Managing MDR tuberculosis in Nepal

The burden of multidrug and extensively drug resistant tuberculosis might be underevaluated among Nepalis, threatening bordering countries. Sophie Cousins reports from Kathmandu.

For more than a month, Ram could not stop sweating and coughing. The 29-year-old from west Nepal—who lives in Kathmandu for his studies—did not know what was wrong. He had never heard of multidrug-resistant (MDR) tuberculosis until he visited Kalimati Chest Hospital in the capital for a check-up 2 weeks before, when he was faced with a grim reality. Ram was diagnosed with MDR tuberculosis and was told he needed to start treatment immediately. Doctors started him on a treatment regimen of seven drugs, including 4 months of daily injections of kanamycin.

“The injection is so painful, but at least I'm on the shorter treatment”, he said. Because Ram is HIV-positive and lives far from any treatment centre, he was admitted to the 15-bed hostel attached to the hospital that has specifically been set up for patients with MDR tuberculosis like him.

Case detection

Last year, more than 35 000 cases of tuberculosis were documented in Nepal, according to the latest data of the Nepal's National Tuberculosis Programme (NTP) seen by The Lancet.

The figure is likely much higher, said Naveen Prakash Shah, consultant chest physician at the National Tuberculosis Centre (NTC)—the focal point of the NTP located between Kathmandu and Bhaktapur—partly because a large number of patients in urban areas seek care in the private sector, which by law does not have to notify the government of confirmed cases.

Although, according to WHO data, Nepal's tuberculosis incidence has been stagnant over the past decade, the number of MDR tuberculosis cases is increasing. The NTC estimates that currently more than 1100 people have MDR tuberculosis, but only 343 patients are in contact with the country's poorly functioning health system.

“It's difficult to know how many cases of drug resistance we have. We're missing a lot of cases”, Shah said.

Nepal also estimates that the number of extensively-drug resistant (XDR) tuberculosis cases—a form of tuberculosis resistant to at least four of the core groups of second-line anti-tuberculosis drugs—is increasing. Last year, 19 cases of XDR tuberculosis were reported, but Shah fears that the reality is much worse.

Diagnosis of MDR tuberculosis has become easier with the increased availability of an effective diagnostic device called GeneXpert—a nucleic acid amplification test that tests sputum samples for Mycobacterium tuberculosis DNA and resistance to rifampicin. Experts point to this as one reason for the increase in detected and reported MDR tuberculosis cases.

However, although diagnosing patients has become simpler, late diagnosis—or lack of diagnosis—is still a concern, experts warn.

Bhawana Shrestha, a tuberculosis specialist working at the Kalimati Chest Hospital, which is part of the Nepal Anti-Tuberculosis Association, a non-profit organisation aimed at raising awareness about tuberculosis, said she was diagnosing an increasing number of MDR tuberculosis cases.

“All the new MDR tuberculosis cases I've recently seen are people who have never had tuberculosis before”, she said.

For Shrestha, because diagnosis remains slow in Nepal, undiagnosed patients living with MDR tuberculosis can still spread the disease, and “the chain of transmission continues”. According to WHO, emergence and spread of multiple-drug resistance are due to person-to-person transmission and mismanagement of tuberculosis treatment, including the use of ineffective formulations of drugs, incorrect use of drugs, and treatment interruption. Shah said he was concerned the private sector could be contributing to this by failing to detect resistance and not prescribing the right drug regimen for treatment, although he understands how the private system could be more appealing to a patient. “Private hospitals are well equipped, [whereas] the government sector is busy, crowded, and patients have to wait a long time [to be seen]”, he said. A tuberculosis act was recently endorsed by the government. When implemented, the private sector will be required to notify the government of any confirmed tuberculosis case every 2 months.

A shorter treatment regimen

There are currently 30 GeneXpert centres across Nepal and 18 sites that provide MDR tuberculosis treatment. Four of those sites began offering the shorter MDR tuberculosis treatment regimen of 9 to 12 months—comprising an intensive phase of 4 to 6 months of treatment—in January. The remaining MDR tuberculosis treatment sites offer the standard 20-month treatment, which includes an 8-month intensive phase of daily injections.

WHO included the shorter regimen in its updated guidelines for drug-resistant tuberculosis in 2016. Although this recommendation was based on limited evidence, it was thought that the regimen would be less costly and would improve patient retention rate in the so-called continuation phase of the treatment, which can be challenging, notably for those who live far away from the treatment centres. For Shah, the longer treatment regimen takes “a long time, with not very good success rates”.

According to data available from the NTP, the rate of successful MDR tuberculosis treatment has decreased over the past 5 years. The success rate currently stands at 67%, a decrease of 4% on previous years. Experts are unsure of the reasons for this decrease. Most patients with XDR tuberculosis have died.

Migration an epidemiological challenge

Every day, more than 1500 Nepalis leave the country for opportunities abroad, primarily in India, Gulf countries including Qatar and Saudi Arabia, and Malaysia. Research from the National Institute of Development Studies shows that almost 10% of the Nepal's total population—2·2 million—are currently working abroad. That figure does not include the number of Nepalis who leave to work illegally.

Affected by poverty and poor job opportunities, many end up working and living in terrible conditions that are perfect breeding grounds for tuberculosis. “They stay in hazardous situations with no nutritious foods, with 18 people in one room, no air, and the problems get worse. Some of those cases turn into MDR tuberculosis because they never seek treatment”, said Sudeep Uprety, a former tuberculosis researcher with HERD International, a research and development agency in Kathmandu.

Ramisetty Venkata Rama, head of the migration health assessment programme at the International Organization for Migration (IOM), said the organisation is seeing an increase in MDR-tuberculosis cases among prospective migrants and refugees. The IOM is responsible for screening immigrants leaving Nepal for countries including New Zealand, Australia, and the USA for work or study, and also Bhutanese refugees.

“We're really concerned about it. It's a trend in the country”, she said.

Unlike countries such as Australia and the UK, which follow rigorous health assessments for visa applicants, there is no standardised health assessment for those migrating to the Gulf and India. That means health checks are not immune to falsification, Rama said.

“These people are desperate for a job, so some doctors say they've been vaccinated or they write that they're not sick when they are. That means they carry infectious diseases to other countries and are not given support in host countries”, she said.

Rama and her colleagues said their main concern was there was no proper health policy around labour migration in Nepal.

Radheshyam Kc, migration health physician and former national health officer for the IOM, estimates that 90% of the Nepalis deported from the Gulf for medical reasons are because of tuberculosis.

Cross-border migration to India is also a concern, particularly for the spread of MDR and XDR tuberculosis, Kc said. The porous, unregulated border between Nepal and India is almost 2000 km long. Although Nepalis do not need a visa or passport to legally work in India, most cross illegally at unofficial border crossings without going through a health screening, Uprety said.

The proliferation of over-the-counter purchasing of tuberculosis drugs in the Terai, a lowland region in southern Nepal that borders India, and among migrants in India itself, further complicates the issue, the IOM said. “[Migrant Nepalis] work for a very small wage and find it difficult to ever seek health care”, Uprety said. But Uprety said poor data and research on migrant health in Nepal made it difficult to advocate for improving the situation.

A migrant health policy—the first of its type in Nepal—is currently under review by a range of ministries. The policy includes a standardised health check, a standard orientation process for all migrant workers, and mandatory post mortems to be completed on migrant workers who die abroad. Uprety said it was a step in the right direction but stressed a migrant health policy at the regional level was needed.

Another complicating factor in the country's fight against MDR tuberculosis is the small number of health-care workers willing to work in the field. In the past 8 years, 21 health-care workers have died from MDR tuberculosis, Shah said. He blamed the deaths on inusufficient precautions taken inside tuberculosis wards. Shrestha, who has been working on tuberculosis for three decades, is a prime example. She said she only began wearing a mask to protect herself 2 years ago.

Next to the hospital, Ram is chatting with his new friends at the hostel. But Ram is not happy here. “I've got many friends here but I'm so homesick”, he said, wiping the tears off his cheeks.


Source: The Lancet

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By Sophie Cousins

Published: May 5, 2018, 12:36 a.m.

Last updated: May 5, 2018, 12:40 a.m.

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