ABSTRACT

Cystic echinococcosis (CE) in children is a public health problem. To describe the clinical and epidemiological profile of CE, we reviewed the records of 55 children admitted to our institution with a confirmed diagnosis of CE between 2017-2019, analyzing demographic data, clinical manifestations, and treatment. Of the population, 61.8% (34/55) were male. The mean age was 9.25 years (SD: 2.79); 16.4% had previous CE diagnosis, and 50.9% had contact with dogs. The median time of illness was 2 months. Of the patients, 65.5% had hepatic involvement, 56.4% had pulmonary involvement, and 21.8% had both hepatic and pulmonary involvement. The most frequent symptoms were abdominal pain (80.6%) and cough (80.6%). Surgical treatment was performed in 87.5% of patients with hepatic CE, in 100% of those with pulmonary CE and in 100% of those with hepatic and pulmonary CE. Albendazole was prescribed in 100% of hepatic cases, in 73.7% of pulmonary cases, and in 75% of those with both conditions. Mortality was not reported.

Keywords:
Echinococcosis; Echinococcus granulosus, Echinococcosis, Hepatic; Echinococcosis, Pulmonary; Children

INTRODUCTION

Cystic echinococcosis (CE) is a parasitic disease caused by Echinococcus granulosus sensu lato (sl) which produces chronic, often silent, infections in humans ¹1. Eckert J, Deplazes P. Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clin Microbiol Rev. 2004;17(1):107-35. doi: 10.1128/CMR.17.1.107-135.2004.
https://doi.org/10.1128/CMR.17.1.107-135... . Echinococcus spp causes the following diseases: cystic echinococcosis (CE), alveolar echinococcosis (AE) and neotropical echinococcosis (NE) ²2. Vuitton DA, McManus DP, Rogan MT, Romig T, Gottstein B, Naidich A, et al. International consensus on terminology to be used in the field of echinococcosis. Parasite. 2020;27:41. https://doi.org/10.1051/parasite/2020024.
https://doi.org/https://doi.org/10.1051/... .

Parasites of the species E. granulosus sensu stricto (genotypes G1/G3) cause the majority of human infections (88%) ³3. Alvarez Rojas CA, Romig T, Lightowlers MW. Echinococcus granulosus sensu lato genotypes infecting humans--review of current knowledge. Int J Parasitol 2014;44:9-18. doi: 10.1016/j.ijpara.2013.08.008.
https://doi.org/10.1016/j.ijpara.2013.08... . E. granulosus is distributed worldwide, but is frequently found in South America, Africa and Asia; and endemic in Argentina, Brazil, Uruguay, Chile and Peru, countries with important livestock and grazing activity ⁴4. Benenson AS. Manual para el control de las enfermedades transmisibles. Rev Esp Salud Publica [Internet]. 1997;71(5):499-500..

E. granulosus sl. requires two mammalian hosts to complete its life cycle; the adult tapeworm is found in the small intestine of dogs and other canids, while the larval stage is located in the viscera of ungulates, especially sheep and goats ⁵5. Larrieu E, Gavidia CM, Lightowlers MW. Control of cystic echinococcosis: Background and prospects. Zoonoses Public Health 2019;66:889-99. doi: 10.1111/zph.12649.
https://doi.org/10.1111/zph.12649... . Transmission occurs between definitive hosts (canids) and intermediate hosts (herbivores). Dogs play an important role in the life cycle of E. granulosus sl. because they can contaminate the environment with parasite eggs, which can remain viable for a long time ⁽⁶6. Thompson RCA. Biology and systematics of Echinococcus. Adv Parasitol 2017;95:65-109. doi: 10.1016/bs.apar.2016.07.001.
https://doi.org/10.1016/bs.apar.2016.07.... ^,77. Ebrahimipour M, Budke CM, Harandi MF. Control of cystic echinococcosis in Iran: Where do we stand? Trends Parasitol 2020;36:578-81. doi: 10.1016/j.pt.2020.04.007.
https://doi.org/10.1016/j.pt.2020.04.007... . Thus, man becomes an accidental host by coming into direct contact with parasitized dogs or by ingesting parasite eggs ⁸8. Bhutani N, Kajal P. Hepatic echinococcosis: A review. Ann Med Surg (Lond) 2018;36:99-105. doi: 10.1016/j.amsu.2018.10.032.
https://doi.org/10.1016/j.amsu.2018.10.0... .

In 2012, the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) ranked E. granulosus second among foodborne parasites of global public health importance ⁹9. Batz MB, Hoffmann S, Morris JG Jr. Ranking the disease burden of 14 pathogens in food sources in the United States using attribution data from outbreak investigations and expert elicitation. J Food Prot 2012;75:1278-91. doi: 10.4315/0362-028X.JFP-11-418.
https://doi.org/10.4315/0362-028X.JFP-11... . Most cases are diagnosed in adults because of the slow growth of the parasite, and only 10-20% of cases are diagnosed in children under 16 years of age ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... . The existence of pediatric cases suggests an active community transmission cycle ¹¹11. Khan A, Ahmed H, Khan H, Saleem S, Simsek S, Brunetti E, et al. Cystic echinococcosis in Pakistan: A review of reported cases, diagnosis, and management. Acta Trop 2020;212:105709. doi: 10.1016/j.actatropica.2020.105709.
https://doi.org/10.1016/j.actatropica.20... . This zoonosis is an important public health problem in several countries and an emerging and re-emerging disease in others ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... .

The aim of the study was to describe the clinical and epidemiological characteristics of pediatric patients with CE in a referral surgical center in Peru.

THE STUDY

Design and study population

Retrospective study in patients under 18 years of age with confirmed diagnosis of CE, attended at the Instituto Nacional de Salud del Niño San Borja (INSN-SB), in Lima, between 2017 and 2019. We excluded patients with incomplete data in the clinical record regarding the analyzed variables.

Study variables

The studied epidemiologic variables were sex, age, place of origin, previous diagnosis of CE in patients and family members, and contact with dogs. The clinical variables were time of illness measured from symptom onset to contact with a healthcare center and symptoms such as cough, hemoptysis, dyspnea, chest pain, abdominal pain, vomiting, nausea, fever, decreased weight, and decreased appetite.

Confirmatory diagnosis of CE was made by histopathological study of the surgical and/or serological specimen, with Western blot and/or IgG ELISA. We characterized the cysts according to the WHO-IWGE ¹²12. WHO Informal Working Group. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop 2003;85:253-61. doi: 10.1016/s0001-706x(02)00223-1.
https://doi.org/10.1016/s0001-706x(02)00... echotomographic classification, which monitors the natural history, from a simple cyst to a transitional stage and ends with its inactivation. The treatment variables were the type of therapy, dosage, frequency and duration. Finally, hospital stay was evaluated considering the final status of the patient.

Data analysis

Stata® v16 statistical software (Stata Corporation, College Station, Texas, USA) was used for the analysis. Descriptive statistics were used, quantitative variables were represented by measures of central tendency and dispersion according to their normality distribution, while qualitative variables were summarized using frequencies and percentages.

FINDINGS

We identified 55 patients under 18 years of age with CE diagnosis; 61.8% (34/55) were male. The mean age was 9.25 years (SD: 2.79) and the greatest number of cases (67.3%, 37/55) were between 6 and 11 years old. From the total of patients, 81.8% (45/55) were from the provinces, with Pasco being the department with the highest number of cases (21.8%, 12/55). Cases reported in the department of Lima accounted for 18.2% (10/55) (Table 1). Contact with dogs was observed in 50.9% (28/55) of the patients; previous CE diagnosis in patients and in their relatives was 16.4% (9/55) and 3.6% (2/55), respectively. Most patients presented symptoms (94.5%, 52/55), and only three were diagnosed incidentally. The median time of illness was 2 months (IQR: 1-4). Liver involvement was found in 65.5% (36/55) of the patients, 56.4% (31/55) showed pulmonary involvement, while 21.8% (12/55) had both hepatic and pulmonary involvement.

In cases of hepatic CE, the most frequent symptom was abdominal pain (80.6%, 29/36); 75.0% (27/36) had cysts larger than 5 cm and 33.3% (12/36) had more than one lesion. In cases of pulmonary CE, the most frequent symptom was cough (80.6%, 25/31); 67.7% (21/31) had single cyst and 61.3% (19/31) had cysts larger than 5 cm (Table 2).

According to the WHO-IWGE classification ¹²12. WHO Informal Working Group. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop 2003;85:253-61. doi: 10.1016/s0001-706x(02)00223-1.
https://doi.org/10.1016/s0001-706x(02)00... , we found a higher percentage of cysts in early stages (CE1) (52.8%, 19/36). Tomography (56.4%, 31/55) was the most frequent diagnostic method, and 74.5% (41/55) of the cases were confirmed by pathological anatomy (Table 3). Among the patients with CE serology, 37.5% (6/16) had positive IgG Elisa, and 76.9% (10/13) of those who underwent Western blot for CE (13/16) were positive.

Surgery was needed in 87.5% (21/24) of the cases of hepatic CE; of these, 76.2% (16/24) had pre-surgical albendazole prophylaxis, and 100% (21/21) received albendazole post-surgery for four weeks of treatment, on average. Those cases that only received albendazole (12.5%, 3/24) had cysts smaller than 4 cm.

All pulmonary CE cases (100%, 19/19) were surgically treated; of these, 26.3% (5/19) received pre-surgical prophylaxis with albendazole for ruptured cysts or fissures (Table 4). The dose used for albendazole was 7.5 mg/kg/dose every 12 h (maximum 400 mg every 12 h). Of all the cases, 9.1% (5/55) had new lesions after treatment; 60.0% (3/5) after 12 months and the other two cases at 7 and 8 months. The median number of days of hospitalization was 9 (IQR: 7-16). No mortality was reported.

DISCUSSION

Most CE cases treated at INSN-SB were patients between 6 and 11 years of age with hepatic involvement, who received surgical and medical treatment, with no mortality. This profile is similar to that published by Huamán G. et al. ¹³13. Huamán GI, Marocho CL, López UT, Gavidia CC. Frecuencia de Hidatidosis en Niños y adolescentes hospitalizados en el Instituto Nacional de Salud del Niño (Periodo 1996-2005). Rev Investig Vet Perú. 2010;21(1):54-60. and Stiglich et al. ¹⁴14. Stiglich WM, Vega-Briceño L, Gutiérrez SM, Trefogli RP, Chiarella OP. Hidatidosis pulmonar pediátrica: Reporte de 12 años de experiencia. Rev Chil Pediatr. 2004;75(4):333-8. doi: 10.4067/S0370-41062004000400004.
https://doi.org/10.4067/S0370-4106200400... who reported a higher percentage in children between 5 and 9 years of age (50.8% and 64.0%, respectively). This implies contact with the parasite at an early age, given that cystic growth is approximately 1 cm per year ¹⁵15. Larrieu EJ, Frider B. Human cystic echinococcosis: contributions to the natural history of the disease. Ann Trop Med Parasitol. 2001;95(7):679-87. doi: 10.1080/00034980120094730.
https://doi.org/10.1080/0003498012009473... . In our study we found a low proportion of family members with previous CE diagnosis, probably due to the lack of a search for intrafamilial cases at the local level.

From 2009 to 2014, 29,559 new human CE cases of were reported in Argentina, Brazil, Chile, Peru, and Uruguay, with approximately 880 deaths reported in the five countries; the proportion of cases in children under 15 years of age was 15%, showing active community transmission to children ¹⁶16. Pavletic CF, Larrieu E, Guarnera EA, Casas N, Irabedra P, Ferreira C, et al. Cystic Echinococcosis in South America: A Call for Action. Rev Panam Salud Publica. 2017;41:e42.. Departments located in the central highlands reported the highest number of cases. These regions have intense livestock and grazing activity and poor sanitary conditions, which would favor fecal-oral transmission with dog feces through close and playful contact ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... .

Several studies report that hepatic involvement in CE is frequent; our casuistry also shows a higher percentage of cases with hepatic involvement; a retrospective study in Spain ¹⁷17. Herrador Z, Siles-Lucas M, Aparicio P, Lopez-Velez R, Gherasim A, Garate T, et al. Cystic echinococcosis epidemiology in Spain based on hospitalization records, 1997-2012. PLoS Negl Trop Dis 2016;10:e0004942. doi: 10.1371/journal.pntd.0004942.
https://doi.org/10.1371/journal.pntd.000... showed that 55% of children under 15 years of age had hepatic involvement. In contrast, Huamán G. et al. ¹³13. Huamán GI, Marocho CL, López UT, Gavidia CC. Frecuencia de Hidatidosis en Niños y adolescentes hospitalizados en el Instituto Nacional de Salud del Niño (Periodo 1996-2005). Rev Investig Vet Perú. 2010;21(1):54-60. found a greater pulmonary involvement (44%) compared to hepatic (23.2%).

Clinical manifestations are diverse and depend on the site, size and state of the cyst. Hepatic CE may be asymptomatic until the cyst reaches a certain size. We found that abdominal pain is the most frequent symptom in hepatic CE ¹⁸18. Tersigni Chiara, Venturini Elisabetta, Montagnani Carlotta, Bianchi Leila, Chiappini Elena, de Martino Maurizio, Galli Luisa. Should Pediatricians Be Aware of Cystic Echinococcosis?. A Literature Review. Pediatr Gastroenterol Nutr: February 2019 - Volume 68 - Issue 2 - p 161-168 doi: 10.1097/MPG.0000000000002182.
https://doi.org/10.1097/MPG.000000000000... and cough is the most frequent one in pulmonary CE, which is similar to what was reported by Huamán et al¹³13. Huamán GI, Marocho CL, López UT, Gavidia CC. Frecuencia de Hidatidosis en Niños y adolescentes hospitalizados en el Instituto Nacional de Salud del Niño (Periodo 1996-2005). Rev Investig Vet Perú. 2010;21(1):54-60.. Most primary infections in humans consist of a single cyst ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... , as found in our study for both hepatic and pulmonary CE.

Techniques such as diagnostic imaging or immunoassays are reported as diagnostic tools. Abdominal ultrasound is an important technique for hepatic CE because of its availability and usefulness in defining dimensions, number, site and status of cysts. Computed tomography can provide additional information when cysts are not visible during ultrasound. In our study, computed tomography was the most commonly employed method, while serology was used in a smaller proportion.

Although antibody testing is useful when confirming the diagnosis, not all patients with CE have a detectable immune response ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... . The sensitivity of serological tests varies between 75 to 80% and is inversely related to the degree of antigens sequestration within the cyst; thus, intact cysts elicit minimal immune response, in contrast, fissured or ruptured cysts exhibit greater immune response ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... .

False negative results may be related to early (CE1) or late (CE5) stages of the disease. The Western blot assay is used as a confirmatory test due to its higher sensitivity and specificity; it is also reported that antibody titers decrease after surgical treatment, not being able to discriminate between active and past infections ¹⁹19. Lissandrin R, Tamarozzi F, Piccoli L, Tinelli C, De Silvestri A, Mariconti M, et al. Factors influencing the serological response in hepatic Echinococcus granulosus infection. Am J Trop Med Hyg 2016;94:166-71. doi: 10.4269/ajtmh.15-0219.
https://doi.org/10.4269/ajtmh.15-0219... . In our study, 76.9% (10/13) of the patients had positive serology for CE Western blot.

The preferred treatment for CE is surgical, and complete excision of the cyst without leakage leads to cure ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... . In the case of unresectable cysts or cysts smaller than 5 cm, benzimidazole derivatives such as albendazole have shown to be effective as an alternative or complementary therapy to surgery, showing a significant regression of the cyst size and relief of symptoms ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... ^,1212. WHO Informal Working Group. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop 2003;85:253-61. doi: 10.1016/s0001-706x(02)00223-1.
https://doi.org/10.1016/s0001-706x(02)00... . In our study we found a higher percentage of surgical treatment for both cases. Patients were treated with albendazole at a dose of 7.5 mg/kg/dose every 12 h orally (maximum 400 mg every 12 h). Albendazole is the most commonly used drug in children with CE, with limited experience in the treatment of children under 6 years of age. Although in the past albendazole was used 14 days per month for 3 months, it is currently prescribed for 3 to 6 consecutive months ²⁰20. Moroni S, Moscatelli G, Bournissen FG, González N, Ballering G, Freilij H, et al. Abdominal cystic echinococcosis treated with albendazole. A pediatric cohort study. PLoS One 2016;11:e0160472. doi: 10.1371/journal.pone.0160472.
https://doi.org/10.1371/journal.pone.016... ; however, few studies are available on the indication and length of treatment in children.

Few cases have recurrence after treatment; therefore, it is important to follow-up using diagnostic imaging every 3 months (ultrasound or tomography) for a minimum of 3 years ¹⁰10. Moro P, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13(2):125-33. doi: 10.1016/j.ijid.2008.03.037.
https://doi.org/10.1016/j.ijid.2008.03.0... . Likewise, it is recommended to screen the patient’s relatives in order to have a timely and early diagnosis of possible new cases.

In our study, hospital stay was short and showed adequate postoperative evolution. Few cases had complicated CE (complicated liver cyst and cholangitis; complicated liver cyst with more than ten lesions, liver cyst plus intra-abdominal abscess and pulmonary cyst plus empyema). No mortality was reported.

An active epidemiological surveillance program in endemic areas is also necessary to control the disease. Early CE diagnosis in asymptomatic children will be achieved as long as access to imaging and serologic tests improves

Our study had limitations, such as the lack of standardization of the clinical information from the medical records, the correct classification and detailed description of the cysts, time of albendazole therapy and the criteria for the prescription of antiparasitic prophylaxis. Since INSN-SB receives patients referred with previous laboratory results from various centers and laboratories in the country, the information from these auxiliary tests was included for surgical decision making in each case.

In conclusion, CE was more frequent in school-age children, the liver was the most affected organ, most patients were surgically treated and no fatal events were reported.

Acknowledgments:

We thank the INSN-SB Research, Technology and Teaching Development Unit (UDITD) for the support provided for the development of this research.

References

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