Ophthalmological Features of Kyasanur Forest Disease Virus (KFDV)

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Disease Entity

Kyasanur Forest Disease Virus (KFDV) is a zoonotic disease due to a single-stranded, positive-sense RNA arbovirus that is part of the Flavivirus genus within the Flaviviridae family. KFDV is the cause of Kyasanur Forest Disease (KFD), a biphasic illness which is comprised of an acute and convalescent phase with a case fatality of up to 5%. Pathological manifestations of the acute phase may include frontal headache, fever, chills, body aches, hemorrhagic pneumonitis, parenchymatic degeneration, hepatomegaly, nephrosis, thrombocytopenia, leucopenia, anemia, elevated liver enzymes, and reticulo-endothelial cell findings in the liver and spleen. The convalescent phase symptoms may include hemorrhagic fever manifestations, bradycardia, conjunctival inflammation, meningoencephalitis, coma, stiff neck, abnormal reflexes, tremors, mental disturbance, light-headedness, and confusion. This Eyewiki will emphasize the ocular findings of KFDV.[1] [2]

Modes of Transmission

KFDV is transmitted to humans from the bite of infected Haemophysalis spinigera ticks or contact with an infected animal, most commonly a sick or recently deceased monkey.[1]

Epidemiology

KFDV is endemic to south India and was first identified in Karnataka, India in 1957. During the past five decades, an incidence of 400-500 KFDV cases are reported annually.[1][2]

Pathophysiology

Although it is theorized that the ocular features of KFDV may result from the hemorrhagic nature of the virus or from an immune-mediated response, the ocular pathophysiology remains ill defined.[2]

Primary Prevention

Currently there is no licensed human vaccine protective against KFDV despite it being listed by the National Institute of Allergy and Infectious Diseases (NIAID) as a risk group 4 (i.e., causes severe human disease and is a serious hazard to laboratory workers. Presents a high risk of spread to the community and there is usually no effective prophylaxis or treatment) and NIAID Category C priority (i.e. emerging pathogen that could be engineered for mass dissemination in the future because of availability; ease of production and dissemination; and potential for high morbidity and mortality rates and major health impact) pathogen. Therefore, preventive strategies include measures against tick vector exposure and the use of long-sleeved clothing and insect repellants are strongly recommended for KFDV endemic areas.[1]

Ocular Manifestations

Ophthalmological features of KFDV may include hemorrhages in the retina, vitreous humor, and conjunctiva, opacity of the lens, keratitis, and mild iritis.1 The most common ocular finding reported is conjunctival congestion in palpebral conjunctiva accompanied by serous discharge. On fundoscopic examination, findings may include retinal and vitreous hemorrhages and less commonly, papilledema secondary to encephalitis. In addition, visual acuity less than 6/60 (Snellen 20/200) may be seen in cases from the anterior (superficial punctuate keratitis, lenticular) or posterior (vitreous, and/or retinal opacity) involvement by KFDV.[2] [3]

Diagnosis

Diagnostic testing for KFDV includes molecular tests (e.g., real time polymerase chain reaction (RT-PCR), IgG, and IgM antibody capture ELISA). Challenges with diagnosis of KFDV include the indistinguishable overlap of symptomology with other hemorrhagic fevers and the lack of a point-of-care diagnostic tool.[4][5]

Ocular Signs

Conjunctival congestion, subconjunctival hemorrhage, superficial punctuate keratitis, mild iritis, retinal superficial and deep hemorrhage, retinal hard exudates, vitreous hemorrhage, papilledema

Ocular Symptoms

Conjunctivitis, diplopia, photophobia, vision loss

Differential Diagnoses

The following illnesses should be taken into consideration for the differential diagnoses of KFDV.[1][2][5]

  • Dengue virus/Dengue Hemorrhagic Fever
  • Crimean-Congo hemorrhagic fever
  • Rift Valley Fever
  • Zika Virus
  • Yellow Fever
  • Japanese encephalitis Virus
  • West Nile Virus
  • Ebola Virus
  • Marburg Virus
  • Typhoid Fever
  • Malaria
  • Meningococcemia
  • Leptospirosis
  • Other Rickettsial infection
  • Other Viral hemorrhagic fever

Management

General management includes early intervention supportive therapy with fluid replacement.[2]

Medical Therapy

Presently there is no FDA-approved treatment for KFDV infection. Iatrogenic use of aspirin, hepatotoxic analgesics, and non-steroid anti-inflammatory drugs need be avoided in order to reduce the risk of hemorrhagic complications.[6]

Prognosis

The majority of patients with KFDV begin to recover after 14 days within a 7-14 period of remission. Although, in some cases neurologic manifestations such as defective vision, photophobia, eye pain, rigidity, tremors, mental disturbance, and severe headache may persist longer. Overall, long-term sequelae of infection are rare.[6]

Summary

KFDV can produce ophthalmic findings in the anterior (acute hemorrhagic conjunctivitis) or posterior segment (retinal hemorrhages, papilledema). There is no proven effective treatment or vaccine for KFDV. Primary prevention focuses on reducing exposure and tick bite. Travel to or from south India is the main epidemiologic risk factor.

Additional Resources

https://www.cdc.gov/vhf/kyasanur/index.html

References

  1. 1.0 1.1 1.2 1.3 1.4 Singh S, Kumar S. Ocular Manifestations of Emerging Flaviviruses and the Blood-Retinal Barrier. Viruses 2018;10: 530.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Ranjan R, Ranjan S. Ocular Pathology: Role of Emerging Viruses in the Asia-Pacific Region. Asia-Pac J Ophthalmol 2014;3: 299-307.
  3. Ocular Manifestations of Kyasanur Forest Disease (A Clinical Study). Indian J Ophthalmol.1983;31: 700–702.
  4. Shah S, Jabbar B, Ahmed N, Rehman A, Nasir H, Nadeem S, Jabbar I, Rahman Z, Azam S. Epidemiology, Pathogenesis, and Control of Tick-Borne Disease-Kyasanur Forest Disease: Current Status and Future Directions. Front Cell Infect Microbiol. 2018;8:149.
  5. 5.0 5.1 Chaubal G, Sarkale P, Kore P, Yadav P. Development of single step RT-PCR for detection of Kyasanur forest disease virus from clinical samples. Heliyon 2018;4(2):e00549.
  6. 6.0 6.1 Holbrook M. Kyasanur Forest Disease. Antiviral Res. 2012;96(3):353-362.