MRC/info4africa KZN Community Forum | July 2014 | Dr Elizabeth Spooner | TB in SA

29 JULY 2014

HPRU

TB : Where are we and where are we going?

MRC/Info for Africa KZN Community Forum

Background and Pathogenesis

Background• ‘Phthisis’ appears in Ancient Greek literature as a cause of disease that was

almost always fatal, and ‘Consumption’ or The Great White Plague was an epidemic though Europe in the 17th century. • 1882 Robert Koch was the first scientist to isolate Mycobacterium Tuberculosis

and culture it and stain it and document the cell mediated immune response.• BCG (Bacille Calmette- Guerin) vaccine was discovered in 1906 and first used

on humans in 1921 in France.• Still the only vaccine used commonly today (childhood meningitis)• 1944 Streptomycin was used for TB successfully, Isoniazid (1952),

Pyrazinamide (1954) Ethambutol(1962) and Rifampicin (1963)• 50 yrs later these are still the mainstay of 1st line TB treatment

Pathogenesis• Tuberculosis is spread from person to person through the air by droplet nuclei spread. Droplet nuclei are 1-5 microns

and contain 1-5 bacilli which are highly infectious.• One cough can produce 300 000 droplet nuclei and a sneeze up to 1 million. 1-10 bacilli are needed for infection.• Direct sunlight kills bacteria but they can remain alive and airborne for many hours in poorly ventilated areas.

Primary TB – first exposure• The TB Bacillus divides slowly – every 25-32 hours• Takes 2-12 weeks to illicit a cellular immune response to prevent growth.• Before the cellular immune response TB can spread via the lymphatics and blood and common sites to seed are the upper lung lobes, kidneys, brain and bones• Usually asymptomatic – 90%, 10% develop disease (children most commonly)• 10% clear all bacilli, 90% have latent TB infection (LTBI) with dormant bacilli (uninfectious)

Post Primary/Secondary TB- previously exposed• Reactivation of latent TB bacilli or re-infection• Commonly with Immune compromise

HIV – TB Syndemic• HIV and Tuberculosis have a synergistic relationship, that is not fully understood• HIV positive patients are susceptible to TB even at a high CD4 count• 85% of South Africans have Latent TB (LTBI)• HIV negative – 10% lifetime risk of developing TB (5% in first 2 yrs) ie. 90% of people with latent TB never develop disease • HIV positive - 10% per year chance of developing TB or 12-20 times greater risk

than for HIV negative people• HIV + TB patients have a low transmission of TB (30% smear positive)

• HIV negative TB patients are driving the epidemic!

(JID 2012 Incipient and Subclinical Tuberculosis: Defining Early Disease States in the Context of Host Immune

ResponseJacqueline M. Achkar and Elizabeth R. Jenny-Avital)

• HIV-negative people are estimated to be sputum smear positive (i.e., with acid fast bacilli observed in sputum) 1–3 y prior to diagnosis in resource-poor settings (9, 10). By these estimates, a single person with active TB could infect as many as 45 other individuals.

(Understanding Latent Tuberculosis: A Moving Target Philana Ling Lin and JoAnne L. Flynn Journal of Immunology 2010)

The Global Tuberculosis Epidemic

• 1993 TB was declared a GLOBAL HEALTH EMERGENCY by the WHO

• 22 High burden countries (HBC) identified including South Africa

• Millennium Development Goals (MDG’s) address TB under 6c

• 2001 Stop TB Partnership was formed – 1100 partners hosted by WHO

2012

• 8.6 million people TB disease (1.15million

HIV+ …..14%)

• 1.3 million deaths (340 000 HIV positive….26%))

MDR/XDR TB in SA• 2012 Estimated 8100 pts with MDR TB in SA• 1.8% of new cases and 6.7% of retreatment cases• 9% of MDR pts are found to have XDR TB

• RR-TB is Rifampicin resistant TB – treat as MDR TB for 18-24 months• MDR-TB is Rif and Isoniazid resistant TB• XDR-TB is also resistant to 2 MDR 2nd-line drugs

MDR treatment in KZN Dr Iqbal Master at King Dinizulu Hospital• If Rifampicin resistant on GeneXpert inform MDR facility in 24 hrs and

take sputum for culture and DST and refer• Start all MDR patients on treatment in 5 days• Currently there is a 3-5 week wait for outpatients to be seen at KDH• Start standard treatment in the mean time until appointment at KDH• Nurse initiated MDR treatment is being piloted – really needed in KZN

Causes of Death in SA – Mortality 2009-2011 • TB is the leading cause of death in SA• Absolute numbers of TB deaths are decreasing by 1% per year (ART)• More men die of TB than women• TB is the leading cause of death in 7 provinces, 2nd to respiratory tract

infections in Free State and Limpopo• KZN has nearly double the TB deaths of any other province (Gauteng

and EC)

• TB is the leading cause of Maternal Death• TB is the leading cause of Community Acquired Pneumonia

TB in Health Care Workers (Ch 17 pg 81)• All categories of health care worker have an increased risk of TB• Encourage all health care workers to know their HIV status and place

positive staff in low risk areas.

• ?? Should we do sputum screen 6 monthly irrespective of symptoms

Isoniazid Prophylaxis IPT• Found in DOH Adult ART Guidelines 2013.

• Negative TST does not exclude TB disease

• Integration of HIV and TB care• Means different things to different people• REGISTERS!• Pg 71

Other points of interest…….pg 42

pg 26

Infection Control

TB Infection Control- prevent exposure to patients and staff

A. Work Practise/Administration• Clinic flow• Education• Separation• FAST queue• Integration of HIV TB

B. Environmental Control• Ventilation• Filtration• Ultraviolet Germicidal Irradiation

(UVGI)

DO NOT WORK ON THEIR OWNMUST HAVE A.

Administration for Infection Control

1. Screen – all coughing pts 2. Educate – cough hygeine and provide with mask/tissue3. Separate – FAST queue4. Integrate HIV services – fast track through HCT, ART and other services5. Investigate and Treat – Point of Care (POC) diagnosis optimally does this on same day

Research

Bedaquiline• 2012 FDA granted accelerated approval for Bedaquiline• WHO issued guidance on how it’s use should be monitored• In SA in 2011 MSF, Right to care approached MCC re use of

Bedaquiline in the ‘Compassionate use programme’• For Individually tailored pts with limited treatment options – XDR and

Pre-XDR.• This was approved in Dec 2012• At 4 MDR sites in SA

• TB LAMP• Molecular test (PCR) on sputum• Point of Care• ‘as good as GeneXpert’• Sensitivity 97% HIV-, 77% HIV+

• TB LAM• Lateral flow assay on urine• Point of Care• Highest sensitivity low CD4

(60%)

UNIT : HPRU

TOPIC : TB: Where are we and where are we going?

PRESENTER : Beth Spooner : Dr

E-MAIL : [email protected]