Treatment and management of MDR-TB in Latvia
Latvia has consistently ranked among the countries with the highest rates of MDR-TB in the world. In the first Global Tuberculosis Drug Resistance Survey (1996), 14.4%, or 1 out of 7, of all newly diagnosed sputum smear-positive tuberculosis cases in Latvia were diagnosed as MDR-TB.1
Data also show that the proportion of cases with additional resistance to second-line anti-tuberculosis drugs is high. In the meantime, HIV seroprevalence is increasing among TB patients.
Latvia, with an estimated population of 2.35 million, joined the European Union on 1 May 2004. The Latvian economy had been severely affected by the collapse of the Soviet Union, with gross domestic product (GDP) per capita falling by nearly 35% in real terms in 1992. The GDP per capita in 1999 was US$ 4200, increasing to US$ 11 500 in 2004. Latvia concurrently experienced dramatic increases in TB morbidity and mortality peaking in 1998, together with the appearance of drug-resistant and MDR-TB.2,3
Latvia adopted WHO’s recommended DOTS strategy for TB control in 1996 and subsequently introduced MDR-TB management4 in 1997. This relies on MDR-TB treatment with individualized regimens under the consilium or expert consultation process. The treatment is provided at four inpatient treatment centres (including a prison TB ward) followed by outpatient directly observed therapy. All funding for TB and MDR-TB control comes from the government. In 2000 Latvia’s National Tuberculosis Program (NTP) sought MDR-TB management support from the Green Light Committee (GLC) and got approval to treat 350 more MDR-TB patients. The GLC enabled Latvia to treat all patients diagnosed with MDR-TB.
In 1991, the incidence of TB was 29 cases per 100 000 population,5 increasing to 74/100 000 in 1998 and then declining to 53.5/100 000 in 2005. Case finding shows 49% case detection by smear microscopy.
Drug-resistant TB case detection strategy in Latvia is based on drug sensitivity tests (DST) on solid media. For high-risk MDR-TB cases, the BACTEC/MIGT system is used, as well as the INNO LiPA test to detect rifampicin resistance in 2–4 days.
Extensive resistance to first- and second-line drugs among MDR-TB patients is well known in Latvia. One of the reasons is the country’s long and extensive use of second-line drugs before implementing the DOTS strategy. Extensive resistance affects the MDR-TB treatment regimen and outcomes. For cohorts registered from 2000 to 2005, resistance to kanamycin was 49%; capreomycin, 39%; ofloxacine, 9%; protheonamide, 30%; para-aminosalycilic acid, 31%; and thiacethasone, 23%.
In the first worldwide survey, published in May 2006, estimates for years 2000–2004 showed that 19% of MDR-TB patients have resistance to first-line drugs defined as MDR-TB plus resistance to three drugs of six classes of second-line drugs.6
Using the new revised extensive drug resistance (XDR-TB) definition of resistance to at least rifampicin and isoniazid, additional resistance to any fluoroquinolone and to any of three second-line injectable drugs (capreomycin, kanamycin or amikacin), such extensively resistant TB was found in 39 cases, or 5.2% of all MDR-TB cases registered during the past six years.
Two-thirds, or 67%, of MDR-TB patients out of 820 treated in the years 2000–2003 were cured; 6% were dead; 14% defaulted; and treatment failed in 13% of cases.7,8 The treatment success rate for XDR-TB patients is low: out of all 48 patients treated from 2000 to 2005 (including MDR-TB retreatment cases with XDR-TB), only 18 (38%) were cured, while treatment failed for 22 (46%).
Among all MDR-TB cases in the cohorts, 3% were co-infected with HIV; this proportion increased to 12% among XDR-TB cases. Treatment success for TB/HIV co-infected new patients, at 74%, is similar to overall treatment success for new TB patients, but the HIV-associated MDR-TB success rate is 56%.
Overall, Latvia’s success with the DOTS program is encouraging: 84% of all registered cases, including outcomes of MDR-TB after 2 years, were cured in cohort 2002, which is close to the level of performance (85%) recommended by WHO (Table 1).9 Newly registered MDR-TB cases were reduced by 46%, with 332 cases in 1997 falling to 153 registered in 2005.
MDR-TB management is effectively implemented under routine program conditions in Latvia. Using an individual approach to the management of MDR-TB can cure more than two-thirds of patients in settings with high MDR-TB prevalence and extensive resistance to first- and second-line drugs.10
Challenges for TB care in Latvia
An area of concern is treatment default, especially among MDR-TB cases (14%), among those with TB/HIV and MDR-TB/HIV11 co-infection, and among patients with extensive drug resistance.
Rapid drug-resistant case detection, appropriate treatment, extended contact investigation, infection control measures and case management strengthening to decrease treatment interruptions and default are the main challenges Latvia faces in achieving the TB-related Millennium Development Goals. ■
- Anti-tuberculosis drug resistance in the world: the WHO/IUATLD Global Project on Anti-Tuberculosis Drug Resistance Surveillance. Geneva: WHO; 2005 (WHO/TB/97.229). Available at: http://www.who.int/tb/surveillanceworkshop/status_analysis/dr_global_project.htm
- R Zalesky, J Leimans, I Pavlovska. The epidemiology of tuberculosis in Latvia. Monaldi Arch Chest Dis 1997; 52: 142-6.
- Karklina A, Zaleskis R, Binkin N. Drug-resistant Mycobacterium tuberculosis in Latvia, 1994-1995. Int J Tuberc Lung Dis. 1996; 77(2):63.3-8.
- WHO guidelines for establishing DOTS-Plus pilot projects for the management of multidrug-resistant tuberculosis. Geneva: WHO; 2000 (WHO/CDS/TB/2000.279).
- G Skenders. Multidrug-resistant tuberculosis detection, Latvia. Emerg Infect Dis 2005; 11: 1461-3.
- Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs – worldwide, 2000-2004 MMWR 2006; 55: 301-5.
- E Nathanson, C Lambrehts-van Weezenbeek, MI Rich, R Gupta, J Bayona, K Blöndal, et al. Multidrug-resistant tuberculosis management in resource-limited settings. Emerg Infect Dis 2006; 12: 1389-97.
- Lasersen KF, Thorpe LE, Leimane V, Weyer K, Mitnick C.D, Riekstina V et al. Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis. Int J TB Lung Dis 2005;9(6):640-5.
- V Leimane, J Leimans. Tuberculosis control in Latvia: integrated DOTS and DOTS Plus program. Euro Surveil 2006; 11: 29-33.
- V Leimane. Clinical outcome of individualized treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study. Lancet 2005; 365: 318-26.
- I Morozova, V Riekstina, G Sture, C Wells, V Leimane. Impact of the growing HIV-I epidemic on multidrug-resistant tuberculosis control in Latvia. Int J Tuberc Lung Dis 2003; 7: 903-6.
- The State Agency of Tuberculosis and Lung Diseases of Latvia, p.o.Cekule, Riga region, LV-2118, Latvia.