COVID-19 is a new infectious disease caused by the SARS-CoV-2 virus. It has affected 234 million people and resulted in about 4 million deaths worldwide.¹ Low- and middle-income countries were the most affected by this virus primarily due to an increasing economic burden for medical care, abrupt individual socio-economic instability, and limited access to diagnostic methods and treatment.² As a result, the local control of endemic diseases and chronic patients was interrupted.

Tuberculosis (TB) is a historical bacterial disease affecting both developing and non-developing countries worldwide. Globally, an estimated 10.0 million (range 8.9-11.0 million) people fell ill with TB in 2019.³ Considering the high TB incidence among low-income countries and the long-lasting economic impact of the current pandemic, it is likely that COVID-19 will have catastrophic effects on TB control.

According to an investigation developed by the StopTB Alliance, it is probable that within the next five years, about 6.3 million new TB cases will appear, and 1.4 million people infected with TB will die because of the current isolation measures.⁴ People living in densely populated areas will be the most affected; isolation is unrealistic because it implies the reduction of their already scarce incomes.⁵

In this context, reviewing the local regulatory framework for TB management and the socio-economic reality behind the COVID-19 pandemic in developing countries might help us create measures to combat endemic diseases during this pandemic. The COVID-19 pandemic has disrupted local control of active TB. The current regulatory framework is focused on prevention, surveillance, and follow-up; however, this may be insufficient under the existing socio-economic and sanitary necessities.

Global economic expenses increased dramatically for healthcare, causing a smaller treatment coverage and fewer follow-up possibilities. Similarly, laboratories and medical appointments were oversaturated, contact surveillance was limited, and distribution and transportation of medication were hampered. Finally, the mandatory physical isolation and high congestion inside medical care centers could presumably exacerbate the dissemination of TB and the onset of new COVID-19 cases.⁶

Relationship between TB and COVID-19

The global TB fatality rate was 14% in 2019, down from 23% in 2000³; together, COVID-19 aggravated TB infection fatality rate. Co-infection between TB and other coronaviruses has already been reported.^7-10 It is possible that massive cytokine release and a disruption of transient cellular immunity by either TB or COVID-19 predisposes the patient to a new infection or the reactivation of a latent disease.^11-16 It has also been documented that either latent tuberculosis infection (LTBI) or active TB increases the risk of SARS-CoV-2 infection.^17-20 Whether LTBI represents a higher or lower risk factor for COVID-19 than other comorbidities is still unclear.²¹

According to the World Health Organization (WHO) statement on SARS-CoV-2 impact on TB control and management, the infection by coronavirus seems to hinder the diagnosis and treatment services affecting those who are already infected with TB. That gives the impression that the following infection worsens the clinical condition and causes ultimate death in the affected patient. However, as fewer people with TB are diagnosed, they are treated slower and remained affected for a longer period, making it the primary infection the real cause of death.

Although the clinical and physiopathological interaction between the infection by SARS-CoV-2 and TB is still ambiguous, it has been proposed that similar to HIV infection, another viral infection such as SARS-CoV-2 may negatively impact the progression of TB infection. Nevertheless, that is controversial.

Batista et al. (2022) showed data suggestive that the infection by COVID-19 may not have a major role in advancing TB infection to TB disease.²² However, the condition known as post-TB lung disease (PTLD) may impact the prognosis of patients that later acquire COVID-19. This condition may cause either obstructive or restrictive patterns that reduce exercise capacity, impair quality of life, and ultimately make people more susceptible to more severe infection by the novel coronavirus.

Current Regulatory Framework

According to the World Bank data, Ecuador has had an increased incidence of TB infection since 2016, with a value of 48 infected people per 100 000 citizens. According to the WHO, the incidence in developing countries is explained by the lack of economic and human resources that predisposes undiagnosed and untreated cases. Such a scenario adds to concomitant problems that include overcrowding in small spaces, malnutrition, chronic diseases, and immunosuppression secondary to HIV infection and malnutrition.

For low- and medium-income countries with undeniable huge socio-economic disparities that partially explain the higher incidence of uncontrolled TB infection, the impact of COVID-19 infection in the population further aggravated the situation. Emerging economics already flew low when the novel coronavirus hit and they seemed to have run out of gas to keep on float by this time. A hard landing was expected and it is mostly preceded by the uncontrol of previously controlled diseases such as TB.

After the WHO declared TB as a global health emergency in 1993, each country adopted policies for delivering health care created on the country’s existing infrastructure and economic feasibility.²³ However, it is estimated that about 30 000 people acquire this disease every day, and up to 4 000 die from it.³

In Ecuador, the government established the DOTS program to control TB in 1994. It consisted of five major elements: political engagement, active case finding through AFB smear, direct observed treatment, the regular provision of drugs, and a standardized system for registration and notification of cases (Figure 1).

Active patient finding requires correct characterization of respiratory symptoms. Once a case is suspected, two sputum samples are taken separated by 24 hours. When sensitivity is proven, a formal request for the medication is asked. All doses are provided to the first care facility, which is in charge of administering the medicine daily (direct observed treatment, DOT).

Surveillance of the patients and their contacts requires filling out a specific epidemiological control form.^24,25 Finally, an epidemiological map is developed to implement new control strategies.

However, given the novel COVID-19 pandemic, these current disease control protocols may be overwhelmed by the lack of human and economic resources, making it more challenging to identify new cases and initiate TB treatment, monitor patients and assess their evolution.

Disruption of TB Disease Control by COVID-19 Pandemic

TB surveillance, treatment, and follow-up have always required a substantial annual governmental investment, especially for developing countries. The new COVID-19 infection caused severe reductions in health service availability as it consumed part of the economic funding, human resources, and physical assets usually implemented for the detection and surveillance of other diseases.^26,27

As a result, this limitation hindered the possibility of a prompt diagnosis, proper treatment, and effective local TB control.²⁸ The WHO estimated that about a third of the populations having TB were either not diagnosed, not treated, or not reported in 2019.²⁹

The STOP TB partnership that included the analysis of three high-burden countries (India, Kenya, and Ukraine) predicted that an additional 6.3 million TB cases will be seen between 2020 and 2025, considering a possible three-month lockdown and ten months for restoration of health services. Similarly, up to 1.4 million deaths due to TB infection are predicted to occur in this same period.

In addition, medication manufacture, storage, transportation, and distribution will probably be still impaired after the resolution of the social crisis.

Jain et al. reported limited access to regular hospital visits, inability to provide adverse events surveillance and counseling, plus an increased amount of treatment abandonment due to poor adherence.³⁰

Furthermore, there is possibly a priority to diagnose COVID-19 rather than TB, leading to delayed diagnosis, decreased active surveillance, and redistribution of resources. These include management centers, critical care units, ventilators, and medication.^30-33

COVID-19 might disrupt mental health and reduce the treatment of comorbidities that increase the likelihood of this infection, such as HIV, diabetes, hypertension, obesity, and cancer. As a result, primary TB diagnosis could be delayed, disrupting active TB infection control and possible LTBI reactivation.^28,34

Physical distancing may limit TB transmission outside the household, where most cases tend to occur.^4,35 This advantage might compensate for TB disruption services.^4,35 Whether this assumption is factual or even applies to low-income countries with a high TB epidemiological burden is still uncertain. It was proposed that social distancing helped to maintain TB incidence but did not affect the total number of deaths per year. According to this model, it is probable that even though quarantine kept people from spreading TB, it still caused more severe cases that resulted in a higher mortality rate.³⁶

Measures to Combat TB during COVID-19 Pandemic

Specific protocols for TB management during the COVID-19 pandemic should be constructed after considering the needs of the following groups: general population, asymptomatic and symptomatic COVID-19 patients, LTBI, active TB, and co-infection SARS-CoV2/TB.

A few countries in Latin America, such as Colombia and Honduras, have released formal local regulation protocols for the prevention and control of TB in the context of the COVID-19 pandemic. Authorities aimed to prioritize the linkage of human resources to keep and sustain activities regarding surveillance of endemic diseases.^6,37-39

However, Ecuador has not launched an official countermeasure to combat TB during the COVID-19 pandemic. The current regulatory framework is probably inefficient given the high TB burden and reduced physical and human resources availability. Table 1 summarizes proposed TB control and prevention strategies during the COVID-19 pandemic.

For confirmed TB cases, patients should implement actions to avoid acquiring COVID-19, and family members should prevent transmitting either disease to themselves or the infected patient. Patients should be educated on respiratory hygiene, flu-like symptoms suggestive of the COVID-19 disease, and the benefits of fulfilling treatment.^17,18

Contacts require adequate ventilation, a physical distancing of at least 1 meter, and all airborne control measures, including masks and facial protectors, for at least two weeks, and probably much longer, after starting the anti-tuberculosis medication to avoid reinfecting the patient.¹⁷

Basic biosecurity measures apply for both diseases in congregate settings such as health care facilities, including cough etiquette and patient triage.^37,40,41 Timely refills to TB patients decrease the transmission probability and possibly protect the patient from acquiring a new disease.¹⁷ Furthermore, active case finding, contact tracing, and prompt diagnosis for COVID-19, TB, or both is essential.

Laboratories may benefit from the same sample, transportation media, and contact center. Community-based clinics should be preferred over hospitals for TB patients to reduce resistance and severity of the disease. Adequate stocks of TB medicine should be provided. Electronic medication monitors and video-supported therapy can help keep patient adherence to the medication and continue surveillance of the extent of the disease in the community.⁴⁰

There also exists evidence about the benefits of BCG vaccination in decreasing COVID-19 severity. It has been shown that it produces positive immune effects that ameliorate the response against other pathogens.⁴² Some in vitro studies verify BCG vaccine protection by increasing IFN-gamma release by CD4 cells.⁴³ Despite this emerging evidence, developing countries must not fall into false security and inaction against novel SARS-CoV-2 and the probability of coinfection.

LTBI screening and treatment should also be considered depending on the epidemiologic and socio-economic risk of the population.^17,18 It is estimated that about one-third of the world’s population has LTBI.²¹ High TB burden countries have a TB incidence equal or more than 100 per 100 000 people.²¹ Populations at risk include HIV-positive patients, household contacts of pulmonary TB cases, and patients either diagnosed with silicosis or treated with anti-TNF drugs, dialysis, or organ transplantation.

For low TB burden countries, only HIV-positive people and children under 5 years who are household contacts of active TB cases should be considered for testing.²¹ High-risk populations with a high TB burden do not require an LTBI test prior to treatment; therefore, these groups should receive isoniazid daily for six months.²¹ Because of the relationship between LTBI and COVID-19, national tuberculosis programs might benefit from local risk stratification tools intended to improve active case finding and preventive measures toward members of high-risk households.⁴⁴

In May 2020, the WHO released a note to report that simultaneous testing of TB and COVID-19 in case of either infection should only occur if clinical features are common to both diseases, concurring exposure to both diseases was possible and there were risk factors for poor outcomes to either disease. Nevertheless, all countries might need to reconsider the patient background. For example, more than three people living in a single bedroom (or the same environment) and inconsistently using biosecurity measures may warrant routine simultaneous testing.^17,18,40,45

Whether medical history analysis or a certified LTBI test is enough or even possible given the pandemic economic burden and the reality of developing countries is still imprecise. Either way, early LTBI screening may help prepare appropriate isolation environments to prevent TB spread if reactivation occurs, assemble special medical resources such as ventilators or ECMO therapy, and consider treatment options and their interactions.¹⁸ For instance, immunosuppressive therapy should be deeply reconsidered if there exists the possibility of TB reactivation in a COVID-19-positive patient.¹⁸