Appropriateness of extending the intensive phase of treatment based on smear results.
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Antitubercular Agents↗
Biomedical subjects
H Ramarokoto
Publications and source records attributed to H Ramarokoto.
[A case of pulmonary multiresistant Mycobacterium bovis tuberculosis in Madagascar].
We report a chronic case of pulmonary tuberculosis in a Malagasy citizen from Antsohihy (West of Madagascar), who was infected with a multi-drug resistant Mycobacterium bovis strain. This is the first case reported of the isolation of such a strain in Madagascar.
Amikacin↗
Bacteriological follow-up of tuberculosis treatment: a comparative study of smear microscopy and culture results at the second month of treatment.
SETTING: Significance of a positive bacillary examination of sputum at 2 months of treatment in relation to the viability of the bacilli and the final treatment result. OBJECTIVE: To compare the results of smear microscopy and sputum culture at the second month of tuberculosis treatment and to follow the progress of the patients. METHODS: Follow-up of 297 patients with smear-positive pulmonary tuberculosis in Madagascar, 152 of whom were smear-positive at 2 months of treatment and 145 smear-negative. The number of bacilli was recorded, as were the culture results and the final outcome of treatment. RESULTS: Among the 152 patients who were smear-positive at the second month, 77 (51%) were culture-negative; there were 12 (8%) treatment failures and four relapses (4.6%). Among the 145 smear-negative patients, 22 (15%) were culture-positive, of which one was a treatment failure (1%). CONCLUSION: The majority of failures and relapses were observed in the group of smear-positive patients. It is important to reinforce the surveillance of these patients in order to reduce the number lost to follow-up. Furthermore, a positive smear microscopy at the end of the second month is not sufficiently specific for early identification of treatment failures. It is preferable to wait until the fifth month, as the great majority of patients who are positive at 2 months achieve cure. The treatment strategy currently recommended in Madagascar is satisfactory.
Antitubercular Agents↗
[Tuberculosis in children less than 11 years old: primary resistance and dominant genetic variants of Mycobacterium tuberculosis in Antananarivo].
Tuberculosis during childhood is often due to Mycobacterium tuberculosis primo-infection. Tuberculosis is highly prevalent in Madagascar and most people are infected during childhood. Our objectives were to evaluate the primary resistance of M. tuberculosis and to determine the genotypes responsible for recent infection in the population. Thus we studied 142 isolated strains from 97 children (66 with pulmonary tuberculosis and 31 with extra-pulmonary tuberculosis) recruited in different health centers in Antananarivo from 1997 to 2000. Excepting one strain resistant to isoniazide, all strains were susceptible to the four antibiotics (streptomycin, isoniazid, ryfampicin and ethambutol). This result confirms the low rate of primary resistance reported during the two surveys in 1994-1995 and 1999-2000. 67 strains of 1997-2000 were typed with the genetic marker IS6110, 44 has been assigned to 13 clusters containing each 2 to 8 similar strains. Some IS6110 clusters have already been reported in 1994-1995. Some genotypes observed in 1994-1995 seemed to have disappeared in 1997-2000. (As the rate of the frequency of some genetic variants according to the period are more likely due to a difference in strain virulence). Since there is minimal antibiotic resistance versus M. tuberculosis in Madagascar, one can not explain the appearance or disappearance of certain variants because of drug resistance. Rather, this is due to the virulence of the various M. tuberculosis strains.
Age Distribution↗
[Mycobacterium tuberculosis resistance to antitubercular agents in Antananarivo in 2000].
In 1991, the National Tuberculosis control Program (NTP) of Madagascar adopted the short treatment course and the Directly Observed Treatment Strategy (DOTS), according to the recommendations of the OMS/UICTMR. Development of M. tuberculosis primary resistance to the four antituberculosis drugs (streptomycin [S], rifampicine [R], isoniazid [H], ethambutol [E]) is an indicator of the NTP efficiency. We report results from a five-year survey among patients with new smear positive pulmonary tuberculosis. Acquired resistance is assessed among recurrent cases. During the first survey, carried out in 1994-1995 in four large cities, multidrug resistance (MDR) rate to the major antituberculosis drug H and R was low, 0.25% for primary MDR and 5% for acquired MDR. No primary MDR was found in Antananarivo; on the other hand, acquired resistance rate was the highest there (22%). Because of logistical reasons, the second survey (1999-2000) was only carried out in the capital, Antananarivo. Results obtained among 789 new patients with smear positive pulmonary tuberculosis and 79 recurrents cases in 9 diagnostic centres showed low primary and acquired resistance of 11.1% to any drug. Primary resistance to one drug was 10.6%, mainly due to streptomycin 8.5%. MDR rates are comparable with those observed in 1994-1995: 0.1% for primary MDR and 4% for acquired MDR. These results show that ten years after the new NTP implementation, only a few MDR strains are circulating in Antananarivo, which suggests that NTP has been effective.
Antibiotics, Antitubercular↗
[Central inter-laboratory quality control for microscopic diagnosis of tuberculosis in Madagascar in 2000].
Since June 1997, a quarterly quality control of sputum smear exam for the tubercle diagnosis, depending on double reading of slides, was implemented between both central laboratories of the Mycobacteria National Reference Centre in Madagascar (mycobactoria laboratories of Institut Pasteur Madagascar [IPM] and Institut Hygiène Sociale [IHS]--Health Ministry). In 2000, four controls were done, in the course of which 240 slides were coloured by auramine, coming both from IPM and IHS, and another 80 slides from IHS were coloured by Ziehl-Neelsen. All the results were in agreement for the samples stained with auramine, while two false negatives were found for the samples stained with Ziehl-Neelsen. The maintenance of this quality control between the two laboratories is necessary to insure the reliability of their results and the controls that they make for the peripheral laboratories.
Bacteriological Techniques↗
A combination of two genetic markers is sufficient for restriction fragment length polymorphism typing of Mycobacterium tuberculosis complex in areas with a high incidence of tuberculosis.
The incidence of tuberculosis (TB) in Madagascar is 150 cases per 100,000 people. Because of this endemicity, we studied the genetic diversity of Mycobacterium tuberculosis strains isolated in four big cities in 1994 to 1995 with the aim of monitoring TB transmission. Isolates from 316 cases of pulmonary TB (PTM(+)) were typed by Southern hybridization with genetic markers IS6110 and DR. Of the 316 PTM(+) strains, 66 (20.8%) had a single IS6110 band and were differentiated by the DR marker into 33 profiles. Using both markers, 37.7% (119) of the patients were clustered, a proportion similar to that in countries with a high prevalence of TB. There was no significant difference between clustered and nonclustered patients in age, sex, Mycobacterium bovis BCG status, and drug susceptibility of strains. Clustering was significantly greater in the capital, Antananarivo, than in the other cities, suggesting a higher rate of transmission. However, most of the patients in clusters were living in different areas, and, within a distance of 0.7 km, we did not find epidemiologically unrelated strains with the same restriction fragment length polymorphism profile. Despite an apparently low polymorphism, genetic markers such as IS6110 are potentially valuable for monitoring TB transmission. However, the high proportion of Malagasy isolates with a single IS6110 copy makes this marker alone unsuitable for typing. Additional markers such as DR are necessary for the differentiation of the isolates and for epidemiological surveys.
Adolescent↗
Predictive values of the ICT Tuberculosis test for the routine diagnosis of tuberculosis in Madagascar.
The rapid commercialised ICT Tuberculosis test has been tested in Madagascar for the diagnosis of smear-positive pulmonary (SM+) and extra-pulmonary tuberculosis (EPT), using microscopy, culture and histopathology as reference tests. Specificity was 83.3% and sensitivity 68.2% for SM+ patients and 65.2% for EPT patients. With a prevalence of 22.2% for SM+ patients and 52.4% for confirmed EPT among consulting patients in the National Reference Laboratory, the ICT Tuberculosis assay was not sufficiently predictive for application in the tuberculosis control programme.
Developing Countries↗
45/47 kilodalton (APA) antigen capture and antibody detection assays for the diagnosis of tuberculosis.
SETTING: APA complex (45/47 kDa) is an antigen specifically excreted by Mycobacterium tuberculosis and could therefore be a good candidate for diagnosis. OBJECTIVES: To develop three APA immunocapture ELISA assays using monoclonal antibodies (Mabs) and one IgG anti-APA ELISA test, and to determine their usefulness for the diagnosis of tuberculosis in Madagascar. DESIGN: For the Ag assays, 23 negative sputum and serum samples and 64 pairs of sputum and serum from active smear-positive patients (PTM+) were tested. For antibody assay, 116 negative controls, 143 PTM+ and 54 extra-pulmonary tuberculosis patients were tested. RESULTS: The sensitivities of the APA antigen detection assays were low (less than 40%) for a specificity of 95.6%, using either monoclonal antibodies or clinical specimens. The anti-APA serology was more sensitive (76.9% for PTM+ patients) but less specific (73.2%). Due to their poor predictive values, these tests cannot be recommended for the routine diagnosis of tuberculosis in Madagascar.
Antibodies, Bacterial↗
[Laboratory network for the microscopic diagnosis of tuberculosis in Madagascar: quality control of slides].
As part of the National Tuberculosis Program (NTP), a quality control of the slides (search of acido-fast bacilli in the sputa) of the Treatment and Diagnosis Centers (TDC) forming the National Laboratory Network is carried out each year. In 1999, 76 TDC out of the 174 (44%) had been controlled using the method of double reading of the smears. The global concordance of the results in the 76 TDC is satisfactory (98%). Reability was 91% for the positive smears and 92% for the negative smears. A good quality of smears was observed in 53% of the centers. The TDC reliable at 100% for both positive and negative smears were 51 (67%) of which 36 (47%) had also a good quality of smears. Those later were mainly found in Toamasina, Fianarantsoa, Antananarivo and Mahajanga.
Bacteriological Techniques↗
Replacement of streptomycin by ethambutol in the intensive phase of tuberculosis treatment: no effect on compliance.
SETTING: Seven tuberculosis clinics in the National Tuberculosis Programme of Madagascar. OBJECTIVE: To compare the treatment efficacy and tolerance of regimens including either streptomycin or ethambutol for patient compliance during initial treatment of smear-positive tuberculosis. DESIGN: The 1023 patients included in the study were randomly divided into two treatment groups-one to receive streptomycin (S), isoniazid (H), rifampicin (R) and pyrazinamide (Z) (SHRZ), and the other to receive EHRZ, where streptomycin was replaced by ethambutol (E). During the 2-month intensive phase, drug delivery was completely supervised. The same 6-month continuation regimen was then given in both groups. Follow-up consisted of a clinical and bacteriological examination at the end of the second, fifth and eighth months. RESULTS: There was no significant difference between the two regimens as regards compliance with treatment, the number of patients lost or who died, or for bacteriological response during the intensive phase. EHRZ was better tolerated. During the continuation phase, the results of the two groups remained comparable, but treatment failures occurred earlier in the patients who had received streptomycin. CONCLUSION: Patient compliance was not better with streptomycin. The ethambutol-containing regimen was as efficient as the other, and better tolerated. There is no argument for preferring streptomycin in the intensive phase of treatment of smear-positive tuberculosis.
Adolescent↗
Prevalence of Mycobacterium bovis in human pulmonary and extra-pulmonary tuberculosis in Madagascar.
The prevalence of human tuberculosis (TB) due to Mycobacterium bovis was determined in Madagascar in 1994-1995. A prevalence of M. bovis of 1.25% was observed among sputum smear-positive patients and 1.3% among extra-pulmonary TB patients. This study was conducted in urban areas and will be extended to rural zones, where the majority of the population lives.
Adolescent↗
Anti-tuberculosis drug resistance in Madagascar in 1994-1995.
SETTING: A new tuberculosis control programme has been implemented in Madagascar since 1991. A survey on Mycobacterium tuberculosis resistance to the major drugs was conducted between August 1994 and December 1995. OBJECTIVE: To determine primary and acquired resistance in pulmonary tuberculosis patients in four main cities. DESIGN: Were included 401 randomly sampled new smear positive patients (36.2% of declared new patients) and 137 recurrent cases (72.9% of declared cases) from 8 centres. Drug susceptibility testing was performed on Löwenstein Jensen medium according to the proportion method. RESULTS: The male to female ratio was 1.35:1 in new patients (age range 11-74 years) and 1.98:1 in recurrent patients (age range 16-76 years). The primary resistance rate to any drug was 20% (95% Confidence Interval [CI] 16-23) and the acquired resistance rate 40% (95% CI 32-48, P < 2.10(-7). Primary resistance to one drug was 18% (95% CI 15-22), mainly attributable to streptomycin resistance (14.5%). Multidrug resistance (MDR) to isoniazid and rifampicin was 0.25% (95% CI 0-0.7) for primary resistance and 5% (95% CI 2.6-10.6) for secondary resistance. No difference was observed between sexes or ages. CONCLUSION: This survey conducted in big cities gives a very negative picture of resistance in Madagascar.
Adolescent↗
[Microscopy laboratories for the diagnosis of tuberculosis in Madagascar: quality control].
As part of the National Tuberculosis Program (NTP), a quality control of the slides (search of acido-fast-bacilli in the sputa) of the Treatment and Diagnosis Centers (TDC) forming the National Laboratory Network was carried out in 1996. 60 TDC of the 165 TDC (36%) had been controlled according to the system of double reading of the smears. The global concordance of the results in the 60 TDC is satisfactory since it was of 94%. Reliability of smears positive was of 83%. For the negative smears reliability, 14% of the TDC had a low or insufficient level. A good quality of smears was observed in 40% of the centers. The TDC that had both positive and negative reliability at 100% were 23 (38%) of which 13 had good quality of smears. Those were especially found in Antananarivo, Toliara, Fianarantsoa and Mahajanga.
Bacteriological Techniques↗
[The National Tuberculosis Control Program in Madagascar].
In 1991, the National Tuberculosis Control Program could start in Madagascar, thanks to the financial support of the French Cooperation. Within 3 years, this allocation of resources allowed the management, respecting the new standards, of 56% of the country's health structures and of more than 75% of the sick. The number of detected and treated patients increased of 80%. During the same period, the recovery rate increased from less than 35% to more than 65%. Those primary results were satisfactory in terms of working but they were not enough in epidemiological terms as the aims were still far: the detection rate of smear-positive pulmonary tuberculosis was 40% whereas it ought be 60%, and their recovery rate was 65% whereas it ought to be over 80%. The geographic extension of the Program and its progress depend on a structural strengthening needing an obvious political will and on the intervention of financial partners cooperating with France and willing to set up a long lasting partnership.
Financial Support↗
[National Laboratory for Mycobacterias. Evolution, missions and activities from 1991 to 1994].
The setting up of a new nationwide tuberculosis control programme allowed the creation of a National Mycobacteria Reference Laboratory. This latter originated from the small bacteriology laboratory of the antitubercular dispensary of the Institut d'Hygiène Sociale (IHS) and its activities increased tenfold within three years. Extension of rooms, a more numerous staff and the acquisition of a modern equipment explained those results. However, to carry out the tasks of such a laboratory a rapid modification of structures and a new job distribution facilitated by a cooperation with the Institut Pasteur de Madagascar are necessary.
Academies and Institutes↗
[Genetic polymorphism of M. tuberculosis strains in Antananaviro].
The genetic polymorphism of the mycobacteria of the tuberculosis complex in the city of Antananarivo was studied on 126 strains isolated from positive microscopy pulmonary tuberculosis patients. The genetic profiles established using the RFLP technic and the IS6110 marker yielded 83 clusters of 1 to 29 strains. There were 34 strains with a IS6110 unique band profile of which 29 had a band located at 1.4-1.5 kb. These strains could be differentiated using a second marker, the DR marker. 3 strains with an unique IS6110 band located at 1.8-1.9 kb were identified as M. bovis. In general, there was no evident epidemiological relationship between the patients presenting with identical profiles. In the prison of Antananarivo, the IS6110 typing of 36 strains yielded 28 clusters of 1 to 3 strains. Excepting 2 clusters showing an internal contamination, the absence of profiles specific to the jail suggests that the patients were probably contaminated before their entrance. This preliminary study shows that the RFLP profiles of M. tuberculosis, using the IS6110 and the DR markers, were polymorphic enough for using this method to study the transmission in Antananarivo.
Cluster Analysis↗