PubMed Health⌕ Search

Biomedical subjects

D K Koech

Publications and source records attributed to D K Koech.

88 records · Page 5Linked to original sources
PubMed1983

The Kenyan Saradidi community malaria project: I. Response of Plasmodium falciparum isolates to chloroquine in 1981 and 1982.

In 1981, 41 schoolchildren from Saradidi, Kenya, infected with Plasmodium falciparum were treated with chloroquine. All 41 infections were sensitive in vivo: parasitaemia cleared by day 3 and remained absent through day 7. All 17 (of 27) isolates successfully tested for chloroquine sensitivity in vitro were sensitive in the Rieckmann macro test: greater than 1% schizont development did not occur at chloroquine concentrations of greater than 1.25 nmol per ml of blood. In 1982 in the same area 20 P. falciparum infections were sensitive in vivo: parasitaemia cleared by day 5 and did not recur through day 7. Two of the 20 isolates were resistant in vitro with persistent schizont development at greater than 1% of control values at chloroquine concentrations of 1.5 and 3.0 nmol/ml in the macro test and 16 and 32 pmol/well in the Rieckmann micro test (compared with inhibition at less than or equal to 1.25 nmol/ml and less than or equal to 5.7 pmol/well, respectively, for sensitive isolates). In a modified 48-hour test, growth of two additional isolates was not inhibited until chloroquine concentration of 0.06 nmol per ml of medium, a pattern intermediate between that observed with known chloroquine-sensitive (less than or equal to 0.03 nmol/ml) and resistant (greater than or equal to 0.1 nmol/ml) P. falciparum isolates. The results demonstrate a changing pattern of the in vitro response of P. falciparum isolates in Saradidi to chloroquine.

Animals↗
PubMed1983

High-dose sodium stibogluconate treatment of cutaneous leishmaniasis in Kenya.

Cutaneous leishmaniasis caused by Leishmania aethiopica usually responds poorly to conventional doses of pentavalent antimonial drugs. We treated three patients with cutaneous leishmaniasis acquired in Kenya, presumed or documented to be caused by L. aethiopica, with intravenous sodium stibogluconate, 18 to 20 mg Sb/kg body-weight twice daily for 30 days. All patients had a good response to treatment, with disappearance of parasites from skin smears and cultures after 14 to 27 days, clinical healing of the lesions, and no recurrence during a three to 18-month follow-up. Side effects of treatment were minor. We conclude that this high dose sodium stibogluconate regimen is safe and effective for treating cutaneous leishmaniasis caused by L. aethiopica in Kenya.

Adolescent↗
PubMed1983

Plasmodium falciparum in Kisumu, Kenya: differences in sensitivity to amodiaquine and chloroquine in vitro.

Sensitivity to amodiaquine and chloroquine was examined in 11 Plasmodium falciparum isolates from Kisumu, Kenya, and three chloroquine-resistant parasites. All 11 Kisumu isolates were sensitive to amodiaquine in vivo. Six of 10 Kisumu isolates successfully tested were more sensitive to amodiaquine in a microtest (minimal inhibitory concentration [MIC], less than or equal to 114 nM for amodiaquine vs 160 nM for chloroquine) and/or 48-hr in vitro tests (MIC, 60 nM for amodiaquine vs 100 nM for chloroquine). All nine successfully cultured Kisumu isolates had a lower 50% inhibitory dose (ID50) for amodiaquine (9.0-18.2 nM) than for chloroquine (24.9-75.4 nM) in a radioisotopic assay. Five were also more sensitive when retested in the 48-hr test. The chloroquine-resistant parasites had reduced in vitro sensitivity to chloroquine (ID50, greater than or equal to 103 nM; MIC, 300 nM) but not to amodiaquine (ID50, less than or equal to 22 nM; MIC, less than or equal to 100 nM). These data indicate that amodiaquine is more potent than chloroquine and should be evaluated for efficacy against P falciparum in areas where RI and RII chloroquine resistance occurs.

Amodiaquine↗
PubMed1983

Chloroquine resistance in Plasmodium falciparum from Kenyan infants.

Forty-two infants, aged 6 to 24 months, infected with Plasmodium falciparum were identified in Kisumu, Kenya. Because of their age, all were presumably not semi-immune to malaria. Each infant was treated with 25 mg/kg chloroquine base and followed for 7 days. Forty-one infections were sensitive to chloroquine in vivo; asexual parasites disappeared in all by day 4 and were not present on days 5, 6, or 7. One infection was resistant in vivo; parasites disappeared by day 3 but recrudesced on day 4. Rieckmann micro in vitro tests for chloroquine were done on the 42 isolates. Interpretable results were found in 25. In vitro resistance was demonstrated in 18 (72%) isolates, including the patient with in vivo resistance; greater than or equal to 99% inhibition of schizont development only occurred in wells containing greater than or equal to 8 pmol chloroquine base (compared with less than or equal to 5.7 pmol/well for known sensitive isolates). This is the first demonstration of in vivo and in vitro chloroquine-resistant P. falciparum in a Kenyan. Comparison of these results with results from other studies carried out in the same area on the same area on older individuals suggests that the immune response may be playing a role in modifying the expression of resistance.

Child, Preschool↗
PubMed1983

Immunosuppression in Kenyan visceral leishmaniasis.

Cell-mediated immune responses were evaluated in 15 patients with active visceral leishmaniasis from Masinga location in eastern Kenya where the disease is endemic. Age and sex matched controls were selected from a village school in the same area. In vivo studies were carried out by skin testing with leishmanin, tuberculin, streptococcal and candida antigens. Lymphocyte blastogenic transformation to the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) and the antigens purified protein derivative (PPD), streptokinase-streptodornase (SKSD) and leishmanial antigen (LA) was studied in vitro. The results showed that immunosuppression in visceral leishmaniasis in Kenya was both specific and non-specific. In the majority of patients there was complete anergy to all antigens in vivo and in vitro. The suppression of responses to mitogens was less marked. Recovery of non-specific responses preceded the development of specific immunity. In a small number of patients (23%) immune unresponsiveness to leishmanial antigens persisted 1 year after parasitological cure.

Adolescent↗
PubMed1980

Oxidation of glucose by mouse peritoneal macrophages: a comparison of suspensions and monolayers.

Macrophages, when maintained in vitro, take up glucose from the medium and oxidize it to CO2. The rate of oxidation of glucose varies considerably, depending on the physical state of the cell preparation. Cells in suspension oxidize glucose at a level six-fold that of cells in monolayers. The differences cannot be attributed to change in the rats of transport of glucose. On the other hand, an increase in intracellular glycogen (about three-fold) and free glucose plus glucose-6-P (many-fold) was found in the cells prepared as monolayers. During subsequent incubation with glucose-14C, this could be the cause of an isotope dilution effect and could explain the lower production of 14CO2 by the adherent cells. Since oxidation of glucose-1-14C to 14CO2 is used by many investigators to indicate the functional state of macrophages, we suggest close attention be paid to the system used, i.e., monolayers vs. suspensions.

Animals↗
PubMedDate not supplied

Variability in the metabolism of proguanil to the active metabolite cycloguanil in healthy Kenyan adults.

Extensive metabolizers (EM) and poor metabolizers (PM) of the malaria chemoprophylactic drug proguanil have been identified by measuring the proguanil/cycloguanil ratio in urine following a single dose of the pro-drug. The pharmacokinetic characteristics of proguanil were similar in 8 EM and 8 PM subjects, but there were significant differences between the 2 groups with respect to cycloguanil pharmacokinetics. In none of the PM subjects could cycloguanil be detected in whole blood samples at any time after proguanil dosage. Plasma cycloguanil was measureable in only 2 of 8 PM subjects, despite an analytical sensitivity in the high-performance liquid chromatographic assay of 1 ng/ml cycloguanil. A comparatively high proportion of Black Kenyan adults appear to metabolize proguanil poorly, possibly because they lack the specific mixed function oxidase which will accept proguanil as substrate.

Adult↗
PubMedDate not supplied

Experimental transmission of Leishmania major to vervet monkeys (Cercopithecus aethiops) by bites of Phlebotomus duboscqi (Diptera: Psychodidae).

Experimental transmission of Leishmania major to vervet monkeys (Cercopithecus aethiops) was accomplished by bites of Phlebotomus duboscqi sandflies. Three-day-old, laboratory-reared P. duboscqi were fed on leishmanial lesions on hamsters infected with L. major. The flies were re-fed on monkeys 10 d after infection. Five adult male vervet monkeys were used in concurrent transmission trials. Two of the monkeys received subcutaneous inoculations with stationary-phase promastigotes (2 x 10(6) promastigotes in 0.1 ml of medium) on the base of the tail. Putatively infected P. duboscqi were allowed to feed on the remaining 3 monkeys at sites on the base of the tail and on the right eyebrow. Challenges by sandfly bites resulted in multiple leishmanial lesions at all bite sites and, consequently, more lesion area than was produced by needle challenges. Post-feeding dissection of sandflies indicated that multiple lesions could be caused by bites of a single fly, and that probing alone, without imbibing blood, was sufficient for transmission. These first experimental transmissions of L. major to vervets by bites of P. duboscqi demonstrate that sandfly challenge is an efficient alternative to needle challenge, making available a unique Leishmania-sandfly-non-human primate model for use in vaccine development.

Animals↗
PubMedDate not supplied

A new rural focus of cutaneous leishmaniasis caused by Leishmania tropica in Kenya.

We have identified a new rural focus of cutaneous leishmaniasis caused by Leishmania tropica in Muruku sublocation, Salama location, Laikipia district, Rift Valley province, Kenya. Based on a few available case histories, previous reports of L. tropica in Kenya indicated a tentative geographical distribution. Recently 6 indigenous Kenyans from the new focus, who had never travelled outside Kenya, developed cutaneous lesions on the face and/or extremities found to contain Leishmania by culture and smear. Most of the patients manifested the typical 'urban' dry sore which grew slowly into a nodule measuring 2 x 1 cm to 9.5 x 3 cm, and after some months formed a central crust surrounded by small satellite papules. After treatment with Pentostam (sodium stibogluconate), about 40% of the sores failed to heal completely, either scarring centrally with fulminating papules at the edges and spreading peripherally, or healing but then recrudescing at the edge of the scar. Stationary-phase promastigotes from culture isolates were analysed by cellulose acetate electrophoresis. Isoenzyme profiles of 6 isolates were compared with those of World Health Organization reference strains using 12 enzyme loci; they were indistinguishable from those of 2 L. tropica reference strains. All 6 case sites lay within a radius of 4 km. Several other suspected cases from the same area are being investigated.

Adolescent↗
PubMedDate not supplied

Field application of an ELISA using redefined Leishmania antigens for the detection of visceral leishmaniasis.

Two soluble antigens from Leishmania donovani of 116 kDa and 70 kDa molecular mass, and a soluble mixture of crude antigens, were used in an enzyme-linked immunosorbent assay (ELISA) for the detection of visceral leishmaniasis (VL) in the field, and compared with the direct agglutination test (DAT). The tests were carried out on 8 VL patients, 34 normal individuals from an area endemic for the disease, and 68 former visceral leishmaniasis patients 1-5 years after treatment. The 70 kDa ELISA and the DAT had a sensitivity and specificity of 100% (95% confidence interval 63-100%), while the 116 kDa ELISA and the soluble crude antigen ELISA were 37.5% (9-76%) and 50% (16-84%) sensitive, respectively. When using ELISA (116 kDa or 70 kDa), 68-69% of sera tested 1-2 years, and 92-94% of sera tested 5 years, after treatment were negative. In contrast, when DAT or ELISA with crude antigen were used, the negativity rate was 31% 1-2 years, and 53% 5 years, after treatment. DAT was therefore not an accurate test for diagnosis in the field. The use of the 70 kDa antigen in ELISA was an accurate alternative to DAT in the detection of VL.

Agglutination Tests↗
PubMedDate not supplied

Antifolate drug resistance and point mutations in Plasmodium falciparum in Kenya.

Due to increased chloroquine resistance, the antifolate/sulpha drug combinations are becoming increasingly important in the chemotherapy of falciparum malaria. However, point mutations in the dihydrofolate reductase gene lead to resistance to the antifolate drugs. We therefore investigated the prevalence of the 6 reported point mutations in this gene among field isolates of Plasmodium falciparum from Kenya, to determine if the mutations correlated with resistance to pyrimethamine and the biguanides cycloguanil and chlorcycloguanil. We used a mutation-specific polymerase chain reaction technique to test for these reported mutations in 21 Kenyan isolates and 4 reference lines. We also amplified and directly sequenced the dihydrofolate reductase coding sequence from these parasites to confirm the results and test for other possible mutations. Of the reported mutations, we found S108N, which is the central mutation of pyrimethamine resistance, and mutations N51I and C59R, which modulate the levels of resistance and may confer decreases in response to cycloguanil that are folate and p-aminobenzoic acid dependent. No isolate possessed the paired point mutations S108T and A16V, or I164L and S108N, which have been associated with cycloguanil resistance in previous studies. These results provided supportive evidence for the combined use of a cycloguanil-class drug (e.g., chlorproguanil) and a sulpha drug (e.g., dapsone) against P.falciparum malaria in Kenya.

Animals↗