Lujo Hemorrhagic Fever (LUHF) Explainer: Cause, Outbreak, Symptoms, Diagnosis, and Treatment

History

Lujo hemorrhagic fever was first discovered during a small outbreak in 2008 in Johannesburg, South Africa [4]. In the same year, the National Health Laboratory Service (NHLS) and the National Institute for Communicable Diseases (NICD) in South Africa isolated the pathogen in cooperation with other international scientific partners. 

They proposed the name Lujo to acknowledge the viral infection’s association with Lusaka and Johannesburg, the cities where cases were initially reported [5]. While rodents are believed to be the primary reservoir for the virus, there is no definitive proof to confirm this [6].

Epidemiology

Most viruses that cause hemorrhagic fevers in humans are usually spread by rodents or arthropods. Occurrence is confined to regions where these hosts are present in large numbers, including Africa, America, Asia, Europe, and certain islands in the Pacific. 

Globally, there has only been one Lujo hemorrhagic fever outbreak. The disease is endemic to Africa, and the first case was reported in Lusaka, Zambia [7,8]. The Lujo outbreak affected five patients who were between the ages of 33 and 47 years. Four of these patients were female, and one was male. Four, including the male, died within 10 to 13 days after the onset of symptoms. This single case led to a fatality rate of 80%. 

In general, laboratory workers, field workers, and healthcare professionals, as well as the sexual partners of members of these groups, are at greater risk of getting a Lujo infection [8]. The detailed epidemiology of the five Lujo cases (see below) shows the devastating effect emerging infectious diseases can have on frontline healthcare workers. 

• Case 1: The first person diagnosed with LUHF was a 36-year-old Caucasian female from Zambia, Africa. She lived on the outskirts of Lusaka, Zambia on a farm with horses, dogs, and cats. The farm had a high rodent population. Signs of illness began with a fever, muscle pain, sore throat, and severe headache that worsened within a few days. The infected individual fell into a coma and was admitted to a hospital in Johannesburg after 11 days of being sick. She died two days later. 
• Case 2: The second person diagnosed with LUHF was a 33-year-old Caucasian paramedic. This individual came in contact with the first patient when transferring her from Zambia to South Africa. The paramedic also intubated the patient. He died on the 12th day of his illness. This patient was admitted to the same hospital as the first patient.
• Case 3: The third patient was a 33-year-old Black nurse who took care of the first patient for nine days. She turned and cleaned the patient. She died on the 10th day of her illness after a similar clinical sequence.  
• Case 4: The fourth patient was a 38-year-old Black female who worked as a cleaner in the hospital where the first patient was admitted. Although she could not recall being exposed to the infected person’s bodily fluids, she fell ill 13 days after cleaning the patient’s room. She also had a history of advanced human immunodeficiency virus infection. She died on the 10th day of her illness.
• Case 5: A 47-year-old Caucasian woman working as an ICU nurse cared for a second patient and became the fifth person infected with the Lujo virus. She was exposed to the vomit and blood of the infected person. She was the only person infected with Lujo to recover. She developed non-scarring alopecia, which resolved four months later. However, she continues to suffer from long-term neurologic complications, such as anxiety, mood fluctuations, peripheral neuropathy, myopathy, and tremors [4]. 

Some other deadly viral hemorrhagic fevers include Crimean-Congo hemorrhagic fever (CCHF), Dengue fever, Ebola hemorrhagic fever (EHF), Hantavirus-related infections, Marburg hemorrhagic fever (MHF), lymphocytic choriomeningitis (LCM) (caused by the lymphocytic choriomeningitis virus [LCMV]), and Lassa fever (LF) [7].

How is it spread?

Lujo hemorrhagic fever can spread from person to person. People can get infected in the following ways:

• Inhaling the aerosolized virus from the urine or feces of infected rodents.
• Being in direct contact with the urine or feces of infected rodents by touching contaminated surfaces or clothes [9].
• Contacting the urine or semen of an infected person (people infected with arenaviruses excrete the virus in urine or semen for weeks after recovery) [10].

Biology of the disease

Not much is known about Lujo infections, but all viral hemorrhagic fevers do have something in common. During the infection, the viruses enter the body and begin replicating within macrophages and dendritic cells, the first line of defense in the immune system. 

In response to the viral attack, macrophages release cytokines and chemokines into the bloodstream. This process is normal in small doses; however, when too many of these signaling proteins are released, the process morphs into a cytokine storm — a vicious cycle of immune activation and inflammation. Cytokine storms can lead to widespread damage to tissues and organs and cause severe illness, sepsis, and even death. 

Arenaviruses can also trigger mechanisms that cause blood clots throughout the body and block smaller blood vessels. When impaired, dendritic cells can cause excessive lymphocytic apoptosis (cell death of immune cells) [7]. Infected individuals then become more susceptible to infections and chronic conditions.

Symptoms

Based on the limited clinical information described in the five patients, the incubation period of LUHF is between 7 and 13 days. The sickness in these first and only victims of the disease began with a fever, headache, and muscle pain. As the disease progressed, infected individuals experienced the following symptoms: 

• Rashes on the face and body
• Swelling on the face and neck
• Sore throat
• Diarrhea

Other clinical presentations included:

• Low white blood cell count
• Low blood platelet count
• Elevated liver function test results

Patients who died due to the illness experienced rapid deterioration with respiratory distress, neurological symptoms, and circulatory collapse.

Pregnant women face another risk: miscarriage. Unlike other arenaviruses, the Lujo virus has the potential to enter the fetus through the mother [11].

Diagnosis

During the 2008 outbreak, clinicians made epidemiological links between patients, but because it was an unknown virus, the diagnosis was initiated only after the last patient fell sick [6]. Blood samples of patients were collected 2 to 13 days after the disease onset to isolate the virus. The virus was also isolated from the liver tissues of individuals who had died from the illness.

A complete genomic analysis was done at NICD and NHLS in Johannesburg using RT-PCR, antigen detection, antibody detection, and enzyme-linked immunosorbent assays. Serologic diagnosis using indirect immunofluorescent assay and ELISA was also performed. These tests were effective in detecting the pathogen [4,12].

Treatment

Since there were only five cases, there was no uniformity in the treatment given to those infected by LUHF in 2008. Patients were treated in three different hospitals and received supportive care [6]. 

The supportive care included: 

• Keeping the patient hydrated by providing fluids (oral and intravenous).
• Providing sedation.
• Managing shock.
• Administering medications to relieve pain.
• Following preventive measures for patients with bleeding disorders.
• Performing blood transfusions when necessary.
• Providing convalescent plasma therapy to reduce mortality [10].
• Using ribavirin, an antiviral drug, to prevent disease progression. Clinicians believe that the rapid use of ribavirin may have helped the last patient survive [6].

Prevention

The following are a few preventive measures to protect against LUJV infections (bearing in mind that this information is based on the limited knowledge gained from only five cases):

• Using rodent-control measures in areas of high infestation. Strategies include sealing holes in doors, walls, and other entrances to prevent rodents from entering the house or property. Also, placing rodent traps in buildings may help. 
• Cleaning up food waste and keeping all food in closed containers or bins [13,14]. 
• Wearing personal protective equipment while handling people suspected or confirmed to be infected by LUJV [13].

The CDC recommends the following precautions for people living in places endemic to VHFs (viral hemorrhagic fevers) in general:

• Avoiding close contact with people infected or suspected to be infected with VHF.
• Avoiding contact with animals that are dead or sick.
• Wearing personal protective equipment, such as masks, gowns, gloves, and face shields, especially while handling people infected or suspected to be suffering from VHF.
• Sterilizing needles and other medical equipment properly.
• Washing hands regularly with soap and water. 
• Abstaining from eating the meat of wild animals, primates, or rodents [15]. 

There are still so many unknowns when it comes to the Lujo virus. But what we do know about it is a reason for extreme caution. The virus can cause severe illness and death and is similar to other deadly hemorrhagic fevers with regard to how it infects people. It is most likely spread by rodents (a taxonomic order of mammals known to carry and transmit many other diseases to humans). 

All these factors can serve as a wakeup call for rodent-infested regions to make the following proactive measures:

• Raise awareness about the Lujo virus.
• Educate frontline clinicians about detecting signs and symptoms.
• Implement preventive measures.
• Report suspected and confirmed cases to public health authorities.

Meanwhile, while hemorrhagic fever infections are not common, they are potential bioterrorism agents because they can cause widespread damage and panic. Most arenaviruses have no treatment, cure, or vaccine. Carrying out epidemiological research is a vital diagnostic tool that helps public health officials better prepare for outbreaks. It may even help them prevent the next global pandemic.

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