An 11-Year-old Boy With Fever and Rash : The Pediatric Infectious Disease Journal

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An 11-Year-old Boy With Fever and Rash

Bégué, Rodolfo E. MD

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The Pediatric Infectious Disease Journal 42(1):p 85-86, January 2023. | DOI: 10.1097/INF.0000000000003643
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CASE

An 11-year-old boy presented to the emergency department in June 2021 with a chief complaint of fever. Seven days before admission he had developed a right temporal headache with no aura or visual changes, that improved with rest. Four days before admission, he developed decreased activity due to vague, uncomfortable leg pain mainly on his calves that worsened when walking and improved with ibuprofen. Progressively, body aches became more diffuse and generalized to include neck and left upper quadrant abdominal pain, but no nausea, vomiting, diarrhea or urinary symptoms were reported. On the day of admission, he developed fever (38.2°C), as well as red eyes and red spots on his feet and body. He had 8 dogs at home, and no cats; there was a rat problem outside the house but no rat bite was reported. He denied hiking or walking to forests, tick or flea bites; denied swimming in freshwater streams, but went in the ocean frequently. He denied COVID-19 exposure and had not received a COVID-19 vaccine. He was born preterm at 24 weeks gestational age, required the closure of a persistent ductus arteriosus; had grade II intraventricular hemorrhage, posthemorrhagic hydrocephalus, requiring ventricular assist device placement in 2009 and removal in 2013; no current medications or allergies. On admission, he was awake and alert, responsive but slow. He appeared ill, but not critical, in no acute distress. Pertinent findings included bilateral scleral injection but no eye discharge. The neck was tender posteriorly but easily mobile. Lungs and heart were normal. The abdomen was soft and depressible, with some tenderness on the left upper quadrant; the liver or spleen was not palpable. Extremities showed some myalgia but no arthralgia. He had a diffuse, faint, maculopapular rash; a few nonblanching, petechiae were noted mainly on the trunk and extremities (Fig. 1A,B). Neurologically, he was slow to respond but oriented; normal tone and muscle power; no focal deficit was noted. Laboratory investigation showed a low white blood (3100 cells/μL) and platelet (60,000 cells/μL) count with normal hemoglobin (12.6 g/dL) and lymphopenia (500 cells/μL). His serum sodium was low (129 mmol/L), with other electrolytes at normal levels and normal aspartate aminotransferase (33 U/L) and alanine aminotransferase (ALT: 18 U/L). C-reactive protein (121.2 mg/L), procalcitonin (2.16 ng/mL) and lactic dehydrogenase (418 U/L) were elevated. Urinalysis and cerebrospinal fluid analyses were normal. After admission, he developed borderline low blood pressure and tachycardia, responsive to fluids. Ceftriaxone and vancomycin were started and the infectious diseases service was consulted. A test was sent to confirm the diagnosis.

For Denouement see P. 86.

F1
FIGURE 1.:
Maculopapular rash with petechial component shown on the back (A) and lower leg (B) of a 11-year-old febrile boy. 

DENOUEMENT

(Pediatr Infect Dis J 2023;42:86)Continued from P. 85.

The differential diagnosis of a school-age child presenting in the summer with a maculopapular, petechial rash, history of multiple exposures and appearing moderately ill, is broad. It includes bacterial infections (eg, meningococcemia and leptospirosis), viral infections (eg, dengue) and rickettsiosis. While empiric antibiotics were justified at the beginning, a negative blood culture ruled out bacterial infection. Multisystem inflammatory syndrome in children (MIS-C) was also considered, given the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, persistent fever and increased inflammatory markers, but was ruled out by a negative nucleic acid amplification test and negative SARS-CoV-2 antibodies. The exposure to rodents raised the possibility of leptospirosis or murine typhus. The infectious diseases consultant believed that the combination of laboratory findings of hyponatremia, thrombocytopenia and elevated ALT favored a rickettsiosis. Doxycycline 100 mg twice daily for 7 days was recommended. Testing for Leptospira antibody IgM (Hawai’I Department of Health) was negative. Next-generation sequencing of a blood specimen (Karius Test) was positive (3977 DNA molecules/μL) for Rickettsia typhi; acute-phase serum titer for R typhi was negative (<1:64 for IgG and IgM), but a convalescent-phase titer was positive (>1:1024 for IgG and IgM) 4 weeks later.

R. typhi is the agent of murine typhus. It frequently infects rodents (rats, mice and mongoose). Fleas (mainly Xenopsylla cheopis) get secondarily infected when they bite rodents and ingest blood. R typhi then establishes in flea’s midgut and when fleas bite humans and defecate, contaminated feces can be inoculated into skin cuts or scrapes and lead to human infection; alternatively, the infection can be acquired by inhalation of dry rat feces [1]. Murine typhus is seen mainly in areas with tropical and subtropical climates. In the US, the main affected areas are southern California, Texas and Hawai’i [2]. After an incubation period of about 1–2 weeks, fever, body aches, malaise, myalgias, decreased appetite, abdominal pain, nausea and vomiting develop; some patients may present cough. The rash appears around day 5 of illness in half of the patients and is initially maculopapular, which may progress into petechia. Severe cases, requiring intensive care, are unusual and occur mainly among those with delayed treatment. Laboratory tests typically show low serum sodium, elevated ALT and a cell blood count with leukopenia, lymphopenia and thrombocytopenia. Diagnosis is mainly confirmed with the use of serological tests, with the caveat that a specimen tested during the acute phase is frequently negative and a convalescent-phase test (at least 2–3 weeks later) is needed to document seroconversion. Due to the delayed seroconversion, most cases are treated presumptively, if the epidemiology, clinical findings and laboratory results are supportive of the diagnosis. Not doing the convalescent-phase test, especially when the patient is improving, leads to underdiagnosis. More recently, molecular diagnostic tests, such as next-generation sequencing are emerging as an option [3] – even though the cost may be an issue. Treatment is with doxycycline at 100 mg (2.2.mg/kg body weight for children) twice daily for 7–10 days (at least 3 days after cessation of fever). Old reticence in the use of doxycycline in children due to potential adverse effects is now downplayed by the American Academy of Pediatrics when clinically indicated [4]. The response is usually good with prompt resolution of fever (2–3 days) and progressive recovery. Mortality is rare and estimated at 1%–4% [5]. There is no vaccine against R typhi. Prevention includes environmental and personal protective measures to avoid contact with rodents and use of repellents; pets should also be treated regularly for fleas [1,2].

Murine typhus is endemic in Hawai’i and on average 5–6 cases are described every year [6] – even though underdiagnosis or underreporting are likely. In 2002 an outbreak of murine typhus occurred in Hawai’i with 47 cases detected in 5 of the islands [7]. Most cases (72%) presented during July–October, with a wide age range (1–68 years), and 60% male. The most common symptoms were fever (98%), malaise (89%), headache (87%), myalgia (81%) loss of appetite (81%), chills (81%), arthralgia (72%), nausea (66%), vomiting (54%), backache (53%), abdominal pain (51%), stiff neck (47%) and skin rash (45%). Severe complications included acute renal failure, gastrointestinal bleed and meningitis (2 each) and encephalitis, pneumonitis, and congestive heart failure (1 each). No death was reported.

This case demonstrates the importance of a thorough history and clinical evaluation, as well as sound knowledge of local epidemiology and cooperation with local Public Health authorities for a focused and specific diagnostic approach. With expected climatologic changes and increased travel, it is anticipated that vector-borne infectious diseases may increase in the future and present in areas that are not familiar with the disease. Increased awareness is recommended.

References

1. Dasch GA, McQuiston JH. Other Rickettsia species: Rickettsia typhi. Long SS, Pickering LK, Prober CG, eds. In: Principles and Practice of Pediatric Infectious Diseases. Churchill Livingstone: 2003; 2nd Edition, Chapter 194: pp 947–948.
2. Centers for Disease Control and Prevention. Flea-borne (murine) typhus. Available at: https://www.cdc.gov/typhus/murine. Accessed February 26, 2022.
3. Centeno FH, Lasco T, Ahmed AA, et al. Characteristics of Rickettsia typhi Infections Detected with Next-Generation Sequencing of Microbial Cell-Free Deoxyribonucleic Acid in a Tertiary Care Hospital. Open Forum Infect Dis. 2021;8:ofab147.
4. American AcSademy of Pediatrics. Murine Typhus. Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. In: Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics: 2021: pp 827–828.
5. Dumler JS, Taylor JP, Walker DH. Clinical and laboratory features of murine typhus in south Texas, 1980 through 1987. JAMA. 1991;266:1365–1370.
6. State of Hawai’i, Department of Health, Disease Outbreak Control Division, Murine Typhus. Available at: https://health.hawaii.gov/docd/disease_listing/murine-typhus. Accessed February 26, 2022.
7. Centers for Disease Control and Prevention. Murine Typhus – Hawaii, 2002. MMWR Morb Mortal Wkly Rep. 2003;52: 1224–1226.
Keywords:

murine typhus; rickettsiosis; Rickettsia typhi; flea-borne infection

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