Appendix 3: DM screening among TB patients

Draft Guideline For Management of Diabetes Mellitus-

TuberculosisComorbidity

December 2014

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Table of ContentsForward.................................................................................................................................................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

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ForwardDiabetes 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

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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.

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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

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Technical Working Group

Name Institutions/organizations Role

1 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

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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.

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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

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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 CambodiaSituated 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

3.1. Screening for TB in DM patientsEvery 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.

Pulmonary TB (PTB): One of the most common symptoms of PTB is “chronic cough” which is defined as a cough of at least two weeks. Other symptoms of PTB include[10]: fatigue, chest pain, shortness of breath, loss of appetite and hemoptysis.

Extra-pulmonary TB (ETB):

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There are different forms of ETB. The most commonly observed forms of ETB include: lymph node TB, pleural TB, pericardial TB, meningitis TB, and bone TB. General symptoms of ETB are similar to that of PTB: unexplained weight loss, nocturnal fever, and drenching nigh sweat. Other symptoms are varied depending on the affected organs.

All DM patients that have presented TB symptoms should be tested for TB. Diagnosis of PTB and ETB can be done using one of the following methods:

Sputum Smear: - Smear Positive:

At least two sputum specimens positive by microscopic examination, OR One sputum specimen positive by microscopic examination AND

radiological abnormalities consistent with PTB, OR One sputum specimen positive by microscopic examination, and culture

positive for Mycobacterium Tuberculosis.- Smear Negative: At least 6 sputum specimens negative by microscopic examination

including radiological abnormalities consistent with active PTB Chest Xray: In active pulmonary TB, a chest Xray can show opacification, infiltrates or

consolidations and/or cavities with or without mediastinal or hilar lymphadenopathy or pleural effusions (tuberculous pleurisy). In miliary TB, a pattern of many tiny nodules throughout the lung fields is common. In HIV and other immunosuppressed persons, any abnormality may indicate TB or the chest X-ray may even appear entirely normal.

GeneXpert: A cartridge-based, automated diagnostic test that can identify Mycobacterium tuberculosis (MTB) DNA and resistance to rifampicin (RIF) by nucleic acid amplification technique (NAAT). It is recommended by CENAT for diagnosing PTB among high risk groups such as diabetic patients, elderly, those living with a PTB patient, HIV patients and prisoners.

Culture: Mycobacterial culture is more sensitive than sputum smear and can identify drug resistant strains. However, this method takes a long time to produce results. There are different methods for mycobacterial culture. Solid media is a traditional culture method for mycobacterium and drug susceptibility testing (DST). The growth of TB bacilli on traditional solid medium requires 4-8 weeks and 28-42 days to know drug susceptibility testing (DST). Liquid culture is another method recommended by WHO to be used in low income settings. This culture method is more sensitive than solid culture. For DST, this method takes only 10 days. However this system is more prone to contamination.

Histology: In general, for extra-pulmonary TB, there are fewer M. bacterium organisms in infected sites. In this case, culture and histological examination of tissue specimens, such as may be obtained by needle biopsy of lymph nodes, are important diagnostic tests.

3.2. Screening for DM in TB patientsTB patients are considered to be a high risk group for developing DM, and the current rate of diabetes among TB patients is higher than among the general population. According to the WHO and International Union Against Tuberculosis and Lung Diseases, screening for DM should be done in all TB cases at the beginning of TB detection or at any time during the TB treatment course[5].

Primary screening for DM among TB patients can be done using a glucometer in the TB ward, at HCs or during outreach within communities by trained staff consisting of doctors, nurses, laboratory technicians, and/or DOT workers. The following tests should be conducted:

The fasting blood sugar (FBG) test: performed at least 8 hours after last meal The random blood sugar (RBG) test: performed at any time

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Postprandial blood glucose (PPBG) tests: performed at least 2 hours after the last meal.

According to the clinical practice guideline for type 2 diabetes in Cambodia [11], if FBS is ≥126 mg/dl (7mmol/L) or RBS (at least 2 hours after meal) is ≥200 mg/dl (11.1mol/L), patients are likely to have diabetes and this should be confirmed by a repeated test on another occasion unless there are obvious symptoms. In this case, the patients have to be referred to a DM clinic for DM work up and management. If someone is found to have impaired fasting glucose (FBS is 110-125mg/dl) then they are at increased risk of developing diabetes and other cardiovascular complications. Healthcare providers should give advice on how to maintain a healthy diet, the proper amount of physical activity, appropriate weight management and smoking cessation [11]. A repeat DM screening should be done 4 weeks after the first test.

4 Referral mechanismsIn order to detect TB in DM cases and DM in TB cases as early as possible, all healthcare providers should have clear guidance outlining WHEN and HOW to refer suspected/confirmed cases to the appropriate services.

4.1 Referring DM patients with TB/suspected TB from DM clinic to TB ward All DM patients with suspected or confirmed TB have to be screened and/or referred to a TB ward.

In health facilities, especially at referral hospitals (RHs) where both DM and TB services are available, referral must be made internally. If a diabetes clinic recognizes a potential case of TB, they should refer the TB patient to the TB ward with a referral letter (Apendix1).

If TB is diagnosed, patients will be registered in a TB registration book which is currently being used in Cambodia. The diagnosis of DM must also be recorded in the TB registration book.

If TB is ruled out, patients will be registered in the outpatient department (OPD) book.

The algorithm for screening TB among DM patients can be seen in Appendix 2.

4.2 Referring TB patients with DM from TB ward to DM clinicAll TB patients with DM must be referred to the DM clinic.

In health facilities, especially at RHs where both DM and TB services are available, referral must be made internally. When a TB ward recognizes a case of DM, they should refer the patient to the DM clinic ward referral letter (Appendix 1). Patients should be recorded in a registration book. (See Appendix 3 for the algorithm of DM screening among TB cases)

5 Management of TB-DM comorbidity patients

5.1 Clinical managementThe clinical management of patients with diabetes and tuberculosis comorbidity must confront many additional challenges not seen in the treatment of patients with either TB or DM alone [12]. One such challenge is the possible interaction of TB and DM drugs, which can have negative effects on the patient. For example, the TB drug rifampicin increases the hepatic metabolism of all sulphonylurea derivatives. Thus, exposure to the drug is strongly reduced in patients with TB-DM comorbidity which can in turn result in poor TB treatment outcomes. In diabetes management, blood sugar can be

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poorly controlled due to chronic inflammation, drug interactions and poor adherence to drug treatment. This will worsen TB treatment outcomes and could lead to other diabetes complications [12].

5.2 Treatment of TB-DM comorbidityUnfortunately, an optimal treatment strategy for patients with TB-DM comorbidity has not yet been developed. There is no scientific evidence to support different treatment regimens for patients with TB alone and patients with TB and DM comorbidity[12]. As a result, current treatment plans for TB-DM comorbidity have to follow the individual treatment guidelines for TB and DM, without any guidance on integrated care.

Table 2 and 3 summarize the TB treatment regimen patients based on the National Treatment Guideline 2011: Treatment Category 1: This treatment category is for:

- New smear positive PTB- Smear negative PTB, severe form- Extra PTB, severe form- TB/HIV patients.

Table 2: Category 1 treatment (initial and continuous phases) for 6 months duration in Cambodia Initial Phase: 2 months: 2RHZE Continuation Phase: 4 months: 4RH

Patients have to take 4 TB drugs every morning for 2 months under direct observation by health center staff or a trained person called “DOT”. The 4 drugs are: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol

Patients have to take 2 TB drugs every morning for 4 months under direct observation by health center staff or a trained person called “DOT”. The 2 drugs are: Rifampicin, Isoniazid

Drug DosagesPatients’ Weight

Initial Phase Continuation PhaseRHZE (150/75/400/275 mg) RH (150/75 mg)

30-39 kg 2 tablets 2 tablets40-54 kg 3 tablets 3 tablets55-70 kg 4 tablets 4 tablets> 70 kg 5 tablets 5 tablets

Dosage/kg/day: R: 10mg, H: 5mg, Z: 25mh, E: 15mg

For TB meningitis, or miliary TB, we add streptomycin during initial phase because it can better diffuse through meningeal barriers. The infection of streptomycin has also to be done under DOT. The dosage of the drug is as follow:

Patients’ Weight

Initial Phase Continuation PhaseRHZE (150/75/400/275 mg) Streptomycin 1000mg RH (150/75 mg)

30-39 kg 2 tablets 500 2 tablets40-54 kg 3 tablets 750 3 tablets55-70 kg 4 tablets 1000 4 tablets> 70 kg 5 tablets 1000 5 tablets

Dosage/kg/day: R: 10mg, H: 5mg, Z: 25mg, E: 15mg, S: 15mg Treatment Category 2: This treatment category is for:

- Relapse cases- Failure cases- Return after default cases

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- OthersTablet 3: Category 2 treatment for 8 months period (initial and continuous phases)

Initial Phase: 3 months: 2RHZE/S and 1RHZE Continuation Phase: 5 months: 5RH/5EIn first 2 months, patients have to take 4 combined TB tablets and receive injection every morning under direct observation by health center staff or trained person called “DOT”. The 4 combined drugs are: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol. Injection drug is streptomycin.In 3rd month, patients need to take only the 4 combined tablets above under DOT.

Patients have to take 3 TB drugs every morning for 5 months under direct observation by health center staff or trained person called “DOT”. The 3 drugs are: Rifampicin, Isoniazid (combined) and Ethambutol

The dosages of the treatment are as follow:

Patients’ Weight

Initial Phase Continuation PhaseMonth 1 and month 2 Month 3 Month 4 to Month 8

RHZE 150/75/400/275mg

Streptomycin 1000mg

RHZE 150/75/400/275mg

RH150/75 mg

E400 mg

30-39 kg 2 tablets 500 2 tablets 2 tablets 1.5 tablets40-54 kg 3 tablets 750 3 tablets 3 tablets 2 tablets55-70 kg 4 tablets 1000 4 tablets 4 tablets 3 tablets> 70 kg 5 tablets 1000 5 tablets 5 tablets 3.5 tablets

Dosage/kg/day: R: 10mg, H: 5mg, Z: 25mg, E: 15mg, S: 15mg

Treatment Category 3: This treatment category is for: - Smear negative PTB, non-severe form- Extra PTB, non-severe form

Table 4: treatment category 3 (initial and continuous phases) for 6 months duration in Cambodia Initial Phase: 2 months: 2RHZE Continuation Phase: 4 months: 4RH

Patients have to take 4 TB drugs every morning for 2 months under direct observation by health center staff or trained person called “DOT”. The 4 drugs are: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol

Patients have to take 2 TB drugs every morning for 4 months under direct observation by health center staff or trained person called “DOT”. The 2 drugs are: Rifampicin, Isoniazid

Drug DosagesPatients’ Weight

Initial Phase Continuation PhaseRHZE (150/75/400/275 mg) RH (150/75 mg)

30-39 kg 2 tablets 2 tablets40-54 kg 3 tablets 3 tablets55-70 kg 4 tablets 4 tablets> 70 kg 5 tablets 5 tablets

Dosage/kg/day: R: 10mg, H: 5mg, Z: 25mh, E: 15mg

Summary of the 2014 Type 2 Diabetes Treatment Guideline in Cambodia:

LIFESTYLE MANAGEMENT Maintain healthy weight: - Control weight: Normal BMI is between 18.6-22.9 kg/m2

- Control central Obesity: Men should be < 85cm; women should be < 80cm Healthy Diet: - Eat a variety of foods at each meal

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- Eat smaller but regular portions of starchy carbohydrate at each meal e.g. rice, noodles or beans.

- Increase the amount of fruit and vegetables every day and eat a variety. Eat one or two servings of fruit (especially low GI) per day.

- Avoid foods with high amounts of sugar such as soft drinks (coca cola), sweets or condensed milk.

- Reduce saturated fat and high fat foods such as fried foods (e.g. deep fried banana), Prohok and pork fat.

- Use unsaturated vegetable oils such as sunflower, olive or canola during cooking, rather than saturated oils (palm oil or coconut oil) or pork fat. Cut off fat before cooking.

- Decrease salt intake, limit intake of Prohok, MSG, fish sauce, soy sauce and salted meat or fish.

- Use other flavors (e.g. lemon juice, pepper) and herbs.- Reduce alcohol, especially strong alcohols like rice wine, whisky.- Most people in Cambodia do not eat enough protein. Good sources of protein include tofu,

beans, fish, eggs and chicken. Physical Activities:- The best activity is brisk walking 30 minutes per day on most days of the week is

recommended (>150 min/week).- If weight loss is desired then this may require longer periods of activities such as 50 – 60

minutes of moderate intensity on most days and avoid sedentary activities such as TV.- Those who have peripheral neuropathy should do other activities such as cycling or

resistance exercise.- Proper foot wear must be worn- Look for opportunities to walk or bicycle instead of using a motorbike/car. Smoking cessation: - Ask all patients if they smoke.- Advise about the importance of smoking cessation: (reduce risk of cardio-vascular diseases,

better glycemic control, decrease risk of neuropathy, decrease risk of end-stage renal failure, decrease risk of peripheral vascular disease which a risk factor of amputation).

- Assist them by encouraging them to set a quit date and giving educational material- Arrange for follow-up.- Give counseling yourself or contact a counselor in your region (Example: staff from ADRA

or from National Centre for Health Promotion).

ANTI-DIABETIC AGENTS:Lifestyle interventions should remain the underlying theme throughout the treatment. If patients’ blood glucose level is very high (e.g. fasting BSL>180 or postprandial >360 or HbA1c>9%) then medication needs to be used early to decrease glucose levels and relieve symptoms AND TITRATE to a second agent more rapidly if sugars not falling.

- Oral drugs: Obese patients with DM 2: (BMI ≥ 23mg/m2):

Step1: Lifestyle advice and Metformin. If glycemic target is not met Step2Step2: Add additional oral agent and titrate: Sulfonylurea or Thiazolidinedione. If

glycemic target is not met Step3Step3: Further Adjustments. Add third oral agent or start Insulin

Lean patients with DM2:Step1: Lifestyle advice. If glycemic target is not met Step2

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Step2: Start oral agent, titrate, and add other if needed: Sulfonylurea (Exam: Glibenclamide, Meformin, Thiazolidinedione). If glycemic target is not met Step3

Step3: Further Adjustments. Add third oral agent or start Insulin

- Insulin: If morning fasting glucose is > 126mg/dl, commence evening intermediate acting insulin (such as protaphane) before patient going to bed. It can be started from 8-10 units (0.1-0.2 unit/kg) and increase 2-4 units every 4-5 days or until glycemic target is met. Metfromin and Sulfonylurea can be continued. If blood sugar is still high despite night time insulin then twice daily intermediate acting insulin or twice daily mixed insulin maybe required.

5.3 Drug Interaction: Drug interaction during the treatment of patients with TB-DM comorbidity can lead to poor TB treatment outcomes and poor glycemic control. Concentration of Rifampicin which is a core drug for the treatment of TB can be reduced. Rifampicin increases hepatic metabolism of all sulphonylurea derivatives and biguanides and lowering their plasma levels resulting in hyperglycemia[13]. In addition the use of metformin in patients with tuberculosis can increase risk of gastro-intestinal side-effects and in rare cases, lactic acidosis[12]. This may result in poor adherence to medications.

6 Management of Healthcare Personnel

6.1 Diagnosis:Healthcare providers at the TB clinic and DM clinic should be clear on how to screen for suspected TB among DM patients and suspected DM among TB patients. All suspected cases have to be further investigated for making diagnosis. Both doctors and nurses must be involved in this process.

6.2 Treatment:When TB or DM is diagnosed, patients will be referred to the TB or DM clinic respectively for treatment. At this time, close follow up must be done to make sure that patients receive appropriate treatment.

6.3 Follow up:During the treatment course, follow up for patients with TB and DM comorbidity should be more frequent than patients with TB or DM alone. The following points should be focused on during each follow up: glycemic level (well control or not), diabetes complications (especially peripheral neuropathy), site effect of drugs (especially gastro-intestinal effect). For patients with BK (+), the conversion to BK (-) may take longer time.

6.4 Team meeting:Healthcare providers from the TB ward and DM clinic should have regular joint meetings. The purpose of these meetings are to report on the progress of TB-DM comorbidity cases, to share lessons learned on TB-DM comorbidity management, and/or to review past TB-DM comorbidity cases.

6.5 Capacity building: Providing some basic knowledge on TB to DM healthcare providers and on DM to TB healthcare providers is necessary. At the DM clinic, healthcare providers should understand at a minimum how to prevent or minimize TB transmission, basic TB symptoms and how to initially screen for TB, available TB services, how to make proper referrals and the potential for poor DM treatment outcomes (poor glycemic control) if TB co-exists. At the TB ward, healthcare providers should understand at a minimum the basic DM symptoms, how to screen for DM (using a glucometer), DM

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risk factors, availability of DM services, how to make proper referrals, and the potential for poor TB treatment outcomes if TB co-exists.

This knowledge-sharing will enable both the TB and DM teams to detect cases early, allowing for patients to be initiated on treatment sooner, and resulting in better management overall of both diseases which will in turn lead to improved treatment outcomes.

7 Prevention of TB-DM comorbidityCoordination between communicable and non-communicable disease services is a synergistic strategy to alleviate the burden of TB and DM[3]. Without providing clear guidelines and information to healthcare providers and patients regarding TB-DM comorbidity, this health concern will only continue to increase.

References 1. WHO. Tuberculosis, Fact sheet N°104. 2014; Available from:

http://www.who.int/mediacentre/factsheets/fs104/en/.

2. Tiemersma, E.W., et al., Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review. PLoS ONE, 2011. 6(4): p. e17601.

3. Lönnroth, K., G. Roglic, and A.D. Harries, Improving tuberculosis prevention and care through addressing the global diabetes epidemic: from evidence to policy and practice. The Lancet Diabetes & Endocrinology, 2014. 2(9): p. 730-739.

4. Wang, Q., et al., Prevalence of Type 2 Diabetes among Newly Detected Pulmonary Tuberculosis Patients in China: A Community Based Cohort Study. PLoS ONE, 2013. 8(12): p. e82660.

5. WHO and International Union Agaisnt Tuberculosis and Lung Disease, Collaborative Framework for Care and Control of Tuberculosis and Diabetes. 2011.

6. Dye, C., et al., Targets for global tuberculosis control [Short Communication]. The International Journal of Tuberculosis and Lung Disease, 2006. 10(4): p. 460-462.

7. Ministry of Planning and National Institute Of Statistics, Cambodia Inter-Censal Population Survey, 2013. 2012.

8. National Center for Tuberculosis and Leprosy Control, Tuberculosis Report 2012. 2012, National Center for Tuberculosis and Leprosy Control: Phnom Penh, Cambodia

9. National Institute of Statistics Ministry of Planning, Directorate General for Health Ministry of Health, and ICF Macro, Cambodia Demographic and Health Survey 2010. 2011: Phnom Penh, Cambodia and Calverton, Maryland, USA.

10. Ministry of Health, Tuberculosis Standard Treatment Regimens. 2011, National Center for Tuberculosis and Leprocy Comtrol: Phnom Penh, Cambodia.

11. Department of Preventive Medicine, Clinical Practice Guidelines Type 2 Diabetes, Cambodia 2006. 2006: Phnom Penh, Cambodia.

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12. Riza, A.L., et al., Clinical management of concurrent diabetes and tuberculosis and the implications for patient services. The Lancet Diabetes & Endocrinology, 2014. 2(9): p. 740-753.

13. Niazi, A. and S. Kalra, Diabetes and tuberculosis: a review of the role of optimal glycemic control. Journal of Diabetes & Metabolic Disorders, 2012. 11(1): p. 28.

14. Odone, A., et al., The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets. The Lancet Diabetes & Endocrinology, 2014. 2(9): p. 754-764.

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Appendix 1: Referral form

Referral form for TB-DM Screening

Patient’s Name: ...................................................................Sex: ....................... Age: ..........................Current disease: TB Diabetes (ID in registration book: ..............................)Name of Health Facility: ....................................................................................................................Refer from: ............................................................... To: .....................................................................

REFERRAL (To completed by referrer)

Reason for referral: TB suspicion ( Cough Fever Night sweats Weight loss Other: ..................................................................)

DM suspicion ( FBS: ………………..mg/dl RBS:……...… …mg/dl Other: ..................................................................)

Refer to: TB department DM departmentTreatment given: .................................................................................................................................

Date:…....../....../......... Name of referrer: ............................... Signature: ................, Tel: ........................

DIAGNOSIS (To completed by receiver)

Diagnosis: TB ( Sputum smear (+) GeneXpert Clinical evaluation Other: ........................................................................................................)

DM: ( FBS ………………………… RBS: ……………… Other: ……………….)

Other: ………………………………………………………………………………………………….

Date of diagnosis: .....................................................Treatment given: ..................................................................................................................................................

Date:…....../....../......... Name of physician: .......................................... Signature: ……..............., Tel: ........................

Please ask patient to brink this form back to original health department

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Appendix 2: TB screening among DM patients

DIABETES CLINIC

SCREENING FOR TB IN DM PATIENTS

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NOYESNO

YES

NOYES

Start TB management according to national guideline: Be aware of poor treatment outcome

Continue DM management: Be aware of poor blood sugar control

Education and counselling: TB & DM treatment adherence and psychological support

Regularly follow-up for both TB and DM

Continue DM management Be aware of TB symptoms Adherence to treatment

Refer to TB clinic for TB work up (Based on national guideline)

Is TB diagnosed?

FOLLOW-UP: According DM schedule OR come back early if TB symptoms present

Continue DM management Check for TB symptoms at each follow-up: Is TB

suspected?

SCREEN FOR TBDo the patients have one of the following symptoms

for at least two weeks: cough? Fever? Drenching night sweat? Unexplained weight loss?

ALL REGIDTERED DM PATIENTS

Appendix 3: DM screening among TB patients

TB CLINIC

SCREENING FOR DM IN TB PATIENTS

20

NOYES

NO

YES

NOYES

Start DM management according to national guideline: Be aware of poor blood sugar control

Continue TB management: Be aware of poor TB treatment outcome

Education and counselling: TB & DM treatment adherence and psychological support

Regularly and strictly follow-up

Continue TB management: Stop smoking, stop alcohol drinking, do

physical exercise, healthy diet Be aware of DM symptoms Adherence to TB medications

Refer to DM clinic for DM work up (Based on national guideline)

Is DM diagnosed?

Start/Continue TB management according to national guideline

Be aware of DM symptoms: Polyuria? Polydipsia? Polyphagia? Weight loss? Blurred vision? Numbness/tingling?

Adherence to TB medications

FOLLOW-UP: According to TB schedule. Repeat glycemic test every 2 months OR if DM symptoms present

Do patients have FBS ≥ 126mg/dl OR RBS (at least 2 hours after meal) ≥ 200mg/dl?

DO GLYCEMIC TEST Do patients have FBS ≥ 126mg/dl OR RBS (at

least 2 hours after meal) ≥ 200mg/dl?

ALL REGIDTERED TB PATIENTS