Arboviruses and viral hemorrhagic fevers Dr Katongole Paul
What are VHFs? Initial nonspecific prodromal stage Fever Malaise Headache Myalgia/ arthralgia Abdominal pain Non-bloody diarrhea Clinical multi-system illness associated with fever & bleeding tendencies caused by several distinct families of viruses . Symptoms include;
Then Progresses to more severe symptoms & death Hemorrhage (not all cases) Increased vascular permeability Hypotension and Shock Multi-organ failure Many cause rapidly progressive illness & high mortality rates
Causative Viral groups (4) Viral group Representative viruses 1- Filoviruses Ebola V and Marburg V 2- Flaviviruses (82 members) -Yellow fever V –West Nile V – Dengue Fever V 3- Bunyaviruses ( Rift Valley fever virus (RVV), Crimean-Congo hemorrhagic fever (CCHF) virus , and Hantavirus pulmonary syndrome (HPS) . 4 - Arenavirus Lassa Fever V New World Arena Viruses
Virology of vhf (features of the viruses) All are single-stranded RNA. All are enveloped Infectious during viremia stage. Low infectivity dose (1-10 viruses can cause infections). Geographically restricted to areas where host lives. Humans are not the natural reservoir but accidentally infected when comes in contact with infected hosts. Human outbreaks are sporadic and irregular . When human is infected can infect another human No established treatment (with few exceptions) The best treatment is control of infection . Role in bioterrorism – except dengue virus
Epidemiology of Hemorrhagic fever Disease( hfv ) Transmission - HFVs are zoonosis: Animal hosts (Rodents) and arthropod vectors are main reservoirs. A. Natural infection of humans (mode of transmission): 1. Bite of infected arthropod (ticks or mosquitos) 2. Aerosol from infected rodent excreta 3. Direct contact with infected animals/carcasses or fomites.
B- Human to Human & Nosocomial Transmission Possible for most HFVs - Most person-to-person spread due to direct contact with infected blood & body fluids (Hospital acquires infections ) - Mucous membrane contact, - Aerosolized, (airborne in Ebola, Lassa, Junín, & may be yellow fever) Semen, vomitus, Sweat . Incubation period ranging from 2 to 21 days for all of them .
pathogenesis The target organ is the vascular bed (hemorrhage) The replication of virus is intracellularly Cytokine release leads to shock and hypotension. Affects platelet functions and numbers (thrombocytopenia) Affects bone marrow and clotting factors .
Case-fatality (mortality) rate Virus Mortality rate Filoviruses Around 90% for Ebola virus (the highest) Flaviviruses 0.5% Arenaviruses 15-30% Causes of death: 1- Hemorrhagic diathesis ( several body sites & orifices) 2- Shock 3- Multi-organ failure
FILOVIRUSES A- Ebola viral disease (EVD), B- Marburg virus (MVD) 1. Category A bioweapon (bioterrorism) agents (CDC 1999). 2- Potential to cause widespread illness / death Ease of dissemination or person-to-person transmission. First appeared in Zaire and Sudan simultaneously in 1976. Outbreak in 2013 in guinea then to Liberia, Sierra Leone, and lately Nigeria .
Case fatality rate (CFR) approaches 90%. The virus was transmitted to humans from wild animals . Fruit Bats are considered as the natural host for the virus . Other reservoirs rodents and plant virus?
EBOLA VIRUS DISEASE TRANSMISSION 1- By direct human-to-human contact with the blood, or other body secretions (saliva, breast milk, tears, stool, skin, or semen) of infected persons or even Dead bodies. (N.B. Lab staff at risk) 2- Transmission through semen may occur up to 7 weeks after clinical recovery (Sexual transmission ). 3- Indirect contact transmission via environment contaminated with such infected secretions . 4- By handling ill or dead infected chimpanzees or other infected animals. 5- Health care workers (HCWs) have frequently been infected while attending patients (direct contact body fluids, Needle sticks, aerosols).
Health care workers (HCWs) have critical situations
Filoviruses: Ebola & Marburg - Cause severe HF that similar to fulminant septic shock. - Mortality Rate: Ebola: 50-90% ,Marburg : 25-30% - Incubation period: 2-21 days for Ebola (Mean 8 -10 ).3-10 days for Marburg ,9.6 days (mean) from symptom onset to death
Virology Filovirus family includes Ebola and Marburg viruses. Single stranded-RNA (ssRNA), enveloped virus. Ebola virus contains 5 strains with different phylogenic tree (Zaire, Sudan, Ivory Coast, Reston & New 5 th Guinea strain. High mutational potentials. Rapidly replicating within 8 Hs. U or 6-shape virus.
Flaviviruses A- Yellow Fever B- Dengue Fever C- Omsk HF D- Kyasanur Forest Disease N.B . Flavus in Latin means yellow.
Mode of transmission - Yellow Fever – Aedes mosquito ( A. aegypti , A. africanus , A. simpsoni , A. furcifer , A. luteocephalus , and A. albopictus (Asian tiger mosquito) - Dengue Fever – mosquito ( Aedes aegypti ) - Omsk HF/ Kyasanur FD: Tick bite No reported cases of person to-person transmission
A- Yellow Fever Incubation period: short - 3-6 days. C/P: 1- Initial symptoms; Fever , chills, severe HA, back pain, muscle aches, nausea, fatigue. Most symptomatic patients develop only this stage however , in 15% of symptomatic patients severe form will develop after short period of symptom remission (Toxic shock). 2- Toxic phase - fever returns with initial symptoms PLUS Coagulopathy & hemorrhage - hematemesis (black vomit), Jaundice , Hypotension, shock, metabolic acidosis, arrhythmias Confusion, seizures, and coma can occur.
90% of yellow fever cases occur in Africa
- Described as “breakbone fever” by Benjamin ,Rush in 1789. - Endemic throughout Americas, Asia & Africa - Vector - Aedes aegypti & Aedes albopictus. - Virus replicates in mosquitos. - Very Rare by blood transfusion, organs transplant. & Vertical transmission ). - Incubation period: 3-14 days. The Most prevalent mosquito-borne viral disease in the world. - 1/3 of world populations are exposed (400 million cases yearly) B- Dengue Fever
- > 100 countries have endemic dengue transmission. - In USA: Dengue - 10.4% of post-travel systemic febrile illness for travelers returning from endemic areas. No vaccine available (in 2015 new one is used successfully by Sanofi Pasteur for people in endemic areas). No specific treatment. -
B unya viruses : A- Rift Valley Fever B- Hantavirus C- Crimean Congo HF Viral hosts : arthropod vectors & rodents. Mosquitoes – Rift Valley Fever Ticks – Crimean Congo Fever Rodents – Hantaan Virus All can be acquired by: - Exposure to infected animals or their carcasses - Contact with blood & bodily secretions of infected persons - By aerosol
A- Rift Valley Fever - Mosquito-borne disease affects primarily sheep & goats, also cattle , buffalos and camels. - Most human infections are unapparent Self limited febrile illness first reported in Kenya’s Rift Valley in the early 1910s . Rare severe forms (Ocular; retina, Meningoencephalitis, or Hemorrhagic fever form) - 1% develops typical VHF. - Short incubation: 3-6 days. - Mortality (variable) but less than 1%.
Humans acquire infection by: - Bite of infected mosquito (several species- vertical trans for yrs ) - Contact with infected animal tissues - Aerosolization of virus from infected animal carcasses (Lab Staff) - Ingestion of contaminated raw animal milk??? (No reported cases of human-to-human transmission- still theoretical risk to HCWs ). Standard precautions are enough. Vaccination of animals but not during epidemics. Inactivated human vaccine is not licensed for use.
IV- Arenavirus A- Lassa Fever B- New World Arena Viruses
- Arenaviruses - rodent borne HFVs mainly rats and mice - Severe VHF in Africa & S. America - One case in North America - Incubation period: 3-19 days 2 Types : Old World & New World i - Old World – Africa & Europe - Lassa Fever - Lymphocytic Choriomeningitis (LCM) ii- New World - Americas - South American HFVs - Junin (Argentine HF) - Machupo (Bolivian HF) - Whitewater Arroyho (North America) -Sabia virus (Brazilian HF)
Mode of transmission : - Inhaled aerosols of rodent urine/feces - Ingestion of food or water contaminated with rodent excreta - Direct contact of rodent excreta with abraded skin / mucous membranes - Contact with contaminated fomites Contact with rodent blood Sexual transmission is likely in Lassa virus (3 months in semen).
Person to person transmission does occur however; - Direct contact with blood, urine, pharyngeal secretions & other body fluids of patients (HCWs) - Airborne transmission possible (HCWs) - Sexual transmission likely (Lassa fever virus detected in semen up to 3 months after acute infection).
Diagnosis of VHF & HFVs Case Definition , VHFs – Ebola, Marburg, New World Arenaviruses, Old World Arenaviruses, and CCHF (CDC 2011). Patient must have: One or more of the following Fever ≥ 40 o C . - No predisposing factors for hemorrhagic manifestations -AND no established alternative diagnosis -Severe headache -Muscle pain -Erythematous maculopapular rash on the trunk with fine desquamation 3–4 days after rash onset - Vomiting -Diarrhea - Abdominal pain -Thrombocytopenia - Bleeding not related to injury - Pharyngitis (arenavirus only) - Retrosternal chest pain (arenavirus only) - Proteinuria (arenavirus only).