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A J Oloo

Publications and source records attributed to A J Oloo.

54 records · Page 3Linked to original sources

Natural antibody responses against the non-repeat-sequence-based B-cell epitopes of the Plasmodium falciparum circumsporozoite protein.

Synthetic peptides and human serum or plasma samples from regions of Brazil, Papua New Guinea, and Kenya in which malaria is endemic were used to identify B-cell epitopes localized outside the repeat region of the circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum. In agreement with recent observations, our results confirm the presence of two non-repeat-region-based B-cell epitopes of the CS protein. Of these two epitopes, only the region I epitope (KPKHKKLKQPGDGNP) was previously shown to be recognized by human sera. In this study, we show that human immune sera from malarious regions recognize another B-cell epitope, ENANANNAV, that resides carboxyl to the repeat region. The present study reveals that (i) the repeat-sequence (NANP)-based B-cell epitope of the CS protein is an immunogenic but not immunodominant epitope; (ii) the natural expression of antibody responses to the two non-repeat-region-based B-cell epitopes of the CS protein varies in different populations in which malaria is endemic; (iii) although the host immune responses to the non-repeat-region-based B-cell epitopes increase as a function of host age, this increase is not statistically significant for the region I epitope but is significant for the other epitope; and (iv) the Th1R T-cell site but not the Th2R or Th3R T-cell site induces an antibody response in the human host. This study confirms the immunogenic potential of non-repeat-region-based B-cell epitopes and suggests that antibody pressures may also contribute to the maintenance of the antigenic diversity of the CS protein.

Adolescent↗

Effectiveness of permethrin-impregnated bed nets and curtains for malaria control in a holoendemic area of western Kenya.

The effectiveness of village-wide use of permethrin-impregnated bed nets or eave, window, and door curtains as control measures for Plasmodium falciparum malaria was evaluated during two successive high-transmission seasons in western Kenya. Pairs of villages were assigned to one of three study groups: bed net, curtain, or control. Clinical, parasitologic, and entomologic measures were made from March to July 1990 and again 12 months later. When compared with the controls in 1990 and 1991, we observed a marked reduction in the incidence of P. falciparum infections in children less than six years old in the bed net villages (reduced by 40% and 48%) and a smaller but still significant reduction in the curtain villages (10% and 33%). Significant reductions were also seen in the incidence of P. falciparum parasitemias greater than 2,500/mm3 in the bed net group (reduced by 44% and 49%) and curtain group (16% and 32%). Additionally, we observed significant reductions in the incidence of documented fevers in association with P. falciparum parasitemia in bed net (reduced by 63%) and curtain villages (53%) when compared with controls. Entomologic inoculation rates in both bed net and control villages decreased by more than 50% below control values during both high transmission seasons. The results of this study, together with a 1988 study in the same area during the low transmission season, show that bed nets offer greater year-round of protection against P. falciparum infection than curtains. However, during the high transmission season, this technique reduces the frequency of P. falciparum infection rather than preventing it entirely.

Animals↗

The effect of permethrin impregnated sisal curtains on vector density and malaria incidence: a pilot study.

Impregnation of bednets and curtains with suitable pyrethroids may reduce entomological inoculation rates (EIR) and malaria incidence. We conducted a quasi-experimental pilot study over 3 months in Western Kenya on 20 houses with 54 children. Ten houses in the experimental site received sisal curtains treated with permethrin at either 0.5g/m2 or 0.1g/m2. Control houses had untreated curtains or none. Mosquito vector density (MVD), man biting rates (MBR), and residual insecticidal effects (RIE) of permethrin were determined every two weeks. MVD was reduced by 97.7% and 98.7% in houses from the 2 experimental groups with a 60% reduction with unimpregnated curtains. MBR varied from 6.4 (no curtains), 1.7 (unimpregnated), 0.7 (0.5g/m2 curtains) to 0.4 (1.0g/m2 curtains). RIE begun to decline after the fourth month. Malaria incidence remained similar at the two sites. We conclude that covering of eaves and windows with permethrin impregnated sisal curtains can reduce MVD and the number of mosquito bites to individuals sleeping in protected houses.

Animals↗

The effect of participatory school health programme on the control of malaria.

Two hundred primary level school children, aged between 7 and 18 years took part in a comparative pilot study of the effect of participatory school health education in Kisumu, Western Kenya in 1988. An experimental cohort of 100 pupils had participatory health education versus a passive control of another 100. An initial KAP survey revealed comparable sociological variables as well as morbidity statistics. No significant change occurred on the knowledge of the disease between the groups after 3 months. However, positive change in attitude here determined by positive antimalarial practices, was observed more frequently in the experimental group than in the control group. Efforts to environmental manipulation increased by 69% vs 1%, while parasite rates decreased by 32% vs an increase of 5%, respectively. Similarly there was a decrease in absenteeism of 25% vs an increase of 5% between the groups. Clinical malaria was reported less frequently in the experimental group than the control (26% against 8%). In conclusion, this pilot study suggests that participatory approach in effective health education to school children should be investigated further to determine its potential in the intersectoral malaria control strategy.

Adolescent↗

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↗

Sensitivity of falciparum malaria to chloroquine and amodiaquine in four districts of western Kenya (1985-1987).

In-vivo and in-vitro studies to determine the sensitivity of Plasmodium falciparum malaria to chloroquine and amodiaquine were conducted in 4 districts of Western Kenya over a 2-year-period. Patients aged 5-60 years, were treated with chloroquine or amodiaquine base 25 mg/kg over 3 days. Recurrence of parasitaemia within 7 days (R1 resistance) or failure to clear parasites (R11 resistance) was observed in 27% of infections in West Pokot district, 51% in Busia, 45% in Bungoma and 19% in Rusinga Island. R111 resistance (failure to decrease parasitaemia by at least 75%) was documented in Rusinga Island. The proportions of parasites with minimum inhibitory concentrations (MICs) for chloroquine greater than 114 nM in in-vitro tests ranged from 37% in Busia to 68% in Bungoma. For amodiaquine, 20% of 30 isolates tested had MICs greater than 80 nM. We conclude that resistance to chloroquine is now established in the area and amodiaquine may be useful in uncomplicated chloroquine resistant falciparum infections in the region.

Adolescent↗

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↗

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↗

Changing response to chloroquine of Plasmodium falciparum in Saradidi, Kenya, from 1981 to 1984.

From 1981 through 1984, the response of Plasmodium falciparum to chloroquine was monitored in Saradidi, Kenya, as a part of a community-based health programme to provide treatment for malaria in each village. Before 1983, all 71 infections treated with chloroquine were sensitive in vivo; parasitaemia cleared by day 3 and remained absent to day 7. In June 1983, 23.1% of 26 infections treated with chloroquine base 10 mg kg-1 either recrudesced in seven days (RI resistance, five infections) or decreased but failed to clear (RII resistance, one infection). In September 1983, 16.2% of 68 and in February 1984, 13.2% of 53 infections were resistant in vivo after treatment with chloroquine base 10 mg kg-1. A course of chloroquine base 25 mg kg-1 over three days remained effective; only two (1.6%) of 129 infections examined were resistant in vivo; in both, parasitaemia cleared then recurred (RI). In September 1984, however, nine (10.2%) infections were resistant after treatment with chloroquine base 25 mg kg-1; in four of these parasitaemia decreased but never cleared (RII). Similar results were observed in vitro. In the Rieckmann macro in vitro test, 63.3% of 30 P. falciparum isolates tested were resistant to chloroquine (minimal inhibitory concentration (MIC) greater than or equal to 1.25 X 10(-6) mol 1(-1) blood) in June 1983, as were 61.8% of 34 isolates in the Rieckmann micro test (MIC greater than or equal to 1.14 X 10(-6) mol 1(-1) blood).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Epidemiology of chloroquine-associated pruritus in Saradidi, Kenya.

The association of pruritus and ingestion of chloroquine phosphate in Saradidi, Kenya, was determined by randomly giving 437 children (less than 18 years) and 182 adults either 10 mg base kg-1 of regular chloroquine, 10 mg base kg-1 of enteric-coated chloroquine, 10 mg base kg-1 of amodiaquine, or one 300 mg tablet of enteric-coated ferrous sulphate. Before treatment, a blood smear was taken. Paired urine samples were tested for 4-aminoquinolines to exclude prior drug ingestion, to document drug absorption, and to exclude chloroquine or amodiaquine intake in persons who received iron. The following day, the incidence of itching was ascertained. More adults (20.3%) reported itching than did children (12.8%) (P less than 0.05); no significant difference between males and females was noted. A history of itching 24 hours after treatment was not significantly more common in persons with malaria parasitaemia. Pruritus was more frequent in those receiving regular chloroquine (21.5% of 186) and enteric-coated chloroquine (17.8% of 118) than after amodiaquine (11.6% of 173) or iron (8.5% of 142) (P less than 0.005). Amodiaquine which is a 4-aminoquinoline like chloroquine did not appear to cause significant pruritus in this population. These results demonstrate that chloroquine-associated pruritus is experienced frequently in Saradidi. This side effect of malaria treatment could influence usage of chloroquine phosphate provided by village health workers.

Adolescent↗

Response of falciparum malaria in vivo to a standard regimen of chloroquine in Kisumu District, Western Kenya.

The sensitivity of Plasmodium falciparum to chloroquine was studied in 140 children in two locations in Western Kenya. The standard WHO in vivo field test was used and chloroquine phosphate 25 mg base/kg administered in divided doses over three days. In one area 13.2% of cases had recrudescent parasitaemias, while in the other area 8.2% of infections were resistant, with 3.5% having an RII pattern. The remaining isolates were sensitive to chloroquine. Further in vivo and in vitro tests in the region are needed to document the extent and level of resistance.

Blood↗

All-cause mortality among young children in western Kenya. VI: the Asembo Bay Cohort Project.

Although all-cause mortality has been used as an indicator of the health status of childhood populations, such data are sparse for most rural areas of sub-Saharan Africa, particularly community-based estimates of infant mortality rates. The longitudinal follow-up of more than 1,500 children enrolled at birth into the Asembo Bay Cohort Project (ABCP) in western Kenya between 1992 and 1996 has provided a fixed birth cohort for estimating all-cause mortality over the first 5 yr of life. We surveyed mothers and guardians of cohort children in early 1999 to determine survival status. A total of 1,260 households were surveyed to determine the survival status of 1,556 live births (99.2% of original cohort, n = 1,570). Most mothers (66%) still resided but 27.5% had migrated, and 5.5% had died. In early 1999, the overall cumulative incidence of all-cause mortality for the entire 1992-1996 birth cohort was 26.5% (95% confidence interval, 24.1-28.9%). Neonatal and infant mortality were 32 and 176 per 1,000 live births, respectively. These community-based estimates of mortality in the ABCP area are substantially higher than for Kenya overall (nationally, infant mortality is 75 per 1,000 live births). The results provide a baseline description of all-cause mortality among children in an area with intense Plasmodium falciparum transmission and will be useful in future efforts to monitor changes in death rates attributable to control programs for specific diseases (e.g., malaria and HIV/AIDS) in Africa.

Adolescent↗