The mystery illness in Panzi was malaria, flu and hunger, a lab investigation confirms

In late 2024, a cluster of deaths from an unexplained febrile illness in a remote health zone of the Democratic Republic of the Congo produced weeks of global speculation about a new pathogen. A laboratory and epidemiological investigation published in Nature Medicine now reports what was found when the samples were sequenced. The answer contains no novel virus.

What happened at the time

The alert came on 29 November 2024, raised by health zone authorities in Panzi, Kwango province, after an increase in deaths — particularly among children under five — following febrile illness [s2]. With no diagnosis available, surveillance used a deliberately broad syndromic case definition: any person living in Panzi health zone from September 2024 onward presenting with fever, cough, body weakness and runny nose, with or without chills, headache, difficulty breathing, malnutrition or body aches [s2].

A definition that wide will capture a great deal, and it did. Between 24 October and 16 December 2024, 891 cases and 48 deaths across 25 of Panzi's 30 health areas met it [s2]. WHO noted at the time that the case count itself was not considered particularly unusual in a setting with a high burden of pneumonia, malaria and acute respiratory infection at the start of the rainy season — it was the rise in deaths that triggered the alert [s2].

Children under five made up 47% of cases and 54% of deaths while representing around 18% of the population [s2]. The main symptoms associated with death were difficulty breathing, anaemia and signs of acute malnutrition [s2].

By 16 December, results from 430 samples had returned positives for malaria and for common respiratory viruses including influenza A(H1N1)pdm09, rhinoviruses, SARS-CoV-2, human coronaviruses, parainfluenza viruses and human adenovirus [s2]. WHO's preliminary reading was that seasonal viral respiratory infection combined with falciparum malaria, compounded by acute malnutrition, had driven the increase in severe infections and deaths [s2].

What the published investigation found

The Nature Medicine paper reports the systematic version of that work. Describing the event as an outbreak of over 400 cases of undiagnosed febrile illness presenting predominantly as fever and cough, the investigators prospectively collected clinical data and specimens from 108 individuals [s1].

Of those 108, 59 (54.6%) were female, and children under five were the most affected group at 47 of 108 (43.5%) [s1]. Among the subset assessed, 14 of 32 (43.7%) were malnourished [s1].

Oro- and nasopharyngeal swabs from 96 of the 108 were tested by PCR, and 26 blood samples were sequenced [s1].

Plasmodium falciparum was detected in 56 of 108 individuals (51.8%) [s1]. Co-infections were common: among those 56, influenza A(H1N1)pdm09 virus was found in 16 (28.6%) and SARS-CoV-2 in 10 (17.9%) [s1].

Metagenomic sequencing detected no novel pathogens [s1].

The authors' conclusion is that the outbreak was primarily associated with a surge in malaria cases with concurrent viral respiratory infections, and they argue for increasing decentralised laboratory capacity and strengthening broader health systems to enable faster outbreak detection and investigation [s1].

Two counts, two definitions

The case totals in the two documents differ, and the difference is instructive rather than contradictory. WHO's syndromic surveillance figure was 891 cases as of 16 December 2024 under a case definition designed to capture anything febrile in the area [s2]; the published investigation describes an outbreak of over 400 cases and analysed specimens from 108 people [s1].

Broad syndromic definitions are used precisely when the pathogen is unknown, because the cost of missing cases is higher than the cost of including unrelated illness. They are not designed to produce an accurate count of a disease that has not yet been identified, and reading them as though they were is a recurring source of confusion in early outbreak reporting.

What this does and does not close

The metagenomic result is the strongest claim in the paper: no novel pathogen was detected in the 26 blood samples sequenced [s1]. That is a meaningful negative, and it is bounded by its sample size. Twenty-six sequenced samples cannot exclude a rare novel agent circulating alongside the malaria and respiratory infections that were found.

The investigation also cannot establish which infection killed any individual patient. Half the tested individuals had falciparum malaria [s1]; the most common causes of death recorded during the event were difficulty breathing, anaemia and acute malnutrition [s2]. In a malnourished child with malaria and influenza simultaneously, attribution to one cause is a clinical convention rather than a finding.

Why it matters beyond Panzi

The three weeks in which this outbreak had no name generated substantial international attention, and the eventual answer — endemic diseases hitting a malnourished population hard, in a place without the laboratory capacity to identify them quickly — is the answer that most such alerts resolve to.

The authors' recommendation follows directly from the delay itself: decentralised laboratory capacity, so that samples do not have to travel to answer a question that determines whether a global response is warranted [s1]. WHO made a parallel point at the time, framing the event as evidence of the burden common infectious diseases impose on populations facing food insecurity, and of the need to address malnutrition as an underlying cause of vulnerability [s2].

Sources

• [s1] Deciphering the etiology of the 2024 outbreak of undiagnosed febrile illness in Panzi, Democratic Republic of the Congo. Nature Medicine, 18 February 2026. https://doi.org/10.1038/s41591-026-04235-7
• [s2] Acute respiratory infections complicated by malaria (previously undiagnosed disease) — Democratic Republic of the Congo. WHO Disease Outbreak News, 27 December 2024. https://www.who.int/emergencies/disease-outbreak-news/item/2024-DON547