Ebola virus

Overview

• In general, Several viruses of the family Filoviridae cause severe and frequently fatal viral hemorrhagic fevers in humans.
• Moreover, Introduction of filoviruses into human populations is an extremely rare event that most likely occurs by either direct or indirect contact with healthy mammalian filovirus hosts or by contact with infected, sick, or deceased nonhuman primates.[1]

Epidemiology

Causes

The family Filoviridae includes three genera: Cueva virus, Ebolavirus, also Marburg virus

These genomes contain six or seven genes that encode the following seven structural proteins:

nucleoprotein, polymerase cofactor (i.e. VP35), matrix protein (i.e. VP40), glycoprotein (e.g. GP1,2), transcriptional cofactor (VP30), secondary matrix protein (VP24), and RNA-dependent RNA polymerase (L protein). [1]

Types of Ebola virus

Zaïre Ebolavirus

• Among the five strains, Zaïre Ebolavirus carries the highest mortality rate.
• A virus of the genus Ebolavirus is considered member of the species Zaire ebolavirus if:

• It is found in the Democratic Republic of the Congo, Gabon, or the Republic of the Congo.
• It has a genome with two or three gene overlaps (VP35/VP40, GP/VP30, VP24/L).
• It has a genomic sequence that differs from the virus type by less than 30%.

Sudan Ebolavirus

• A virus of the genus Ebolavirus is considered member of the species Sudan ebolavirus if:

• It is endemic in Sudan and/or Uganda.
• It has a genome with three gene overlaps (VP35/VP40, GP/VP30, VP24/L).
• It has a genomic sequence different from Ebola virus by ≥30%, but different from that of Sudan virus by <30%.

Reston Ebolavirus

• A virus of the genus Ebolavirus is considered member of the species Reston ebolavirus if:

• If its genome diverges from that of the prototype Reston virus, the Reston virus variant Pennsylvania, by ≤10% at the nucleotide level.

Tai (Ivory Coast) Ebolavirus

• A virus of the genus Ebolavirus is considered member of the species Tai Forest ebolavirus if:

• It is endemic in Côte d’Ivoire.
• It has a genome with three gene overlaps (VP35/VP40, GP/VP30, VP24/L).
• It has a genomic sequence different from Ebola virus by ≥30% but different from that of Tai Forest virus by <30%.

Bundibugyo Ebolavirus

• A virus of the genus Ebolavirus is considered member of the species Bundibugyo ebolavirus if:

• It is endemic in Uganda.
• It has a genome with three gene overlaps (VP35/VP40, GP/VP30, VP24/L).
• It has a genomic sequence different from Ebola virus by ≥30%, but different from that of Bundibugyo virus by <30%.(3)

Risk factors Of Ebola Fever

• Percutaneous (e.g., needle stick) or mucous membrane exposure to blood or body fluids of EVD patient while the patient was symptomatic
• Exposure to the blood or body fluids (including but not limited to feces, saliva, sweat, urine, vomit, and semen) of a person with Ebola while the person was symptomatic without appropriate personal protective equipment (PPE)
• Processing blood or body fluids of a person with Ebola while the person was symptomatic without appropriate PPE or standard biosafety precautions
• Direct contact with a dead body without appropriate PPE in a country with widespread Ebola virus transmission
• Having lived in the immediate household and provided direct care to a person with Ebola while the person was symptomatic.
• In countries with widespread Ebola virus transmission: direct contact while using appropriate PPE with a person with Ebola while the person was symptomatic
• Close contact in households, health care facilities, or community settings with a person with Ebola while the person was symptomatic. Close contact is defined as being for a prolonged period of time while not wearing appropriate PPE within approximately 3 feet (1 meter) of a person with Ebola while the person was symptomatic.
• Having brief direct contact (e.g., shaking hands) while not wearing appropriate PPE, with a person with Ebola while the person was in the early stage of disease
• Brief proximity, such as being in the same room for a brief period of time, with a person with Ebola while the person was symptomatic
• In countries without widespread Ebola virus transmission: direct contact while using appropriate PPE with a person with Ebola while the person was symptomatic
• Traveled on an aircraft with a person with Ebola while the person was symptomatic. (3)

Pathogenesis Of Ebola Fever

Ebola virus enters the body through mucous membranes, breaks in the skin, or by parenteral introduction. It infects many cell types, including monocytes, macrophages, dendritic cells, endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, and epithelial cells. The incubation period is 2 to 21 days. [5]

Pathophysiology

Tropism

• Ebola virus infects mainly the cells of the mononuclear phagocyte system, but also fibroblasts, hepatocytes, spongiocytes, adrenal cortical cells and endothelial cells.
• The infection of the mononuclear phagocyte system cells plays a key role in the pathogenesis and spread of the disease as they carry the virus from of the initial infection site, through the lymphatic system and blood, to the regional lymph nodes, spleen and liver.

• Immune response

  • The virus activates the macrophages synthesis of interleukins (IL), which leads the Th1/Th2 balance towards a more pronounced Th1-cell mediated response.
  • Some inflammatory mediators produced during the Ebola virus infection include interferon (IFN)-alpha, IFN-beta, IL-2, IL-6, IL-8, IL-10, interferon-inducible protein 10; monocyte chemoattractant protein 1; regulated upon activation normal T cell expressed and secreted (RANTES); TNF-alpha; and reactive oxygen and nitrogen species.
  • Some viral proteins, such as VP35 and VP24, block the type I interferon response, which plays a key role of the pathogenesis of the disease.
  • The reactive oxygen and nitrogen species contribute to the cell and tissue damage, and therefore vascular and organ damage.
  • The nitric oxide is known to be an important vasodilator; therefore it plays and important role in the development of hypotension and shock.

  Coagulation system

  • Ebola infection is associated with hemorrhage in 50% of patients.
  • Alterations of the coagulation system are induced by the ebola virus, and are thought to be mediated by the production of tissue factor:

  • Consumption of clotting factors
  • Increased concentrations of fibrin degradation products
  • Disseminated intravascular coagulopathy

• The next table summarizes the pathogenesis of the disease according to the virus tropism. (3)

Clinical Features Of Ebola Fever

The clinical features of Ebola virus disease (EVD) are variable and nonspecific in the initial stages, making diagnosis challenging.

Early symptoms include fever, fatigue, muscle pain, headache, and sore throat.

These may progress to vomiting, diarrhea, abdominal pain, and unexplained bleeding or bruising. [6]

Sign & Symptoms Of Ebola Fever

• Fever
• Aches and pains, e.g. severe headache and muscle and joint pain
• Weakness also fatigue
• Sore throat
• Loss of appetite
• Gastrointestinal symptoms including abdominal pain, diarrhea, also vomiting
• Unexplained either haemorrhaging, bleeding or bruising

Clinical examination Of Ebola Fever

Appearance of the Patient

The general appearance of the patient depends on the stage of the disease. Typically, patients demonstrate prostration, may be nauseated and vomiting, and less commonly present with signs of hemorrhage, such as epistaxis or gingival bleeding. In later stages of the disease, patients are often brought with convulsions or are in a state of shock, stupor, or coma.

Vitals

Temperature

• High-grade fever is often present in more than 80% of patients. Fever is the most common presenting sign of Ebola virus infection.

Pulse

• Tachycardia
• Relative bradycardia

Blood Pressure

• Hypotension (SBP<90 mmHg and/or DBP<60 mmHg)
• Postural hypotension is common in dehydrated patients with inadequate volume repletion

Respiratory Rate

• Signs of respiratory difficulty may be present, such as:

• Intercostal retractions
• Paradoxical breathing
• Nasal flare

• Tachypnea often precedes death during final hours of infection.

Skin

Hemorrhagic manifestations tend to occur during the more severe stages of the disease and may include:

• Maculopapular rash on the trunk, usually between the 5th and 7th day of the condition, associated with different stages of erythema and desquamation, which is a valuable finding in differentiating Ebola from other diseases.
• Petechiae is a common finding
• Ecchymoses is a common finding
• Mucosal hemorrhages is a common finding
• Uncontrolled bleeding from venipuncture locals is a common finding

Eyes

• Conjunctival hemorrhage is a the most common sign of abnormal clotting
• Conjunctivitis

Nose

• Epistaxis may be present.
• Nasal discharge may be present.

Throat

• Mucosal hyperemia of the oral cavity is a common finding.
• Bleeding gums is a common finding.

Abdomen

• Abdominal tenderness may suggest pancreatitis, intestinal swelling, or mesenteric lymphadenopathy
• Abdominal distention may suggest paralytic ileus
• Tender hepatomegaly
• Splenomegaly

Extremities

• Edema may be present.

Neurologic

• Obtundation may be present.
• Stupor
• Coma (3)

Diagnosis Of Ebola Fever

• Basically, Filovirus infections cannot diagnose on the basis of clinical presentation alone.
• Acute-phase blood/serum is the preferred diagnostic specimen because it usually contains high titers of filovirions also filovirion-specific antibodies.
• Consequently, diagnostic samples should collect with great caution and with use of proper personal protective equipment and strict barrier nursing techniques.
• In detail, With adherence to established bio safety precautionary measures, samples should sent in suitable transport media to national or international WHO reference laboratories.
• All in all, Direct IgM and IgG or IgM capture ELISA use for the detection of filovirion-targeting antibodies from patients in later stages of disease [1]

Differential diagnosis

• Shigellosis & other bacterial enteric infections
• Typhoid fever
• Malaria
• Lassa fever
• Yellow fever
• Flaviviridae (3)

Complications

Given the severe immunosuppression induced by filovirus infection, secondary infections should be kept in mind and appropriately treated as early as possible.

Pregnancy and labour cause severe and frequently fatal complications in filovirus infections due to clotting factor consumption, fetal loss, and/or severe blood loss during birth. [1]

Investigation

• Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing
• IgM ELISA
• Polymerase chain reaction (PCR)
• Virus isolation
• IgM and IgG antibodies
• Immunohistochemistry testing
• PCR
• Virus isolation
•  

Treatment of Ebola virus

• Any treatment of patients with suspected or confirmed filovirus infection must be administered under increased safety precautions by experienced specialists using appropriate personal protective equipment .
• Postexposure vaccination with filovirus GP1,2.
• Expressing recombinant replicating vesicular stomatitis Indiana virus; administration of specific filovirus genome- or transcript-targeting small interfering RNAs or phosphorodiamidate morpholino oligomers.
• Administration of filovirus specific antibodies or antibody cocktails ; and use of a synthetic adenosine analog  that acts as a non-obligate RNA chain terminator.
• In the absence of these candidate treatments, measures to stabilize patients include those generally recommended for severe septicemia/sepsis/shock.
• Pain management and administration of antipyretics and antiemetic should always be considered. [1]

Prevention

• Avoid contact with blood and body fluids (such as urine, feces, saliva, sweat, vomit, breast milk, amniotic fluid, semen, and vaginal fluids) of people who are sick.
• Avoid contact with semen from a man who has recovered from EVD, until testing shows that the virus is gone from his semen.
• Avoid contact with items that may have come in contact with an infected person’s blood or body fluids (such as clothes, bedding, needles, and medical equipment).
• Avoid funeral or burial practices that involve touching the body of someone who died from EVD or suspect EVD.
• Avoid contact with bats, forest antelopes, and nonhuman primates (such as monkeys and chimpanzees) blood, fluids, or raw meat prepared from these or unknown animals (bushmeat).
• Ebola vaccine is given as a single dose vaccine and has been found to be safe and protective against Zaire ebolavirus, which has caused the largest and most deadly Ebola outbreaks to date.(4)

Homeopathic Treatment of Ebola virus

Homeopathy treats the person as a whole. It means that homeopathic treatment focuses on the patient as a person, as well as his pathological condition. The homeopathic medicines selected after a full individualizing examination and case-analysis. 

Which includes 

• The medical history of the patient, 
• Physical and mental constitution,
• Family history, 
• Presenting symptoms,
• Underlying pathology,
• Possible causative factors etc. 

A miasmatic tendency (predisposition/susceptibility) also often taken into account for the treatment of chronic conditions. 

What Homoeopathic doctors do? 

A homeopathy doctor tries to treat more than just the presenting symptoms. The focus is usually on what caused the disease condition? Why ‘this patient’ is sick ‘this way’? 

The disease diagnosis is important but in homeopathy, the cause of disease not just probed to the level of bacteria and viruses. Other factors like mental, emotional and physical stress that could predispose a person to illness also looked for. Now a days, even modern medicine also considers a large number of diseases as psychosomatic. The correct homeopathy remedy tries to correct this disease predisposition. 

The focus is not on curing the disease but to cure the person who is sick, to restore the health. If a disease pathology not very advanced, homeopathy remedies do give a hope for cure but even in incurable cases, the quality of life can greatly improve with homeopathic medicines. 

Homeopathic Medicines for Ebola virus: 

The homeopathic remedies (medicines) given below indicate the therapeutic affinity but this is not a complete and definite guide to the homeopathy treatment of this condition. The symptoms listed against each homeopathic remedy may not be directly related to this disease because in homeopathy general symptoms and constitutional indications also taken into account for selecting a remedy, potency and repetition of dose by Homeopathic doctor. 

So, here we describe homeopathic medicine only for reference and education purpose. Do not take medicines without consulting registered homeopathic doctor (BHMS or M.D. Homeopath).  

Medicines of Ebola virus:

Crotalus horridus:

• Specifically in Bilious fever with yellow face, gnawing, aching pain in liver, bloody evacuation, right lung hepatized, dry tongue, urine dark, unconsciousness, cold clammy perspiration.
•  All fevers which present a either hemorrhagic or putrescent character, with epistaxis, extreme prostration and induration of tonsils.

Arsenicum album:

• High temperature. Periodicity marked with adynamic, Septic fevers.
• Paroxysms incomplete, with marked exhaustion, Hay fever.
• Cold sweats. Additionally, Typhoid, not too early, Complete exhaustion.
• Besides this, Delirium; worse after midnight. Great restlessness. Great heat especially, about 3 a.m. Sordes.

Lachesis:

• Chilly in back; feet icy cold; hot flushes also hot perspiration.
• Paroxysm returns after acids. Intermittent fever especially in every spring.

Millefolium:

• Especially indicated in Ebola virus infection.
• Intermittent fever: quartan; tertian; irregular. Furthermore, Scarlet fever epidemic, with excessive angina and violent fever.
• Chilliness with pains in left kidney. Exanthema of difficult development and delirium. Hectic fever with hemoptysis.
• Colliquative sweats. Fever heat with thirst.
• Phosphorus: Chilly every evening. Cold knees at night. Adynamic with lack of thirst, but unnatural hunger.
• Hectic, with small, quick pulse; viscid night- sweats. foolish delirium. Lastly, Profuse perspiration.

Baptisia:

• Chill, with rheumatic pains and soreness all over body. Heat all over, with occasional chills.
• Chill about 11 a.m. Adynamic fever, Typhus fever. Shipboard fever.[2]

Diet & Regimen

• Avoid cold drinks /cold food
• Eat fresh food
• Maintain cleanliness
• Drink Hurble tea
• Respiratory exercise

Do’s and Don’ts

of Ebola virus

Do’s:

• Practice good hygiene: Wash your hands frequently with soap and water or use an alcohol-based hand sanitizer.
• Seek medical care immediately: If you experience symptoms such as fever, headache, muscle pain, vomiting, diarrhea, abdominal pain, or unexplained bleeding or bruising, consult a healthcare professional immediately.
• Follow infection control measures: If you are caring for someone with suspected or confirmed Ebola, wear personal protective equipment (PPE) such as gloves, masks, gowns, and goggles.
• Report any suspected cases: Inform health authorities immediately if you suspect someone has Ebola.
• Get vaccinated: If a vaccine is available, get vaccinated to protect yourself from Ebola.

Don’ts:

• Do not touch bodily fluids: Avoid contact with blood, vomit, feces, urine, saliva, sweat, or semen of individuals with suspected or confirmed Ebola.
  
   
• Do not handle items that may have come into contact with an infected person: Avoid touching clothing, bedding, needles, or other personal belongings of individuals with suspected or confirmed Ebola.
• Do not participate in burial rituals: Avoid participating in traditional burial practices that involve direct contact with the body of someone who has died from Ebola.
• Do not eat bushmeat: Avoid eating or handling wild animals (bushmeat) as they can be a source of Ebola virus transmission.
• Do not travel to areas with Ebola outbreaks: Avoid nonessential travel to regions experiencing an Ebola outbreak.

Remember, early detection and prompt medical attention are crucial in managing Ebola virus disease. By following these do’s and don’ts, you can help protect yourself and others from this deadly virus.

Terminology

Reference

1. Harrisons_Principles_of_Internal_Medicine-_19th_Edition-_2_Volume_Set
2. Materia Medica By Boericke W.
3. Ebola risk factors – wikidoc
4. GOVERNMENT OF INDIA MINISTRY OF HEALTH AND FAMILY WELFARE DEPARTMENT OF HEALTH AND FAMILY WELFARE LOK SABHA UNSTARRED QUESTION NO. 4225 TO BE ANSWERED ON 24.04.2015
5. .Harrison’s Principles of Internal Medicine, 21st Edition, by Dennis L. Kasper, Anthony S. Fauci, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, Joseph Loscalzo (2022) Publisehed by McGraw Hill Medical
6. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th edition, by John E. Bennett, Raphael Dolin, Martin J. Blaser (2020), Published by Elsevier