A rare case of pythium brain infection presenting as severe neurological deterioration in a pediatric patient: A case report and literature review

Abstract

Human pythiosis, caused by Pythium insidiosum, is a rare and often fatal infection that carries high morbidity, particularly when the central nervous system is affected. We describe a severe case in a 2-year-old boy from Saudi Arabia who was previously healthy and presented with a two-week history of intermittent fever, diplopia, and abnormal limb movements, which progressed to generalized seizures and rapidly worsening neurological deficits. Initial imaging demonstrated space-occupying lesions in the basal ganglia and thalamus with extensive edema and hydrocephalus, raising suspicion for neoplasm or meningoencephalitis. Surgical intervention with craniotomy and external ventricular drain insertion was performed. Histopathological examination revealed necrotizing granulomatous inflammation containing rare fungal hyphae demonstrated by silver staining, while microbiological studies confirmed Pythium species. Despite antifungal therapy and intensive supportive care, the patient’s condition deteriorated, and he died due to extensive brain involvement. Review of published literature indicates that central nervous system pythiosis is exceedingly rare, typically associated with rapid progression and uniformly poor outcomes, even with combined surgical and medical management. This case emphasizes the importance of maintaining clinical suspicion in children with unusual space-occupying brain lesions, the need for rapid histopathological and molecular confirmation, and the limitations of currently available treatment options. Early recognition and development of more effective therapies are urgently required to improve survival in pediatric patients with this devastating condition.

Introduction

Human pythiosis is a severe and often fatal infection that typically requires surgical intervention because of its high morbidity and mortality [1]. The causative agent, Pythium insidiosum, is an aquatic oomycete, a fungus-like organism found in stagnant or slow-moving water [2]. Infection occurs when humans are exposed to the motile zoospore form of the pathogen, which penetrates tissue and initiates disease [3].

The prevalence of human pythiosis has been increasing in tropical, subtropical, and even some temperate regions. Reported cases come from Thailand, India, Malaysia, China, Japan, Australia, New Zealand, Spain, Israel, Colombia, Brazil, Costa Rica, Jamaica, and the United States [1]. Transmission usually follows contact with or ingestion of contaminated water [4,5].

Clinical manifestations vary widely. Vascular pythiosis, affecting medium and large arteries, and ocular pythiosis are the most frequently reported forms [6]. Less common but more severe presentations include necrotizing cellulitis, deep neck abscesses, carotid aneurysms, meningitis, brain abscesses, and disseminated disease [6,7]. Carotid artery involvement, though rare, is particularly dangerous and can result in complications such as meningitis or cerebral septic emboli [7].

Immunocompromised patients, particularly those with hematologic disorders or neutropenia, may develop rapidly progressive disease within days, even in the absence of direct aquatic exposure [8,9].

Here, we report the case of a previously healthy 2-year-old boy from Saudi Arabia who developed massive Pythium brain infection with severe and rapid neurological deterioration. This report adds to the limited literature on central nervous system involvement, which remains exceedingly rare and uniformly associated with poor outcomes.

Case presentation

A 2-year-4-month-old boy from Saudi Arabia, the product of a full-term pregnancy with no NICU stay, was previously healthy, developmentally appropriate, and fully vaccinated. His past medical and surgical history was unremarkable. There was positive consanguinity but no family history of hematological, neurological, or immunodeficiency disorders, and he was not on any chronic medications.

He presented with a two-week history of intermittent fever and right eye squint. During this period, he developed abnormal shivering-like movements of the left upper limb, a generalized skin rash affecting the lower limbs, and progressive left-sided weakness that culminated in inability to walk. He was initially admitted to a local hospital for two days but discharged against medical advice. He later presented to the emergency department at King Fahad Central Hospital, Jazan, with persistent weakness, recurrent seizures, and rash.

On arrival, he was afebrile and irritable but alert, with a Glasgow Coma Scale (GCS) score of 15/15. Neurological examination revealed left hemiparesis (power 3-4/5), hyperreflexia, and a positive Babinski sign on the left. Dermatological examination showed xerosis cutis with postinflammatory hyperpigmentation, while ophthalmological evaluation demonstrated optic disc pallor without papilledema.

Initial laboratory studies demonstrated leukocytosis of 12.1 × 10⁹/L (reference 4-10), microcytic anemia with hemoglobin 10.1 g/dL (11-13) and MCV 60 fL (75-87), thrombocytosis of 841 × 10⁹/L (150-450), and a mildly elevated C-reactive protein (CRP) of 4.2 mg/L (<3).

A noncontrast CT scan of the brain performed at presentation revealed intra-axial lesions in the basal ganglia and thalamus with extensive vasogenic edema, obstructive hydrocephalus, and a significant midline shift (Fig. 1). An MRI obtained approximately two weeks later confirmed multiple lobulated intra-axial masses, with sagittal FLAIR showing transependymal permeation surrounding the left lateral ventricle (Fig. 2). Postcontrast axial T1-weighted images demonstrated multiple lobulated ring-enhancing lesions in the right basal ganglia and thalamus, with significant mass effect including cortical sulcal effacement, compression of the right lateral ventricle, and secondary dilatation of the left lateral ventricle (Fig. 3).

Fig. 1.

Noncontrast axial CT scan of the brain at presentation, showing intra-axial lesions in the basal ganglia and thalamus (white arrows), associated with vasogenic edema, obstructive hydrocephalus, and midline shift.

Fig. 2.

Sagittal FLAIR MRI obtained two weeks later, demonstrating periventricular high signal intensity (white arrows) surrounding the left lateral ventricle, consistent with transependymal permeation.

Fig. 3.

Axial postcontrast T1-weighted MRI showing multiple well-defined lobulated intra-axial ring-enhancing lesions (white arrows) in the right basal ganglia and thalamus. The lesions produce significant mass effect, including cortical sulcal effacement, compression of the right lateral ventricle, and secondary dilatation of the left lateral ventricle.

In the third week of illness, the patient underwent decompression of the lesion via osteoplastic craniotomy with partial resection and insertion of an external ventricular drain (EVD), which was removed three days later due to leakage. Histopathology of the brain biopsy revealed necrotizing granulomatous inflammation (Fig. 4A), with Grocott’s methenamine silver (GMS) stain highlighting rare fungal-like hyphae (Fig. 4B). Acid-fast bacilli stain, cerebrospinal fluid analysis, and bacterial cultures were negative, but molecular testing confirmed Pythium species.

Fig. 4.

(A) Histopathology of brain tissue demonstrating necrotizing granulomatous inflammation (H&E stain, × 200). (B) Grocott’s methenamine silver (GMS) stain highlighting rare fungal-like hyphae.

Empirical vancomycin and ceftazidime were administered initially. Following microbiological confirmation, antifungal therapy was initiated with voriconazole and terbinafine, later combined with trimethoprim–sulfamethoxazole. Despite aggressive medical and surgical interventions, seizures became refractory, requiring intubation, sedation, and intensive care. His neurological condition progressively deteriorated, with fixed dilated pupils, absent brainstem reflexes, and a decline in GCS to 3/15. Given the poor prognosis and lack of further neurosurgical options, a do-not-resuscitate order was signed, and the patient was pronounced deceased shortly thereafter.

Discussion

Human pythiosis, caused by the aquatic oomycete Pythium insidiosum, is a rare but highly aggressive infection with high morbidity and mortality. Prognosis is often poor because of diagnostic challenges and the lack of effective therapeutic agents [10]. Clinical manifestations are typically categorized into four forms: vascular, ocular, cutaneous/subcutaneous, and disseminated [1,10,11]. Central nervous system involvement, as in our patient, is exceedingly rare and almost uniformly fatal. Most reported cases have occurred in individuals with underlying conditions such as thalassemia or paroxysmal nocturnal hemoglobinuria, often leading to severe vascular complications and requiring radical surgical interventions [7,12,13]. Survival beyond six months without complete eradication of the pathogen is uncommon [14]. For example, a 14-year-old boy with β Thal/HbE disease developed multiple vascular complications, including an external carotid artery aneurysm and mandibular abscesses, yet survived following aggressive surgical and medical management [15]. In contrast, a previously healthy 2-year-old boy with preseptal cellulitis and maxillary sinusitis survived after biopsy and a year-long antifungal regimen [16]. Adult cases have generally been less favorable: a 44-year-old man with paroxysmal nocturnal hemoglobinuria and orbital cellulitis, and a 26-year-old woman with thalassemia presenting with a hemorrhagic brain mass, both died despite surgical and antifungal therapy [16]. Collectively, these reports highlight that while survival is occasionally possible, CNS involvement is particularly aggressive and almost always fatal. Our patient shared several features with previously described cases, including rapid neurological deterioration and poor response to antifungal therapy. However, unlike most published reports, he had no underlying hematologic or immunologic disorder. His relentless clinical decline, despite decompressive craniotomy and combination antifungal therapy (voriconazole, terbinafine, and trimethoprim–sulfamethoxazole), underscores that CNS pythiosis can also occur in otherwise healthy children and is associated with devastating outcomes. With respect to therapy, itraconazole and terbinafine have consistently demonstrated the lowest minimum inhibitory concentrations (MICs) against P. insidiosum [16,17]. Newer triazoles such as voriconazole and posaconazole also exhibit activity, although with higher MIC values [17]. Combination regimens—particularly itraconazole plus terbinafine—have shown in vitro synergy, though this has not been uniformly observed across geographic isolates [16,17]. Clinical outcomes remain discouraging. A 10-year-old girl with necrotizing orbital and facial pythiosis survived after multiple reconstructive surgeries and prolonged antifungal therapy, including itraconazole, terbinafine, and later posaconazole/voriconazole, with follow-up extending to eight years [18]. In contrast, a 27-year-old man with β Thal/HbE disease and secondary hemochromatosis, and a 57-year-old man with chronic anemia and alcoholism, both died despite repeated surgeries and antifungal treatment [8,18]. These contrasting outcomes emphasize that survival is rare and depends heavily on early diagnosis, localized disease, and aggressive multimodal therapy. Definitive diagnosis requires culture of the pathogen from infected tissue. Traditional serodiagnostic tests such as immunodiffusion are highly specific but have limited sensitivity. More advanced modalities, including enzyme-linked immunosorbent assay (ELISA) and Western blot, improve diagnostic yield and are increasingly available. Polymerase chain reaction (PCR) amplification and sequencing provide rapid, accurate confirmation and are valuable for early identification [19,20]. This case highlights several important lessons. Clinicians should maintain a high index of suspicion for Pythium infection in children presenting with rapidly progressive neurological deterioration and space-occupying brain lesions, particularly in endemic regions [13,14]. Early histopathologic and molecular confirmation is essential, as cultures are often negative. Finally, despite aggressive multimodal interventions, the prognosis of CNS pythiosis remains poor, underscoring the urgent need for improved diagnostic tools, more effective antifungal regimens, and standardized treatment protocols.

Limitations of the study

This study is limited by its focus on a single case, which restricts the generalizability of the findings. The rarity and rapid progression of Pythium brain infection also limited the ability to evaluate the full range of potential treatment options. Diagnosis relied heavily on histopathology and molecular testing, which may not be available in all clinical settings, potentially delaying recognition and management. In addition, primary immunodeficiency disorders were not excluded in our patient, which may represent an unrecognized contributing factor. Finally, the absence of long-term follow-up precludes assessment of outcomes beyond the acute clinical course.

Conclusion

This case highlights the severity and rapid progression of central nervous system pythiosis in pediatric patients without known underlying immunosuppressive conditions. The disease often mimics neoplastic processes on imaging, creating diagnostic challenges and delaying appropriate management. Despite aggressive surgical intervention and antifungal therapy, the prognosis remains extremely poor once extensive brain involvement has occurred. Clinicians should maintain a high index of suspicion when evaluating children with unusual space-occupying brain lesions, particularly in endemic regions, and pursue early histopathologic and molecular testing to expedite diagnosis. Future research should focus on the development of improved diagnostic tools, more effective therapeutic regimens, and multicenter collaborations to establish standardized management protocols for this rare but devastating infection.

CRediT authorship contribution statement

Alhamoud and Dhayhi served as joint principal investigators, conceived the report, and supervised all stages of the work. Alhamoud drafted the first version of the manuscript. BinHussain, Arishi, and Alqassimi managed the patient and collected clinical data. Majrashi and Mobarki performed and interpreted the histopathology studies. Qumayri acquired and interpreted the neuroimaging. Maashi and Matabi organized the dataset, prepared figures, and assisted in manuscript revision. All authors contributed substantially to the design, analysis, and interpretation of the study, critically reviewed the manuscript for important intellectual content, approved the final version, and agree to be accountable for its accuracy and integrity.

Ethical approval

This case report was reviewed and approved by the Jazan Health Cluster Ethics Committee, Saudi Arabia (Approval No. 2434; Date: 16 July 2024). The committee confirmed that patient data were obtained solely from medical records without access to personally identifiable information. Administrative approval from King Fahad Central Hospital was also obtained prior to data collection.

Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy and ethical restrictions.

Patient consent

Written informed consent for the publication of this case report was obtained from the patient’s guardian.