double-blind randomized fashion with either one, two or three tablets of Fansimef. All patients in the three treatment groups showed an S-type response. The rates of clearance of parasitaemia and fever were similar in all treatment groups. Tolerance was good at all dose levels. The main side-effects were abdominal discomfort, weakness and lassitude, dizziness, and pruritus, but these were mild, transient and required no specific treatment. Vomiting occurred only in 4% of patients given the highest dose of three tablets. The results of various haematological and biochemical investigations and urinalysis were not adversely altered by the administration of Fansimef.

A "healthy carrier" of Trypanosoma rhodesiense: a case report.

A case of a 56-year-old, healthy carrier of Trypanosoma rhodesiense infection was identified in a total village survey for trypanosomiasis. All initial laboratory tests were negative for trypanosomes but two blood-inoculated mice were both positive 11 days after inoculation. The epidemiological significance of human healthy carriers of trypanosomes is discussed.