Draft Guideline
For Management of Diabetes Mellitus-Tuberculosis
Comorbidity
December 2014
Table of Contents
Forward 3
Acknowledgements 4
Abbreviation 5
Name of Technical Working Group 5
1. Introduction 7
1.1 What is tuberculosis (TB)? 7
1.2 What is diabetes mellitus (DM)? 7
1.3 Current TB-DM comorbidity in the world 8
1.4 Current burden of TB-DM comorbidity in Cambodia 8
2. Rational for development TB-DM comorbidity management guideline 9
3. Screening for DM and TB 9
3.1. Screening for TB in DM patient 9
3.2. Screening for DM in TB patients 10
4 Referral mechanisms 10
4.1 Refer DM patients with TB suspected/TB from DM clinic to TB ward 10
4.2 Refer TB patients with DM from TB ward to DM clinic 11
5 Management of TB-DM comorbidity patients 11
Clinical management 11
5.1 Treatment TB-DM comorbidity 11
5.2 Drug Interaction: 14
6 Team management 14
6.1 Decision on diagnosis: 14
6.2 Decision on Treatment: 15
6.3 Decision on follow up: 15
6.4 Team meeting: 15
6.5 Capacity building: 15
7 Prevention diabetes-tuberculosis comorbidity 15
8 References 16
Appendix 1: Referral form 17
Appendix 2: TB screening among DM patients 18
Appendix 3: DM screening among TB patients 19
Forward
Diabetes mellitus (DM) and tuberculosis (TB) comorbidity is emerging as a public health concern in Cambodia. Diabetes triples the risk of developing TB, and the rates of TB are higher in people with DM than in the general population. Furthermore, treatment outcomes of individuals with both conditions is poorer than that of individuals with DM or TB alone. Diabetes can worsen the clinical course of TB, and TB can worsen glycemic control in people with DM. Therefore, individuals with both conditions require careful clinical management. Early detection of DM among TB patients and early detection of TB among DM patients are crucial to better manage the diseases.
Given the absence of a national guideline to manage TB-DM comorbidity, the National Center for Tuberculosis and Leprosy Control (CENAT), Department of Preventive Medicine (DPM), World Health Organization (WHO), Cambodia Diabetes Association (CDA) and other relevant stakeholders, with the support and coordination of the Center for Health and Social Development (HSD), have set up a Technical Working Group (TWG) to address this gap. The ultimate goal of the TWG will be to draft a comprehensive guideline for the management of TB-DM comorbidity that can be adapted and implemented on a national scale.
I strongly believe that this guideline will become a helpful tool to help health care providers who are currently working in TB service or in DM service. Patients with TB-DM comorbidity will be effectively managed through better coordination between the two services, early case detection, high quality of clinical management and proper follow up.
Finally I would like to acknowledge all members in the technical working group for their contribution to develop this guideline. Taking this opportunity, I would like to deeply thank the Center for Health and Social Development for their coordination and financial support for the guideline development.
Phnom Penh, ………………….. 2014
Dr. Mao Tan Eang
Acknowledgements
We would like to thank Dr. Mao Tan Eang, Director of National Center for Tuberculosis and Leprosy Control; Prof. Prak Piseth Rainsey, Director of Department of Preventive Medicine and Dr. Neeraj Kak, University Research Co., LLC for their valuable and strong support in developing this national guideline for TB-DM comorbidity management.
Special thanks to all members of the Technical Working Group from both National Center for Tuberculosis and Leprosy Control (CENAT) and Department of Preventive Medicine (DPM); World health Organization; Cambodia Diabetes Association (CDA); MoPoTsyo; FHI 360; Operation ASHA; Sihanouk Hospital Center of Hope; HelpAge Cambodia and Health and Social Development (HSD) for great participation and contribution in drafting the guideline on case management of TB-DM comorbidity.
Last but not least, a special thanks to the World Diabetes Foundation (WDF) for their coordination and financial support, through HSD, to make this guideline happen.
Abbreviation
CDA Cambodia Diabetes Association
CDHS Cambodia Demographic Health Survey
CENAT National Center for Tuberculosis and Leprosy Control
DM Diabetes Mellitus
DOT Directly Observed Therapy
DPM Department of Preventive Medicine
ETB Extra-Pulmonary Tuberculosis
HIV Human Immunodeficiency Virus
IDDM Insulin-Dependent Diabetes Mellitus
MDR-TB Multi-Drug Resistant Tuberculosis
MoH Ministry of Health
NCD Non-Communicable Diseases
NGO None Governmental Organization
NIDDM Non-Insulin Dependent Diabetes Mellitus
PTB Pulmonary Tuberculosis
TB Tuberculosis
TWG Technical Working Group
WHO World Health Organization
Technical Working Group
Name / Institutions/organizations / Role1 / Dr. Mao Tan Eang / CENAT / Chairman
2 / Prof. Prak Piseth Rainsey / DPM / Co-chairman
3 / Dr. Khun Kim Eam / CENAT / Member
4 / Dr. Lim Keurky / CDA / Member
5 / Dr. Bit Bun Leng / CENAT / Member
6 / Dr Rajendra-Prasad Yadav / WHO / Member
7 / Dr. Khim Sam Ath / WHO / Member
8 / Dr. Chhoun Loun / NCD-MoH / Member
9 / Dr. Sok Kong / NCD-MoH / Member
10 / Dr. Ly Minea / FHI-360 / Member
11 / Dr. Touch Khun / CDA / Member
12 / Dr. An Yom / HSD/URC / Member
13 / Dr. Soy Ty Kheang / HSD/URC / Member
14 / Mr. Maurots Vanpelt / MoPoTsyo / Member
15 / Ms. Men Samphoan / HelpAge Cambodia / Member
16 / Dr Thai Sopheak / Center of HOPE / Member
17 / Ms Jacqueline Chan / Operation ASHA / Member
DRAFT GUIDELINES FOR MANAGEMENT OF TB-DM
COMORBIDITY
1. Introduction
1.1 What is tuberculosis (TB)?
TB is an infectious disease caused by the bacillus Mycobacterium tuberculosis. It typically affects the lungs (pulmonary TB) but can affect other sites as well (extrapulmonary TB). TB is spread through the air when patients with pulmonary TB (PTB) expel bacteria, for example, by coughing. In general, around 10% of people infected with M. tuberculosis will develop TB disease. However, the probability of developing TB is about 3 times higher among people with diabetes and 26-31 times higher among people infected with HIV. TB is also more common among men than women, and affects mostly adults in economically productive age groups [1].
The most common method for diagnosing TB worldwide is sputum smear microscopy (developed more than 100 years ago), in which bacteria are observed in sputum samples examined under a microscope. Diagnosis using sputum smear microscopy can be made within a day, but this test is not able to detect several less infectious forms of TB, and sometimes provides false negatives making it less reliable. In countries with more developed laboratory capacity, cases of TB are also diagnosed via culture methods (the current reference standard). While culture tests are much more accurate than sputum smear microscopy, one drawback to their use is the length of time it takes to obtain results (2 – 6 weeks). Following recent breakthroughs in TB diagnostics, the use of rapid molecular tests for the diagnosis of TB and drug-resistant TB is increasing (GeneXpert). These tests greatly improve the accuracy and timeliness of TB diagnosis, simultaneously detecting TB and rifampicin drug resistance (a reliable indicator for multi-drug resistant TB). In Cambodia, TB diagnoses are made through sputum smear, X-ray, culture and GeneXpert.
TB mortality rates are high for patients who do not receive treatment. The mortality among pulmonary TB, HIV-negative cases with sputum smear positive is around 70% within 10 years of infection. Additionally, the mortality rate among sputum smear negative (but culture-positive) cases is approximately 20% within 10 years [2].
Based on the current Cambodia National TB treatment guideline, the recommended 1st line treatment for new TB cases is six-months of Isoniazid, Rifampicin, Ethambutol and Pyrazinamide. In 2012, treatment success rates among new and relapse cases were at 94%.
Treatment for multidrug-resistant TB (MDR-TB), defined as resistance to Isoniazid and Rifampicin (the two most powerful anti-TB drugs) is longer, and requires more expensive and more toxic drugs. For patients with MDR-TB, the current standard treatment duration recommended by the National Center for Tuberculosis and Leprosy Control (CENAT) is 20 months. MDR-TB treatment breaks down into two phases: intensive phase (8 months) and continuation phase (12 months), detailed in Table 1 below.
Table 1: Standard Treatment Regimen as the first choice for MDR-TBDrugs in intensive phase: 8 months / Drugs in continuation phase:12 months
- Kanamycine (KM) injection
- Levofloxacin PO
- Ethionamide PO
- Cysloserine PO
- Pyrazinamid PO (Ethambutol PO if there is no DST confirmed to be resistant) / - Levofloxacin PO
- Ethionamide PO
- Cysloserine PO
- Pyrazinamid PO (Ethambutol PO if there is no DST confirmed to be resistant)
According to recent WHO findings, the treatment success rate for patients with MDR-TB is only 86%.
1.2 What is diabetes mellitus (DM)?
Diabetes mellitus (DM), also known as sugar diabetes or simply diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period. This high blood sugar produces the symptoms of frequent urination, increased thirst, and increased hunger. Untreated, diabetes can cause many complications. Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. Serious long-term complications include heart disease, stroke, kidney failure, foot ulcers and damage to the eyes.
Diabetes occurs when the pancreas does not produce enough insulin, or any insulin at all, when the body cannot effectively use the insulin it produces (insulin resistance), or both. There are several types of diabetes mellitus, described in detail below:
· Type 1: results from the body's failure to produce enough insulin. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes". The cause is unknown.
· Type 2: begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses, a lack of insulin may also develop. This form was previously referred to as "non-insulin-dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". The primary cause is excess body weight and lack of exercise.
· Gestational diabetes: occurs when pregnant women without a previous history of diabetes develop a high blood glucose level.
· Other rare types of diabetes can be caused by conditions such as pancreatitis, cystic fibrosis, or exposure to a virus or to certain drugs.
1.3 Global TB-DM comorbidity
DM and TB comorbidity is a public health concern in many developing countries where healthcare resources are limited. There is strong epidemiological evidence on the relationship between DM and TB. People with DM have 2 to 3 times higher risk of developing TB than people without DM, and having diabetes is a risk factor to adverse TB treatment outcomes[3]. Similarly, the risk of developing DM is about 3 times higher among TB patients than among non-TB patients[4], and TB has been shown to worsen glycemic control[5].
It is currently estimated that the prevalence of DM will increase from about 382 million in 2013 to around 592 million in 2030. In 2013, about 80% of DM patients lived in developing countries where healthcare resources were limited. Of even greater concern, about 48% of these patients with DM were undiagnosed[5].
With the increased number of DM patients among low-resource health care systems, TB-DM comorbidity will inevitably increase as well. This will in turn hamper WHO’s target to scale down global TB incidence by 90%, or less than 10 cases per 100,000 population, in 2035[3] and will further impede the world’s long-term vision to eliminate TB as a public health concern by reducing TB incidence to less than 1 case per million of population by 2050[6].
1.4 Current burden of TB-DM comorbidity in Cambodia
Situated in the southern portion of the Indochina Peninsula in Southeast Asia, Cambodia is among the poorest countries in the world. With a total population of 14,676,591 (Male: 48.5%, Female: 51.5%)[7], a staggering 19% were living under the poverty line as of 2012. The majority of Cambodians (79%) live in rural areas, where access to quality health care is difficult.
Based on a 2012 CENAT report, the rate of TB is 817 per 100 000 population (22nd highest TB burden in the world)[8]. Additionally, a nationwide WHO stepwise approach to surveillance (STEP) survey conducted in 2010 found the prevalence of DM to be around 3% among population ages between 25 and 64 years old[9].
In 2013, a study on TB-DM comorbidity conducted by the Cambodia Demographic and Health Survey (DHS) program found the prevalence of DM among TB patients to be 5% in Prey Veng province and 7% in Siem Reap province, with adults aged between 38-48 years considered most at-risk. TB prevalence among DM patients was also much higher (4.4%) than in the general population (only about 0.8%).
2. Rational for development of a TB-DM comorbidity management guideline
In order to adequately respond to the growing concern of TB-DM comorbidity, cooperation between DM and TB services through a well-structured coordinating mechanism will be necessary in order to maximize efficient use of resources. While there are disease-specific guidelines for both TB and DM, there is currently no guideline for the management of TB-DM comorbidity in Cambodia. Therefore, knowledge regarding the proper management of TB-DM comorbidity among healthcare providers is low and public knowledge on TB-DM comorbidity is very limited. The National Tuberculosis Program (NTP) and non-governmental organizations (NGOs) gear their messages towards TB and DM separately, without any emphasis on TB-DM comorbidity. This lack of awareness among both health care providers and patients may lead to poor treatment outcomes. Therefore, a comprehensive guideline for TB-DM comorbidity management is needed in order to improve TB-DM comorbidity management in Cambodia.
3. Screening for DM and TB
1.
2.
3.
3.1. Screening for TB in DM patients
2
3
3.1
Every patient with diabetes (new or follow-up cases) has to be routinely screened for TB symptoms lasting more than 2 weeks (cough, fever, night sweats and unexplained weight loss) during each diabetes consultation[5]. Moreover, patients should be asked to come back early if they present one of the above symptoms.