Drug-Resistant Tuberculosis on the Rise in Eastern Europe

Author: Ingrid Hein

An epidemic of drug-resistant tuberculosis (TB) is mounting in Eastern Europe, and without intervention on multiple fronts there is little hope the spread will slow. For several years, we have been hearing that there is “a need for urgent action,” said Daria Podlekareva, MD, PhD, from Rigshospitalet at the University of Copenhagen. It needs to be addressed now, she told Medscape Medical News.

However, cultural and political issues mean that it is “not always easy to adopt international guidelines or initiate research projects,” she said at the International AIDS Society 2017 Conference in Paris.

“It’s difficult to go into Eastern Europe and initiate projects and do studies,” she explained. “Some Eastern Europe countries are still behind an iron wall.”

It can be easier to conduct research into infectious disease in other places — even African countries — than in most formerly Soviet Union countries. To help curb the epidemic in Eastern Europe, the World Health Organization (WHO), the Stop TB Partnership, and the European Union should collaborate to encourage governments to recognize TB as a public health emergency and to implement international programs and standards of care, said Dr Podlekareva.

Eastern Europe Is a “Perfect Storm” for TB

TB continues to be a major public health issue, according to the 2017 WHO report — Tuberculosis Surveillance and Monitoring Report in Europe 2017 — released in March. Most of the 323,000 new TB cases and the 32,000 deaths due to TB in the WHO European Region in 2015 occurred in Eastern Europe and Central Asia.

Eastern Europe is a “perfect storm” for the spread of TB because it has high rates of incarceration, HIV infection, and injection drug use, and it has disintegrated healthcare systems, suboptimal TB diagnosis and treatment, and poor adherence rates, Dr Podlekareva said.

In addition, nearly half of all TB cases are multidrug-resistant, which requires longer, more expensive treatment than drug-susceptible TB, and leads to more adverse effects. Treatment is also less accessible in the region.

And because rates of HIV infection are on the rise in Eastern Europe, where antiretroviral therapy coverage is low, the fast progression of immunosuppression leads to increases in the rate of TB and HIV coinfection.

More Likely to Die From TB in Eastern Europe

In an international cohort study on the management of concurrent HIV and TB, Dr Podlekareva and her colleagues found that TB-related deaths were significantly more common in Eastern Europe than in Western Europe or Latin America (Lancet HIV2016;3:e120-e131).

In that study, 1406 consecutive HIV-positive patients aged 16 years or older with a tuberculosis diagnosis were followed up for 12 months at one of 62 HIV and tuberculosis clinics in 19 countries.

The prognosis was far worse for the 834 patients treated in Eastern Europe than for the 317 treated in Western Europe or the 255 treated in Latin America.

Of the 264 (19%) deaths in the study cohort, 188 (71%) were related to tuberculosis.

Cause of Death Eastern Europe, % Western Europe, % Latin America, % P-Value
All 29 4 11 <.0001
TB 23 1 4 <.0001
 “Latin America and Eastern Europe have comparable economies, as middle-or poor-resource settings,” Dr Podlekareva said. But “Latin American patients did better — much better — than the Eastern European patients.”

In Eastern Europe, diagnosis is often made on the basis of clinical judgment, not laboratory confirmation, she pointed out. And treatment is often suboptimal, including very few active drugs. Moreover, disintegrated healthcare systems in Eastern Europe are detrimental to treatment, and care centers for TB and HIV are not combined. Plus, opiate-substitution therapy — an effective treatment for drug dependence — is limited or prohibited in most regions.

“Nearly 40% of our cohort had multidrug-resistant TB,” Dr Podlekareva reported.

Eastern Europe does not have to invent its own solutions; it can adopt “what we already know,” she told Medscape Medical News. Experience from the 1980s HIV epidemic in Western countries can be a guide. There are thousands of publications on the strategies and standards of care that work.

Prisons and Drugs Contribute

In Russia, illicit drug use is a criminal offense, and “methadone treatment is prohibited,” Dr Podlekareva said. “In Eastern European countries, like the Ukraine and Belarus, there are some drug-treatment programs, but they are not widely used as a standard of care.”

With no methadone support and very few social supports for injection drug users, access to treatment, adherence, and retention in care are a challenge.

Clinicians need to ramp up their efforts to convince patients to get treated. “There is a need for clinicians to be more willing to work together, to support these patients,” she said. “When we ask why a patient is not on antiretroviral therapy, they say the patient refused it, but I think it’s the clinician’s task to convince the patient.”

When injection drug users are thrown in jail, as they are in Russia, TB transmission proliferates, Dr Podlekareva explained. A previous study showed that intrapopulation transmission in prisons, population-to-prison transmission, intraprison transmission, and prison-to-population transmission have driven overall population-level differences in TB incidence, prevalence, and mortality rates in countries of the former Soviet Union (Proc Natl Acad Sci USA.2008;105:13280-13285. 

She is not alone in her assessment. “The problem in Eastern Europe will not go away, especially multidrug-resistant TB, if the infrastructure is not improved,” said Christoph Lange, MD, from the tuberculosis unit of the German Center for Infection Research and Research Center Borstel in Germany.

“Patients have been getting treatment on and off,” so new strains of multidrug-resistant TB are emerging, he told Medscape Medical News. “People are now getting infected with drug-resistant strains,” and most Eastern European countries are not equipped to treat multidrug-resistant TB.

Dr Lange said that in the past year he has seen five Armenian patients with multidrug-resistant TB looking for treatment at his clinic. He referred to them as “health-seeking migrants,” and said, “we expect to see more.”

“The number of people with drug-resistant TB is increasing more than 20% every year,” he reported. The current targets of elimination are not credible and they don’t work under the current circumstances; health organizations and governments have to acknowledge that.

“Instead of having the goal of elimination, we need to work toward low incidence,” Dr Lange said. “We have to redefine our goals and address what is most endangering public health.”

Drs Podlekareva and Lange have disclosed no relevant financial relationships.

Source: International AIDS Society (IAS) 2017 Conference. Presented July 2017.

PrEP: effective and empowering

Author: Marieke Bak

Pre-exposure prophylaxis (PrEP) is a new HIV prevention method that consists of a daily pill taken by HIV-negative people to reduce their risk of becoming infected with HIV. PrEP is highly effective in preventing HIV transmission, as scientific research shows. A large international study among gay men and transgender women, the so-called iPrEx trial suggested that PrEP can reduce the risk of HIV infection by at least 92% when the pills are taken consistently. PrEP is also effective when used by heterosexual men and women, as well as by people who inject drugs.

Although PrEP is more expensive than other HIV prevention methods, it can be a cost-effective tool, especially when delivered to people at high risk of HIV. By preventing the costs of lifetime HIV treatment, PrEP may even lead to healthcare savings, especially when the drug patents expire and the cost drops.

Moreover, PrEP is the first method of HIV prevention that is directly under the control of the at-risk individual. This is in contrast with treatment as prevention (TasP), which is dependent upon partners’ HIV treatment adherence to ensure suppressed viral load. Besides, because PrEP separates the act of prevention from the sexual encounter, it can be used without sexual partners knowing and provides additional protection when condoms are not used consistently.

The World Health Organization now recommends that PrEP should be offered as a choice to key populations affected by HIV as well as to anyone else at substantial risk of HIV infection.

TRANSFORMING HIV INFECTION

PrEP is a pill consisting of anti-retroviral drugs that needs to be taken every day in order to be effective. Currently, the only drug approved for use as PrEP is sold by Gilead Sciences and is called Truvada, which consists of a combination of tenofovir and emtricitabine (TDF/FTC). Truvada was first approved for prevention in 2012 in the United States of America.

In contrast to PEP, or post-exposure prophylaxis, PrEP is taken before exposure to HIV to prevent any possible transmission. PrEP works by blocking an enzyme called HIV reverse transcriptase, thereby preventing HIV from establishing itself in the body. While PEP can be thought of as a “morning-after pill” for HIV prevention, PrEP can be compared to the contraceptive pill that is taken every day. Similarly, PrEP may transform HIV infection just like the pill transformed family planning.

The most common side effects of Truvada for PrEP are nausea, vomiting, dizziness, headache and fatigue, although these symptoms usually resolve within a few weeks. Some people in trials also experienced small changes in kidney function or a decrease in bone mineral density. An updated version of Truvada was created that contains a new form of tenofovir, which is thought to be safer for bones and kidneys. At the moment, the so-called “Discover study”, is being set up in North America and Europe to investigate the new PrEP medicine called Descovy.

By the way, PrEP does not protect from sexually transmitted diseases (STDs). Fears that PrEP might be used as a “party drug” exist. However, in the iPrEx study as well as in a meta-analysis by the World Health Organisation, it was shown that PrEP does not lead to an increase in the number of STDs and has no effect on condom use. Rather, PrEP reduces the fear and anxiety that often comes with sexual activity for those at high risk of HIV.

However, because PrEP is not 100% effective and because it does not protect from STDs, it should not be used as a standalone prevention method. According to WHO guidance, PrEP should be offered as part of so-called “combination prevention” which includes the use of condoms as well as regular follow-ups and HIV testing.

PREP IN EASTERN EUROPE AND CENTRAL ASIA

Despite the recommendation to offer PrEP to people at high risk of HIV infection, the global availability of PrEP remains limited. The PrEP target set by UNAIDS in their strategy on ending the HIV pandemic is to get three million people on PrEP by 2020. However, only 2% of this target had been reached in June 2016.

At the moment, Truvada for PrEP has been approved in the United States, Canada, Australia, Peru, South Africa, Kenya, Zimbabwe, Israel, and the European Union. Approval is pending in Brazil and Thailand. In the European Union, PrEP has been approved by the European Medicines Agency (EMA) although the implementation of PrEP programmes is the responsibility of each member state separately. To date, only France and Norway have made PrEP available as part of their healthcare system. Scotland recently announced that it will do the same.

In Eastern Europe and Central Asia (EECA), PrEP is not available yet. However, demonstration projects are currently being set up in Georgia, Ukraine and Azerbaijan. These pilot studies consist of several phases. In Georgia, the first stage of PrEP implementation included a training session for those involved in the pilot, as well as the conducting of a needs assessment among Georgian men who have sex with men (MSM) and capacity building for local NGOs, before the actual start of the pilot in 2017. In Central Asian countries, there seems to be less interest in PrEP, although the Ministry of Health of Kyrgyzstan is planning to start an evaluation on the possibilities of introducing PrEP in the country.

Challenges of introducing PrEP in EECA may include the cost of PrEP, but also the high levels of stigma and discrimination in some countries. However, with HIV incidence in EECA rising by 57% between 2010 and 2015, treatment alone will not stop the epidemic. Given its proven effectiveness, providing PrEP to key populations can be a significant step in controlling the explosive growth of the HIV epidemic in this region.

The Union demands that TB be included in the WHO list of bacteria for which new antibiotics urgently needed

social-shareToday, 28 February, International Union Against Tuberculosis and Lung Desease stated that it is unacceptable that tuberculosis (TB) was excluded from the World Health Organization’s (WHO) published list of antibiotic-resistant ‘priority pathogens’, released yesterday.

The Union further added that the WHO must revise the list to include TB – the world’s leading infectious disease killer – with immediate effect and called upon the international community to support demands that TB be included in the catalogue of bacteria posing the greatest threat to human health – and for which new antibiotics are urgently needed.

The bacteria that cause TB kill more people than any other infectious pathogen. Latest WHO figures state that in 2015, 1.8 million people died, including 210,000 children. An estimated 580,000 people were reported to have drug resistant versions of TB – both multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) – while actual numbers affected could be even higher.

The only way of treating TB is with antibiotics. Current treatments for resistant forms of TB are arduous and are accompanied by side effects that include deafness and psychosis, as well as practical difficulties for families, communities, health systems and livelihoods.

TB R&D has been systematically underfunded during the previous decade. The current spending of $620 million on all TB R&D (vaccines, diagnostics and treatment) is only one third of the $2 billion annual funding target outlined in the 2011–2015 WHO Global Plan. Funding in TB drug R&D is only 28% of the $810 million called for in the Global Plan to End TB 2016-2020. This is counter to the global aim of accelerating progress against TB in order to reach the ‘End TB Strategy’ by 2030.

“It is outrageous to sideline TB from global antimicrobial resistance (AMR) efforts. The Union strongly urges WHO to include TB on its list of priority pathogens. Among the group of antimicrobial-resistant diseases, drug-resistant TB is a leading cause of sickness and death.

Failing to include TB on its list was a dramatic departure from the data, and it undermines efforts to find the new and better treatments that patients desperately need. This is particularly critical for those countries where drug-resistant TB is epidemic,” said José Luis Castro, Executive Director, The Union.

“As G20 leaders are set to meet and discuss an agenda for tackling antimicrobial resistance, The Union strongly urges them to follow the data. They should include TB in any G20 initiatives aimed at increasing R&D investments and piloting models to deliver new medicines used to treat antimicrobial-resistant disease,” said Dr Jeremiah Chakaya Muhwa, President of The Union.

Source: The Union

Reversing the HIV Epidemic

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Source: European Centre for Disease Prevention and Control (ECDC)

HIV remains a significant public health problem in the 31 countries of the European Union and European Economic Area (EU/EEA), with around 30 000 newly diagnosed HIV infections reported each year over the last decade. In a two-day conference organised in collaboration between the Maltese Presidency of the Council of the European Union and ECDC, HIV experts from across the European Union discussed how to reverse this trend and how to prepare Europe to achieve the set target of ending AIDS by 2030.

“This conference arose from excellent collaborative work with ECDC and Malta’s commitment and recognition of the importance of placing HIV higher up on the EU agenda during its Presidency Term” says Mr Chris Fearne, Minister for Health, Malta. “We believe that concerted efforts must include all stakeholders: including governments, healthcare providers, civil society, people living with HIV and the specialised agencies like WHO and ECDC. We believe that tackling HIV is a regional, national, corporate and individual responsibility. They all have a role to play in terms of political commitment, preventive action, universal access to healthcare, affordability and access to medicines, testing, linkage to care, focus on key populations, zero tolerance to stigma AND individual behavioural responsibility.“

He added areas of action: “Scaling up of testing is essential to reach our first 90 target. We need to make better use of various settings to enhance testing, incorporate innovative approaches to testing and reduce the barriers, especially in key populations. Knowledge of HIV status ‘in unaware persons’ might also help reduce new HIV infections – those resulting negative may then take less risks, and if linked to care should achieve viral suppression, the third 90“.

“If we take a look at the available data, we can see that Europe needs to improve its HIV response in several areas”, says ECDC Acting Director Andrea Ammon. “Currently, two out of three EU/EEA countries tell us that they do not have sufficient funding for prevention interventions. And every one in seven people living with HIV in the region are not aware of their infection. To reduce the number of new HIV infections in Europe, we need to focus our efforts in three main areas: prioritising prevention programmes, facilitating the uptake of HIV testing, for example by introducing new approaches like community-based testing or self-testing to diagnose those infected. And, of course, easier access to treatment for those diagnosed”.

Pharmaceuticals-Healthcare-Pill-World-Map-Earth-1185076Status quo of Europe’s HIV response: new ECDC report
On the occasion of the Presidency meeting, ECDC publishes an overview of achievements and gaps in the European HIV response, illustrating how countries addressed the HIV epidemic in 2016, based on their commitment outlined in the Dublin Declaration on Partnership to Fight HIV/AIDS in Europe and Central Asia.

The results show, amongst others, that HIV treatment overall starts earlier across the EU/EEA and more people receive life-saving treatment. But one in six people in the EU/EEA diagnosed with HIV are still not on treatment. Those who are on treatment, however, show how effective current HIV treatment is: almost nine out of ten people living with HIV on treatment are virally suppressed. This means the virus can no longer be detected in their blood and they cannot transmit the virus to others.
The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) contributed to this overview with data on the HIV situation and prevention coverage among people who inject drugs.

EMCDDA Director Alexis Goosdeel states: “People who inject drugs have the highest proportion of late diagnosis of HIV, compared to other transmission groups. Providing voluntary testing for infectious diseases, risk behaviour counselling and assistance to manage illness at drug treatment facilities is an important additional avenue to reach this group and is among the new EU minimum quality standards for demand reduction” .

The introduction and scaling up of effective drug treatment and harm reduction measures, such as needle and syringe provision, have significantly reduced drug injecting and related HIV transmission in Europe. However, this overall positive development hides large variations between countries. Marginalisation of people who inject drugs, the lack of prevention coverage, and appearance of new drugs can trigger local HIV outbreaks, as documented in five EU countries in the recent past.

Source: European Centre for Disease Prevention and Control 

Reasons for Drug Policy Reform

Michel_Kazatchkine_2012

Text: Michel Kazatchkine, UN secretary general special envoy on HIV/AIDS in Eastern Europe and Central Asia

Why is eastern Europe the only region in the world that still has a growing HIV epidemic? In one of the region’s countries, Russia, more than two thirds of all HIV infections, and 55% of the near 100 000 new infections reported last year, resulted from drug injection.

Some 3.2 million people in eastern Europe inject drugs, and about 1.5 million of them are in Russia. In 2007 the number of newly reported HIV cases among Russian people who inject drugs (12 538) was similar to the number in the rest of eastern Europe (12 026). But since then the numbers have diverged hugely.

Scaling up of harm reduction programmes in several countries coincided with a stabilising of HIV rates—and fewer than 7000 new cases outside Russia in 2014. In Russia, however, where access to sterile needles and syringes is low and opioid substitutes remain illegal and unavailable, the number of people who inject drugs newly infected with HIV climbed to nearly 22 500 in 2014.

Criminalisation of drug use

The reasons for Russia’s high figures include the prohibition and effective criminalisation of drug use, repressive law enforcement, and stigma around drug use. These factors lead people to inject in unsafe conditions for fear of police and arrests and result in needle sharing and overdose.

In 2015, the United Nations’ secretary general, Ban Ki-Moon, called for “careful rebalancing of the international policy on controlled drugs.”

“We must consider alternatives to criminalisation and incarceration of people who use drugs,” he said. “We should increase the focus on public health, prevention, treatment, and care.”

The World Health Organization, the United Nations Office on Drugs and Crime, and UNAIDS jointly recommend a package of harm reduction interventions as best practice to reduce the risk of acquiring, and improve treatment of, HIV, hepatitis, and tuberculosis among people who inject drugs. Such strategies, which do not require prohibition of harmful behaviours, are key to reducing death and disease because drug dependency is characterised by people’s inability to abstain.

Continue reading here.

AFEW Director is the Chair of TB/HIV Working Group

ankeAFEW executive director Anke van Dam became the chair of Wolfheze Working Group on TB/HIV collaborative activities. The group will document and promote the best models and identify research priorities of integrated TB/HIV care in the European region. Members of the group will also identify barriers in TB/HIV services and collaboration.

“I am very honoured to be part of the group,” – Anke says. – “AFEW is implementing integrated HIV/TB activities in the EECA region for quite some years now. I will bring this experience into the group, and hope to contribute to collecting best models. There is still so much to gain in improving the care and health of people living with both HIV and TB.”

Wolfheze TB/HIV Working Group started a year ago in The Hague, The Netherlands. There, Wolfheze and WHO National TB Programme Managers’ meeting participants discussed the need for strengthening TB/HIV collaborative activities in the context of the WHO End TB Strategy. They agreed to create a Working Group on TB/HIV collaborative activities taking into account specific challenges and opportunities in the WHO European region.

Website about Health for Migrants is Available in 13 Languages

 

health-site_engThe information about body, family planning and pregnancy, infections, sexuality, relationships and feelings, rights and law can be found on the website Zanzu – my body in words and images. This projects for migrants was developed by the Flemish Expertise Centre for Sexual Health Sensoa and the German Federal Centre for Health Education (Bundeszentrale für gesundheitliche Aufklärung) BZqA. The information is available in 13 languages, including Russian and English.

Information on the website is presented in easy interactive form. Pushing the image brings the reader to other pictures, behind which they can find important information. Section “Dictionary and translations” will provide users with the translations of most widely-used words on the topics mentioned above. On the website there are also contacts of the doctors who help migrants with their health issues.

Besides, on the site there is information for professionals in English, Dutch and French languages. This section contains advice to the foreign professionals on how to talk to migrants and why it is important to discuss their health issues. The content on the website was approved by an international advisory board of European experts in the field of sexual and reproductive health including representatives of WHO.