474-pa11 defaulting in smear-positive tuberculosis patients in urban area of cairo, egypt

1
Abstracts 83 2HRZ/4HR (8 patients), 2HRZE/4HR (1 patient) and 7 patients received an extended continuation phase: 2HRZS/5 or 6 or 7 or 8 HR. 36 patients (50%) were considered cured, 15 (21%) were defaults, 2 (3%) failures, 3 (4%) died and 16 (22%) were transferred. Treatment was directly observed in 42 patients (58%): 7 in both phases of whom 6 (85%) cured, 35 had DOT only during in the intensive phase (17 cured - 48.5%) and 30 did not have DOT with 13 of them cured (43%). 436-PAll Treatment efficiency of pulmonary tuberculosis in rural patients Tolstikh, A.S. The State Institute for Advanced Medical Studies, Irkoutsk, Russia An annual tuberculosis morbidity in rural area of Easten Siberia during the last 5 years was from 55 to 64 in 100000 people and was 30-35% more than that in the urbans areas. Bacillary and destructive pulmonary tuber- culosis forms were observed in 20-25%, more frequent in rural patients than in urbans. Immunity condition in rural was characterized by low level of T-lymphocytes and phagocytosis. Treatment courses include combinations of isoniazid, rifampicin, pyrazinamide and ethambutol or streptomycin. Nevertheless, the treatment efficiency of tuberculosis in a rural area was insufficient: suspending of M. tubercu- losis excretement registered in 85% of patients, shutting of destruction cavities only in 60% of cases. The treat- ment in hospital has been broken by 30-40% of rural patients. Treatment efficiency in rural patients may be in- creased by the treatment's tactics changing and using immunocorrection. 474-PAll Defaulting in smear-positive tuberculosis patients in urban area of Cairo, Egypt De Coster, E.J.M., Tolba, F.M., E1 Ibiary, S. NTP, Cairo, Egypt Objectives: To identify risk factors for defaulting, to assess reasons given by patients for defaulting, to assess suggestions given by patients to avoid defaulting, and to assess the fate of the defaulters. Method: Case-control study on 287 new smear-positive patients (73 defaulters, failures or died and 214 cured or completed treatment), in 4 chest clinics, Cairo. Analysis of routine data of clinical records and home visits and interviews of patients and their relatives. Findings: No obvious defaulter profile was found. Ac- ceptance of hospitalization for DOT predicts better treat- ment completion (OR: 2.56). However, 22% of patients do not accept hospitalization. Reasons for defaulting given were: loss of income, loss of motivation to con- tinue treatment because of clinical improvement, social stigma, quarrelling with staff, duration of treatment. Suggestions to prevent defaulting were: financial com- pensation for loss of income, home treatment, better information, shorter and more effective treatment regi- mens. One third of the defaulters completed their treat- ment by other means, such as private health care. Conclusions: More attention should be paid to socio- economic factors to prevent defaulting; besides hos- pitalization, alternative ways for DOT should be investigated. TUBERCULOSIS: RESISTANCE TO ANTITUBERCULOSIS DRUGS - BASIC STUDIES 055-PAll Increased production of interleukin-10 by human blood mononuclear cells stimulated with multidrug-resistant Mycobacterium tuberculosis (MDRTB) Fujiwara, H., Aotani, 7"., Tsuyuguchi, I. Osaka Prefectural Habikino Hospital, Osaka, Japan Macrophages produce various cytokines in response to Mycobacterium tuberculosis, including interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-c0. IL-10 has been shown to down-regulate a number of different macrophage functions, including microbicidal activity against intracellular bacteria or parasites. IL-t0 also inhibits both IFN- 7 production and antigen-specific pro- liferation of Thl cells mediating immunologic resistance to mycobacterial infection. In contrast, TNF-~ activates macrophages and may augment mycobactericidal activity. In this study, peripheral blood mononuclear cells (PBMC) obtained from a healthy tuberculin-reactor were stimulated in vitro with multidrug-resistant M. tuberculosis (MDRTB) or drug sensitive M. tuberculosis (DSTB) to produce IL-10 or TNF-c~ and to proliferate. We obtained one mycobacterial strain from each patient, preparing a total of 12 strains of MDRTB and !3 strains of DSTB. MDRTB-stimulated PBMC released a signifi- cantly larger amount of IL-10 than PBMC stimulated with DSTB (MDRTB, 150.1 _+ 30.5 pg/ml; DSTB, 81.8 + 9.2 pg/ml; p < 0.05). However, there was no differ- ence in the ability to induce TNF-c~ production between MDRTB and DSTB (MDRTB, 3986.8 + 845.4 pg/ml; DSTB, 4421.2 _+ 661.4 pg/ml; p = 0.69). Neutralizing anti-IL-10 mAb significantly enhanced the proliferative response of PBMC stimulated with MDRTB or DSTB, indicating that endogenous IL-10 production inhibits PBMC proliferation. Increased production of IL-10 by MDRTB-stimulated PBMC might be a factor in the intractable tuberculosis. 069-PAll Caracttrisation de la cible moltculaire de l'isoniazide chez M. tuberculosis Qudmard, A.*, Dessen, A. §, Sacchettini, J.C.§, Jacobs, W.R.§, Blanchard, J.S.§ *LPTF-CNRS, Toulouse, France; §Albert Einstein College of Medicine, NY, USA La majorit6 des souches de M. tuberculosis multi- rdsistantes sont r6sistantes ~ l'isoniazide (INH), un des

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Abstracts 83

2HRZ/4HR (8 patients), 2HRZE/4HR (1 patient) and 7 patients received an extended continuation phase: 2HRZS/5 or 6 or 7 or 8 HR.

36 patients (50%) were considered cured, 15 (21%) were defaults, 2 (3%) failures, 3 (4%) died and 16 (22%) were transferred. Treatment was directly observed in 42 patients (58%): 7 in both phases of whom 6 (85%) cured, 35 had DOT only during in the intensive phase (17 cured - 48.5%) and 30 did not have DOT with 13 of them cured (43%).

436-PAll Treatment efficiency of pulmonary tuberculosis in rural patients

Tolstikh, A.S. The State Institute for Advanced Medical Studies, Irkoutsk, Russia

An annual tuberculosis morbidity in rural area of Easten Siberia during the last 5 years was from 55 to 64 in 100000 people and was 30-35% more than that in the urbans areas. Bacillary and destructive pulmonary tuber- culosis forms were observed in 20-25%, more frequent in rural patients than in urbans. Immunity condition in rural was characterized by low level of T-lymphocytes and phagocytosis.

Treatment courses include combinations of isoniazid, rifampicin, pyrazinamide and ethambutol or streptomycin. Nevertheless, the treatment efficiency of tuberculosis in a rural area was insufficient: suspending of M. tubercu- losis excretement registered in 85% of patients, shutting of destruction cavities only in 60% of cases. The treat- ment in hospital has been broken by 30-40% of rural patients.

Treatment efficiency in rural patients may be in- creased by the treatment's tactics changing and using immunocorrection.

474-PAll Defaulting in smear-positive tuberculosis patients in urban area of Cairo, Egypt

De Coster, E.J.M., Tolba, F.M., E1 Ibiary, S. NTP, Cairo, Egypt

Objectives: To identify risk factors for defaulting, to assess reasons given by patients for defaulting, to assess suggestions given by patients to avoid defaulting, and to assess the fate of the defaulters.

Method: Case-control study on 287 new smear-positive patients (73 defaulters, failures or died and 214 cured or completed treatment), in 4 chest clinics, Cairo. Analysis of routine data of clinical records and home visits and interviews of patients and their relatives.

Findings: No obvious defaulter profile was found. Ac- ceptance of hospitalization for DOT predicts better treat- ment completion (OR: 2.56). However, 22% of patients do not accept hospitalization. Reasons for defaulting given were: loss of income, loss of motivation to con- tinue treatment because of clinical improvement, social stigma, quarrelling with staff, duration of treatment. Suggestions to prevent defaulting were: financial com- pensation for loss of income, home treatment, better

information, shorter and more effective treatment regi- mens. One third of the defaulters completed their treat- ment by other means, such as private health care.

Conclusions: More attention should be paid to socio- economic factors to prevent defaulting; besides hos- pitalization, alternative ways for DOT should be investigated.

T U B E R C U L O S I S : R E S I S T A N C E T O A N T I T U B E R C U L O S I S D R U G S - B A S I C S T U D I E S

055-PAll Increased production of interleukin-10 by human blood mononuclear cells stimulated with multidrug-resistant Mycobacterium tuberculosis (MDRTB)

Fujiwara, H., Aotani, 7"., Tsuyuguchi, I. Osaka Prefectural Habikino Hospital, Osaka, Japan

Macrophages produce various cytokines in response to Mycobacterium tuberculosis, including interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-c0. IL-10 has been shown to down-regulate a number of different macrophage functions, including microbicidal activity against intracellular bacteria or parasites. IL-t0 also inhibits both IFN- 7 production and antigen-specific pro- liferation of Thl cells mediating immunologic resistance to mycobacterial infection. In contrast, TNF-~ activates macrophages and may augment mycobactericidal activity.

In this study, peripheral blood mononuclear cells (PBMC) obtained from a healthy tuberculin-reactor were stimulated in vitro with multidrug-resistant M. tuberculosis (MDRTB) or drug sensitive M. tuberculosis (DSTB) to produce IL-10 or TNF-c~ and to proliferate. We obtained one mycobacterial strain from each patient, preparing a total of 12 strains of MDRTB and !3 strains of DSTB. MDRTB-stimulated PBMC released a signifi- cantly larger amount of IL-10 than PBMC stimulated with DSTB (MDRTB, 150.1 _+ 30.5 pg/ml; DSTB, 81.8 + 9.2 pg/ml; p < 0.05). However, there was no differ- ence in the ability to induce TNF-c~ production between MDRTB and DSTB (MDRTB, 3986.8 + 845.4 pg/ml; DSTB, 4421.2 _+ 661.4 pg/ml; p = 0.69). Neutralizing anti-IL-10 mAb significantly enhanced the proliferative response of PBMC stimulated with MDRTB or DSTB, indicating that endogenous IL-10 production inhibits PBMC proliferation.

Increased production of IL-10 by MDRTB-stimulated PBMC might be a factor in the intractable tuberculosis.

069-PAll Caracttrisation de la cible moltculaire de l'isoniazide chez M. tuberculosis

Qudmard, A.*, Dessen, A. §, Sacchettini, J.C.§, Jacobs, W.R. §, Blanchard, J.S.§ *LPTF-CNRS, Toulouse, France; §Albert Einstein College of Medicine, NY, USA

La majorit6 des souches de M. tuberculosis multi- rdsistantes sont r6sistantes ~ l'isoniazide (INH), un des