GeneXpert Implementation for diagnosing TB in HIV patients in Jos, Nigeria

BRIAN POOLE, MAXWELL AKANBI, CHAD ACHENBACH Introduction

• TB diagnosis and treatment is challenging in resource-limited areas,

especially in patients with HIV co-infection. • Smear microscopy, the standard for TB diagnosis, has a low sensitivity

ranging from 25-68.9% (1,2) for TB diagnosis in HIV patients. • Cepheid’s GeneXpert uses nucleic acid amplification to detect TB and

rifampicin resistance simultaneously in 2 hours. • GeneXpert has a sensitivity of 84-97.8% (1,3) for detecting TB in HIV

patients • The growth and spread of multi-drug-resistant tuberculosis (MDR-TB) in

high TB burden countries like Nigeria is a growing concern. • The World Health Organization (WHO) recently recommended that

GeneXpert be used to screen all patients suspected of TB in resource-limited settings.

• Even at the reduced rate of $9.80 USD per GeneXpert cartridge, the cost and the infrastructure necessary to effectively utilize GeneXpert remain a challenge.

• In early 2013, the AIDS Prevention Initiative Nigeria (APIN) Center (Fig. 4 a,b,d) at Jos University Teaching Hospital (JUTH) installed a GeneXpert (Fig 1) with a grant from the Centers for Disease Control (CDC).

• We began a project in June 2013 to look at the use of GeneXpert in resource-limited settings, to assess the predictive value of current WHO stratification guidelines of people at risk for MDR-TB, and to develop an algorithm for incorporating GeneXpert into TB diagnosis for HIV patients in resource-limited settings.

Research Question What is the prevalence of MDR-TB in Jos, Nigeria? How does this compare to the prevalence that has been reported elsewhere in Nigeria? Are there additional factors beyond the WHO guidelines that are predictive of MDR-TB?

Methods We began this project in June 2013 with a plan to enroll a convenience sample of 500 HIV-infected patients suspected of having TB at an outpatient clinic visit.

• We collect data on demographics, prior TB infection, and risk factors for MDR-TB from each patient (Figure 3). • Additional data on HIV disease and treatment are extracted from the APIN electronic medical record. • Each patient provides two sputum samples, one for smear microscopy testing and another for GeneXpert testing.

117 patients were tested with GeneXpert prior to the start of our project. As a preliminary assessment, we collected the results of their GeneXpert and smear microscopy tests and compared them to assess the ability of GeneXpert versus smear microscopy to detect TB.

Results We found that implementation of the GeneXpert has been challenging for several reasons: • Cartridge supply to the clinic is highly unreliable resulting in frequent

periods of a week or longer where GeneXpert is not operational. • The need for uninterrupted power by GeneXpert required the installation

of a costly inverter system to power it. • The clinic staff do not utilize the quicker results from GeneXpert to

initiate earlier treatment except in the case of detected rifampicin resistance.

• GeneXpert reports TB levels as very low, low, medium, high, or very high. Some clinic staff interpret different levels as a positive result.

• The APIN clinic is expected to relocate to the JUTH permanent site (Fig 4c) in the next few years, 12 km away from the city, which will make it more difficult for patients to attend the clinic.

• The civil unrest in recent years has also greatly impacted many patients who relocated and have been lost to follow-up or who lost their ability to come to clinic appointments as a result of the fighting.

Of the 117 patients tested using GeneXpert prior to our project start: • 28 tested positive for TB with GeneXpert • 1 of those positive with GeneXpert had rifampicin resistance • 16 were positive with smear microscopy.

Of note, no microscopy results were on record for 9 of the patients who tested positive with GeneXpert. Our overall project examining MDR-TB prevalence and predictors is ongoing with completion of enrollment expected by January 2014.

Conclusion and Recommendations • It appears from our preliminary analysis that GeneXpert has the potential

to increase TB detection by as much as 75% (28 vs. 16). • GeneXpert can provide much earlier diagnosis of TB and MDR-TB, which

is important given that MDR-TB treatment in Nigeria requires travel and lengthy hospitalization.

• The APIN clinic can better utilize the faster turnaround from GeneXpert to initiate earlier treatment by more proactively contacting patients and having them return sooner

• The APIN clinic should ensure that all staff is using the same standard in interpreting GeneXpert results.

• The future of the funding for GeneXpert in Jos is also uncertain. The Nigerian government has not committed to funding the machine though it has been asserted that the ability of GeneXpert to provide early diagnosis would make adoption of it less costly than current diagnostic methods.(2)

References 1. Carriquiry G, Otero L, Gonzalez-Lagos E, Zamudio C, Sanchez E, Nabeta P, Campos M, Echevarria J, Seas C, Gotuzzo E. A diagnostic accuracy study of Xpert(R)MTB/RIF in HIV-positive patients with high clinical suspicion of pulmonary tuberculosis in Lima, Peru. PloS one. 2012;7(9):e44626. doi: 10.1371/journal.pone.0044626. PubMed PMID: 22970271; PubMed Central PMCID: PMC3436871. 2. Gray JM, Cohn DL. Tuberculosis and HIV coinfection. Seminars in respiratory and critical care medicine. 2013;34(1):32-43. doi: 10.1055/s-0032-1333469. PubMed PMID: 23460004. 3. Scott LE, McCarthy K, Gous N, Nduna M, Van Rie A, Sanne I, Venter WF, Duse A, Stevens W. Comparison of Xpert MTB/RIF with other nucleic acid technologies for diagnosing pulmonary tuberculosis in a high HIV prevalence setting: a prospective study. PLoS medicine. 2011;8(7):e1001061. doi: 10.1371/journal.pmed.1001061. PubMed PMID: 21814495; PubMed Central PMCID: PMC3144192.

Figure 3 Patient Information Questionnaire

Figure 1 GeneXpert setup similar to APIN’s (left) from ilexmedical.com and GeneXpert cartridge (right) from sciencespeaksblog.org

Figure 2 View overlooking Jos, Nigeria. Population of Jos is approximately 900,000. Figure 4. a) At the APIN Centre. b) The main APIN clinic (formerly the site of JUTH). c) JUTH permanent hospital approx. 12 km from Jos , a 30 minute drive. Plans exist to relocate the APIN Centre here. d) APIN Centre. e) Patient waiting area at APIN. Patients line up and wait for hours to be seen by a doctor in one of the side offices. f) Typical doctors office at APIN

a. b. c.

d. e. f.