Clinical contribution of mNGS in the diagnosis and management of imported falciparum malaria in a malaria-free region: a five-case series from northern China.

BACKGROUND: Although malaria transmission has been eliminated in China, imported Plasmodium falciparum malaria remains a diagnostic challenge, particularly in non-endemic regions where clinical experience is limited. The nonspecific manifestations and potential for rapid progression to severe disease may result in delayed diagnosis and inappropriate management. Metagenomic next-generation sequencing (mNGS) has emerged as a complementary diagnostic approach for complex infectious diseases; however, its role in imported malaria management remains insufficiently characterized.

METHODS: We retrospectively reviewed five patients with imported P. falciparum malaria in whom mNGS contributed to diagnosis or clinical management in a malaria-free region of northern China. Demographic characteristics, epidemiological exposure, clinical manifestations, laboratory findings, mNGS results, treatment strategies, and outcomes were analyzed. Clinical scenarios in which mNGS provided additional diagnostic information were summarized.

RESULTS: All patients had travel or residence histories in malaria-endemic regions in Africa. mNGS detected P. falciparum sequences in all patients, while peripheral blood smear examination demonstrated malaria parasites, with sequencing reads ranging from 121 to 212,513. Clinical presentations ranged from uncomplicated febrile illness to severe malaria with multiorgan involvement, including impaired consciousness, severe anemia, thrombocytopenia, and acute kidney injury requiring continuous renal replacement therapy. In four patients, mNGS was incorporated into early etiological evaluation, whereas in one patient it was used for reassessment of recurrent fever and suspected concomitant infection. In this patient, mNGS provided additional evidence supporting malaria-related evaluation without identifying clinically significant alternative pathogens.

CONCLUSION: Imported P. falciparum malaria remains challenging to diagnose and manage in malaria-free regions. This case series highlights that mNGS may provide complementary information beyond pathogen detection, particularly in patients with complex presentations or uncertain clinical trajectories. Integration of mNGS with conventional parasitological methods and clinical assessment may facilitate the management of imported malaria in non-endemic settings.