Molecular Diagnosis of Extrapulmonary Tuberculosis and Rifampicin Resistance Using Genexpert MTB/RIF in Morocco

Kholoud Maafi; Ismail Nafi; Firdaous Laariche; Marwa Nabil; Hamza Abidar; Karim Souly; Souad Aboudkhil

doi:10.63095/NBSEH.26.455534

Authors

Kholoud Maafi Laboratory of Biotechnology, Agri-Food, Materials and Environment, Hassan II University of Casablanca (ROR: https://ror.org/001q4kn48)
Ismail Nafi Faculty of Medicine and Pharmacy of Rabat, Mohamed V University (ROR: https://ror.org/00r8w8f84), Morocco
Firdaous Laariche Ibn Sina University Hospital in Rabat (ROR: https://ror.org/038zpvz53), Morocco
Marwa Nabil Ibn Sina University Hospital in Rabat (ROR: https://ror.org/038zpvz53), Morocco
Hamza Abidar Ibn Sina University Hospital in Rabat (ROR: https://ror.org/038zpvz53), Morocco
Karim Souly Ibn Sina University Hospital in Rabat (ROR: https://ror.org/038zpvz53), Morocco
Souad Aboudkhil Laboratory of Biotechnology, Agri-Food, Materials and Environment, Hassan II University of Casablanca (ROR: https://ror.org/001q4kn48)

DOI:

https://doi.org/10.63095/NBSEH.26.455534

Keywords:

Extrapulmonary tuberculosis, GeneXpert MTB/RIF, PCR

Abstract

Extrapulmonary tuberculosis (EPT) is a form of tuberculosis caused by Mycobacterium tuberculosis, affecting sites other than the lungs. GeneXpert MTB/RIF is an automated PCR-based assay for rapid detection of the Mycobacterium tuberculosis complex and rifampicin resistance and is recommended by the WHO as a reliable alternative. This study aimed to evaluate the performance of GeneXpert in diagnosing EPT in a hospital laboratory in Morocco. A retrospective descriptive study over 36 months included 155 confirmed EPT cases, with a mean age of 34.32 ± 20.67 years and a male-to-female ratio of 0.87. The most frequent site was neuro-meningeal, followed by lymphatic and digestive sites. Tuberculosis was sensitive in 98.71% of cases, with rifampicin resistance in 1.29%. Positivity rates were 0.57% for microscopy, 14.61% for GeneXpert, and 32.26% for culture. Compared to culture, GeneXpert showed a sensitivity of 85.71%, specificity of 88.63%, and a negative predictive value of 100%. GeneXpert is a rapid and effective diagnostic tool and may be considered a reference method for EPT diagnosis.

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References

World Health Organization, 2024, Global tuberculosis report 2024. World Health Organization. https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2024

World Health Organization, 2023, La riposte à la tuberculose reprend après la pandémie, mais il faut agir plus vite pour atteindre de nouveaux objectifs, (November 7) https://www.who.int/fr/news/item/07-11-2023-tuberculosis-response-recovering-from-pandemic-but--accelerated-efforts-needed-to-meet-new-targets

Moeti, M., 2024, (World Tuberculosis Day 2024: Message from WHO Regional Director for Africa. WHO Regional Office for Africa, March 24). https://www.afro.who.int/regional-director/speeches-messages/world-tuberculosis-day-2024

Ministère de la Santé et de la Protection Sociale, 2024, Plan stratégique pour la prévention et le contrôle de la Tuberculose au Maroc 2024-2030 https://www.sante.gov.ma/Documents/2023/11/Plan%20strateìgique%20National%20TB%202024-2030.pdf

Purohit, M., & Mustafa, T., 2015, Laboratory diagnosis of extra-pulmonary tuberculosis (EPTB) in resource-constrained setting: State of the art, challenges and the need. Journal of Clinical and Diagnostic Research 9(4), EE01–EE06. https://doi.org/10.7860/JCDR/2015/5792

Ghariani, A., Jaouadi, T., Smaoui, S., Mehiri, E., Marouane, C., Kammoun, S., Essalah, L., Driss, M., Messadi, F., & Slim-Said, L., 2015, Diagnosis of lymph node tuberculosis using the GeneXpert MTB/RIF in Tunisia. International Journal of Mycobacteriology 4(4), 270–275. https://doi.org/10.1016/j.ijmyco.2015.05.011

Guillet-Caruba, C., Martinez, V., & Doucet-Populaire, F., 2014, Les nouveaux outils de diagnostic microbiologique de la tuberculose maladie. La Revue de Médecine Interne 35(12), 794–800. https://doi.org/10.1016/j.revmed.2014.05.001

Khan, A. S., Ali, S., Khan, M. T., Ahmed, S., Khattak, Y., Abduljabbar, Irfan, M., & Sajjad, W., 2018, Comparison of GeneXpert MTB/RIF assay and LED-FM microscopy for the diagnosis of extra pulmonary tuberculosis in Khyber Pakhtunkhwa, Pakistan. Brazilian Journal of Microbiology 49(4), 819–825. https://doi.org/10.1016/j.bjm.2018.02.011

Kohli, M., Schiller, I., Dendukuri, N., Dheda, K., Denkinger, C. M., Schumacher, S. G., & Steingart, K. R., 2018, Xpert® MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance. Cochrane Database of Systematic Reviews 2018(8), CD012768. https://doi.org/10.1002/14651858.CD012768.pub2

Lawn, S. D., & Nicol, M. P., 2011, Xpert® MTB/RIF assay: Development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiology, 6(9), 1067–1082. https://doi.org/10.2217/fmb.11.84

Piatek, A. S., Telenti, A., Murray, M. R., El-Hajj, H., Jacobs, W. R., Jr., Kramer, F. R., & Alland, D., 2000, Genotypic analysis of Mycobacterium tuberculosis in two distinct populations using molecular beacons: Implications for rapid susceptibility testing. Antimicrobial Agents and Chemotherapy 44(1), 103–110. https://doi.org/10.1128/AAC.44.1.103-110.2000

Boehme, C. C., Nabeta, P., Hillemann, D., Nicol, M. P., Shenai, S., Krapp, F., Allen, J., Tahirli, R., Blakemore, R., Rustomjee, R., Milovic, A., Jones, M., O’Brien, S. M., Persing, D. H., Ruesch-Gerdes, S., Gotuzzo, E., Rodrigues, C., Alland, D., & Perkins, M. D., 2010, Rapid molecular detection of tuberculosis and rifampin resistance. The New England Journal of Medicine 363(11), 1005–1015. https://doi.org/10.1056/NEJMoa0907847

Helb, D., Jones, M., Story, E., Boehme, C., Wallace, E., Ho, K., Kop, J., Owens, M. R., Rodgers, R., Banada, P., Safi, H., Blakemore, R., Lan, N. T. N., Jones-López, E. C., Levi, M., Burday, M., Ayakaka, I., Mugerwa, R. D., McMillan, B., Winn-Deen, E., Christel, L., Dailey, P., Perkins, M. D., Persing, D. H., & Alland, D., 2010, Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. Journal of Clinical Microbiology 48(1), 229–237. https://doi.org/10.1128/JCM.01463-09

Organisation mondiale de la Santé, 2014, Manuel de mise en œuvre du test Xpert MTB/RIF : Guide technique et opérationnel – considérations pratiques. Organisation mondiale de la Santé. https://iris.who.int/handle/10665/112469

Ministère de la Santé et de la Protection Sociale, 2023, Lignes directrices nationales pour le diagnostic et la prise en charge de la tuberculose extra-pulmonaire. Programme National de Lutte Antituberculeuse, Direction de l’Épidémiologie et de Lutte contre les Maladies. https://www.sante.gov.ma/Documents/2024/04/Version%20Finale%20Lignes%20Directrices%20TEP%20PNLAT%20Version%20finale%20%20Ao%C3%BBt%202023.pdf

Mechal, Y., Benaissa, E., El mrimar, N., Benlahlou, Y., Bssaibis, F., Zegmout, A., Chadli, M., Malik, Y. S., Touil, N., Abid, A., Maleb, A., & Elouennass, M., 2019, Evaluation of GeneXpert MTB/RIF system performances in the diagnosis of extrapulmonary tuberculosis. BMC Infectious Diseases 19, 1069. https://doi.org/10.1186/s12879-019-4687-7

Yamouni, F., Henniche, F. Z., Ifticene, M., Chabani, M., Bensersa, D., Ouadah, N. E. H., Nihad, M., & Zerouki, A., 2024, Évaluation du GeneXpert® MTB/RIF dans le diagnostic moléculaire de la tuberculose et de la résistance à la rifampicine en Algérie. Médecine Tropicale et Santé Internationale 42, 301. https://doi.org/10.48327/mtsi.v42.2024.301

Marouane, C., Smaoui, S., Kammoun, S., Slim, L., & Messadi-Akroun, F., 2016, Evaluation of molecular detection of extrapulmonary tuberculosis and resistance to rifampicin with GeneXpert® MTB/RIF. Médecine et Maladies Infectieuses 46(1), 20–24. https://doi.org/10.1016/j.medmal.2015.10.012

Hefzy, E. M., Ahmed, M. I., Abdelrahman, M. A., & Ali, D. Y., 2021, Utility of GeneXpert MTB/RIF assay for the diagnosis of pulmonary and extra-pulmonary tuberculosis: A report from Egypt. Novel Research in Microbiology Journal 5(1), 1146–1161. https://doi.org/10.21608/nrmj.2021.149391

Diallo, A. B., Kollo, A. I., Camara, M., Lo, S., Walbang, G. O., Mbow, M., Karam, F., Fall Niang, M. Y., Thiam, A., Ndiaye Diawara, A., Mboup, S., & Gaye Diallo, A., 2016, Performance of GeneXpert MTB/RIF in the diagnosis of extrapulmonary tuberculosis in Dakar: 2010–2015. Pan African Medical Journal 25, Article 129. https://doi.org/10.11604/pamj.2016.25.129.10065

Bemba, E. L. P., Okemba Okombi, F. H., Bopaka, R. G., & Ossale Abacka, K. B., 2020, Performance du GeneXpert MTB/RIF dans le diagnostic de la tuberculose pleurale à Brazzaville : étude préliminaire. Revue des Maladies Respiratoires Actualités 12(1), 269. https://doi.org/10.1016/j.rmra.2019.11.612

Niang, S., Mbaye, F. B. R., Cissé, M. F., Gueye Dia, D., Ndiaye, E. M., Dieye, A., Thiam, K. H., Kane, Y. D., Diatta, A., & Touré Badiane, N. O., 2022, Apport du test Xpert MTB/RIF dans le diagnostic de la tuberculose toute forme à Saint-Louis. Mali Medical 37(3), 40–43. https://www.malimedical.org/wp-content/uploads/2022/09/8_37_3_2022.pdf

Rakotoarivelo, R., Ambrosioni, J., Rasolofo, V., Raberahona, M., Rakotosamimanana, N., Andrianasolo, R., Ramanampamonjy, R., Tiaray, M., Razafimahefa, J., Rakotoson, J., Randria, M., Bonnet, F., & Calmy, A., 2018, Evaluation of the Xpert MTB/RIF assay for the diagnosis of smear-negative pulmonary and extrapulmonary tuberculosis in Madagascar. International Journal of Infectious Diseases 69, 20–25. https://doi.org/10.1016/j.ijid.2018.01.017

Ngakoutou, R., Ahmet, A., Dieudonne, D., Mbainadji, L., Toralta, J., Allawaye, L., Mahamat, A. B., & Mad-Toingue, J., 2023, Performance du GeneXpert dans le diagnostic de la tuberculose extra pulmonaire au Centre Hospitalier Universitaire (CHU-RN) de N’Djamena au Tchad : une étude de 110 cas. Health Sciences and Disease 24(8), 44–47. https://doi.org/10.5281/hsd.v24i8.4676

Billard-Pomares, T., Cruaud, P., Lo, S., Méchaï, F., Addane, A., Zahar, J.-R., Bouchaud, O., & Carbonnelle, E., 2018, Performance de la PCR GeneXpert MTB/RIF dans le diagnostic des tuberculoses extrapulmonaires ? Médecine et Maladies Infectieuses 48(4, Suppl.), S116–S117. https://doi.org/10.1016/j.medmal.2018.04.294

Méchaï, F., Billard-Pomares, T., Cruaud, P., Zahar, J.-R., Bouchaud, O., & Carbonnelle, E., 2017, Diagnostic de la tuberculose extrapulmonaire : quelle place pour le GeneXpert ? Médecine et Maladies Infectieuses 47(4, Suppl.), S102. https://doi.org/10.1016/j.medmal.2017.03.249

Malbruny, B., Le Marrec, G., Courageux, K., Leclercq, R., & Cattoir, V., 2011, Rapid and efficient detection of Mycobacterium tuberculosis in respiratory and non-respiratory samples. The International Journal of Tuberculosis and Lung Disease 15(4), 553–555. https://doi.org/10.5588/ijtld.10.0497

Ramamonjinirina, T. P., Rakotondravelo, S. M., Rakotojoelimaria, E., & Rakotoarivelo, R. A., 2019, La tuberculose extra- pulmonaire chez l’enfant en milieu hospitalier à Fianarantsoa Extra-pulmonary tuberculosis in children hospitalized at Fianarantsoa hospital. Revue Malgache Pédiatrie 2(1), 110-118. https://scholar.googleusercontent.com/scholar?q=cache:xCY8Epo4kH8J:scholar.google.com/

Mouhib, H., Zahir, H., Arsalane, L., Kamouni, Y., Miloudi, M., & Zouhair, S., 2020, GeneXpert's performance in the diagnosis of pulmonary and extrapulmonary tuberculosis. American Journal of Laboratory Medicine 5(1), 14–17. https://doi.org/10.11648/j.ajlm.20200501.12

Elbrolosy, A. M., El Helbawy, R. H., Mansour, O. M., & Abdel Latif, R., 2021, Diagnostic utility of GeneXpert MTB/RIF assay versus conventional methods for diagnosis of pulmonary and extra-pulmonary tuberculosis. BMC Microbiology 21, Article 144. https://doi.org/10.1186/s12866-021-02210-5

Talbi, M., Marzouk, M., Jaziri, H., Dhaou, M., Garrouche, F., Hazgui, O., Hannachi, N., Ben Salem, Y., & Boukadida, J., 2021, Apport de la PCR en temps réel dans le diagnostic de la tuberculose extra-pulmonaire. In 30ᵉ Congrès national de la Société Tunisienne de Pathologie Infectieuse & 1er Congrès francophone de pathologie infectieuse et de microbiologie clinique (Abstract P0404, p. 369). https://www.infectiologie.org.tn/congresenligne2021/unify-main/home/cahierdesresumes2021.pdf

Chiali, A., Khelil, A., Mahmoudi, N. H., Dali Ali, A., Khodja, A. A., Sabeur, Y. G., & Touil, S. C., 2018, Apport de la réaction de polymérisation en chaîne (PCR) dans le diagnostic de la tuberculose cutanée: Contribution of polymerase chain reaction (PCR) in the diagnosis of cutaneous tuberculosis. Journal de la Faculté de Médecine d’Oran 2(1). https://doi.org/10.51782/jfmo.v2i1.64

Revue de Médecine Pratique, 2021, Tuberculose extra-pulmonaire : Progression alarmante au Maroc (N° 118), (24 novembre). https://www.medecinepratique.ma/tuberculose-extra-pulmonaire-progression-alarmante-au-maroc/

Moufid, H., 2019, Diagnostic moléculaire de la tuberculose Extra-pulmonaire par PCR. Thèse de doctorat en pharmacie, Université Mohammed V‐Rabat Faculté De Médecine Et De Pharmacie de Rabat, N.01-2019. https://toubkal.imist.ma/bitstream/handle/123456789/19014/P0012019.pdf

Kane, Y., Lemrabott, A. T., Faye, M., Cissé, M. M., Ka, E. H. F., Niang, A., & Diouf, B., 2017, Apport du GENEXPERT dans le diagnostic de la tuberculose chez les hémodialysés chroniques au sud du Sénégal. Néphrologie & Thérapeutique 13(5), 330. http://dx.doi.org/10.1016/j.nephro.2017.08.146

Aazri, L., 2018, Prise en charge de la tuberculose extra-pulmonaire : Expérience du service de pneumologie de l’Hôpital Militaire Avicenne de Marrakech (Thèse de doctorat en médecine). Faculté de Médecine et de Pharmacie de Marrakech, Université Cadi Ayyad.

https://wd.fmpm.uca.ma/biblio/theses/annee-htm/FT/2018/these197-18.pdf

Semega, K. B., 2020, Apport du GeneXpert MTB/RIF (Xpert/MTB/RIF) dans le diagnostic de la tuberculose extra-pulmonaire au CHNU de Fann (Thèse de doctorat en médecine). Faculté de Médecine, de Pharmacie et d’Odontologie, Université Cheikh Anta Diop de Dakar. http://196.1.97.20/viewer.php?c=thm&d=thm_2020_0202

World Health Organization, 2023, Global tuberculosis report 2023. World Health Organization. https://iris.who.int/server/api/core/bitstreams/cc23b85f-72c0-4177-8137-cb1161da1025/content

Organisation mondiale de la Santé, 2014, Technique automatisée d’amplification de l’acide nucléique en temps réel pour la détection rapide et simultanée de la tuberculose et de la résistance à la rifampicine : utilisation du test Xpert MTB/RIF pour le diagnostic de la tuberculose pulmonaire et extrapulmonaire chez l’adulte et chez l’enfant : mise à jour de la politique. Organisation mondiale de la Santé.

https://apps.who.int/iris/handle/10665/250633

Organisation mondiale de la Santé, 2024, Tuberculose : tuberculose multirésistante (TB-MR) ou tuberculose résistante à la rifampicine (TB-RR). Organisation mondiale de la Santé (20 mai). https://www.who.int/fr/news-room/questions-and-answers/item/tuberculosis-multidrug-resistant-tuberculosis-(mdr-tb)