TB, HIV and diabetes: Voices from the field

Scientific evidence, policy and programmatic linkages between TB and HIV as well as TB and diabetes (and HIV and NCDs) have been getting more attention in recent years, but still lot more synergy between different 'silos' is warranted for optimal public health outcomes. At the 48th Union World Conference on Lung Health, several experts from range of countries presented their studies looking at these connections between diseases. If governments are to deliver on the promises of the Sustainable Development Goals (SDGs) integrated responses from grounds up are indeed an imperative!

Stephan Lawn TB HIV Research Prize 2017

Dr Leonardo Martinez from Stanford University School of Medicine was awarded the Stephan Lawn TB HIV Research Leadership Prize 2017. The Stephen Lawn TB-HIV Research Leadership Prize was established in 2016 through a global partnership between the TB Centre in London, UK, the Desmond Tutu HIV Centre in Cape Town, South Africa and The Union. It acknowledges young researchers (under 40 years old) conducting promising work focused on reducing the disease burden of TB and HIV/AIDS in Africa.

Dr Leonardo Martinez was part of key researchers behind the first ever population based study that found diabetes (and pre-diabetes) increases risk of latent TB infection. Usually the risk for people with diabetes to get latent TB goes up two times, but higher risk was found for those with poor glycaemic control.

Diabetes increases deaths among TB patients

Patients with type-2 diabetes are at an increased risk for developing active TB disease and experience worse treatment outcomes. But use of metformin reverses this risk, found research done by Dr Nicholas Degner from Johns Hopkins Bloomberg School of Public Health.
Metformin activates a regulator of autophagy (AMPK). Dr Amit Singhal and other researchers have earlier demonstrated that metformin inhibited the growth of TB bacteria in macrophages. Studies have shown reduced lung bacillary load in a mouse model of TB. Dr Singhal and team also showed that metformin decreased TB severity and improved clinical outcomes.
Dr Nicholas studied 2416 TB patients in Taipei's National Taiwan University Hospital between 2000-2013, out of which 29% had diabetes. Among patients with TB and diabetes both, 76.4% were males.
The study found that TB patients who had diabetes had significantly more co-morbidities than those without diabetes. 24.2% of patients with both diabetes and TB had Chronic Kidney Disease (CKD) compared to 9% CKD among those who did not have diabetes but just TB. Tobacco use was also found to be higher in people with diabetes and TB both (38%) whereas 29% among those those who had TB but no diabetes, reported tobacco use.

Death rates were significantly higher among patients with TB and diabetes both: 29%, whereas deaths among TB patients who had no diabetes was at 13.7%.
Metformin use along with standard TB treatment appears to reverse the increased mortality associated with diabetes, said Dr Nicholas.

TB diabetes bidirectional screening is key

Dr Shepherd Mufudzi Machekera from Zimbabwe country office of International Union Against TB and Lung Disease (The Union), said that diabetes has been on the rise in the country. Despite high burden, 71.4% of people with diabetes were undiagnosed. Dr Leonardo Martinez’s study had found that people with uncontrolled or poorly controlled diabetes had higher risk of latent TB too. People with undiagnosed diabetes were particularly likely to have uncontrolled diabetes and thus at very high risk of latent TB too.

Dr Shepherd Machekera said that diabetes increased the risk of developing active TB disease by 2-3 fold. People with TB and diabetes both are at higher risk of treatment failure, relapse, multi drug resistant TB (MDR-TB), and death.

Diabetes patients who develop TB are at risk of poor glycaemic control and developing diabetes-related complications. When Dr Shepherd’s project funded by World Diabetes Foundation was implemented in Zimbabwe there was no diabetes and TB collaborative programme in place in the country. That is why he studied feasibility of doing routine bidirectional screening for TB and diabetes in primary health settings of Zimbabwe.

His study engaged all stakeholders such as TB and non-communicable diseases (NCDs) programmes, in the Ministry of Health Zimbabwe, to arrive at a consensus for implementation of bidirectional screening. This multi-stakeholder team produced guidelines, standard operating procedures (SOPs), training material, other information education and communications (IEC) materials, as well as recording and reporting tools for better data and analysis. The project also trained healthcare workers on bidirectional screening of TB and diabetes and procured glucometers and testing strips.

Dr Shepherd shared that a technical working group review meetings had established an algorithm for screening of TB patients for diabetes, and screening of diabetes patients for TB.

Dr Shepherd recommended that any diabetes patient who reports any one of the following symptoms should get screened for TB:
  • Any current cough
  • Night sweats
  • Unexplained weight loss
  • Fever
'Yes' answer to any of the above 4 signs meant that sputum samples be collected and sent for Gene Xpert testing for TB as well as MDR-TB.

Does bidirectional screening find more patients?

Dr Shepherd shared that across study sites for bidirectional screening in Zimbabwe, 1830 TB patients were identified between April 2016 and March 2017. Out of them 43% had elevated glucose levels and 7% [63/1830] of TB patients were linked to diabetes care.

Likewise, over 860 diabetes patients were screened for TB between April 2016 - March 2017, 17% were presumed to have TB, and 1% of those presumed to have TB were diagnosed with TB and linked to TB care.

Dr Shepherd summarized that it is feasible and of public health value to screen TB patients for diabetes at primary health settings using rapid blood sugar and fasting blood sugar testing. It is also feasible to carry out intensified case finding for active TB disease among diabetes patients in primary health settings as, in this study, 1% of all diabetes patients screened were found to have TB too and were successfully linked to care.

Infection control: is that an issue?

Dr Shepherd emphasized that all primary health facilities involved in his study in Zimbabwe had adequate infection control practices, but a Mexican delegate raised this serious concern because infection control in such settings was likely to be inadequate in Mexico, thereby increasing the risk of spread of TB and other infectious diseases. With fragile health systems, overwhelming disease burdens, and poor infection control practices, it is important to not forget the basics: infection control must be boosted in healthcare settings as well as in communities and homes.

Another benefit if HIV+ on ART: TB deaths decline

Robust scientific studies (such as HPTN-052) have already proven that the risk of developing and dying of TB is majorly reduced if people living with HIV (PLHIV) are put on antiretroviral therapy (ART) right after their HIV test. If viral load is undetectable then risk of HIV transmission from PLHIV is negligible (as treatment also works as prevention) and they live normal lifespans comparable to those without HIV. All scientific rigour points towards putting  PLHIV on ART for a range of significant public health outcomes. Governments cannot meet SDGs if we fail to take evidence into account for policy making and programming on the ground!

Dr Osman Abdullahi from Pwani University in Kilifi, Kenya, said that TB deaths are rising in areas such as Kilifi in Kenya where drug use and sex work were also coexisting. Large numbers of tourists also come to Kilifi, a coastal area in Kenya. National review meeting in Kenya has already flagged the increase in TB deaths despite declining new TB case notification.

During 2012-2015 in Kilifi, Kenya, 9032 new TB patients began treatment out of which 29% had HIV, 14% did not complete treatment, 470 deaths occured and 191 were lost to follow up.

When do more deaths occur during TB treatment?

Over 50% of TB deaths occur during the first two months of the treatment, while 70% of deaths of TB patients occur during first three months of TB treatment. 

Despite decline in new TB case notifications, why is TB case fatality ratio rising up? Dr Osman Abdullahi explained that if we look at the data carefully, it will become evident that case fatality ratio for HIV negative individuals who were seeking TB care was almost flat, but death rates rose for  PLHIV who were on TB treatment. People living with HIV had 3 times higher risk of death during TB treatment compared to those who were HIV negative but receiving TB treatment.

Dr Osman's study found that those PLHIV who were on ART and/or cotrimoxazole preventive therapy (CPT), had significantly lower risk of death during TB treatment. ART coverage is 70% for adults and 45% for children in Kilifi, Kenya.

Big missed opportunity?

Despite emphasis on TB and HIV collaborative activities, only 49% of children and 31% of adults were screened for TB during HIV clinic visits in Kilifi, Kenya. This is a big missed-opportunity, rightly said Dr Osman Abdullahi.

Another missed opportunity is that almost half of those PLHIV who were tested for TB had latent TB infection (not active TB disease), were not provided Isoniazid Preventive Therapy (IPT). Community based contact tracing could have further enhanced programme outcomes, said Dr Osman.

Lessons from the Mozambique

From a debilitating war-torn past, it was only since 1992 that Mozambique started inching towards recovery. According to the World Health Organization (WHO), "despite greater availability of health resources and positive socio-economic developments, inequities in health continue to persist."

Dr Sugata Mukhopadhyay, a noted TB and HIV expert who has contributed to the fight against AIDS and TB both in several countries, is now part of the team of ADPP in Mozambique. While most of the world is credited for declining HIV rates, the incidence of the virus is on the rise in some places and key affected populations. Mozambique is one of the African nations where HIV rates have gone up from 11.5% in 2009 to 13.2% in 2015. 65% of adult people living with HIV are on ART.

Sharing his ADPP Mozambique experience, Dr Mukhopadhyay said packaging interventions and approaches, that are locally customised and evidence-based, gives hope. One highlight he shared was the role counsellors are playing in the package ADPP and partners are developing. These project counsellors perform symptomatic screening of the indexed HIV case and other household members. They refer the presumptive TB cases to the local health facilities. They provide treatment adherence education, follow up test support and family education to those who had TB and started treatment. Most importantly, they link the new TB patients to support groups ('Duo'- patient with one of the family members, or 'Trio' - where patient is grouped with one of the family members and one of the accepted community members). They also help document the treatment outcomes after completion.

Dr Sugata Mukhopadhyay summarised that the protection package has helped in early access to HIV counselling and testing services through home-based tracking of the indexed HIV cases and their family members and sexual partners. It has also helped in early initiation of ART among newly detected HIV positive people. Early detection of TB and initiation of TB treatment are important outcomes of this package. Ensuring viral suppression through treatment adherence support, family/ community support and CD4 count monitoring is another outcome of the package. It is important for Mozambique to pay attention to the strong evidence of using viral load testing instead of CD4 machines for monitoring of ART. Also more collaborative activities between HIV and TB programmes, and those for NCDs must be on the cards for enhancing public health outcomes for Mozambique.

Integrated responses are critical for #SDGs

Divided we fall, united we stand the only chance to win on #SDGs, should be the mantra. We cannot end AIDS (or end TB) unless HIV (or TB) responses are intertwined with social influencers as well as every other 'silo' where it makes sense. Same goes for other issues- we cannot, for instance, end poverty unless we pay attention to how catastrophic healthcare costs push people into deeper levels of poverty; or how climate change threatens to reverse gains made in the fight against malaria. Integrated response is the only promising path ahead that gives us hope to deliver on sustainable development.

Bobby Ramakant, CNS (Citizen News Service)
17 October 2017
(Bobby Ramakant is the Policy Director at CNS (Citizen News Service) and a WHO Director General's WNTD Awardee (2008). He is part of CNS Correspondents Team with support from the Lilly Global Health Partnership for thematic coverage of the 48th Union World Conference on Lung Health. Follow him on twitter: @bobbyramakant or visit www.citizen-news.org)

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