Hidden Malaria Duo: First Evidence of Delayed Dual Plasmodium Infection in an Ivorian Patient

A single case report from a French hospital laboratory is drawing attention to one of the most underappreciated blind spots in malaria medicine: the simultaneous infection of a patient by two different Plasmodium species, only one of which announces itself at first. Writing in BMC Infectious Diseases, a team led by Mohammad Akhoundi of Avicenne Hospital, part of the Assistance Publique–Hôpitaux de Paris and Sorbonne Paris Nord University, describes what they identify as the first documented evidence of a Plasmodium falciparum and Plasmodium ovale co-infection in an Ivorian patient, with the second species surfacing months after the first and without any new exposure to mosquitoes. The case, published as an open-access case report on 13 October 2026, is a technical reminder that the parasites responsible for malaria do not all follow the same biological script, and that diagnostic systems built around the dominant species can quietly miss the others.

The patient at the center of the report was a 69-year-old man from Côte d’Ivoire who was residing in France. He had traveled to the Man District in the western part of the country, a region where malaria transmission remains intense. Côte d’Ivoire is among the West African countries where malaria is highly endemic, and repeated exposure to infective mosquito bites means that residents and returning travelers alike face a substantial risk not only of single-species infections but also of mixed infections involving more than one Plasmodium species at the same time. In much of sub-Saharan Africa, Plasmodium falciparum is overwhelmingly the dominant parasite, responsible for the vast majority of acute clinical cases and nearly all of the severe ones. That dominance shapes clinical expectations: when a febrile patient from an endemic region presents with malaria, P. falciparum is the species clinicians and laboratories anticipate.

That expectation is precisely what makes this case instructive. The patient’s initial malarial episodes were attributed to P. falciparum, which was detected and treated in the standard way. But a subsequent episode of illness occurred in the complete absence of re-exposure — the patient had not traveled again, and there was no new mosquito-borne inoculation that could explain a fresh infection. When the laboratory investigated this later episode, the parasite identified was not P. falciparum at all but P. ovale, a species that behaves very differently from its more notorious relative. The temporal dissociation between the two detections, the authors argue, strongly suggests that both species had been acquired during the same period of exposure in Côte d’Ivoire, meaning the patient had likely been carrying a mixed infection from the start, even though only one species was visible to the diagnostic process at the time.

The biology underlying this delayed presentation lies in a feature that separates P. ovale, along with P. vivax, from the other human malaria parasites. P. falciparum is a one-stage parasite in clinical terms: after inoculation, it develops in the liver, floods the bloodstream, and causes disease, and once the blood-stage infection is cleared by treatment, the parasite is gone. P. ovale, by contrast, is capable of forming dormant hepatic stages known as hypnozoites. These hypnozoites can sit quietly inside liver cells for weeks or months, producing no symptoms and no detectable blood-stage parasites, before reactivating to seed a new blood-stage infection. In this patient, the clinical recurrence attributable to P. ovale occurred four months after the primary infection, a timing that, in the absence of any recent travel or new exposure, supports the hypothesis of hypnozoite reactivation rather than reinfection. The late clinical presentation is therefore not an anomaly but a direct consequence of the parasite’s life-cycle strategy.

Why, then, did the P. ovale infection not declare itself alongside the P. falciparum infection in the first place? The authors point to two interacting factors. The first is parasitemia: at the time of the later diagnosis, the P. ovale parasitemia was extremely low, at approximately 0.02 percent of infected red blood cells. Such low-level parasitemia can fall below the detection threshold of routine microscopy and even of some rapid diagnostic tests, particularly when a laboratory is not specifically looking for non-falciparum species. The second factor is plausible interspecies competition. When two Plasmodium species occupy the same host simultaneously, they compete for red blood cells, host resources, and immunological space. P. falciparum, with its explosive replication and high parasitemias, can effectively dominate the host environment, keeping the slower-growing P. ovale population suppressed and subclinical. Only after the falciparum infection was treated and cleared would the ovale parasites have faced reduced competition, allowing the dormant liver stages eventually to reactivate into a clinically apparent relapse.

The diagnostic challenges highlighted by this case are considerable and systemic rather than idiosyncratic. Conventional microscopy, the backbone of malaria diagnosis in most endemic settings, relies on a trained microscopist distinguishing parasite morphologies on stained blood films — a task in which low-density non-falciparum infections are easily missed, especially when the observer’s attention is anchored by an abundant and obvious falciparum population. Rapid diagnostic tests, widely deployed because they are fast and simple, are similarly optimized for the species that matter most epidemiologically, and their sensitivity for low-density P. ovale is limited. The authors emphasize the critical role of sensitive molecular diagnostic tools, including polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP-PCR), which can detect and differentiate Plasmodium species at parasite densities far below what microscopy can achieve. In this case, molecular methods were what allowed the second species to be identified with confidence months after the first.

The clinical implications extend beyond diagnosis to treatment strategy. Blood-stage antimalarial drugs clear parasites circulating in the bloodstream, but they do nothing against hypnozoites hiding in the liver. To prevent relapses from P. ovale or P. vivax, patients require so-called radical treatment — typically a drug such as primaquine, which targets the dormant hepatic stages. The safe use of such drugs depends on the patient’s glucose-6-phosphate dehydrogenase (G6PD) status, because individuals with G6PD deficiency risk hemolysis when exposed to these medications. The report underscores that appropriate radical treatment strategies must target both the blood-stage parasites and the dormant hepatic forms, and that this two-front approach can only be planned rationally when clinicians know which species they are dealing with. A patient treated for falciparum malaria alone, as this one initially was, leaves the liver reservoir untouched and the relapse clock running.

Under-recognition of mixed-species infections is not a marginal problem. Because P. falciparum predominates in the regions where malaria burden is highest, and because co-infections with non-falciparum species produce few distinctive clinical signs of their own, the true frequency of mixed infections is thought to be substantially higher than routine surveillance suggests. Complex interspecies interactions — competition, facilitation, and modulation of the host immune response — can alter the course of disease, the accuracy of diagnostic tests, and the response to therapy. When the co-infecting species is one capable of hypnozoite formation, the consequences can surface months later, often in a setting far from the place of exposure, where the treating physicians may have no reason to suspect malaria at all. For travelers returning to non-endemic countries, as in this case of an Ivorian resident of France, the delayed presentation can easily be mistaken for an unrelated febrile illness unless the travel history is carefully elicited and the laboratory work-up is species-aware.

The report also carries a message for malaria control programs in endemic countries such as Côte d’Ivoire. If mixed infections are systematically under-detected, then treatment policies that focus exclusively on blood-stage clearance will leave a reservoir of relapsing parasites in the population, contributing to recurrent episodes that are misattributed to reinfection and potentially sustaining transmission. The authors argue that variable incubation periods and mixed-species infections deserve a place in diagnostic and clinical management algorithms, and that investment in molecular surveillance would provide a more truthful picture of the parasite landscape. Their study received no external funding and was conducted under ethical protocol 95/99/AVC/ESA approved by the Avicenne Hospital Research Ethics Committee, in accordance with the Declaration of Helsinki, with written informed consent obtained from the patient for participation and publication.

As a single case, the report cannot quantify how often P. falciparum–P. ovale co-infections occur or how frequently they produce this kind of delayed, species-switching presentation. What it does establish is a proof of concept: that a co-infection acquired in a single exposure window can split itself across time, with one species causing acute disease and the other lying dormant in the liver before reactivating four months later. For clinicians, the practical lessons are concrete — consider mixed infections in patients from endemic regions, use species-specific molecular testing when the clinical picture does not fit, and remember that a negative follow-up smear months after treatment for falciparum malaria does not exclude a relapsing non-falciparum infection. For researchers, the case is an invitation to study the interspecies dynamics that keep one parasite quiet while another rages, knowledge that could ultimately refine both diagnosis and treatment for the millions of people living where these parasites overlap.

Subject of Research: Mixed-species Plasmodium falciparum and Plasmodium ovale malaria co-infection with delayed relapse due to hypnozoite reactivation

Article Title: First evidence of plasmodium falciparum-plasmodium ovale co-infection with delayed clinical presentation in an Ivorian patient: observations and diagnostic challenges

Article References: First evidence of plasmodium falciparum-plasmodium ovale co-infection with delayed clinical presentation in an Ivorian patient: observations and diagnostic challenges. (n.d.). https://doi.org/10.1186/s12879-026-14628-1

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14628-1

Keywords: malaria, Plasmodium falciparum, Plasmodium ovale, co-infection, hypnozoites, Côte d'Ivoire, molecular diagnostics, PCR, LAMP-PCR, radical treatment, parasitology, tropical medicine