Tanzania reach the first milestone in TB deaths since 2015.

In this interview, Dr Mnyambwa Nicholaus, a research scientist at the National Institute for Medical Research (NIMR), Muhimbili Centre, explains to Orton Kiishweko how Tanzania has managed to reach the first milestone-a 35% reduction in TB deaths since 2015.

Case notification has increased and treatment outcomes and service provisions have significantly improved in the country. TB services have been decentralized to the community level, he says.

Despite this progress, the strategy to end the pandemic by 2035 generally seems to be ambitious. It faces multiple challenges, including the current underdiagnoses, about 30% of all TB cases in the country go undiagnosed and untreated every year.

Question: Please tell us a bit about yourself and your expertise in tuberculosis (TB)?

Answer: I am a research scientist at the National Institute for Medical Research (NIMR), Muhimbili Centre. My current research focuses mainly on understanding how tuberculosis (TB) disease spreads among patients and the link between disease severity and the characteristics of the TB strain infecting the patient. I received my Ph.D. from the Nelson Mandela African Institution of Science and Technology, Arusha. I also served as a fellow at the Afrique One-African Science Partnership for Intervention Research Excellence (ASPIRE), a Pan-African research consortium. In 2021, I became a visiting fellow at the National Institutes of Health (NIH) in the United States. This program is sponsored by NIH and the Bill and Melinda Gates Foundation, in partnership with the African Academy of Sciences, a program building the research capacity of talented African leaders in science. My long-term research goals are geared towards advancing and consolidating expertise in basic and clinical research to further scientific discoveries, particularly in clinically drug-resistant TB.

Q: Can you tell us a bit about TB?

A: Tuberculosis is one of the world’s greatest killers of all time. It was almost certainly a death sentence until the early 1940s, when the first effective antibiotic, Streptomycin, was discovered. Tuberculosis disease is caused by the Mycobacterium tuberculosis bacteria. It is spread when a person with active lung TB exhales or coughs tiny infected droplets. These droplets can remain in the air for several hours where others in close contact can possibly inhale them. Bovine TB is zoonotic and is transmitted to humans from infected animals, mainly cattle, primarily through the consumption of unpasteurized milk, or raw milk products. Lungs are the primary site of the infection, known as pulmonary TB, but the bacteria can also affect other parts of the body, known as extra-pulmonary TB. Symptoms of TB disease include sickness, weakness, coughing, fever, night sweats and weight loss. The discovery of the first effective TB antibiotic is considered by some as the beginning of the modern era of TB treatment, but the true treatment revolution began some years later, following the discovery of other effective antibiotics including Isoniazid and Rifampicin.

Q: What is the difference between Latent TB infection and TB disease?

A: Well, once a person inhales droplets containing TB bacteria, the bacteria travel to the lungs where it may cause infection. Now, in most healthy people, the immune system can recognize and control the bacteria. However, the immune system may not be able to completely eradicate the bacteria, but the person may be asymptotic and unable to spread the bacteria to others. Only a TB test can confirm the presence of the bacteria. This is what we call a latent TB infection. In some people, often later in life, such an infection can progress to active TB disease, which causes symptoms and can be contagious and very serious. In a few people, especially those with low immunity, the progression to disease occurs rapidly after infection, while it may take years, or not occur at all, in other people.

Q: What are the common misconceptions surrounding TB?

A: Advocating for appropriate information for patients, persons at risk and the community is critical for effective control of TB. There are several myths and misconceptions about TB that contribute to stigma and discrimination that can delay or deny patient treatment. Delaying care can result in serious disease and lung damage that makes treatment more difficult. Some believe there is no cure for TB; this is false. It can be fatal without treatment, but with modern medicine, clinicians can successfully cure the illness. There are also traditional beliefs and superstitions surrounding the transmission and treatment of the disease. In some cultures, the disease is attributed to superstition, some believe it is a genetic disease, while others believe patients should be separated from others. The right information is that it is a disease caused by bacteria. Others believe even talking to patients will make them sick. Even if the patient is infected with TB of the lungs, which is contagious, transmission only happens when other precautions such as mask wearing are not taken. People should also know extra-pulmonary TB affects other parts of the body, and it is not contagious, so no quarantining is required.

Q: How have you seen the diagnosis, treatment, and management of TB change over time in Tanzania in the last decade or so?

A: The diagnostic process starts when a person experiencing symptoms seeks care, or a clinician evaluates someone suspected of having TB. The process continues with appropriate testing, treatment and patient monitoring.

For the past 10 years or so, the diagnosis, treatment and management of TB has dramatically changed, not only in Tanzania, but worldwide. For decades, TB programs have relied on microscopy as the frontline test. However, microscopy has low sensitivity and cannot detect drug-resistant TB. In 2010, the World Health Organization endorsed a new molecular-based technique, called GeneXpert, for simultaneous detection of TB DNA and Rifampicin resistance within two hours. This was a major step in improving diagnosis. GeneXpert has excellent sensitivity and performs well in HIV coinfected patients, and in some cases of extra pulmonary TB, where diagnosis has been a challenge because of very low numbers of bacteria. GeneXpert requires similar laboratory safety and infection control as those for microscopy, allowing placement of the system at lower-level health facilities and improving access to testing. TB programs worldwide have been scaling up the use of this technology. GeneXpert was introduced in Tanzania at the program level in 2012. This was followed by a pilot installation of the internet-based “GxAlert” system which connects the GeneXpert devices for automated real-time reporting of diagnostic results to facilitate case management. As we speak today, nearly all regional and district hospitals have GeneXpert machines, with nearly 400 GeneXpert machines throughout the country.

In terms of treatment and management of TB, the national TB program has adopted new guidelines, especially for people with Multi-drug resistant TB (MDR-TB), involving new oral drugs, such as Bedaquiline and Linezolid, that reduce treatment duration. Between 2013 and 2015, Kibong’oto Infectious Disease Hospital in Kilimanjaro Region was the only specialized reference hospital for the treatment of MDR-TB. To date, the government has decentralized MDR-TB therapy, expanding services to the district level and providing the choice for patients to receive treatment and disease management closer to home. As a result, only a few complex cases are referred to Kibong’oto for further treatment and management.

Q: You mentioned about Multidrug-resistant tuberculosis (MDR-TB), what is it?

A: We use the term “drug resistance” to describe disease-causing agents that have developed mechanisms to survive in the presence of medicines used to treat them. Patients infected with drug-resistant pathogens do not respond to treatment and have an increased risk of unfavorable clinical outcomes than patients infected with a non-resistant pathogen of the same type. MDR-TB is when the TB bacteria develops resistance to the two most potent (effective) anti-TB drugs, which are Rifampicin and Isoniazid. These drugs are among the four antibiotics that are the first-line of anti-TB therapy: the others being Ethambutol and Pyrazinamide. There are other forms of TB resistance, including extensive drug resistance or XDR. XDR TB extends its resistance to other second-line drugs which are used to treat MDR-TB.

Q: How common is MDR-TB in Tanzania?

A: Data on drug resistance is scarce because of limited diagnostic infrastructure in Sub-Saharan Africa, including Tanzania. An increase in MDR-TB cases in Tanzania was first noted in 2005, resulting in concerted efforts by the Ministry of Health which designated Kibong’oto Infectious Diseases Hospital as the first center for treatment of MDR-TB. Generally, the prevalence of MDR-TB in the country is low in comparison to most African countries. According to Tanzania’s national TB program, 400-500 MDR-TB cases are reported out of more than 80,000 annual TB cases. The latest national TB drug resistance survey reported an overall prevalence of 1%, with nearly 5% among previously treated cases.

Q: How is TB treated?

A: The most common treatment for a latent TB infection is the antibiotic Isoniazid. For individuals with drug sensitive TB, clinicians prescribe a combination of anti-TB medications for 6-12 months. A common combination is Isoniazid with Rifampin, Pyrazinamide, and Ethambutol, referred to as first-line anti-TB drugs. People who have MDR-TB need to take at least six drugs (first-line, plus other drugs which are referred as second-line) for longer-up to two years-to fight off the infection.

Q: How far has Tanzania come in eliminating the disease? Please share your contextual understanding of this journey.

A: In 2014, the WHO’s World Health Assembly adopted a new global plan with the target to end the global TB epidemic by 2035. According to the latest WHO report, Tanzania, which is among 30 countries with the highest TB burden, is one of only a few countries that are on track to end the epidemic. The country has managed to reach the first milestone-a 35% reduction in TB deaths since 2015. Case notification has increased and treatment outcomes and service provisions have significantly improved in the country. TB services have been decentralized to the community level.

Despite this progress, the strategy to end the pandemic by 2035 generally seems to be ambitious. It faces multiple challenges, including underdiagnosis-currently, about 30% of all TB cases in the country go undiagnosed and untreated every year. The emergence and spread of MDR-TB, non-communicable diseases and an HIV co-epidemic also present significant hurdles. So, more work remains and more resources are needed to reach all individuals and families in Tanzania, and to address many other barriers, like stigma and misconceptions about TB.

Q: During the current pandemic, research and resources were prioritized for a novel infectious disease, that is, COVID-19. How has the pandemic impacted TB research and management?

A: During the pandemic, much of TB resources and funding were redirected to pandemic management. In addition to reduction in funding to support TB research, most laboratory bench work and research interventions were suspended. Public transportation became unavailable making access to TB services difficult. These disruptions resulted in a decline in TB detection rates and enrollment in treatment. In 2020 and 2021, clinicians reported a worldwide increase in TB-related deaths-the first time in many years.

Q: Controlling infectious diseases is a global effort. How can countries best work together to help eradicate TB?

A: TB eradication will only be achieved through a wide collaboration within and across governments and with partners from civil society, communities, the scientific community, the private sector, and development agencies. With political commitment, sustainable funding, and expanding multisectoral collaboration, we can change the game.

Q: What does the future of TB research and treatment look like?

A: Future TB research aims to accelerate drug and vaccine discovery. One of the fundamental challenges in the treatment of TB is the long duration of therapy. The scientific community envisages new approaches for discovery of new medications that shorten treatment duration for all TB cases. A shorter treatment duration (1-2 months) would allow more TB patients to be cured, resulting in less transmission and a reduced burden on healthcare systems that treat TB. In addition, we need to accelerate research and development of a new, effective, and affordable vaccine that will facilitate elimination of TB globally.