Metagenomic Sequencing Reveals Hidden Fungal Co-Infection in Fatal Infant Pertussis Case

A case report published in BMC Pediatrics describes the death of a two-month-old girl whose severe whooping cough was complicated by an unexpected fungal lung infection, a diagnosis that only came to light through metagenomic next-generation sequencing, or mNGS. The report, authored by Fang Guo, Yali Wang, Yanhong Jia, Xiaoyuan Wu and Lei Kang of Hebei Children’s Hospital in Shijiazhuang, China, adds to a small but clinically important body of literature on co-infection in infants with pertussis, and it underscores how modern sequencing tools can uncover pathogens that conventional tests miss entirely.

Pertussis, commonly known as whooping cough, is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis. While vaccination has dramatically reduced its burden in many countries, infants too young to complete their primary immunization series remain the most vulnerable group. In its severe form, infant pertussis can produce violent coughing paroxysms, an inspiratory whoop, cyanosis and profound respiratory distress. Complications such as pneumonia, pulmonary hypertension and encephalopathy contribute to the disease’s continued mortality in the youngest patients, and clinicians have long recognized that bacterial or viral co-infections can worsen outcomes substantially.

The infant in this case arrived with classic signs of whooping cough: paroxysmal coughing fits, crowing sounds during inspiration and increasing difficulty breathing. Laboratory evaluation painted a picture consistent with severe pertussis. Her white blood cell count was markedly elevated, a hallmark of the disease that reflects the toxin-driven lymphocytosis characteristic of Bordetella infection. A polymerase chain reaction test performed on sputum came back positive for Bordetella pertussis, confirming the diagnosis. Echocardiographic assessment revealed pulmonary hypertension, a dangerous elevation of pressure in the vessels supplying the lungs that is a recognized and feared complication of severe infant pertussis.

Based on these findings, the clinical team initiated treatment directed at the pertussis infection. Over the following days, two of the key indicators improved: the abnormally high leukocyte count came down, and the pulmonary artery pressure fell significantly. By conventional markers, the infant appeared to be responding to therapy. Yet her respiratory distress did not ease. This discordance, in which laboratory values normalize while the patient’s clinical condition deteriorates or fails to improve, is precisely the scenario in which clinicians should suspect that a second, undetected pathogen may be driving ongoing lung injury.

That suspicion led the team to deploy metagenomic next-generation sequencing, an unbiased diagnostic technique that differs fundamentally from targeted tests. Whereas PCR assays and cultures are designed to detect specific, suspected organisms, mNGS extracts all genetic material present in a clinical sample, in this case from the respiratory tract, and sequences it without any prior assumption about what might be found. Bioinformatic analysis then maps the resulting reads against comprehensive databases of bacterial, viral, fungal and parasitic genomes, allowing the technique to identify unexpected or fastidious pathogens directly from the sample. The approach has proven especially valuable in critically ill patients, in immunocompromised hosts and in infections where standard diagnostics repeatedly return negative results.

In this infant, mNGS detected genetic material from Pneumocystis jirovecii, an opportunistic fungus that causes Pneumocystis pneumonia, abbreviated PJP. The finding was significant for several reasons. Pneumocystis jirovecii is a yeast-like fungus that most commonly causes pneumonia in people with profoundly weakened immune systems, particularly those with untreated HIV, transplant recipients on immunosuppressive drugs, and children with severe primary immunodeficiencies. Its detection in an infant who was not known to be immunocompromised is rare, and co-infection with Pneumocystis in the setting of severe pertussis has been seldom reported in the medical literature. The authors note that PJP carries a higher mortality, making its timely recognition all the more critical.

The diagnosis, however, arrived late in the infant’s illness. Despite the eventual identification of the fungal co-pathogen, the delay meant that targeted therapy against Pneumocystis came after substantial lung damage had already accumulated. The girl died on the fifteenth day after admission. The authors draw a sobering conclusion from this outcome: Pneumocystis pneumonia can occur even in immunocompetent children with severe pertussis, and a delayed diagnosis may increase mortality. Their central recommendation is that mNGS should be performed when a patient with severe pertussis fails to respond to appropriate treatment, because the technique can provide an effective basis for identifying hidden co-infections that would otherwise remain undiagnosed until autopsy.

The case highlights a broader diagnostic dilemma in pediatric intensive care. Severe pertussis in young infants can produce a devastating pneumonia on its own, and the radiographic and clinical picture of Pneumocystis pneumonia overlaps considerably with other causes of diffuse lung injury, including viral pneumonias and the direct pulmonary effects of Bordetella itself. Furthermore, Pneumocystis cannot be reliably cultured in the laboratory, which means that conventional microbiological workups are structurally blind to it. Microscopic examination of induced sputum or bronchoalveolar lavage fluid with special stains has historically been the diagnostic mainstay, but these methods depend on adequate sampling, experienced microscopists and a clinician who thought to test for the organism in the first place. In an infant whose initial workup convincingly explained her illness with pertussis, the impetus to look for a second pathogen may only arise when the expected recovery stalls.

This is precisely the gap that mNGS is increasingly filling. Studies across adult and pediatric intensive care settings have shown that metagenomic sequencing can shorten the time to diagnosis of opportunistic infections, detect mixed infections involving multiple pathogens simultaneously and reveal organisms that were never suspected clinically. The technology is not without limitations: it is more expensive than targeted tests, results require careful interpretation because sequencing can detect colonizing organisms or environmental contaminants alongside true pathogens, and the quantity of genetic material recovered depends heavily on sample quality. Quantitative thresholds and clinical correlation remain essential to distinguish meaningful detections from background noise. Nevertheless, for critically ill children whose conditions defy explanation, the case-by-case evidence continues to mount that early deployment of unbiased sequencing can change management and, in some instances, alter outcomes.

The Hebei Children’s Hospital team also raises the question of why an apparently immunocompetent infant would develop Pneumocystis pneumonia at all. The report’s listing of related subjects includes severe combined immunodeficiency, and clinicians reading such a case would typically consider an underlying immune defect as a possible predisposing factor, since Pneumocystis infection in infancy can occasionally be the first manifestation of a primary immunodeficiency that had not previously come to attention. Severe pertussis itself may also perturb immune defenses in ways that create an opening for opportunistic organisms, though the precise mechanisms linking the two infections in this patient cannot be established from a single case. The authors’ work was approved by the ethics committee of Hebei Children’s Hospital, carried out in accordance with the Declaration of Helsinki, and published with written informed consent from the child’s legal guardian.

For the wider pediatric community, the report arrives at a moment of renewed attention to pertussis. Resurgence of the disease has been documented in multiple countries in recent years as vaccination rates fluctuate and immunity wanes, returning whooping cough to the differential diagnosis of infant respiratory illness with new urgency. The study, supported by the Medical Science Research Project of Hebei under grant number 20241732, was published open access on October 12, 2026, and its message is directed squarely at frontline clinicians: in an infant with severe pertussis whose respiratory distress persists despite improving leukocyte counts and falling pulmonary pressures, do not stop looking. A second pathogen may be hiding in the lungs, and metagenomic sequencing offers a way to find it before the window for effective treatment closes.

Subject of Research: Diagnosis of Pneumocystis jirovecii co-infection in severe infant pertussis using metagenomic next-generation sequencing

Article Title: Case report of a child with severe pertussis complicated by pneumocystis pneumonia diagnosed through mNGS

Article References: Guo, F., Wang, Y., Jia, Y., Wu, X., & Kang, L. (2026). Case report of a child with severe pertussis complicated by pneumocystis pneumonia diagnosed through mNGS. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07820-4

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07820-4

Keywords: pertussis, Bordetella pertussis, Pneumocystis jirovecii, pneumocystis pneumonia, metagenomic next-generation sequencing, mNGS, co-infection, infants, pulmonary hypertension, pediatric intensive care, case report, diagnostics