Imported Pediatric Paragonimiasis in China: Two Cases From Zhaotong to Hangzhou

Introduction

Paragonimiasis, a food-borne parasitic zoonosis caused by trematodes of the genus Paragonimus, constitutes a serious public health concern in endemic regions of Asia, Africa, and the Americas [1]. Human infection typically occurs through ingestion of raw or undercooked freshwater crabs or crayfish containing metacercariae [2].

In China, paragonimiasis is primarily caused by Paragonimus westermani and Paragonimus skrjabini; its distribution mainly occurs in provinces such as Sichuan and Yunnan [2]. Conversely, Paragonimus heterotremus has been identified only in Guangxi and Yunnan Provinces [3,4]. Due to socioeconomic development and improvements in hygienic dietary practices, the national infection rate has declined since 2010 [5]. Between 2010 and 2023, slightly more than 200 cases were reported in Zhejiang Province [5]. Hangzhou remains a low-incidence area in which only sporadic cases have been documented. However, population mobility has led to imported paragonimiasis in non-endemic regions, creating a critical diagnostic blind spot – exacerbated by the disease’s long incubation period, atypical presentations, and insufficient clinician awareness – that results in frequent misdiagnosis.

Pleural effusion, a common complication of thoracopulmonary paragonimiasis [2,6,7], often coexists with eosinophilia, a combination that is underrecognized by diagnostic algorithms in non-endemic areas. This challenge is amplified in children, among whom atypical symptoms may further hinder clinical judgment.

Our description of this imported pediatric family cluster addresses the need to improve recognition of such cases in non-endemic urban settings amid increasing population mobility. This report focuses on the diagnostic challenges of imported paragonimiasis, emphasizing the value of integrating migration history and family clustering into clinical reasoning to fill migration-related diagnostic gaps and provide practical guidance for clinicians in non-endemic regions.

Case Reports

CASE 1:

A previously healthy 4-year-old boy was admitted with an 8-day history of fever and cough, in the absence of hemoptysis, dyspnea, chest pain, or abdominal pain. On the fifth day of illness, he had been evaluated at a local hospital. Laboratory testing revealed a white blood cell count of 14.4×109/L, a neutrophil proportion of 59.3%, an eosinophil proportion of 19.0% (absolute count, 2.74×109/L), and a C-reactive protein level of 57.27 mg/L. Chest computed tomography (CT) demonstrated pneumonia involving the right middle and lower lobes, accompanied by bilateral pleural effusion, including loculated right-sided pleural effusion with pleural thickening (Figure 1A, 1B). Thoracic ultrasonography confirmed bilateral pleural effusion with multiple septations. Based on these findings, a diagnosis of bacterial pneumonia was made. However, after 3 days of intravenous ceftriaxone therapy, the fever persisted, and the patient was transferred to our hospital for further evaluation. This initial misdirection toward bacterial pneumonia, without consideration of paragonimiasis, led to a diagnostic delay – a key contrast with the streamlined diagnostic process in his older cousin (Case 2).

The patient had no history of exposure to infectious diseases or foreign body aspiration; he also had no family history of malignancy, pulmonary tuberculosis, or related conditions. He had been born and raised in Zhaotong City, Yunnan Province, a region endemic for paragonimiasis, and presented to our hospital due to his parents’ employment in the area. He had a history of drinking untreated stream water. Both the patient and his family denied consumption of undercooked crustaceans.

On admission, total immunoglobulin E (IgE) levels exceeded 1080 IU/mL, and the immunoglobulin G (IgG) level was 16.72 g/L. Procalcitonin, T-SPOT.TB assay, respiratory pathogen nucleic acid testing, and blood culture results all were negative; the purified protein derivative test was nonreactive.

Given the large right-sided pleural effusion, diagnostic thoracentesis was performed, yielding 100 mL of yellow, turbid fluid (Figure 1C). Pleural fluid analysis revealed a nucleated cell count of 37 950×106/L, with eosinophil predominance. Biochemical analysis showed a total protein level of 55.3 g/L, adenosine deaminase level of 50 U/L, lactate dehydrogenase level of 3939 U/L, and glucose concentration of 0.14 mmol/L. Both pleural fluid culture and targeted pathogenic microorganism sequencing revealed negative findings. No parasitic eggs were identified in stool, sputum, pleural fluid, or bronchoalveolar lavage fluid. Enzyme-linked immunosorbent assay (ELISA) results were positive for anti-Paragonimus IgG antibodies. Although the child had no clinical symptoms of central nervous system or abdominal involvement, cranial magnetic resonance imaging (MRI) and abdominal MRI were performed to further exclude involvement in these regions. Cranial MRI showed no abnormalities, whereas abdominal MRI demonstrated a small amount of pelvic effusion.

Following confirmation of paragonimiasis, the child received oral praziquantel (PZQ) at a dose of 75 mg/kg/day for 3 days, administered over 3 courses. Follow-up chest CT at 1 month post-treatment demonstrated near-complete resolution of bilateral pleural effusion, although a gas-containing nodular lesion persisted in the right lower lobe (Figure 1D, 1E). Two months after treatment, peripheral eosinophil counts had normalized. A third course was administered for safety considerations, due to the prolonged diagnostic delay and logistical constraints that impeded timely follow-up. A chest radiograph obtained at 6 months post-treatment confirmed complete radiological resolution (Figure 1F).

CASE 2:

A 9-year-old boy was admitted with a 1-week history of persistent cough, in the absence of fever, hemoptysis, chest pain, or other symptoms. He had no significant medical history and was an older cousin of the patient in Case 1. Similar to that patient, he resided in Zhaotong, Yunnan, had exposure to untreated stream water, and denied consumption of undercooked crustaceans. Notably, symptom onset occurred 1 month after the case involving his cousin; this intrafamilial temporal clustering directly influenced diagnostic reasoning. Unlike Case 1 (in which paragonimiasis was not initially considered), this sequential presentation prompted immediate suspicion of paragonimiasis, timely testing, and a substantially reduced time to diagnosis.

On admission, laboratory investigations revealed a white blood cell count of 9.88×109/L, neutrophil proportion of 23.4%, eosinophil proportion of 37.1% (absolute count, 3.67×109/L), and normal C-reactive protein level. The T-SPOT.TB assay and purified protein derivative test both showed negative results. Total IgE levels exceeded 1080 IU/mL, and the IgG level was 22.74 g/L. Chest CT demonstrated inflammation of the right middle and lower lobes, thickening of the interlobar fissures, and free pleural effusion on the right (Figure 2A–2C). Diagnostic thoracentesis on the day of admission yielded 245 mL of yellow pleural fluid (Figure 2D). Pleural fluid analysis showed a total nucleated cell count of 6321×106/L, with eosinophils representing 50%. Biochemical analysis revealed a total protein level of 104.3 g/L, adenosine deaminase level of 34.8 U/L, lactate dehydrogenase level of 749 U/L, and glucose concentration of 0.81 mmol/L. Pleural fluid culture findings were negative. No parasitic eggs were identified in stool, sputum, or pleural fluid specimens. Serological testing demonstrated positivity for anti-Paragonimus IgG antibodies, enabling definitive diagnosis within days – substantially faster than the prolonged diagnostic course in Case 1. Although the child had no clinical symptoms indicating involvement of other systems, cranial MRI was performed as a precaution; no abnormalities were evident. Flexible bronchoscopy was not performed given the prompt definitive diagnosis, reflecting the diagnostic advantage conferred by intrafamilial temporal clustering.

The patient received 2 courses of oral PZQ therapy. Following treatment, eosinophil counts returned to normal. Follow-up chest CT performed 25 days after initiation of therapy showed pronounced resolution of pleural effusion, with the development of a localized cavity in the right lower lobe (Figure 2E, 2F). The contrast between the delayed diagnosis in Case 1 and the prompt confirmation in Case 2 highlights an important clinical implication: recognition of intrafamilial temporal clustering can redirect diagnostic priorities and improve efficiency in managing endemic infections with nonspecific presentations.

Both pediatric patients exhibiting imported paragonimiasis from Yunnan presented with typical epidemiological histories and consistent laboratory and imaging findings; they achieved favorable outcomes after praziquantel treatment. The patients primarily differed in age at onset, clinical manifestations, and the type of pleural effusion. The patient in Case 1 required an additional treatment course due to delayed diagnosis and limited follow-up.

Discussion

Paragonimiasis is a food-borne zoonotic disease caused by trematodes of the genus Paragonimus. The main transmission routes include ingestion of undercooked or pickled freshwater crustaceans [4,5,8,9]. However, epidemiological uncertainty remains regarding the potential role of untreated water ingestion as a transmission pathway, leading to diagnostic ambiguity in clinical practice. Several studies have suggested that drinking untreated water in endemic areas is a possible risk factor [2,6,9–11], with support from reports that 17.9% to 48.36% of affected patients have a history of such exposure [2,9,11]. Nevertheless, there is a lack of definitive evidence to confirm this route, and it should be regarded as a theoretical possibility requiring further investigation. Such uncertainty influenced the diagnostic reasoning in both pediatric cases described in this report. Detailed history-taking indicated that both patients had exposure only to untreated stream water; the patients and their families denied consumption of raw crustaceans. However, the inherent limitations of dietary recall in young children require cautious interpretation of these findings. In this context, classical food-borne transmission remains the most biologically plausible route of infection, and water exposure should be considered an epidemiological correlate rather than a confirmed transmission mechanism. These observations highlight how ambiguous exposure histories can complicate diagnostic judgment, particularly in non-endemic settings.

A core challenge affecting the diagnosis of imported pediatric paragonimiasis in non-endemic regions is the underrecognition of pleural effusion with eosinophilia in routine diagnostic algorithms, despite well-established clinical and pathogenetic associations. Although the parasites can involve multiple organs, resulting in diverse clinical manifestations and classification into 5 distinct types [2,12,13], thoracopulmonary paragonimiasis is the most common form; both cases in the present report met criteria for this category. Pleural effusion is a hallmark of thoracopulmonary paragonimiasis, with reported prevalence rates of 79.1% to 81.8% in pediatric cohorts [2,6], consistent with manifestations in our patients. Notably, the first patient presented with loculated pleural effusion – a finding typically attributed to bacterial pneumonia, pulmonary tuberculosis, or malignancy in pediatric populations in non-endemic areas [14,15]. In Case 1, initial diagnostic reasoning prioritized bacterial pneumonia based on elevated inflammatory markers and the absence of known tuberculosis exposure; the combination of pleural effusion and pronounced eosinophilia, along with residence in a paragonimiasis-endemic area, was overlooked. This oversight emphasizes that pleural effusion with peripheral eosinophilia remains an underrecognized diagnostic clue during routine clinical workflows in non-endemic settings, where parasitic etiologies are not routinely included in differential diagnoses.

In addition to pleural effusion, chest CT in thoracopulmonary paragonimiasis may demonstrate atelectasis, consolidation, nodules, pleural thickening, cavities, hydropneumothorax, and the characteristic “tunnel sign” [2,7,16–19]. The tunnel sign – a relatively specific imaging feature of paragonimiasis – appears as tunnel-shaped hypodense tracts within areas of pulmonary consolidation and shows a predilection for the peripheral lung fields. After the resolution of peripheral pulmonary consolidation, this sign may evolve into isolated intrapulmonary hypodense, tunnel-like shadows [16]. Zhang et al identified the tunnel sign in 8 of 28 patients (28.6%) [11], whereas another study documented it in 24 of 69 cases (34.8%) [16]. In the present report, both patients initially presented with pleural effusion and developed cavitary nodules later in the clinical course, consistent with the dynamic radiological manifestations of paragonimiasis. Neither patient demonstrated the characteristic tunnel sign; this absence may be attributed to the disease stage, parasite migration pathway, and host inflammatory response, all of which influence formation of this radiological feature.

ELISA is currently the most widely used method for clinical detection of Paragonimus antibodies, with a sensitivity of 90.2% and specificity of 100.0% [20]. However, false-positive results may occur due to cross-reactivity with homologous antigens among different species [21,22]. Multiple studies have shown that IgG antibody levels substantially decrease after successful treatment with PZQ, allowing ELISA to be used for diagnosis and treatment response monitoring [23,24]. Parasitological testing remains the gold standard for confirming paragonimiasis and relies on repeated examination of sputum, feces, and biopsy or surgical tissue samples to identify flukes or their eggs. Nevertheless, the reported egg detection rate is relatively low (11.7%) [25]. Nakamura-Uchiyama et al found that eggs were present in the sputum of only 10% (3/30) of infected patients [26]. In our 2 pediatric cases, Paragonimus antibodies were detected, but no parasite eggs were evident in sputum or feces, consistent with the low detection rate reported in the literature and indicating that parasitological confirmation was not achievable. Both patients were from paragonimiasis-endemic areas and presented with respiratory symptoms, peripheral eosinophilia, pleural effusion, and positive serum Paragonimus IgG antibody results. In accordance with established clinical diagnostic criteria and international standards [9], both patients were diagnosed with paragonimiasis.

Huang et al [2] demonstrated that, in addition to eosinophil counts, elevated serum IgG and IgE levels can serve as useful diagnostic indicators for paragonimiasis. Kong et al [27] reported similar findings. Notably, both pediatric patients in the present report showed pronounced elevations in serum IgG and IgE, supporting the clinical diagnosis of paragonimiasis.

PZQ is the first-line treatment for paragonimiasis. The recommended regimen is 75 mg/kg/day administered orally in 3 divided doses for 3 consecutive days, and a single course is sufficient for most patients [25,28–32]. However, multiple studies have demonstrated suboptimal clinical responses after a single 3-day course, and a substantial proportion of patients require 2 to 3 courses to achieve satisfactory outcomes [2,6,11,30,33]. Qian et al reported that 63.6% of patients required more than 1 course [6]; Huang et al found that all 213 pediatric patients received a mean of 2.6 courses [2]; and Gong et al reported that only 23.6% of children required retreatment [34]. These discrepancies may be attributed to differences in disease severity and treatment initiation timing across study populations. Oh et al [30] indicated that patients with prolonged respiratory symptoms, persistently elevated ELISA antibody titers, or multiple pulmonary lesions were more likely to require additional PZQ treatment after completion of the initial course. In our 2 clinically diagnosed cases, both patients received at least 2 treatment courses due to multiple pulmonary lesions. The first patient received 3 standard courses, and the third was administered for safety due to delayed diagnosis and follow-up constraints. Both patients achieved resolution of pleural effusion and normalization of eosinophil counts.

In Yunnan Province, P. skrjabini is the primary etiological agent of paragonimiasis, and Zhaotong City consistently reports the highest incidence within the province [2]. The 2 pediatric patients in the present report were cousins, both originally from Zhaotong, who migrated to Hangzhou, Zhejiang Province, with their migrant worker parents. This migration indicates that population mobility is an important epidemiological risk factor for imported pediatric paragonimiasis in Hangzhou and demonstrates a case of family clustering; together, these factors meaningfully increase the pretest probability of the disease and provide an important reference for clinical diagnosis. The disease has nonspecific clinical manifestations, and chest imaging findings (pleural effusion, cavitation, tunnel sign) and serological testing can provide strong support for diagnosis; however, misdiagnosis remains common in non-endemic areas [6,28]. Qian et al [6] reported that 45.5% of patients were initially misdiagnosed with conditions such as eosinophilic pneumonia, cerebral abscess, tuberculosis, or intracranial neoplasms. Persistent misdiagnosis reflects gaps in clinical awareness and diagnostic practice, rather than deficiencies in biomedical knowledge. In summary, when assessing pediatric patients with unexplained pleural effusion in non-endemic areas, clinicians should consider eosinophil counts, history of residence in or travel to endemic areas, and evidence of family clustering; they also should include paragonimiasis in the differential diagnosis to reduce diagnostic delays and improve patient outcomes.

Conclusions

In non-endemic regions, imported pediatric paragonimiasis is highly susceptible to misdiagnosis due to its atypical clinical presentation. The present cases illustrate how pediatric paragonimiasis can present as pleural effusion with eosinophilia in non-endemic settings because of population mobility, and they demonstrate how family clustering can serve as a critical diagnostic accelerator. The integration of epidemiological history with laboratory findings is essential to reduce diagnostic delays in patients with imported parasitic diseases.

Based on clinical diagnosis and treatment experience, the following recommendations are proposed for imported paragonimiasis in non-endemic regions: clinicians should maintain a high index of suspicion and routinely consider paragonimiasis-related screening for patients with a history of residence in endemic regions, unexplained eosinophilia, and pleural effusion. Additionally, given the continued increase in global population mobility, collaboration with disease control authorities and improvements to case follow-up management are necessary to reduce the risk of disease transmission.