Am. J. Trop. Med. Hyg., 101(6), 2019, pp. 1212–1218
doi:10.4269/ajtmh.18-0850
Copyright © 2019 by The American Society of Tropical Medicine and Hygiene
Serologic Evidence of Zoonotic Alphaviruses in Humans from an Indigenous Community in the
Peruvian Amazon
Jocelyn G. Pérez,1* Jean-Paul Carrera,2 Emmanuel Serrano,3,4 Yaneth Pittı́,2 Jorge L. Maguiña,5 Gregorio Mentaberre,3,6
Andrés G. Lescano,5 Anayansi Valderrama,2 and Pedro Mayor3
1University of Liverpool, Liverpool, United Kingdom; 2GorgasMemorial Institute of Health Studies, Panama City, Panama; 3Universitat Autònoma
de Barcelona, Barcelona, Spain; 4Universitá di Torino, Torino, Italy; 5Universidad Peruana Cayetano Heredia, Lima, Peru; 6Universitat de Lleida,
Lleida, Spain
Abstract. Alphaviruses (Togaviridae, Alphavirus) are arthropod-borne single-stranded RNA pathogens that cause
febrile and neurologic disease in much of Latin America. However, many features of Alphavirus epidemiology remain
unknown. In 2011, we undertook a cross-sectional study in Nueva Esperanza, an indigenous community in the Peruvian
Amazon. Here, we present the first serologic evidence of Mayaro (MAYV), Venezuelan equine encephalitis (VEE) complex
alphavirus, Una (UNAV), and Madariaga (MADV) viruses reported in humans (24%, 16%, 13%, and 1.5%, respectively)
fromanAmazonian indigenous community inPeru. Hunting activity andcohabitingwith hunterswere themain risk factors
forMayaro seroconversion, but only huntingwasassociatedwithUNAVseropositivity.Our results suggest that alphavirus
infection in this region is common, but we highlight the high UNAV seroprevalence found and corroborate the lowMADV
prevalence reported in this region. Furthermore,MAYV-neutralizing antibodieswere also detected in stored samples from
wild animals (18%) hunted by Nueva Esperanza inhabitants and another mestizo community located close to Iquitos.
Further serological surveys of VEE complex alphaviruses, UNAV, and MADV in wild animals and assessing the ability of
the MAYV seropositive species to transmit the virus will be relevant.
INTRODUCTION studying this region. Furthermore, the continuous ecologi-
cal disturbance in the Amazon rainforest through human
Arthropod-borne zoonotic alphaviruses (Togaviridae, activities such as hunting, logging, and ecotourism may be
Alphavirus) are positive-sense single-strand RNA viruses significant risk factors for infection with these viruses.4,14
that are recognized as an important cause of acute febrile Therefore, we sought to investigate the epidemiology of
illness in humans in Latin America. In the Peruvian Amazon, these viruses through a cross-sectional serosurvey, in-
Mayaro virus (MAYV) accounts for nearly 1% of outpatient volving humans and wildlife, in an indigenous community of
evaluations for febrile disease,1 and cases have been re- the Peruvian Amazon.
ported in Latin American countries as well as in travelers
returning from the Amazon Basin.2,3 Venezuelan equine
encephalitis (VEE) complex alphaviruses, such as VEE virus MATERIALS AND METHODS
(VEEV), have caused outbreak within the urban areas of Human and animal survey. This study was conducted in
Iquitos, the largest city in the Peruvian Amazon, but few
4,5 Nueva Esperanza (S 04
19.53 W 71
57.33), 302 km northeast
neurological cases and deaths have been observed. Less from Iquitos (Figure 1). This is an indigenous community of 297
is known about Madariaga virus (MADV) infection in this inhabitants, whose main occupations are small-scale agri-
region. Despite the enzootic circulation and intensive sur- culture, fishing, logging, and subsistence hunting. In 2011, we
veillance, only few seropositive individuals and no neuro- collected human serum samples from 70 volunteers (ranged
logic disease or fatal cases have been reported.6 However, from age 5 to 81 years) of this community. Between 2007 and
encephalitis cases and mild or asymptomatic cases mostly 2008, we also collected blood samples from 90 wild animals
affecting children have been attributed to MADV recently in harvested by local hunters from Nueva Esperanza and Sol
Venezuela, Haiti, and Panama.7–10 Finally, although Una Naciente (S 03
38.26 W 73
12.57), a mestizo community lo-
virus (UNAV) has been isolated from mosquitos of the cated 26 km from Iquitos where agricultural land use has
Peruvian Amazon, it has been rarely associated with human
11,12 partially replaced the forest.
disease. Therefore, its distribution and the human dis- Laboratory testing. Human samples were first tested by
ease risk in this region remain unknown. plaque reduction neutralization tests (PRNT) against MAYV
Although these alphaviruses are a well-recognized cause (strain TRVL15537), MADV (chimeric SIN/MADV derived from
of human disease in the Americas, prior research studies Brazilian MADV strain BeAn436087), and VEE complex
were only carried out in the peri-urban area of Iquitos. An alphavirus (vaccine strain TC-83).15,16 All samples with
important reason behind this is the challenge of conducting PRNT80 titers ³ 20 were considered positive. To complement
research in Amazonian communities because of different PRNT results and as a secondary goal because of the low
barriers (e.g., geographical, sociocultural, and health ser-
13 serum volume available, the leftover sample was tested in
vice access). The lack of surveillance studies in in- triplicate for IgG antibodies to antigens of MAYV, MADV, and
digenous communities and the identification of potential VEE complex viruses. We used a capture ELISA.17 For the
wildlife hosts in the Amazon highlight the importance of ELISA, the TRVL15537 strain was used for MAYV and
sucrose-acetone antigens were prepared from MADV- (pre-
* Address correspondence to Jocelyn G. Pérez, University of Liver- pared by Dr. Robert Shope at the Yale Arbovirus Research
pool, 8 West Derby St., Liverpool L69 7BE, United Kingdom. E-mail: Unit in August 1989), and VEE complex alphaviruses (vaccine
jgpl16@liverpool.ac.uk strain TC-83 andMosso dasPedras 78V3531) infectedmouse
1212
ZOONOTIC ALPHAVIRUSES IN THE PERUVIAN AMAZON 1213
FIGURE 1. Nueva Esperanza and Sol Naciente communities in the Department of Loreto, Peru. This figure appears in color at www.ajtmh.org.
brain (provided by the US CDC and University of Texas RESULTS
Medical Branch (UTMB)World ReferenceCenter for Emerging
Viruses and Arboviruses, respectively). To discriminate MAYV Characteristics of the human population. A total of 70
positives from cross-reactivity with UNAV, the leftover from all participants (23.6% of local inhabitants) who belong to 22
the samples was houses (48.9%of total houses) were surveyed. The age range
first screened in 1:20 dilution of the UNAV
strain BT-1495-3 and then tested by PRNT80. Chikungunya was 5–81 years, with a median age of 20 (Q1 = 10 and Q3 =
virus was not tested because these samples were collected in 34.5). The proportion of females was 58.8%. A total of 18.6%
2011, before chikungunya virus circulated in the Americas. of participants declared to hunt, whereas 14.3% declared to
Wild animal samples were tested only by PRNT against participate in logging activities. The total number of persons
MAYV (strain TRVL15537). Plaque reduction neutralization per house ranged between one and seven (Table 1).
tests for VEE complex alphaviruses, MADV, and UNAV could Human seroprevalence. Based on our PRNT results, the
not be performed because of insufficient samples. seroprevalence for MAYV, VEE complex alphavirus, UNAV,
Statistical analysis. We used a recursive modeling ap- and MADV in people from Nueva Esperanza was 24% (17/70,
proach with classification trees to identify major risk factors 95%CI [16–35]), 16% (11/67, 95%CI [9–27]), 13% (6/48, 95%
linked to the presence of antibodies against these alphavi- CI [6–25]), and 1.5% (1/67, 95% CI [0–8]), respectively
ruses using the package “rpart” version 4.1–13 of the statis- (Supplemental Table 1). For MAYV, the most parsimonious
tical software R version 3.4.2.18,19 Risk factors evaluated for tree model explained 27% of likelihood of showing antibodies
prior human infection were gender, hunting activity, logging against MAYV, including two risk factors: hunting activity and
activity, and cohabitation with seropositive people. Model cohabitation with seropositive people (Figure 2). This means
simplification takes into consideration the complexity pa- that being a hunter (75%, 95%CI [42.81–94.51]) or not being a
rameter of the tree showing the minimum relative error after hunter but sharing home with MAYV seropositive people
10-fold cross-validations. (21%, 95%CI [9.5–37.3]) were the main risk factor associated
Ethics. Research protocols were approved by the Peruvian with MAYV circulation. Individuals who were nonhunters and
Forestry and Wildlife Agency (041-2007-DGFFS), the In- not living in a seropositive household were seronegative. The
stitutional Animal Care and Use Committee of U.S. Naval UNAV treemodel also showedhunting activity as themain risk
Medical Research Unit No. 6, and Instituto Nacional de Salud factor (80%, 95% CI [28.4–99.5]) for the virus infection,
del Perú (#08-982). explaining 49% of the observed UNAV seropositive variability.
1214 PÉREZ AND OTHERS
TABLE 1
Characteristics of PRNT– positive individuals (n = 40) and laboratory findings*
Venezuelan equine
Mayaro virus Madariaga virus encephalitis complex virus Una virus
Sample ID Gender Age (years) Hunter Logger House PRNT PRNT titer ELISA PRNT PRNT titer ELISA PRNT PRNT titer ELISA Screen PRNT PRNT PRNT titer
MIS0963 F 21 No No A − − − − − + + 20 + − − −
MIS0965 F 35 No No A + 20 + NP NP NP NP NP NP NP NP NP
MIS0967 M 41 Yes Yes A − − + − − + − − − + + 20
MIS0968 F 33 No No A + 40 + − − NP − − NP NP NP NP
MIS0969 M 8 No No A + 40 + − − NP − − NP NP NP NP
MIS0972 M 7 No No D − − + − − + + 80 − − − −
MIS0974 M 67 Yes No E − − + − − − − − − + + 80
MIS0975 F 64 No No E + 160 + − − + − − − NP NP NP
MIS0977 M 29 No Yes F − − + − − NP + 80 NP NP NP NP
MIS0980 M 81 Yes No F + 160 + − − − − − − + + 80
MIS0983 M 70 Yes No G + 40 + − − −− − − − + + 40
MIS0985 M 33 No Yes H + 20 + − − + − − − NP NP NP
MIS0986 M 30 Yes No H + 40 + NP NP NP NP NP NP NP NP NP
MIS0988 M 39 Yes Yes I + 20 + − − NP − − NP NP NP NP
MIS0990 F 32 No No J − − − − − − − − − + + 40
MIS0991 F 26 No No K − − + − − + + 120 − NP NP NP
MIS0992 M 10 No No K + 40 + − − NP − − NP NP NP NP
MIS0994 F 20 No No L − − + − − − − − − − − −
MIS0995 M 45 Yes Yes L + 40 + + 40 NP − − NP NP NP NP
MIS1000 F 31 No No M − − + − − + + 40 + + + 80
MIS1001 F 6 No No M − − + − − − − − − − − −
MIS1004 F 25 No No N − − + − − − − − − − − −
MIS1006 M 52 Yes Yes N + 40 + − − NP − − NP NP NP NP
MIS1007 M 46 Yes Yes N + 20 + − − NP − − NP NP NP NP
MIS1008 F 13 No No O − − + − − − + 160 + − − −
MIS1011 M 30 Yes Yes Q − − + − − + − − − NP NP NP
MIS1013 M 13 No No R − − + − − − − − − − − −
MIS1014 M 10 No No S − − + − − + + 40 + − − −
MIS1018 F 7 No No T − − + − − − − − − − − −
MIS1021 M 18 Yes No U − − + NP NP NP NP NP NP NP NP NP
MIS1022 M 47 No Yes U + 20 + − − NP − − NP NP NP NP
MIS1023 M 74 Yes No U + 20 + − − NP − − NP NP NP NP
MIS1024 M 67 Yes No Z + 40 + − − − + 40 + − − −
MIS1025 F 8 No No Z − − + − − + + 80 + − − −
MIS1026 F 20 No No Z − − + − − + + 80 + NP NP NP
MIS1028 M 20 No No Z − − + − − + − − − − − −
MIS1029 F 17 No No NA + 20 + − − NP − − NP NP NP NP
MIS1030 F 6 No No NA − − + − − − − − − − − −
MIS1031 F 12 No No NA − − + − − − − − − − − −
MIS1032 F 35 No No NA − − + − − + + 40 − NP NP NP
M = males; F = females; NA = data not available; NP = not performed because of insufficient sample; PRNT = plaque reduction neutralization test.
* Each letter represents a house.
People who did not report hunting had a lower UNAV sero- common.2,16,20 Herein, we demonstrate endemic infection
prevalence of 4–7% (95% CI [0.6–16.2]). No other variables with new world alphaviruses in the Amazon region of Peru. In
were associated. Una virus seropositiveswere also exposed to addition, we provide serologic results of potential wildlife
MAYV or other alphavirus, but some individuals only showed hosts of MAYV.
exposure to UNAV. Despite the high seroprevalence (16%) of Madariaga virus is the new designation for the South
VEE complex virus, the tree models showed that none of the American isolates of eastern equine encephalitis virus.21 In
studiedvariableswere related to thepositivecases.Risk factors South America, this virus has caused equine encephalitis
to MADV infection were not evaluated because of concerns outbreaks, but only two human caseswere detected to date
about the representativeness of the sample because only one (in Brazil and Trinidad).6 The low MADV seroprevalence
sample was found seropositive. observed in this study corroborates a previous study in
Animal seroprevalence. Anti–MAYV-neutralizing anti- Iquitos that showed a seroprevalence of 3% (9/359).6 This
bodieswere detected inwild animals (18%, 95%CI [11–27%]) result is in contrast to the high human seroprevalence and
collected near Nueva Esperanza and Sol Naciente commu- cases reported in Panama.8 Cross-protective antibodies
nities. The highest MAYV seroprevalence in wild animals was may be one of the factors limiting the infection and disease
observed in armadillos (40%), followed by nonhuman pri- in South America.6 Although the virus was isolated from
mates (33%), peccaries (11%), and rodents (10%) (Table 2). Culex mosquitoes in areas near Iquitos, our study found
only one seropositive individual, a 45-year-old male hunter
DISCUSSION and logger who also showed exposure to MAYV.11 Evi-
dence of exposure to only MADV is unusual: most sero-
Recent epidemiological and surveillance studies have positive individuals also show exposure to MAYV, VEEV, or
shown that human alphavirus infections in Latin America are UNAV.6
ZOONOTIC ALPHAVIRUSES IN THE PERUVIAN AMAZON 1215
accounted for 63 cases and one fatality.4,5 In contrast, a
higher fatality rate was reported in Panama (5%, two deaths
from 39 cases studied). Different factors may be associated
with this difference: a more active surveillance in Panama
during outbreaks, underreporting of VEEV cases in Peru, or
other factors involved in the emergence of the enzootic
VEEV (virus adaptation to mosquito species or mosquito
abundance).22 In this study, the vaccine strain TC-83,
closely related to subtype ID, was used for the PRNT. Un-
fortunately, PRNTs were not performed using other VEE
complex viruses that are geographically relevant, limiting
our ability to definitively state which VEE complex virus was
involved in these cases. Interestingly, the VEE complex vi-
rus titers are low, presumably because of the infection with
sympatric alphaviruses inducing PRNT cross-reaction.
However, antibody titers waning over time is also a possi-
bility, as most of the VEE complex virus positives are in
older age.
Mayaro infections have been principally recognized dur-
ing outbreaks in South America; however, risk factors for the
FIGURE 2. Complete (A) and final (B) classification trees exploring infection and the clinical spectrum of MAYV infections are
the influence of gender and hunting or logging behaviors on the poorly understood.1,23–26 The high seroprevalence (24%)
probability of showing antibodies againstMayaro virus in the Peruvian found in our study corroborates previous studies in indig-
Amazon forest. The factor “cohabit” indicatespeoplewhoshare home enous groups of the Brazilian Amazon, where MAYV sero-
with a Mayaro seropositive person. Note that gender was initially
retained but later excluded after model simplification. Left branches prevalence ranged from 20% to 47%, with an overall of 42%
indicate no hunters or no cohabitation, whereas the right branches for all the groups together.27 A greater seroprevalence was
summarize the probability for male hunters or cohabiting people. also found in ethnic groups of French Guiana living in contact
with the forest comparedwith thosewhodo not.28 Despite the
Venezuelan equine encephalitis complex viruses such as growing concern of MAYV as an emerging virus that may
VEEV are known to cause human disease in the Peruvian potentially spread and cause human outbreaks in theWestern
Amazon. The most recent VEEV outbreak caused by the Hemisphere, less is known about the virus ecology.29 Most
enzootic Panama/Peru ID genotype in Iquitos, in early 2006, evidence comes from Brazilian studies, which proposed
TABLE 2
Mayaro virus seroprevalence in wild animals hunted by Nueva Esperanza and Sol Naciente communities in the northeastern Peruvian
Amazon
Group Common name Scientific name No. PRNT positive (%)*
Mammals Edentate Nine-banded armadillo Dasypus novemcinctus 2/4 (50.0)
Three-toed sloth Bradypus sp. 0/1 (0.0)
Subtotal 2/5 (40)
Primate Poeppig’s woolly monkey Lagothrix poeppigii 6/11 (54.5)
Red howler monkey Alouatta seniculus 1/1 (100.0)
Red uakari Cacajao calvus 1/3 (33.3)
Large-headed capuchin Sapajus macrocephalus 1/6 (16.7)
Squirrel monkey Saimiri macrodon 0/3 (0.0)
White-fronted capuchin Cebus albifrons 0/2 (0.0)
Monk saki Pithecia monachus 0/1 (0.0)
Subtotal 9/27 (33)
Artiodactyla Collared peccary Pecari tajacu 1/6 (16.7)
Red brocket deer Mazama americana 0/3 (0.0)
Subtotal 1/9 (11)
Rodent Wild black agouti Dasyprocta fuliginosa 3/27 (11.1)
Lowland paca Cuniculus paca 1/10 (10.0)
Northern Amazon red squirrel Sciurus igniventris 0/1 (0.0)
Spiny rat Proechimys sp. 0/1 (0.0)
Subtotal 4/39 (10)
Carnivora South American coati Nasua nasua 0/4 (0.0)
Subtotal 0/4 (0)
Subtotal 16/84 (19)
Birds Blue-and-yellow macaw Ara ararauna 0/2 (0.0)
Great tinamou Tinamus major 0/2 (0.0)
Rufescent tiger heron Tigrisoma lineatum 0/1 (0.0)
Speckled chachalaca Ortalis guttata 0/1 (0.0)
Subtotal 0/6 (0)
Total 16/90 (18)
PRNT = plaque reduction neutralization test.
* Samples were first tested with an ELISA for the presence of Mayaro virus antibodies, and in those screening positive, a confirmatory PRNT was performed.
1216 PÉREZ AND OTHERS
nonhumanprimates as themost important amplifying hosts.23 whereas VEEV may cause fatal encephalitis.1 Unfortunately,
The virus was isolated from a marmoset (Callithrix sp.) cap- no medical history was available to associate the seroposi-
tured during an MAYV outbreak in Brazil, and experimental tivity with the presence of chronic arthralgia or neurologic
infections in these animals confirmed the occurrence of vire- disease.
mia post-MAYV infection.23 The virus was also isolated from Although wild animals may have contributed to the am-
only one migrating bird (Icterus spurius) from a total of 1,300 plification of MAYV during past Amazonian outbreaks,
birds studied in the United States in 1967.30 Serologic studies reservoir hosts for MADV, UNAV, and VEE complex alpha-
foundMAYVantibodies in other sylvatic vertebrates andbirds, viruses in the Peruvian Amazon remain unknown.23 We also
but their exact role in the transmission of the virus is not do not rule out the possibility that some MAYV seropositive
determined.31–33 This study detected anti–MAYV-neutralizing animal samples could be due to a cross-reaction with UNAV;
antibodies in wild animal species, which are consistent with however, this hypothesis could not be tested because of
previously described epidemiologic patterns of the sylvatic insufficient samples. In humans, we found antibodies against
cycle,where arboreal anddiurnalwild animalsweremore likely both MAYV and UNAV in two individuals, but most MAYV
to be infected.32 Nevertheless, other terrestrial and nocturnal seropositives were not tested for UNAV. The sample limita-
species were also seropositive in our study. Similar to our tion did not allowus to indicate a reliable proportion ofMAYV/
findings, previous studies indicated that nonhuman primates UNAV cross-reactions. It is unclear whether the cross-
had high MAYV seropositive rates, presumably reflecting neutralizing patterns shown in these two individuals are due
these animals’ preference for a lower to mid-canopy habitat, to cross-reaction among these viruses or real independent
where potential vectors are often present.23,32 We also found infections. Future studies should evaluate this possibility in a
seropositive rodents and marsupials, possibly infected by prospective follow-up of patients.
Haemagogus janthinomys mosquitoes, known enzootic vec- The cross-sectional nature of the study design does not allow
tor of MAYV that reside in upper and lower canopy in the us to draw a conclusion of temporal association between the
Peruvian Amazon.34 These mosquitoes are daytime feeders, exposure to the virus and infection. However, our study was
which may explain why hunting was a risk factor. This result designed to explore potential factors of alphavirus infection and
corroborates a previous study in the Amazon rainforest of not to test hypothesis-driven questions. As sympatric alphavi-
Ecuador, where the high seroprevalence detected in the ruses circulate in the Amazon region of Peru, it is possible to
Amazon-native personnel of the Ecuadorian armed forces observe cross-reaction among members of the genus
was associated with hunting.14 The higher MAYV risk due to Alphavirus.8,39 However, we used PRNT, which is the gold
cohabitation may suggest the presence of infected dwelling standard for alphavirusdiagnosisandprovidesahighlyaccurate
species, opening up the possibility for a human–mosquito– classification among members of the same antigenic complex.
human transmission cycle. Although H. janthinomys is re- In summary, we provide the first evidence of human
ported to have a low activity near houses in the Amazon alphavirus infection in an indigenous community from the
rainforest, the lack of MAYV isolation from other mosquito Peruvian Amazon. Our results also suggest that sympatric
species and vector competence studies are unable to human alphavirus infections are common in the Amazon re-
confirm a human-mosquito-human transmission.23,35 Mayaro gion of Peru.
virus has been isolated from Aedes (Ochlerotatus) serratus,
Psorophora ferox,Psorophoraalbipes, andCulexspp.captured Received October 23, 2018. Accepted for publication August 15,
indoor and outdoor in a village in the Iquitos region and at the 2019.
forest area.36 Evaluating the capacity of these species to Published online September 30, 2019.
transmit the virus is highly relevant. Urban-adapted species
such as Aedes aegypti and Aedes albopictus, known vectors Note: Supplemental table appears at www.ajtmh.org.
of other human arboviruses (e.g., dengue and chikungunya) in Acknowledgments: We thank the citizens of Nueva Esperanza and
Iquitos, are proved competent MAYV vectors in laboratory Sol Naciente. We are especially grateful for the institutional support
conditions. However, other species, for example, Anopheles provided by Wildlife Conservation Society, Servicio Nacional de
Sanidad Agraria, Instituto Nacional de Salud, and Dirección General
spp., may also be important vectors that sustain the trans- Forestal y de Fauna Silvestre from Peru. We also thank Eric Halsey,
mission of MAYV.35,37 CarolinaGuevara, and Julia Ampuero for their support in the execution
Here, we also demonstrate the highest observed human of this study and Karen Neira and Stephanie Montero for their tech-
prevalence of UNAV reported to date in Latin America. Low nical assistance.
UNAV prevalence was previously reported in Iquitos and peri- Financial support: This research was supported by a grant from
urban and urban areas in Argentina and Paraguay where it is SENACYT FID 16-201 to J. P. C. and A. V., Secretarı́a Nacional de
less likely to be in contact with the enzootic cycle.6,12,38 Our Ciencia y Tecnologı́a from Panama; by the grant for neglected dis-
eases studies in Panama 1.11.1.3.703.01.55.120 from the Ministry of
results show that hunting was a main risk factor for UNAV Economy and Finance of Panama to J. P. C. and A. V.; and by
infection, and this suggests that introduction into the forest ERANet17/HLH-0271. Scott Weaver also supported this study
potentially increases the contact with humans and the trans- through the World Reference Center for Emerging Viruses and Arbo-
mission cycle. Ecological evidence suggests that Ae. viruses, NIH grant R24AI120942. Dr. Lescano is sponsored by the
training grant D43 TW007393 awarded by the Fogarty International
(Ochlerotatus) fulvus,P. ferox, andPsorophora albigenumight Center of the US National Institutes of Health. J. L. M. is a doctoral
be themosquito species involved in the enzootic circulation of candidate studying an Epidemiological Research Doctorate at Uni-
UNAV, which is principally distributed in sylvatic areas of Latin versidad Peruana Cayetano Heredia under FONDECYT/CIENCIAC-
American countries.11 TIVA scholarship EF033-235-2015 and also supported by training
Although disease severity varies between individuals, the grant D43 TW007393. A. V. is a member of the Sistema Nacional de
Investigación dePanamá (SNI), SENACYT. E. S.was supportedby the
chronic debilitating joint pain associated with Mayaro fever Spanish Ministerio de Ciencia Innovación y Universidades (MICINN)
may severely impair the livelihoods of MAYV-infected people, through a Ramon y Cajal agreement (RYC-2016-21120).
ZOONOTIC ALPHAVIRUSES IN THE PERUVIAN AMAZON 1217
Authors’ addresses: Jocelyn G. Pérez, University of Liverpool, Liver- 16. Vittor AY et al., 2016. Epidemiology of emergent Madariaga
pool, United Kingdom, E-mail: jgpl16@liverpool.ac.uk. Jean-Paul encephalitis in a region with endemic Venezuelan equine
Carrera, Yaneth Pittı́, and Anayansi Valderrama, Gorgas Memorial encephalitis: initial host studies and human cross-
Institute of HealthStudies, PanamaCity, Panama, E-mails: jpcarrera@ sectional study in Darien, Panama. PLoS Negl Trop Dis
gorgas.gob.pa, ypitti@gorgas.gob.pa, and avalderrama@gorgas. 10: e0004554.
gob.pa. Emmanuel Serrano, Universitat Autònoma de Barcelona, 17. Lennette EH, Lennette DA, Lennette ET, 1995. Diagnostic Pro-
Barcelona, Spain and Universitá di Torino, Torino, Italy, E-mail: cedures for Viral, Rickettsial, and Chlamydial Infections.
emmanuel.serrano@uab.cat. Jorge L. Maguiña and Andres G. Washington, DC: American Public Health Association.
Lescano, Universidad Peruana Cayetano Heredia, Lima, Peru, E-mails: 18. Therneau T, Atkinson B, 2018. Rpart: Recursive Partitioning and
jorge.luis.maguina@upch.pe and willy.lescano@upch.pe. Gregorio Regression Trees. Available at: https://CRAN.R-project.org/
Mentaberre, Universitat Autònoma deBarcelona, Barcelona, Spain and package=rpart. R Package Version 4. 1–13.
Universitat de Lleida, Lleida, Spain, E-mail: gregorio.mentaberre@uab. 19. R Core team, 2019. R: A Language and Environment for Statisti-
cat. Pedro Mayor, Universitat Autònoma de Barcelona, Barcelona, cal Computing. Vienna, Austria: R Foundation for Statistical
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20. Aguilar PV, Estrada-Franco JG, Navarro-Lopez R, Ferro C,
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