The results are reported of the application of a short-course regimen for pulmonary tuberculosis in routine service in three districts in Kenya. All patients were treated in hospital for one month receiving Streptomycin, Isoniazid,... more
The results are reported of the application of a short-course regimen for pulmonary tuberculosis in routine service in three districts in Kenya. All patients were treated in hospital for one month receiving Streptomycin, Isoniazid, Rifampicin and Pyrazinamide daily and followed by Rifampicin and Isoniazid daily on outpatient basis for five months. There was no failure of chemotherapy among 194 patients with pre-treatment sensitive strains at the end of chemotherapy. Six (3.9%) had a doubtful status but none relapsed during follow-up. Among 123 patients assessed after completion of follow-up only one (0.8%) relapsed and 16 of 22 patients with pretreatment resistant strains had a favourable response at the end of chemotherapy and follow-up. The therapeutic results achieved are excellent under programme conditions though of necessity with some amount of supervision that is not routinely available. Considering the advantages of short course regimens, a case for the choice of an appropriate short regimen to be used nationwide in the near future is made.
Research Interests: Kenya, Adolescent, Humans, Female, Male, and 17 moreMicrobial genetic and drug resistance, Follow-up studies, Recurrence, Middle Aged, Adult, Time Factors, Tablets, Combination drug therapy, Streptomycin, Pulmonary Tuberculosis, Clinical Protocols, Isoniazid, Ambulatory Care, Pyrazinamide, Clinical Trials as Topic, Randomized Controlled Trials as Topic, and Child preschool
Although treatment of sputum using bleach has shown increased sensitivity in smear microscopy, the safety aspect of sodium hypochlorite (NaOCl) has not been addressed. To determine the biocidal effect of NaOCl on Mycobacterium... more
Although treatment of sputum using bleach has shown increased sensitivity in smear microscopy, the safety aspect of sodium hypochlorite (NaOCl) has not been addressed. To determine the biocidal effect of NaOCl on Mycobacterium tuberculosis when used as a safety measure in direct sputum smear microscopy for the diagnosis of tuberculosis (TB). A total of 156 smear- and culture-positive pooled sputum specimens were assessed for the viability of M. tuberculosis after treatment with NaOCl. Each specimen was divided into 11 equal portions. One portion was directly cultured. Each of five portions was treated with 3.5% NaOCl and the other five with 5% NaOCl. Specimens were then cultured at intervals of 15 min and 1, 3, 15 and 24 h. A total of 18 (11.5%) specimens showed growth after treatment with NaOCl. Of these, 5 (3.2%) showed growth upon treatment with 3.5% NaOCl at 15 min and 15 and 24 h. Ten (6.4%) showed growth after treatment with 5% NaOCl between 15 min and 3 h, but none showed gro...
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Restriction fragment length polymorphism and hybridization of DNA extracted from Mycobacterium tuberculosis, nontuberculous mycobacteria, and nonmycobacterial species with a probe derived from IS6110 confirmed that IS6110 was specific to... more
Restriction fragment length polymorphism and hybridization of DNA extracted from Mycobacterium tuberculosis, nontuberculous mycobacteria, and nonmycobacterial species with a probe derived from IS6110 confirmed that IS6110 was specific to M. tuberculosis complex. In addition, DNA amplification with IS6110-specific primers yielded a 181-bp fragment only in DNA from M. tuberculosis complex isolates.
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Twenty-two of the 42 administrative districts in Kenya. To determine the prevalence of drug resistance in newly diagnosed patients with pulmonary tuberculosis, to determine possible risk factors associated with resistance, and to... more
Twenty-two of the 42 administrative districts in Kenya. To determine the prevalence of drug resistance in newly diagnosed patients with pulmonary tuberculosis, to determine possible risk factors associated with resistance, and to establish standard routine surveillance of drug resistance. Cross-sectional study. Sputum samples from newly diagnosed patients with smear-positive pulmonary tuberculosis were analysed using standard procedures. Of 638 patients, 85% were culture positive for Mycobacterium tuberculosis. Of 491 patients tested for susceptibility to isoniazid, streptomycin, rifampicin and ethambutol, 90.8% had fully sensitive strains and 9.2% had a strain resistant to one or more drugs. Of 445 patients with no history of previous chemotherapy, 6.3% had a resistant strain. Of 46 patients with a history of previous chemotherapy, 37% had a resistant strain. No resistance to either rifampicin or ethambutol was detected. There was a strong association between previous chemotherapy ...
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Bacillus Calmette Guerin (BCG) vaccination is essential in the control of tuberculosis (TB) especially in countries like Kenya where TB is still a public health problem and BCG is given to all children at birth as a matter of policy. The... more
Bacillus Calmette Guerin (BCG) vaccination is essential in the control of tuberculosis (TB) especially in countries like Kenya where TB is still a public health problem and BCG is given to all children at birth as a matter of policy. The present survey was launched in 1986 to assess both BCG vaccination coverage and to compare its findings with the 1979/81 BCG scar survey results. Using random cluster sampling procedures, all primary school children aged 6-13 years from schools in each of 12 districts were included in the survey. A total of 46357 school children were registered. Of these, 3642 (7.9%) were excluded from the survey for a variety of reasons. Of the remaining 42715 (92.1%) children, 26781 (62.7%) had BCG scars present. Overall there was a significant upward trend of 15% in BCG vaccination coverage in the country. However, in some districts the coverage was found to have fallen quite significantly.
Research Interests: Kenya, Adolescent, Linear models, Schools, Humans, and 6 moreChild, Female, Male, Cluster Analysis, Health surveys, and BCG vaccine
Few tuberculosis studies carried out in Kenya since 1948 have reported on the variations of the occurrence and geographical distributions of non-tuberculous Mycobacteria infection. They have however not been able to clearly relate... more
Few tuberculosis studies carried out in Kenya since 1948 have reported on the variations of the occurrence and geographical distributions of non-tuberculous Mycobacteria infection. They have however not been able to clearly relate infection outcome to the use of tuberculin tests as epidemiologic and clinical tool. The present survey, conducted by Kenya Medical Research Institute in collaboration with the International Union Against Tuberculosis and Lung Diseases between 1986 and 1990 among school children aged 6-13 years in 18 randomly selected districts, investigated the following: the prevalence of sensitivity to tuberculin PPD RT 23 and PPD scrofulaceum RS 95 sensitin; geographic distribution of the reactions from the tests and; the influence of non-tuberculous Mycobacteria on the tuberculin results. The WHO cluster sampling procedures were used to select 30 schools in each of the 18 districts. Each child was tested with an intradermal dose of 2 TU of PPD RT 23 with Tween 80 (PPD...
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Tuberculosis (TB) suspects from Rhodes Chest Clinic, Nairobi, Kenya, were subjected to three sputum smear microscopy (Ziehl-Neelsen) examinations and a chest X-ray (CXR). Results were compared with Löwenstein- Jensen culture as the gold... more
Tuberculosis (TB) suspects from Rhodes Chest Clinic, Nairobi, Kenya, were subjected to three sputum smear microscopy (Ziehl-Neelsen) examinations and a chest X-ray (CXR). Results were compared with Löwenstein- Jensen culture as the gold standard to establish the effi- ciency of the routine diagnostic process. All laboratory tests and the CXR were available for 993 (71%) of the 1398 enrolled suspects.
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The early bactericidal activities (EBAs) of 300 mg isoniazid, 18.5 mg isoniazid, 600 mg rifampicin and 800 mg ofloxacin given daily to 262 patients with newly diagnosed pulmonary tuberculosis in Cape Town, Nairobi, Madras and Hong Kong... more
The early bactericidal activities (EBAs) of 300 mg isoniazid, 18.5 mg isoniazid, 600 mg rifampicin and 800 mg ofloxacin given daily to 262 patients with newly diagnosed pulmonary tuberculosis in Cape Town, Nairobi, Madras and Hong Kong were measured by counting cfu and total acid-fast bacilli in sputum collections taken pre-treatment (S1), at 2 days (S3) and at 5 days (S6). In Cape Town, Nairobi and Madras, the cfu findings suggested that isoniazid produced a massive kill, perhaps of actively growing organisms, during the first 2 days (mean S1-S3 EBAs of 0.636-1.006) but was almost inactive thereafter (mean S3-S6 EBAs of 0.000-0.081), whereas rifampicin maintained moderate activity against slowly growing organisms throughout the 5 days (mean S3-S6 EBAs of 0.242-0.305). This finding suggests that EBAs measured during the 2-5 day interval might be able to assess the sterilizing activity of drugs. Ofloxacin had moderately high mean S1-S3 EBAs of 0.130-0.391. However, in Hong Kong rifampicin appeared to be the most bactericidal drug from the start, possibly because patients had more chronic disease. A method of adjusting the cfu EBAs using total counts was devised which decreased the variability between patients within a treatment group without altering the mean cfu EBA. This resulted in a large gain in precision in Hong Kong, suggesting that their estimates were greatly affected by type II variation, due to dilution of pus by saliva and bronchial secretions, whereas small or no gains were obtained in the other three centres, suggesting that the main cause of variability was type I, due to other factors.
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This study was undertaken to describe treatment outcomes in patients started on a re-treatment drug regimen, assess the quality of follow up procedures and the adequacy of the currently advocated re-treatment drug regimen in Nairobi,... more
This study was undertaken to describe treatment outcomes in patients started on a re-treatment drug regimen, assess the quality of follow up procedures and the adequacy of the currently advocated re-treatment drug regimen in Nairobi, Kenya. A retrospective study. Mbagathi District Hospital (MDH), Nairobi, a public hospital that serves as the Tuberculosis (Tb) referral centre for Nairobi. The Tb register at the MDH was used to identify patients who were on the re-treatment regimen for Tb. Case records for these patients were then retrieved. From these sources, information on age, sex, HIV status, previous and current tuberculosis disease and drug regimens, adherence to treatment and treatment outcomes, was obtained. Descriptive statistics was used to analyse the data. Of the total of 4702 patients registered at the MDH between 1996 and 1997, 593 (12.6%) were patients with either recurrent Tb, returning to treatment after default or had failed initial treatment. Of the 593 patients, case records were unavailable for 168 and 17 were children below the age of ten in whom the diagnosis of Tb was uncertain making a total of 185 patients who were excluded from the study. Of the remaining 408 patients, 77 (18.9%) were cured, 61 (15.0%) completed treatment without confirmation of cure, two (0.5%) defaulted, six (1.5%) died and 262 (64.2%) had no outcome information. There were no treatment failures. Treatment success defined as cure or treatment completion was achieved in 94.5% of the 146 patients in whom outcome data were available. HIV positive patients had a statistically significant poorer success rate (34/40, 85%) when compared with HIV negative patients (104/106, 94%), p=0.004. Mycobacterium tuberculosis culture and drug susceptibility testing, was not done. The high number of patients with no treatment outcome information at the MDH is worrying, as these patients may harbour drug resistant bacilli and reflects an inadequate follow up service for Tb re-treatment in Nairobi. However, where treatment outcomes could be assessed, the currently advocated re-treatment regimen achieved a high success rate. These observations point to an urgent need to improve Tb documentation and follow up procedures within the public service in Nairobi in order to forestall the emergence and spread of drug resistant Tb.
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Urban clinic, Nairobi. To evaluate the impact of specimen quality and different smear-positive tuberculosis (TB) case (SPC) definitions on SPC detection by sex. Prospective study among TB suspects. A total of 695 patients were recruited:... more
Urban clinic, Nairobi. To evaluate the impact of specimen quality and different smear-positive tuberculosis (TB) case (SPC) definitions on SPC detection by sex. Prospective study among TB suspects. A total of 695 patients were recruited: 644 produced > or =1 specimen for microscopy. The male/female sex ratio was 0.8. There were no significant differences in numbers of men and women submitting three specimens (274/314 vs. 339/380, P = 0.43). Significantly more men than women produced a set of three 'good' quality specimens (175/274 vs. 182/339, P = 0.01). Lowering thresholds for definitions to include scanty smears resulted in increases in SPC detection in both sexes; the increase was significantly higher for women. The revised World Health Organization (WHO) case definition was associated with the highest detection rates in women. When analysis was restricted only to patients submitting 'good' quality specimen sets, the difference in detection between sexes was on...
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To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. Patients with cough > or=2 weeks, two sputum smear-negative results, no... more
To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. Patients with cough > or=2 weeks, two sputum smear-negative results, no response to 1 week of amoxicillin and abnormal chest X-ray were defined as smear-negative suspects. One sputum sample was collected, decontaminated and divided into two: half was tested with FASTPlaqueTB in the clinic laboratory and the other half was cultured on Löwenstein-Jensen medium in the Kenyan Medical Research Institute. Test sensitivity and specificity were evaluated in all patients and in human immunodeficiency virus (HIV) infected patients. Feasibility was assessed by the contamination rate and the resources required to upgrade the laboratory. Of 208 patients included in the study, 56.2% were HIV-infected. Of 203 FASTPlaqueTB tests, 95 (46.8%) were contaminated, which interfered with result interpretation and led to the interruption of the study...
Research Interests: Global Health, Tropical Medicine, Developing Countries, Tuberculosis and Infectious Disease, Kenya, and 19 moreProspective studies, Tuberculosis, Humans, Mycobacterium tuberculosis, Female, Feasibility Studies, Male, Neglected tropical diseases, Middle Aged, Anti-Bacterial Agents, Observer Variation, Adult, Amoxicillin, Reproducibility of Results, Sputum, Sensitivity and Specificity, Pulmonary Tuberculosis, Cough, and Predictive value of tests
A major out-patient tuberculosis clinic in Nairobi, Kenya. To ascertain the cost-effectiveness of the polymerase chain reaction (PCR) for the diagnosis of tuberculosis in an urban setting in a developing country. A cost-effectiveness... more
A major out-patient tuberculosis clinic in Nairobi, Kenya. To ascertain the cost-effectiveness of the polymerase chain reaction (PCR) for the diagnosis of tuberculosis in an urban setting in a developing country. A cost-effectiveness analysis of PCR and direct smear microscopy examination based on theoretical modelling. The cost-effectiveness was expressed in costs per correctly diagnosed tuberculosis patient for each of the two diagnostic techniques. Data were obtained from the literature, from the staff and the register at the health facility and from structured interviews with patients. Assumptions were made when no data were available. The PCR is expected to be more specific and sensitive than the routine procedure for diagnosis, but it is also more costly. The routine procedure based on direct smear microscopy turned out to be 1.8 times as cost-effective as PCR. It is concluded that the PCR method can potentially be a cost-effective screening procedure for tuberculosis, provide...
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Bleach sedimentation is a method used to increase the diagnostic yield of sputum microscopy for countries with a high prevalence of human immunodeficiency virus (HIV) infection and limited resources. To compare the relative... more
Bleach sedimentation is a method used to increase the diagnostic yield of sputum microscopy for countries with a high prevalence of human immunodeficiency virus (HIV) infection and limited resources. To compare the relative cost-effectiveness of different microscopy approaches in diagnosing tuberculosis (TB) in Kenya. An analytical decision tree model including cost and effectiveness measures of 10 combinations of direct (D) and overnight bleach (B) sedimentation microscopy was constructed. Data were drawn from the evaluation of the bleach sedimentation method on two specimens (first on the spot [1] and second morning [2]) from 644 TB suspects in a peripheral health clinic. Incremental cost per smear-positive detected case was measured. Costs included human resources and materials using a micro-costing evaluation. All bleach-based microscopy approaches detected significantly more cases (between 23.3% for B1 and 25.9% for B1+B2) than the conventional D1+D2 approach (21.0%). Cost per ...
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To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. Patients with cough > or=2 weeks, two sputum smear-negative results, no... more
To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. Patients with cough > or=2 weeks, two sputum smear-negative results, no response to 1 week of amoxicillin and abnormal chest X-ray were defined as smear-negative suspects. One sputum sample was collected, decontaminated and divided into two: half was tested with FASTPlaqueTB in the clinic laboratory and the other half was cultured on Löwenstein-Jensen medium in the Kenyan Medical Research Institute. Test sensitivity and specificity were evaluated in all patients and in human immunodeficiency virus (HIV) infected patients. Feasibility was assessed by the contamination rate and the resources required to upgrade the laboratory. Of 208 patients included in the study, 56.2% were HIV-infected. Of 203 FASTPlaqueTB tests, 95 (46.8%) were contaminated, which interfered with result interpretation and led to the interruption of the study...
Research Interests: Global Health, Tropical Medicine, Developing Countries, Tuberculosis and Infectious Disease, Kenya, and 19 moreProspective studies, Tuberculosis, Humans, Mycobacterium tuberculosis, Female, Feasibility Studies, Male, Neglected tropical diseases, Middle Aged, Anti-Bacterial Agents, Observer Variation, Adult, Amoxicillin, Reproducibility of Results, Sputum, Sensitivity and Specificity, Pulmonary Tuberculosis, Cough, and Predictive value of tests
Urban health clinic, Nairobi. To evaluate the impact on tuberculosis (TB) case detection and laboratory workload of reducing the number of sputum smears examined and thresholds for diagnosing positive smears and positive cases. In this... more
Urban health clinic, Nairobi. To evaluate the impact on tuberculosis (TB) case detection and laboratory workload of reducing the number of sputum smears examined and thresholds for diagnosing positive smears and positive cases. In this prospective study, three Ziehl-Neelsen stained sputum smears from consecutive pulmonary TB suspects were examined blind. The standard approach (A), > or = 2 positive smears out of 3, using a cut-off of 10 acid-fast bacilli (AFB)/100 high-power fields (HPF), was compared with approaches B, > or = 2 positive smears (> or = 4 AFB/100 HPF) out of 3, one of which is > or = 10 AFB/100 HPF; C, > or = 2 positive smears (> or = 4 AFB/100 HPF) out of 3; D, > or = 1 positive smear (> or = 10 AFB/100 HPF) out of 2; and E, > or = 1 positive smear (> or = 4 AFB/100 HPF) out of 2. The microscopy gold standard was detection of at least one positive smear (> or = 4 AFB/100 HPF) out of 3. Among 644 TB suspects, the alternative approache...
Research Interests: Microscopy, Global Health, Tropical Medicine, Kenya, Urban Health, and 17 moreTuberculosis, Humans, Mycobacterium tuberculosis, Female, Male, Neglected tropical diseases, Workload, Gold Standard, Adult, Reproducibility of Results, Urban Population, Sputum, Pulmonary Tuberculosis, Prospective Study, Predictive value of tests, Acid-fast bacilli, and Ziehl-Neelsen
Kibera, the largest slum in Nairobi, Kenya. To determine the tuberculosis (TB) knowledge, attitude and practices (KAP) of private health care providers (PHCPs) to identify their training needs and willingness to participate in a National... more
Kibera, the largest slum in Nairobi, Kenya. To determine the tuberculosis (TB) knowledge, attitude and practices (KAP) of private health care providers (PHCPs) to identify their training needs and willingness to participate in a National Leprosy and Tuberculosis Control Programme (NLTP) guided TB control effort in the slum. A cross-sectional survey. The KAP of PHCPs was assessed using an interviewer administered questionnaire. Of 75 PHCPs interviewed, the majority (96.0%) were paramedics; 51 (77.1%) did not consider sputum smear microscopy crucial in patients presenting with prolonged cough or when a chest X-ray was suggestive of TB; of 29 (38.7%) who indicated familiarity with the drugs used in TB treatment, 20 (58.5%) would have chosen the NLTP-recommended regimens for the treatment of the various types of TB; 16 (21.3%) PHCPs indicated that they treated TB, six (37.5%) of whom were not familiar with anti-tuberculosis drug regimens. All the PHCPs referred TB suspects to the public...
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Nairobi City Council Chest Clinic, Kenya. To establish the efficiency, costs and cost-effectiveness of six diagnostic strategies using Ziehl-Neelsen (ZN) and fluorescence microscopy (FM). A cross-sectional study of 1398 TB suspects... more
Nairobi City Council Chest Clinic, Kenya. To establish the efficiency, costs and cost-effectiveness of six diagnostic strategies using Ziehl-Neelsen (ZN) and fluorescence microscopy (FM). A cross-sectional study of 1398 TB suspects attending a specialised chest clinic in Nairobi subjected to three sputum examinations by ZN and FM. Lowenstein-Jensen culture was used as the gold standard. Cost analysis included health service and patient costs. Of 1398 suspects enrolled, 993 (71%) had a complete diagnostic work-up involving three sputum specimens for ZN and FM, culture and chest X-ray (CXR). Irrespective of whether ZN or FM was used on one, two or three smears, the overall diagnostic process detected 92% culture-positive cases. Different strategies affected the ratio of smear-positive to smear-negative TB; however, FM was more sensitive than ZN (P < 0.001). FM performance was not affected by the patient's HIV status. The cost per correctly diagnosed smear-positive case, includi...
Research Interests: Poverty, Fluorescence Microscopy, Developing Countries, Kenya, Adolescent, and 17 moreProbability, Tuberculosis, Humans, Mycobacterium tuberculosis, Human Resources for Health, Female, Male, Confidence intervals, Aged, Middle Aged, Adult, Cost Benefit Analysis, Urban Population, Sensitivity and Specificity, Pulmonary Tuberculosis, Cross Sectional Studies, and Logistic Models
Tuberculosis (TB) suspects from Rhodes Chest Clinic, Nairobi, Kenya, were subjected to three sputum smear microscopy (Ziehl-Neelsen) examinations and a chest X-ray (CXR). Results were compared with Löwenstein-Jensen culture as the gold... more
Tuberculosis (TB) suspects from Rhodes Chest Clinic, Nairobi, Kenya, were subjected to three sputum smear microscopy (Ziehl-Neelsen) examinations and a chest X-ray (CXR). Results were compared with Löwenstein-Jensen culture as the gold standard to establish the efficiency of the routine diagnostic process. All laboratory tests and the CXR were available for 993 (71%) of the 1,398 enrolled suspects. Of these, 554 (56%) were culture-positive. The routine diagnostic process was very sensitive, able to detect 92% of culture-positive cases but missing 8%. The specificity was low (66%), and 23% of the patients started on treatment were culture-negative, mainly due to the low specificity of the CXR. It may be possible to increase the efficiency of the diagnostic process by specifying better criteria for CXR examination, improving the quality of CXR reading and counselling patients to return when complaints persist.
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A major out-patient tuberculosis clinic in Nairobi, Kenya. To ascertain the cost-effectiveness of the polymerase chain reaction (PCR) for the diagnosis of tuberculosis in an urban setting in a developing country. A cost-effectiveness... more
A major out-patient tuberculosis clinic in Nairobi, Kenya. To ascertain the cost-effectiveness of the polymerase chain reaction (PCR) for the diagnosis of tuberculosis in an urban setting in a developing country. A cost-effectiveness analysis of PCR and direct smear microscopy examination based on theoretical modelling. The cost-effectiveness was expressed in costs per correctly diagnosed tuberculosis patient for each of the two diagnostic techniques. Data were obtained from the literature, from the staff and the register at the health facility and from structured interviews with patients. Assumptions were made when no data were available. The PCR is expected to be more specific and sensitive than the routine procedure for diagnosis, but it is also more costly. The routine procedure based on direct smear microscopy turned out to be 1.8 times as cost-effective as PCR. It is concluded that the PCR method can potentially be a cost-effective screening procedure for tuberculosis, provide...
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Pulmonary tuberculosis (PTB) is the most common presentation of tuberculosis (TB) in Kenya. For the diagnosis of PTB the sputum smear is used because it is technically simple, non-invasive and cheap. The reliability of direct smear... more
Pulmonary tuberculosis (PTB) is the most common presentation of tuberculosis (TB) in Kenya. For the diagnosis of PTB the sputum smear is used because it is technically simple, non-invasive and cheap. The reliability of direct smear examination for the diagnosis of TB has however frequently been questioned. To address this problem, a study comparing the reliability of fluorescence microscopy (FM) and Ziehl-Neelsen (ZN) staining method for examination of direct smear in the diagnosis of PTB was carried out at the Respiratory Disease Research Unit Laboratory, Nairobi, Kenya. A total of 1480 sputum specimens collected from patients with suspected PTB were analyzed. Two direct smears were prepared from each specimen, one stained using FM and the other using the ZN method. Culture results were used as the gold standard for assessment. Specificity was 97% and 96% for FM and ZN methods, respectively. The sensitivity of the FM method was 80% and that of the ZN method 65% (p < 0.001). Over...
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Our experience at the Respiratory Diseases Research Unit (RDRU), over the last 10 years (1981-1990) on the initial drug resistance pattern, focusing on three drugs viz: isoniazid (H), streptomycin (S) and rifampicin (R) is presented.... more
Our experience at the Respiratory Diseases Research Unit (RDRU), over the last 10 years (1981-1990) on the initial drug resistance pattern, focusing on three drugs viz: isoniazid (H), streptomycin (S) and rifampicin (R) is presented. Records on all isolates of M. tuberculosis from one specimen of every newly diagnosed patient recruited countrywide between 1981-1990 were reviewed. We analyzed records of 6,514 isolates and found that total resistance to the three drugs had increased from 8.9% to 14.4%. Resistance to H alone increased from 6.8% to 10.2% while that of S alone from 0.8% to 1.8%. Resistance to R was between 0.1% and 0.3%. Generally, the increase in the resistance trend to both H and S was statistically significant (p = < 0.05 and 0.03, respectively). Although in our analysis we did not address the possible impact of HIV infection, we hope that these findings form a basis for evaluation of this and other possible factors on the emergence of anti-TB drug resistance in fu...
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Research Interests: Global Health, Fluorescence Microscopy, Tropical Medicine, Urban Health, Multidisciplinary, and 16 moreProspective studies, Tuberculosis, Humans, Health Services, Female, Male, Neglected tropical diseases, Young Adult, PLoS one, Middle Aged, Sodium Hypochlorite, Adult, Room Temperature, Prospective Study, Ziehl-Neelsen, and Light Emitting Diode
... Farzana Rana; Mark P. Hawken; Helen K. Meme; Jeremiah M. Chakaya; Willie A. Githui; Joseph A. Odhiambo; John DH Porter; Keith PWJ McAdam; §Sebastian J. Lucas. * Department of Human Pathology; Kenyatta National Hospital. ...
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A group of 122 patients with culture-proven pulmonary tuberculosis were recruited to examine the concentrations of Mycobacterium tuberculosis in sputum and the relationship to HIV-1 antibody status. They were followed for up to 28 days... more
A group of 122 patients with culture-proven pulmonary tuberculosis were recruited to examine the concentrations of Mycobacterium tuberculosis in sputum and the relationship to HIV-1 antibody status. They were followed for up to 28 days from the start of antituberculous chemotherapy to assess the early bacillary response to two chemotherapeutic regimens. Of 67 treated with streptomycin, thiacetazone, and isoniazid 17 were HIV positive, and subsequently 55, of whom 20 were HIV positive, were treated with streptomycin, rifampin, isoniazid, and pyrazinamide. The mean initial concentration of M. tuberculosis in the sputum of the HIV-negative patients was significantly higher than in HIV-positive patients (6.95 and 6.34 log colony-forming units respectively; p = 0.019). The HIV-positive patients had less radiologic evidence of disease and significantly fewer zones of lung affected with cavities. The response to treatment was similar, but with HIV-positive patients more likely to become culture negative by 28 days. The differences that exist between HIV-positive and HIV-negative patients are minor, and standard regimens are at least as effective in HIV-positive patients in the first month of treatment.
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Retrospective studies suggest that the mortality rate from HIV-1-associated tuberculosis is greater than that from tuberculosis alone, but it is not clear if this is due to failure of antituberculosis treatment or to the complications of... more
Retrospective studies suggest that the mortality rate from HIV-1-associated tuberculosis is greater than that from tuberculosis alone, but it is not clear if this is due to failure of antituberculosis treatment or to the complications of HIV-1 infection. We have carried out a prospective cohort study of patients with tuberculosis in Nairobi, Kenya, to compare mortality rates, risk factors, and causes of death in HIV-1 positive and HIV-1 negative patients. One hundred seven HIV-1 positive and 174 HIV-1 negative patients with tuberculosis attending two tuberculosis treatment centers in Nairobi were enrolled and followed monthly. Mortality was significantly higher in HIV-1 positive than in HIV-1 negative patients within 6 months of the start of antituberculosis treatment after adjustment for age, sex, and education (rate ratio = 3.8; 95% confidence interval, 1.7 to 8.1; p less than 0.001). Most of the excess mortality occurred after the first month of treatment and was due to nontuberculous infections. Predictors for mortality differed greatly between HIV-1 positive and HIV-1 negative patients. Mortality was greater in HIV-1 positive patients treated with a &quot;standard&quot; regimen for tuberculosis than in HIV-1 positive patients receiving a &quot;short-course&quot; regimen (p = 0.08 when adjusted for all independent risk factors). Tuberculosis control programs in developing countries need to implement &quot;short-course&quot; regimens and train health workers to recognize and treat nontuberculous infections to maintain their effectiveness in the face of the HIV epidemic.
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... W. Githui * , P. Nunn Corresponding Author Contact Information , * , † , E. Juma * , F. Karimi * , R. Brindle * , ‡ , R. Kamunyi ** , S. Gathua § , C. Gicheha * , J. Morris † and M. Omwega *. † London School of Hygiene and Tropical... more
... W. Githui * , P. Nunn Corresponding Author Contact Information , * , † , E. Juma * , F. Karimi * , R. Brindle * , ‡ , R. Kamunyi ** , S. Gathua § , C. Gicheha * , J. Morris † and M. Omwega *. † London School of Hygiene and Tropical Medicine, London, UK. ...
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Research Interests: Algorithms, Global Health, Fluorescence Microscopy, Tropical Medicine, Kenya, and 24 moreAdolescent, Urban Health, Multidisciplinary, Tuberculosis, Humans, Mycobacterium tuberculosis, Female, Feasibility Studies, Male, Semiconductor Lasers, Resource Limitation, Neglected tropical diseases, Light, Young Adult, Efficiency, PLoS one, Middle Aged, Adult, Ease of Use, Sputum, Sensitivity and Specificity, Prospective Study, Ziehl-Neelsen, and Light Emitting Diode
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Research Interests: HIV, Clinical Microbiology, Biological Sciences, Tuberculosis, Humans, and 17 moreMycobacterium tuberculosis, Developing Country, Clinical, Polymerase Chain Reaction, Netherlands, Cost effectiveness, Prevalence, Gold Standard, Human immunodeficiency virus, Reproducibility of Results, Low Income Countries, Sputum, Lowenstein Jensen, Sensitivity and Specificity, High Sensitivity, Ziehl-Neelsen, and Chest X-ray
ABSTRACT Background: Increasing development of tuberculosis (TB) resistance to the currently available drugs including second-line anti-TB drugs that are being used for treatment of Multi-Drug Resistant TB (MDR-TB) patients has frustrated... more
ABSTRACT Background: Increasing development of tuberculosis (TB) resistance to the currently available drugs including second-line anti-TB drugs that are being used for treatment of Multi-Drug Resistant TB (MDR-TB) patients has frustrated efforts to control TB worldwide. Ethionamide (Eth) is one of the drugs used in the regimen for treatment of these patients. Objective: To determine level of Ethionamide resistance among second-line anti-tuberculosis drugs in Mycobacterium tuberculosis (MTB) strains isolated in Kenya. Design: A retrospective lab-based study involving archived strains from previous studies carried out at the Centre for Respiratory Diseases Research (CRDR), Kenya Medical Research Institute (KEMRI) from 2002 to 2007. Setting: Centre for Respiratory Diseases Research (CRDR), Kenya Medical Research Institute (KEMRI). Methods: A total of 216 MTB strains with pre-determined first-line drug susceptibility testing (DST) results were used including 78 first-line resistant to individual and combined drugs, and 138 susceptible to streptomycin, rifampicin, isoniazid and ethambutol. The strains were subjected to DST to ethionamide among other second-line. Results: Thirty two [32/216 (14.8%)] strains showed resistance to second-line drugs. Resistance to Eth was the highest [18/32 (56.3%)] including co-resistance with isoniazid [8/18 (44.4%)]. Nine [9/18 (50%)] strains were fully resistant and 9 [9/18 (50%)] were intermediate resistant to Eth. Conclusion: Unexplainable high levels of Eth resistance is a cause for concern. This will impact negatively on the outcome of management of MDR-TB especially in Kenya where the use of this drug is almost mandatory. Close monitoring of Eth before initiating individual patient management may be necessary. Key words: Ethionamide, Resistant, MDR-TB.
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Research Interests:
Research Interests:
Measurements and Main Results: Of 640 study patients, 116 (18%) had fluoroquinolone exposure in the 12 months before diagnosis, and 16 (2.5%; 95% confidence interval [CI], 1.4–4.0%) M. tuberculosis isolates were fluoroquinolone resistant.... more
Measurements and Main Results: Of 640 study patients, 116 (18%) had fluoroquinolone exposure in the 12 months before diagnosis, and 16 (2.5%; 95% confidence interval [CI], 1.4–4.0%) M. tuberculosis isolates were fluoroquinolone resistant. Among the 54 patients with more ...
Research Interests:
To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults. Randomized,... more
To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults. Randomized, double-blind, placebo-controlled trial in Nairobi, Kenya. Six hundred and eighty-four HIV-1-infected adults. Development of tuberculosis and death. Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median CD4 lymphocyte counts at enrolment were 322 and 346 x 10(6)/l in the isoniazid and placebo groups, respectively. The overall median follow-up from enrolment was 1.83 years (range, 0-3.4 years). The incidence of tuberculosis in the isoniazid group was 4.29 per 100 person-years (PY) of observation [95% confidence interval (CI) 2.78-6.33] and 3.86 per 100 PY of observation (95% CI, 2.45-5.79) in the placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92 (95% CI, 0.49-1.71). The adjusted rate ratio for tuberculosis for isoniazid versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI, 0.23-1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55-2.76). The overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95% CI, 0.79-1.75). Stratifying by TST reactivity gave an adjusted mortality rate ratio in those who were TST-positive of 0.33 (95% CI, 0.09-1.23) and for TST-negative subjects, 1.39 (95% CI, 0.90-2.12). Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.