Tuberculosis: A National Menace

GLOBAL SCENARIO

Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis that kills more people than HIV/AIDS every year. The WHO Global TB Report 2020 found that 98% of the world’s registered TB cases were in low- and middle-income countries (LMICs).

In LMICs, low awareness of TB is one of the leading risk factors for high prevalence. Lack of TB awareness has become a severe social concern affecting population health, given the risk of spread of TB.

Inadequate knowledge about TB leads to further transmission and delay in diagnoses and treatment. There are 3.6 million people with TB who are undiagnosed and hence do not receive treatment from healthcare facilities in LMICs.

NATIONAL SCENARIO

In 1965, the national TB program (NTP) of Nepal was implemented by the Nepalese government in collaboration with the WHO and the United Nations International Children’s Emergency Fund (UNICEF).

The main aim of the program is to effectively monitor and control TB incidence and prevalence and ensure better access to quality TB treatment services in Nepal. Since 2006, almost 85% of TB cases in Nepal have been successfully treated through the NTP, and the incidence of TB has decreased gradually, by 3% per year until 2019.

Despite efforts made by government and international organizations to end TB, around 40% of Nepalese participants in the End TB program did not seek TB care and treatment. The results of the national survey indicate that there is inadequate knowledge of access to TB health services; thus, there is a need to increase awareness of the availability of quality TB diagnostics, care and treatment.

National health policy priorities include: achievement of the main goal, TB elimination; reducing the numbers of new TB cases and TB deaths (by enhancing TB awareness among the entire Nepalese population); removal of barriers to equitable access to TB treatment and care, to improve community wellbeing in regional Nepal.

All of those targets were set by the NTP at the central level and at local levels as well, in accordance with the goal of the national strategic plan, to End TB by 2030 in Nepal. The level of TB awareness is associated with various demographic and socioeconomic factors such as education level, socioeconomic status and area of residence.

In LMICs, including Nepal, specific locations and places at greater distances from TB treatment facilities are susceptible to poor community TB awareness and weak adherence to TB treatment as a health-seeking behavior.

MULTI DRUG RESISTANCE & ADDED BURDEN

Multidrug-resistant TB (MDR-TB), a form where the infecting strain is resistant to two important first-line drugs (isoniazid and rifampicin), has created havoc in TB control and has greatly hampered the TB elimination process.

The majority of patients with MDR-TB have prior anti-TB therapy and 60% had failed a 6–8 month treatment regimen with first-line drugs. This is in contrast with the high success rate of drug susceptible TB and not on par with the incidence of MDR-TB (15.4% of retreatment cases are MDR-TB based on drug resistance survey carried out in 2011/2012).

Despite use of DOTS, these patients might have been patients with MDR-TB misdiagnosed as drug-susceptible TB due to unavailability of GeneXpert MTB/RIF and therefore put on an ineffective first-line regimen; or they might have acquired resistance to rifampicin/isoniazid during the course of treatment with first-line drugs; or they may have been reinfected with drug-resistant bacilli from a source patient having MDR-TB.

In Nepal, the primary drugs resistance is high. The routine drug resistance survey in Nepal showed a higher proportion of resistance to second-line drugs; with resistance to fluoroquinolones alone at 39.3% among patients with MDR-TB. This implies that 40% of the patients with MDR-TB in Nepal might require pre-XDR TB treatment.

In 2017 alone, around 35.4% of confirmed MDR-TB cases were pre-XDR. In 2017, overall treatment success rate of pre-XDR TB was 58% and XDR TB was 61%. The death rate was quite high among XDR TB cases (39%) and encouragingly, there was no lost to follow-up among XDR TB cases.

Clinical diagnosis of pre-XDR TB is not possible, this calls for a massive scale up of genotypic susceptibility testing in decentralized TB treatment centers and subcentres, to adequately diagnose patients and start appropriate treatment.

Later generation fluoroquinolones (levofloxacin and moxifloxacin) are key drugs in both standardised (20–24 months duration), short course 9-month and all-oral 20-month regimens in use for treating MDR-TB.

With the new all-oral 20-month regimen which includes drugs like bedaquiline and delamanid, the overall proportion of adverse events was reasonably low compared with standardized 20–24 month regimen with injectable agents.

More evidence is needed to assess the tolerability of the new all oral regimen, especially in settings with limited resources where short 9-month regimen has demonstrated to be safe and effective.

Furthermore, linezolid, a narrow therapeutic index drug, is frequently used in the all oral regimen; therefore, balancing efficacy and toxicity is crucial. Therapeutic drug monitoring (TDM) can be used as a tool to ensure target attainment while preventing toxicity.

INTROSPECTION AND WAY FORWARD

In the light of available evidence, examining the demographic and socioeconomic factors associated with TB awareness is important for understanding the socioeconomic gaps that can help to drive infectious TB control in the work to eliminate TB.

Low public awareness and knowledge about TB have been identified as correlated with several socioeconomic factors including family income, education level and gender.

In addition, enhanced awareness of TB could improve access to appropriate treatment and better outcomes, especially in socioeconomically vulnerable groups who have limited access to information about TB due to weak community engagement and certain areas of residence.

The six basic principles of tuberculosis control i.e. EARLY diagnosis, EFFECTIVE drug selection; ADEQUATE drug doses; COMBINED drug regimen; MONITORED recording; and COMPLETE treatment are the main stay for tuberculosis control.

The failure of treatment and rise in drug resistance cases could be attributed to lapse in any step of the basic principle at the local DOTS center. Therefore it is very important that the health care providers at all levels should be regularly trained for proper counseling; address adverse drug reaction; monitor weight: drug proportion; and increase patient adherence to treatment.

Moreover, the link between various risk factors like diabetes mellitus, HIV, alcoholic liver disease, chronic kidney disease, advanced age, low body weight, adverse events and treatment outcomes in patients under a standardized regimen for both drug susceptible and MDR-TB treatment requires further study and evaluation.

Dr. Asmitananda Thakur
MBBS, MD, DM
Senior Consultant Pulmonologist & Physician
Biratnagar, Nepal