Prophylactic and curative activities of extracts from Warburgia ugandensis Sprague (Canellaceae) and Zanthoxylum usambarense (Engl.) Kokwaro (Rutaceae) against Plasmodium knowlesi and Plasmodium berghei.

ETHNOPHARMACOLOGICAL RELEVANCE: This work reports the anti-plasmodial activities of Warburgia ugandensis and Zanthoxylum usambarense commonly used as phytomedicines against malaria by some Kenyan communities. AIM OF STUDY: To determine the anti-plasmodial activities of extracts from Warburgia ugandensis and Zanthoxylum usambarense against Plasmodium knowlesi and Plasmodium berghei. MATERIALS AND METHODS: Eight plant extracts were screened for in vitro anti-plasmodial activity against Plasmodium knowlesi, in a 96-well plate incubated at 37 degrees C on a RPMI culture medium supplemented with baboon serum. Of the eight, three were investigated for prophylactic and curative activities in BALB/c mice against drug-sensitive Plasmodium berghei in a 4-day test at a dose rate of 200mg/kg/day. RESULTS: Inhibitory concentrations (IC(50)) values of between 3.14 and 75 microg/ml, up to 69% chemosuppression of parasites growth and over 80% survivorship of treated mice were observed. CONCLUSION: The two medicinal plants, Warburgia ugandensis and Zanthoxylum usambarense possess bioactive compounds against malaria parasites and could be exploited for further development into malaria therapy.

Isolation of multidrug-resistant tuberculosis strains in patients from private and public health care facilities in Nairobi, Kenya.

SETTING: Health care facilities in Nairobi, Kenya. OBJECTIVE: To document the presence of multidrug-resistant tuberculosis (MDR-TB) strains in patients from Nairobi between September 1999 and October 2001. DESIGN: Descriptive study. RESULTS: Of the 983 referred patients who submitted sputum for culture and drug susceptibility testing (DST), 59% were males. Two hundred and nine (21.3%) patients had a positive culture, of whom 15.2% had a request for DST against isoniazid, rifampicin, streptomycin and ethambutol. Of these, 65 (43.6%) had an isolate resistant to one or more drugs, while 17 (11.4%) had MDR-TB. Ten (59.0%) cases were referred from public health care facilities while seven (41%) were from the private sector. Sixteen isolates were resistant to all four drugs. All MDR-TB cases but one were from Nairobi. CONCLUSION: The emergence of MDR-TB in Nairobi is a cause for concern. An outbreak would be catastrophic, creating not only increased morbidity and mortality but also a tremendous strain on already limited health care resources. Lack of policies for the treatment and management of MDR-TB and the unavailability of appropriate diagnostic facilities may increase its spread. Efforts to prevent outbreaks of MDR-TB should be emphasised.

Identification of MDR-TB Beijing/W and other Mycobacterium tuberculosis genotypes in Nairobi, Kenya.

SETTING: Suspected tuberculosis (TB) patients in Nairobi, Kenya. OBJECTIVE: To identify the presence of multidrug-resistant (MDR) Beijing/W type and other genotypes of Mycobacterium tuberculosis. METHODS: Thirty-three isolates resistant to one or more drugs (resistance ratio method), including 15 MDR isolates and 40 susceptible isolates selected at random, were analysed by dot-blot hybridisation for mutations associated with resistance to isoniazid, rifampicin, streptomycin and ethambutol. All strains were genotypically classified using spoligotyping. RESULTS: Of the 33 drug-resistant isolates, 21 (64%) were from males and 12 (36%) were from females. Mutations associated with resistance to isoniazid (katG 315) and rifampicin (rpoB526, 531) were confirmed in 83.3% and 100% of the isolates, respectively, and in 87% of the MDR isolates. Mutations were detected in 25% and 71.5% of the isolates resistant to streptomycin (rpsL43) and ethambutol (embB306), respectively. No mutations were detected in drug-susceptible isolates. Spoligotyping grouped the isolates into 25 groups. Ten of these groups corresponded to previously identified strain groups, including seven families in the international database. One of these families (CAS1) comprised six (40%) of the 15 MDR isolates. Another family (Beijing) had six (8.3%) isolates, of which two (33.3%) were MDR (Beijing/W). CONCLUSION: This study is the first in Kenya and the second in sub-Saharan Africa to report the presence of MDR Beijing/W type and other possible drug-resistant outbreak strains. Application of the molecular techniques and markers will allow us to monitor the spread of existing drug-resistant strains and the appearance of new ones.

Thymidine kinase from Tetrahymena thermophila. Purification and immunological analysis.

Thymidine kinase is an enzyme involved in DNA precursor metabolism and DNA replication. The synthesis of this enzyme is highly regulated during the cell cycle and the activity of the enzyme is also regulated by feedback inhibition. Genes encoding thymidine kinase have been extremely useful as selectable markers for introducing DNA into a number of cells. In order to study cell cycle regulation of thymidine kinase, the gene which encodes this enzyme, as well as aspects of DNA replication in the ciliated protozoan Tetrahymena thermophila, we have purified thymidine kinase from Tetrahymena. Two forms of thymidine kinase with native molecular masses of 59 kDa and 80 kDa have been identified and purified 6800- and 4600-fold, respectively. The 59-kDa enzyme, a homodimer of 30-kDa subunits, has been purified to near homogeneity and polyclonal antibodies have been raised against the 30-kDa subunit. Serological studies indicate that the two enzymes are antigenically distinct. The antibody against the Tetrahymena protein cross-reacts with a polypeptide in Chinese hamster ovary (CHO) cell extracts of 26 kDa which corresponds to the reported size of Chinese hamster thymidine kinase protein.

Investigation of the effectiveness of measles vaccination in children in Kenya.

Laboratory studies were performed on 128 children clinically diagnosed as measles when seen at the Infectious Diseases Hospital, Kenyatta National Hospital (IDH), Nairobi (86 cases) and the Rural Health Training Centre, Maragua, Central Province (42 cases) between 9 July and 31 August 1984. A concurrent measles infection was confirmed in 95% of the children seen at IDH and in 85% of those seen at Maragua, with similar proportions of confirmations in children who had, and who had not, received measles vaccine. No differences in the number of sero-conversions nor in the absolute levels of acute or convalescent HI antibody titres could be detected between vaccinated and unvaccinated children. Analysis of the cases seen at Maragua indicates that about two thirds of the children who had received vaccine were protected. A pilot study of vaccinating children at 8 months and again at 12-13 months is suggested in an attempt to eradicate measles.