Washington D.C., USA, 22-27 July 2012 Implementing Xpert ® MTB/RIF in Rural Zimbabwe Impact on diagnosis of smear-negative TB and time-

Washington D.C., USA, 22-27 July 2012www.aids2012.org

Implementing Xpert® MTB/RIF in Rural Zimbabwe

Impact on diagnosis of smear-negative TB and time-to-initiation of TB treatment in smear-negative

patients co-infected with HIV

S. Van Den Broucke1, S. Simons1, D. Munyaradzi1, B. Nyagadza1, K. Ncube2, C. Metcalf3, H. Bygrave3

1Medecins Sans Frontieres, Harare, Zimbabwe2Ministry of Health and Child Welfare Zimbabwe, Buhera, Zimbabwe3Medecins Sans Frontieres, South African Medical Unit, Cape Town, South Africa


Background

• Tuberculosis (TB) is the most common cause of morbidity and mortality in people living with HIV

• High # of Smear Negative cases in high prevalence HIV settings

→ Delay in diagnosis of TB in PLHIV


Many high-burden settings rely solely on smear microscopy

130 years old


Xpert® MTB/RIF (“GeneXpert”)• New TB diagnostic• Molecular method: detects DNA• In <2 hours, able to detect:

– Mycobacterium TB (MTB)– Resistance to rifampicin (RIF)

• Almost fully automated (cartridges)• Increased sensitivity: One test able to detect

TB in 72.5% of ‘smear-negative, culture-positive’ cases (Boehme et al NEJM 2010: Sep;363(11):1005-15)


Recommended by WHO

• WHO has recommended that the new molecular TB diagnostic Xpert® MTB/RIF be:“used as the initial diagnostic test in individuals suspected of having MDR-TB or HIV-associated TB”.

• December 2010


Setting

Zimbabwe

Harare

Buheradistrict


HIV prevalence 14%

Network of 2 hospitals, 26 clinics

14,000 patients on ART

BUHERA DISTRICT- POPULATION 230,000


Implementation in Buhera

• Xpert® MTB/RIF was installed:– in BBH Hospital April ‘11– in MMH Hospital May ‘11


Development and Training on Xpert® MTB/RIF Clinical Algorithm


Objectives

1. Assess operational challenges of implementing Xpert® MTB/RIF in a rural district laboratory setting

2. Assess the impact on laboratory based TB diagnosis and TB case-finding

3. Assess impact on time-to-initiation of smear-negative HIV Co-infected TB cases


Methods

• First 6 months of Xpert implementation: parallel testing with both smear and Xpert® MTB/RIF on specimens from all TB suspects

• Data was entered into an electronic database (XACT)

• Analysed to assess the increase in laboratory confirmed TB


Methods (2)

• TB Case-finding data was compared:– July-December 2010 (Pre-Xpert)– July-December 2011 (Post-Xpert)

• For the same time periods data was extracted from patient files to determine the time-to-diagnosis for smear negative co-infected TB cases at both hospital and decentralized clinics


Analysis & Outcomes


Operational Challenges

• Logistical preparations – Stable electrical power supply– Air conditioning: temp <30ºC for machine and storage

of cartridges

• Training– Lab technicians– Clinicians

• Initial high error rate (Error 5011) leading to a change of module


Results of parallel phaseIncrease in laboratory based TB diagnosis

Total Sputum Specimens Tested 1357

Smear Positive Smear Negative Total

Xpert Positive 146 102 248

Xpert Negative 6 1103 1109

Total 152 1205 1357


Increase in Laboratory Confirmed TB

Smear Xpert0tan28a566028

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Confirmed TB Cases

63% Increase


Pooled results from 7 African sites supported by MSF OCB

719 samples were Xpert MTB+ of 4169 tested

449 smear-positive 270 smear-negative

Þ Lab confirmation of TB increased by an average of ~60 % among the 7 sites (range: 22.4 - 127%) Less empiric diagnosis of TB

P. Saranchuk, H. Bygrave, et al

Impact of Xpert MTB/RIF on diagnosis of TB in 7 African sites


Case-finding Pre and Post Xpert

Pre Xpert Post Xpert

TB Suspects 2854 1973

TB Cases 717 600

% of Suspects Diagnosed

with TB25% 30%


TB Case-finding

Pre Xpert Post Xpert

Smear Positive 29% 32%

Smear Negative 46% 52%

Smear not done 9% 9%

EPTB 16% 7%


Time to TB Treatment Initiation for Smear-negative Patients Co-infected with HIV

Hospital Decentralised Clinics0tan28a566028

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Pre-Xpert Post-Xpert

Day

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Increase in detection of DR-TB

• Of the 245 Xpert positive patients diagnosed over 6 months Rifampicin resistance was detected in 14 patients– Risk of ‘false positive’ Xpert RIF+ result– Requires confirmation

• The number of DR-TB cases is expected to approximately triple to quadruple:– In 24 months pre-Xpert, 18 cases of DR-TB diagnosed– In 6 months post-Xpert, 14 TB patients have had Xpert

RIF+


Take Home Message

Introduction of Xpert® MTB/RIF

in resource poor settings is possible.......


Conclusions (1)

• Xpert® MTB/RIF increased the proportion of laboratory based diagnoses

• Xpert® MTB/RIF increased the number of laboratory-confirmed TB cases

• Both of these advantages support ‘task-shifting’ of TB diagnosis and initiation of TB treatment to lower levels of health care workers

• And reduces the need for some patients to travel to hospital for CXR


Conclusions (2)

• Time-to-initiation of Smear negative TB in HIV positive patients at decentralized clinics was reduced:

– potential to reduce morbidity in individuals– reduce the risk of TB transmission to others

• Xpert® MTB/RIF triples/quadruples the number of DR-TB cases diagnosed

• Challenges of introducing Xpert® MTB/RIF :– Initial logistical investments

– Cost per cartridge

– High initial rates of ‘inconclusive results’ in most settings


Acknowledgements

• MOH and MSF health workers in Buhera district

• MSF South African Medical Unit (SAMU)• Buhera patients

Documents

Washington D.C., USA, 22-27 July 2012 Implementing Xpert ® MTB/RIF in Rural Zimbabwe Impact on diagnosis of smear-negative TB and time-