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Posts Tagged ‘MDR-TB’

Dr. Prakash Mishra, director of the Regional TB Centre in Pokhara, Nepal, looks at a chest X-ray of a patient. Photo by Kiran Panday

KATHMANDU, Nepal – In a walk-up doctor’s office, off a busy street in Kathmandu, Dr. Dirgh Singh Bam sees patients every day in relative anonymity. His walls, though, reveal a history of being in the limelight: plaques and ribbons and framed photographs covering every inch, highlighting Dr. Bam’s efforts in leading Nepal’s TB control program from 1995 to 2004.

With assistance from the World Health Organization, Bam and a dedicated team of health workers ushered in an era of DOTS – directly observed treatment, short-course – by traveling all around the mountainous country to ensure that the strategy was followed. Health workers had to watch each patient swallow their TB pills every day.

“We made sure we had a DOTS committee in every sub-health post, every health post, every district hospital and the central hospital,’’ Bam said. “We went to mosques, temples, churches, all religious organizations, just to make sure they supported us.’’

In five years, Nepal installed the DOTS strategy across the country. In 1995, Nepal’s TB cure TB rate was around 45 percent; today it is 90 percent.

These advances made Nepal a model country around the world in TB control. But the question today is whether the country can remain a leader.

It has a major new challenge: controlling the spread of multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB). (more…)

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This post is by Global Center Director Christine Lubinski.

Viet Nam was an fitting spot for last week’s meeting of the Stop TB Partnership Coordinating  Board, since the country’s anti-TB efforts demonstrate both the challenges and the potential for progress in  combating this deadly disease.

Viet Nam’s Vice Prime Minister and Minister of Health welcomed members of the Stop TB Partnership Coordinating Board and expressed pride about the pace of Viet Nam’s economic development, as it stands on the threshold of moving from status as a low-income country to a lower middle-income country.

Viet Nam is one of the world’s 22 high burden TB countries, with significant rates of HIV/TB co-infection that have  contributed to an increase in TB prevalence in young adults.  Viet Nam’s national TB manager outlined the dimensions of the TB problem in the nation, as well as the response that began with a nationwide expansion of DOTS coverage in the 1990s. That effort now includes responding to co-infection and officials have also started to address the 2.7 percent of TB cases that are drug-resistant.  The country just began providing treatment to multidrug-resistant TB patients in 2009 and still only reaches a fraction of those infected with deadly resistant TB disease.  He outlined a number of critical challenges that plague highburden developing countries:

  • Human resources—about 50 percent of TB district staff are brand new and require additional training
  • Inadequate regulation of  TB drugs in the pharmacy market, leading to self-medication
  • ART access for patients co-infected with HIV and TB has improved but remains inadequate.  The 3 Is—Isoniazid preventive therapy, intensified case-finding, and infection control–also need to be strengthened.
  • MDR-TB is an emerging threat and the supply mechanism for second-line TB drugs is insufficient
  • Addressing TB in  so-called “closed settings”—prisons and re-education centers–and the coordination of these institutions with the national TB program
  • Strengthening the role of civil society in TB  control
  • Monitoring and evaluation

The TB manager identified scaling up TB/HIV activities, the response to pediatric TB, and responding to TB human resource needs as key next steps.

Viet Nam’s national TB program hosted a site visit to the Hanoi Hospital on Tuberculosis and Lung Disease, as well as a district health center making great strides in TB control with a burgeoning migratory population moving to the Hanoi area from rural areas of the country.

Outside the Hanoi Hospital on Tuberculosis and Lung Disease

The hospital director described the hospital’s key role in patient care, training, scientific research and providing leadership to the network of 29 district level clinics and providers providing T B services.

Viet Nam treats TB patients for 8 months, with the first two months using the DOTS model at the clinic daily.  After this, patients are given several weeks of medication and must check in with health providers frequently. There are more than 5,000 TB cases a year in Hanoi, and in 2009, almost 12 percent of these cases were TB/HIV co-infection.  Only about half of the TB patients were actually tested for HIV, so the number of co-infected patients is likely to be higher.  The mortality rate among the co-infected patients is 21 percent.  Half of all deaths at this hospital occur among co-infected individuals.  Notably, only 45 percent of the co-infected patients have access to ART.  

Eligibility for ART in Viet Nam is a CD4 count of under 200 or clinical symptoms of WHO Stage IV HIV infection.  Officials hope to move to a CD4 count of 250 soon for ART eligibility and to generally improve access to ART for co-infected individuals.  They have been successful in providing ART to some HIV patients with pulmonary TB.  It is also worth noting the CD4 diagnostic capability is not available everywhere.

Not all TB services are free in Viet Nam.  Patients must pay for physician services, chest X-rays and medical care related to extra-pulmonary TB, which occurs much more frequently in persons living withy HIV infection.

A visit to a district health facility offered an inspiring picture of dedicated staff working to provide TB and HIV services to a growing population of migrants.   This center has substantially ramped up screening of HIV-infected persons for tuberculosis and now ensures that nearly 100 percent of  TB patients are screened for HIV infection. The staff have engaged peer educators in their work to support co-infected patients.  The majority of persons living with HIV infection are injection drug users and center’s staff were excited to report that they are now offering methadone – the first pilot program in north Viet Nam.  They credit donor support for their ability to respond to the multiple health care needs of this complex and vulnerable population.  That donor is PEPFAR. 

The clinic director identified the need for strong support from local political leaders and the engagement of community members as key ingredients of this successful program.

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This post is by the Global Center’s Rabita Aziz.
 
Dr. Luis Sambo, the World Health Organization’s Regional Director for Africa, spoke to global health professionals and African diplomats today at an event sponsored by the Center for Strategic and International Studies (CSIS), about progress made toward achieving goals in the Abuja Declarations made roughly a decade ago.
 
The first Declaration, signed in 2000 by many African heads of state,  made commitments to reduce prevalence and consequently mortality from malaria by 50 percent by 2010.  In a second Abuja Declaration, signed in April 2001, heads of states declared HIV/AIDS to be a matter of emergency.
 
African leaders resolved to place the fight against HIV/AIDS at the forefront of their respective national development plans, as well as consolidate the foundations for the prevention and control of the disease through a comprehensive, multisectoral strategy involving all development sectors of government.  The leaders pledged to take more responsibility for the HIV/AIDS response, while also calling for an increase of external resources. 
 
In addition, the Abuja Declaration removed all taxes, tariffs, and other economic barriers to access funding for HIV/AIDS related activities.  Leaders also pledged to allocate 15 percent of their annual budgets to the improvement of health sectors.  The Declaration called for improving the availability of medical products and technologies, as well as supporting the development of vaccines.
 
Sambo said not all of these goals have been achieved.  For example, African nations on average allocate 6 percent of their budget to health sectors, instead of the pledged 15 percent, due in part to budget deficits.
 
But he also noted many successes in the fight against HIV.  Since the Declaration, there has been an improvement in diagnostics, care and support, and prevention, and dramatically higher coverage of antiretroviral therapy. In 2002, only 2 percent of patients in need of treatment were receiving it; in 2008, that number jumped to 44 percent.  HIV prevalence has dropped from 5.8 percent to 5.2 percent, and the rate of new infections has declined by 25 percent in that timeframe.  And since 2004, the annual number of HIV-related deaths has fallen by 18 percent.
 
Sambo said much of these successes were achieved thanks to external funding mechanisms, such as PEPFAR and the Global Fund.  He stressed that Global Fund and PEPFAR funds made significant contributions to change lives and provide hope.  Sambo also expressed high hopes for President Obama’s new Global Health Initiative, and expects it to be a powerful initiative that will bring many positive results.
 
Despite these achievements, Sambo warned that not enough is being done and gaps in funding are allowing prevalence and mortality numbers to remain high.  For every HIV patient being treated, three more are newly infected, he noted.  Fifty- five percent of HIV infected pregnant women are not receiving ART prophylaxis, while 58 percent of all infected people have no access to ARV treatment.  Life expectancy in the continent has dramatically shortened, with an average life expectancy of at least 60 years in the 1990s, to less than 50 years in 2010. 
 
Sambo also stressed that HIV-TB co-infection continues to be an emerging problem, as the number of TB cases continues to increase and remains the leading cause of death among HIV patients.  The emergence of MDR- and XDR-TB is making the HIV response even more difficult.  Sambo expressed that the failure of integrating HIV and TB services has caused many of the difficulties, and that it’s difficult to achieve integration when two-thirds of funding needs for HIV-TB co-infection are unmet.
 
Health programs, he said, are receiving half of the funding needed for the HIV response.  In total, Africa requires $12 billion to deal with the HIV/AIDS crisis, but is receiving $6 billion.  He said $2 billion is required for the TB response, but $1 billion is available.  In addition, he said $10 billion is needed for health systems strengthening, but African nations have $5 billion at their disposal.
 
But Sambo said funding wasn’t the only issue.  He said African nations need to take on more responsibilities and ownership of programs, and broaden their health policies to go beyond disease control.  In particular, he said, broader health determinants need to be addressed, such as poverty, lack of food security, lack of education, and environmental degradation.

He cited a need for increased support for maternal and child health, as well as a larger focus on women’s and girl’s development.  Nations also need to develop capacity for health research and information systems.  Most importantly, leaders need to make a renewed commitment to fighting the HIV epidemic, as well as use funds more efficiently.

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Last week, the Global Center released a new issue brief on drug-resistant TB to mark World TB Day. Included in the brief was this interview with Dr. Sarita Shah, who recently presented new research showing that strains of extensively drug-resistant TB (XDR-TB) in Tugela Ferry, South Africa, are becoming more resistant.

Tugela Ferry is ground zero for XDR, where doctors first described this deadly bug in 2005. Soon, 53 patients were diagnosed with XDR-TB; 52 of those patients died within an average of 16 days after they sought medical care. Since those first cases emerged, over 500 patients in Tugela Ferry have been diagnosed with XDR-TB, and cases of this deadly infection have been reported in 58 countries. And because of inadequate treatment, XDR-TB strains have developed resistance to an even greater number of drugs than before. In this Q&A, Dr. Shah, an assistant professor of medicine and of epidemiology and population health at Albert Einstein College of Medicine, describes a global health system that essentially guarantees the continued spread of multidrug-resistant TB (MDR-TB) and XDR-TB and talks about innovative efforts to transform the treatment of drug-resistant TB.

Q: You presented new research at the Union World Conference on Lung Health in 2009 showing that XDR has become more resistant. Why and how is this happening?

A: In July 2005, most of the XDR we analyzed in Tugela Ferry was resistant to four to five drugs. By 2009, 100% of patients in our study had XDR that was resistant to at least 6 drugs—and most to 8 drugs. This is a very worrying trend. But it’s not a surprise that drug resistance is going to increase if we have weak TB programs, not enough support, and not enough attention to this critical issue. This is happening because in many places, MDR is being treated in a completely unsupported, chaotic way. That treatment fails, and then we get XDR. And it’s not surprising that if we don’t treat XDR properly, it’s going to get ever more resistant. We will run out of letters soon, and we’ll be at the end of the road, with no more medicines available.

Q: Can you talk about the lineage of XDR and how it was initially passed along?

A: XDR has been around for a very long time. It was present in South Africa as early as 2001. Now that people are looking for it, we’re finding it everywhere. It isn’t a person spreading it around. It’s the conditions that create XDR, and those are everywhere—weak public health infrastructure and inadequate patient support for completing treatment, plus HIV/AIDS.

Q: Can you describe what’s happening on the ground now in KwaZulu-Natal Province, where you and your colleagues do much of your work on drug-resistant TB?

A: What happens in South Africa—and in many other countries around the world—is there’s a centralized, specialty hospital that treats all patients with MDR-TB, because the drugs used for treatment are complicated, expensive and specialized. So, it is felt that treatment should be by specialists who can use the drugs correctly and monitor for side effects appropriately. In KwaZulu-Natal, this hospital used to be able to admit all MDR patients for six months, during which patients are assured to take their medicines every single day. And then for the remaining year and a half of MDR treatment, the patients are supposed to come back every month for a check-up and more medicines. You can probably imagine that not everyone comes back. They live far away. They’re probably feeling better. They can’t afford to miss a day of work. So what happens? In South Africa, we had an MDR default rate of 15–20% percent, so you’re at XDR.

Starting about four years ago, that referral hospital became completely overwhelmed. They have 160 beds, and we diagnose over 2,500 MDR cases in our province alone per year, so you can see how that math doesn’t work. Since the central hospital couldn’t admit everyone anymore, there were long waiting lists to get into the hospital, which is the only way to get the MDR medicines. Half of the diagnosed cases might die before being admitted. The same thing happens in other places as well—or worse, no MDR treatment is available in the country at all—so it’s important to realize South Africa isn’t unique in this sense. The issue of getting MDR patients access to good drugs in a timely way is a major global effort led by the Green Light Committee.

But let’s say a patient manages to get in to the MDR hospital. The doctors would try to give him or her medicines, but they might discharge the patient after 3 or 4 months because they have to face the daily reality of the long waiting lists of patients who are, literally, dying while waiting to get access to the medicines. So, patients are discharged early—with all the best intentions of trying to get more people into care—but, this is the way you get more resistance and also transmit disease to others.

Q: What’s the fix for this kind of situation that guarantees failed treatment, more transmission, and greater resistance?     (more…)

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This post is by the Global Center’s Rabita Aziz. 

After graduating from the University of Mississippi in 2008, Max Woodliff backpacked through Southeast Asia with three friends.  He came back to the United States in the fall, ready to begin a new chapter in his life as a graduate student.  But the next chapter was anything but normal. For starters, he was quarantined and told he might die. The reason? He had contracted multidrug-resistant tuberculosis. That was the beginning of an 18-month ordeal that continues today.

“He’s endured what nobody should have to endure,” said Rep. Eliot Engel, D-N.Y., at a World TB Day briefing in the U.S. House of Representatives, entitled “Tuberculosis– Why U.S. Leadership on this Global Health Threat is Essential.” Rep. Engel joined with four other leading tuberculosis advocates to urge lawmakers to take aggressive action to combat and reverse the current trajectory of the disease, which claimed 1.8 million lives in 2008.

Woodliff described his horrific ordeal to raise awareness and to encourage lawmakers and civil society alike to take action against TB.  “I was shocked I had contracted this disease that many American’s think doesn’t exist anymore,” he said.  Woodliff became aware of his condition after taking a TB test required for admission into a teaching program.  He left school when he was diagnosed with MDR-TB, after doctors found that his cultures were resistant to four TB drugs.  He was placed into quarantine for one month at the National Jewish Hospital, where doctors told him he had a 25 percent chance of dying from the disease, which had not yet caused any physical symptoms. 

He was placed on powerful antibiotics that wreaked havoc on his body; he compared the treatment to chemotherapy in its intensity.  After being released from the hospital, he returned home to Jackson, where medical personnel came to his home twice a day to administer more drugs.  One of these drugs produced serious psychological trauma, which he described as similar to schizophrenia.  At one point in his treatment, he said he lost all sense of logic and reasoning for several days, an extremely frightening episode.  Nearly two years later, Woodliff is still not done with his treatment.   He urged lawmakers to put more effort into TB research and to develop new drugs that don’t have such dangerous side effects.

Rep. Engel used Woodliff’s story to emphasis the point that TB knows no borders and that we cannot isolate ourselves from this deadly threat.  Rep. Engel, who sponsored the TB portion of the Lantos-Hyde Act, expressed disappointment at the Obama Administration’s failure to meet the authorized Lantos-Hyde funding levels for TB. He promised to fight for more funding to combat TB.  Engel, who began his career representing the 17th district of New York during the TB epidemic that struck New York City in the late 1980s, noted that it takes only about $20 to treat a normal case of tuberculosis, but that price shoots up to nearly $500,000 to treat MDR-TB. 

“With TB we know what needs to be done,” he said. “It is a disgrace that we don’t provide what is needed to control it.”

Dr. Randall Reves, medical director of the Denver Metro TB Program and the former Chair of Stop TB USA, echoed moderator Philip LoBue of the CDC, who stated that just treating one patient with MDR-TB in the United States can eat up one state’s entire TB budget. Dr. Reves discussed the urgent need to develop a shorter, more effective drug regimen. The current regimen requires patients to four drugs daily for six months, and that’s for drug-susceptible tuberculosis.  For MDR-TB and XDR-TB, patients have to take more toxic and more expensive drugs for 18 to 24 months.   

“We’re being forced to use TB treatments abandoned 50 years ago,” Dr. Reeves said.  At the current rate of progress, he said, we will not reach the goal of TB eradication (now set for 2050) for another 100 years.  Urgent action and fully funding are needed to address the situation, Dr. Reves said.

Diana Weil, the coordinator for policy and strategy at the World Health Organization’s Stop TB Department, highlighted the successes achieved by the WHO in combating TB while discussing the vital need for more to be done.  The Directly Observed Treatment, Short-course (DOTS) method, pursued in over 184 countries, has resulted in 36 million TB cases treated and 9 million lives saved between 1995 and 2008.  Weil said that although the global average rate of prevalence has fallen, cure rates are much lower in Africa and Eastern Europe.  Global case detection has stagnated at around 60 percent.  The emergence of MDR and XDR-TB has greatly impacted cure rates for TB.  While 90 percent of regular TB patients are cured, the number goes down to 60 percent for MDR patients, and around 30 percent for XDR patients.  Weil stated that the reversal of these numbers requires health systems strengthening, from laboratory strengthening, to greater infection control, to generally improving health systems, all of which will have a positive impact on other areas, such as maternal health.  She also highlighted the importance of improving drug access for the sick in developing countries, citing that diagnostic capacities are advancing faster than treatment access. 

Dr. Ann Ginsburg, chief medical officer for the Global Alliance for TB Drug Development, discussed how problematic it is to use antiquated tools to deal with modern strains of TB.  For example, the diagnostic tool most widely used today, sputum-smear microscopy, was developed in the 1880s. The BCG vaccine, which is largely ineffective when administered to adults, was developed in the 1920s, while current first-line drugs were introduced between 1940 and 1970. Ginsburg emphasized that we need simpler, faster, safer, and better tolerated drugs that are also compatible with antiretroviral therapy, as HIV/TB co-infection is a deadly combination.  Ginsburg would like to see treatment regimens shortened to two to four months, and eventually to 10 days. She said biologically, there is no reason why this cannot be achieved.  All that’s needed is commitment from legislators for full support and funding, as there is currently a $6.2 billion funding gap over 10 years for TB elimination plans.

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There were plenty of frightening statistics and unsettling trends highlighted at today’s World TB Day briefing on Capitol Hill. But one photo captured the true scope of the problem in scaling up diagnosis and treatment of the global TB epidemic.

Celine Gounder, MD, an IDSA member and TB/HIV specialist at Johns Hopkins University, described a recent trip to Malawi, where she saw shopkeepers volunteering to collect sputum samples from customers with chronic coughs. The accompanying photo: a man transporting the sputum samples to a laboratory in a small wooden box balanced on the back of his bicycle.

Dr. Celine Gounder discusses the TB epidemic at a Senate briefing

As Dr. Gounder noted, this small community had overcome one of the hurdles in getting suspected TB patients access to proper care. But many others remain. For starters, those specimens so carefully balanced on the bike would be examined using sputum smear microscopy, the only widely available diagnostic test for TB in Malawi. But Malawi has one of the highest HIV prevalence rates in the world, and the vast majority of HIV-related TB cases will be missed by sputum smear microscopy. A more accurate TB test, culture, is not available in the country because of lack of funding. So many of the patients will get false negative results, and continue to transmit the TB bug.

Her presentation provided compelling evidence of the need for more resources devoted to increased laboratory capacity and better diagnostics for TB. But she noted the gap between rhetoric and reality when it comes to TB funding. See Dr. Gounder’s power point here: CGounder_US Senate Briefing_20100324 and below is a video of her presentation.

“Despite the clear need for a heightened response to the global TB problem, funding that has been appropriated for these activities falls short of what was authorized by the Lantos-Hyde Act and what is needed to make decisive progress,” she said. “USAID, which is the primary US agency conducting global TB activities, received only $225 million in FY 2010 of the $650 million dollars authorized.”

She noted in particular that the White House’s Global Health Initiative includes TB treatment targets that are much lower than those set out in the Lantos-Hyde Act, which reauthorized PEPFAR. And she said HIV/TB co-infection was getting particularly short-shrift.

“Little more than lip service has been paid to delivery of TB-related interventions by HIV programs,” Gounder said.  “Only 16% of all TB patients were tested for HIV in 2007. Only 2.2% of HIV patients were screened for TB. And only 30,000 of HIV patients, 2% of the target, received isoniazid preventive therapy, which has been proven to reduce the risk of TB and mortality by one-third to two-thirds.”

Gounder’s remarks came at a Senate briefing on the global TB epidemic, which included a special focus on drug-resistant TB. The event, entitled “Bringing Methods to Scale: New Perspectives in the Changing World of TB,” also featured a presentation by Ernesto Jaramillo, team leader for MDR-TB for the World Health Organization’s Stop TB Department, who detailed the WHO’s newest data on drug-resistant TB. (more…)

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What is more worrisome when it comes to drug-resistant TB: What we do know about the epidemic? Or what we don’t know?

The latest World Health Organization report on the epidemic provides plenty of both—some grim facts and some disconcerting question marks.  Take these nuggets:

*A shocking 41 percent of countries cannot provide reliable data on the scope of drug-resistant TB within their borders, according to the report, on the eve of World TB Day.

*The up-to-date tools needed to diagnose drug-resistant TB are not available in more than half of the 27 countries most heavily affected by multidrug-resistant TB (MDR-TB).

*An estimated 440,000 new cases of MDR-TB emerge each year, but only 7 percent of those cases are actually being detected. And even fewer are being treated. One-third of the estimated new cases each prove fatal. As for extensively drug-resistant TB (XDR-TB), there’s even less information.

In many of the places that do report good data, the WHO found MDR-TB at record levels; in one region of northwestern Russia, for example, 28 percent (more than 1 in four) new TB cases involved a strain of the bug that could not be treated with standard TB medicines. Other places could be even worse. But poor surveillance, inadequate laboratories, and antiquated diagnostics obscure the full scope of the threat.

 Dr. Mario Raviglione, Director of the WHO Stop TB Department, and Dr. Marcos Espinal, Executive Secretary of the Stop TB Partnership, ran through some of this data in a briefing for TB advocates and experts in Washington today. They also highlighted the lack of adequate funding or political commitment to TB, saying this urgent global health threat simple was not getting the attention it requires.

Dr. Raviglione said Europe is “de facto” asleep when it comes to TB, no UN leader “has ever recognized TB as a priority,” and no rich countries have ever launched a presidential-level initiative to combat the disease. They two WHO officials commended U.S. leadership on TB but said much more needs to be done here and around the world.

Click here to see the full WHO report.

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