The Condition of Mycobacterium Tuberculosis Lineages and Resistances in Indonesia

Background: Tuberculosis is a disease caused by Mycobacterium tuberculosis. Indonesia ranks second worldwide in TB incidence in the country. Content: The spread of the disease is happening across Indonesia. Each area of Indonesia had different types of lineage M. tuberculosis and TB incidence number. Drug resistance is threatening to society and it needs full attention and immediate medication to control the disease. Therefore, this paper is composed of reviews from 10 journals that reported drug resistance TB in several different locations in Indonesia using different methods available. Conclusion: The number of TB cases and their lineages differ in each area in Indonesia, one of which is due to the availability of diagnostic tools and level of self-awareness in each area. There are reported findings of drug resistance TB in Indonesia that are concerning. Currently, many TB treatments are under development to produce the best therapy to treat the disease.


Introduction
Even after the whole world has gone into a state of pandemic, tuberculosis (TB) is still the leading cause of death worldwide. It even landed in second place just after COVID-19, causing approximately 1.5 million deaths in 2020 with Indonesia in second place after India. Its high mortality rate makes TB one of the global health burdens that need to be managed.
There are several factors contributing to the high number of incidences as well as the high number of death, where one of which is multidrug resistance (MDR-TB). MDR-TB has become a world concern which caused health crises globally, including in Indonesia. 1 The high number of TB and MDR-TB incidents in Indonesia signifies the need for controlling and preventing tuberculosis. 2 Indonesia is an archipelago country, with numerous islands spread from Sabang to Merauke. TB spreads differently in each area of Indonesia. Asides from geographical factors, lack of medical staff and utilities may also affect the disease spread in remote areas. 3 Recent research by Noviyani et al. found that the highest prevalence of TB in Indonesia was found on Sumatra.
Due to the concerning high number of TB and MDR-TB cases worldwide and also in Indonesia, the condition of TB across Indonesia needs to be assessed to evaluate the differences in TB incidence numbers in such areas, and what are the factors contributing to the phenomenon. This brief literature review wished to discuss Mycobacterium tuberculosis lineage and its resistance in Indonesia. streptomycin. 37.5% of resistance in Indo-Oceanic lineage is higher than in other lineages such as Euro-American and East Asian strains but the latter was found to possess most of the multiple mutations. This report may portray the potential of using WGS as a rapid and comprehensive test to predict drug resistance to TB. 6

Tuberculosis resistance
The resistance of M. tuberculosis isolates develops in two ways, infection from the resistant bacteria or indiscreet use of antibiotics by patients may lead to resistance or metabolic problem.
Guidelines for laboratory testing of M. tuberculosis are available. 8  Indonesia. 17

South Halmahera
Dewi reported that 8% of drug-resistant TB was found in South Halmahera, Eastern Indonesia. 11 out of 13 patients had MDR-TB while the rest had pre-extensively drug-resistant. In which only 8 patients receive the treatment, 4 patients died and 1 lost contact. 19

Makassar, South Sulawesi
Analyzing the gene responsible for drug resistance M. tuberculosis was done in Makassar by analyzing several genes which play roles in resistance. Umar et al. did an analysis and found rifampicin resistance in 80% of patients from a mutation in rpoB (S450L, H445D, D435V, S441L, I491F, and Q432P). There is an 11.42% case, in which mutation in katG leads to rifampicin resistance, not isoniazid resistance. Mutation points in katG are P280P, G279R, E340Q, T271I, E340*stop codon, R373G, and S315N. two strains mutation leading to streptomycin resistance because of mutation present in rrs gene (G878A and/or S514R). 20

Potential treatments for TB
There is a lot of potential substance to treat TB, Mudaliana  After the insertion, the expression was then analyzed by using a western blot, and the results are the forming of bands was found to be higher than expected. 23 Indonesia with WHO is planning to eliminate TB by 2030 with the support of the government.
The recent report with WHO global held in October 2021 resulted in the six strategies to be implemented by Indonesia to achieve control of TB. 24 This study limitation to the limited amounts of articles available online thus the results of this study may not be able to represent the whole number of tuberculosis incidence in Indonesia. Thus, further research regarding the subject may be needed in the future.

Conclusions
The incidence of TB in Indonesia is high ranking second in the world. The number may differ in each area in Indonesia, several factors may affect those numbers one of which is the availability of tools in the area and the level of self-awareness. MDR-TB is also jeopardizing society and the numbers are also high in Indonesia. Research regarding the treatment of TB is plentiful, thus the development of MDR-TB treatment may not be far anymore for those who need it.

Conflict of Interest
There is no conflict of interest in this research

Funding Sources
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Acknowledgment
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