The Pediatric Infectious Disease Journal • Volume 33, Number 11, November 2014
Aslan et al
conjunctival injection with no exudates, tender right pre-auricular lymphadenopathy and associated right-sided facial edema. A faint erythematous macular rash was present on the abdomen and trunk. He was hospitalized and treated with ceftriaxone. A nasopharyngeal swab for a multiplex polymerase chain reaction respiratory panel (FilmArray, Biofire Diagnostics, Salt Lake City, UT) was positive for enterovirus/rhinovirus but it was negative for adenovirus. The white blood cell count was 5000 cells/μL with 36% segmented neutrophils, 20% band forms, 4% monocytes, 34% lymphocytes and 5% atypical lymphocytes. The hemoglobin was 13.4 g/dL and the platelet count was 197,000/μL. The ALT was 61U/L and AST was 72 U/L. The admission blood culture reported no growth at 5 days. The patient continued to have multiple daily fever spikes between 38.7°C and 40.3°C with chills and gentamicin was added on the 3rd day because of suspected oculoglandular tularemia. Fever persisted and on the fourth hospital day doxycycline was began for a possible Rickettsial infection. Fever resolved 24 hours after doxycycline was started and the patient was discharged home on doxycycline. Serology for B. henselae and F. tularensis were negative. R. typhi IgG was positive at a titer of 1/1024 and the IgM was positive at a titer of 1/512.
DISCUSSION Murine typhus is a zoonotic disease found in southern Texas, south eastern Gulf coast states, southern California and Hawaii. The causative organism, R. typhi is transmitted usually by the rat flea Xenopsylla cheopis after it feeds on an acutely ill rat. The fleas shed the organism in their feces and humans are infected when fecal particles enter through the broken skin surface or by inhalation of fecal material. Fleas transfer the organism to their progeny transovarialy, thus becoming a large reservoir of infection after rats.2,3 The incubation period after a flea bite is 6–14 days.4 Fever, headache, nausea, myalgia and a macular or less commonly, a maculopapular rash are the most common symptoms. The rash appears on days 4–7 of the illness and lasts 4–8 days. Diagnosis is confirmed by antibody titers demonstrating a 4-fold rise in titers tested 2–3 weeks apart by indirect fluorescence antibody testing, latex agglutination or enzyme immunoassay. Serologic tests cannot accurately differentiate murine typhus from epidemic typhus or other types of typhus without antibody cross-absorption tests. Such tests are not readily available. Immunohistochemical staining, polymerase chain reaction amplification tests and isolation of the organism from tissues can be performed at the Centers for Disease Control and Prevention. Rickettsia felis causes murine typhus-like illness. As previously mentioned, serologic tests show cross-reactivity between R. felis and R. typhi and other Rickettsial agents.3 The cat flea, Ctenocephalides felis is a vector that could have been a possible mode of transmission to our patient. Cat fleas have a higher infection rate with R. felis than with R. typhi.2 Cats, opossums and household pets infested with C. felis are important domestic modes of transmission. Doxycycline is the drug of choice for treatment of endemic typhus. The duration of treatment is suggested as at least 3 days after defervescence and for 5–10 days after clinical improvement is documented.4 B. henselae infection has been typically associated with Parinaud’s oculoglandular syndrome. Other microorganisms known to cause oculoglandular syndrome are B. quintana, Francisella tularensies, Yersinia enterocolitica, Yersinia pseudotuberculosis, Treponema pallidum, Rickettsia conorii, Listeria monocytogenes, Mycobacterium tuberculosis, Chlamydia trachomatis, Hemophilus ducreyi, Actinomyces species, Herpes Simplex type 1, Epstein Barr virus, Adenovirus, Paramyxovirus,
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Sporotrichosis, Blastomyces, Coccidiodomycosis and Paracoccidioidomycosis.1,5–8 These are, to our knowledge, the first reported cases of endemic typhus causing Parinaud’s oculoglandular syndrome. REFERENCES 1. Parentin F, Molin GD, D’Agaro P, et al. Parinaud’s oculoglandular syndrome due to herpes simplex virus type 1. Ocul Immunol Inflamm. 2007;15:139– 141. 2. Boostrom A, Beier MS, Macaluso JA, et al. Geographic association of Rickettsia felis-infected opossums with human murine typhus, Texas. Emerg Infect Dis. 2002;8:549–554. 3. Azad AF, Sacci JB Jr, Nelson WM, et al. Genetic characterization and transovarial transmission of a typhus-like rickettsia found in cat fleas. Proc Natl Acad Sci U S A. 1992;89:43–46. 4. Fergie JE, Purcell K, Wanat D. Murine typhus in South Texas children. Pediatr Infect Dis J. 2000;19:535–538. 5. Costa PS, Hollanda BV, Assis RV, et al. Parinaud’S oculoglandular syndrome associated with paracoccidioidomycosis. Rev Inst Med Trop Sao Paulo. 2002;44:49–52. 6. Martin X, Uffer S, Gailloud C. Ophthalmia nodosa and the oculoglandular syndrome of Parinaud. Br J Ophthalmol. 1986;70:536–542. 7. Pinna A. Ocular manifestations of rickettsiosis: 1. Mediterranean spotted fever: laboratory analysis and case reports. Int J Med Sci. 2009;6:126–127. 8. Charbel Issa P, Eis-Hübinger AM, Klatt K, et al. Oculoglandular syndrome associated with reactivated Epstein-Barr-virus infection. Br J Ophthalmol. 2008;92:740, 855.
ACUTE TRANSVERSE MYELITIS COMPLICATING BREAKTHROUGH VARICELLA INFECTION Aslı Aslan, MD, Zafer Kurugol, MD, and Sarenur Gokben, MD Abstract: We report a 10-year-old girl who presented with acute transverse myelitis after breakthrough varicella infection. The diagnosis was based on the development of motor weakness, paraparesis and bladder dysfunction, spinal magnetic resonance imaging findings and detection of anti-varicella zoster virus IgG antibody in the cerebrospinal fluid. This case report highlights that breakthrough varicella can result in serious complications such as acute transverse myelitis. Key Words: breakthrough varicella, transverse myelitis, varicella vaccine, acute paralysis Accepted for publications May 14, 2014. From the Department of Pediatrics, Ege University Medical Faculty, Bornova, Izmir, Turkey. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Aslı Aslan, MD, Ege University Medical Faculty Department of Pediatrics, Bornova, Izmir, Turkey. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000418
V
aricella vaccine is about 80–85% effective in preventing any varicella disease and 95% effective in preventing severe disease1 Therefore, about 15–20% of children who receive 1 dose of varicella vaccine have the potential to develop varicella disease, known as breakthrough varicella. Breakthrough varicella disease has been described as clinically milder, with fewer skin lesions, fewer symptoms and a shorter duration of illness but recent studies report that breakthrough varicella infection can result in serious complications similar to those occurring in unvaccinated individuals.2–7 We present here a 10-year-old girl with acute transverse myelitis after breakthrough varicella infection despite receiving a single dose of varicella vaccine at 12 months of age. To our knowledge, © 2014 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 33, Number 11, November 2014
there has been only 1 previously published case of postvaricella acute transverse myelitis in a vaccinated individual.8
CASE REPORT A 10-year-old girl was admitted to our hospital with the complaints of paralysis in the lower extremities and urinary retention. Sixteen days before, she had developed a papulovesicular rash consistent with varicella infection despite having received a varicella vaccine (Okavax) at 12 month of age. According to medical records, she presented with mild disease with about 20–25 skin lesions without fever. Fourteen days after the resolution of the breakthrough disease, bilateral leg paresthesias, weakness and unsteady gait developed. On examination at our hospital, she was afebrile without rash. Her vital signs were stable. Consciousness, mental status, cranial nerve and cerebellar testing were normal. Muscular motor power was normal in the upper extremities, whereas it was decreased in both lower extremities (Grade 2/5). Deep tendon reflexes were normal in the upper extremities, but were scored 3/4 in the lower extremities. Plantar responses were flexor. Diminished sensation to pain and light touch was noted below the T8 dermatome. Laboratory findings for complete blood cell count, liver enzymes, glucose, urea, creatinine, electrolytes, C-reactive protein, erythrocyte sedimentation rate and urinalysis were all normal. Serological tests for hepatitis B and C, brucellosis, cytomegalovirus, herpes simplex virus, Epstein-Barr virus and human immunodeficiency virus were all negative. Anti-varicella zoster virus (VZV) IgG and anti-VZV IgM were positive in blood. Tests for antinuclear antibodies and anti-double stranded DNA were negative. The cerebrospinal fluid (CSF) contained 10 white blood cell/ cu mm, 64 mg/dL glucose and 40 mg/dL protein. Varicella zoster virus DNA was not detected by polymerase chain reaction. AntiVZV IgG antibody in the CSF was detected using a micro enzyme immunoassay method (Euoroimmun, Germany), with a result of 4390 U/mL (normal,
Aslan et al
conjunctival injection with no exudates, tender right pre-auricular lymphadenopathy and associated right-sided facial edema. A faint erythematous macular rash was present on the abdomen and trunk. He was hospitalized and treated with ceftriaxone. A nasopharyngeal swab for a multiplex polymerase chain reaction respiratory panel (FilmArray, Biofire Diagnostics, Salt Lake City, UT) was positive for enterovirus/rhinovirus but it was negative for adenovirus. The white blood cell count was 5000 cells/μL with 36% segmented neutrophils, 20% band forms, 4% monocytes, 34% lymphocytes and 5% atypical lymphocytes. The hemoglobin was 13.4 g/dL and the platelet count was 197,000/μL. The ALT was 61U/L and AST was 72 U/L. The admission blood culture reported no growth at 5 days. The patient continued to have multiple daily fever spikes between 38.7°C and 40.3°C with chills and gentamicin was added on the 3rd day because of suspected oculoglandular tularemia. Fever persisted and on the fourth hospital day doxycycline was began for a possible Rickettsial infection. Fever resolved 24 hours after doxycycline was started and the patient was discharged home on doxycycline. Serology for B. henselae and F. tularensis were negative. R. typhi IgG was positive at a titer of 1/1024 and the IgM was positive at a titer of 1/512.
DISCUSSION Murine typhus is a zoonotic disease found in southern Texas, south eastern Gulf coast states, southern California and Hawaii. The causative organism, R. typhi is transmitted usually by the rat flea Xenopsylla cheopis after it feeds on an acutely ill rat. The fleas shed the organism in their feces and humans are infected when fecal particles enter through the broken skin surface or by inhalation of fecal material. Fleas transfer the organism to their progeny transovarialy, thus becoming a large reservoir of infection after rats.2,3 The incubation period after a flea bite is 6–14 days.4 Fever, headache, nausea, myalgia and a macular or less commonly, a maculopapular rash are the most common symptoms. The rash appears on days 4–7 of the illness and lasts 4–8 days. Diagnosis is confirmed by antibody titers demonstrating a 4-fold rise in titers tested 2–3 weeks apart by indirect fluorescence antibody testing, latex agglutination or enzyme immunoassay. Serologic tests cannot accurately differentiate murine typhus from epidemic typhus or other types of typhus without antibody cross-absorption tests. Such tests are not readily available. Immunohistochemical staining, polymerase chain reaction amplification tests and isolation of the organism from tissues can be performed at the Centers for Disease Control and Prevention. Rickettsia felis causes murine typhus-like illness. As previously mentioned, serologic tests show cross-reactivity between R. felis and R. typhi and other Rickettsial agents.3 The cat flea, Ctenocephalides felis is a vector that could have been a possible mode of transmission to our patient. Cat fleas have a higher infection rate with R. felis than with R. typhi.2 Cats, opossums and household pets infested with C. felis are important domestic modes of transmission. Doxycycline is the drug of choice for treatment of endemic typhus. The duration of treatment is suggested as at least 3 days after defervescence and for 5–10 days after clinical improvement is documented.4 B. henselae infection has been typically associated with Parinaud’s oculoglandular syndrome. Other microorganisms known to cause oculoglandular syndrome are B. quintana, Francisella tularensies, Yersinia enterocolitica, Yersinia pseudotuberculosis, Treponema pallidum, Rickettsia conorii, Listeria monocytogenes, Mycobacterium tuberculosis, Chlamydia trachomatis, Hemophilus ducreyi, Actinomyces species, Herpes Simplex type 1, Epstein Barr virus, Adenovirus, Paramyxovirus,
1196 | www.pidj.com
Sporotrichosis, Blastomyces, Coccidiodomycosis and Paracoccidioidomycosis.1,5–8 These are, to our knowledge, the first reported cases of endemic typhus causing Parinaud’s oculoglandular syndrome. REFERENCES 1. Parentin F, Molin GD, D’Agaro P, et al. Parinaud’s oculoglandular syndrome due to herpes simplex virus type 1. Ocul Immunol Inflamm. 2007;15:139– 141. 2. Boostrom A, Beier MS, Macaluso JA, et al. Geographic association of Rickettsia felis-infected opossums with human murine typhus, Texas. Emerg Infect Dis. 2002;8:549–554. 3. Azad AF, Sacci JB Jr, Nelson WM, et al. Genetic characterization and transovarial transmission of a typhus-like rickettsia found in cat fleas. Proc Natl Acad Sci U S A. 1992;89:43–46. 4. Fergie JE, Purcell K, Wanat D. Murine typhus in South Texas children. Pediatr Infect Dis J. 2000;19:535–538. 5. Costa PS, Hollanda BV, Assis RV, et al. Parinaud’S oculoglandular syndrome associated with paracoccidioidomycosis. Rev Inst Med Trop Sao Paulo. 2002;44:49–52. 6. Martin X, Uffer S, Gailloud C. Ophthalmia nodosa and the oculoglandular syndrome of Parinaud. Br J Ophthalmol. 1986;70:536–542. 7. Pinna A. Ocular manifestations of rickettsiosis: 1. Mediterranean spotted fever: laboratory analysis and case reports. Int J Med Sci. 2009;6:126–127. 8. Charbel Issa P, Eis-Hübinger AM, Klatt K, et al. Oculoglandular syndrome associated with reactivated Epstein-Barr-virus infection. Br J Ophthalmol. 2008;92:740, 855.
ACUTE TRANSVERSE MYELITIS COMPLICATING BREAKTHROUGH VARICELLA INFECTION Aslı Aslan, MD, Zafer Kurugol, MD, and Sarenur Gokben, MD Abstract: We report a 10-year-old girl who presented with acute transverse myelitis after breakthrough varicella infection. The diagnosis was based on the development of motor weakness, paraparesis and bladder dysfunction, spinal magnetic resonance imaging findings and detection of anti-varicella zoster virus IgG antibody in the cerebrospinal fluid. This case report highlights that breakthrough varicella can result in serious complications such as acute transverse myelitis. Key Words: breakthrough varicella, transverse myelitis, varicella vaccine, acute paralysis Accepted for publications May 14, 2014. From the Department of Pediatrics, Ege University Medical Faculty, Bornova, Izmir, Turkey. The authors have no funding or conflicts of interest to disclose. Address for correspondence: Aslı Aslan, MD, Ege University Medical Faculty Department of Pediatrics, Bornova, Izmir, Turkey. E-mail: [email protected]. Copyright © 2014 by Lippincott Williams & Wilkins DOI: 10.1097/INF.0000000000000418
V
aricella vaccine is about 80–85% effective in preventing any varicella disease and 95% effective in preventing severe disease1 Therefore, about 15–20% of children who receive 1 dose of varicella vaccine have the potential to develop varicella disease, known as breakthrough varicella. Breakthrough varicella disease has been described as clinically milder, with fewer skin lesions, fewer symptoms and a shorter duration of illness but recent studies report that breakthrough varicella infection can result in serious complications similar to those occurring in unvaccinated individuals.2–7 We present here a 10-year-old girl with acute transverse myelitis after breakthrough varicella infection despite receiving a single dose of varicella vaccine at 12 months of age. To our knowledge, © 2014 Lippincott Williams & Wilkins
The Pediatric Infectious Disease Journal • Volume 33, Number 11, November 2014
there has been only 1 previously published case of postvaricella acute transverse myelitis in a vaccinated individual.8
CASE REPORT A 10-year-old girl was admitted to our hospital with the complaints of paralysis in the lower extremities and urinary retention. Sixteen days before, she had developed a papulovesicular rash consistent with varicella infection despite having received a varicella vaccine (Okavax) at 12 month of age. According to medical records, she presented with mild disease with about 20–25 skin lesions without fever. Fourteen days after the resolution of the breakthrough disease, bilateral leg paresthesias, weakness and unsteady gait developed. On examination at our hospital, she was afebrile without rash. Her vital signs were stable. Consciousness, mental status, cranial nerve and cerebellar testing were normal. Muscular motor power was normal in the upper extremities, whereas it was decreased in both lower extremities (Grade 2/5). Deep tendon reflexes were normal in the upper extremities, but were scored 3/4 in the lower extremities. Plantar responses were flexor. Diminished sensation to pain and light touch was noted below the T8 dermatome. Laboratory findings for complete blood cell count, liver enzymes, glucose, urea, creatinine, electrolytes, C-reactive protein, erythrocyte sedimentation rate and urinalysis were all normal. Serological tests for hepatitis B and C, brucellosis, cytomegalovirus, herpes simplex virus, Epstein-Barr virus and human immunodeficiency virus were all negative. Anti-varicella zoster virus (VZV) IgG and anti-VZV IgM were positive in blood. Tests for antinuclear antibodies and anti-double stranded DNA were negative. The cerebrospinal fluid (CSF) contained 10 white blood cell/ cu mm, 64 mg/dL glucose and 40 mg/dL protein. Varicella zoster virus DNA was not detected by polymerase chain reaction. AntiVZV IgG antibody in the CSF was detected using a micro enzyme immunoassay method (Euoroimmun, Germany), with a result of 4390 U/mL (normal,
