30 March 2012

Nigeria: Resistant Tuberculosis - Our Daunting New Challenge


As the world marked World Tubercuosis Day last Saturday March 24, setting new targets to combat the disease which claims millions of lives annually, Nigeria worried about emerging cases of multi-drug resistant tuberculosis which poses a threat to the global effort to stop TB. Kingsley Obom-Egbulem examines this development and the country's readiness to deal with it

Stigma and discrimination against people living with HIV/AIDS can be devastating. Coping with the clinical challenges of the human immunodeficiency virus itself is tough. Add that to a loss of job, loss of apartment, rejection by friends and family members, excommunication from church and even expulsion of children from school by intolerant and unenlightened proprietors, and you have someone under pressure. Ask anyone living openly with HIV/AIDS; its tough!

Abigail Obetan Atireni lived and coped with all of these for over ten years, often using the media and other available platforms, to address and educate the public, including her adversaries, to love and not leave people living with HIV; to accept and relate with them as kith and kin because that is who they are.

But there was something Abigail could not cope with. At some point in her sojourn with HIV, she developed Tuberculosis (TB), a highly infectious disease which is the bane of many people living with HIV. The battle against TB turned out to be one of Abigail's fiercest. In fact, her fiercest. It cost her her life.

Tuberculosis is a common, and in many cases, lethal infectious disease caused by the bacteria Mycobacterium tuberculosis. It typically affects the lungs but can also spread to other parts of the body. It is spread from person to person through the air. When people with lung TB cough, sneeze or spit, they propel the TB germs into the air, and all an uninfected person needs do to become infected is inhale a few of these germs from the droplets of the already infected person.

Tuberculosis was first declared a global emergency in 1993 by the World Health Organization (WHO). Between the 1950s and the late 1980s, the disease was practically eradicated in most parts of the world, particularly North America. In the early 1990s, however, the world became alarmed when incidence of the disease dramatically escalated. This resurgence was attributed to the increased susceptibility to tuberculosis of people infected with HIV. TB is one of the main opportunistic infections affecting people living with HIV. It typically becomes more severe in people with AIDS than in those with a healthy immune system.

According to WHO, someone becomes infected with the bacteria that cause TB every second. One-third of the world's population is infected with the bacteria, and as many as one in ten of those infected will develop active symptoms of tuberculosis at some point in their lives with people living with HIV said to be at much greater risk than others.

"The reality is that many people harbour the bacteria but have no symptoms of disease because they still have a strong immune system that can withstand the disease", says Dr. Dan Onwujekwe, an infectious diseases specialist and Senior Research Fellow at the Nigerian Institute of Medical Research (NIMR), Lagos.

"Because HIV weakens our immune system, these dormant bacteria becomes active, chronic and infectious and when symptoms develop, they include coughing, chest pain, shortness of breath, loss of appetite, weight loss, fever, chills, and fatigue. "

These were some of the signs and symptoms Abigail faced.

"In 2007, I was pleasantly surprised to see her walk into our Abuja office. I noticed she was coughing intermittently-it was a deep throaty cough and I had to confront my fears about her health", wrote Olayide Akanni, Executive Director, Journalists Against AIDS (JAAIDS) in her tribute to Abigail.

Abigail was apparently coming from the hospital where she had gone to undergo some TB tests, the results of which revealed that she had developed a multi-drug resistant strain of tuberculosis (MDR-TB).

MDR-TB refers to tuberculosis that is resistant to isoniazid (INH) and rifampicin (RMP), the two most powerful first-line anti-TB drugs.

Abigail's situation was a frightening reality as help was not close by, given Nigeria's capacity then with respect to TB intervention.

"As at that time, only two centres in the country had the required capacity to conduct tests for drug resistant TB. Besides, the World Health Organisation (WHO) had only approved for a pilot MDR-TB treatment programme in Nigeria." said Olayide.

"We discussed with some officials in the National TB and Leprosy Control Programme and WHO Nigeria to see how she could access drugs under the pilot programme", Olayide continues. "However, approvals for this process could take some time. On the other hand, she also contacted a US-based Non Governmental Organisation who were willing to support her treatment. However, that would require travelling to the United States."

So, while awaiting enrolment on the pilot programme of the National TB and Leprosy Programme, she pursued the option of seeking comprehensive treatment outside the country. Unfortunately, she was refused a US Visa.

And on Saturday, January 15, 2011, Abigail, having battled with tuberculosis for more than four years, finally succumbed. She died leaving behind concerns and critical questions about Nigeria's TB response and its potential to contend with MDR-TB.

What is the size of Nigeria's MDR-TB burden? What are we doing to ensure we routinely test patients to know those with MDR-TB? What facilities are on ground to respond to detected cases of MDR-TB?

"We do not test patients to know whether or not they have been infected with MDR-TB before showing up at our centres. We are not able to test for MDR-TB routinely unless if the regular treatment fails. If treatment fails, we suspect that the person has MDR-TB by first asking whether they took the drugs as prescribed and if they tell you that they took the drugs as prescribed, then we send them for culture and drug susceptibility test (DST) to establish if it's a case of MDR-TB or not", says Onwujekwe, one of Nigeria's most consistent TB researchers.

Tuberculosis drug susceptibility test (DST) should ordinarily be done on a routine basis. But it is not. "This is not because we are concerned about cost", says Onwujekwe. "If our politicians know the implication of having our name on the list of countries with high cases of MDR-TB , they will spend anything to address it."

Well, Nigeria is already on that list. And so are many countries for that matter, according to the WHO. But how can we cope with the challenge of this variant of the tuberculosis bacteria and rescue the rising population of people with MDR-TB from imminent death in our country?

Patients with MDR-TB are coping in many countries. If Abigail were a UK citizen or living in the UK, for instance, it is likely she would be alive today. Paul Thorn alluded to this possibility at an MDR-TB experience sharing session in 2009 in Geneva.

"I am alive today because I am British, living in Britain where there are provisions for people like me to stay alive despite being infected with MDR-TB. But a lot of people are dying of MDR-TB across the world; they are dying not necessarily because MDR-TB is a killer, they are dying because of where they were born and what part of the world they live in".

Thorn, currently one of the faces of MDR-TB and a vocal TB treatment advocate is an attestation to the triumph of political will and a coordinated response over an infectious and difficult-to-treat tuberculosis.

By itself, TB is already bad news being one of the world's worst killers, accounting for 9.4 million cases and 1.7 million deaths in 2009, according to the WHO. Treatment for TB is also not simple, since it requires at least eight months of taking a combination of unpleasant tasting pills with equally unpleasant side effects.

And because some patients default in adhering to treatment instructions and others stop treatment completely the moment they start feeling well (even when they still have several pills to take), cases of drug resistance TB (DR-TB) will continue to develop.

Cases of multi-drug resistant (MDR-TB) and extensively drug-resistant (XDR, TB) which mean that the TB infection is resistant to the first-choice drugs, require that the patient, instead, be treated with a larger cocktail of "second-line" drugs, which are less effective, have more side effects, and take much longer times (sometimes two years) to effect a cure. Experts say XDR -TB is resistant to the three first-line drugs and several of the nine or so drugs usually recognized as being second choice.

There are even cases of Totally Drug Resistant TB (TDR-TB) with 12 patients already diagnosed in India late 2011 and 15 diagnosed in 2009 in Iran. As the name implies, these cases of TB cannot be treated with any of the known first line and second line drugs.

The WHO predicts there would be 2 million MDR-TB or XDR-TB cases in the word by 2012. This is a gloomy picture in every sense. And according to Onwujekwe, Nigeria should not be prominent in this picture if she had given her fight against TB all the seriousness it deserves.

"Multidrug-Resistant TB was declared an emergency in Nigeria in 2006 but it is not just enough to declare an emergency, we need to take an emergency step as well as sustainable steps to address the emergency".

But it is not all gloomy for the most populous black nation in the world. A landmark achievement for Nigeria as the world marked the 2012 World TB Day last Saturday was the announcement that the country now occupies the tenth spot on the list of high burden countries.

"That is some good news considering the fact that we were occupying the fourth position. It shows we are making progress", says Onwujekwe.

But he is quick to add: "However, we have to celebrate with caution because we are still grappling with MDR-TB".

The celebration of the country's progress can be sustained if the 40-bed facility recently commissioned in Lagos to cater for patients with MDR-TB lives up to expectation. The celebration could peak if the facilities in Ibadan and Calabar as well as the 60-bed facility in Zaria are able to consistently carry out effective screening and treatment of patients with MDR-TB.

"For the first time we have a marshal plan against MDR-TB. We have facilities and enough drugs to place 101 patients on admission for eight complete months and another 12 months after discharge", says Onwujekwe.

Could this so-called marshal plan have saved Abigail if we had it in place earlier? Could it ensure we do not lose more people to MDR-TB?

The answers we may never know for sure. But perhaps we can safely say, "most likely".

But like Onwujekwe noted, there is a constant fear; "those we are likely going to be treating in the MDR-TB facility may have infected people with a TB strain that is already resistant even before commencement of treatment. How do we track these people and ensure they are screened and placed on treatment early?"

That is the bigger question which constant awareness and mass TB screening would likely resolve.

Key facts

•Tuberculosis (TB) is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent.

•In 2010, 8.8 million people fell ill with TB and 1.4 million died from TB.

•Over 95 per cent of TB deaths occur in low- and middle-income countries, and it is among the top three causes of death for women aged 15 to 44.

•In 2009, there were about 10 million orphan children as a result of TB deaths among parents.

•TB is a leading killer of people living with HIV causing one quarter of all deaths.

•Multi-drug resistant TB (MDR-TB) is present in virtually all countries surveyed.

•The estimated number of people falling ill with tuberculosis each year is declining, although very slowly, which means that the world is on track to achieve the Millennium Development Goal to reverse the spread of TB by 2015.

•The TB death rate dropped 40% between 1990 and 2010.

UNICEF, Others Intensify Polio Eradication Efforts

United Nations Children's Fund (UNICEF), Bill and Melinda Gates Foundation, the Centers for Disease Control and Prevention (CDC) and the Polio Eradication Initiative (PEI) Partners are collaborating to scale up a Volunteer Community Mobilizer to end polio in Nigeria.

To achieve their goal, the network is targeting the most high-risk States of Kebbi, Kano and Sokoto by March and Zamfara, Jigawa, Borno, Katsina and Yobe by May 2012, which is part of the Nigeria PEI Emergency Plan to reduce the percentage of missed children of oral polio vaccine.

A statement by UNICEF Nigeria Representative, Dr. Suomi Sakai said in total, over 2,150 settlement level volunteer mobilizers will be recruited, trained and deployed in the settlements (villages) where missed children and refusals of oral polio vaccine are still persistent.

A breakdown shows that, in the first phase, these volunteer mobilizers cover 557 settlements in Kano, 200 in Kebbi and 200 in Sokoto, as Sakai reviled that, the first training of trainers (ToT) session took place in Kebbi and Kano early March with cascade training for settlement volunteers to follow so that at least 200 mobilizers will be operational in some of the high risk settlements before the March IPDs at the end of the month.

"Through this extensive social mobilization effort and increased house-to-house behavior change communication, Polio Eradication Initiative aims to achieve the goal of immunizing all missed children in those high risk settlements, and make Nigeria polio-free," Sakai noted.

Sakai explained that, the volunteer community mobilizers who were selected from their settlements will be trained to work as 'change agents' in their respective communities and would be responsible for resolving non-compliance and tracking unimmunized children in their own high risk settlement and carrying out door-to-door communication interventions with caregivers on issues related to immunization and key household practices. He said the volunteer community mobilizers will among other things identify, characterize and facilitate the vaccination of chronically missed children, mobilize non-compliant parents through community friendly approach and resolve all cases of non-compliance.

They will also create conducive environment in the community through networking and partnership, as well as create interpersonal counselling on immunization and key household practices and will also carry out door-to-door and person-to-person enlightenment programmes.

Group to Unveil Drugs for Resistant TB

As the World Tuberculosis Day celebration was being rounded off, an international organization, Global Health Alliance has unveiled plans for the first clinical tests of a new treatment regimen for tuberculosis, including for patients with resistance to existing multidrug programs.

The World Health Organisation (WHO) has said that one third of the global population is suffering from tuberculosis without knowing and lately a threatening strain of the disease which is resistant to multi-drugs is emerging.

The TB Alliance, which is funded by several governments and foundations, said the new drug combination offers promise in the fight against TB, which kills an estimated 1.4 million people each year, mostly in Africa.

Health experts said the new program could be particularly useful for an estimated 650,000 people around the world who suffer from multidrug-resistant TB (MDR-TB), a number expected to rise, and could shorten treatment times.

The President and Chief Executive of the TB Alliance Mel Spigelman said "there is new momentum and new hope in TB research, as shown by this and several other novel regimen trials that will soon be launched. The novel TB drug regimen has the potential to unlock a new and more efficient approach to tackling TB."

He further stated that "in essence, it's a step toward erasing the distinction between TB and MDR-TB -- and in the process, dramatically shortening, simplifying, and improving treatment."

Currently, someone with TB must take a course of drugs daily for six months, while those with MDR-TB must take a daily injection for the first six months and a dozen or more pills each day for 18 months or more.

Many TB patients fail to complete treatment because they cannot tolerate the difficult side effects of the medications or cannot adhere to the long-term treatment, according to the TB Alliance.

A Double Dose of Debilitating Conditions

Recent studies indicate that diabetes can worsen the clinical course of Tuberculosis, and TB can worsen glucose control in people with diabetes. The challenge of these serious conditions co-existing in the same patients is now a source of concern to many health workers. You should be concerned too. Kingsley Obom-Egbulem reports

Even when it is unconnected with another disease, Diabetes Mellitus on its own, offers little cheering news. It is a terminal disease that has no known cure. But it is preventable and that is the only cure being advocated by experts.

Patients with diabetes produce insufficient insulin - a hormone that helps the body's cells absorb glucose (sugar) so it can be used as a source of energy. In people with diabetes, glucose levels build up in the blood and urine, causing excessive urination, thirst, hunger and problems with fat and protein metabolism.

Now, imagine diabetes and tuberculosis in one patient.

That is the reality that may soon be confronting many patients living with diabetes (yet to test for TB) as well as TB patients currently undergoing treatment without doing regular diabetes check. And it's already happening.

"In 2008, a survey of TB patients receiving treatment at the Lagos University Teaching Hospital (LASUTH) showed that the prevalence of under-diagnosed diabetes was 6 percent. And for most endocrinologists, this trend is a worrisome reality that needs to be given some measure of attention", says Dr. Anthonia Ogbera, Head ,Endocrine Department at the Lagos State University Teaching Hospital (LASUTH),Ojo.

Her colleague at the Lagos University Teaching Hospital (LUTH) Dr.Olufemi Fasanmade lends credence to her submission.

"TB patients with diabetes can actually have their blood sugar increased when they commence TB treatment due to the effects of Isoniazid, one of the drugs used in TB treatment", says Fasanmade who is consultant endocrinologist at LUTH.

But Dr. Dan Onwujekwe, Senior Research Fellow and TB clinician at the Nigerian Institute of Medical Research (NIMR) has what looks like the flip side to this.

"It is a known fact that diabetes lowers the immune system and affects the body's ability to cope with diseases and so you become prone to infections; and not just that, the TB bacteria thrive in sugar environment hence, we will rather advice that those currently treating diabetes should screen regularly for TB because they are highly susceptible".

Some call it a chicken and egg situation, which comes first; the threat of diabetes in people infected with TB or the threat TB poses among patients living with diabetes?

Whichever way it sounds, the warning bell definitely has a tone which patients suffering from either of the disease can conveniently interpret. And the World Health Organisation(WHO) seems to be helping anyone willing to listen.

"Diabetes prevalence is increasing worldwide, and people with diabetes have a 2-3 times higher risk of TB than people without diabetes. In addition, diabetes can worsen the clinical course of TB, and TB can worsen glucose control in people with diabetes", says WHO in a recent report developed in concert with the International Union Against TB and Lung Disease to create Collaborative Framework for Care and Control of Tuberculosis and Diabetes.

The framework is expected to establish mechanisms for collaboration between national TB programmes and suitable counterparts responsible for care and control of diabetes, improve detection and management of TB in patients with diabetes, as well as, improve detection and management of diabetes in patients with TB.

"I think one of the achievements we want to celebrate perhaps soon would be the day endocrinologists and other infectious disease specialists managing TB patients can sit down together to work modalities on how to effectively ensure the best outcomes for those of us affected by diabetes who are already vulnerable to TB", says Ranti Adeleye (not real name), a diabetic who is concerned about the growing incidents of TB and diabetes co-morbidity.

This proposed collaboration perhaps can come by way of co-location of treatment centers for diabetes, TB, HIV and AIDS. "That way, we can ensure that diabetes patients can also have the opportunity to access TB diagnoses and care within the same facility", says Fasanmade.

The WHO even recommends specific and measurable activities that can drive and focus such collaborations. These include: conducting surveillance of TB disease prevalence among people with diabetes in medium and high-TB burden settings, conducting surveillance of diabetes prevalence in TB patients in all countries, intensifying detection of TB among people with diabetes, ensuring TB infection control in health-care settings where diabetes is managed and ensuring high quality TB treatment and management in people with diabetes and detecting and managing diabetes in patients with TB.

These no doubt addresses Adeleye's concern but considering the fact that diabetes is a lifestyle disease, the responsibility is first for Nigerians to cultivate health-seeking behaviour and in Fasanmade's opinion such behaviour begins with eating healthy food.

"In Nigeria, obesity seems to have become a sign of good living but overseas, obesity is a disease of the poor. The rich are slim while the obese are apparently poor but here one of the signs that you have arrived is your size and when you are slim it's a sign that you are not eating well and that is why we have people who are really sick but would not admit it until it is too late just because of the picture our society has painted about a healthy person", says Fasanmade who is Consultant Endocrinologist at the Lagos University Teaching (LUTH).

According to Fasanmade, with excess weight comes obesity and obesity comes with the fear of diabetes and the threat of TB.

"Over the years, the diets of the average Nigerian has changed from fruits, vegetables, fish to fast food, juices and junks and this is not happening without its consequences, part of which is diabetes and now TB", says Ogbera .

"Diabetes is both a disease of poverty and affluence, especially in Africa, and I can say without any fear of contradiction that some people wouldn't have had diabetes if not for the fact that the food they eat and how they live changed with an increase in their income", she added.

Tuberculosis is also a disease of poverty given the fact that most high burden countries are places where over 60 percent of the population live below the poverty line. Perhaps the threat of TB among diabetics may just be an eye opener and a call to caution for Nigeria's growing league of the affluent whose wealth may be pushing them towards unhealthy living.

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