Addressing TB in a High HIV Prevalence Setting in Rural South …cira.yale.edu/sites/default/files/events/120920yacs... · 2020-01-03 · Isoniazid Preventive Therapy is recommended

Yale AIDS Program Section of Infectious Diseases

Yale University School of Medicine Sheela Shenoi MD MPH

September 20, 2012

Addressing TB in a High HIV Prevalence Setting in Rural South Africa: the 3Is

Outline Background on Tuberculosis and HIV epidemics South Africa & Tugela Ferry WHO 3Is Infection Control Intensive Case Finding Isoniazid Preventive Therapy Future Plans

M.tb & Global Epidemiology • Mycobacterium tuberculosis

• TB transmission occurs exclusively via airborne route • Coughing, sneezing, talking • Inhibited by UV light

• HIV infected patients are particularly susceptible • Diminished immune response • Complicates diagnosis and treatment • Increased morbidity and mortality

• 8.8 million new cases of TB in 2010 • 1.45 million deaths from TB in 2010

• 350,000 deaths in HIV infected patients

WHO, 2011

Reported TB Cases United States, 1982–2010*

Year No. Rate*

2005 14,068 4.8

2006 13,732 4.6

2007 13,286 4.4

2008 12,905 4.2

2009 11,537 3.8

2010 11,182 3.6

*Updated as of July 21, 2011

No.

of C

ases

Year

MMWR, 2012

TB and HIV Globally 8.8 million incident TB cases (2010) 13% HIV coinfection 80% in Africa

1.4 million deaths 350,000 (25%) deaths among HIV infected

HIV status known in 24% 440,000 cases of MDR TB (2008)

34 million PLWH (2010) 68% in sub-Saharan Africa 1.8 million deaths 20-30% of eligible receiving antiretroviral therapy (ART)

WHO, 2010

UNAIDS, 2010 WHO TB 2011 UNAIDS 2011

Estimated TB Incidence Rates, 2010

Estimated HIV Prevalence in New TB Cases, 2010

WHO, 2011

Presenter

Presentation Notes

These are the latest WHO maps up above illustrating overall TB incidence

Drug Resistant TB Multiple Drug Resistant (MDR) TB: resistance to isoniazid, rifampin

XDR TB defined as: MDR plus resistance to a fluoroquinolone, and an injectable agent (amikacin, kanamycin, capreomycin)

In 2005-06, 53 patients with XDR TB identified in Tugela Ferry, South Africa with 98% mortality within 16 days of obtaining culture Now reported throughout South Africa and from 58 countries South Africa has greatest case load Jeopardizes TB & antiretroviral (ARV) rollouts globally Mortality from MDR TB: 73% Mortality from XDR TB: 82%

WHO, 2011 Gandhi, Lancet, 2006 Moodley, 2011

Presenter

Presentation Notes

Here I’ll describe the problem of drug resistant TB. While MDR TB or multiple drug resistant TB is resistance to isoniazid and rifampin only, XDR TB, or extensively drug Resistant Tuberculosis or XDR TB, goes beyond that and defined as resistance to isoniazid, rifampin, any fluoroquinolone, and an injectable. This is a relatively new entity that was first described in 2006 by the U.S. CDC – the first and largest group of patients was reported from Tugela Ferry, South Africa where my mentor has been working for 10 years. There were 53 patients reported who had very high and rapid mortality. Since then, XDR TB has been reported throughout South Africa and from a total of 58 countries. So this was not an isolated outbreak, but an epidemic. Drug resistant TB is a threat to public health globally and has the potential to disrupt national TB programs as well as antiretroviral rollouts. Since 2006, there have been more than 500 patients diagnosed from Tugela Ferry alone with persistently high mortality. However, with more attention and improved treatment regimens, mortality has come down somewhat to 82%. From this group a small number of survivors has emerged. There are many questions related to XDR TB patients and how best to respond to this epidemic in a resource limited environment. Thus, we sought to better characterize these patients to inform health planners. We looked at demographic, clinical, and treatment characteristics of a representative group of XDR TB patients.

WHO, March 2011

Multi Drug Resistant

(MDR) TB

Global XDR TB October 2011

South Africa - TB Population: 50,133,000 (2010) Incidence: 981 cases per 100,000/year *U.S.: 3.6/100,000 per year* 5th in the world in TB cases 4th in the world of drug resistant TB cases 1st in the world in number of HIV/TB cases (36% of global burden) Estimated mortality from TB: 50% Diagnosis: AFB is the standard

Culture is not widely utilized, but increasing

WHO TB, 2011 WHO, 2012 MMWR, 2011

The HIV and TB epidemics in South Africa

0

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1989 1991 1993 1995 1997 1999 2001 2003 2005 2007 Year

TB c

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rate

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pop

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HIV

Pre

vale

nce

(%) HIV

TB

Tugela Ferry, Rural South Africa 180,000 traditional Zulu people 31% HIV antenatal prevalence 1074/100,000 TB incidence Extreme poverty high employment (85%) no electricity (70%) no access to clean water (70%)

Served by 350 bed district hospital Tugela Ferry

Presenter

Presentation Notes

Our site is inland in KwaZulu Natal province in eastern South Africa, about 3 hrs drive from Durban. We are in a rural impoverished area of ~180,000 people who live traditionally in Zulu huts widely dispersed throughout ~2000 sq km. The population is characterized by high unemployment, and generally lacks electricity and access to clean water. The HIV prevalence among pregnant women is extremely high at 38% and the TB incidence is also very high at nearly 1100/100,000. From 2006-2008, there were 705 cases of XDR TB documented in KZN province. Our site is served by a 350 bed district government hospital as well as our partner NGO, Philanjalo.

The 3Is World Health Organization TB control strategy

1. Infection Control

2. Intensive Case finding (ICF)

3. Isoniazid Preventative Therapy

WHO, 2008

Presenter

Presentation Notes

Currently the WHO’s strategy for controling TB/HIV coinfection is a 3 fold platform: ICF, Infection Control, and IPT. Accumulating data emphasizes that the 4th one should be Initiation of ARVs. Furthermore, integration of HIV testing and ARVs into TB management is essential. This is important for clinicians as well as policy makers – these are two clinical problems affecting the same patient and should managed in an integrated fashion.

Infection Control

TB Infection Control

• Nosocomial transmission of TB to patients and healthcare

workers is well-described • XDR-TB epidemic in Tugela Ferry likely driven by nosocomial transmission

• Community transmission of XDR-TB estimated to predominate by 2012 • Household contacts are at increased risk: 3.3% of MDR/XDR-TB patients

concurrently have active TB

• Airborne Infection Control • Administrative Controls • Personal Protection • Environmental Controls

PROJECT: Effect of natural ventilation at the household level Joshi et al., PLoS Medicine, 2006 Jarvis, Research in Microbiology, 1993 Basu et al., Proc Nat Academy Sci 2009 Vella et al, IJTLD, 2011 WHO Policy on TB Infection Control, 2009 Shenoi et al., CID 2010

Intensive Case Finding

Intensive Case Finding Early diagnosis for both improved outcomes and decreased transmission

Actively looking for TB cases instead of waiting passively for TB cases to come to the health care system

Areas of concern: Which tools to diagnose TB?

Symptoms only, sputum smear/culture, chest xray

Which populations to screen? HIV positive patients

Where to screen them? inpatient wards, outpatient clinics

Who will perform screening? dedicated staff, clinical vs. nonclinical

Intensive Case Finding Historical focus on TB case finding among known HIV patient populations

Novel Community-Based Strategy

Project: Community Based Intensive Case Finding (NIAID K23) In conjunction with local Department of Health TB screening effort with integrated HIV services Team of nurses, HIV counselors, field health workers HIV testing with phlebotomy for CD4 cell count TB symptom screen with sputum collection Evaluation of clinical outcomes

Congregate community sites

Municipality events Pension pay points

Home based care events

Taxi ranks

Prisons Secondary schools

Health fairs

Isoniazid Preventive Therapy (IPT)

Community Based ICF & IPT Isoniazid Preventive Therapy is recommended for all HIV+ persons,

regardless of: Age (Adults & children) Pregnancy status TB history CD4 count

Isoniazid daily for 6 months to reduce incidence of TB Durability ~18 months

Currently only being offered to those already in HIV care (CD4<350)

Project: Implementation of IPT through ICF (CDC award)

Other Future Plans Rapid point of care CD4 count assay (NIAID R21) Evaluation in community setting Comparison to standard phlebotomized sample Task shifting evaluation

Summary The WHO’s 3Is form a comprehensive platform for combatting TB We are developing and implementing community based interventions

in all 3 areas: Infection Control Intensive Case Finding Isoniazid Preventive Therapy

Application at the community level is essential to early detection and

interrupting transmission

Presenter

Presentation Notes

HIV drives the TB epidemic and contributes to massive morbidity and mortality

Acknowledgements • Ralph Brooks

• Rick Altice

• Rob Dubrow

• Dan Zelterman

• Gerald Friedland

• Laurie Andrews

• Anthony Moll

• Mdu Mntambo

• Tassos Kyriakides

• Devesh Upadhya

• Sara Sani

• Melissa Lygizos

• Fogarty International Center

• Fulbright

• PEPFAR/ICAP

• Gilead Foundation

• NIAID

• USAID/URC

• Aurum Institute

• Irene Diamond Fund

• Yale AIDS Program

Questions?

Documents

Addressing TB in a High HIV Prevalence Setting in Rural South …cira.yale.edu/sites/default/files/events/120920yacs... · 2020-01-03 · Isoniazid Preventive Therapy is recommended