Tropical Flavivirus Infections

Roadmap - Hopefully short and sweet

• Canadian woman who doesn't have Snowshoe Hare virus
  
  
  
• American women just gets back from Brazil
  
  
  
• An American woman is misdiagnosed with flu in Boston
  
  
  
• A German who had a bad outcome

• A 26 y/o presented to the ED in Toronto in early September with fever, myalgia, and headache. Headache started 3 days earlier. It was intermittent and was accompanied by some mild diplopia. She vomited twice yesterday and had no other GI symptoms.

• She recently returned from a trip to Thailand where she had bloody diarrhea about two weeks ago that resolved in a day with administration of an unknown antibiotic. Her trip was last minute and she did not consult a travel clinic. She had not traveled abroad previously. Most of her time in country was spent trekking through the forests and rice field areas.

• Histories

  • No PMH
  • No PSH
  • No Meds
  • No allergies

• On admission

  • PE: WNL
  • Labs: WBC = 12.3, Na = 124, Everything else WNL
  • Micro: Thick and thin smears negative

• On 2nd day post-admission

  • Diminished consciousness
  • Neck stiffness
  • Drooling
  • Lower extremity stiffness

• Blood:
  • Negative for CHIKV, rabies, herpes B, Snowshoe hare virus
  • Positive for Dengue IgM, WNV (1:10 titer)
• LP: Leuks = 218, PMN = 52%, Protein = 82 mg/dL, Glucose = 78 mg/dL
  • PCR: Negative for bacterial, fungal, mycobacterial, HSV, EBV, WNV, adenovirus, and enterovirus
• Rectal Swab: Positive for Salmonella paratyphi B
• MRI: Normal

• Diagnosis is best with a PCR panel on blood (true for most flaviviruses)

  • Isolation from CSF is often unsuccessful but is useful during fulminant disease
  • There is a lot of overlap in arbo-flavivirus serologies

• No specific treatment

  • Supportive care should focus on the electrolyte abnormalities that lead to seizures

• Vaccine is available in the US by brand name Ixiaro

  • Approved in those 2 months and up (doses change with age)
  • Primary series is 2 IM injections 28 days apart (plan ahead)
  • This is an inactivated vaccine
  • No clinical efficacy data is available
  • However, other vaccines licensed in the endemic have shown dramatic reductions in infection rates

• A 47 y/o American woman presents to the ED two days after returning from a trip to Sao Paulo, Brazil with her 13 y/o son. Three days ago she began feeling acutely ill with high fever, chill, frontal headache, back pain, and muscle pain. The next day she boarded a direct flight to Chicago. During the flight, she felt weak and developed a sore throat. Yesterday, she developed non-bloody diarrhea with nausea.

• Since symptom onset she has been receiving amoxicillin and acetaminophen.

• On physical exam, she is in acute distress. No signs of bleeding and a normal neuro exam.

• Vitals are temperature of 35.6C, HR 60, BP 120/80

• What do we think she has?

• CBC and CMP

  • Platelets = 98K, WBC = 4K
  • Cr = 6.9, BUN = 151, Alk Phos = 228

• Liver Function

  • ALT/AST = 23K/49K
  • Tbili = 3.5
  • Dbili = 2.6

• Coagulation studies

  • PT = 26% normal
  • INR = 3.3
  • CRP = 13.8

• What do we think she has?

• Has been around a long time; at least until 1600s

  • Relatively easy to spot... hence the yellow

• Can occur many times annually as discrete sporadic outbreaks

  • Modelling suggests around 50 countries affected and about 100,000 severe cases annually
  • Unknown burden of mild disease
  • Currently there is an outbreak in Brazil
  • An outbreak in Angola and Uganda just stopped last semester

• Approximately 200,000 cases annually

  • Survives the dry season in mosquito eggs

• Initial infection

  • 5% to 50% of infections are asymptomatic
  • Incubation time of 3-6 days
  • Begins with fever, headache, and myalgias
  • Relatively mild initial disease with some conjunctival injections, facial flushing and bradycardia

• Some patients progress to fulminant hemorrhagic fever or hepatorenal dysfunction

• It may be easiest to distinguish this as hepatitis + hemorrhagic fever, but that occurs in a minority of patients

• Albuminuria can usually distinguish YF from other types of hepatitis

• Can diagnosis serologically but it is rife with issues

  • Lots of cross-reactivity
  • Vaccination status can make IgM positive
  • In first several days, PCR can be successful, but by the time the fulminant symptoms appear the virus is typically undetectable

• No specific treatment

  • Avoid aspirin and NSAIDS
  • Protect patient from mosquito exposure for 5 days after onset

• Vaccine is available

  • Approved for 9 months and older
  • Live-attenuated vaccine (Check contraindications)

• A 27-year-old woman was seen in the emergency department of this hospital during the summer because of myalgias and a rash. She had just returned from a trip to Turks and Caicos.

• The patient had been well until 5 days before this evaluation, when myalgias in her legs and shoulders developed, along with back pain, neck pain, and a retro-orbital headache.

• Later that day, fever occurred (temperature, 39.0°C) and was accompanied by chills, nausea, decreased appetite, and sore throat. She also noted a vaginal ulcer, ulcers on the side of her tongue, decreased taste sensation, and enlarged, tender lymph nodes in her neck and groin.

• The next morning, the patient awoke with a rash on her right forearm. The lesions were pink, pruritic, and nonpainful. Within 1 hour, the rash spread to her torso and both arms and legs.

• Her gums bled easily when she brushed her teeth, but the rash remitted.

• On the fifth day of illness, a new pruritic, erythematous rash developed, beginning on her palms and spreading to her arms, chest, abdomen, back, and legs, sparing the soles of her feet.

• The patient appeared well. The temperature was 36.4°C, the pulse 69 beats per minute, the blood pressure 135/87 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 98% while she was breathing ambient air.

• There was subtle swelling of soft tissue in the hands but no joint effusions.

• Tourniquet test was positive

• What do we have in the differential?

• In general, even a patient with DHF should not die

  • Appropriate supportive care reduces mortality 50 to 100 fold

• If they die one of two things likely happened

  • They presented way too late
  • Healthcare providers fluid overloaded them

• IVIg has not been shown to provide benefit

  • Corticosteroids provide no benefit

• Vaccines

  • One licensed in Mexico; Dengvaxia
  • Many others in development
  • Connection between cross-reactivity and DHF not well established

• A 45-year-old woman was seen in an outpatient clinic in Heidelberg, Germany for fever of up to 39°C and rash covering her trunk, arms, and legs.

• Fever had started on 2 days previously, which was 6 days after she had returned from a 3-week vacation to peninsular Malaysia and Sabah, Malaysian Borneo.

• Laboratory analyses showed a slightly elevated C-reactive protein level of 5.2 mg/L (reference range <5.0), but liver function test and complete blood count results were within reference range.

• During the next 3 days, the fever subsided, but the patient experienced a sore throat, bilateral conjunctivitis, and a burning sensation of the palms and soles. These symptoms were accompanied by swelling of the hands and increasing arthralgia of the wrists, palms, and fingers. There was no lymphadenopathy.

• Two days later, the patient experienced sudden bilateral dull and metallic hearing; in her left ear, she experienced a very short delay between a sound and her perception of the sound.

• What do we have in the differential?

• Disease

  • Mild fever, skin rash, conjunctivitis, muscle and joint pain, malaise or headache. These symptoms normally last for 2-7 days.

• Epidemiology

  • 223 Cases in US due to local transmission
  • First case of local transmission in Texas occured in Brownsville in November
  • 36,383 in US territories due to local transmission (325 from viremic blood donors)
  • In November, WHO accepted that this was likely uncontrollable
  • Currently, 84 countries have local transmission

• Diagnosis

  • First 14 days, try nucleic acid tests on serum
  • First 14 days, should always test urine with nucleic acid test
  • A positive nucleic acid test is confirmatory
  • A negative nucleic acid test does not rule out infection
  • A Zika IgM should be sent, if NAT is negative
  • IgM is postive from 4 to 90 days post infection
  • Congenital versus early infancy diagnosis is complicated and often wrong

• In summary: Testing is a nightmare, contact the state health department and CDC if you are concerned

• No specific treatment

  • Rarely an issue for adults
  • Generally, only a problem for neurotropic effects in utero
  • Many vaccines are in development

• For reproductive age people, there is extensive guidance

  • First virus since Rubella that causes cogenital deformities
  • Risk of microcephaly with first trimester is likely around 1% but could be higher
  • https://www.cdc.gov/zika/geo/countries-territories.html

• Hepatitis C Virus... should be comfortable here

• St. Louis Encephalitis

  • Mostly around bird reservoirs

• West Nile Virus

  • Could be tropical or not

• Omsk Virus

  • Found only in Russia

• Tick-borne Encephalitis

  • Many different viruses fall in here

• Kyasanur Forest disease virus

  • There is actually a vaccine for this