Marburg Virus Disease

 

Shanees. E

Vice Principal, Manoj Jain Memorial College of Nursing Science and Research Center, Satna, Madhya Pradesh.

 

ABSTRACT:

Marburg virus disease (MVD) is a rare but severe hemorrhagic fever which affects both people and non-human primates. MVD is caused by the Marburg virus, a genetically unique zoonotic (or, animal-borne) RNA virus of the filovirus family¹. The six species of Ebola virus are the only other known members of the filovirus family. Marburg virus was first recognized in 1967¹. Two fatal cases of Marburg virus disease (MVD) were reported from Ashanti region, Ghana. On 28 June 2022, these cases were notified to health authorities as suspected viral hemorrhagic fever (VHF) cases and tested positive for Marburg virus on 1 July 2022². The reservoir host of Marburg virus is the African fruit bat, Rousettus aegyptiacus. Marburg virus is the causative agent of Marburg virus disease (MVD), a disease with a case fatality ratio of up to 88%, but can be much lower with good patient care. Marburg and Ebola viruses are both members of the Filoviridae family (filovirus). Though caused by different viruses, the two diseases are clinically similar¹. The incubation period (interval from infection to onset of symptoms) varies from 2 to 21 days². Many patients develop severe haemorrhagic manifestations between 5 and 7 days, and fatal cases usually have some form of bleeding, often from multiple areas. It can be difficult to clinically distinguish MVD from other infectious diseases such as malaria, typhoid fever, shigellosis, meningitis and other viral haemorrhagic fevers. Currently there are no vaccines or antiviral treatments approved for MVD². However, supportive care – rehydration with oral or intravenous fluids – and treatment of specific symptoms, improves survival. Healthcare workers caring for patients with suspected or confirmed Marburg virus should apply extra infection control measures to prevent contact with the patient’s blood and body fluids and contaminated surfaces or materials such as clothing and bedding².

 

 

INTRODUCTION:

Marburg virus disease (MVD), formerly known as Marburg haemorrhagic fever, is a severe, often fatal illness in humans. The virus causes severe viral haemorrhagic fever in humans. Marburg virus disease (MVD; is a viral hemorrhagic fever in humans and primates caused by either of the two Marburgviruses: Marburg virus (MARV) and Ravn virus (RAVV). Its clinical symptoms are very similar to those of Ebola virus disease (EVD).

 

 

In 1967, two outbreaks of VHF occurred simultaneously in Marburg, Germany, and in Belgrade, Serbia (historically Yugoslavia) among laboratory workers in Europe working with tissues of African green monkeys imported from Uganda, as well as among medical personnel who cared for the laboratory workers. Nine people of the 37 cases died, with some cases spreading through household or nosocomial contact. MARV was named after the German city where it was first characterized³. In 2022, three cases were reported in the Ashanti region of Ghana⁴.

 

What is Marburg Virus Disease?

Marburg virus disease is a highly virulent disease that causes haemorrhagic fever, with a fatality ratio of up to 88%.³

 

Marburg virus disease (MVD) is a rare but severe hemorrhagic fever which affects both people and non-human primates². MVD is caused by the Marburg virus, a genetically unique zoonotic (or, animal-borne) RNA virus of the filovirus family³.

 

Epidemiology:

In 1967, two outbreaks of VHF occurred simultaneously in Marburg, Germany, and in Belgrade, Serbia (historically Yugoslavia) among laboratory workers in Europe working with tissues of African green monkeys imported from Uganda, as well as among medical personnel who cared for the laboratory workers. Nine people of the 37 cases died, with some cases spreading through household or nosocomial contact. MARV was named after the German city where it was first characterized. The largest outbreak to date, in Uige Province, Angola (2004–2005) resulted in 374 cases and 329 deaths (case fatality rate 88%)⁵. Two fatal cases of Marburg virus disease (MVD) were reported from Ashanti region, Ghana. On 28 June 2022, these cases were notified to health authorities as suspected viral hemorrhagic fever (VHF) cases and tested positive for Marburg virus on 1 July 2022. An outbreak of MVD may represent a serious public health threat as it is severe and often fatal⁴.

 

The Pathogen:

Marburg viruses are filamentous, enveloped, single-stranded, negative-sense RNA viruses that belong to the family Filoviridae, genus Marburgvirus. There is a single species Marburg marburgvirus, that includes two viruses: Marburg and Ravn virus with approximately 20% genetic divergence⁵

 

Transmission:

The virus spreads through direct contact (such as through broken skin or mucous membranes in the eyes, nose, or mouth) with¹:

·       Blood or body fluids (urine, saliva, sweat, feces, vomit, breast milk, amniotic fluid, and semen) of a person who is sick with or died from Marburg virus disease, or

·       Objects contaminated with body fluids from a person who is sick with or has died from Marburg virus disease (such as clothes, bedding, needles, and medical equipment).

·       Semen from a man who recovered from MVD (through oral, vaginal, or anal sex). The virus can remain in certain body fluids (including semen) of a patient who has recovered from MVD, even if they no longer have symptoms of severe illness. There is no evidence that Marburg virus can spread through sex or other contact with vaginal fluids from a woman who has had MVD¹.

Clinical Features and Sequelae:

The incubation period lasts from five to 10 days (range 3–21 days), and is most likely related to the infectious dose and the route of infection.Transmission does not occur during the incubation period⁵.

 

The clinical course can be divided into three phases:

The first generalised phase (days 1–4), early organ phase (days 5–13), followed by either a late organ or a convalescence phase (days 13+). In this stage, supportive care can maintain the patient until the virus is eradicated spontaneously . Survivors rarely show the most severe symptoms of the disease and may never reach the late organ phase⁵

 

These symptoms usually begin abruptly⁶:

·       High fever

·       Severe headaches

·       Intense malaise, or general feeling of illness

·       Muscle aches and pains

·       Severe, watery diarrhea (usually on the third day, lasting until a week after symptoms occur)

·       Abdominal pain and cramping (usually on the third day after symptoms occur)

·       Nausea and vomiting (usually on the third day after symptoms occur)

·       Ghost-like features (deep-set eyes, expressionless face)

·       Severe fatigue

·       Blood may appear in vomit or stool, or  might bleed from nose, gums, or vagina. During this intense period, patient might have a high fever that results in confusion, aggression, and irritability⁶.

·       Orchitis, which is inflammation of one or both testicles, often happens late in the disease (around 15 days after the first symptoms).

·       In fatal cases, great blood loss and shock usually lead to death around 8 to 9 days after the first symptoms appear⁶.

 

Diagnosis²

It can be difficult to clinically distinguish MVD from other infectious diseases such as malaria, typhoid fever, shigellosis, meningitis and other viral haemorrhagic fevers. Confirmation that symptoms are caused by Marburg virus infection are made using the following diagnostic methods²:

·       Antibody-capture enzyme-linked immunosorbent assay (ELISA)

·       Antigen-capture detection tests

·       Serum neutralization test

·       Reverse transcriptase polymerase chain reaction (RT-PCR) assay

·       Electron microscopy

·       Virus isolation by cell culture.

 

 

Samples collected from patients are an extreme biohazard risk; laboratory testing on non-inactivated samples should be conducted under maximum biological containment conditions. All biological specimens should be packaged using the triple packaging system when transported nationally and internationally².

 

Treatment:

Currently there are no vaccines or antiviral treatments approved for MVD. However, supportive care – rehydration with oral or intravenous fluids – and treatment of specific symptoms, improves survival².

 

There are monoclonal antibodies (mAbs) under development and antivirals e.g. Remdesivir and Favipiravir that have been used in clinical studies for Ebola Virus Disease (EVD) that could also be tested for MVD or used under compassionate use/expanded access².

 

In May 2020, the EMA granted a marketing authorisation to Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo). against EVD . The Mvabea contains a virus known as Vaccinia Ankara Bavarian Nordic (MVA) which has been modified to produce 4 proteins from Zaire ebolavirus and three other viruses of the same group (filoviridae). The vaccine could potentially protect against MVD, but its efficacy has not been proven in clinical trials².

 

Prevention:

Risk reduction messaging should focus on several factors²:

·       Reducing the risk of bat-to-human transmission arising from prolonged exposure to mines or caves inhabited by fruit bat colonies. During work or research activities or tourist visits in mines or caves inhabited by fruit bat colonies, people should wear gloves and other appropriate protective clothing (including masks). During outbreaks all animal products (blood and meat) should be thoroughly cooked before consumption².

 

·       Reducing the risk of human-to-human transmission in the community arising from direct or close contact with infected patients, particularly with their body fluids. Close physical contact with Marburg patients should be avoided. Gloves and appropriate personal protective equipment should be worn when taking care of ill patients at home. Regular hand washing should be performed after visiting sick relatives in hospital, as well as after taking care of ill patients at home².

 

·       Communities affected by Marburg should make efforts to ensure that the population is well informed, both about the nature of the disease itself and about necessary outbreak containment measures².

·       Outbreak containment measures include prompt, safe and dignified burial of the deceased, identifying people who may have been in contact with someone infected with Marburg and monitoring their health for 21 days, separating the healthy from the sick to prevent further spread and providing care to confirmed patient and maintaining good hygiene and a clean environment need to be observed².

 

·       Reducing the risk of possible sexual transmission. Based on further analysis of ongoing research, WHO recommends that male survivors of Marburg virus disease practice safer sex and hygiene for 12 months from onset of symptoms or until their semen twice tests negative for Marburg virus. Contact with body fluids should be avoided and washing with soap and water is recommended. WHO does not recommend isolation of male or female convalescent patients whose blood has been tested negative for Marburg virus².

 

CONCLUSION:

Marburg virus is the causative agent of Marburg virus disease (MVD), a disease with a case fatality ratio of up to 88%, but can be much lower with good patient care. Marburg virus disease was initially detected in 1967 after simultaneous outbreaks in Marburg and Frankfurt in Germany; and in Belgrade, Serbia². All recorded MVD outbreaks have originated in Africa. MVD is not an airborne disease and is considered not to be contagious before symptoms appear. Direct contact with the blood and other body fluids of infected people and animals or indirect contact with contaminated surfaces and materials like clothing, bedding and medical equipment is required for MARV transmission [1]. As a result, if proper infection prevention and control precautions are strictly followed, the risk of infection is regarded as minimal. There is no approved vaccine for MVD; however, several candidate MVD vaccines are in clinical trials⁵.

 

REFERENCES:

1.      Marburg (Marburg Virus Disease). CDC Viral Hemorrhagic Fevers (VHFs). Marburg Virus Disease. https://www.cdc.gov/vhf/marburg/prevention/index.html

2.      Marburg virus disease. https://www.who.int/news-room/fact-sheets/detail/marburg-virus-disease

3.      Marburg Disease. https://en.wikipedia.org/wiki/Marburg_virus_disease

4.      Marburg virus – Ghana. https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON402

5.      Factsheet about Marburg virus Disease. https://www.ecdc.europa.eu/en/infectious-disease-topics/z-disease-list/ebola-virus-disease/facts/factsheet-about-marburg-virus

6.      Alexandra Benisek. Marburg Virus Disease: What to Know. Medically Reviewed by Melinda Ratini, DO, MS on July 28, 2022. https://www.webmd.com/a-to-z-guides/marburg-virus-disease

 

 

 

Received on 27.08.2022           Modified on 10.09.2022

Accepted on 14.10.2022          © A&V Publications all right reserved