Clinical Characteristics of Pediatric Pleuropulmonary Paragonimiasis with Pleural Effusion: A Single-Center Retrospective Analysis

ABSTRACT.

Paragonimiasis, a cause of pleuropulmonary disease, is a neglected etiology of pediatric pleural effusion. We retrospectively analyzed children with paragonimiasis-induced pleural effusion admitted to our center, aiming to summarize their diagnosis, treatment, and prognosis. A total of 103 children were included, with a mean age of 8.2 years, and 87.4% resided in rural areas. 81/91 (89.0%) were initially misdiagnosed with other infectious diseases including community-acquired pneumonia (43.9%; 40/91) and tuberculosis (16.5%; 15/91). The predominant blood test findings included hypereosinophilia (98.1%), leukocytosis (95.1%), thrombocytosis (42.7%), hyperglobulinemia (78.6%), and elevated immunoglobulin G levels (85.4%; 76/89). Multiple serous cavity effusions exhibited higher globulin levels (44.7 g/L versus 36.7 g/L) and lower albumin–globulin ratios (0.8 versus 1.0) than single pleural effusions, and loculation was more common in medium or large pleural effusions. After 3 days of praziquantel treatment at a dosage of 75–90 mg/(kg·day), with a median of four courses, all of the children improved, but no patients were cured with a single course of therapy. Almost half of the patients (44/99) continued to exhibit medium or small residual effusion on chest computed tomography scans. Additionally, various types of lung lesions remained, and the incidence of pleural lesions increased during the follow-up period. Unexplained pediatric pleural effusion with eosinophilia requires paragonimiasis evaluation. Early diagnosis and accurate treatment critically improve clinical prognosis, whereas post-paragonimiasis pulmonary injuries necessitate clinical attention.

INTRODUCTION

Paragonimiasis, which is caused by Paragonimus, is a zoonotic parasitic infection and a significant foodborne trematode disease. Foodborne trematode infections are estimated to result in ∼2 million life-years lost to disability and death annually, with paragonimiasis alone affecting ∼1 million individuals each year.^1,2 To date, multiple Paragonimus species capable of causing human disease have been recognized worldwide, such as Paragonimus westermani (P. westermani), Paragonimus skrjabini (P. skrjabini), Paragonimus miyazakii, Paragonimus heterotremus (P. heterotremus), Paragonimus africanus, Paragonimus uterobilateralis, Paragonimus kellicotti and Paragonimus mexicana.^3–5 Paragonimiasis exhibits distinct regional distributions, with cases reported in parts of East Asia, Southeast Asia, Central and West Africa, and the Americas.¹ In China, endemic areas are mainly in the southwest, northeast, and southeast, where three Paragonimus species are known to infect humans: P. westermani, P. skrjabini, and P. heterotremus.^2,6 However, in an era of intensified human interconnectedness, increasing mobility significantly influences the distribution and prevalence of infectious diseases,⁷ which may blur the boundaries of endemic areas and pose diagnostic challenges in nonendemic regions.

The transmission of Paragonimus to humans primarily occurs through the consumption of raw or undercooked freshwater crabs or crayfish (e.g., pickled, fermented, or grilled preparations, which may not kill the Paragonimus metacercariae), as well as the ingestion of water contaminated with metacercariae.^6,8 After ingestion, metacercariae are released from their capsules in the intestine. Subsequently, they penetrate the intestinal wall, enter the abdominal cavity, pass through the diaphragm into the pleural cavity, and mature into adult worms in the lung. These worms can also migrate to extrapulmonary tissues or organs, such as subcutaneous tissue, the muscles, the heart, and the brain, causing disseminated infections.⁴ Paragonimus can either invade the pleura directly or, if its migration to the lungs is hindered, reside in the pleural cavity, leading to inflammation and pleural effusion.⁹

Pediatric patients are particularly vulnerable to pulmonary infections that are complicated by pleural effusion.¹⁰ Among the various causes of pleural effusion, paragonimiasis is less commonly recognized and is characterized by nonspecific symptoms and radiographic features, often resulting in diagnostic delays, misdiagnosis, and inappropriate treatment. Although misdiagnosed cases have been reported, clinical data remain scarce, with most evidence derived from individual case reports. The relatively higher incidence of paragonimiasis in children compared with adults, combined with its diagnostic challenges, poses a significant clinical concern.^6,11 Thus, in this study, we aim to summarize the clinical manifestations, laboratory features, treatment strategies, and prognosis of children with paragonimiasis-induced pleural effusion, underscore the importance of recognizing this condition, and provide a reference for future clinical practice.

MATERIALS AND METHODS

Study design.

This retrospective study was conducted at the Public Health Clinical Center of Chengdu, the sole nonprofit-designated institution for the diagnosis and treatment of infectious diseases in Sichuan Province, China. The center is also responsible for the diagnosis and treatment of parasitic diseases across the province. Pediatric patients with first-time hospitalization for paragonimiasis-induced pleural effusion between January 2018 and March 2024 were retrospectively enrolled based on the following criteria: 1) age <18 years at diagnosis; 2) absence of preexisting comorbidities, including congenital and organic cardiopulmonary disorders, chronic hepatorenal pathologies, autoimmune connective tissue disorders, and neoplastic diseases; 3) no prolonged use (>1 week) of immunosuppressive agents or systemic corticosteroids; and 4) no previous antiparasitic therapy before admission to our center. All patients were followed from the initiation of antiparasitic therapy until completion of the treatment regimen, with the final follow-up concluding in July 2024.

Diagnostic criteria and data collection.

We developed clinical diagnostic criteria for paragonimiasis-induced pleural effusion based on the “Diagnosis of Paragonimiasis” (WS 380-2012) issued by China’s National Health Commission. These criteria include 1) a positive epidemiological history (e.g., the consumption of raw or semi-raw crab or crayfish or raw river water); 2) symptoms such as cough, chest pain, tachypnea or other non-respiratory systemic symptoms; 3) elevated eosinophils in multiple peripheral blood tests (absolute value >0.5 × 10⁹/L); 4) seropositivity for Paragonimus-specific antibodies (Shenzhen Aikang Biological Technology Co., Ltd., Shenzhen, China; Reg. No. 20142220140); 5) confirmation of pleural effusion through chest imaging or ultrasound; 6) pleural eosinophilic inflammation manifesting as either eosinophilic pleural effusion or eosinophilic tissue infiltration (eosinophilic granuloma, Charcot–Leyden crystal, etc.) on a pleural biopsy; and 7) no evidence for other causes of pleural effusion other than the effectiveness of the deworming treatment. A definitive diagnosis requires the identification of parasites or eggs in pleural effusion or pleural tissue specimens.

The demographic information (age, sex, place of residence, ethnicity, etc.), epidemiological history, primary clinical manifestations, laboratory test results, imaging results, treatment, and prognosis of the included subjects were retrospectively recorded. At least two experienced specialist doctors reviewed the images and reports of the computed tomography (CT) and ultrasound scans. The laboratory test results were judged based on the highest values of leukocyte, eosinophil, globulin, platelet, and IgG, as well as the lowest values of albumin and hemoglobin. The criteria included leukocytosis (absolute value >10 × 10⁹/L), hypereosinophilia (absolute value >1.5 × 10⁹/L in at least two tests, with an interval of >1 month),¹² anemia (hemoglobin <110 g/L), thrombocytosis (absolute value >450 × 10⁹/L), hyperglobulinemia (absolute value >35 g/L), and hypoalbuminemia (absolute value <30 g/L).

STATISTICAL ANALYSES

Statistical analysis was performed by using SPSS 24.0 (IBM Corp., Armonk, NY). Continuous data with a normal distribution are presented as mean ± SD ($\overline{\text{x}}$ ± SD), whereas nonnormally distributed data are expressed as the median (25th percentile, 75th percentile). Categorical variables are described as counts (n) and percentages (%), representing the number of cases over the total. The Student’s t-test or Mann–Whitney U test was used to analyze continuous data, and the χ² test was used to analyze categorical data to assess differences between groups. Additionally, correlation analysis was conducted to explore potential factors influencing the number of deworming treatment courses. A P-value less than 0.05 was considered statistically significant.

RESULTS

Diagnostic information, demographics, and clinical manifestations.

A total of 103 pediatric patients who met the criteria were included, and their diagnostic information was retrospectively summarized in Figure 1. Of these patients, 91 exhibited abnormal symptoms or signs, whereas 12 were asymptomatic. All patients exhibited elevated eosinophils on repeated peripheral blood tests and had pleural effusion confirmed via thoracic ultrasound or imaging. Epidemiological histories related to paragonimiasis were identified in 85 patients. A preliminary diagnosis of paragonimiasis was established in all cases on the basis of seropositivity for Paragonimus-specific antibodies, which were detected via ELISA with a licensed commercial kit. To further clarify the association between pleural effusion and paragonimiasis, additional pleural fluid or tissue testing was required. However, 75 patients or their guardians declined further invasive procedures. In the absence of evidence for alternative etiologies, diagnostic antiparasitic therapy demonstrated efficacy. Among the 28 patients who underwent pleural fluid or pleural tissue analysis, 11 underwent pleural biopsies, including nine surgical specimens and two needle biopsy specimens. Eosinophilic inflammation was observed in 22 patients, all of whom showed clinical improvement after anti-parasitic therapy. Definitive diagnoses were confirmed in six cases: parasite eggs or worms were identified in pleural biopsies from five patients (one with polymerase chain reaction confirmation), whereas the remaining case was diagnosed via the next-generation sequencing of pleural fluid. The pathological detection rate of Paragonimus eggs or worms in pleural biopsies was 45.5% (5/11).

Figure 1.

Diagnostic information for 103 children with paragonimiasis-induced pleural effusion.

Among the included children, 68.9% (71/103) were male, with a male-to-female ratio of 2.2:1 and a mean age of 8.2 ± 3.5 years (range 1.7–17 years). All patients, except three, were from Sichuan Province; details are given in the Supplemental Information (Supplemental Figure 1). A total of 38.8% (40/103) of the patients were residents of Leshan City, whereas 11.7% (12/103) and 16.5% (17/103) resided in Ebian County and Mabian County, respectively, both of which are administered by Leshan City. A total of 87.4% (90/103) of the children were long-term residents of rural areas. A total of 35.0% (36/103) were from minority ethnic groups, of whom 83.3% (30/36) were of the Yi nationality.

The initial symptoms and signs were recorded upon presentation. The most common reasons for seeking medical care were cough (32.0%; 33/103), fever (26.2%; 27/103), abdominal pain (24.3%; 25/103), and chest pain (18.4%; 19/103). Subcutaneous masses (20.4%; 21/103) were often encountered during physical examinations. However, 11.7% (12/103) of the patients had no relevant clinical findings, with abnormalities detected accidentally in routine blood tests. Specifically, six cases were found in health checkups, and six were found in preoperative tests for hernia or posttraumatic fracture surgery.

A total of 89.0% (81/91) of the cases were initially diagnosed with other infectious diseases, including community-acquired pneumonia (CAP; 43.9%; 40/91) and tuberculosis (16.5%; 15/91) (Supplemental Figure 2). The treatment status of 87 children was collected, with 78.2% (68/87) receiving antibiotic treatment of durations ranging from 3 to 32 days. A total of 4.6% (4/87) of these patients received antituberculosis treatment that lasted 2–18 months. The median time from onset to diagnosis was 1.0 (0.5, 1.5) months, and 45.6% (47/103) of the patients had two or more hospitalizations before diagnosis at different facilities.

Laboratory findings and imaging examination.

All children underwent blood routine and biochemical examinations before deworming. All 103 patients exhibited eosinophilia, with hypereosinophilia observed in 98.1% (101/103) of cases. Other abnormalities included leukocytosis in 95.1% (98/103), thrombocytosis in 42.7% (44/103), anemia in 35.0% (36/103), hypoproteinemia in 3.9% (4/103), and hyperglobulinemia in 78.6% (81/103) of patients. The mean albumin–globulin ratio was 0.9 ± 0.2. IgG was quantitatively detected in 89 patients, of whom 85.4% (76/89) exhibited increased levels. Details are presented in Table 1.

Table 1.

Primary blood test results of children with paragonimiasis-induced pleural effusion before antiparasitic treatment

Items	Cases (N)	$\overline{\text{x}}$ ± SD or M (P25, P75)	Range [Min–Max]
Initial leukocyte count ×109/L	103	18.5 (13.0, 24.5)	[5.1–49.0]
Initial eosinophil count ×109/L	103	9.1 (4.8, 13.9)	[0.7–39.2]
Initial platelet count ×109/L	103	433.8 ± 115.6	[187.0–795.0]
Minimum hemoglobin value (g/L)	103	113.3 ± 9.6	[89.0–143.0]
Peak globulin value (g/L)	103	40.9 (35.4, 47.5)	[25.7–66.1]
Minimum albumin value (g/L)	103	35.6 (33.5, 37.3)	[23.6–43.4]
Peak IgG value (g/L)	89	21.4 (16.3, 30.0)	[10.5–59.0]
Albumin–globulin ratio	103	0.9 ± 0.2	[0.4–1.4]

M = median; P25 = 25th percentile; P75 = 75th percentile.

Before deworming, chest CT scans were conducted on 103 patients, all of whom exhibited pulmonary abnormalities. Lesions are presented with various characteristics, including spot or patch shadows, nodules, strip signs, cavities, and consolidations. Additionally, some patients displayed pleural abnormalities such as thickening, adhesion, and calcification (Figure 2).

Figure 2.

Chest computed tomography images from children with paragonimiasis-induced pleural effusion. (A and B) An 11-year-old child developed a large pleural effusion caused by Paragonimus infection, which required closed thoracic drainage. Following drainage, pleural thickening and adhesions (indicated by the arrow) restricted lung re-expansion, leading to pneumothorax. (C) A 5-year-old child with paragonimiasis-induced pleural effusion showed calcified nodules of parasite eggs in the pleura. (D) Chest CT of a child showed cavity and nodule shadows in the lung parenchyma.

Examination of effusion.

All patients underwent echocardiography, abdominal or pelvic ultrasound, or imaging examination before deworming. Multiple serous cavity effusions (defined as pleural effusion plus ≥1 additional site involvement: peritoneal, pericardial, or pelvic) were observed in 47.6% (49/103) of cases. The distribution of effusion sites included peritoneal (34), pericardial (28), and pelvic (9). Combined effusions were observed in 10 patients with both pericardial and peritoneal involvement, two with peritoneal and pelvic involvement, and five with effusions in all three sites. Compared with patients with simple pleural effusions, those with multiple effusions exhibited higher globulin levels and a lower albumin–globulin ratio (P <0.001; Table 2). Regarding pleural effusion type, 16.5% (17/103) of patients exhibited loculated pleural effusion. Bilateral pleural effusion was found in 48.5% (50/103) of cases. Right-sided effusion occurred in 30.1% (31/103) of cases, whereas left-sided effusion was present in 21.4% (22/103) of cases. In terms of the degree of pleural effusion, a small amount accounted for 59.2% (61/103), medium accounted for 23.3% (24/103), and large accounted for 17.5% (18/103) of the total. Loculated development was more common in medium or large pleural effusions (P = 0.006; Table 2).

Table 2.

Comparison of different types of pleural effusion in 103 children with paragonimiasis

Variables	Different Amounts of Pleural Effusion			Multiple Serous Cavity Effusion and Single Pleural Effusion
	Small Amounts (n = 61)	Medium or Large Amounts (n = 42)	P-Value	Single Thorax (n = 54)	Multiple Serous Cavities (n = 49)	P-Value
Age ($\overline{\text{x}}$ ± SD, years)	8.2 ± 3.8	8.3 ± 3.2	0.895	8.5 ± 3.6	7.9 ± 3.5	0.391
Deworming courses, M (P25, P75), times	4 (3, 4)	3 (3, 4)	0.094	3 (3, 4)	4 (3, 5)	0.170
Diagnosis interval, M (P25, P75), months*	1.0 (0.5, 1.5)	0.8 (0.5, 1.5)	0.874	0.9 (0.5, 1.5)	1.0 (0.4, 1.5)	0.908
Initial leukocyte count ×109/L, M (P25, P75)	19.0 (12.7, 24.7)	17.2 (13.4, 24.7)	0.869	17.4 (12.0, 22.4)	20.3 (13.8, 27.5)	0.081
Initial eosinophil count ×109/L, M (P25, P75)	9.1 (5.5, 14.7)	8.8 (4.5, 12.9)	0.346	8.9 (4.4, 10.8)	10.6 (5.1, 16.6)	0.061
Initial platelet count ×109/L ($\overline{\text{x}}$ ± SD)	421.7 ± 125.2	451.3 ± 99.0	0.203	418.8 ± 107.9	450.3 ± 122.6	0.169
Peak globulin value × g/L, M (P25, P75)	39.9 (35.5, 47.6)	42.1 (35.4, 46.9)	0.351	36.7 (33.1, 45.8)	44.7 (39.3, 49.1)	<0.001
Albumin–globulin ratio ($\overline{\text{x}}$ ± SD)†	0.9 ± 0.2	0.9 ± 0.2	0.150	1.0 ± 0.2	0.8 ± 0.2	<0.001
Loculated pleural effusion, n (%)	5 (8.2)	12 (28.6)	0.006	8 (14.8)	9 (18.4)	0.628

M = median; P25 = 25th percentile; P75 = 75th percentile.

^*Diagnosis interval, the median time from onset to diagnosis.

^† The original values for the “Small amounts” and “Medium or large amounts” groups were 0.92 ± 0.23 and 0.85 ± 0.23, respectively.

Treatment and follow-up outcomes.

After the paragonimiasis diagnosis, all patients were administered praziquantel tablets for parasite eradication at a dosage of 75–90 mg/(kg·day), which was provided in three oral doses per day over a 3-day treatment course. The median number of treatment courses was four (3, 4; range 2–7 courses). A correlation analysis showed that the number of deworming courses was negatively correlated with the rates of decrease in leukocytes (R = −0.267; P = 0.006) and eosinophils (R = −0.668; P <0.001; Supplemental Table 1). Methylprednisolone at a dosage of 1–2 mg/(kg·day) was used for anti-inflammatory purposes in the initial phase of treatment. Meanwhile, 17.5% (18/103) of the patients underwent pleural drainage procedures, including closed thoracic drainage in 10 cases and puncture drainage in eight cases. A total of 8.7% (9/103) patients underwent surgical intervention because of ineffective effusion absorption (resulting in loculated pleural effusion or empyema) and pleural lesions, with three patients exhibiting pleural fibrosis (the presence of “thick fibrous pleural rind”) and two patients presenting with thoracic cage collapse.

The median time from the first deworming to the last follow-up review was 3.5 (2.1, 5.2) months. During the follow-up period, three patients were infected with influenza, and five were infected with coronavirus disease 2019, all of whom were quickly cured. One suffered from septicemia, resulting in new lung consolidation and purulent pericarditis, but recovered after anti-infective treatment and pericardial drainage. All children exhibited symptomatic improvement, with eosinophil and white blood cell counts approaching normal levels, and demonstrated favorable prognoses by the end of the follow-up period.

A total of 99 children underwent follow-up chest CT scans after antiparasitic treatment. Imaging findings from the last available CT were collected and compared with the initial pretreatment scans. The follow-up scans showed that 55.5% (55/99) of the cases exhibited the complete resolution of pleural effusion, 39.4% (39/99) exhibited residual small amounts of pleural effusion, and 5.1% (5/99) exhibited medium amounts of pleural effusion. A general trend of absorption was observed in pulmonary lesions; however, various abnormalities persisted in the majority of cases. In contrast, an increasing trend was observed in pleural lesions (including thickening, adhesions, or calcification). Only 3.0% (3/99) of the children showed complete radiological resolution compared with baseline imaging. Details are presented in Figure 3.

Figure 3.

Changes in the proportions of chest computed tomography abnormalities before and after antiparasitic treatment in 99 children.

DISCUSSION

The clinical manifestations of pleuropulmonary paragonimiasis vary widely, ranging from asymptomatic to overt disease. Compared with other pathogens that cause pleural effusion in children, paragonimiasis is rarer and often overlooked by clinicians. Here, we have summarized the clinical characteristics and treatment experience of children with paragonimiasis-induced pleural effusion to improve disease recognition.

In our study, the etiological diagnosis for patient inclusion was primarily determined by detecting Paragonimus-specific antibodies using the ELISA method. Pediatric paragonimiasis remains a diagnostically elusive disease because of the suboptimal performance of traditional parasitological methods in detecting Paragonimus eggs in sputum, stool, or pleural fluid. Microscopic examination of sputum has been reported to yield low sensitivity results, often between 28–38% in controlled studies. It is critical to note that eggs may not appear in sputum until 2–3 months into the infection, further complicating timely diagnosis.¹³ Moreover, children’s tendency to swallow sputum makes it hard to collect samples, which may cause the sensitivity to decline further in pediatric cases. ELISA is used to detect anti-Paragonimus IgG antibodies with 92.9% sensitivity and 91.9% specificity, offering significant advantages.¹⁴ The limitations of parasitological methods, including low sensitivity, delayed positivity, and pediatric-specific sampling challenges, render them inadequate as standalone diagnostic tools. Serological ELISA addresses these gaps by enabling early detection, high throughput, and extrapulmonary diagnosis.

A total of 103 pediatric patients were included in the study. The children predominantly resided in rural areas such as Leshan and Bazhong in Sichuan Province, with a mean age of 8.2 years and an ethnic minority representation of 35.0%. Areas conducive to host breeding feature rugged mountainous terrain and pristine natural ecological environments.² The mountainous regions of southwest China, which are characterized by dense river networks, create a conducive habitat for freshwater crabs and other intermediate hosts. Rural children frequently engage in activities near their homes, such as playing in streams, consuming untreated water, harvesting and consuming self-prepared crabs, and exhibiting low hygiene awareness. Additionally, some ethnic minority groups traditionally consume raw food.

The diversity and lack of specificity of clinical symptoms and low sensitivity of laboratory tests can easily lead to the misdiagnosis of children with paragonimiasis-induced pleural effusion. Our study revealed a median time from onset to diagnosis of one month, with 45.6% of patients experiencing two or more hospitalizations at different facilities, which is likely due to patient delay and clinician inexperience. Some children had been misdiagnosed with tuberculosis, CAP, suppurative pleurisy and peritonitis, and more than 78.2% of the children had received ineffective antibiotic treatment in our study. A total of 15 patients were either suspected or diagnosed with pulmonary tuberculosis, with four receiving an extended course of antituberculosis therapy. Paragonimiasis is prone to misdiagnosis as pulmonary tuberculosis because of its respiratory manifestations and lack of response to common antibiotics. Additionally, chest imaging frequently reveals similar lesions, such as nodules, cavities, and enlarged mediastinal lymph nodes, in the lungs.^15,16

Elevated eosinophil counts can be a significant indicator for diagnosing parasitic infections. These infections stimulate the excessive production of interleukin-5, leading to the clonal expansion of eosinophils and an increase in the total leukocyte count.¹⁷ In addition to the migratory invasion of Paragonimus, activated eosinophils cause tissue damage by releasing toxic granules, lipid mediators, and cytokines.¹⁸ In our study, all patients showed a reduction in eosinophil count, and their levels approached normal after treatment. However, the number of treatment courses required varied among patients. Patients with greater decreases in eosinophil and white blood cell counts after the first course needed fewer subsequent courses, regardless of initial peak values. We speculate that this may result from interindividual variations in drug sensitivity and the rate at which inflammation resolves.

The serum albumin–globulin ratio has been widely used as a representative biomarker for assessing nutrition and inflammation status.¹⁹ In our study, only a few pediatric patients (3.9%; 4/103) exhibited hypoalbuminemia due to protein depletion caused by Paragonimus infection, whereas the majority (78.6%; 81/103) developed hyperglobulinemia, leading to a decreased albumin–globulin ratio. Elevated IgG levels, which have been reported in previous studies,^20–22 are primarily responsible for the hyperglobulinemia. Multiple serous cavity effusions were observed, which were associated with higher globulin levels and a lower albumin–globulin ratio compared with single pleural effusion. The primary reason might be the more intense and prolonged chronic inflammatory stimulation caused by Paragonimus at multiple sites.

Both internal medicine and surgical interventions are essential in the comprehensive management of pleural effusion.^23,24 In a recent study, 213 clinically diagnosed pediatric patients with paragonimiasis from Yunnan, China, received oral praziquantel treatment, averaging 2.6 treatment courses, with 121 patients (56.8%) also receiving glucocorticoid therapy and 45 patients (21.1%) undergoing surgical intervention.²⁵ In this study, human paragonimiasis was treated with a 3-day course of praziquantel, with a median of four courses. Methylprednisolone at a dosage of 1–2 mg/(kg·day) was usually used for anti-inflammatory purposes in the initial phase of treatment. Interestingly, there is a drug interaction between steroids and praziquantel. When administered together, the levels of praziquantel are significantly lowered,²⁶ which may be the reason that none of the patients were cured with the initial course of therapy. However, we believe that the use of intravenous corticosteroids during the initial phase of antiparasitic treatment is both necessary and reasonable in patients with pleural effusion caused by paragonimiasis. The marked eosinophilia observed in some patients indicates a heightened immune response. The release of parasitic antigens after worm death may further intensify this response, thereby worsening pleural inflammation and exudation. Therefore, corticosteroids are concurrently used to suppress immune reactions, alleviate tissue damage, and reduce further pleural exudation. In addition to the administration of praziquantel for deworming, 17.5% (18/103) of the patients underwent therapeutic puncture and drainage, whereas 8.7% (9/103) required surgical operation for ineffective effusion absorption and concurrent pleural lesions. Unfortunately, some pediatric patients or their guardians rejected the acceptance of potential risks, leading to an underestimation of the true need for surgical intervention. When the volume of the effusion progressively increases and a loculation or empyema develops, drainage becomes necessary.^23,27 Given the migratory and invasive characteristics of Paragonimus and its pathway from the pleural cavity to the lung, it is postulated that paragonimiasis-induced pleural effusion may rapidly progress to empyema. Additionally, our study revealed that medium or large pleural effusions were more likely to develop into loculations. Therefore, it is crucial to aggressively monitor effusion changes and evaluate for potential deterioration to ensure timely drainage intervention. Moreover, intrapleural fibrinolysis or surgical operation may be necessary when satisfactory drainage effectiveness cannot be achieved.^23,24,28 There is currently no clear preferred recommendation because of factors such as technology, cost, and patient preference.^29,30 Notably, surgical operation can serve as a secondary option after unsuccessful fibrinolytic therapy, particularly in cases of empyema accompanied by severe pleural lesions (e.g., the presence of “thick fibrous pleural rind”).^23,24

Chest CT results before deworming treatment revealed lung lesions in all the children, who presented with various abnormalities such as spots, nodules, strip signs, and cavity shadows, which were consistent with findings from other studies.^11,31 Although a comparison of pre- and posttreatment results revealed an overall improvement in lesion types, residual lesions still persisted to varying degrees at the end of the follow-up period. Increased pleural lesions most likely suggest that the pathophysiological process of pleural effusion is progressing. Consequently, there might be a risk of loculation or empyema in residual effusion and further thickening and adhesions in the pleura, potentially causing restrictive ventilation obstruction or other lung function impairments. Follow-up on the prognosis of children with empyema has revealed a high incidence of residual imaging abnormalities, impaired pulmonary function, and diaphragm movement dysfunction.^32,33 Notably, pleural effusion can also lead to other severe complications, such as pneumothorax and bronchopleural fistula, particularly in cases of parapneumonic effusion.³⁴ Furthermore, in the context of paragonimiasis, pleural effusion is closely associated with pneumothorax, with another study revealing that 78.9% of cases with paragonimiasis-associated pneumothorax were accompanied by pleural effusion.³⁵ Apart from treating the paragonimiasis-induced pleural effusion with anthelmintics, it is essential to conduct a pulmonary function assessment and strive for pulmonary rehabilitation as part of management and follow-up. Although our primary focus in this study is the short-term prognosis of the patients and the results may be influenced by the timing of the review, attention must be paid to the occurrence of lung injury after paragonimiasis-induced pleural effusion in pediatric cases.

This study has several limitations. First, as a retrospective study, limitations in quality control may exist. Rigorous dual-radiologist assessments cannot fully eliminate diagnostic subjectivity or occasional errors in CT interpretation. Second, as a single-center study, its findings are limited to the clinical features observed in children from Sichuan. Third, there was an insufficient assessment of lung injury caused by paragonimiasis-induced pleural effusion, including a lack of pulmonary function tests. Fourth, because of time constraints, more comprehensive follow-up is required for children with residual effusion, lung lesions, and pleural lesions. Finally, expanding the sample size may provide more robust and significant conclusions.

CONCLUSION

In conclusion, rural residency, endemic areas or positive epidemiological history, elevated eosinophils, hyperglobulinemia, and pleural effusion indicate an increased likelihood of paragonimiasis. We strongly recommend the administration of immunological tests when doctors encounter patients with fever, cough, subcutaneous nodules, elevated eosinophils, hyperglobulinemia, and chest imaging that mimics tuberculosis in endemic areas. Longer courses of praziquantel therapy and aggressive drainage strategies should be required in the treatment of patients with paragonimiasis and medium or large pleural effusions. Pulmonary lesions exhibit slow resolution, and residual effusion and pleural lesions may compromise lung function. Further attention is needed for post-paragonimiasis pulmonary injuries in children.

Note: Supplemental materials appear at www.ajtmh.org.