• 10-year assessment of treatment outcome among Cambodian refugees with sputum smear-positive tuberculosis in Khao-I-Dang, Thailand.

      Sukrakanchana-Trikham, P; Puéchal, X; Rigal, J; Rieder, H L; Médecins sans Frontières Tuberculosis Programme, Khao-I-Dang, Prachinburi, Thailand. (International Union Against Tuberculosis and Lung Disease, 1992-12)
      Tuberculosis control among displaced persons is fraught with difficulties to ensure adherence of patients to treatment for a prolonged period of time. In the Khao-I-Dang camp for Cambodian refugees an approach with daily, directly observed treatment throughout the course of 6 months duration was chosen to address the problem. Of a total 929 patients with sputum smear-positive tuberculosis who were enrolled from 1981 to 1990, 5.0% died, 75.5% completed treatment and were bacteriologically cured with a day-to-day adherence of more than 98%, none failed bacteriologically, 19.2% were transferred to another camp where continuation of treatment was guaranteed, and only 0.4% absconded from treatment. These data suggest that the approach to tuberculosis control in this refugee camp was very effective in cutting the chain of transmission of tuberculosis in a highly mobile population and in reducing substantially unnecessary morbidity and mortality.
    • Moderate to severe malnutrition in patients with tuberculosis is a risk factor associated with early death.

      Zachariah, R; Spielmann M P; Harries, A D; Salaniponi, F M L; Médecins Sans Frontières-Luxembourg, Thyolo District, Malawi. zachariah@internet.lu (Elsevier, 2008-02-07)
      A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi to determine (i) the prevalence of malnutrition on admission and (ii) the association between malnutrition and early mortality (defined as death within the first 4 weeks of treatment). There were 1181 patients with TB (576 men and 605 women), whose overall rate of infection with human immunodeficiency virus (HIV) was 80%. 673 TB patients (57%) were malnourished on admission (body mass index [BMI] < 18.5 kg/m2). There were 259 patients (22%) with mild malnutrition (BMI 17.0-18.4 kg/m2), 168 (14%) with moderate malnutrition (BMI 16.0-16.9 kg/m2) and 246 (21%) with severe malnutrition (BMI < 15.9 kg/m2). 95 patients (8%) died during the first 4 weeks. Significant risk factors for early mortality included increasing degrees of malnutrition, age > 35 years, and HIV seropositivity. Among all the 1181 patients, 10.9% of the 414 patients with moderate to severe malnutrition died in the first 4 weeks compared with 6.5% of the 767 patients with normal to mild malnutrition (odds ratio 1.8, 95% confidence interval 1.1-2.7). In patients with TB, BMI < 17.0 kg/m2 is associated with an increased risk of early death.
    • Multidrug-Resistant Tuberculosis in Central Asia.

      Cox, H; Orozco, J D; Male, R; Ruesch-Gerdes, S; Falzon, D; Small, I; Doshetov, D; Kebede, Y; Aziz, M; Médecins Sans Frontières Aral Sea Area Programme, Uzbekistan and Turkmenistan, Tashkent, Uzbekistan. hom@msfh-tashkent.uz (2004-05)
      Multidrug-resistant tuberculosis (MDR-TB) has emerged as a major threat to TB control, particularly in the former Soviet Union. To determine levels of drug resistance within a directly observed treatment strategy (DOTS) program supported by Médecins Sans Frontières in two regions in Uzbekistan and Turkmenistan, Central Asia, we conducted a cross-sectional survey of smear-positive TB patients in selected districts of Karakalpakstan (Uzbekistan) and Dashoguz (Turkmenistan). High levels of MDR-TB were found in both regions. In Karakalpakstan, 14 (13%) of 106 new patients were infected with MDR-TB; 43 (40%) of 107 previously treated patients were similarly infected. The proportions for Dashoguz were 4% (4/105 patients) and 18% (18/98 patients), respectively. Overall, 27% of patients with positive smear results whose infections were treated through the DOTS program in Karakalpakstan and 11% of similar patients in Dashoguz were infected with multidrug-resistant strains of TB on admission. These results show the need for concerted action by the international community to contain transmission and reduce the effects of MDR-TB.
    • Passive Versus Active Tuberculosis Case Finding and Isoniazid Preventive Therapy Among Household Contacts in a Rural District of Malawi.

      Zachariah, R; Spielmann M P; Harries, A D; Gomani, P; Graham, S; Bakali, E; Humblet, P; Operational Research (HIV/TB), Medical Department, Médecins sans Frontières-Brussels Operational Centre, Brussels, Belgium. zachariah@internet.lu (International Union Against TB and Lung Disease, 2003-11)
      SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis.
    • Treatment outcome of patients with smear-negative and smear-positive pulmonary tuberculosis in the National Tuberculosis Control Programme, Malawi.

      Harries, A D; Nyirenda, T E; Banerjee, A; Boeree, M J; Salaniponi, F M L; National Tuberculosis Control Programme, Community Health Science Unit, Lilongwe, Malawi. epicentre@imul.com (Elsevier and the Royal Society of Tropical Medicine and Hygiene, 1999)
      National tuberculosis control programmes (NTPs) in sub-Saharan Africa do not routinely record or report treatment outcome data on smear-negative pulmonary tuberculosis (PTB) patients. Twelve-month treatment outcome on patients with smear-negative PTB registered in all district and mission hospitals in Malawi during the year 1995 was collected, and was compared with 8-month treatment outcome in smear-positive PTB patients registered during the same period. Of 4240 patients with smear-negative PTB, 35% completed treatment, 25% died, 9% defaulted and 7% were transferred to another district with no treatment outcome results available. In 24% of patients treatment cards were lost and treatment outcome was unknown. These results were significantly inferior to those obtained in 4003 patients with smear-positive PTB in whom 72% completed treatment, 20% died, 4% defaulted, 2% were transferred and 1% had positive smears at the end of treatment. These differences between patients with smear-negative and smear-positive PTB were similar when analysed by sex and by most age-groups. Higher mortality rates in patients with smear-negative PTB are probably attributable to advanced HIV-related immunosuppression, and higher default and treatment unknown rates probably reflect the lack of attention paid by TB programme staff to this group of patients. As a result of this country-wide study the Malawi NTP has started to record routinely the treatment outcomes of smear-negative TB patients and has set treatment completion targets of 50% or higher for this group of patients.
    • Tuberculosis recurrence and mortality after successful treatment: impact of drug resistance.

      Cox, H; Kebede, Y; Allamuratova, S; Ismailov, G; Davletmuratova, Z; Byrnes, G; Stone, C; Niemann, S; Rüsch-Gerdes, S; Blok, L; et al. (PLoS, 2006-10)
      BACKGROUND: The DOTS (directly observed treatment short-course) strategy for tuberculosis (TB) control is recommended by the World Health Organization globally. However, there are few studies of long-term TB treatment outcomes from DOTS programs in high-burden settings and particularly settings of high drug resistance. A DOTS program was implemented progressively in Karakalpakstan, Uzbekistan starting in 1998. The total case notification rate in 2003 was 462/100,000, and a drug resistance survey found multidrug-resistant (MDR) Mycobacterium tuberculosis strains among 13% of new and 40% of previously treated patients. A retrospective, observational study was conducted to assess the capacity of standardized short-course chemotherapy to effectively cure patients with TB in this setting. METHODS AND FINDINGS: Using routine data sources, 213 patients who were sputum smear-positive for TB, included in the drug resistance survey and diagnosed consecutively in 2001-2002 from four districts, were followed up to a median of 22 months from diagnosis, to determine mortality and subsequent TB rediagnosis. Valid follow-up data were obtained for 197 (92%) of these patients. Mortality was high, with an average of 15% (95% confidence interval, 11% to 19%) dying per year after diagnosis (6% of 73 pansusceptible cases and 43% of 55 MDR TB cases also died per year). While 73 (74%) of the 99 new cases were "successfully" treated, 25 (34%) of these patients were subsequently rediagnosed with recurrent TB (13 were smear-positive on rediagnosis). Recurrence ranged from ten (23%) of 43 new, pansusceptible cases to six (60%) of ten previously treated MDR TB cases. MDR M. tuberculosis infection and previous TB treatment predicted unsuccessful DOTS treatment, while initial drug resistance contributed substantially to both mortality and disease recurrence after successful DOTS treatment. CONCLUSIONS: These results suggest that specific treatment of drug-resistant TB is needed in similar settings of high drug resistance. High disease recurrence after successful treatment, even for drug-susceptible cases, suggests that at least in this setting, end-of-treatment outcomes may not reflect the longer-term status of patients, with consequent negative impacts for patients and for TB control.