What Caused Boy in Rural Area to Develop High Fever and Hemoptysis?

What to do for this 7-year-old boy who was admitted to hospital 1 week after developing a fever that reached temperatures up to 40.2°C (104.4°F)? He was very lethargic and spitting up phlegm when he coughed, and his symptoms had persisted despite taking oral cefuroxime for 3 days, reported Penggao Wang, MD, of Zhengzhou Children's Hospital in China, and colleagues in JAMA.

When he presented to hospital, clinicians learned that the boy had been in good health until the onset of symptoms. He lived in rural China and was in close contact with dogs, cattle, and sheep.

His vital signs were:

• Blood pressure: 93/60 mm Hg
• Heart rate: 100/min
• Respiratory rate: 26/min
• Oxygen saturation: 94% on room air

On lung auscultation, clinicians found they could not detect breath sounds on the right hemithorax. His abdomen was soft and not tender on palpation, and his spleen and liver were normal in size.

Lab tests revealed a white blood cell count of 8,000/μL, with 25.8% eosinophils (reference range 0%-9%). His C-reactive protein level was normal.

Clinicians also ordered a tuberculin skin test, an interferon-γ release assay, nucleic acid amplification testing for tuberculosis, an acid-fast bacilli smear microscopy, and HIV antibody testing, all of which returned normal results.

A CT scan of the thorax and abdomen showed that a giant cystic mass (10 × 9 × 5 cm) on the upper lobe of the patient's right lung had ruptured, resulting in compression of the right main bronchus. The CT scan of the abdomen also revealed three round water-density cysts located in the right anterior lobe, right posterior lobe, and left lateral lobe of the liver.

Clinicians recognized that the location of cysts in the lung and liver were highly suggestive of cystic echinococcosis. Accordingly, the patient had serologic testing for Echinococcus granulosus antibodies, which detected enzyme-linked immunosorbent assay antibodies to Echinococcus, and the diagnosis of cystic echinococcosis was confirmed.

They scheduled the patient for a surgical removal of the right upper lobe of the lung, and started him on albendazole (15 mg/kg orally twice daily). He underwent surgery 1 week later, and continued with medical treatment for the next 5 months after surgery.

The surgery involved excision of a 12 × 12 × 8-cm pulmonary cyst. Histologic examination showed extensive necrosis and calcification, and evidence of E. granulosus was noted on hematoxylin and eosin stain.

Five months after his initial surgery, the patient underwent laparotomy; three liver cysts were completely removed, with no spillage of their contents, clinicians said.

They continued the patient on albendazole for 3 months after the surgery. At a follow-up assessment 2 months after the liver surgery, clinicians noted that the patient had recovered well. An ultrasound of his abdomen at that time showed that cysts had not recurred.

Discussion

"Cystic echinococcosis is caused by infection with the larval stage of a tapeworm called E. granulosus," Wang and team wrote. Every year, over 1 million people worldwide develop E. granulosus infections. While it is rarely seen in the U.S., it may affect immigrants from endemic regions such as western China, Central Asia, South America, Mediterranean countries, and east Africa.

Hosts include domestic and wild dogs, as well as wolves, who become infected after eating organs of animals that contain hydatid cysts. Once ingested, the cysts develop into adult tapeworms, which shed eggs in their fecal matter. The tapeworm eggs can also contaminate the soil and be eaten by intermediate hosts -- livestock such as sheep, goats, pigs, and cattle.

Humans can become hosts after ingesting contaminated soil, food, or water, or due to close contact with infected animals, the authors explained. "After reaching the intestine, E. granulosus eggs hatch and embryos penetrate the intestinal wall, migrating through blood or lymphatic vessels to organs, where they develop into hydatid cysts that gradually enlarge and produce more cysts," they wrote.

The disease manifests differently in adults than it does in children, Wang and co-authors said. About 70% of infected adults develop liver cysts versus 10% to 30% who have pulmonary involvement. In children with cystic echinococcosis, the lungs are the dominant site of involvement. Other less common sites of hydatid cysts include the brain, spleen, kidney, pancreas, and heart.

The disease may present with complications when the cysts compress adjacent organs, as happened in this young patient's case; the cysts may also rupture, cause superinfection, or trigger immuno-allergic reactions to Echinococcus, such as urticaria, angioedema, and, in rare instances, anaphylaxis.

Pediatric cystic echinococcosis also differs from that in adults in terms of the rate of cyst growth, the authors noted. Pulmonary cysts that occur in children tend to increase in size at a faster rate compared with liver cysts seen in adults, which typically grow larger over the course of many years.

The size of pulmonary cysts can range from 1 cm to 20 cm, the authors said; those with a diameter of 10 cm or more are considered giant cysts. In the absence of complications, pulmonary hydatid cysts generally do not cause any symptoms. Patients "with complicated (ruptured or infected) cysts may experience cough, dyspnea, chest pain, hemoptysis, and fever. Pulmonary cyst rupture can cause cough productive of salty-tasting fluid or membrane fragments, empyema, and hydropneumothorax," Wang's group wrote.

The disease is diagnosed based on patient history, and findings from imaging, blood tests, and histologic examination. Typically, chest x-rays or CT scans will reveal cysts on the lungs, and abdominal ultrasound or CT scan will show cysts on the liver, they noted.

The diagnosis may be confirmed with blood tests that detect antibodies against Echinococcus; however, the authors cautioned that "the sensitivity and specificity of serology each vary from 60% to 90%, and the sensitivity of serology is not well defined in children." About one in four patients with confirmed cystic echinococcosis will have eosinophilia.

Factors that help determine approaches to treatment of cystic echinococcosis include the size and location of the cyst, whether there are complications, and access to equipment and medical expertise. The condition may be cured by successful surgical removal of the cyst, Wang and team said. "Other treatments include PAIR (percutaneous puncture, aspiration, injection, and reaspiration), antihelminth therapy, and watchful waiting for smaller cysts," they wrote.

Although there are few studies describing optimal drug therapy, the authors noted that in patients with hepatic cysts that are inoperable, are located in several organs, or are isolated and of small or medium size, albendazole or albendazole-praziquantel may be considered.

"Antihelminth therapy as an adjunct to surgery or interventional procedures decreased the risk of echinococcosis dissemination and recurrence," Wang and co-authors noted. After treatment, about 6.5% of patients will have a relapse.

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