Isoniazid-monoresistant pulmonary tuberculosis in a COVID-19 positive man: the world’s first such case in the current pandemic

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Tuberculosis (TB) is a major public health problem and has been known for ages [1]. Nearly a quarter of the world’s population is infected with Mycobacterium tuberculosis (MTB) [1]. Making it one of the deadliest infectious diseases, with an estimated 1.5 million deaths in 2020 [2]. According to the latest WHO statistics for the year 2021 in India, the incidence and prevalence of TB in India is 188 and 312 per one lakh (0.1 million) population [3]. This is remarkable as the National Tuberculosis Elimination Program (NTEP) is operating as per guidelines and efforts are aimed at eliminating Tuberculosis in India by 2025. [4]. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has so far caused considerable devastation in both developed and developing countries [5]. The situation is alarming in countries where infectious diseases such as tuberculosis are rampant [6]. This pandemic has, to some extent, had a negative impact on national programs such as tuberculosis elimination programs [4].

Drug-resistant tuberculosis (DR-TB) constitutes a significant proportion of all tuberculosis cases in high-prevalence countries [6]. The most common form of drug-resistant TB worldwide is isoniazid-resistant rifampicin-susceptible TB (HR-TB) which is resistant to drugs like isoniazid (H), which is a potent bactericidal drug and plays an important role in the management of TB programs [7]. According to one estimate, HR-TB is seen in nearly 7% of new TB cases and 8-11% of previously treated TB cases [8].

Reports of co-infections of COVID-19 and tuberculosis are rare and are available in the literature mainly as case reports [6]. Here, a case of isoniazid mono-resistant primary pulmonary tuberculosis in a COVID-19 positive Indian man is reported. A case of such presentation of HR-TB with COVID-19 has not yet been reported in the medical literature.

A 20 year old Indian man presented to our Outpatient Department (OPD) with chief complaints of cough with expectoration for two weeks, right side chest pain for one week, fever with night sweats for one week and loss of appetite for a week. week with generalized weakness.

In the detailed anamnesis, the cough was continuous, associated with non-malodorous greenish-yellow sputum and worse with exertion. The right sided chest pain was mostly in the upper chest and was worse when coughing. The fever was mostly low grade, increased in the evening, and was relieved by taking over-the-counter antipyretics. He also mentioned loss of appetite for a week and general weakness for about seven days.

This patient was a delivery agent by profession and worked during the COVID-19 pandemic, except during local shutdowns. There was no history of drug abuse. His medical and surgical history was insignificant. Additionally, there was no history of similar complaints in the past against him or any of his family members. And there was no history of infectious diseases like tuberculosis or COVID-19 in the family or any contacts. Again, the patient was a nonimmigrant with no history of imprisonment, unemployment, contact with drug dealers, or sex workers.

On general examination, he was afebrile with a pulse of 101/minute, blood pressure of 135/85 mmHg, respiratory rate of 30 breaths/minute, and SpO2 was 92% on ambient air. His SpO2 dropped 89% on ambient air after walking. Chest pain worsened with walking and improved with rest.

Systemic examination was remarkable with a dull note on percussion over the right hemithorax and vocal repercussions were diminished, and on auscultation there were crackles over the upper and middle lobes of the right lung. The remainder of the systemic examination was unremarkable.

He was diagnosed as a probable case of tuberculosis and received symptomatic treatment with cough syrup (ambroxol hydrochloride) and an antipyretic (paracetamol) in addition, he was referred to the laboratory for his sputum for the test of acid-fast bacilli (AFB), sputum cartridge nucleic acid amplification test (CBNAAT), chest X-ray along with other routine tests including reverse transcriptase polymerase chain reaction test ( RT-PCR) for SARS-CoV-2.

AFB sputum results suggested Mycobacterium tuberculosis (MTB) detected and the same was confirmed with CBNAAT. However, no rifampicin resistance was detected. In accordance with NTEP guidelines, a sample was sent for online probe testing (LPA) and culture for first and second line anti-tuberculosis drug susceptibility testing to the Intermediate Reference Laboratory (IRL).

Meanwhile, RT-PCR was reported as positive for SARS-CoV-2 specific RNA and the posteroanterior (PA) view of the chest X-ray suggested consolidations at the upper lobe of the right lung with indistinct borders (Figure 1). Further investigations revealed a low lymphocyte count (1 × 10seven/L), elevated erythrocyte sedimentation rate (70 mm in the first hour), increased levels of C-reactive protein (61 mg/L) and lactate dehydrogenase (LDH) (558 U/L). LPA results indicated resistance to isoniazid and susceptibility to rifampicin. Additionally, there was resistance to the katG gene.

Therefore, a diagnosis of isoniazid-mono-resistant primary pulmonary tuberculosis with COVID-19 was made and treatment was initiated according to NTEP guidelines and national guidelines for COVID-19. He was started on rifampicin, ethambutol, pyrazinamide, and levofloxacin for six months based on his weight, and simultaneously symptomatic management of COVID-19 was initiated, which included paracetamol, hydroxychloroquine, inhaled budesonide, vitamin B complex, vitamin C, and betadine gargles. . At his request, he was not admitted to the health facility and was kept in home isolation for two weeks with regular SpO.2 monitored and advised to report to the emergency room any drop in oxygen saturation or any other major complaint. He was advised breathing exercises and yoga which helped immensely and there were no episodes of falling SpO2. After two weeks, the patient underwent a new RT-PCR from a private laboratory for COVID-19 and tested negative. Due to the non-cooperation of the patient due to his weak economic situation and the government’s oversaturated free slots for CT scans, due to the pandemic, the same was not done. Thus, he was continued on anti-tuberculosis treatment and regularly monitored in the OPD. Currently, the patient has completed five months of treatment and is doing well without any significant complaints. At his request to continue the rest of his treatment, he was referred to his village.

The current COVID-19 pandemic has affected the care of patients with other infectious diseases [6]. Reporting of TB cases was down at the start of the pandemic [4]. As a result, a significant proportion of cases went unreported or died. The situation was the same, i.e. for drug-susceptible TB and drug-resistant TB cases [4].

Drug-resistant TB can be of several types, i.e. isoniazid-resistant (H) TB, rifampicin-resistant (RR) TB and multidrug-resistant (MR) TB (resistant to RR and H) , pre-drug resistant TB (pre-XDR-TB) resistant to rifampicin (MDR/RR-TB) and any fluoroquinolone, and XDR-TB resistant to rifampicin (MDR/RR-TB), plus any fluoroquinolone, plus minimally to one of the drugs, bedaquiline and linezolid [4]. Drug-resistant TB is generally considered to be the result of inappropriate treatment of drug-susceptible TB [9,10]. However, cases of primary drug resistance in the absence of any history of tuberculosis or any known contacts are also available. [6]. Concomitant pulmonary tuberculosis infections with COVID-19 are rare and require a high index of suspicion because they share many similar clinical features [6]. In countries with a high TB ​​burden, the pandemic has already overwhelmed health systems and therefore rapid diagnosis supported by prompt treatment of these two infections is very important. [6]. In a recent meta-analysis, mean in-hospital mortality rates for co-occurring TB and COVID-19 cases were reported to be 22.5% (95% CI: 19.0% to ~26.0%) in low/middle income countries (India, Philippines, South Africa) [11]. This showed that there is a high mortality risk in cases of these two infections [11]. However, there is little literature on the prevalence, treatment, and long-term outcomes in these countries in COVID-19 cases with drug-resistant TB cases.

Isoniazid is an important antituberculosis agent due to its early bactericidal activity, low cost and comparatively fewer side effects [1]. Development of mono-resistance H is alarming as it suggests negative treatment outcomes and progression to MDR-TB, especially in children and people living with HIV/AIDS [12]. Reports of H-mono resistant primary pulmonary tuberculosis in the absence of a history or known contacts are even more alarming as such cases are extremely rare and a very high degree of suspicion is required to establish the diagnosis. [6]. This case will serve as an important new addition to existing knowledge on the management of HR-TB, thereby assisting healthcare workers.

This case highlights the importance of a thorough history and physical examination, particularly in high TB ​​settings. The signs and symptoms of several diseases resemble COVID-19 and therefore it is imperative to diagnose cases with an eye for rare or never-before-seen presentations of different diseases. This case would be an important addition to the literature, as the diagnosis of primary isoniazid mono-resistance with COVID-19 is never reported to date and whether untreated HR-TB is associated with an increased risk of developing further drug resistance and progress to MDR-TB.

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