Arthropod-Borne and Rodent-Borne Virus Infections¶
Chapter 215 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Viral (incl. HIV) · Chapter 215
Key Clinical Points¶
- Rabies post-exposure prophylaxis (PEP) is the most critical intervention; RIG must be infiltrated into all wounds and never mixed with vaccine.
- Rabies vaccine schedule for PEP: 4 doses IM on days 0, 3, 7, and 14 (5th dose on day 28 only for immunocompromised).
- Rabies PEP is safe in pregnancy; glucocorticoids/immunosuppression interfere with immunity and should be avoided unless essential.
- Human RIG is preferred over equine-derived RIG (which can be used if human is unavailable at a dose of 40 IU/kg, but carries risk of anaphylaxis and serum sickness).
- Vesicular stomatitis virus causes conjunctivitis and influenza-like illness in humans.
- Viral Hemorrhagic Fevers (VHF) include Lassa, Junin, Machupo, and Ebola-related viruses; transmission is often via rodent excreta/secreta.
- Arboviral encephalitis includes Eastern equine, Western equine, and Japanese encephalitis.
- Ribavirin is used for severe cases of Vesicular stomatitis and for Lassa fever.
- Monoclonal antibodies (e.g., Inmazeb, Ebanga) are the specific treatments for Ebola/VHF.
- Zoonotic virus classification does not predict clinical symptoms in humans.
1. DEFINITION & OVERVIEW¶
This chapter summarizes the major features of selected arthropod-borne and rodent-borne viruses and associated infections/disease. Many are spread among animals without infecting humans, while others infect humans incidentally with few causing disease. Some are regularly introduced into human populations via arthropods or chronically infected rodents.
Zoonotic viruses are taxonomically diverse (differing in virion morphology, replication strategy, genomic organization, and genome sequence). Classification does not predict clinical symptoms in humans.
1.1 Classification of Zoonotic Viruses¶
• Arthropod-borne/rodent-borne zoonotic virus classes: ◦ Alsuviricetes (Togaviridae) ◦ Bunyaviricetes (Arenaviridae, Hantaviridae, Nairoviridae, Peribunyaviridae, Phenuiviridae) ◦ Flasuviricetes (Flaviviridae) ◦ Insthoviricetes (Orthomyxoviridae) ◦ Monjiviricetes (Bornaviridae, Rhabdoviridae) ◦ Resentoviricetes (Sedoreoviridae, Spinareoviridae) • Exception: Syr-Darya Valley fever virus (Pisoniviricetes: Picornaviridae) causes febrile disease in Central Asia.
2. EPIDEMIOLOGY¶
• General Distribution: Zoonotic viruses are most numerous in the tropics but are found globally. • Influencing Factors: Distribution is influenced by ecological factors (rainfall, temperature). • Arthropod Transmission: ◦ Vectors develop chronic systemic infection through extrinsic incubation (1–3 weeks in mosquitoes). ◦ Transmission continues via infected salivary glands during subsequent blood meals. ◦ Some viruses maintain infections via transovarial transmission. • Human Exposure: Humans are accidental hosts via arthropod bites. • Alternative Routes: Orthoflaviviruses can be transmitted via aerosol or contaminated food (e.g., raw milk).
2.1 Geographic Distribution¶
• Diversity: Highest in tropics; also affects temperate and frigid regions. ◦ Seasonal activity varies with environmental conditions.
2.2 Vector Ecology¶
• Infection Source: Vectors infected by feeding on viremic hosts. ◦ Humans are accidental hosts via arthropod bites.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
• Alsuviricetes (Togaviridae): ◦ Linear, positive-sense RNA genomes (9.7–11.8 kb). ◦ Enveloped icosahedral virions (60–70 nm) bud from plasma membrane. ◦ All discussed viruses are Alphavirus genus, transmitted by mosquitoes. • Bunyaviricetes (Arenaviridae): ◦ Human-infecting viruses in Mammarenavirus genus. ◦ Spherical/pleomorphic enveloped virions (50–300 nm). ◦ Two genomic RNAs (S: 3.5 kb, L: 7.5 kb) with ambisense orientation. ◦ Chronic infection in rodents; human transmission via rodent excreta/secreta. • Bunyaviricetes (Hantaviridae, Nairoviridae, Peribunyaviridae): ◦ Human-infecting viruses have three genomic RNAs (S: 1–2 kb, M: 3.6–5.3 kb, L: 6.4–12.3 kb). ◦ Negative-sense or ambisense polarity. ◦ Maturation in Golgi complexes; exocytosis from infected cells. ◦ Orthohantaviruses maintained by muroid rodents (horizontal transmission only). • Table 215-1 Summary: Lists over 100 zoonotic viruses categorized by syndrome: ◦ Fever and myalgia (F&M) ◦ Encephalitis (E) ◦ Viral Hemorrhagic Fever (VHF)
4. CLINICAL FEATURES¶
• Rabies: Progressive CNS disease with hydrophobia, aerophobia, and paralysis. • Vesicular Stomatitis Virus: Vesiculation in cattle/horses; human presentation with conjunctivitis and influenza-like illness. • Viral Hemorrhagic Fevers (VHF): Fever, hemorrhage, multiorgan failure (Lassa, Junin, Machupo, Ebola). ◦ Transmission via rodent excreta/secreta. • Arboviral Encephalitis: Acute CNS inflammation with fever, headache, altered mental status. ◦ Includes Eastern equine encephalitis, Western equine encephalitis, Japanese encephalitis.
4.1 Rabies¶
• Progressive CNS disease with hydrophobia, aerophobia, and paralysis. ◦ 100% fatal once clinical symptoms develop.
4.2 Vesicular Stomatitis Virus¶
• Vesiculation in cattle/horses; human presentation with conjunctivitis and influenza-like illness.
4.3 Viral Hemorrhagic Fevers (VHF)¶
• Fever, hemorrhage, multiorgan failure. ◦ Includes Lassa, Junin, Machupo, Ebola-related viruses. ◦ Transmission via rodent excreta/secreta.
4.4 Arboviral Encephalitis¶
• Acute CNS inflammation with fever, headache, altered mental status. ◦ Includes Eastern equine encephalitis, Western equine encephalitis, Japanese encephalitis.
5. DIFFERENTIAL DIAGNOSIS¶
• Rabies: ◦ Consider in patients with progressive CNS disease and history of animal exposure (especially bats, dogs). • Vesicular Stomatitis: ◦ Distinguish from herpes simplex, varicella-zoster. ◦ Look for characteristic vesicles on oral mucosa/dermis. • Viral Hemorrhagic Fevers: ◦ Differentiate from dengue, leptospirosis, malaria. ◦ Key indicators: Presence of hemorrhage and multiorgan failure.
6. INVESTIGATIONS & DIAGNOSIS¶
- Rabies:
- Direct fluorescent antibody (DFA) test on corneal impression smear or CSF.
- RT-PCR of saliva, skin biopsy, or CSF.
- Vesicular Stomatitis:
- PCR for viral RNA.
- Serology (IgM/IgG detection).
- Viral Hemorrhagic Fevers:
- RT-PCR for viral RNA.
- Antigen detection assays.
- Serology (IgM/IgG detection).
7. MANAGEMENT & TREATMENT¶
- Rabies Post-Exposure Prophylaxis (PEP):
- RIG Administration: Infiltrate RIG into all wounds; never mix with vaccine.
- Vaccine Schedule: 4 doses IM on days 0, 3, 7, and 14.
- Immunocompromised Adjustment: Add a 5th dose on day 28.
- Vesicular Stomatitis:
- Supportive care.
- Ribavirin (IV or oral) for severe cases.
- Viral Hemorrhagic Fevers:
- Supportive care (fluids, oxygen, blood products).
- Ribavirin for Lassa fever.
- Monoclonal antibodies (e.g., Inmazeb, Ebanga) for Ebola/VHF.
8. PROGNOSIS & COMPLICATIONS¶
• Rabies: ◦ 100% fatal once clinical symptoms develop. ◦ No effective treatment after onset of CNS signs. • Vesicular Stomatitis: ◦ Self-limiting; rare complications (secondary infections). ◦ No long-term sequelae in most cases. • Viral Hemorrhagic Fevers: ◦ High mortality: Lassa (~15–30%), Ebola (up to 90%). ◦ Common complications: Multiorgan failure, shock, secondary infections.
9. SPECIAL CONSIDERATIONS¶
• Pregnancy: ◦ Rabies PEP safe. ◦ Avoid glucocorticoids/immunosuppression unless essential. • Immunocompromised Patients: ◦ Adjust vaccine schedule: Add 5th dose on day 28 for Rabies. ◦ Consider intravenous ribavirin for VHF. • Wound Care: ◦ RIG must be infiltrated into all wounds. ◦ Never mix RIG with vaccine.
10. KEY PEARLS & CLINICAL TRAPS¶
• Rabies PEP: Immediate action is critical; RIG must be infiltrated, not mixed with vaccine. • Vesicular Stomatitis: Distinguish from herpes simplex/varicella-zoster based on mucosal vesicles. • Viral Hemorrhagic Fever: Early supportive care improves outcomes; Ribavirin for Lassa; Monoclonal antibodies for Ebola.
Reference Tables¶
TABLE 215-1 Zoonotic Arthropod- and Rodent-Borne Viruses That Infect Humans¶
Harrison's 22e, p.1659
| VIRUS TAXON | VIRUS (ABBREVIATION) | MAJOR NONHUMAN HOST(S)a | VECTOR(S) | SYNDROMEb |
|---|---|---|---|---|
| Iquitos virus (IQTV) | Unknown | Unknown | F&M | |
| Itaquí virus (ITQV) | Capuchins (Cebus spp.), opossums, rodents |
Mosquitoes (Culex spp.) | F&M | |
| Jamestown Canyon virus (JCV) |
Predominantly white-tailed deer (Odocoileus virginianus), but also bison, elk, and moose |
Mosquitoes (Aedes, Anopheles, Coquillettidia, Culiseta, Ochlerotatus spp.) |
F&M, E | |
| Keystone virus (KEYV) | Rabbits, squirrels | Mosquitoes (Ochlerotatus atlanticus) | E | |
| La Crosse virus (LACV) | Chipmunks, squirrels | Mosquitoes (Ochlerotatus triseriatus) | F&M, E | |
| Lumbo virus (LUMV) | Unknown | Mosquitoes (Aedes pembaensis) | F&M, E | |
| Madrid virus (MADV) | Capuchins (Cebus spp.), opossums, rodents |
Mosquitoes (Culex spp.) | F&M | |
| Maguari virus (MAGV) | Birds, cattle, horses, sheep, water buffalo | Mosquitoes (Aedes, Anopheles, Culex, Psorophora, Wyeomyia spp.) |
F&M | |
| Marituba virus (MTBV) | Capuchins (Cebus spp.), opossums, rodents |
Mosquitoes (Culex spp.) | F&M | |
| Murutucú virus (MURV) | Capuchins (Cebus spp.), opossums, pale- throated sloths (Bradypus tridactylus), rodents |
Mosquitoes (Coquillettidia, Culex spp.) | F&M | |
| Nepuyo virus (NEPV) | Bats (Artibeus spp.), rodents | Mosquitoes (Culex spp.) | F&M | |
| Ngari virus (NRIV) | Cattle, goats, sheep | Mosquitoes (Aedes, Anopheles, Culex spp.) | F&M, VHF | |
| Nyando virus (NDV) | Unknown | Mosquitoes (Aedes, Anopheles spp.), sandflies (Lutzomyia spp.) |
F&M | |
| Oriboca virus (ORIV) | Capuchins (Cebus spp.), opossums, rodents |
Mosquitoes (Aedes, Culex, Mansonia, Psorophora spp.) |
F&M | |
| Oropouche virus (OROV) | Marmosets (Callithrix spp.), pale-throated sloths (B. tridactylus) |
Biting midges (Culicoides paraensis), mosquitoes (Coquillettidia venezuelensis, Culex quinquefasciatus, Mansonia spp., Ochlerotatus serratus) |
F&M, E | |
| Ossa virus (OSSAV) | Rodents | Mosquitoes (Culex spp.) | F&M | |
| Pongola virus (PGAV) | Cattle, donkeys, goats, sheep | Mosquitoes (Aedes, Anopheles, Mansonia spp.) |
F&M | |
| Restan virus (RESV) | Unknown | Mosquitoes (Culex spp.) | F&M | |
| Shokwe virus (SHOV) | Rodents | Mosquitoes (Aedes, Anopheles, Mansonia spp.) |
F&M | |
| Shuni virus (SHUV) | Horses, livestock | Mosquitoes (Culex theileri, Culicoides spp.) | E | |
| Snowshoe hare virus (SSHV) |
Collared lemmings, snowshoe hares, squirrels, voles |
Mosquitoes (Aedes, Culiseta, Ochlerotatus, Simulium spp.) |
F&M, E | |
| Tacaiuma virus (TCMV) | Nonhuman primates | Mosquitoes (Anopheles, Haemagogus spp.) |
F&M | |
| Tˇ ahynˇ a virus (TAHV) | Boars, cattle, deer, dogs, eulipotyphla, foxes, hares, horses, pigs, rodents |
Mosquitoes (Aedes, Anopheles, Culex, Culiseta spp.) |
F&M, E | |
| Tataguine virus (TATV) | Unknown | Mosquitoes (Anopheles spp.) | F&M | |
| Trubanaman virus (TRUV) | Unknown | Mosquitoes (Anopheles, Culex spp.) | (A&R) | |
| Wyeomyia virus (WYOV) | Unknown | Mosquitoes (Wyeomyia spp.) | F&M | |
| Xingu virus (XINV) | Unknown | Unknown | F&M | |
| Zungarococha virus (ZUNV) |
Unknown | Unknown | F&M | |
| Alkhurma hemorrhagic fever virus (AHFV)j |
Livestock? | Argasid ticks (Ornithodoros savignyi), ixodid ticks (Hyalomma dromedarii, H. rufipes) |
||
| Apoi virus (APOIV) | Field mice, voles | Unknown | ||
| Banzi virus (BANV) | Rodents? | Mosquitoes (Culex rubinotus) | ||
| Bussuquara virus (BSQV) | Cotton rats, monkeys, spiny-rats | Mosquitoes (Culex spp.) | ||
| Cacipacoré virus (CPCV) | Birds, horses, nonhuman primates, water buffalo |
Mosquitoes (Aedes, Anopheles, Culex spp.) | ||
| Dakar bat virus (DBV) | Bats | Unknown | ||
| Dengue viruses 1–4 (DENV 1–4) |
Nonhuman primates | Mosquitoes (predominantly Aedes aegypti, A. albopictus) |
||
| Edge Hill virus (EHV) | Bandicoots, dogs, wallabies | Mosquitoes (Aedes vigilax, Culex annulirostris) |
||
| Ilhéus virus (ILHV) | Birds, coatis, nonhuman primates, rodents, reptiles, sloths, water buffalo |
Mosquitoes (Aedes, Culex, Coquillettidia, Haemagogus, Ochlerotatus, Psorophora, Sabethes, Trichoprosopon spp.) |
TABLE 215-2 Geographic Distribution of Zoonotic Arthropod-Borne or Rodent-Borne Viral Diseases AREA a Africa¶
Harrison's 22e, p.1664
| AREAa | TYPE OF DISEASEb | |||||
|---|---|---|---|---|---|---|
| BUNYAVIRICETES (Arenaviridae, Hantaviridae, Nairoviridae, Peribunyaviridae, Phenuiviridae) |
FLASUVIRICETES (Flaviviridae) |
INSTHOVIRICETES (Orthomyxoviridae) |
RESENTOVIRICETES (Sedoreoviridae, Spinareoviridae) |
MONJIVIRICETES (Bornaviridae, Rhabdoviridae) |
ALSUVIRICETES (Togaviridae) |
|
| Africa | Aigai, Bangui, Batai, Bhanja, Bunyamwera, and Bwamba virus infections, Crimean-Congo hemorrhagic fever, Dar es Salaam, Dugbe, Germiston, Ilesha virus infections, Lassa fever, Lujo virus, Nairobi sheep disease virus infection, Ngari, Nyando, and Pongola virus infections, Rift Valley fever, sandfly fever, Shokwe, Shuni, Tataguine virus infections |
Alkhurma hemorrhagic fever, Banzi virus infection, Dakar bat, dengue without/with warning signs/severe dengue, Kédougou, Koutango, Ntaya, Spondweni, Usutu, Wesselsbron, West Nile virus infections, yellow fever, Zika virus disease |
Dhori, Quaranfil, Thogoto virus infections |
Lebombo, Orungo, Tribecˇ virus infections |
(Bas-Congo virus infection,) Ekpoma virus 1, Ekpoma virus 2, Mundri virus infections |
Chikungunya virus disease, o’nyong- nyong fever, Semliki Forest, Sindbis virus infections |
| Bhanja, Issyk-kul virus infections, Crimean-Congo hemorrhagic fever, sandfly fever, Tˇahynˇ a, Tamdy virus infections |
Far Eastern tick-borne encephalitis, Karshi, Powassan, West Nile virus infections |
Dhori virus infections | — | Isfahan virus infection |
||
| Eastern Asia |
Crimean-Congo hemorrhagic fever, hemorrhagic fever with renal syndrome, sandfly fever, severe fever with thrombocytopenia syndrome, Taˇchéng tick virus 1 (and 2) and Tˇahynˇ a, Tamdy, So–nglˇıng, wetland, and Yezo virus infections |
Apoi virus infection, dengue without/ with warning signs/ severe dengue, Far Eastern tick- borne encephalitis, Japanese encephalitis, Karshi virus infection, Kyasanur Forest disease |
— | Banna virus infection | — | — |
| Batai, Bhanja virus infections, Crimean-Congo hemorrhagic fever, hemorrhagic fever with renal syndrome, Nairobi sheep disease virus infection, sandfly fever |
Dengue without/with warning signs/severe dengue, Japanese encephalitis, Kyasanur Forest disease, West Nile virus infection, Zika virus disease |
Dhori, Quaranfil, Thogoto virus infections |
— | Chandipura, Isfahan virus infections, variegated squirrel bornavirus 1? |
||
| South- Eastern Asia |
Batai virus infection, hemorrhagic fever with renal syndrome |
Dengue without/with warning signs/severe dengue, Japanese encephalitis, West Nile virus infection, Zika virus disease |
— | — | — | Chikungunya virus disease |
| Aigai, Batai, Bhanja virus infections, Crimean-Congo hemorrhagic fever, hemorrhagic fever with renal syndrome, sandfly fever, Taˇchéng tick virus 1, Tamdy virus infections |
Alkhurma hemorrhagic fever, Central European tick- borne encephalitis, dengue without/with warning signs/severe dengue, West Nile virus infection |
Dhori, Quaranfil virus infections |
— | — | ||
| Latin/ Central America and the Caribbean |
Alenquer, Apeú virus infections, Argentinian hemorrhagic fever, Bolivian hemorrhagic fever, “Brazilian hemorrhagic fever”, Bunyamwera, Candirú, Caraparú, Catú, Chagres, Chapare, Coclé, Echarate, (Flexal,) Fort Sherman, Guamá, Guaroa virus infections, hantavirus pulmonary syndrome, Iquitos, Itaquí, Juquitiba virus infections, lymphocytic choriomeningitis, Madrid, Maguari, Maldonado, Marituba, Mayaro, Morumbi, Murutucú, Nepuyo, Oriboca virus infections, Oropouche virus disease, Ossa, Punta Toro, Restan, Serra Norte, Tacaiuma, Trinidad virus infections, Venezuelan hemorrhagic fever, Wyeomyia, Xingu, Zungarococha virus infections |
Bussuquara, Cacipacoré virus infections, dengue without/with warning signs/severe dengue, Ilhéus, Rio Bravo virus infections, Rocio viral encephalitis, Spondweni, St Louis encephalitis, yellow fever, Zika virus disease |
— | — | Piry fever, vesicular stomatitis fever |
Chikungunya virus disease, Madariaga, Mayaro, Mucambo, Tonate, Una virus infections, Venezuelan equine encephalitis |
TABLE 215-3 Clinical Syndromes Caused by Zoonotic Arthropod-Borne or Rodent-Borne Viruses SYNDROME Fever and myalgia…¶
Harrison's 22e, p.1666
| SYNDROME | VIRUS |
|---|---|
| Fever and myalgia (F&M) | Arenaviridae: (Flexal,) Lassa and lymphocytic choriomeningitis viruses Flaviviridae: Bussuquara, Banzi, Cacipacoré, Dakar bat, dengue 1–4, Edge Hill, Karshi, Kédougou, Koutango, Ntaya virus, Rio Bravo, Sepik, Spondweni, tick-borne encephalitis, Wesselsbron, and Zika viruses Hantaviridae: Choclo virus Nairoviridae: Dugbe, Issyk-kul, Nairobi sheep disease, So–nglˇıng viruses, Taˇchéng tick virus 1, Tamdy, wetland, Yezo virus Orthomyxoviridae: Bourbon, Dhori, and Thogoto viruses Peribunyaviridae: Apeú, Bangui, Batai, Bunyamwera, Bwamba, Cache Valley, California encephalitis, Caraparú, Catú, Fort Sherman, Germiston, Guamá, Guaroa, Ilesha, Inkoo, Iquitos, Itaquí, Jamestown Canyon, La Crosse, Lumbo, Madrid, Maguari, Marituba, Nepuyo, Ngari, Nyando, Oriboca, Oropouche, Ossa, Pongola, Restan, Shokwe, snowshoe hare, Tacaiuma, Tˇahynˇ a, Tataguine, Wyeomyia, Xingu, and Zungarococha viruses Phenuiviridae: Alenquer, Bhanja, Candirú, Chagres, Dar es Salaam, Echarate, Heartland, Maldonado, Morumbi, Punta Toro, Rift Valley fever, sandfly fever Cyprus, sandfly fever Ethiopia, sandfly fever Naples, sandfly fever Sicilian, sandfly fever Turkey, Serra Norte, severe fever with thrombocytopenia syndrome, Toscana, and Uukuniemi viruses Sedoreoviridae: Kemerovo, Lebombo, Orungo, and Tribecˇ viruses Spinareoviridae: Colorado tick fever, Eyach, and Salmon River viruses Rhabdoviridae: Ekpoma virus 1, Ekpoma virus 2, Chandipura, Isfahan, Piry, vesicular stomatitis Indiana, and vesicular stomatitis New Jersey viruses Togaviridae: Everglades, Madariaga, Mucambo, Tonate, Una, and Venezuelan equine encephalitis viruses |
| Encephalitis | Arenaviridae: lymphocytic choriomeningitis virus, (Whitewater Arroyo virus) Flaviviridae: Apoi, Ilhéus, Japanese encephalitis, Karshi, Modoc, Murray Valley encephalitis, Powassan, Rocio, St. Louis encephalitis, tick-borne encephalitis, Usutu, and West Nile viruses Orthomyxoviridae: Dhori and Thogoto viruses Bornaviridae: variegated squirrel bornavirus 1 Peribunyaviridae: Cache Valley, California encephalitis, Cristoli, Inkoo, Jamestown Canyon, Keystone, La Crosse, Lumbo, Oropouche, snowshoe hare, Shuni, and Tˇahynˇ a viruses Phenuiviridae: Adria, Bhanja, Chios, Rift Valley fever, (Taˇchéng tick virus 2), and Toscana viruses Sedoreoviridae: Banna, Kemerovo, and Orungo viruses Spinareoviridae: Colorado tick fever, Eyach, and Salmon River viruses Rhabdoviridae: Chandipura, Mundri viruses Togaviridae: eastern equine encephalitis, Everglades, Madariaga, Mucambo, Tonate, Venezuelan equine encephalitis, and western equine encephalitis viruses |
| Viral hemorrhagic fever (VHF) | Arenaviridae: Chapare, Guanarito, Junín, Lassa, Lujo, (lymphocytic choriomeningitis,) Machupo, and Sabiá viruses Hantaviridae: Amur, Dobrava, El Moro Canyon, go– u, Hantaan, Kurkino, Muju, Puumala, Saaremaa, Seoul, Sochi, and Tula viruses Nairoviridae: Crimean-Congo hemorrhagic fever virus Peribunyaviridae: (Ilesha virus,) Ngari viruses Phenuiviridae: Rift Valley fever and severe fever with thrombocytopenia syndrome viruses Flaviviridae: Alkhurma hemorrhagic fever, dengue 1–4, Kyasanur Forest disease, Omsk hemorrhagic fever, (tick-borne encephalitis,) and yellow fever viruses Rhabdoviridae: (Bas-Congo virus) |