TB drugs: poor countries hanging by the thread

Julius Kiiza, 26, was like many youths his age a few years back. He loved to hang out and live a good life. Never in his wildest dreams did he think he was developing a virulent form of Tuberculosis – the multi drug resistant TB (MDR-TB).

I met him at Hoima regional referral hospital TB ward. As he motioned towards me, it was as if his legs would snap under the weight of his body.

Kiiza, a father of four, was diagnosed with MDR-TB on November 28, 2013. Prior to this, Kiiza was already grappling with HIV which was discovered in 2011.

He was to later develop a wracking cough, characterized with chest pain.

“I would lose breath especially at night because of chest congestion,” he said.

Kiiza was diagnosed with TB and was started on the regular eight month drug regimen. Five months down the road Kiiza was found to have MDR-TB.

MDR-TB occurs when bacteria do not respond to Isoniazid and Rifampicin, the two most powerful, first-line anti-TB drugs.

Because of Kiiza’s co-infection (HIV and TB), he swallows at least 20 pills a day and he will be receiving an anti TB injection daily for six months.

 NEW RESEARCH ELUDES LDCs

While identifying those with the active disease will provide a long-term public health benefit, Moses Mulumba, a patent lawyer says that without new, simple and affordable treatments for MDR-TB, this is impossible.

“If pharmaceuticals developed one tablet a day for TB, this would mean reduced pill burden and greater adherence. However, such developments for the developing world are deficient due to the lack of return on investment opportunities for pharmaceutical companies,” says Mulumba, the executive director of Center for Health, Human Rights and Development (CEHURD).  

Most recently, Britain/Sweden pharmaceutical, AstraZeneca announced it was pulling out of all early stages of research and development for malaria, TB and neglected tropical diseases to instead focus on cancer, diabetes and hypertension.

Welcome to the world of intellectual property (IP), where giant pharmaceuticals determine drug availability and pricing.

Prices of drugs vary depending on whether the drug is under patent – 20-year protection by the manufacturer – or generic, where the patent has expired.

In the private sector market, the brand/patented version of Linezolid, an MDR-TB treatment drug, costs $65 (approximately Shs 166,400) for a daily pill. For a patient taking a pill a day for two years, this amounts to over $49,000 (over 125m). It is produced by Pfizer, an American pharmaceutical corporation.

Generic versions of the drug, produced by Hetero, an Indian pharmaceutical company, cost of $8 (Shs 20,000) per pill.

When asked whether he would have afforded Linezolid had it not been provided freely, Kiiza laughed sarcastically: “I think I would have died a long time ago because I don’t have a cent!”

Because majority of Ugandans still survive on less than $1 (Shs 2,560) a day, Uganda receives TB drugs through aid.

The case of ARVs provides a dramatic illustration of the global impact of Indian drug firms.

In 2001, Indian drug company Cipla, introduced first line treatment for HIV at $ 350 (Shs 896,000) per person per year, a stunning offer at the time.

Other Indian firms followed Cipla’s model and today, 80 per cent of people living with HIV who are on treatment in developing countries rely on Indian generic drugs. 

TRADING AWAY LIVES

Uganda being a member of the World Trade Organization (WTO) is under obligation to develop rules that comply with WTO guidelines. Among these is the Trade Related Aspects of Intellectual Property (TRIPS) agreement requiring all members to standardize minimum standards of IP, including patents for pharmaceuticals.

IP rights give the creator an exclusive right over the use of his or her creations for a certain period of time, such as 20 years, for a scientific innovation like medicine.

The pharmaceutical industry in developed countries strongly depends on the patent system in order to recoup research and development costs.

“TRIPS sustain a regime of private monopoly rights which impedes access to essential medicines because of prohibitive prices. It also delays production and market entry of generics because producers will have to wait 20 years for a patent to expire,” Mulumba explains.

Moreover, countries such as India and Brazil where generics are produced now grant medicines patents in order to comply with their obligations as WTO members. New drugs are already patented in these countries meaning that production of affordable generics is now restricted.

Such a restriction led Cipla to establish Quality Chemicals Limited in Uganda because that law does not hold for LDCs.

Under TRIPS, LDCs are supposed to enforce patents on all medicines by 2021. Tentatively, this means the end of all generic drugs.

In response to the TRIPS agreement, WTO delegates issued the Doha declaration on November 14, 2001 which exempts LDCs from implementing patent law for pharmaceuticals until January 1, 2016. This was extended to 2021 last year.

ENFORCING PATENTS IN UGANDA

To guarantee intellectual property rights to innovators, parliament this year passed the Industrial Properties Act. It spells out protection for products and processes in all fields of technology, including medicine.

Mulumba forecasts that the law will only work if there is government commitment to invest in research and development, develop human capacity and offer attractive incentives such as tax holidays to innovators.

“The law integrates flexibilities such as the bolar provision which enables researchers’ reverse-engineer drugs even when the patent on it has not yet expired. But all the seven plants we have are not doing research because of high production costs,” he says.

Another policy is the Anti-Counterfeit Goods law which prohibits the manufacture, trade and release of fake goods on to the market. Contentious, however, is the fact that it regards generics as counterfeits.

 “This is part of a global agenda to keep developing countries from importing from third parties like India and Brazil where the cost of production is much cheaper. All these things are happening because we are a disorganized lot. We Africans are doomed unless we wake up!” says Edgar Tabaro, a patent lawyer with Karuhanga, Tabaro and Associates.

SOLUTIONS TO A GLOBAL CRISIS

In 2000, the UN Security Council declared HIV a global security issue and resolved to establish a Global Fund (GF). GF is the biggest financer for HIV and TB programmes in Uganda, having channeled at least $ 200m over the years.

“In October, Uganda is sending the GF another proposal for HIV/TB funding to enable us scale up prevention and treatment efforts,” Prof Vinand Nantulya, chairman Uganda Aids Commission said.

Uganda is also a member of WHO’s Global Drug Facility (GDF), the largest supplier of quality TB treatments. Nantulya says it is through this that the country procures TB medicines and innovative tools such as the GeneXpert at reduced prices.

“Uganda needs to develop collaborative research so that our scientists can catch up with others in the developed world and partnerships such as the Global Alliance for TB drug development should be more actively supported to allow for the development of drugs that are free of patent restriction,” Tabaro urges.

Currently, 11 TB vaccines are in clinical trials worldwide. WHO estimates that the earliest a vaccine could be licensed is 2020. BCG (Bacille Calmette Guerin) vaccine remains the only vaccine against TB in general use.

This story was supported by the African Center for Media Excellence. 

Better TB management urgently needed

I had heard about Tuberculosis (TB) and the wreckage it causes in a patient’s life just in the passing, until I set out to document issues hindering drug access.

The dismal condition of a patient I found at Bulondo Health Centre III in Wakiso district exceeded my saddest expectations.

Fred Musoke’s lips were chapped, dry and red, bones almost visible and his skin dark as ebony.

He tossed and turned, seeking comfort, coughing and spitting into his lesu.

Death, he said, would be a reprieve.

“I feel feverish all the time and do not have appetite. The woman that I wanted to marry left me about two months ago because of this sickness,” he muttered from behind a dark green mask covering his mouth and nose. He keeps the mask on to avoid spreading the TB to others. Before I could talk to him, I was handed one too.

Before getting TB, Musoke, 31, was a market vendor selling second hand clothes. Then five months ago he was diagnosed with TB.

“I was admitted two weeks ago after becoming so ill one weekend that I could not walk,” he said.

Because Musoke has HIV, he is no stranger to the health centre. It is here that he has been getting ARVs. 

However, his struggle is further complicated by inadequate drugs at the facility.

“Many of our health facilities do not have some of the most required drugs such as Ethambutol, Isoniazid and Rifampicin needed to treat regular TB and also Septrin which is necessary in fighting opportunistic infections like TB in people with HIV,” says Expedit Mwambazi, Wakiso district’s TB focal person

The centre’s laboratory room was crawling with spiders and wasps instead of diagnostic equipment. It has been so for over five years according to one of the health workers. 

Many health centres do not have TB units, which has perpetuated the mixture of TB patients with other patients. The World Health Organization (WHO) warns that people with TB can infect up to 15 other people through close contact.

TB remains the biggest killer of people living with HIV, causing nearly 50 per cent of deaths. Primah Kazoora, a TB survivor, says malnutrition, living in slums and poorly ventilated houses also accelerate the development of TB.

THE LETHAL ANNIHILATOR

Tuberculosis is one of the deadliest and most disabling diseases. It is an airborne disease caused by a type of bacterium; mycobacterium tuberculosis, transmitted by being in proximity to coughing, talking or sneezing patients. 

If not treated promptly and consistently, says Dr Alphonse Okwera the head of Mulago hospital’s TB treatment centre, it weakens the patient, damages the lungs and may spread throughout the body.

In its advanced stages, the sputum comes with blood.

TB affected lungs/Photo-Courtesy

TB kills some 4,700 Ugandans every year.

In its 2013 report, WHO noted that of the 8.6 million people that fell ill with TB in 2012, 1.3 million died. At least 95 per cent of these deaths were recorded in middle and low income countries such as Uganda, Ethiopia and Swaziland.

“In 2012, an estimated 530,000 children became ill with TB and 74,000 HIV-negative children died of TB. At any given moment, 12 million people globally are suffering from an active infection,” reads the report.

TB kills someone approximately every 25 seconds and an estimated nine million new cases develop each year.

The WHO report ranks Uganda 18th out of 22 high-burden countries that account for 80 percent of new TB infections worldwide. According to Ministry of Health and the National TB and Leprosy Programme (NTLP), there were approximately 49,000 new TB cases in Uganda in 2011. 

“The high burden of the TB disease is mainly in the urban and peri-urban centres, with Kampala accounting for 7,800 cases, Wakiso 1,300 cases and other regional towns account for between 1,300 – 1,600 cases each,” says Dorothy Namutamba, the program officer at the International Community of Women Living with HIV/Aids, Eastern Africa (ICWEA).

Although its burden is spread across all age groups, TB exacts its greatest toll on individuals during their most productive years, from ages 15 to 44.

CHALLENGES IN THE TB COMBAT

Uganda in 2000 pledged, as part of the Millennium Development Goals (MDGs), to halve TB prevalence and deaths by 2015. But despite setting up over 1,200 diagnostic centers nationwide it is still far from these goals.

Namutamba says one of the major setbacks is lack of priority and limited information about TB in communities.

“Unlike HIV which has gained ground through community sensitizations and literacy programmes implemented by government and the civil society efforts, TB has been left to the laboratories and the health care providers,” she says.

In an assessment study by ICWEA on the availability and accessibility of TB/HIV services in Kampala, Wakiso, Mityana and Mubende districts between 2010 and 2012, majority of the interviewees showed low knowledge on TB .

“When a person develops active TB, the symptoms including cough, fever, night sweats, weight loss and blood stained sputum, may be mild for many months. This may lead to delays in seeking care,” says Dr Okwera.

Another challenge is the long duration of treatment, lasting at least eight months. 

RISE OF A SUPERBUG

Because of the seemingly long duration, many patients abandon the drugs. 

“Only 78 per cent of those with the disease undergo successful treatment and the other fraction are those that die, fail on treatment and those for whom follow up is lost,” says Dr Frank Mugabe, the acting program manager, NTLP.

Lack of drug adherence has urshered in new drug resistant forms of the bacterium, spreading a new phenomenon of Multi Drug Resistant TB (MDR-TB).

MDR-TB is a form of TB caused by bacteria that do not respond to, at least, Isoniazid and Rifampicin, the two most powerful, first-line anti-TB drugs.

Currently, the two year drug regimen for MDR-TB costs $3,000 compared to $10 to treat regular TB.

“[Comprising] about 20 pills a day and painful injections for six months, MDR-TB treatment is difficult to adhere to. Even if patients adhere, half are likely to die from this type of TB,” says Dennis Kibira, a pharmacist and deputy director of the Coalition for Health Promotion and Social Development (HEPS-Uganda).

In a move to nip resistance in the bud, Dr Mugabe says the country has improved its ability to test for drug-resistant TB by introducing the GeneXpert, a rapid testing machine that can diagnose TB in sputum samples in less than two hours.

GeneXpert machine/Photo-Courtesy

Nevertheless, there are only 14 treatment sites in the country. The ICWEA survey notes that Mubende hospital at the end of March 2013, had five patients who had been confirmed with MDR TB but sent them home because of the hospital did not have drugs to treat them.

“We need a shorter treatment option to transform TB treatment from an agonizing ordeal, to a shorter, more tolerable, more effective and more affordable treatment course,” urges Kibira.

In our second part, we shall examine how patent rights are prohibiting access to new drugs and diagnostic technology in Uganda. 

This story was supported by the African Centre for Media Excellence.