Case report: Three's a crowd: A case report examining the diagnostic and pharmacokinetic challenges in hiv-tuberculous meningitis-malaria co-infection [version 2; referees: 2 approved]

Jayne Ellis, Prosperity C. Eneh, Kenneth Ssebambulidde, Morris K. Rutakingirwa, Mohammed Lamorde, Joshua Rhein, Fiona V. Cresswell, David R. Boulware, Melanie R. Nicol

Research output: Contribution to journalArticlepeer-review

Abstract

In 2016, 10.4 million cases of tuberculosis (TB) were reported globally. Malaria also continues to be a global public health threat. Due to marked epidemiological overlap in the global burden of TB and malaria, co-infection does occur. An HIV-infected, 32-year-old male presented with a two-week history of headache with fevers to Mulago National Referral Hospital, Uganda. Five months prior, he was diagnosed with pulmonary TB. He endorsed poor adherence to anti-tuberculous medications. Mycobacterium tuberculosis in CSF was confirmed on Xpert MTB/RIF Ultra. On day 2, he was initiated on dexamethasone at 0.4mg/kg/day and induction TB-medications were re-commenced (rifampicin, isoniazid, ethambutol, pyrazinamide) for TBM. He continued to spike high-grade fevers, a peripheral blood smear showed P. falciparum parasites despite a negative malaria rapid diagnostic test (RDT). He received three doses of IV artesunate and then completed 3 days of oral artemether/lumefantrine. To our knowledge this is the first published case of HIV-TBM-malaria co-infection. TBM/malaria co-infection poses a number of management challenges. Due to potential overlap in symptoms between TBM and malaria, it is important to remain vigilant for co-infection. Access to accurate parasitological diagnostics is essential, as RDT use continues to expand, it is essential that clinicians are aware of the potential for false negative results. Anti-malarial therapeutic options are limited due to important drug-drug interactions (DDIs). Rifampicin is a potent enzyme inducer of several hepatic cytochrome P450 enzymes, this induction results in reduced plasma concentrations of several anti-malarial medications. Despite recognition of potential DDIs between rifampicin and artemisinin compounds, and rifampicin and quinine, no treatment guidelines currently exist for managing patients with co-infection. There is both an urgent need for the development of new anti-malarial drugs which do not interact with rifampicin and for pharmacokinetic studies to guide dose modification of existing anti-malarial drugs to inform clinical practice guidelines.

Original languageEnglish (US)
Article number111
JournalWellcome Open Research
Volume3
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
Grant information: This work was supported by a Wellcome Trust PhD Fellowship for F.V.C. (210772/Z/18/Z), the National Institute of Neurologic Diseases and Stroke (R01NS086312), the Fogarty International Center (K01TW010268, R25TW009345), the National Institute of Allergy and Infectious Diseases (T32AI055433), United Kingdom Medical Research Council / DfID / Wellcome Trust Global Clinical Trials (M007413/1), NIH National Institute of Allergy and Infectious Diseases K08 AI134262 for M.R.N. and Wellcome Trust (210772/Z/18/Z) for D.R.B.

Funding Information:
This work was supported by a Wellcome Trust PhD Fellowship for F.V.C. (210772/Z/18/Z), the National Institute of Neurologic Diseases and Stroke (R01NS086312), the Fogarty International Center (K01TW010268, R25TW009345), the National Institute of Allergy and Infectious Diseases (T32AI055433), United Kingdom Medical Research Council / DfID / Wellcome Trust Global Clinical Trials (M007413/1), NIH National Institute of Allergy and Infectious Diseases K08 AI134262 for M.R.N. and Wellcome Trust (210772/Z/18/Z) for D.R.B.

Publisher Copyright:
© 2019 Ellis J et al.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Case report
  • Drug-drug interactions
  • HIV/AIDS
  • Malaria
  • Pharmacokinetics
  • Tuberculosis
  • Tuberculous meningitis

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