Dr Kalyan Krishna Velivela, Medical Coordinator, MSF specialises in TB, especially drug resistant TB and has recently returned from Uzbekistan which is one of the many countries in Asia with a high burden of drug-resistant TB (DR-TB). In an email interview with Viveka Roychowdhury, he describes how MSF engages with public health authorities to tackle these public health issues and lists some learnings which can be adapted and adopted in India
Dr Kalyan, your expertise lies in clinical diagnosis and treatment of TB and drug-resistant TB (DR-TB). What have been the latest advances in the techniques/ technologies to diagnose/detect TB?
There are quite some advances in the initial diagnosis of MDR-TB and TB in HIV patients. These include Xpert MTB/RIF, through which initial diagnosis for TB and rifampicin (one of the key TB drugs) resistance is diagnosed rapidly (within two hours) as well as accurately. This results in immediately offering proper treatment. Xpert MTB/RIF (also called GeneXpert) is a better diagnostic with regard to sensitivity and specificity of the test, compared to microscopy. Other new technologies include HAIN MTBDR Plus and advance liquid based cultures using BACTEC.
MSF uses these new technologies like Xpert MTB/RIF in all its integrated TB programmes, even in resource limited settings e.g. South Sudan etc. and has tests/technologies such as BACTEC (MGIT) liquid cultures and drug sensitivity tests (DSTs) in vertical programmes in Uzbekistan and Swaziland.
Are these cost effective enough in the quantities required to tackle the disease burden?
Xpert MTB/RIF is cost effective for diagnosis of TB as compared to others. However, at approximately $17,000 per machine, the costs for Xpert MTB/RIF are still high. Since high TB burdens and case-loads exist in resource limited countries, these costs are still higher for these countries to purchase, and implement strategies to tackle the overall burden of the disease. Although, USAID, UNITAID and Bill & Melinda Gates Foundation finalised an agreement with Cepheid to further reduce the negotiated price of the Xpert MTB/RIF test for eligible customers of the FIND country list to $9.98. However, given the prevalence of the disease in low and middle income countries, the cost per cartridge continues to pose a challenge in effective diagnosis and subsequent administration of treatment.
Given that TB and DR-TB has reached almost epidemic proportions in resource scarce areas, what is MSF’s strategy to manage such a major public health burden?
MSF has integrated TB and DR-TB components in all its projects including those for Internally Displaced Persons (IDPs) and in refugee camps where the case load is high/burden is higher. This is to ensure accurate diagnosis and treatment options within MSF projects and areas of work.
Within its vertical TB projects in Uzbekistan and Swaziland etc., MSF works in close collaboration with national authorities (national TB programmes) and other NGOs/actors in developing and implementing different models for improved diagnostics and treatment options; models and approaches to improve adherence to available treatments; adequate infection control methods and operational research. All this is done through a patient-centred approach.
For case detection and diagnosis, MSF focuses on universal access to improved and rapid TB diagnostics in all its projects and programmes, including those for IDPs and refugee camps that MSF supports and works in.
For treatment options and strategies, in Uzbekistan, a high TB burden country with high rates of MDR-TB, MSF is piloting a nine month short course MDR-TB treatment programmes against the standard treatment regimen of 20-24 months. Enrolments are complete and all MDR-TB patients are being followed up with. The results are expected by end of 2016. This might give options for shortened treatment options, with improved adherence and better outcomes.
In addition, MSF also recognises the urgent need for shorter and better treatment regimens for MDR-TB and XDR-TB treatment using new TB drugs. These regimens should have fewer drugs, with fewer side-effects (better tolerated), and improved outcomes. With this aim, MSF plans to perform a clinical trial / research in some countries like Uzbekistan and Swaziland in close collaboration with the National TB programmes/authorities.
You have served at a wide spectrum of sites, spanning Africa to Uzbekistan in primary care settings dealing with tropical diseases like kala-azar as well as the debilitating effects of malnourishment, especially on maternal and neonatal and child health. As medical coordinator, MSF how do you engage with the local public health authorities to continue the work started by MSF?
In majority of our project countries (from South Sudan to Uzbekistan), we always make sure to involve national programmes/Ministry of Health in whatever we do as MSF while maintaining and emphasising MSF principles, and standards of patient care and management.
For kala-azar (visceral leishmaniasis), in South Sudan, we (MSF) have been working closely with the national kala-azar programme, WHO and other key actors. This included writing diagnosis, treatment and prevention guidelines, developing strategies and supporting national programme/authorities in the implementation of the developed strategies. We were also involved in many trainings/regional workshops to build the capacity of the national staff and Ministry of Health staff. Similar example for kala-azar can be high-lighted in Tajikistan, where we were involved in revising the national guideline; training almost more than 200 MoH staff members; providing diagnostic tests and treatments for the initial re-start of the kala azar programme; identifying different actors to aid the process; and resource mobilisation for the continuity of the programme. This is a more sustainable approach.
For TB, in Uzbekistan, MSF has been working in the Karakalpakstan region since 17 years. MSF was the first international medical organisation in the country to start WHO’s DOTS plus programme and treatment of DR-TB (MDR-TB and XDR-TB). Many new approaches and strategies like ambulatory care and initiation of MDR-TB treatment with a comprehensive TB care model was developed. All this was done in close collaboration with national TB staff (doctors and nurses), National TB Programme and Ministry of Health. With this, we were able to continue our activities. Most of these new approaches and models were well accepted by national authorities, were further approved, adapted by national programme and authorities as well as rolled out further by them. Not only is this approach more sustainable but also well adaptable.
TB/DR-TB almost always coexists with HIV. What are the best strategies, from both a clinical and public health policy point of view, to increase awareness and adherence in such cases?
To increase awareness:
Effective health education strategies and health education tools should be made available;
There exists an increased need to focus more on community engagement and community centric models;
Of course, overall, IEC material and larger campaigns, not only to address awareness, but, to also address stigma related issues, cultural myths and beliefs, which is also crucial.
To improve adherence:
As much as possible TB/DR-TB and HIV diagnosis and management should be a ONE STOP SERVICE. This translated into increased integration of TB services within HIV facilities, and vice-versa. Further, these centres should be patient friendly.
Effective psycho-social support, counselling should be made available to the patients.
Shorter options of treatments for both the diseases will result in lower pill burden for patients and shall improve compliance to treatment. For instance, HIV treatment could benefit from fixed dose combinations (FDCs). Similarly, shorter treatment regimens for DR-TB could be of significance in the TB landscape. Such instances coupled with a strong clinical focus and effective management of drug side effects, and drug interactions can improve adherence.
Can you highlight some of the positive outcomes from your projects across the world in these settings?
For TB in Uzbekistan, MSF’s pilot on nine month short course regimen (9 m SCR) is well recognised by the Central Asian region as well as WHO. With the outcomes expected by end of 2016, this might give opportunities and results to adapt the 9m SCR in other regions around the world. In addition, MSF’s comprehensive TB care model with focus on ambulatory care v/s hospitalisation is also recognised within the region, and other NGOs are planning to implement and scale it up in the region.
For kala-azar, MSF’s advocacy for Liposomal Ambisome price reduction and modified treatment regimen has resulted in better outcomes, adaptation to national programmes in eastern African countries, and also in South-East Asian countries.
Though most of your work has been out of India, what are the learnings that you feel can be adapted and adopted in India to tackle the high disease burden due to TB/DR-TB and HIV?
Patient-centred models of care for TB/DR-TB facilitate individualised treatment regimens and reduce the risk of further resistance development. This works best as TB is associated with a deep seated stigma, which can only be dispelled through a sensitive approach. Hence, RNTCP or state programmes could benefit from adapting more patient centric models.
Use and scale up of rapid initial diagnostic techniques like Xpert MTB/RIF, and importantly, decentralisation of Xpert MTB/RIF or diagnostics to ensure availability in all government hospitals (or urban health centres), can facilitate rapid diagnosis of MDR-TB. This will reduce the need for patients to be referred to regional reference labs for initial diagnosis of DR-TB which otherwise results in longer waiting periods, delayed treatment, as well as development of resistance (or amplification of resistance in cases which fail to respond to 1st line TB drugs). Earlier initiation of appropriate treatment benefits the patients and the community curbing the spread of TB.
Consider piloting other treatment options such as the nine month short course regimen for treatment of MDR-TB (the Bangladesh regimen) to assess its suitability within the Indian context. Within other contexts this has proven to be an effective approach to MDR-TB treatment which simplifies the implementation of care and subsequently access to care. Such models could be adapted in parts of the country where acceptable and possible. The shorter regimens improve compliance to treatment with improved adherence and might be cost-effective compared to standard treatment regimens that are 20-24 months in duration.
Importantly, as one of the preventive measures, the implementation of policies and the application of increased regulations for the prescribing and use of WHO approved and pre-qualified TB drugs in the states and the country may be expected to impede the incidence of MDR-TB development. This needs to be followed through.
Implementation of regulations aimed at preventing availability and sale of over the counter first line TB drugs; strict prescription and distribution within approved and accredited/certified centres and facilities can prevent further resistance to potent TB drugs.
Development and implementation of regulations for use of some of the potent second line drugs like Levofloxacin, Moxifloacin and second line injectables is important. This is not easy; however, these drugs/antibiotics should only be used based on prescriptions, and NOT used in any patients suspected to be having TB.
It is important to ensure supply mechanisms exist to prevent TB drug ruptures, and stock outs resulting in uninterrupted drug supply, through centralised stock and supply management (either at state level and/or central level).
On a personal note, dealing with disease on a daily basis, and in such resource scarce situations, when the dice always seems loaded against your work and positive outcomes, who/what has been your inspiration to keep going?
Good team cooperation and spirit is the key in any MSF project mission or context. In addition, in my experience as a medical coordinator, better understanding of the context, culture and people mitigates a lot of challenges and enables us to move forward. I plan better; analyse all corners well before taking a chance and moving ahead.
What has been the most disheartening aspect of your role? And the most inspiring?
The most disheartening aspect of my role: In some situations, where we (as MSF) work so hard to develop and implement a programme (e.g. TB and HIV programme in one of the states in South Sudan), see it running and create a system, it is hard to absorb, and think now (after a year), when everything collapses (all the systems and structures and services) due to a man-made war/violence, which is currently the situation in South Sudan.
The most inspiring aspect of my role: Working with MSF, in different contexts (stable and unstable), different programmes (epidemics / disease outbreaks, violence /war related etc.) gives me an immense opportunity to offer, learn, gain experience and exposure at both professional and personal fronts.
My role as medical coordinator is not an easy role as I am responsible for the medical component within the mission- from planning to implementation of medical components-along with a multi-cultural and multi-expertise team. It is important to maintain good relations with counter parts – Ministry of Health, national programmes, and other NGOs and INGOs, and actors related to medical issues.
On the other hand, with my background as a doctor and experience in tropical diseases- TB and HIV-I also play the role of a technical advisor where needed to the project/programme teams. This is a mix of technical and managerial role.