SDL Viral haemorrhagic fever

Dengue virus family

Flaviviridae

Dengue virus genome

Positive sense single stranded RNA

Dengue virus structure

Spherical enveloped virion with icosahedral nucleocapsid

Dengue virus entry

Via mosquito saliva into fibroblasts and dendritic cells

Dengue virus spread

To lymph nodes, spleen, liver, infecting Kupffer cells and hepatocytes

Dengue viremia

High titre in first days of infection

Dengue immune response

Exuberant cytokine, complement and coagulation activation

Severe dengue theory one

Antibody dependent enhancement with heterologous serotype infection

Severe dengue theory two

Genetic drift producing more virulent variants

Dengue fever hallmark

Biphasic saddleback fever

Dengue fever symptoms

Nausea, vomiting, maculopapular rash, retro orbital pain, myalgia, arthralgia

Dengue fever duration

Self limited 2 to 7 days

Dengue haemorrhagic fever signs

Thrombocytopenia, vascular leakage, hypovolemic shock

Dengue haemorrhagic fever bleeding

Skin petechiae, purpura, ecchymoses, epistaxis, gum bleeding, GI haemorrhage, haematuria

Dengue mortality treated

2 to 5 percent

Dengue mortality untreated

Up to 50 percent

Dengue laboratory diagnosis

NS1 antigen detection

Dengue serology

IgM antibody detection

Dengue molecular diagnosis

RT PCR viral RNA detection

Dengue treatment

Supportive care only

Dengue prevention

Vaccine for children with prior infection, mosquito control, personal protection

Yellow fever virus family

Flaviviridae

Yellow fever virus genome

Positive sense single stranded RNA

Yellow fever virus structure

Spherical enveloped virion with icosahedral nucleocapsid

Yellow fever transmission

By Aedes and Haemagogus mosquitoes from primates

Yellow fever cycles

Jungle sylvatic, intermediate savanna, urban

Yellow fever pathogenesis

Local replication then spread to lymph nodes, liver, spleen, kidney, bone marrow, myocardium

Yellow fever organ damage

Direct cytopathology plus ischemic changes from haemorrhage and shock

Yellow fever liver pathology

Mid zone hepatocyte necrosis, Kupffer cell apoptosis, cytokine storm

Yellow fever renal pathology

Direct viral injury plus hepatorenal syndrome

Yellow fever clinical incubation

3 to 6 days

Yellow fever initial symptoms

Fever, chills, headache, back pain, myalgia, nausea, vomiting, fatigue

Yellow fever severe symptoms

Abdominal pain, jaundice, renal failure, GI haemorrhage with hematemesis and melena

Yellow fever mortality

30 to 60 percent

Yellow fever laboratory diagnosis

IgM antibody detection, RT PCR viral RNA, histopathology post mortem

Yellow fever treatment

Supportive care only

Yellow fever prevention

Live attenuated 17D vaccine, mosquito control

Ebola virus family

Filoviridae

Ebola virus genome

Negative sense single stranded RNA

Ebola virus structure

Filamentous enveloped virion with helical nucleocapsid

Marburg virus family

Filoviridae

Marburg virus genome

Negative sense single stranded RNA

Marburg virus structure

Filamentous enveloped virion with helical nucleocapsid

Filovirus entry

Via mucous membranes, skin breaks, parenteral routes

Filovirus target cells

Monocytes, macrophages, dendritic cells, endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, epithelial cells

Filovirus primary replication sites

Macrophages, monocytes, dendritic cells

Filovirus pathology

Liver necrosis, spleen and lymph node follicular necrosis

Filovirus coagulation abnormality

Disseminated intravascular coagulation with fibrin split products and prolonged clotting times

Filovirus cytokine role

Pro inflammatory cytokines cause endothelial leakage, lymphocyte apoptosis, DIC

Filovirus bleeding

Platelet dysfunction and hepatic impairment contribute

Filovirus mortality

Marburg 25 percent, Ebola Sudan 60 percent, Ebola Zaire 90 percent, Ebola Bundibugyo 35 percent

Filovirus clinical incubation

5 to 10 days average

Filovirus initial symptoms

Fever, headache, malaise, myalgia, abdominal discomfort

Filovirus rash

Common but less visible in dark skin

Filovirus bleeding manifestations

Petechiae, ecchymoses, venepuncture site bleeding, melena in less than half cases

Filovirus progression

Nausea, vomiting, prostration, anuria, hypothermia

Filovirus pregnancy outcome

Abortion and maternal infant death

Filovirus death

Multiple organ failure and shock within 6 to 9 days

Filovirus convalescence

Slow with weakness, weight loss, hair loss, desquamation, amnesia

Filovirus laboratory diagnosis

RT PCR viral RNA, antigen detection by ELISA or immunofluorescence, IgM and IgG serology

Ebola treatment

Supportive care plus monoclonal antibodies Inmazeb and Ebanga for Zaire subtype

Marburg treatment

Supportive care only

Ebola prevention

Ervebo vaccine for Zaire subtype, avoid contact with infected fluids, animals, funeral practices

Lassa virus family

Arenaviridae

Lassa virus genome

Bisegmented ambisense single stranded RNA

Lassa virus structure

Spherical enveloped virion with helical nucleocapsid

Lassa virus reservoir

Multimammate rat Mastomys natalensis

Lassa virus transmission

Rodent urine and droppings via ingestion, inhalation, contact with contaminated food or cuts, airborne during cleaning, person to person via blood and secretions

Lassa virus pathogenesis

Pantropic replication in multiple organs, viremia after 1 to 2 weeks incubation

Lassa virus pathology

Ecchymoses and petechiae in skin and organs, multifocal hepatocellular necrosis with Councilman bodies, necrosis in spleen, adrenal, kidney, GI mucosa

Lassa virus coagulation role

DIC not significant until terminal phase

Lassa virus immunity

Cell mediated immunity key to recovery, antibodies appear late and weakly neutralising

Lassa fever endemic areas

West Africa including Sierra Leone, Liberia, Guinea, Nigeria

Lassa fever annual burden

100000 to 300000 infections, 5000 deaths

Lassa fever hospital impact

10 to 16 percent admissions in endemic regions

Lassa fever clinical signs

Occur 1 to 3 weeks after infection, include fever and haemorrhagic features