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INSTRUCTIVE CASES

A case of severe monkeypox virus disease in an American child: emerging infections and changing professional values

ANDERSON, MICHAEL G. JD, MD; FRENKEL, LAWRENCE D. MD; HOMANN, SCOTT MD; GUFFEY, JENNIFER MD

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The Pediatric Infectious Disease Journal: December 2003 - Volume 22 - Issue 12 - p 1093-1096
doi: 10.1097/01.inf.0000101821.61387.a5
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Abstract

INTRODUCTION

Monkeypox virus, an orthopox virus somewhat similar to smallpox but clinically less severe, was first isolated in 1958. 1 Human disease was first described as a rare zoonosis sporadically occurring in the rain forests of Africa. 2 Until 2003 human disease was limited to Central and West Africa. Human to human spread is rare. 3 The disease is thought to originate in animals, with small rodents, especially squirrels, as the main vector. 4 In Africa the case fatality rate is 1 to 15%. 5 Immunization against smallpox (with live vaccinia vaccine) reduces the clinical severity of human monkeypox infection. 5

In late May and early June of 2003, cases of monkeypox virus disease were first recognized in the United States, mostly in the Midwest, and were associated with being bitten by or close contact with prairie dogs. 3 Clinical disease is manifested with an exanthem similar to but distinct from chickenpox caused by the unrelated varicella virus. The exanthem is also similar to but much less severe than smallpox. Approximately 100 cases of human monkeypox infection were investigated as part of this outbreak, with >25% of patients hospitalized. 4 Three of these hospitalized cases were children with moderate to severe disease. This report describes the third child and some of the clinical and professional issues surrounding the care of this child.

CASE REPORT

A school age Caucasian girl was admitted to a Midwest hospital from the emergency department after reporting 24 h of swollen, painful cervical lymph nodes, dysphagia, vomiting, difficulty breathing and an inability to eat or drink. Approximately 1 month before admission, the patient and her family had purchased a prairie dog at a Chicago “swap meet” also known as flea market. Almost immediately after the purchase, the prairie dog inexplicably became sick and died. Subsequently two other pet prairie dogs, which had shared a cage with the deceased newcomer, developed a rash around the mouth. The girl reported that the pets had been licking her fingers through the cage but denied any other direct contact. Approximately 3 weeks before the girl’s admission, a family member noted a news story associating sick prairie dogs with monkeypox. After the state department of health was notified, the family came under medical surveillance by public health officials. The family’s other prairie dogs were confiscated, euthanized and proved by PCR to be infected with monkeypox. Beginning 5 days before admission, the patient had intermittent fevers of 101°F, chills, night sweats, headaches, muscle aches and general fatigue. Three days before admission she developed flat red macules over the trunk, extremities, palms and soles. By the day of admission, the girl reported that the macules had spread all over the body, including the face, mouth and oral pharynx. On the day of admission, the patient’s swollen neck and throat pain were severe enough to prevent her from comfortably swallowing fluids, and she vomited twice that morning.

The patient had no significant past medical history, took no regular medication and reported no allergies. The family history was notable only for maternal scleroderma. Other than an unapproved cross-country family trip during the medical surveillance, the social history was not contributory.

Physical examination at the time of admission revealed an alert, active, mildly irritable child. Neurologic examination was normal, with no focal signs. A few vesicles were observed on the face, including one at the eye lash edge of the right inferior palpebral fissure, without conjunctival involvement. The tongue and peritonsillar area had a few painful vesicles. The neck was impressive for a “bull-neck” appearance resulting from 2- to 3-cm lymph nodes on each side (Fig. 1A) These were very painful to touch. There was no stridor. The macules were ∼3 to 4 mm in diameter, with some as much as 6 or 7 mm in diameter. Most notably the palms and soles had several vesicular lesions (Fig. 1, B and C). Some of the larger lesions were firm pustules, with a punctuate concavity at the center (umbilicated). The skin on the rest of the body was diffusely covered with ∼200 or more macules, some with central vesicles. (Fig. 1D) The body distribution of the lesions was more heavily weighted toward the distal portion of each extremity. A few lesions were present on the external genitalia, but the vulval mucosa was spared. The chest was clear without wheeze or other signs of distress. The rest of the examination was unremarkable.

Fig. 1
Fig. 1:
A, left cervical adenopathy and lesions of head, neck and shoulder; B, papulovesicular lesions, sole of foot; C, papulovesicular lesions, palm of hand; D, papulovesicular lesions on legs.

Laboratory data revealed an elevated peripheral white blood cell count of 17 900 cells/mm3 (absolute counts of 10 810 neutrophils, 5440 lymphocytes, 1150 monocytes, 470 eosinophils and 40 basophils). Reactive lymphocytes were also present in the peripheral blood smear, and no immature neutrophils were seen. The following day the patient’s blood count was essentially unchanged, with the exception that toxic granulocytes, Doehle bodies and vacuolated neutrophils were present. Routine serum chemistry values were normal and remained so throughout her hospitalization with the exception of protein and albumin which dropped, respectively, from 7.5 g/dl to 5.7 g/dl and from 3.5 g/dl to 2.3 g/dl. Of significance in her urinalysis was a leukoesterase of 25 white blood cells/μl, 50 mg/dl ketones and 4 mg/dl urobilinogen. Two blood cultures taken on the day of admission had no growth.

A chest radiograph was unremarkable. Radiographs of the neck showed markedly swollen soft tissues and findings in the retropharyngeal space consistent with a phlegmon. Computed tomography also demonstrated retropharyngeal phlegmon with low attenuation and was suggestive of a small abscess. The patient’s airway was patent and prominence of her adenoids was noted, as was impressive jugulodigastric lymphadenopathy. An otolaryngology consultant thought that surgical intervention was unlikely to benefit the patient. Subsequent follow-up computed tomographic scans of the neck on the second day of hospitalization showed worsening of the cervical/jugulodigastic lymphadenopathy and more retropharyngeal fluid. There was no airway narrowing.

One unexpected complication of the admission was the difficulty in finding nurses and physicians willing to care for the patient. Many declined with the explanation that they had not received smallpox vaccine, and others declined direct patient contact without explanation. Ultimately a core team composed of a pediatrician, an infectious disease consultant and several volunteer bedside nurses provided direct patient care. The nursing team included a mix of various specialties from administration, anesthesia, cardiac laboratory, pediatrics and a community volunteer who was not originally part of the hospital staff. This volunteer was a nurse who had been vaccinated for smallpox and whose credentialing was expedited so that necessary bedside care could be provided.

Clinically the patient’s agitation and discomfort continued throughout the first hospital day, 6 days after the onset of fever. The rash increased to >250 vesicles, which covered the entire body, including the face, mouth, oropharynx, chest, upper and lower extremities and the palms and soles. The numerous lesions continued to evolve from vesicles to pustules with central umbilication. Oropharyngeal pain kept the patient from taking oral fluids and solids, but intravenous diphenhydramine, lorazepam and morphine helped provide comfort.

On Hospital Day 2 the cervical lymph node increased in tenderness and dimension. The lesion became increasingly firm as the size expanded from 5 to 7 cm in diameter. Infectious disease consultants recommended intravenous ampicillin/sulbactam, 200 mg/kg/day divided every 6 h for the retropharyngeal phlegmon.

On Hospital Day 3 only five additional skin lesions were discovered. Approximately 25% of the existing vesicles had begun to form hard crusts, with most lesions in the same state of development. The patient still complained of cervical lymph node tenderness. Cidofovir had been ordered after a telephone conference with CDC experts; however, on the morning of Hospital Day 4, just before starting the hydration protocol for the cidofovir, the patient appeared remarkably improved with a mild decrease in the extent of cervical lymphadenopathy. She started to eat and drink, and no new skin lesions were noted. More than one-half of the existing skin lesions were now umbilicated, contracted and beginning to crust. Bacitracin cream was applied to the lesions on her face to ameliorate scarring.

By the fourth day of hospitalization, she was eating and drinking without difficulty and the cervical lymphadenopathy continued to shrink. Approximately 80% of the lesions were umbilicated or crusting, with a few actually falling off in the bed. On the seventh day of hospitalization, a repeat computed tomographic scan of the neck showed overall decrease in the prominence of lymphadenopathy and retropharyngeal abscess. Subsequently the patient was discharged home in stable condition.

DISCUSSION

The first case of human monkeypox virus disease was described in a 9-month-old child in 1970 in Zaire 1 year after what we now know was the last case of smallpox that was detected there. 2 This emphasizes the clinical similarities between the two diseases. It was fortunate that epidemiologic doubts led to further studies in this initial infant, who was mistakenly believed to have smallpox, and the demonstration of monkeypox was accomplished. Subsequently other cases of suspect smallpox were proved to be monkeypox.

Laboratory studies including electron microscopy, viral culture, PCR and serology have allowed for the confirmation of monkeypox viral disease in Africa since the 1980s. 5 Data derived from these African children include the characteristic clinical manifestations: the exanthema (lesions first develop on the face in one “crop,” generally evolving together from a macule to a vesicle and then to a pustule before umbilication and crusting). Most of the lesions described are ∼ 0.5 cm in diameter, and most of these African children develop palmar and plantar pox, as well as facial pox. The majority of these patients had painful oral lesions and complained of a sore throat. Cough was present in 40% of cases. Fever was usually noted a few days before onset of the rash, ranging between 101.5 and 104°F and accompanied by headache, backache, malaise and prostration. The fever usually fell after the onset of the rash.

Lymphadenopathy was a prominent symptom that usually manifested by the time the rash was noted. This is a differentiating factor between monkeypox and both smallpox and chickenpox. 5 The nodes ranged between 1 and 4 cm in diameter, were tender and most often involved cervical and submandibular areas. Subsequent suppuration was occasionally observed. The illness generally took 2 to 4 weeks to resolve with secondary bacterial infection of the skin, pneumonia, vomiting and diarrhea as the predominant complications. Corneal ulceration was seen in 4% of cases with one case of fatal encephalitis. The case fatality rate was 15% in children 0 to 4 years of age, 7% in those 5 to 9 years of age and 0% in older children and adults. In Africa vaccination with vaccinia virus decreased morbidity and mortality. 5

The CDC reported nine clinical features of US cases, 4 all of which were manifest in this child: rash, fever, chills, sweats, cough, sore throat, headache, vomiting and lymphadenopathy. One of the three reported American children had encephalopathy. The child reported in this paper showed clinical manifestations essentially identical with most cases described in Africa and, most recently, in the US. The diagnosis in this child was confirmed by electron microscopy. Although cidofovir therapy was considered for the child reported here because of anecdotal reports of benefit, she improved clinically and was discharged without specific treatment.

Globalization has resulted in the recognition of several serious emerging infectious agents in the United States during the past year including the severe acute respiratory syndrome-associated coronavirus, the West Nile arbovirus and monkeypox virus. The tempo of this infectious disease assault combined with the lack of time for the professional health care community to acquire knowledge and come to terms with the handling of these frightening diseases has uncovered an apparent change in the traditional professional values of some medical care practitioners. In this case of monkeypox infection, the admitting hospital had to go to unusual measures to find personnel who were willing to care for the patient. Such is not the public’s traditional expectation from professionals, who are expected to accept personal risk in the care of their patients. 6 Perhaps the novelty of monkeypox and other emerging infections may catch some physicians and nurses unprepared to cope with possible personal danger. Perhaps the last three decades of managed care strategies have eroded traditional values to the point that physicians have forsaken some elements of their historic professionalism. Or perhaps as nonphysician business managers have imposed themselves between physicians and their patients, doctors have adopted a “provider-customer” model for care, leaving behind the traditional “physician-patient” relationship. 6 Whatever the cause this case of an emerging infection may be an alarm to the professional community that professional values are changing and that steps need to be taken for professional remediation. 7

ACKNOWLEDGMENTS

We thank Janet Stull-Snow and Kevin Swan for technical assistance, the Winnebago County Health Department personnel for crucial input and assistance, the CDC for advice about patient management and the physicians and nurses who cared for the patient.

REFERENCES

1. Von Magnus P, Andersen EK, Peterson KB, Birch-Andersen A. A pox- like disease in cynomolgus monkeys. Acta Pathol Microbiol Scand 1959; 46: 156–76.
2. Ladnyj ID, Ziegler P, Kima E. A human infection caused by monkey-pox virus in Basankusu Territory, Democratic Republic of the Congo. Bull WHO 1972; 46: 593–7.
3. Yvan JF, Hutin R, Williams J, et al. Outbreak of human monkeypox, Democratic Republic of the Congo, 1996–1997. Emerg Infect Dis 2001; 7: 434–8.
4. CDC. CDC update: multistate outbreak of monkeypox-Illinois, Indiana, Kansas, Missouri, Ohio and Wisconsin, 2003. MMWR 2003; 52: 561–4, 589–90.
5. Jezek Z, Szczeniowski M, Paluku KM, Mutombo M. Human monkeypox: clinical features of 282 patients. J Infect Dis 1987; 156: 293–8.
6. Johnson K. Patient advocates or patient adversaries? Using fiduciary law to compel disclosure of managed care financial incentives. San Diego L Rev 1998; 35: 951.
7. Anderson MG, Freed GD, Re-professionalizing medicine: enlarging the art of professional responsibility to reclaim public trust. Presented at the University of Michigan Pediatric Research Symposium, Ann Arbor, MI, October 27, 2000.
Keywords:

Monkeypox virus disease; pediatric infectious disease; exanthem; changing professional values

© 2003 Lippincott Williams & Wilkins, Inc.