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PA-595 Hepatotoxicity associated to N-Acetyltransferase type 2 polymorphisms in TB patients with malaria at Jamot Hospital, Yaoundé, Cameroon
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  1. Lionel Ulrich Tiani1,2,3,
  2. AMBASSA Axel Cyriaque1,2,
  3. Jean Paul Assam Assam2,4,
  4. Genevieve Andorseh1,2,
  5. Diane Kamdem Thiomo1,2,
  6. Cedric Tchinda Fossi1,2,
  7. Nkah Leonard Numfor5,
  8. Hortense Gonsu Kamga10,11,
  9. Charles Kouanfack6,
  10. Eric Walters Pefura Yone7,
  11. Jude Daiga Bigoga1,2,
  12. Francine Ntoumi8,9,
  13. Véronique Penlap Beng1,2
  1. 1Department of Biochemistry, Faculty of Science, University of Yaoundé I, Cameroon
  2. 2Laboratory for Tuberculosis Research and Pharmacology, Biotechnology Center, Cameroun
  3. 3Laboratory for Vector biology and control, Biotechnology Center, Cameroun
  4. 4Department of Microbiology University of Yaoundé I, Cameroon
  5. 5Fondation Congolaise pour la Recherche Médicale, Campus WHO/AFRO, Villa D6, Congo
  6. 6Hopital du Jour, Central Hospital in Yaoundé, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Cameroon
  7. 7Pneumology Service, Yaoundé Jamot Hospital, Cameroon
  8. 8Fondation Congolaise pour la Recherche Médicale, Université Marien Gouabi, Congo
  9. 9Institute for Tropical Medicine, University of Tübingen, Germany
  10. 10Department of Internal Medicine and Subspecialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Cameroon
  11. 11Department of Microbiology and Infectious Diseases, Faculty medical Sciences, University of Yaoundé I, Cameroon

Abstract

Background Unlike in developed countries, most infectious diseases such as tuberculosis (TB) and malaria continue to cause deaths in low-income countries. Recent studies have shown that hepatotoxicity during TB treatment may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator polymorphism especially in countries with high TB incidence such as Cameroon. The aim of this study was to determine the NAT2 genetic variation associated with hepatotoxicity in TB/Malaria co-infected patients in Jamot Hospital, Yaoundé-Cameroon.

Methods This was a prospective study from April 2018 - March 2019, aiming to evaluate the genetic variation in NAT2 coding region in TB patients with malaria. A total of 336 pulmonary TB patients with or without malaria infection, aged 15 years and above, were included. Each sputum sample was tested by the Ziehl Neelsen method. Whole blood sample was used for malaria detection using Rapid Diagnostic Test and microscopy. DNA was extracted by chelex method, hepatotoxicity by spectrophotometry, and genotyping done by Polymerase chain reaction followed by restriction fragment length polymorphism analyses with enzymes (KpnI, TaqI, BamHI).

Results Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) values were significantly higher among TB/malaria co-infected cases compared to TB mono infected patients (p=0.03, p=0.01 respectively). In the group of mono-infected TB patients, a significant difference was found for ALT values between day 1 and day 90 (p=0.021). Similarly, a significant association was found between the development of hepatotoxicity and the presence of a slow acetylator phenotype in TB-malaria co-infected (p=0.026).

Conclusion The study suggests that TB/malaria co-infections and NAT2 variant phenotype are risk factors for hepatoxicity induction. Therefore, for a more efficient care, evaluation of NAT2 genotypes might be essential to reduce drug interactions and liver toxicity in case of coinfections.

https://doi.org/10.1136/bmjgh-2023-EDC.246

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