West African country Ghana has officially confirmed two cases of the Marburg virus, the Ghana Health Service said on July 18. The Marburg virus is a highly infectious disease similar to Ebola. 


The Ghana Health Service confirmed the two cases after two persons who later died tested positive for the Marburg virus earlier in July. This is Ghana's first outbreak of Marburg virus disease.


The two people were found to be positive for the Marburg virus on July 10. However, in order for the cases to be considered confirmed, the results had to be verified by a laboratory in Senegal, another west African country, according to the World Health Organization (WHO). 


Samples from each of the two patients were sent to the Institut Pasteur in Dakar. The two patients, who were unrelated, showed symptoms including diarrhoea, fever, nausea and vomiting.


According to the WHO, the laboratory in Senegal corroborated the results from the Noguchi Memorial Institute for Medical Research, Accra, Ghana, which suggested the illness of the two patients was due to the Marburg virus. 


One of the patients was a 26-year-old male who checked into a hospital on June 26 and died on June 27. The other person was a 51-year-old man who reported to the hospital on June 28 and died the same day. 


What Is Marburg Virus Disease?


Marburg virus disease (MVD) was previously known as Marburg haemorrhagic fever. It is a severe illness in humans caused by the Marburg virus. The Marburg virus disease has a case fatality ratio of up to 88 per cent, but can be much lower with good patient care. The case fatality rate depends on the virus strain and case management. 


Marburg virus disease can affect both people and non-human primates. 


Marburg virus disease was detected for the first time in 1967. Simultaneous outbreaks of the disease occurred in Marburg and Frankfurt in Germany, and in Belgrade, Serbia.


Both the Marburg and Ebola viruses are members of the Filoviridae family (filovirus), and cause diseases which are clinically similar. The Marburg virus is a genetically unique zoonotic RNA virus of the filovirus family. 


Both Marburg virus disease and Ebola virus disease are rare. They can result in outbreaks with high fatality rates. 


The initial outbreaks in 1967 were associated with laboratory work using African green monkeys imported from Uganda. As many as 31 people had become ill, according to the Centers for Disease Control and Prevention (CDC). Initially, laboratory workers became ill. After this, several medical personnel and family members who had cared for them started showing symptoms. As many as seven deaths were reported. 


Other regions where subsequent outbreaks and sporadic cases were reported include Angola, the Democratic Republic of Congo, Kenya, South Africa, and Uganda. 


How Is The Marburg Virus Transmitted?


The reservoir host of Marburg virus is the African fruit bat, Rousettus aegyptiacus, which belongs to the Pteropodidae family. 


According to the WHO, the Marburg virus is transmitted to humans from fruit bats and spreads among humans through human-to-human transmission.


While fruit bats infected with Marburg virus do not show obvious signs of illness, primates, including humans, who are infected with Marburg virus may develop serious disease with high mortality. 


It is not known how Marburg virus first transmits from fruit bats to humans. In 2008, two tourists who visited Uganda became infected with the Marburg virus. Unprotected contact with infected bat faeces or aerosols are believed to be the most likely routes of infection.


Human-to-human transmission can take place through direct contact to droplets of body fluids from infected persons, or contact with equipment and other objects contaminated with infectious blood or tissues.


According to the CDC, people who were infected in previous outbreaks had handled infected non-human primates or had come in direct contact with their fluids or cell  cultures. 


The Marburg virus is likely to be spread between humans in close environments and through direct contacts. Healthcare workers in a hospital can be infected through nosocomial transmission.


Direct transmission of the virus can occur through blood or body fluids such as urine, saliva, sweat, faeces, vomit, breast milk, amniotic fluid, and semen of a person who is sick with or died from Marburg virus disease. The virus may be transmitted through broken skin or mucous membranes.


Transmission can also occur through objects contaminated with body fluids from a person who is sick with or has died from the Marburg virus disease, such as clothes, bedding, needles, and medical equipment. 


Healthcare workers treating patients infected with Marburg virus disease can contract the disease if they are in close contact with the patients.


In burial ceremonies, there are chances of direct contact with the body of the deceased, leading to the transmission of Marburg. As long as one's blood contains the Marburg virus, they remain infectious.


What Are The Symptoms Of Marburg Virus Disease


The incubation period of the Marburg virus, which is the interval from infection to onset of symptoms, varies from two to 21 days.


Illness resulting from Marburg virus infection begins abruptly, with high fever, malaise, severe headache, and muscle aches.


On the third day, abdominal pain, watery diarrhoea, nausea, cramping, and vomiting may occur. Moreover, diarrhoea can persist for a week. 


At this phase, patients may have "ghost-like" drawn features, expressionless faces, deep-set eyes, and extreme lethargy, according to the WHO. 


Non-itchy rash was a feature observed in most patients during the 1967 European outbreak, between two and seven days after the onset of symptoms. 


Several patients develop severe haemorrhagic manifestations between five and seven days. Bleeding from multiple areas may occur in the fatal cases. Sometimes, traces of fresh blood are found in the patients' vomit and faeces. There could also be bleeding from the nose, vagina, and gums. A maculopapular rash, most prominent in the trunk, which includes the chest, back, and stomach, may occur around the fifth day after the onset of symptoms. A macule is a flat, reddened area of skin present in a rash, while a papule is a raised area of skin in a rash. The term maculopapular is used to describe a rash with both flat and raised parts.


Sometimes, symptoms may become increasingly severe and can include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive haemorrhaging, and multi-organ dysfunction.


Spontaneous bleeding may occur at venipuncture sites, which are the regions where intravenous access is obtained to give fluids or obtain blood samples. 


Patients can have sustained high fevers during the severe phase of illness. If the central nervous system is affected, it can cause confusion, irritability, and aggression.


In the late phase of disease, which is after 15 days, orchitis or inflammation of one or both testicles has been reported occasionally.


Death may occur between eight and nine days after symptom onset, in fatal cases, and is usually preceded by severe blood loss and shock.


How Can Marburg Virus Disease Be Diagnosed?


Clinically distinguishing Marburg virus disease from other infectious diseases such as typhoid fever, shigellosis, malaria, and meningitis can be difficult. This is because the signs and symptoms of Marburg virus disease are similar to infectious diseases such as malaria, typhoid fever, or dengue, or viral haemorrhagic fevers such as Lassa fever or Ebola. Several diagnostic methods can be used to confirm that the symptoms seen in a patient suspected to be suffering from Marburg virus disease have been caused by the Marburg virus.


These tests include antigen-capture detection tests, electron microscopy, reverse transcriptase polymerase chain reaction (RT-PCR) assay, virus isolation by cell culture, antibody-capture enzyme-linked immunosorbent assay (ELISA), and serum neutralisation test. The serum neutralisation assay is a serological test to detect the presence and magnitude of functional systemic antibodies that prevent infectivity of a virus. IgM-capture ELISA (immunoglobulin-capture ELISA) can also be used to confirm a case of Marburg virus disease within a few days of symptom onset. 


Virus isolation must be performed in a high containment laboratory with good laboratory practices. 


In order to test patients later in the course of disease or post recovery, the IgG-capture (Immunoglobulin G) ELISA should be used. 


Immunohistochemistry (laboratory method that uses antibodies to check for certain antigens in a sample of tissue), virus isolation, or PCR of blood and tissue specimens are the techniques which can be used to diagnose Marburg virus disease in deceased patients.


Since samples collected from patients are an extreme biohazard risk. Non-inactivated samples should be tested in laboratories under maximum biological containment conditions.


When biological specimens are transported nationally and internationally, they should be packaged using the triple packaging system.


What Is The Treatment For Marburg Virus Disease?


Currently, no vaccines or antiviral treatments have been approved for Marburg virus disease. However, survival can be improved through supportive care such as rehydration with oral or intravenous fluids, and the treatment of specific symptoms. Supportive therapy also includes balancing the patient's fluids and electrolytes, maintaining oxygen status and blood pressure, replacing lost blood and clotting factors, and treatment for any complicating infections. 


No licensed treatment proven to neutralise the virus is available yet. However, a range of blood products, immune therapies and drug therapies are currently under development.


Certain monoclonal antibodies that could be used against Marburg virus disease are under development. Also, antivirals such as Remdesivir and Favipiravir that have been used in clinical studies for Ebola Virus Disease could be tested to see if they are effective against Marburg virus disease. 


In May 2020, the European Medicines Agency (EMA) granted a marketing authorisation to Zabdeno (Ad26.ZeBOV) and Mvabea (MVA-BN-Filo) against Ebola virus disease. According to the WHO, the Mvabea vaccine contains a virus known as Vaccinia Ankara Bavarian Nordic (MVA), which has been modified to produce four proteins from Zaire ebolavirus and three other viruses of the Filoviridae family. 


The Mvabea vaccine could potentially protect against Marburg virus disease, but its efficacy has not been proven in clinical trials. 


How Can Marburg Virus Disease Be Prevented?


In order to control outbreaks of the Marburg virus disease surveillance, case management, and contact tracing, a good laboratory service, and safe and dignified burials are important. 


Community engagement is very important to successfully control outbreaks. People should raise awareness about the risk factors for Marburg virus disease and protective measures that individuals can take. These methods are an effective way to reduce human transmission.


If one spends too much time in a cave or mine inhabited by fruit bat colonies, they are likely to contract Marburg virus from infected bats. Therefore, researchers who visit such areas must wear cloves and personal protective equipment. 


In communities affected by Marburg virus, chances of human-to-human transmission of the disease are high. The disease can be spread through direct or close contact with infected patients. Body fluids are highly likely to spread the virus. Therefore, the activities which increase the risk of transmission should be avoided.


People should avoid close physical contact with Marburg patients, and wear gloves and appropriate personal protective equipment when taking care of ill patients at home. 


When the Marburg virus affects communities, they should take necessary action to ensure that the everyone has proper knowledge about the nature of the disease. Also, people should be informed about important steps that should be taken in the wake of an outbreak.


Secondary or person-to-person transmission can be prevented using measures similar to those used for haemorrhagic fevers. Direct physical contact with a patient suspected or confirmed to have Marburg haemorrhagic fever can be prevented using barrier nursing techniques, which include wearing of protective gowns, gloves, and masks, placing the individual in strict isolation, and sterilisation or proper disposal of needles, equipment and patient excretions. 


What Outbreak Containment Measures Should Be Taken?


Prompt, safe and dignified burial of the deceased should be carried out. Also, people who may have been in contact with someone infected with Marburg virus should be identified. Their health must be monitored for 21 days. Healthy individuals should be separated from the sick to prevent further spread of the disease. The patient should be taken good care of and must stay in a hygienic and clean environment.


Though Marburg haemorrhagic fever is a very rare disease, it has the potential to spread to other people when it occurs. Therefore, it is important to increase awareness in communities and among healthcare workers, and improve diagnostic tools. Modern means of transportation that give access to even remote areas ensure that rapid testing of samples can be conducted in disease control centres.


Who Is At Risk Of Exposure To Marburg Virus?


People may be at risk of exposure to Marburg virus if they have close contact with African fruit bats, people sick with Marburg virus disease, and non-human primates infected with Marburg virus.


Family members and hospital staff members who care for patients infected with Marburg virus and have not used proper infection prevention and control measures are among those at the highest risk for the disease.


Other people who may be at increased risk of exposure to Marburg virus include veterinarians and laboratory workers who handle non-human primates from Africa, and travellers visiting endemic regions in Africa who have contact with fruit bats.