First national survey of Mycobacterium tuberculosis drug resistance, Madagascar, 2005-2006.

SETTING: A national survey of Mycobacterium tuberculosis resistance was conducted for the first time in Madagascar between October 2005 and July 2007. OBJECTIVE: To determine resistance rates among new and previously treated cases of pulmonary tuberculosis. METHODS: In a cluster sampling representative of the general population of the country, 1275 smear-positive tuberculosis patients recruited at 34 sites, 926 new patients and 87 previously treated patients underwent drug susceptibility testing against rifampicin (RMP), isoniazid (INH), streptomycin and ethambutol on Löwenstein-Jensen medium using the indirect proportion method. RESULTS: Resistance among new cases was 6.5% (95%CI 4.9-8) and among previously treated cases it was 11.5% (95%CI 4.8-18.2). Monoresistance among new cases was 5.8% (95%CI 4.2-7.3), mainly to INH (3.7%). Multiresistance to INH and RMP was 0.2% (95%CI 0-0.5) among new cases and 3.4% (95%CI 0-7.2) among previously treated cases. No significant difference was noted with regard to sex or age. CONCLUSION: The rates of resistance among new and previously treated cases remain relatively low in Madagascar.

[Mycobacterium tuberculosis resistance to antitubercular agents in Antananarivo in 2000]. / Résistance de Mycobacterium tuberculosis aux antituberculeux à Antananarivo en 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.

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.

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.

[Tuberculosis in the province of Mahajanga]. / La tuberculose dans la province de Mahajanga.

Comparative study of compulsory declarations registered at the provincial level and at the central level between January 1st 1993 and 31st December 1994 showed a high prevalence of tuberculosis in the province of Mahajanga and an under-declaration of cases at the provincial level was almost 25% with regard to data collected at the central level. Smear-positive pulmonary tuberculosis patients were the most frequent (86%), which showed respect towards the National Control Programme instructions. Extrapulmonary tuberculosis were under-estimated (less than 10%) because of the weak diagnosis means. Smear-positive pulmonary tuberculosis under treatment in the city of Mahajanga were cured globally at 80%. The difference between the centres diminished between 1992 and 1993, then it persisted requiring the improvement of tubercular management conditions within the province structures and most particularly within the city of Mahajanga structures which are at the present taking charge of more than 50% of the province tubercular.

[The National Tuberculosis Control Program in Madagascar]. / Le Programme National de Lutte Antituberculeuse (PNLAT) à 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.

[Genetic polymorphism of M. tuberculosis strains in Antananaviro]. / Polymorphisme génetique des souches du complexe M. tuberculosis à Antananarivo.

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.

[Comparison of routine therapeutic protocols used in Madagascar for the treatment of smear-positive pulmonary tuberculosis (preliminary results)]. / Comparison de protocoles thérapeutiques utilisés en routine á Madagascar dans le traitement des tuberculoses pulmonaires á microscopie positive (Résultats préliminaires).

A survey was undertaken in April 1993 to compare the respective benefits of 2 regimens containing either streptomycin (SHRZ) or ethambutol (EHRZ) in the first two months of treatment of smear-positive pulmonary tuberculosis in Madagascar. This operational research was justified by the risks related to the use of parenteral streptomycin in a country where single use material is rare and its purpose was to provide arguments for an eventual recommendation to replace this drug by oral ethambutol which is also less expensive. 907 patients were included. The compliance was not significantly different between the 2 groups, although it was traditionally assumed to be better with streptomycin. The frequency of side effects was significantly lower with EHRZ. Overall treatment failure rates were not significantly different, but all of 6 patients who were negative at 5 months and were again positive at 8 months had received EHRZ. This point obliged to be careful before concluding, because 24% of patients were lost for follow-up. A 2 years surveillance will be necessary to compare the frequency of recurrences.