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.

Highlights

  • In 2016, 10.4 million cases of tuberculosis (TB) were reported globally[1]

  • Discuss this article 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

  • Here; we present the case of a hospitalized HIV-infected adult with HIV/Tuberculous meningitis (TBM)/malaria co-infection, highlighting important diagnostic and pharmacokinetic challenges

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Summary

Introduction

In 2016, 10.4 million cases of tuberculosis (TB) were reported globally[1]. Tuberculous meningitis (TBM) accounts for 1–5% of these[2]. Case report An HIV-infected 32-year-old male presented to Mulago National Referral Hospital, Uganda with a 2-week history of headache with fevers and a 1-day history of confusion (Figure 1) He had been on ART (zidovudine, lamivudine, efavirenz) and co-trimoxazole prophylaxis for 5 years. A peripheral blood smear showed P. falciparum parasites (1+ trophozoites), despite a negative malaria histidine rich protein-2 (PfHPR2)based rapid diagnostic test (Malaria Plasmodium falciparum Rapid Test Cassette, Vaxpert, Florida, USA) Given his ongoing neurological symptoms, which could be compatible with cerebral malaria, the decision was made to treat for severe malaria. Drug-drug interactions (DDIs) between rifampicin and artemisinin compounds, and rifampicin and quinine are recognized (Table 1); a decision was made to treat with IV artesunate as the most efficacious anti-malarial for severe malaria[6] He received three doses of IV artesunate (3 mg/kg), after which a repeat peripheral blood smear showed no malaria parasites. He was discharged on day 8; medication adherence counselling was provided for the patient and his guardian and outpatient follow-up was arranged for the following week

Discussion
Uncomplicated
Preferred
Preferred: Oral
Conclusions
Findings
World Health Organization: Fact Sheets
World Health Organization
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