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Biomedical subjects

A D Brandling-Bennett

Publications and source records attributed to A D Brandling-Bennett.

At least 19 recordsLinked to original sources

Confirmation that Plasmodium falciparum has aperiodic infectivity to Anopheles gambiae.

In preparation for field studies of transmission-blocking malaria vaccines, a study was carried out to determine whether P. falciparum infections obtained in An. gambiae blood-fed at 16.00 hours were quantitatively similar to infections obtained at 23.00 hours. Using a group of children aged 5-12 years from villages at Ahero, near Kisumu in Kenya, 71/74 (96%) of whom were found to be positive for P.falciparum parasitaemia, one batch of fifty colony-bred An.gambiae females were fed on volunteers at 16.00 hours and another batch at 23.00 hours. No statistically significant differences were found in the proportions of mosquitoes becoming infected, the numbers of children infecting mosquitoes or the mean numbers of malaria oocysts developing in mosquitoes blood-fed at the different times. Because mosquito infections obtained by day (16.00 hours) are equivalent in quantity to those obtained at night (23.00 hours), experimental infections can be carried out in the afternoon, when it is most convenient, rather than during the night.

Animals↗

Parasitological, clinical and haematological response of children with Plasmodium falciparum to 4-aminoquinolines and to pyrimethamine-sulfadoxine with quinine in western Kenya.

Children with Plasmodium falciparum infections in Western Province, Kenya, were studied in 1987 for their parasitological, clinical and haematological response to chloroquine, to amodiaquine and to pyrimethamine-sulfadoxine plus quinine. Ninety-eight children under 5 years of age were treated in 1 of 2 hospitals. Of the 56 patients treated with chloroquine base 25 mg/kg, 91% had resistant infections, with 36% having no significant decrease in parasitaemia (RIII resistance); however, 69% responded clinically within a week. Of the 27 patients treated with amodiaquine base 25 mg/kg, 67% had resistant infections, with 7% RIII resistant; 81% responded clinically. The parasites cleared in all 15 children given pyrimethamine-sulfadoxine plus 3 days of quinine. Only when parasites cleared did patients have improved haemoglobins and haematocrits. This study shows that parasitaemia in children hospitalized in western Kenya responds poorly to 4-aminoquinolines, although the patients improve clinically, at least during the first 7 days. Young children may need to clear parasites to avoid the risk of severe anemia and the need for blood transfusions.

Amodiaquine↗

Plasmodium falciparum sensitivity to erythromycin and 4-aminoquinoline combinations in vitro.

Although erythromycin has been reported to be active against Plasmodium falciparum in vitro and P. berghei in vivo and in vitro when given alone or with chloroquine, it has been difficult to demonstrate a beneficial effect for the combination of erythromycin and chloroquine when used for the treatment of P. falciparum infections in humans. We developed a seven-day test of parasite sensitivity to a 4-aminoquinoline and erythromycin combination in vitro. Eight isolates of P. falciparum from the Kenyan coast were culture-adapted and exposed to erythromycin with chloroquine or with amodiaquine. The interaction of the drugs was evaluated by plotting the concentration of each drug needed to inhibit parasite growth. In seven isolates the combination of chloroquine and erythromycin was antagonistic; one isolate showed slight synergy The combination of amodiaquine and erythromycin was synergistic in three isolates but antagonistic in five. An antagonistic interaction may explain why erythromycin does not enhance chloroquine treatment of malaria in vivo in Kenya.

Aminoquinolines↗

Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non-pregnant women, Kakamega District, Kenya.

OBJECTIVE: To compare treatment and protection against falciparum malaria in pregnant and non-pregnant women with three drug regimens. DESIGN: Prospective intervention study with six weeks' follow up. Patients received one of three drug regimens in order of entry. SETTING: Primary care hospital and secondary girls' school in rural western Kenya. PATIENTS: 158 of 988 pregnant women (89 primigravid and 69 multigravid) in the third trimester and 105 of 1488 non-pregnant schoolgirls of reproductive age were parasitaemic (more than 500 asexual forms/microliter. These women were divided into three treatment groups by gravid state. INTERVENTIONS: Women were treated with chloroquine base 25 mg/kg over three days or pyrimethamine 75 mg and sulfadoxine 1500 mg as a single dose or chlorproguanil 1.2 mg/kg and dapsone 2.4 mg/kg as a single dose. MAIN OUTCOME MEASURES: Parasitaemia and haemoglobin concentrations measured at seven day intervals for six weeks. RESULTS: Primigravid women were more likely to be parasitaemic on follow up than multigravidas or nulligravidas, whose response was about the same. Parasites did not clear by day 7 in primigravidas in six (20%) of 30 who received chloroquine, three (8%) of 35 treated with pyrimethamine and sulfadoxine, and none of 23 treated with chlorproguanil and dapsone. At day 28, 83%, 19%, and 67% of primigravidas in these treatment groups were parasitaemic. Haemoglobin concentrations rose in all women, but improvement was sustained only in women who remained free of parasites. CONCLUSIONS: Clearance of parasites was better with either pyrimethamine and sulfadoxine or chlorproguanil and dapsone than with chloroquine. Longest protection was obtained with pyrimethamine and sulfadoxine.

Adolescent↗

Permethrin-impregnated curtains and bed-nets prevent malaria in western Kenya.

The effectiveness of permethrin-impregnated (0.5 g/m2) bed-nets and curtains as malaria control measures was evaluated in Uriri, Kenya in 1988. One hundred five families were randomly assigned to 1 of 3 study groups (control, bed-net, or curtain). All participants were cured of parasitemia with pyrimethamine/sulfadoxine. Selective epidemiologic and entomologic parameters were measured weekly, while knowledge, attitude, and practices surveys were conducted at the beginning and end of the 15 week study. Plasmodium falciparum infections per person week at risk were significantly higher in the control group than in either the curtain group (5.42 vs. 2.35 cases/100 person weeks risk) or the bed-net group (5.42 vs. 3.77 cases/100 person weeks risk). The curtain group had fewer infections per person week at risk than the bed-net group (2.35 vs. 3.77 cases/100 person weeks risk). A difference was found in clinical malaria among the groups: 45% of persons in the bed-net and curtain groups vs. 30% of those in the control group reported no episodes of fever and chills (chi 2, P less than 0.05). Indoor resting Anopheles gambiae or An. funestus were found on 94 occasions in the control houses, but only twice in the treated houses during weekly visits to each house over the study period (chi 2 P less than 0.001). The pyrethrum knockdown method produced similar results with a total of 195, 23, and 3 An. gambiae and An. funestus collected in the control, bed-net, and curtain houses during the same period, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Plasmodium falciparum infection rates in Anopheles gambiae, An. arabiensis, and An. funestus in western Kenya.

Mosquitoes collected monthly for 1 year from human habitations in the Kisumu area of western Kenya were identified by morphological characters as Anopheles gambiae Giles sensu lato (An. gambiae s.l.) or An. funestus. Of the mosquitoes collected, 7,244 (67%) of the An. gambiae s.l. and 8,511 (87%) of the An. funestus were tested by enzyme-linked immunosorbent assay (ELISA) for the presence of Plasmodium falciparum circumsporozoite (CS) protein. ELISA positivity rates were 8.2% for An. gambiae s.l. and 6.1% for An. funestus. Both An. gambiae and An. arabiensis were detected among 432 ELISA-positive and 668 ELISA-negative An. gambiae s.l. identified to species with a ribosomal DNA probe. The species-specific infection rates were calculated to be 9.6% for An. gambiae and 0.4% for An. arabiensis. These results confirm that An. gambiae and An. funestus are the primary malaria vectors in western Kenya and that An. arabiensis is a relatively minor vector.

Animals↗

Malaria incidence and prevention among European and North American travellers to Kenya.

A longitudinal survey was conducted among travellers departing from Nairobi airport to determine the use of malaria prevention measures and assess the risk for malaria while travelling in Kenya. Among 5489 European and North American travellers, 68 different drug regimens were used for prophylaxis, and 48% of travellers used both regular chemoprophylaxis and more than 1 antimosquito measure during travel; 52% of 3469 travellers who used chemoprophylaxis did so without interruption during their travel and for 4 weeks after departure. Compliance was lowest among travellers who visited friends and relatives, who were young, or who stayed more than 3 weeks. Sixty-seven (1%) travellers experienced symptoms of malaria, but the diagnosis could be verified for only 16 of these. Long-stay travellers appeared to be at higher risk for malaria than short-stay travellers, and health information needs to be targeted especially to the former. Similar investigations are needed among international travellers to other malaria-endemic countries. With comparable data available, consistent and effective malaria prevention guidelines can be developed.

Adult↗

Plasmodium falciparum: DNA probe diagnosis of malaria in Kenya.

We previously reported isolation of DNA probe which specifically recognizes Plasmodium falciparum and developed a simple method for its use. The sensitivity and specificity of this DNA probe method have now been extensively field tested in comparison with those of conventional microscopic examination of blood films in two separate studies in Malindi, Kenya, involving a total of 1179 patients. In the second study, which used improved techniques, sensitivity of the DNA probe was 89% when compared to microscopy. We conclude that the DNA probe method compares favorably with conventional microscopy in detecting parasite densities as low as 25 parasites per microliter of blood. A significant advantage of the DNA probe method is that it utilizes a standardized procedure which can simultaneously and reproducibly analyze a large number of samples without opportunity for significant reader bias.

Adult↗

Microgeographic variation in rDNA intergenic spacers of Anopheles gambiae in western Kenya.

The genetic population structure of Anopheles gambiae (Diptera: Culicidae) in western Kenya was investigated by hybridizing a rapidly evolving rDNA intergenic spacer sequence to restriction endonuclease digests of genomic DNA extracted from single mosquitoes from seven localities. Significantly different distributions of restriction fragment arrays were obtained from field sites less than 10 km apart, which suggests restricted gene flow and a subdivided population structure. Eight of twenty-one possible comparisons between pairs of populations yielded significant differences. An eastern Kenya coastal population did not share its restriction fragment arrays with any of the western populations, suggesting that isolation by distance can be complete on a relatively small geographic scale (700 km).

Animals↗

Chloroquine treatment of falciparum malaria in an area of Kenya of intermediate chloroquine resistance.

106 children aged 1-10 years who had pure Plasmodium falciparum infections and temperatures greater than or equal to 38 degrees C were treated with chloroquine base, 25 mg/kg body weight. 29% of the infections were sensitive in vivo, 41% recurred within 4 weeks (RI), 26% were RII resistant, and 4% were RII resistant. Rieckmann micro in vitro tests were successful in 64% of isolates obtained from these children; 63% were resistant to chloroquine. In 58 paired isolates obtained before and after treatment, the level of chloroquine sensitivity was lower in the parasites persisting or recurring after treatment. All children except 2 of the 4 with RIII resistance became afebrile an average of 1.4 d after starting treatment and their other symptoms resolved in an average of 1.8 d. By day 28, 57% of the children with RI resistance and 78% of those with RII resistance had recurrence of fever and other symptoms, compared with 19% of children with sensitive infections. No relationship was observed between the clinical or parasitological response and age, nutritional status, haematocrit, splenomegaly, presence of sickle-cell trait, or seropositivity to malaria by enzyme-linked immunosorbent assay. The study demonstrates that, in most children with malaria in an area of intermediate chloroquine resistance, fever and other symptoms resolve at least temporarily when treated with chloroquine.

Animals↗

Failure of erythromycin to improve chloroquine treatment of Plasmodium falciparum malaria in Kenya.

58 children aged 1 to 10 years who had pure Plasmodium falciparum infections acquired on the coast of Kenya were treated with chloroquine 25 mg/kg given over 3 d and erythromycin 10 mg/kg 4 times a day given for 7 d. After 4 weeks follow-up, 62% had recurrent infections and 11% failed to clear their parasitaemia (1 had an RIII pattern of resistance). Of 38 children treated with chloroquine 25 mg/kg alone, 55% had recurrences and 21% failed to clear (including 1 RIII). In vitro microtests classified 74% of isolates from initial infections and 91% of isolates from recurrent infections as resistant. Erythromycin does not improve chloroquine treatment in children with infections due to P. falciparum having low to moderate levels of chloroquine resistance.

Animals↗

Chlorproguanil/dapsone for the treatment of non-severe Plasmodium falciparum malaria in Kenya: a pilot study.

Chlorocycloguanil, the active metabolite of chlorproguanil, was synergistic in vitro with dapsone against 2 culture-adapted Plasmodium falciparum isolates from Kenya; maximal synergy occurred at lower concentrations that it did with pyrimethamine and sulfadoxine. 48 children with asymptomatic P. falciparum infections were treated with chlorproguanil (at a target dose of 1.2 mg/kg) and dapsone (target dose of 1.2 or 2.4 mg/kg); all were free of parasitaemia by day 7. The following numbers had recurrences on days 14, 21, and 28, respectively: 1 of 48, 7 of 47, and 7 of 40. All 39 children treated with pyrimethamine (target dose 1.2 mg/kg) and sulfadoxine (target dose 24 mg/kg) were cleared of infection, while the following had recurrences on days 14, 21, and 28: 1 of 39, 2 of 38, and 2 of 36. The rate of decrease in parasitaemia was the same in the 2 groups, and there was no change in haematocrit or haemoglobin during the follow-up. The rate of recurrence in the children receiving chlorporguanil/dapsone was higher, probably because these drugs have a much shorter clearance time than pyrimethamine/sulfadoxine. Chlorproguanil/dapsone is an effective combination for treating P. falciparum malaria and deserves further study.

Animals↗

Identification of malaria species by ELISA in sporozoite and oocyst infected Anopheles from western Kenya.

Enzyme-linked immunosorbent assays (ELISAs) for the circumsporozoite (CS) antigens of Plasmodium falciparum, P. malariae, and P. ovale were used to identify species of sporozoite and oocyst infections detected by dissection in Anopheles gambiae s.1. and An. funestus collected in western Kenya. ELISAs identified 92.5% of 1,113 salivary gland infections; Plasmodium species infections included 79.4% P. falciparum, 3.2% P. malariae, 1.7% P. ovale, and 2 or more Plasmodium species were detected in 15.7% of the Anopheles in which the species of parasite was identified. Identification was more likely with greater numbers of sporozoites observed in dissections, increasing from 65% ELISA positivity in mosquitoes with 1-10 sporozoites in their salivary glands to 96% in mosquitoes with over 1,000 sporozoites. ELISAs detected CS antigen in 66% of 294 Anopheles that by dissection had oocysts but uninfected salivary glands. Of 112 Anopheles with a single species of Plasmodium detected in the salivary glands, 29 (25.9%) had 1 or more additional species detected in the midgut, indicating a high potential for multiple infections. Similar proportions of Plasmodium species were found in An. gambiae s.1. and An. funestus.

Animals↗

Comparison of DNA probe and cytogenetic methods for identifying field collected Anopheles gambiae complex mosquitoes.

A recently developed DNA probe method was compared with the standard cytogenetic method for identifying the species of individual mosquitoes in the Anopheles gambiae complex. The complex consists of 6 morphologically indistinguishable sibling species that include the major African malaria vectors. Half-gravid, field collected mosquitoes were split into 2 portions: the abdomen was preserved for ovarian nurse cell cytotaxonomy and the head/thorax portion was desiccated for DNA extraction. Cytogenetic examination of the Kenya specimens showed 88 An. gambiae and 108 An. arabiensis. The Zimbabwe specimens consisted of 6 An. gambiae and 55 An. Quadriannulatus. All samples of the 3 species were polymorphic for the major chromosomal inversions previously recorded in field specimens from eastern and southern Africa, indicating that the collections reflected natural levels of intraspecific variation in the field populations sampled. Approximately 97% of the cytologically identified mosquitoes were also identified to species by the DNA probe method, and in every case the DNA probe and cytogenetic methods of species identification produced concordant results.

Animals↗

Vector density, parasite prevalence, and transmission of Onchocerca volvulus in Guatemala.

Transmission of Onchocerca volvulus at 4 locations with different prevalences of human onchocerciasis in the Atitlán region of Guatemala is described in relation to vector density and infection rates. The percentages of residents with skin biopsies positive for microfilariae of O. volvulus at these locations were 13.8%, 33.3%, 65.4%, and 89.6%. The following variables associated with transmission were calculated from our observations (the values are presented in an order that corresponds with the above prevalence rates): frequency of third-stage larvae (calculated on an annual basis) in parous Simulium ochraceum, 0, 0.004, 0.005, and 0.004; estimated daily biting density of S. ochraceum, 23, 24, 254, and 1,509 flies per day; and estimated annual infective biting density (based on S. ochraceum), 0, 18, 185, and 1,101 potentially infective bites per year. The frequencies of third-stage larvae are very small compared with those observed in Africa, and suggest that transmission of O. volvulus in Guatemala depends on high vector density. Locations with low, and perhaps tolerable, levels of onchocerciasis (less than 15% of female residents with skin biopsies positive for microfilariae) have mean daily biting densities for S. ochraceum of less than or equal to 24 flies, and infected residents normally have mean microfilarial densities of less than or equal to 3 microfilariae per mg of skin. Stratification of prevalence rates by age group proved useful for assessing current transmission within a village.

Adolescent↗