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Synanthropic rodents as virus reservoirs and

transmitters

INTRODUCTION

Rodents (Order: Rodentia) are distributed on all continents except for

Antarctica

1

. Their heterogeneous and cosmopolitan distribution expands as their

interaction with humans increases

2

. Some species are better able to adapt to urban environments

(synanthropism).

In a study conducted in Buenos Aires (Argentina), black rats (Rattus

rattus) were found in residential and industrial areas, while house

mice (Mus musculus) and brown rats (Rattus

norvegicus) were captured in green areas and shantytowns

3

, where their presence was favored by easy access, availability of shelter,

and large food supply

4

. These animals are natural reservoirs of infectious diseases

5

,

6

, and are involved in the emergence and dissemination of viruses, bacteria,

and protozoa. The transmission of these agents can occur through both direct (bite,

contact) and indirect (urine, feces) means, through vectors (ticks, fleas, and

mites) that infest rodents, or when they are predated by other species

1

,

7

,

8

. Although little information is currently available on the size of the population of

synanthropic rats, some indicators allow the subjective estimation of their

presence, such as the presence of excrement, marks on walls, trails on the ground,

food sources, or the visual observation of rodents and/or the damage caused by

them

9

-

11

. To evaluate the size of rodent populations, the concept of the ‘minimum known number’

is used

12

, where individuals have to be captured and recaptured to estimate the

infestation rate. This statistical formula can be simplified by multiplying the

number of animals caught in a trap in a single catch by 100

11

,

13

. A survey carried out in 1529 dwellings in a low-income region of São Paulo (Brazil)

showed an initial synanthropic rodent infestation rate of 40%, which was reduced to

14.4% after the implementation of sanitary education and pest control

13

. Similarly, in Pau de Lima (Bahia, Brazil), 62% of households (137/221)

presented signs of active rodent infestations

14

. Besides synanthropic species, other rodents can cocirculate in rural environments and

wild and urban interface areas, where they contact other animals and people

10

,

15

. Wild rodents are reservoirs for hantavirus, vaccinia virus, and

Lassa virus, among others

16

-

19

. Fernandes et al. (2019)

20

investigated rural settlements in Goiás (Brazil), and found 2.57% (n=12)

positive rate for Orthohantavirus, equally distributed between

women and men (n=6). In contrast, similar studies showed higher frequency in

middle-aged men due to their risk behaviors

21

,

22

. Refugee camps accommodate large number of people and consequently there is

accumulation of food and residues, attracting rodents (synanthropic and wild). In

Africa, studies have revealed the circulation of Mastomys

natalensis infected by Lassa virus in these camps,

which is facilitated by the dissemination routes of the virus (urine, fomites,

consumption of rodents as food)

23

. Bonner et al. (2007)

24

investigated communities of up to 9,000 people and determined that the

quality of housing, external hygiene, and the visualization of rodent burrows were

the main epidemiological factors associated with the spread of Lassa

virus.

Aircrafts and ships may also contribute to the introduction of rodents and even

dissemination of diseases in new areas

25

,

26

. Consequently, the World Health Organization (WHO) has implemented rodent

control measures at airports and ports, including periodic surveys to verify the

absence of rodents onboard vessels. According to reports, 24.7% (270/1093) of moored

ships at the port of Shanwei (China) were infested with rats

25

. In Heilongjian, another Chinese port area, 4.47% of the 649 collected rats

tested positive for hantavirus

27

. Therefore, this article aims to review important viral agents disseminated by

synanthropic rodents (M. musculus, R. rattus, and

R. norvegicus), and thereby contribute to a better

understanding of disease epidemiology and prevention.

SEARCH STRATEGY AND SELECTION CRITERIA

Scientific texts in English and Portuguese were retrieved from the PubMed, Scopus,

Web of Science, and Scielo research platforms using the search term “virus” in

combination with “disease” and “rat or rodent or murine”. Additionally, a second

more refined research was performed with the terms “Hepatitis E,” “Hantavirus,”

“Rotavirus,” “Coronavirus”, or “Arenavirus” associated with “rat or rodent or

murine.”

Among the resulting, studies mainly related to synanthropic rodents (M.

musculus; R. rattus; R. norvegicus)

collected in the field were selected, excluding the studies restricted to animal

experimentation.

Thus, hepatitis E, hantavirus, rotavirus, coronavirus, and arenavirus are the focus

of this review, as they are neglected diseases transmitted by rodents.

HEPATITIS E (HEV)

The hepatitis E virus (HEV) has a single-stranded RNA genome of approximately 7 kb

length

28

. As a member of the Hepeviridae family, the genus

Orthohepevirus has four species (from A to

D)

29

, among which Orthohepevirus A and C have

already been described in rodents

30

. Infection occurs via the fecal-oral route through the consumption of water

contaminated with excrement or the consumption of raw/undercooked meat and the

viscera of infected animals

31

. The prevalence rate in humans reaches 40% in industrialized countries, and

the virus has been detected in blood banks

32

. Socially vulnerable people may be an important epidemiological group at

risk, along with patients who depend on blood transfusions

33

,

34

. The virus shows tropism to digestive system and is eliminated in stool after 4 to 23

days of infection

35

, remaining in this state for additional 5 weeks

36

,

37

. The symptoms are mainly nonspecific, and include fever, headaches, abdominal pain,

but these infections may also be asymptomatic (depending on the HEV dose to which

the patient was exposed), hindering the detection, and potentiating the agent’s

spread

38

-

40

. Mortality rates are higher among infected people presenting previous liver disease,

immunocompromised patients, and pregnant women, as they present higher chances of

renal failure leading to death

33

,

41

,

42

. The role of black rats (R. rattus) and brown rats (R.

norvegicus) as reservoirs and transmitters of this viral agent and its

prevalence rate remains unknown

30

. Orthohepevirus A has seven different genotypes (HEV1-7) defined by

the concatenated amino acid distance between the open reading frames of ORF1

(nonstructural proteins) and ORF2 (capsid proteins)

43

. HEV-1 and HEV-2 occur only in humans; HEV-3 has been isolated from humans

and several animal species; HEV-4 has been isolated from humans and pigs; HEV-5 and

HEV-6 have been identified only in wild boars; and HEV-7 has only been found in

camels

44

. The presence of anti-HEV IgG

30

,

45

, and the detection of viral particles in the feces of these rodents (with or

without seroconversion) have been demonstrated

37

,

46

,

47

. However, only a single study has shown similarities between rodent

(R. norvegicus) strains with regard to the HEV-3 genotype,

which is most closely related to the genotypes found in rabbits

37

. On the other hand, rat HEV (genotype C1), belonging to the

Orthohepevirus C group, has been reported in R.

norvegicus and R. rattus, although its potential to

cause disease in humans is still questioned

37

,

47

. In Vietnam, animals captured at bus stations and hospitals have tested positive for

rat HEV

48

. These findings are supported by serological evidence from domestic animals

and rodents in other studies

45

,

49

,

50

. Detection methods for HEV include serological (specific IgG), histopathological, and

molecular (RT-PCR) techniques

41

. Commercially, there are no specific prophylatic measures available on the

market, although Chinese researchers have developed the HEV p239 vaccine from the

HEV1 genotype

51

. Its efficacy is considered high (> 90%), requiring three doses (0,.1 and

6 months), and it may be used even in pregnant women

52

.

HANTAVIRUS (HV)

Hantaviruses, belonging to the Hantaviridae family, are divided into

four genera: Loanvirus, Mobatvirus,

Thottimvirus, and Orthohantavirus

53

. These enveloped viruses have a negative-sense RNA genome segmented into

three fragments: Large - L (6.8-12 kb), Middle - M (3.2-4.9 kb), and Small - S (1-3

kb). They encode four proteins; the L segment encodes viral polymerase, while the M

and S segments encode the precursor (GPC) of two viral surface glycoproteins (G1 and

G2, alternatively called Gn and Gc), and the nucleocapsid (N) protein,

respectively

54

. More than 50 species of hantaviruses have been reported worldwide

55

; however, some of them do not cause diseases, including the Prospect

Hill virus

56

. Rodents, bats, and moles are reservoirs of these agents

57

; transmission occurs through bites (saliva), and especially via the

inhalation of viral particles from the feces and urine of these animals

58

. Despite a report of transmission between humans, this form is rare

59

. The Orthohantavirus genus includes the greatest number of pathogenic

species of public health importance

60

. Its presence is associated with the geographic distribution of rodents

(Murinae, Avicolinae, and Sigmodontinae families), which can harbor

distinct forms of the disease.

The earliest reports of hemorrhagic fever with renal syndrome (HFRS), caused by

viruses known as Old World hantaviruses (Europe and Asia), come from Chinese

writings dating from 960 BC. Later, in the Korean War (1951-1954), these diseases

caused the death of over 3,000 soldiers

61

. The Hantaan virus (HTNV) species was related to this

outbreak. HTNV was isolated for the first time in 1978

62

and was linked to the rodent Apodemus agrarius; the virus

was detected in blood, urine, feces, and respiratory tract samples. In humans, this

species causes a severe form of HFRS, which has thus far been restricted to rural

areas of China, Korea, and Russia

63

,

64

. Dobrava virus (DOBV) is also associated with HFRS syndrome, for

which men are accidental hosts

65

. Mortality rates vary according to the genotype, ranging from 0.5% (DOBV -

Kurkino) to 12% (DOBV - Dobrava and DOBV -

Sochi)

66

,

67

. The most commonly detected viral agent of this group in Western Europe,

Puumala virus (PUUV), is disseminated by Myodes

glareolus, whose proliferation is favored by the underbrush vegetation

of this region, and the spread of the virus is further affected by virus-host

coevolution

68

. In humans, it causes moderate nephropathy, and can lead to subclinical

infections

69

. Seoul virus usually causes mild infections and without medical care

the mortality rates reach 1%. The host of this virus (R.

norvegicus) is found in urban areas, leading to a cosmopolitan distribution

of the disease, in contrast to those caused by other Old World hantaviruses

60

,

70

. The incubation period varies from 2-3 weeks, and the endothelial cell

tropism of the virus

71

produces nonspecific symptomatology (fever, headaches, muscle pain, nausea,

vomiting), in addition to respiratory problems, dizziness, and diarrhea.

Thrombocytopenia entails the development of petechias, and decreased blood pressure

affects kidney function, causing renal failure followed by disseminated

intravascular coagulation

72

. Hantavirus cardiopulmonary syndrome (HCPS) is another pathology associated with

agents of the genus New World hantaviruses (Americas), and appears to be related to

climatic phenomena such as El Niño

58

. The first report of hantavirus in Brazil dates from 1993, when

Juquitiba virus, transmitted by Oligoryzomys

nigripes, was detected by Silva et al. (1997)

73

. To date, the following viruses have been identified in the

country: (a) Araraquara virus (transmitted by Necromys

lasiurus rodents); (b) Castelo dos

Sonhos virus (Oligoryzomys utiaritensis); (c)

Laguna Negra virus (Calomys callidus); (d)

Anajatuba virus (Oligoryzomys mattogrossae);

and Rio Mamore virus (Oligoryzomys microtis),

among others

20

. The incubation period of HCPS ranges between 16-24 days, with initial nonspecific

HFRS-like symptomatology differentiated by pulmonary edema and lymphoid organ

impairment

74

, which may cause cardiovascular shock and death

72

. Studies indicate that this pulmonary phase lasts approximately 1 week, but

long-lasting sequelae have been reported, such as dyspnea and weakness

61

. According to available data from the Brazilian Ministry of Health, 2061

people had been infected in the country as of 2017, with a lethality rate of

40.1%

75

. In rodents, this virus causes a chronic infection with mild symptomatology such as

decreased growth

76

and renal problems

77

, although it is usually asymptomatic. This can be explained by the

coevolution of rodents with the virus over millions of years

78

. Hantavirus can be diagnosed by associating the patient’s history with the

presence of wild or synanthropic rodents. Tests for hantavirus include specific

serological detection using ELISA (IgM or IgG) or viral detection using RT-PCR or

real-time PCR

79

. The occurrence of HFRS has not yet been reported in Brazil, despite serologically

positive human and rodent samples

80

. For example, in an urban area in Salvador, Brazil, Seoul

virus antibodies were found in R. norvegicus serum samples

81

. A molecular survey conducted in Madagascar detected the

Anjozorobe virus (Thailand Orthohantavirus)

strain in R. rattus and M. musculus, suggesting

viral spillover

82

. To our knowledge, there is no licensed vaccine available on the market that prevents

hantavirus infections. Several clinical trials at different stages are ongoing to

test inactivated (monovalent and bivalent), DNA, and live attenuated vaccines for

both HFRS and HCPS, with effectiveness of approximately 93.77-100% being

reported

83

-

85

. Additionally, studies have demonstrated that the use of antiviral ribavirin

increases the survival rate in hantavirus-infected rats

86

-

88

.

ROTAVIRUS (RV)

Rotavirus (RV) belongs to the Rotavirus genus within the

Sedoreovirinae subfamily of the Reoviridae

family

53

. These nonenveloped viruses have a double-stranded RNA genome of

approximately 18550 bp in length, fragmented into 11 segments. The genome encodes

six structural (VP1, VP2, VP3, VP4, VP6, and VP7) and six nonstructural (NSP1, NSP2,

NSP3, NSP4, and NSP5/6) proteins, as the NSP5/6 gene is bicistronic

89

,

90

. Myriad mechanisms of viral variability occur in RVs, such as point mutations,

rearrangements, reassortments, and intragenic recombination, conferring great

genetic diversity

91

,

92

. This genus is divided into nine different groups (RVA-RVI) based on the

antigenic properties and nucleotide sequences of the VP6 protein

89

,

93

,

94

, and there is a potential candidate tenth group, RVJ

95

. For the RVA group, it is necessary to adopt the notation of

Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-Tx-Ex-Hx, which considers all the variability presented by

the coding genes of the VP7-VP4-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6 proteins,

respectively

96

. To date, this group has at least 36 known G genotypes and 51 known P

genotypes in humans and animals

93

,

97

-

99

. Although rotaviruses are considered species-specific, heterologous infections may

occur

100

. Wa-like and DS1-like (RVA) strains primarily cause disease in humans, and

infections caused by genotypes and serotypes common to animals have also been

documented

100

,

101

. Synanthropic rodents are usually not associated with RVs, however, their efficiency

in disease transmission and their close contact with other animals and people

highlight their importance to the epidemiology of these viruses

101

,

102

. Transmission initially occurs through the fecal-oral route, via particles present in

the soil and water, causing diarrhea due to the loss of absorptive capacity of

injured intestinal cells during viral replication

103

. Diarrhea is a leading cause of infant mortality worldwide, and rotavirus

infections are responsible for more than 35% of these cases

104

. RVs are widely distributed in Brazil, and have been described in animals (both young

and adults) such as cattle

105

, birds

106

, and pigs

107

,

108

. In rodents, there is a single report of RVA associated with swine

production

109

. A metagenomic analysis of R. norvegicus in Germany characterized a

sample of RVA, revealing close identity between the identified strain and other

animal and human strains, namely, genotypes G3, P[3], and N2

110

. In Italy, 40 fecal samples from R. rattus collected on swine farms

were analyzed, and a sample of RVA was characterized

(G3-P[3]-I1-R11-C11-M10-A22-N18-T14-E18-H13), demonstrating an atypical combination

of genotypes

102

. As the associated symptomatology is mainly nonspecific, the diagnosis can easily be

misleading

111

. Commercial ELISA kits, RT-PCR (single or multiplex), and qPCR assays

99

,

102

,

110

are available for the detection of these infections.

To control this disease, animal vaccination (swine and cattle) should be carried out,

mainly in females in the late gestation period. In production animals, prevalence

rates may be higher than 90% in adults

103

. For humans, two vaccines are authorized by the WHO: (a) Rotarix®

(GlaxoSmithKline Biologicals, Rixensart, Belgium, an attenuated strain of G1P

RVA) and (b) RotaTeq® (Merck & Co., Whitehouse Station, NJ, with five strains of

genotypes G1P, G2P, G3P, G4P and G6P).

CORONAVIRUS (COV)

Coronaviruses are enveloped, nonsegmented, positive, single-stranded RNA viruses

associated with the structural N-phosphoprotein in a nucleocapsid with helical

symmetry

112

,

113

. They are found in a wide variety of animals causing respiratory, enteric,

hepatic, and neurological diseases of varying severity

114

. According to the International Committee on Taxonomy of Viruses, two

subfamilies belong to the Coronaviridae family;

Letovirinae, which has one subgenus,

Milecovirus, found only in frogs and a sea hare thus far

115

, and Orthocoronavirinae, which is found in birds and

mammals, and is divided into four genera due to the antigenic and genetic

characteristics of the viruses

53

,

116

. Phylogenetic studies indicate that bats are the gene source for

Alpha and Betacoronaviruses, while birds are

the gene source for Gama and Deltacoronaviruses

117

. Thus, Alpha and Betacoronaviruses are

found mainly in mammals, such as humans, dogs, cats, pigs, bats, mice, rats, horses,

and cattle

114

,

118

-

123

, while Gama and Deltacoronaviruses infect

mainly birds, with exceptions such as the white whale

Gamacoronavirus (Delphinapterus leucas)

124

and the porcine Deltacoronavirus

125

. Among the Alpha and Betacoronaviruses, six are of

public health importance, causing mild (HCoV-229E, NL63, OC43, and HKV1) to severe

respiratory syndromes (SARS and MERS)

120

,

126

,

127

. Despite the many uncertainties about the epidemiology and reservoirs of severe acute

respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), bats

have been identified as the most likely reservoirs, while palm civets

(Paguma larvata)

128

and dromedary camels (Camelus dromedarius)

129

,

130

act as intermediary hosts before dissemination to humans

120

,

131

,

132

. Both diseases have caused worldwide health problems, affecting 27 countries

and causing hundreds of deaths in 2002 (SARS) and 2012 (MERS), aggravated by

nosocomial transmission or transmission by family members

126

. In general, the virion contains at least three proteins: the spike (S), membrane (M),

and envelope (E) proteins. In addition, some coronaviruses include hemagglutinin

esterase (HE)

133

. Proteins M and E are related to viral assembly

134

, while the S protein show hemagglutinating activity and is the main target

for neutralizing antibodies

135

. The S protein, which shows great variability, is responsible for host specificity

because its S1 and S2 subunits are used for binding the virus to host cell

receptors, and are associated with the antigenicity and pathogenicity of the

virus

112

,

136

. Many similarities exist between the CoVs of rats and bats

119

,

120

,

140

,

141

, suggesting that rodents could act as important reservoirs

142

. A survey conducted on 330 intestinal content samples from rodents

(Apodemus sp., Myodes glareolus,

Arvicola terrestris, and Microtus sp.),

collected between 2014 and 2016 in different regions of France

121

, revealed positivity of 6.3% (21 samples), all belonging to

Alphacoronavirus groups. This study also revealed

Alpha and Betacoronavirus in bats, rabbits,

and hedgehogs from the same area

121

. An investigation conducted in China

120

, analyzed 177 rodent intestinal samples from three different species

(Apodemus chevrieri, Apodemus ilex, and

Eothenomys fidelis), and found Alpha and

Betacoronavirus in 13% (23 samples).

Besides field investigations, rodent CoV also has an important role as Murine

hepatitis virus (MHV)

137

, and has been used for experimental infections, mostly for the

identification of potential viruses showing interspecies transmission

119

. Although there is little information about the prevalence and diversity CoV

in rodents

138

,

139

, many new species of Alpha and

Betacoronaviruses (LRNV, LAMV, LRLV, and HKU24) have been

identified in rodents in China and Europe

119

,

120

,

140

,

141

. Some vaccine candidates are being developed only for MERS-CoV, including

whole-virus, vectored virus, DNA, and protein-based vaccines, however, lack of

investment is delaying their development

143

.

ARENAVIRUS (AV)

Arenaviruses (genus Arenavirus, family

Arenaviridae) are enveloped viruses with an RNA genome segmented in

two ambisense single stranded molecules: small (S) and large (L)

53

. The S portion encodes nucleocapsid protein and envelope glycoproteins,

while L segment contains RNA dependent RNA polymerase (RdRp) and zinc-binding

protein genes. Both S and L intergenic regions may potentially form one or more

hairpins, which regulate mRNA transcription

53

,

144

-

146

. This viral family has four genera, based on phylogenetic analysis involving pairwise

sequence comparisons (PASC) of complete genomes

53

,

147

. Antennavirus genus includes viruses that infect

frogfish

148

, Hartmanivirus and Reptarenavirus infect

snakes, and Mammarenavirus, which have been reported in bats,

ticks, rodents, and primates, including humans

146

,

147

. Mammarenaviruses are correlated to the geographical location where

their hosts are found

147

; currently classified as: (a) Old World (OW) (Lassa virus,

Lujo virus, among others), and found mainly in Africa in

rodents of the Murinae family as natural hosts

149

. Although Lymphocytic choriomeningitis virus (LCMV) belongs

to this category, it circulates globally

146

. Approximately 5% of the human population have been exposed to LCMV, due to

the ubiquity of the virus host, M. musculus

150

; (b) New World (NW), found in the American continent, are divided into four

clades (A-D)

151

. Examples of NW viruses are Junin virus - Argentina

152

, Machupo virus - Bolívia

153

, Sabiá virus - Brazil

154

, and Guanarito virus - Venezuela

155

. Sigmodontinae rodents are the main hosts of this class,

even though Tacaribe virus has already been described in bats

156

and Amblyomma americanum ticks

157

. Members of both OW and NW arenaviruses can cause hemorrhagic fever and severe human

diseases affecting the central nervous system

158

. Zoonotic transmission is through contact with rodents’ urine or feces, and

human-to-human transmission is possible

146

. Because of their impact on human health and rapid spread, they are

potential bioterrorism agents

159

. In Colombia, a study conducted with M. musculus, collected from

residential areas, detected 10% (8/80) of positives in serological analysis for

LCMV. When brain samples of the same animals were submitted to RT-PCR, serologically

negative individuals showed positive results in this second analysis, highlighting

the importance of parallel diagnosis

160

. It can be justified by the vertical transmission among rodents that may

deactivate cytotoxic T- lymphocytes, generating immune-complexes that may lead to

misdiagnosis of ELISA reactions

160

. A research conducted in French Guiana sampled 37 animals (M.

musculus) of which two were positive for LCMV by hemi-nested PCR (from

lung and kidney samples)

161

; another inquiry in Argentina reported that 9.4% of the mice collected were

positive for arenavirus, and the serological rate was 4.6% and 2.6% for men and

women, respectively

162

. In Baltimore (USA), 9% of the mice were seropositive for LCMV

163

, and 4.7% of the people were analyzed

164

. In Brazil, to our knowledge, there are no serological records on the

prevalence of LCMV in rodents or humans.

Lassa virus (OW) is endemic in African countries, with

seroprevalence reaching about 50% of the human population; this disease causes about

5,000 deaths every year

165

. Mastomys natalensis is considered the main reservoir of

the virus

166

, but it can also be found in Hylomyscus pamfi and

Mastomys erythroleucus

167

. Surveys conducted in Nigeria reported positive animals for Lassa

virus in M. natalensis and M.

erythroleucus, R. rattus

168

, and M. musculus

169

. In China, RT-PCRs performed in organs of R. rattus and

R. norvegicus showed positive rates of 75% and 17%,

respectively, and a new viral species, the Wenzhou virus, was

isolated

145

. Junin virus is considered endemic in Argentina

170

and sporadic outbreaks have been reported

171

. There are several promising vaccinal prototypes being developed for this

virus, most are in the preclinical stage

172

and one, based on plasmidial DNA, has already reached human test phase

173

. In Brazil, the most remarkable arenavirus is Sabiá virus, reported

in São Paulo (Brazil) in 1994. Initial symptoms were described as flu-like (fever,

sickness, headaches, and lethargy), quickly leading to hemorrhage and death (within

3 days)

154

,

174

. There have been two reports of this virus, caused by occupational exposure

in a laboratory environment, one in Pará (Brazil) and the other in Connecticut

(USA), both with non-fatal courses

175

,

176

. The 4th case was described in São Paulo (Brazil) in 1999

177

and the 5th, on January 2020 in Sorocaba (São Paulo, Brazil)

178

as a natural infection with lethal outcome.

A new arenavirus, namely Pinhal virus, has been characterized as a

New World arenavirus (line C), first isolated from vesper mice (Calomys

tener) in São Paulo (Brazil), but there is still no evidence that this

viral strain causes disease to humans

177

,

179

. Besides Pinhal virus, other arenaviruses have been

reported in Brazil: Xapuri virus was recently isolated from rodents

(Neacomys musseri); Amaparí virus

(Neacomys guianae); Cupixi virus

(Oryzomys megacephalus); Flexal virus

(unidentified Oryzomyini rodent); Oliveros virus

(Necromys lasiurus); Latino virus

(Calomys callosus and Calomys callidus) and

Aporé virus (Oligoryzomys mattogrossae)

180

. Arenaviruses can be diagnosed using: (a) RT-PCR (fluids, feces, and tissues) followed

by viral RNA sequencing for differentiation; (b) serology, through detection of

specific IgG and IgM employing immunofluorescence and/or ELISA tests; (c) viral

isolation in cell culture.

Recommended treatment is support therapy that can be combined with the antiviral

ribavirin, which should be administered during the first 7-10 days after infection.

Despite its efficacy, there are significant side effects, such as hemolytic anemia,

progressive weight loss, respiratory difficulty, insomnia, and dermatitis, among

others

180

-

182

. Alternative drugs with less side effects have been tested, such as

favipiravir

183

and triarylmethane clotrimazole

184

. Cocktails using multiple antiviral drugs that target different steps of the

viral life cycle appear to be the best strategy to limit viral multiplication with

lower risk of drug resistance

185

. In literature we find description of viral rodent-infections, usually from within the

context of biological models or experimentation. In this review, we focus on rodents

within an urban environment, especially R. rattus, R.

norvegicus, and M. musculus, although with the

advancement of human populations, the interaction with wild rodents increases, and

different viruses can emerge. There are relatively few studies addressing the

monitoring of viruses in these hosts, favoring the occurrence of outbreaks.

Control and preventive activities should go beyond the elimination or reduction of

the populations of these hosts and involve sanitary education to aid the human

population in the reduction of shelters for the hosts, the restriction of rodent

access to residences, and the reduction of their water and food supply. Basic

sanitation actions are a generic but effective measure in the reduction of rodents

and, consequently, the propagation of diseases.