Infectious Disease: Ocular Manifestations

Background

Ebola virus disease (EVD) was first described after an outbreak of acute viral hemorrhagic fever occurred in sub-Saharan Africa in 1976. ^, Ebola virus is one of the four viruses in the genus Ebolavirus and accounts for the majority of deaths from EVD. It is a negative-sense RNA virus that occurs in outbreaks, most recently in West Africa where it accounted for over 21,000 cases in 2014, with over 8300 reported deaths. Its ocular manifestations have not been well studied but are reported as conjunctivitis, uveitis, and subconjunctival hemorrhages.

Epidemiology

Ebola virus causes episodic outbreaks of EVD. The first was in 1976 in Sudan and Zaire, but there have been outbreaks since. In 1995, there were several hundred cases in the Democratic Republic of Congo, and in 2000, there was a similar outbreak in Uganda. The most recent epidemic is the largest yet: in 2014, there were over 21,000 reported cases and over 8300 reported deaths in West Africa, including the nations of Guinea, Sierra Leone, Liberia, Nigeria, Senegal, and Mali.

Transmission

EVD is transmitted through contact with the body fluid of the infected animal or person. There have been studies to support that it can be transmitted through droplets ^, ; thus there is known risk of airborne transmission in addition to transmission via direct contact.

Systemic Disease

After exposure to the virus, there is an incubation period that lasts from 6 to 12 days. Symptoms start abruptly with fevers, chills, malaise, vomiting, diarrhea, and myalgia. A diffuse maculopapular rash may develop after 1 week, and more severe symptoms such as altered level of consciousness and seizures may occur.

EVD was traditionally called Ebola hemorrhagic fever because earlier reports emphasized the coagulopathy related to the infection. In this latest outbreak, 20% of the patients developed unexplained hemorrhage including gastrointestinal bleeding, ecchymoses, oozing from venipuncture sites, and mucosal hemorrhages. ^,

Ocular Disease

Known ocular manifestations of Ebola include conjunctival injection, lacrimation, uveitis, and subconjunctival hemorrhage. Conjunctival injection has been reported to occur in as many as 58% of patients and usually presents bilaterally. Lacrimation can be present, but without much explanation of the etiology. Uveitis can be seen in the convalescent stage of Ebola, from anterior, to posterior, to panuveitis. The presentation of uveitis can range from mild to severe, affecting up to 40% of affected individuals. Vision loss from uveitis can come from the usual sequelae caused by severe inflammation leading to cataract, retinal disease, optic neuropathy, hypotony, and eventually phthisis bulbi.

Diagnosis

Diagnosis of EVD starts with a general evaluation of how and when the exposure occurred. ^, Symptomatic patients with history of exposure should be reported to local and state health departments, and diagnostic testing performed. Historically, enzyme-linked immunosorbent assay (ELISA) tests were performed, but the most common diagnostic test used currently is real-time polymerase chain reaction (RT-PCR). ^,

Treatment and Prevention

Treating patients with EVD requires specialty care and a multidisciplinary approach. Proper use of personal protective equipment and proper infection control and precautions are crucial to reduce the risk of spreading the disease. Supportive care is the most important measure: correcting fluid and electrolyte abnormalities, respiratory support, and other supportive measures. Currently, there is no antiviral therapy or vaccines approved for the treatment of EVD, but they are being investigated.

Background

Chikungunya is a viral infection transmitted via a mosquito vector of the Aedes genus, namely Aedes aegypti and Aedes albopictus . It is a disease mostly present in developing countries in Africa and Asia and appears to occur in epidemics followed by periods of disappearance. Symptoms start after an exposure to the chikungunya virus via mosquito vector, with an incubation period of a couple of days to a couple of weeks, and can include symptoms such as fever, intense arthritis, maculopapular rash, myalgia, fatigue, conjunctivitis, and uveitis. There is no known cure for this disease other than supportive care, and the infection may result in a chronic arthritis.

Epidemiology

Chikungunya virus is endemic to West Africa, but outbreaks have occurred in Africa, Asia, Europe, and in the Americas. In 2005, there was a major outbreak on islands in the Indian Ocean. This has been linked to an isolated outbreak in Italy, which was the first outbreak in Europe. ^, In 2006, there were over 1.4 million cases reported in India alone, not including multiple outbreaks in Indonesia, Maldives, Myanmar, and Thailand. In December of 2013, there were confirmed cases in the Caribbean. Since then, there have been multiple outbreaks in the Americas. As of early 2015, there are over 1 million suspected cases of chikungunya in the Caribbean, North, Central, and South Americas.

Transmission

As discussed earlier, transmission of this virus occurs via a mosquito vector. Both A. aegypti and A. albopictus have been implicated in this disease, with A. aegypti causing disease in the tropics, and A. albopictus spreading it in temperate climates. A. albopictus was largely responsible for the spread of this virus outside of its endemic area.

Systemic Disease

Chikungunya is derived from the word “contorted” in Kimakonde, which is the language of the Makonde, a tribe in Southern Tanzania. It is a fitting name for the disease, given that many patients are left with severe arthralgia. The muscle pain, fatigue, fever, and rash are fairly typical for a viral disease, but the distinguishing feature is the arthritis and arthralgia that can accompany the disease.

Ocular Disease

The conjunctivitis of chikungunya can mimic a typical viral conjunctivitis but can also present as an advanced uveitis. Anterior uveitis is the most common presentation and can be granulomatous or nongranulomatous. ^, The posterior segment may become involved, with a retinitis, choroiditis, optic neuritis, or neuroretinitis. ^,

Diagnosis

One should consider chikungunya in the setting of fever and arthralgia, if there is recent travel to an area with active virus activity. Fevers tend to be high grade and usually last 3–5 days. Arthralgia tends to occur a few days after fevers and affect multiple joints. There is a serum immunoglobulin test for the viral antibodies as well as RT-PCR, but viral culture is the gold standard.

Treatment and Prevention

Treatment of chikungunya is supportive care. Most of the effort for prevention has been targeting mosquitoes, as there is no commercially available vaccine against the virus. Vector controlling measures such as elimination of potential breeding sites, use of mosquito nets, and pesticides as well as education have all been instituted to help reduce the burden of this disease.

Background

WN virus is a single-stranded RNA arbovirus that causes disease via a mosquito vector. It has three defined clinical categories: asymptomatic disease, WN fever, and WN meningoencephalitis. Ocular features of this disease are uveitic in nature but can also include vasculitis, optic neuritis, and cranial nerve palsies.

Epidemiology

WN virus was first isolated from the blood of a patient in the WN province of Uganda in 1937. It gained notoriety after an outbreak in New York, in 1999 where it infected 62 people, and caused 7 deaths. Since the 1990s, there have been multiple outbreaks of WN virus infection, with severe neurologic consequences. In the United States, WN virus infections are underreported because many infected people are asymptomatic. Between 1999 and 2013, almost 40,000 cases of WN virus including 17,463 cases of neurologic disease were reported to the CDC in the United States. ^,

Transmission

Mosquitos and birds play a large role in the transmission and maintenance cycle of WN viral infections. The virus is transmitted to humans through mosquito bites, and many species have been implicated in the transmission of the virus, depending on the geography. Birds serve as amplifying hosts of the virus, while remaining mostly asymptomatic. ^,

Systemic Disease

The majority of persons with WN infections are asymptomatic. Symptoms are only seen in approximately 20%–40% of infected people. ^, In those who are symptomatic, there are two clinical courses for WN viral infection: WN fever and neuroinvasive disease.

WN fever is a self-limited disease that causes fever, headache, myalgia, and malaise and is very similar to many other viral syndromes. There are other symptoms that are reported including eye pain, nausea, vomiting, and diarrhea. This typically lasts from a few days to a couple of weeks and resolves with supportive care.

Neuroinvasive disease is much more serious and can lead to meningitis, encephalitis, and various neuropathies. There is a 10% mortality rate in patients with this type of infection. ^,

Ocular Disease

Ocular disease in WN virus infections is typically inflammatory in nature, including uveitis, choroiditis, vasculitis, and retinal hemorrhages. Multifocal choroiditis is one of the more common findings, but other types of inflammation can present, such as optic neuritis, vasculitis, and iridocyclitis.

Diagnosis

WN virus infection should be suspected in the setting of flu-like symptoms, with any neurologic symptoms during mosquito season, or if there is recent travel to an area known to have active disease. Serologic testing including checking for WN virus IgM in serum and cerebral spinal fluid (CSF) seems to be more helpful than PCR detection of viral nucleic acids.

Treatment and Prevention

Similarly to many other viral diseases, treatment is supportive care. Some treatments have been considered, including interferon alfa-2b, ribavirin, and intravenous immunoglobulin, but results have been disappointing.

Prevention of infection seems to be the best way to reduce disease burden. Mosquito control programs and personal protection measures such as mosquito repellant and mosquito nets seem to be the most effective way to decrease spread of this disease.