Lois Anzelowitz Levine is a freelance editor, writer, and consultant. https://www.linkedin.com/in/loislevine/

Lois Levine

 collaborate on rare infectious diseases during Rare Disease Awareness Month. 

 are collaborating on rare infectious diseases for Rare Disease Awareness Month, examining both old and new infectious diseases that health care workers need to know.

While virtually any eye disease, such as conjunctivitis, is unpleasant, other, more unusual conditions can result in serious health deficits, such as scarring and permanent loss of vision. Eric D. Donnenfeld, MD, Ophthalmic Consultants of Long Island, New York, recently spoke with 

® about 3 rare eye conditions that can also be highly infectious. 

“Infections to the eye vary significantly based on their location,” says Donnenfeld. “On the surface of the eye or the cornea, the infections that are rare and highly infectious are mostly viral. One of these, and the most infectious form of pink eye, is called epidemic keratoconjunctivitis (EKC).” 

This highly contagious infection, caused by an adenovirus pathogen, is found on the front surfaces of the eye and, because it is viral, offers no specific treatment. Symptoms can resolve in about 2 weeks, but hygienic practices are key to stopping the infection from spreading to other people. “This infection spreads very quickly, and patients who, for example, touch their eye, then a doorknob, can transmit it to the next person who touches that doorknob and then rubs their eye,” Donnefeld says. Symptoms include eyes turning beet red (it usually infects both eyes), with membranes on the conjunctiva that can then cause scarring.

According to Donnenfeld, “The cornea can have subepithelial infiltrates that can cause a permanent loss of vision: this tends to happen in highly epidemic clusters that occur from time to time around a particular geographic area.” 

Seven years ago, an outbreak of EKC was discovered in an eyecare clinic in Los Angeles, California. At the time, the CDC reported, “On June 22, 2017, the Los Angeles County Department of Public Health (LAC DPH) was notified of seven patients who were seen at an eye care clinic on June 8, 2017, and later developed symptoms of epidemic keratoconjunctivitis (EKC). EKC is a contagious, severe form of viral conjunctivitis that can cause pain and blurred vision for up to 4 weeks.”

Patients with EKC are generally treated with topical corticosteroids to control the inflammation and reduce the scarring, notes Donnenfeld, and while the disease can resolve itself in 1 to 2 weeks, proper hygiene is essential to prevent the spread. “Patients need to avoid contact with other individuals, wash their hands frequently, and, of course, follow up with an eye doctor for potential anti-inflammatory therapy.”

Another unusual eye disease of note is herpes simplex keratitis. While herpes simplex virus (HSV) is, of course, a well-known condition that can affect the mouth and genital areas, “ocular herpes is much more rare, occurring usually in one eye. It usually presents with classic dendritic lesions with terminal bulbs,” Donnenfeld says. Recurrent activations within the sensory ganglion can result in corneal scarring, necrosis, and decreased corneal sensation, all of which can result in vision loss. 

“Although not terribly contagious, once a patient has contracted HSV, it can reoccur in that same patient,” says Donnenfeld. It can also be transmitted through someone with the infection, so avoidance of direct contact with lesions and secretions of a patient with active HSV is key. Treatment is usually topical and/or oral antiviral therapy, such as valacyclovir and ganciclovir. 

For patients with recurrent ocular HSV, long-term oral antiviral therapies of valacyclovir are recommended. “If untreated, herpes of the eye can cause permanent scarring, with loss of vision: these patients need to be monitored very carefully,” warns Donnenfeld.

According to the American Academy of Ophthalmology, risk factors for the development of this disease include direct contact with infected secretions or lesions. In contrast, reactivation of the disease includes triggers such as fever, sunlight, trauma, heat, stress, COVID-19 infection, and COVID-19 vaccination.

While generally also rare, other eye infections can occur after surgery. “These, thankfully, are very uncommon but worth discussing. The most common surgeries performed in ophthalmology are cataract and Lasik surgeries,” says Donnenfeld. In Lasik surgery, a flap is made in the cornea, and it has been shown that, despite the use of prophylactic antibiotics, patients may develop infections in the cornea, which, if left untreated, go on to significant scarring and loss of vision that can even require a corneal transplant.”

These infections are most commonly due to gram-positive organisms such as methicillin-resistant 

 or atypical mycobacterium (late onset). The immediate treatment is to lift the flap and irrigate, culture, and then initiate broad-spectrum antibiotics, sometimes with possible flap amputation for recalcitrant cases. Treatment includes a topical fluoroquinolone monotherapy or a combination therapy of fortified antibiotics, such as cefazolin and tobramycin or gentamicin. The frequency of these drops depends on the severity of the case, and “when treated effectively, these patients usually do very well,” says Donnenfeld.

Endophthalmitis is a rare but serious postoperative condition of cataract surgery, which can result in loss of all light perception in a patient. It is usually contracted from bacteria from the patient’s ocular surface. Preoperative risk factors included conjunctivitis, contact lens wear, and recent immunosuppressive treatment. Proper hand washing and proper use of sterile gloves, face masks, and gowns during surgery can significantly reduce the chance of infection as well. Intracameral injection of the antibiotic cefuroxime after cataract surgery has been noted to cause a reduction in endophthalmitis.

Finally, another form of rare eye disease is related to contact lens use, which has a higher risk for keratitis (the infection of the cornea, also called corneal ulcers). Viruses, bacteria, fungi, or parasites are more likely to invade the eyes when contact lenses are worn for too long or there has been poor adherence to wearing of the lenses, and most likely from gram-positive organisms. 

When these ulcers occur in the visual axis, they can cause permanent loss of vision and possibly the need for corneal transplantation. The most common risk factors for these ulcers are poor hygiene and overnight wear,” says Donnenfeld. Here, common sense prevails; contact lens wearers should wash their hands thoroughly when removing their contact lenses; they should be removed at the end of the day, or however, a health care practitioner has recommended. 

“Daily wear of contact lenses with good hygiene reduces the risk of these infections. These infections should be cultured and treated with broad-spectrum antibiotic therapy,” says Donnenfeld.

References
1. OYong K, Killerby M, Pan CY, Huynh T, Green ND, Wadford DA, Terashita D. Outbreak of epidemic keratoconjunctivitis caused by human adenovirus type D53 in an eye care clinic—Los Angeles County, 2017. MMWR; 67(48)1347-1349. doi:10.15585/mmwr.mm6748a4

2. Nijm LM. Herpes simplex epithelial keratitis. American Academy of Ophthalmology. March 6, 2023. Accessed February 18, 2024. https://eyewiki.aao.org/Herpes_Simplex_Epithelial_Keratitis

3. Niyadurupola N, Astbury N. endophthalmitis; controlling infection before and after cataract surgery. 

Articles

Eric D. Donnenfeld, MD, discusses 3 uncommon yet highly infectious eye diseases, emphasizing the importance of timely treatment and preventative measures.


What You Need to Know About 3 Rare Infectious Eye Diseases

Infection Control Today's Bug of the Month

Bug of the Month helps educate readers about existing and emerging pathogens of clinical importance in health care facilities today. Each column explores the Bug of the Month's etiology, the infections it can cause, the modes of transmission, and ways to fight its spread. The pathogen profiles will span bacterial, viral, fungal, and parasitic species. We encourage you to use Bug of the Month as a teaching tool to help educate health care personnel and start a dialogue about microbiology-related imperatives.

Bug of the Month helps educate readers about existing and emerging pathogens of clinical importance in health care facilities today. 

Bug of the Month: I Like Swimming in Water and Popping Up in Food

Laboratory: ©Imaging L - stock.adobe.com

It’s a great day for mRNA technology, particularly in the field of infectious diseases. Today, Moderna announced it had met its primary endpoints in a phase 3 trial for the company’s influenza vaccine, mRNA-1010. The vaccine had generated a powerful response against all 4 influenza virus strains compared to traditional influenza shots in late-stage trials.

Moderna has recently shows positive clinical results with a number of vaccines in its pipeline, including the completion of a biologics license application for RSV (mRNA-1345); completion of enrollment in its adult phase 3 trial of mRNA-1647, a vaccine for cytomegalovirus (CMV); and a phase 3 trial of mRNA-1283, the next COVID-19 vaccine.

The company is taking advantage of its vast research and development in mRNA technology to add to its robust pipeline that includes clinical benefits for cancer, 3 different rare diseases, and a number of infectious disease vaccines. Six of the company’s programs are in late-stage development, and Moderna plans on doubling its number of programs in phase 3 by 2025, launching up to 15 products in 5 years across cancer, rare disease, and infectious diseases.

On September 11, 2023, the FDA approved a supplemental biologics license application for the COVID-19 vaccine Moderna, now called Spikevax, for persons aged 12 years and older, with emergency use authorization in infants and children aged 6 months to 11 years.

For seasonal influenza, mRNA-1010 vaccine has demonstrated safety and tolerability profiles across all clinical trials, including 3 phase 3 trials, and independent data and safety monitoring boards have raised no concerns.

Moderna continues to work on a number of other influenza vaccine candidates that include additional hemagglutinin (HA) antigens for broader coverage of influenza A strains, as well as a candidate that incorporates HA and neuraminidase antigens to target proteins found in the influenza virus lifecycle, to decrease the potential of viral antigenic escape (mRNA-1020 and mRNA-1030).

Additionally, the company is working on a number of combination vaccines for influenza/COVID-19, and influenza/RSV.

Other viruses that Moderna is working on to develop vaccines for include the Epstein Barr virus; the herpes simplex virus; varicella zoster virus; the norovirus; and HIV.

Reference
Moderna expans the field of mRNA mkedicine with positive clinical results across cancer, rare disease, and infectious disease. News release; Moderna. September 13, 2023. Accessed September 13, 2023. https://investors.modernatx.com/news/news-details/2023/Moderna-Expands-the-Field-of-mRNA-Medicine-with-Positive-Clinical-Results-Across-Cancer-Rare-Disease-and-Infectious-Disease/default.aspx#:~:text=Expanding%20the%20Field%20of%20mRNA%20Medicine&text=The%20Company%20has%20advanced%20a,1345%2C%20mRNA%2D1010).

Besides its influenza pipeline, mRNA technology is helping this pharmaceutical company create a number of new vaccines for cancer, rare diseases, and infectious diseases.

Moderna’s Vaccine Showing Robust Response Against 4 Influenza Strains

Coronavirus COVID-19 macro simulation: ©Oz-stock.adobe.com

(This article was originally published by our sister publication, 

A 21-year-old woman was admitted to the neonatal intensive care unit (NICU) at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center in Florida hospital at 27 weeks of gestation, diagnosed with pneumonia and SARS-CoV-2. Her infant son was delivered via Cesarean section at 32 weeks of gestation. At the time of birth, the mother was negative for COVID-19. The male infant, born with Apgar scores of 4 and 7 at 1 and 5 minutes, displayed seizures and respiratory difficulty, requiring intubation and ventilation. The infant remained in the hospital for 3 months, then discharged, diagnosed with a seizure disorder and microcephaly. Although the seizures resolved, the infant was readmitted several times because of failure to thrive. At 13 months, the child was admitted to the emergency department (ED) for an upper respiratory infection, treated, and discharged. Three days later, the mother found her son unresponsive in bed; paramedics were called and found the child in cardiac arrest. He died shortly thereafter. The autopsy findings included reduction in brain weight and cerebral white matter volume, along with virus throughout the brain.

The second mother gave birth at 39 weeks to a Hispanic female. The 20-year-old mother had been diagnosed with asymptomatic COVID-19 in the second trimester. At the time of delivery, she again tested for (asymptomatic) COVID-19, as well as clinical chorioamnionitis. The infant had Apgar scores of 4 and 6 at 1 and 5 minutes and required nasal continuous positive airway pressure for apnea. She was given antibiotics for presumptive sepsis. At 16 hours of age, the baby developed clinical seizures but no virus or bacteria. At 4 days of age, MRIs revealed diffuse restricted diffusion. The child was discharged at 5 weeks, but there were multiple readmissions for seizures and respiratory disorders. Her exam at 1 year showed microcephaly, an abnormal neurologic examination, and significant neurodevelopmental delay.

Both infants had placentas that revealed thrombosis, recanalization of stem villous vessels, and stromal fibrosis, and increased stromal karyorrhexis of terminal villi, all pointing to high-grade fetal vascular malperfusion. COVID-19 spike proteins were detected in both placentas.

“To our knowledge, this is the first time that neonates born of mothers who tested positive for COVID-19 presented with a neonatal clinical course mimicking hypoxic ischemic encephalopathy of the newborn,” noted the study. Both placentas and brains showed evidence of COVID-19 infections, with the placentas displaying alterations in inflammatory and oxidative stress markets.

Investigators concluded that midtrimester maternal COVID-19 infection can infect the infant’s placenta and fetal or infant brain, triggering inflammatory events in both placenta and fetus, which can be associated with critical brain injury and progressive neurological sequelae. Researchers urge for future studies to assess the impact of timing of in uteroSARS-CoV-2 on placental inflammation and long-term consequences of the infant brain.

Benny M, Bandstra ES, Saad AG, et al. Maternal SARS-CoV-2, placental changes and brain injury in 2 neonates. 

Investigators studied 2 infants experiencing seizures, small head size, and developmental delays born of mothers who had contracted COVID-19 during pregnancy.

New study shows COVID-19 infections in 2 pregnant women caused brain damage in newborns

The FDA has just approved a booster dose of the Pfizer-BioNTech COVID-19 vaccine for children aged 6 months through 4 years. The booster dose must be administered at least 2 months after the competition of the primary vaccination, with 3 doses of the single strain vaccine.

"This is fantastic news," notes Tina Tan, MD, FAAP, FIDSA, FPIDS, editor-in-chief of 

®. "This will allow us to provide optimal protection to the pediatric population aged between 6 months to 4 years against COVID disease and the current subvariants that are circulating."

Kevin Kavanagh, MD, founder and board chairman of Health Watch USA, and  

’s Editorial Advisory Board member, agrees. “Even though children are at a much lower risk for severe disease, there is significant concern that they can spread the virus to others. In Sweden, early on in December 2020, 75% of the nonhealth care outbreaks 

were in elementary (45%), nursery (20%), and grammar (12%) schools

. In addition, children can still develop long COVID along with severe disease. According to findings in a systematic review and meta-analyses by 

 long COVID can develop in 25% of children, with the most prevalent manifestations being mood symptoms, fatigue, and sleep disorders.”

Children of this age group who received the first 2 doses of the monovalent Pfizer-BioNTech COVID-19 vaccine should have completed their 3-dose primary series with the Pfizer-BioNTech COVID-19 vaccine, bivalent. These children would not be eligible for a booster dose of a bivalent vaccine, as they should already have protection against serious COVID-19 consequences. This authorization targets the children who completed their 3-dose primary vaccination series with the monovalent Pfizer-BioNTech COVID-19 vaccine before the Pfizer-BioNTech COVID-19 vaccine, bivalent was authorized to provide the third dose in the 3-dose primary series.

The FDA decided on this approval from several clinical studies, including one which evaluated primary vaccination with the monovalent Pfizer-BioNTech COVID-19 vaccine in children aged 6 months and older; those which evaluated booster vaccination with monovalent Pfizer-BioNTech COVID-19 vaccine in children aged 5 years and older; a study that looked at a booster dose with Pfizer-BioNTech’s investigational bivalent COVID-19 vaccine (original and omicron BA.1) in those greater than 55 years of age; and postmarketing safety data with the monovalent Pfizer -BioNTech COVID-19 vaccine and Pfizer-BioNTech COVID-19 vaccine, bivalent, among other studies. Safety data accrued with the investigational bivalent vaccine and with the monovalent Pfizer-BioNTech COVID-19 vaccine was relevant to the Pfizer-BioNTech COVID-19 vaccine bivalent because the vaccines are created in the same way.

Additionally, the Pfizer-BioNTech COVID-19 vaccine, bivalent, includes an mRNA component that corresponds to the original virus strain and provides an immune response that is protective against COVID-19 and an mRNA component corresponding to the omicron variant BA.4 and BA.5 lineages. This component provides robust protection against the Omicron variant of COVID-19.

The bivalent booster is beneficial, Kavanagh explains. "SARS-C0V-2 can not only cause acute disease but also Long COVID. In addition, there are concerns regarding long-term cardiac disease and 

 which manifests with respiratory syncytial virus and streptococcal infections. Thus, bivalent boosting of children should be strongly considered to help avoid these complications and possibly mitigate the spread to caregivers. Because of possible immune imprinting concerns, using a bivalent formulation for initial vaccination and boosting is important. The bivalent formulation for the initial vaccine doses is not yet available.”


Coronavirus (COVID-19) update: FDA authorizes bivalent Pfizer-BioNTech COVID-198 vaccine as booster dose for certain children 6 months through 4 years of age. US Food & Drug Administration. March 15, 2023. Accessed March 15, 2023. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-bivalent-pfizer-biontech-covid-19-vaccine-booster-dose?utm_medium=email&utm_source=govdelivery

Pfizer's COVID-19 vaccine must be administered at least 2 months after the primary vaccination series.     