# Treatment Failure and Post‐Artesunate Delayed Haemolysis in a Returned Traveller From Uganda With Partially Drug‐Resistant Severe Plasmodium falciparum Malaria

## TL;DR

A man with severe malaria from Uganda experienced treatment failure and delayed haemolysis due to partially drug-resistant Plasmodium falciparum.

## Contribution

This case report highlights the risk of treatment failure in patients with hyperparasitaemia and partial drug resistance.

## Key findings

- The patient showed reduced susceptibility to lumefantrine and an A675V mutation in the pfk13 gene.
- Post-artesunate delayed haemolysis occurred despite initial treatment success.
- Hyperparasitaemia and drug resistance are linked to higher treatment failure risks.

## Abstract

A man aged in his 40s, recently returned from Uganda, was hospitalised with Plasmodium falciparum malaria, with hyperparasitaemia of ~1.5 × 106 parasites/μL (26%). He received intravenous artesunate followed by artemether–lumefantrine. However, parasite clearance was delayed, and despite a negative blood film following treatment, the patient was readmitted 3 weeks later with recurrent parasitaemia. Further testing for drug‐resistant phenotypes and genotypes demonstrated reduced susceptibility to lumefantrine, an A675V mutation in the pfk13 gene and increased ring‐stage survival, consistent with partial artemisinin resistance. The case highlights the high risk of P. falciparum treatment failure in patients with hyperparasitaemia and partial drug resistance.

Intravenous artesunate remains the treatment of choice for all patients with severe malaria and should be commenced without delay. The addition of intravenous quinine may be considered for patients with severe falciparum malaria from regions with established artemisinin resistance.Patients with severe Plasmodium falciparum hyperparasitaemia, particularly if the infection has been acquired in a region with antimalarial drug resistance, are at high risk of treatment failure, and a longer course of artemisinin combination treatment following initial intravenous artesunate should be considered.For patients with P. falciparum malaria returning from a region with antimalarial drug resistance, treatment with atovaquone–proguanil may be considered as an alternative to artemether–lumefantrine.All patients who have received intravenous artesunate should be monitored for post‐artesunate delayed‐onset haemolysis, with haematology checked at 7, 14, 21 and 28 days after initiation of artesunate therapy. Parasitaemia should also be monitored at these time points.

Intravenous artesunate remains the treatment of choice for all patients with severe malaria and should be commenced without delay. The addition of intravenous quinine may be considered for patients with severe falciparum malaria from regions with established artemisinin resistance.

Patients with severe Plasmodium falciparum hyperparasitaemia, particularly if the infection has been acquired in a region with antimalarial drug resistance, are at high risk of treatment failure, and a longer course of artemisinin combination treatment following initial intravenous artesunate should be considered.

For patients with P. falciparum malaria returning from a region with antimalarial drug resistance, treatment with atovaquone–proguanil may be considered as an alternative to artemether–lumefantrine.

All patients who have received intravenous artesunate should be monitored for post‐artesunate delayed‐onset haemolysis, with haematology checked at 7, 14, 21 and 28 days after initiation of artesunate therapy. Parasitaemia should also be monitored at these time points.