Tuberculosis Control Dr. Yeşim YASİN Fall-2013

Outline What is Tuberculosis (TB)? Burden of TB, TB/HIV, MDR-TB Strategy, targets, progress Prevention and Control Programmes of TB Challenges towards elimination

What is TB? One of the oldest diseases known in the history. It is a preventable and a curable disease if detected and treated early.

Prevelance of infection About one-third of the world‘s population is infected with TB bacilli people have been infected by TB bacteria but are not (yet) ill with disease and cannot transmit the disease.

After a healthy person with a healthy immune system breaths in TB bacteria, he or she will have 10% lifetime chance of developing TB. Immune-compromised persons have a much higher risk of falling ill.

results in transmission of the bacteria to others active TB (disease) delays in seeking care/diagnosis/treatment results in transmission of the bacteria to others

People ill with TB (active case) can infect up to 10-15 people through close contact over the course of a year Without proper treatment up to two thirds of people ill with TB will die.

Natural history of TB Factors Agent factors Host factors Social factors

Agent Factors Source of infection communicability Agent The most common source of Tuberculosis infection is the human case whose sputum is positive for the tubercle bacilli, and who has either received no treatment for it or not got treated fully. Such sources can discharge the bacilli in their sputum for years Agent Factors Agent Source of infection communicability Transmitted by droplet nuclei TB bacilli have a thick waxy coat,they are slow growing and they can survive in the body for many years in a dormant or inactive state whereby people are infected but show no signs of TB disease.

Host factors After 20 years of age, TB tends to affect more males due to higher exposure to infection and higher prevalence of risk factors. People who are co-infected with HIV and TB are 21 to 34 times more likely to become sick with TB Host Factors All age groups Males>Females Nutrition İmmunity Host susceptibility is universal, but the risk of infection is directly and mainly related to the degree of exposure.

Over-crowded living con. Social factors Social Factors Population explosion Over-crowded living con. Under- nutrition Lack of education

Incidence of some selected infectious diseases by years (per 100000 population), Turkey Tb incidence was calculated by the WHO, tb incidence 21010 will be provided once it is published in the global tb report 2011 of the WHO. Health statistic year book 2010

2011 Data-Turkey Incidence: 24/100K (WHO estimate) Patients in total: 15.679 (21/100K) registered Patients in total in Istanbul: 4.898 (36/100K) registered New cases in Istanbul: 4.457 AFB+ patients: 1.794 (registered)

TB mortality risk factors Site (higher in positive smear) Type of disease (association to…) Timeliness of diagnosis and treatment Appropriate diagnosis Mistake in reading X-rays Mistake in interpreting signs and symptoms Timely/Delayed diagnosis Timely/Delayed treatment Quality of treatment

Why worry about TB?

Some facts TB is the second (only to HIV/AIDS) greatest killer worldwide due to a single infectious agent. 8.7 million new cases in 2011; 13% is co-infected with HIV 22 high-burden countries account for 80% of the world’s TB cases. 1.4 million people died: 430.000 were HIV+ Almost 60.000 people worldwide lives with MDR-TB The largest number of new TB cases occurred in Asia, accounting for 60% of new cases globally Funding is inadequate Over 95% of TB deaths occur in low- and middle-income countries. TB is among the top three causes of death for women aged 15 to 44.

Estimated number of cases Estimated number of deaths 8.7 million (8.3-9.0 million) 1.1 million (13%) (1.0-1.2 million) Up to 0.5 million 1.4 million (1.3-1.6 million) 430,000 (400,000-460,000) Unknown, but probably>150,000 All forms of TB HIV associated TB MDR-TB

Incidence rates, 2011

TB cases, deaths, 1990-2011 Incidence Mortality All cases Peak > 9 million in early 2000s, 8.7 million in 2011 Total mortality peaked early 2000s at >1.8 million 1.4 million in 2011 millions HIV+ cases HIV+ mortality

TB/HIV Coinfection 80% of all TB/HIV cases are in Africa TB leading cause of death in PLHIV: ¼ of PLHIV worldwide die due to TB. PLHIV infected with TB: 20-40 times more likely to develop active TB. Untreated, TB in PLHIV leads to death in weeks

Distribution of MDR-TB among new TB cases, 1994-2011

Number of MDR-TB cases, 2011 Russian Federation 44,000 (14% of global MDR burden) Ukraine 9,000 Based on survey data Pakistan 10,000 (3% of global MDR burden) China 61,000 (20% of global MDR burden) India 66,000 (21% of global MDR burden) South Africa 8,100 Based on survey data

To date, 84 countries that reported XDR-TB About 9% of MDR-TB cases are XDR

1. Pursue high-quality DOTS expansion 2. Address TB-HIV, MDR-TB, and needs of the poor and vulnerable 3. Contribute to health system strengthening 4. Engage all care providers 5. Empower people with TB and communities 6. Enable and promote research Goal 6: to have halted by 2015 and begun to reverse the incidence… 2015: 50% reduction in TB prevalence and deaths compared to 1990 2050: elimination (<1 case per million population)

Global progress on impact  51 million patients cured, 1995-2011  20 million lives saved since 1995  2015 MDG target on track: global TB incidence rate peaked in early 2000s  BUT, TB incidence declining too slowly, 1.4 million people still dying, MDR-TB response slow, gaps in financing

Prevention and Control of TB

A B

Risk and Prevention-1 Risk and Prevention-1 1- Cough out TB particles - strength of cough (adults>>>children) 2- Live bacteria - smear + or culture + 3- Cavity

Risk and Prevention-2 Risk and Prevention-2 Person A Medication (DOT) Isolation <4 years At night Surgical mask Person B Space Natural ventilation/fan Air purifying respirator (N95) Ultra Violet Germicidal Irradiation (UVGI) High Efficiency Particulate Air (HEPA) Filter Negative pressure

TB CONTROL TB Control Detection and treatment of cases Treatment of latent infection Vaccination

The three priority strategies for TB prevention and control programs are: Identifying and treating individuals who have active TB. Finding and screening individuals who have had contact with TB patients to determine whether they are infected or have active TB, and providing appropriate treatment. Screening populations at high risk for TB infection to detect infected persons and provide therapy to prevent progression to active TB.

Tuberculosis prevention and control programs 1994 “Directly Observed Treatment, Short Course” (DOTS) strategy each country to detect smear-positive TB cases offer standardized DOT , with the objective of curing over 85% of TB patients.

DOTS DOTS Governmental commitment to TB Control Reliable and continious supply of high-quality Anti-TB drugs Microbiologic confirmation of TB diagnosis Supervision (DOT) of standardized short course Anti-TB theraphy-at least during the initial phase System for registration and follow-up

What can DOTS do What can DOTS do? Increase treatment completion and cure rates Reduce the emergence of drug resistant TB Improve cost-effectivenss of TB Control Reduce TB incidence in conjunction with other interventions.

Challenges Challenges HIV epidemic MDR-TB, XDR-TB Health system weakness and political will Poor infrastructure and lack of support Private practitioners Prisons

DOTS in Turkey DOTs in Turkey Since 2003 Ministry of Health performed pilot studies for DOTs (Directly Observed Theraphy Short-course). In 2006 Tuberculosis Control Programme was integrated to primary health care system and DOTs is expanded in Turkey. DOTs is the medication of the tuberculosis patients directly by the health personnel or a competent person until the full treatment is concluded.

DOT DOT DOT can lead to reductions in relapse and acquired drug resistance

Tuberculosis Prevention and Control Program in Turkey Main strategies include: BCG vaccination Case finding Effective chemotheraphy Health education Chemoprophylaxis Monitoring and evaluation system In order to reverse the increasing trend in TB, effective control and prevention is required in all countries. DOT strategy is the main national strategy in TB

BCG vaccination BCG only at birth (or first contact with health services) This is the current recommendation of the EPI (Expanded Program on Immunization) and the Global Tuberculosis Programme and is the policy in our country. BCG protects against serious childhood forms of Tuberculosis, such as TB meningitis and miliary TB. It may not protect to a high degree against adult pulmonary forms of the disease.

Case finding The aim is to reduce the transmission of TB by screening high risk populations (eg. those at an increased risk of exposure to TB infection, most notably contacts of infectious cases) and to detect and treat active disease earlier than would otherwise occur.

Chemoprophylaxis Chemoprophylaxis Primary prevention Decrease incidence rate of TB By using Isoniazid (INH)

Tuberculosis 1 Tuberculosis control and elimination 2010–50: cure, care, and social development Knut Lönnroth, Kenneth G Castro, Jeremiah Muhwa Chakaya, Lakhbir Singh Chauhan, Katherine Floyd, Philippe Glaziou, Mario C Raviglione

Challenges to “elimination” Commitment by governments and stakeholders fluctuating Funding not secure; catastrophic costs for the poor un-resolved Only 2/3 of estimated cases reported or detected TB/HIV major impact in Africa MDR-TB, with high burden in former USSR , China etc Un-engaged non-state practitioners Social and economic determinants maintaining TB Research in need of intensification and investments

1- Lack of commitment

2- Funding Funding gap vs Global Plan ~ US$2–3 billion per year Funding gaps reported by countries US$0.7 billion in 2013 US billions dollars 2013 2014 2015

3- The case detection/notification gap Global notifications Estimated incidence 3: The case detection/notification gap Nearly 3 million TB cases either not notified or not detected 8.7 7.8 TB cases (millions) 5.8 3.7 1990 2000 2010

GeneXpert 85 countries using it by mid-2013 Innovating with GeneXpert essential, but not sufficient to solve the case detection gap 85 countries using it by mid-2013

4- Responding to the TB/HIV epidemic The WHO policy on collaborative TB/HIV activities

4- Responding to TB/HIV epi. through collaborative efforts

The New England Journal of Medicine 5- Responding to MDR-TB The New England Journal of Medicine MDR Tuberculosis — Critical Steps for Prevention and Control Eva Nathanson, M.Sc., Paul Nunn, F.R.C.P., Mukund Uplekar, M.D., Katherine Floyd, Ph.D., Ernesto Jaramillo, M.D., Ph.D., Knut Lönnroth, M.D., Ph.D., Diana Weil, M.Sc., and Mario Raviglione, M.D. Review Article

WHA resolution 2009 (22 May) includes all essential policies

6- Unregulated private sector Private sector is first point of care in many settings. India: 70% of people with cough go first to private practitioners Diverse network of formal and informal providers ranging from hospitals and corporate sector to the traditional healers and quacks Private sector engagement crucial in closing the gap on case detection Contribution to finding people with TB between 10%-40% in countries Collaboration exists but still not enough in many settings. Efforts need to be made on both ends

7- Alleviation of risk factors & soc-economic determinants RR for active TB Weighted prevalence (22 HBCs) Population attributable fraction HIV infection 20.6/26.7 1.1% 19% Malnutrition 3.2 16.5% 27% Diabetes 3.1 3.4% 6% Alcohol use (>40 g/day) 2.9 7.9% 13% Active smoking 2.6 18.2% 23% Indoor air pollution 1.5 71.1% 26%

8- Intensive investments in R&D to develop new tools Diagnostic Vaccine Treatment Sputum smear microscopy BCG 1st-line TB drugs Discovered 1882 Developed 1920s Discovered 1943-1970

8- New tool pipelines in 2013 Diagnostics: 7 new diagnostics or diagnostic methods endorsed by WHO since 2007; 6 in development; yet no Point of Care (PoC) test envisaged Drugs: 1 new drug (Bedaquiline) approved in late 2012, but probably little impact on epidemiology; 1 expected to be approved in 2013; a regimen and other 2-3 drugs likely to be introduced in the next 4-7 years Vaccines: 11 vaccines in advanced phases of development; 1 just reported with no detectable efficacy

8. Research as the key for elimination 1.For elimination one would need rapid diagnostics at point of care, potent short treatments, mass treatment of latent TB infection (TLTBI), and potent pre- and post-exposure vaccines. None is available today 2.Basic research is fundamental to gain further knowledge and R&D pipelines must be expanded, nurtured and well-financed 3.Increased financial resources for research: the need for research is estimated at 2 billion US$ per year; today, about 650 million US$ are invested. 4.Develop coalitions to maximize outcomes and ensure a continuum of research efforts so that basic science and R&D pipelines are informed by needs, and operational research allows rapid adaptation and introduction in high-burden settings

THANK YOU!