Washington D.C., USA, 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 Broucke 1, S. Simons 1, D. Munyaradzi 1, B. Nyagadza 1, K. Ncube 2, C. Metcalf 3, H. Bygrave 3 1 Medecins Sans Frontieres, Harare, Zimbabwe 2 Ministry of Health and Child Welfare Zimbabwe, Buhera, Zimbabwe 3 Medecins Sans Frontieres, South African Medical Unit, Cape Town, South Africa

Washington D.C., USA, July 2012www.aids2012.org 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

Washington D.C., USA, July 2012www.aids2012.org Many high-burden settings rely solely on smear microscopy 130 years old

Washington D.C., USA, July 2012www.aids2012.org 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): )

Washington D.C., USA, July 2012www.aids2012.org 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

Washington D.C., USA, July 2012www.aids2012.org Setting

Washington D.C., USA, July 2012www.aids2012.org HIV prevalence 14% Network of 2 hospitals, 26 clinics 14,000 patients on ART BUHERA DISTRICT- POPULATION 230,000

Washington D.C., USA, July 2012www.aids2012.org Implementation in Buhera Xpert ® MTB/RIF was installed: –in BBH Hospital April ‘11 –in MMH Hospital May ‘11

Washington D.C., USA, July 2012www.aids2012.org Development and Training on Xpert ® MTB/RIF Clinical Algorithm

Washington D.C., USA, July 2012www.aids2012.org 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

Washington D.C., USA, July 2012www.aids2012.org 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

Washington D.C., USA, July 2012www.aids2012.org 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

Washington D.C., USA, July 2012www.aids2012.org Analysis & Outcomes

Washington D.C., USA, July 2012www.aids2012.org 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

Washington D.C., USA, July 2012www.aids2012.org Results of parallel phase Increase in laboratory based TB diagnosis Total Sputum Specimens Tested 1357 Smear PositiveSmear NegativeTotal Xpert Positive Xpert Negative Total

Washington D.C., USA, July 2012www.aids2012.org Increase in Laboratory Confirmed TB

Washington D.C., USA, July 2012www.aids2012.org Pooled results from 7 African sites supported by MSF OCB 719 samples were Xpert MTB+ of 4169 tested 449 smear-positive270 smear-negative  Lab confirmation of TB increased by an average of ~60 % among the 7 sites (range: %)  Less empiric diagnosis of TB P. Saranchuk, H. Bygrave, et al Impact of Xpert MTB/RIF on diagnosis of TB in 7 African sites

Washington D.C., USA, July 2012www.aids2012.org Case-finding Pre and Post Xpert Pre XpertPost Xpert TB Suspects TB Cases % of Suspects Diagnosed with TB 25%30%

Washington D.C., USA, July 2012www.aids2012.org TB Case-finding Pre XpertPost Xpert Smear Positive 29%32% Smear Negative 46%52% Smear not done 9% EPTB 16%7%

Washington D.C., USA, July 2012www.aids2012.org Time to TB Treatment Initiation for Smear-negative Patients Co-infected with HIV

Washington D.C., USA, July 2012www.aids2012.org 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+

Washington D.C., USA, July 2012www.aids2012.org Take Home Message Introduction of Xpert ® MTB/RIF in resource poor settings is possible

Washington D.C., USA, July 2012www.aids2012.org 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

Washington D.C., USA, July 2012www.aids2012.org 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

Washington D.C., USA, July 2012www.aids2012.org Acknowledgements MOH and MSF health workers in Buhera district MSF South African Medical Unit (SAMU) Buhera patients