01Approach to the Critical Patient/attcp62

Immediate priorities

›Airway and breathing threats

›Hemorrhagic manifestations with airway bleeding

›Epistaxis, hemoptysis, or hematemesis compromising airway

›If airway compromise, proceed to definitive airway control immediately

›Respiratory failure from pulmonary edema

›SpO2 < 90% on room air

›PaO2 < 60 mmHg

›Ventilatory failure with encephalitis

›GCS < 8 with rising PaCO2

›If unable to protect airway, proceed to RSI

›Circulatory stabilization

›Hemorrhagic shock recognition

›SBP < 90 mmHg with active bleeding

›MAP < 65 mmHg

›Tachycardia with cool peripheries

›Volume resuscitation with crystalloid

›30 ml/kg IV bolus for shock

›Reassess after each bolus

›If vasopressor required, norepinephrine 0.1–0.3 mcg/kg/min titrated to MAP > 65 mmHg

›Hemorrhagic fever protocol activation

›Isolation precautions

›Contact and droplet precautions immediately

›BSL-3/4 sample handling notification

›Immediate public health notification

›RVF is a notifiable disease and WHO priority pathogen

›Outbreak investigation trigger

›Empiric treatment plan while awaiting confirmatory results

02History/hx62

Exposure history

›Travel or residence in endemic regions

›Sub-Saharan Africa

›Arabian Peninsula (Saudi Arabia, Yemen)

›Indian Ocean islands (Comoros, Madagascar, Reunion)

›Timing relative to heavy rainfall or flooding episodes

›Livestock contact

›Butchering or slaughtering animals

›Handling aborted fetal material or placenta

›Milking sick animals

›Veterinarian or slaughterhouse worker role

›Dietary exposures

›Raw milk consumption from potentially infected animals

›Raw blood or undercooked meat ingestion

›Mosquito exposure

›Aedes and Culex species in endemic area

›Outdoor exposure especially after flooding

›Laboratory exposure risk

›Work with livestock samples or RVFV in research setting

Presenting symptoms

›Febrile prodrome

›Abrupt onset high fever

›Headache (frontal/retro-orbital)

›Severe myalgias and large-joint arthralgias

›Photophobia

›Malaise and weakness

›Incubation period

›2–6 days post-exposure typical

03Physical Exam/exam39

Vital signs

›Hemodynamic assessment

›High fever (often > 39.5 C)

›Relative bradycardia relative to fever (feature of some VHFs)

›Hypotension indicating hemorrhagic shock

›Tachypnea suggesting pulmonary edema or acidosis

General appearance

›Toxicity assessment

›Acutely ill and toxic-appearing in severe cases

›Jaundice visible on skin and sclera

›Altered mental status or confusion

Eyes

›Ophthalmologic findings

›Conjunctival injection or hemorrhage

›Photophobia

›Fundoscopic findings (dilated exam required)

›Macular or paramacular retinal lesions

›Retinal hemorrhages

›Vitreous haze

›Optic disc edema

Skin

›Hemorrhagic manifestations

›Petechiae and purpura distribution

›Ecchymoses at venipuncture sites

›Cutaneous flushing

›Jaundice

Abdomen

›Hepatic and GI findings

04Differential Diagnosis/ddx38

Viral hemorrhagic fevers

›Other VHFs — highest priority mimics requiring exclusion

›Ebola virus disease (A98.4)

›Higher CFR; contact tracing and travel history critical

›Marburg virus disease (A98.3)

›Bat or primate exposure history

›Crimean-Congo hemorrhagic fever (A98.0)

›Tick exposure; widespread Eurasian/African distribution

›Dengue hemorrhagic fever (A91)

›NS1 antigen and serology differentiate

›Thrombocytopenia with characteristic biphasic fever

Malaria and parasitic

›Malaria (B54) — most critical mimic in endemic areas

›Co-infection found in 55% of Tanzanian RVF outbreak cases

›Thick and thin blood smear plus RDT essential

›P. falciparum causes cerebral and severe forms

Viral hepatitis

›Hepatitis A, B, E (B15-B19)

›Jaundice, transaminitis without hemorrhage typically

›Serology panel distinguishes

›Yellow fever (A95)

›Overlapping geography in Africa

›Vaccination history critical

Bacterial infections

›Typhoid/enteric fever (A01)

›Prolonged fever, abdominal pain, hepatosplenomegaly

›Blood culture positive in 50–80%

›Leptospirosis (A27)

05Laboratory Tests/lt41

Hematology

›Complete blood count

›Thrombocytopenia — hallmark finding in severe RVF

›Platelet count < 50 x 10^9/L associated with hemorrhagic risk

›Leukopenia in early febrile phase

›Anemia from hemorrhage or hemolysis

›Leukocytosis may indicate bacterial superinfection

Coagulation

›Coagulation panel

›PT/INR — elevated in hepatic failure and DIC

›aPTT — prolonged in DIC

›Fibrinogen — low in DIC (< 1.0 g/L critical threshold)

›D-dimer — elevated in DIC and VTE

›DIC pattern predicts hemorrhagic death

Hepatic function

›Liver function tests

›AST/ALT markedly elevated (hepatocellular necrosis is hallmark RVF pathology)

›AST elevation often exceeds ALT (hepatocytic destruction)

›Bilirubin elevated in severe hepatic involvement (jaundice in up to 75% of severe cases)

›Albumin low in severe/prolonged illness

›Alkaline phosphatase and GGT

Renal function

›Renal panel

›Creatinine and urea (acute renal failure in 41% of hospitalized cases)

›Electrolytes (sodium, potassium, bicarbonate)

›Urinalysis — hematuria, proteinuria in renal involvement

›Urine sodium and fractional excretion of sodium

06Diagnostic Tests/dt54

Scoring Systems

›No validated RVF-specific clinical scoring tool exists

›WHO criteria for suspected VHF used in resource-limited settings

›Fever plus hemorrhagic manifestations plus epidemiologic link

›Sequential Organ Failure Assessment (SOFA) score

›Tracks multiorgan failure severity

›SOFA > 2 from baseline indicates sepsis-associated organ dysfunction

›Severity markers associated with mortality

›Hepatorenal failure combination (highest CFR up to 42%)

›DIC with active hemorrhage

›GCS < 13 with encephalitis

›Shock on presentation

MRI

›Brain MRI indications

›Altered mental status, seizures, or focal deficits

›T2/FLAIR hyperintensities in white matter suggest encephalitis

›Cerebral edema pattern in severe cases

›Enhancement pattern helps distinguish RVF encephalitis from bacterial meningitis

›Protocol

›T1 with gadolinium for enhancement assessment

›DWI for ischemic vs inflammatory differentiation

›Encephalitis typically develops 2–3 weeks after acute febrile illness

›Orbit/eye MRI

›Retinal detachment, optic neuritis evaluation when CT insufficient

›Useful when fundoscopy inadequate due to vitreous hemorrhage

CT

›CT brain

›First-line when MRI not immediately available

07Disposition/dispo37

Admission criteria

›Mandatory admission indications

›Any hemorrhagic manifestations (petechiae, bleeding)

›Jaundice or hepatic failure evidence

›Acute renal failure (creatinine rising)

›Altered mental status or seizures

›Hemodynamic instability or shock

›Pregnancy with confirmed or suspected RVF

›Inability to maintain oral intake

›Thrombocytopenia < 100 x 10^9/L

›ICU admission indications

›Active hemorrhagic shock

›DIC with clinical bleeding

›Mechanical ventilation requirement

›Multiorgan failure (hepatorenal combination)

›Refractory seizures

Discharge criteria

›Requirements for safe discharge

›Fever resolved for > 48 hours

›Stable hemodynamics without vasopressors

›No active bleeding

›Adequate oral intake

›Improving LFTs, renal function, and platelet count

›Ophthalmologic evaluation completed or scheduled

›Reliable follow-up guaranteed within 1 week

Transfer criteria

›Transfer indications

›Facility lacks BSL-3 laboratory capacity for confirmatory testing

08Treatment/t74

Supportive care

›Fluid management

›Cautious IV fluid resuscitation

›500 ml crystalloid boluses titrated to hemodynamic response

›Avoid fluid overload in hepatic failure (worsens ascites and coagulopathy)

›Target MAP > 65 mmHg and urine output > 0.5 ml/kg/h

›Vasopressor support if fluid-refractory shock

›Norepinephrine 0.1 mcg/kg/min IV infusion

›Titrate by 0.05 mcg/kg/min every 5–10 minutes

›Target MAP > 65 mmHg

›Maximum 3 mcg/kg/min before adding second agent

›Vasopressin 0.03–0.04 units/min as adjunct for refractory shock

Hemorrhage management

›Coagulopathy and DIC treatment

›Fresh frozen plasma

›10–15 ml/kg for active bleeding with elevated PT/INR

›Repeat every 6–12 hours based on coagulation response

›Platelet transfusion

›Threshold < 50 x 10^9/L with active bleeding

›Threshold < 20 x 10^9/L without bleeding (prophylactic)

›Cryoprecipitate

›Fibrinogen < 1.0 g/L with active bleeding

›10 units; recheck fibrinogen after infusion

›Packed red blood cells

›Hemoglobin < 70 g/L in hemodynamically stable patients

›Hemoglobin < 80 g/L in hemodynamically unstable patients

›Avoid NSAIDs and anticoagulants

›Exacerbate hemorrhagic diathesis

›Avoid aspirin

›Platelet dysfunction risk in hemorrhagic state

Antiviral considerations

›No licensed antiviral agents for RVF in humans

›Supportive care is the standard of care

›Ribavirin (investigational/compassionate use)

›Has been used empirically in some VHF outbreaks

›Limited RVF-specific efficacy data in humans

›Animal data: may prevent acute hepatic disease but increases delayed-onset neurologic disease risk

›Absolute contraindication in pregnancy (teratogenic)

›If used (ID consult required): 2000 mg loading dose then 1000 mg q6h x 4 days, then 500 mg q8h x 6 days (weight-based adjustment)

›Favipiravir (T-705) (experimental only)

›Preclinical data show efficacy against RVFV in animal models

›Reduced viral replication

›Protection against both acute and neuroinvasive disease

›Superior to ribavirin in animal studies for neurologic protection

›Not yet approved for human use in RVF; compassionate use consideration with ID

›Favipiravir + nitazoxanide combination

›2026 preclinical data show additive efficacy against RVFV

›Human data not yet available

Antipyretic and supportive medications

›Fever management

›Acetaminophen (paracetamol) preferred

›15 mg/kg orally or IV every 6 hours

›Reduce dose in severe hepatic failure

›Avoid NSAIDs (hemorrhagic risk)

›Antiemetics

›Ondansetron 4–8 mg IV every 6–8 hours for nausea

›Metoclopramide 10 mg IV if ondansetron unavailable

›Seizure management (encephalitis)

›Lorazepam 0.1 mg/kg IV (max 4 mg) for acute seizure

›Levetiracetam 500–1000 mg IV q12h for ongoing seizure prophylaxis

›Phenytoin 15–20 mg/kg IV load if refractory

Renal replacement therapy

›RRT indications

›Anuria or severe oliguria unresponsive to resuscitation

›Creatinine > 350 mmol/L with rising trend

›Hyperkalemia > 6.5 mmol/L

›Metabolic acidosis pH < 7.2 refractory to treatment

›Fluid overload with pulmonary edema

›CRRT preferred in hemodynamically unstable patients

Ocular management

›Retinitis treatment

›Ophthalmology-guided management

›Anterior uveitis may respond to topical corticosteroids

›Cycloplegic agents for ciliary spasm

›Close monitoring for macular scarring, vascular occlusion, optic atrophy (late sequelae)

Infection control

›Standard and contact precautions for all cases

›Gown, gloves, eye protection for all patient contact

›BSL-3/4 protocols for laboratory sample handling

›Avoid needle-stick injuries (blood-borne transmission risk)

›No aerosol precautions required for clinical care (not airborne in human-to-human transmission)

09Special Populations/sp55

Pregnancy

›RVF in pregnancy — high-risk condition

›Spontaneous abortion rate 54% in pregnant cases

›Fetal loss risk persists throughout gestation

›OB/GYN consultation mandatory for all pregnant patients

›Increased risk of severe maternal disease

›Viral replication may be enhanced in pregnancy

›Hepatic decompensation risk amplified

›Medication safety in pregnancy

›Ribavirin is absolutely contraindicated (teratogenic, Category X)

›Acetaminophen safe for antipyresis

›Avoid NSAIDs especially in third trimester

›Corticosteroids may be used cautiously for fetal lung maturity if preterm delivery imminent

›Fetal monitoring

›Fetal heart rate monitoring in viable pregnancies

›Serial ultrasound for fetal growth and intrauterine demise

›Delivery planning

›Minimize invasive procedures if coagulopathy present

›Maternal hemorrhage team on standby for delivery

Geriatric

›RVF in older adults — highest mortality group

›Age > 44 years associated with highest case fatality rate

›Reduced hepatic reserve increases hepatic failure severity

›Reduced renal reserve increases AKI progression

›Polypharmacy considerations

›Review anticoagulants (warfarin, DOACs) — hold if hemorrhagic features

›Avoid NSAIDs for pain management

›Reduce acetaminophen dose if pre-existing hepatic impairment

10Background/b87

Epidemiology

›Geographic distribution

›Endemic throughout sub-Saharan Africa

›East African cattle corridor at highest sustained risk

›Uganda, Kenya, Tanzania, Somalia: repeated outbreaks

›Arabian Peninsula (Saudi Arabia 2000–2001; Yemen)

›Indian Ocean islands (Madagascar, Comoros, Reunion, Mayotte)

›Not yet established in the Americas, Europe, or Asia despite concern for spread

›Incidence and outbreak patterns

›Epidemic cycles linked to El Nino-related heavy rainfall and flooding

›Flooding increases Aedes mosquito breeding

›Livestock abortion storms are sentinel outbreak indicators

›Interepidemic sporadic transmission occurs via direct animal contact

›Human seropositivity rates in high-risk occupations can reach 20–40%

›Mortality data

›Overall case fatality rate in hospitalized patients: 21–42% depending on outbreak

›Uncomplicated febrile illness CFR < 1%

›Hemorrhagic fever form CFR 40–60%

›Encephalitic form CFR 30–50% (survivors may have permanent neurologic sequelae)

›Ocular complications in 1–20% of cases; blindness in up to 50% of retinitis cases

›HIV co-infection associated with 75% mortality in Tanzanian cohort

›Transmission routes

›Direct contact with blood, body fluids, or tissue of infected animals (primary route for humans)

›Butchering and slaughtering highest-risk occupational activities

›Mosquito bite (Aedes, Culex species)

›Consumption of raw or undercooked infected animal products

›Laboratory exposure

›Human-to-human transmission not documented through casual contact

›Healthcare worker transmission via blood-borne exposure (sharps precautions critical)

›ICD-10 coding

›A92.4 — Rift Valley fever

Pathophysiology

›Viral classification

›RVFV: genus Phlebovirus, family Phenuiviridae, order Bunyavirales

›Single-stranded RNA virus with tripartite genome (L, M, S segments)

›NSs protein (S segment) is primary virulence factor

›Inhibits interferon-beta production

›Facilitates immune evasion and unchecked viral replication

›Pathogenesis of organ damage

›Hepatocellular necrosis (hallmark)

›Direct viral cytopathic effect on hepatocytes

›Massive hepatic necrosis with eosinophilic Councilman bodies on pathology

›Kupffer cell destruction

›Hemorrhagic syndrome

›DIC triggered by hepatic failure and endothelial injury

›Factor depletion from hepatic failure

›Platelet consumption in DIC

›Encephalitis mechanism

›RVFV neurotropism in rodent models

›CD4 T cells, CD8 T cells, and monocytes coordinate to contain CNS infection

›RVFV activates multiple cell death pathways in neurons (apoptosis, necroptosis)

›Neuroinvasion occurs later in illness course (2–3 weeks post-acute)

›Retinal disease mechanism

›Direct viral infection of posterior segment

›RVFV infects retinal pigment epithelium and neural retina

›Vasculitis causes macular and paramacular lesions

›1–20% of cases; onset 4–15 days (mean 8.8 days) after acute illness

›Renal failure mechanism

›Prerenal from volume depletion and shock

›Direct tubular injury from viremia and inflammatory mediators

›Hepatorenal syndrome in advanced hepatic failure

›Natural history

›Most infections (approximately 98–99%) self-limited febrile illness resolving in days to weeks

›Severe forms: hemorrhagic fever, encephalitis, retinitis — each in distinct minority

›Symptom duration in survivors: 2 to 120 days

›Natural infection confers long-lasting immunity (IgG persists years)

Therapeutic Considerations

›Antiviral landscape

›No licensed human antiviral agents for RVF

›Ribavirin off-label use debated

›Animal data suggest hepatic protection but neurologic disease amplification

›Teratogenic — absolute contraindication in pregnancy

›Favipiravir (T-705) most promising in preclinical data

›Protects against peracute disease and reduces delayed neurologic disease (unlike ribavirin)

›Favipiravir + nitazoxanide combination shows additive preclinical efficacy (2026 data)

›Not yet approved for human RVF use

›Vaccine development (no licensed human vaccine as of 2026)

›ChAdOx1 RVF — Phase 1 trial in Uganda (2026); safe and immunogenic

›hRVFV-4s live attenuated — Phase 1 trial (Lancet Infect Dis, 2024); dose-escalation study showed safety and immunogenicity

›Neither vaccine licensed yet; candidates remain in clinical trial phase

›Supportive care evidence base

›Systematic review (Rigby et al., Lancet Infect Dis, 2023) of standard of care for VHFs

›Supportive care remains primary treatment across all high-priority VHFs

›No strong evidence base for any specific antiviral in RVF

›Blood product use guided by DIC protocol and clinical hemorrhage, not prophylactically

›Public health considerations

›Notification to WHO through IHR 2005 framework mandatory

›Biosafety precautions for laboratory personnel (BSL-3/4)

›Livestock vaccination during interepidemic periods reduces human outbreak risk

›No human post-exposure prophylaxis protocol established

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Your diagnosis

›You had Rift Valley Fever, a viral infection spread by mosquitoes and contact with infected animals

›The infection is caused by a virus; antibiotics do not treat this illness

›Most people recover fully, but some complications can develop weeks after the initial illness

›Activity and rest

›Rest and avoid strenuous activity until fully recovered

›Expect fatigue and weakness to persist for 2 to 120 days in some cases

›Avoid heavy lifting or vigorous exercise until your follow-up appointment clears you

›Diet and hydration

›Drink plenty of fluids (water, clear soups, oral rehydration solutions)

›Avoid raw milk, raw blood, or undercooked meat from any animal

›Eat small frequent meals if nausea persists

›Medications

›Take only acetaminophen (Tylenol/paracetamol) for fever or pain

›Do not take ibuprofen, aspirin, naproxen, or any blood-thinning medications unless specifically prescribed

›Mosquito and animal protection

›Use DEET-containing mosquito repellent on exposed skin

›Sleep under an insecticide-treated bed net

›Avoid contact with livestock or wild animals until fully recovered

›Wash hands thoroughly after any animal contact

›Follow-up appointments

›Return for repeat blood tests (liver function, kidney function, blood count) within 1 week

›Ophthalmology (eye specialist) appointment within 2 weeks — eye complications can appear up to 3 weeks after the illness even if your eyes feel normal now

›Neurology follow-up if any neurologic symptoms develop — brain complications can appear 2 to 3 weeks after the fever resolves

›Return to the emergency department immediately for

›Any new or worsening bleeding from any site (gums, nose, skin, stool, urine, vomit)

›Jaundice (yellow skin or eyes) or dark tea-colored urine

12References/r28

Guidelines and key sources

›Wright D, Kortekaas J, Bowden TA, Warimwe GM. Rift Valley Fever: Biology and Epidemiology. The Journal of General Virology. 2019. PMID 31310198

›Primary biology and epidemiology reference; endemicity, transmission, immunity

›Anywaine Z, Lule SA, Hansen C, Warimwe G, Elliott A. Clinical Manifestations of Rift Valley Fever in Humans: Systematic Review and Meta-Analysis. PLoS Neglected Tropical Diseases. 2022. PMID 35333856

›Pooled clinical data: thrombocytopenia, leukopenia, hemorrhagic features, mortality rates

›Javelle E, Lesueur A, Pommier de Santi V, et al. The Challenging Management of Rift Valley Fever in Humans: Literature Review of the Clinical Disease and Algorithm Proposal. Annals of Clinical Microbiology and Antimicrobials. 2020. PMID 31969141

›Clinical management algorithm; diagnosis criteria; disposition framework

›Rigby I, Michelen M, Dagens A, et al. Standard of Care for Viral Haemorrhagic Fevers: A Systematic Review of Clinical Management Guidelines for High-Priority VHFs. The Lancet Infectious Diseases. 2023. PMID 36758568

›Supportive care evidence base across VHFs; antiviral evidence review

›Al-Hazmi M, Ayoola EA, Abdurahman M, et al. Epidemic Rift Valley Fever in Saudi Arabia: A Clinical Study of Severe Illness in Humans. Clinical Infectious Diseases. 2003. PMID 12539063

›Landmark clinical description of severe RVF; organ failure characterization

›Scharton D, Bailey KW, Vest Z, et al. Favipiravir (T-705) Protects Against Peracute Rift Valley Fever Virus Infection and Reduces Delayed-Onset Neurologic Disease Observed With Ribavirin Treatment. Antiviral Research. 2014. PMID 24486952

›Key favipiravir vs ribavirin animal study; neurologic disease amplification with ribavirin

›Kahlon SS, Peters CJ, Leduc J, et al. Severe Rift Valley Fever May Present With a Characteristic Clinical Syndrome. American Journal of Tropical Medicine and Hygiene. 2010. PMID 20207858

›Clinical syndrome characterization; fever + arthralgia + GI + hemorrhage pattern

›Anywaine Z, Hansen C, Warimwe GM, et al. Severe Morbidity and Hospital-Based Mortality From Rift Valley Fever Disease 2017–2020, Uganda. Virology Journal. 2024. PMID 38702807

›Acute renal failure 41% of hospitalized cases; mortality data from Uganda cohort

›Al-Hazmi A, Al-Rajhi AA, Abboud EB, et al. Ocular Complications of Rift Valley Fever Outbreak in Saudi Arabia. Ophthalmology. 2005. PMID 15691569

›Ocular complication characterization; retinitis onset timing; blindness rates

Vaccine and emerging therapy references

›Leroux-Roels I, Prajeeth CK, Aregay A, et al. Safety and Immunogenicity of the Live-Attenuated hRVFV-4s Vaccine Against Rift Valley Fever in Healthy Adults. The Lancet Infectious Diseases. 2024. PMID 39068957

›Phase 1 hRVFV-4s vaccine trial; first-in-human dose-escalation safety data

›Anywaine Z, Serwanga J, Ggayi AM, et al. Safety, Tolerability, and Immunogenicity of the ChAdOx1 RVF Vaccine Against Rift Valley Fever Among Healthy Adults in Uganda. The Lancet Infectious Diseases. 2026. PMID 41237791

›Phase 1 ChAdOx1 RVF trial; Uganda adult cohort; immunogenicity results

›Chaput S, Driouich JS, Pastorino B, et al. Preclinical Efficacy of a Favipiravir and Nitazoxanide Combination Against Rift Valley Fever Virus. Antiviral Research. 2026. PMID 41936880

›Combination antiviral preclinical data; additive efficacy against RVFV

›Borio L, Inglesby T, Peters CJ, et al. Hemorrhagic Fever Viruses as Biological Weapons: Medical and Public Health Management. JAMA. 2002. PMID 11980524

›Biodefense and public health management framework for VHFs including RVF

Evidence & Review

Evidence & Review