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The Placenta in a Case of Pregnant Woman Infected by
Chikungunya Virus
Olivar Clemente Castejón Sandoval*
Director of the CIADANA (Center for Research and Analysis Assistancel Teaching of the Nucleus Aragua) Laboratory of Electron Microscopy, Venezuela
Journal of Virology and Retrovirology Open Access
Research Article
Introduction
Chikungunya virus (CHIK V) or chikunguña is a virus
belonging to the group of Arbovirus transmitted by vectors Aedes
aegypti and Aedes albopictus wich are arthropods transmitters of
dengue [1]. Is an alphavirus belonging to the togaviridae family.
Alphavirus are small spherical enveloped viruses, with 60-
70nm diameter [2]. The fever produced by this virus presents a
mortality of 0.4% in child age of a year. The virus appear to be
transmitted from mother to child but it is unknown if this event is
transplacental [3].
Tanzania in 1952. More of 776000 cases of this fever have been
suspicious in caribean islands and in some countries of South
America with 152 deaths provoked by this fever [4]. Fever, eritem
and painful syndrome in the arthiculations that persist during
months are clinical features of this fever [5].
The chikv is an ARN virus that has been found in primates,
rodents, birds and small mammalia [1]. The mothers that have
chikungunya during pregnancy no transmit the chikv to their
baby. Although it has been documented maternal transmission to
the newborn when the mother presents fever days before or in
the moment of the delivery. Caesarian no avoid the transmission.
By this reason pregnancy womans with chikungunya are a group
of risk. This virus is not transmitted through of maternal milk [4].
Chikv produces cytopathic effects in a variety of cellular lines as
Vero cells, BHK-21 and HeLa [1] but is unknown their effect on
the structure of the placental villi.
There are reports of spontaneous abortus after of an infection
by chikv in the mother [6].Chikungunya fever is accompanied
by articular pain, abdominal pain, muscle pain, head pain,
nausea, tiredness, and subcutaneous eruptions. Occasionally
complicated with cardiac and neurological affectations, ocular
and gastrointestinal annoyance [4].
Epidemiologicals [7], clinics [2]. and laboratory studies [8]
have been realized about chikungunya virus but there is absence
of histopathological work in the placental villi showing the
structure of these affected by chikv. Is our proposal to describe
the change provoked by Chikv on the structure of the placental
tissue with scanning electron and light microscopy.
Material and Methods
Two groups of population of placental villi were taken of
placenta normal and placenta study. The group study proceed
from hospitalary institution whose placenta was obtained to
the 37 weeks of pregnancy, of pacient of 32 years old, of low
education level and economic resources who was infected during
the third trimester of pregnancy, with an poor increase of weight
of only 6 kg. The newborn was born alive with 51 cm and 3600gr.
The placenta normal was obtained at 38 weeks of pacient with an
increase of weight of 10 kg, without antecedent of disease. The
IgM/IgG) and nucleic acids detection (RT-PCR). The serology
of pacient with placenta study was negative for Hepatitis B, C,
cytomegalovirus, Epstein Barr virus, rubella and toxoplasmosis.
Without other metabolic disease, genetic, parasitary, or with
malformations and being seronegative to the six weeks of birth.
The infected woman pregnancy had knowledge of informed
Abstract
In this work our proposal is to describe the changes provoked by
chikungunya virus on the structure of the placental tissue with light
and scanning electron microscopy. Placenta was obtained of patient
of 32 years old infected during the third trimester of pregnancy
with low increase of weight. Numerous immature intermediate villi
were seen. Some placental villi were noted, in part, without the
cells. Interruptions of the placental surface were found. Regions of
mature intermediate villi without terminal villi were located. Stem
their vessels. Subtrophoblastic edema, degenerative changes in
stromal zone and villous bad-development were located. The viral
attack has transformed the placental villi in one structure which is
not in their better condition for the fetal transference of gases and
nutrients.
Keywords: Chikv; Placental villi; Degenerative changes
Received: July 23, 2015; Accepted: February 03, 2016; Published: February 18, 2016
*Corresponding author: Prof. Olivar C Castejón, Director of the CIADANA (Center for Research and Analysis Assistancel Teaching of the Nucleus
Aragua) Laboratory of Electron Microscopy, Faculty of Health Sciences, University of Carabobo - Aragua State - Maracay, Venezuela, Apdo. 4944,
Telephone: 58 -0243-2713471; Ext. 404215;Fax: 0243-2713312; E-mail: olivar.ciadanauc@gmail.com
Page 2 of 4
Citation: Castejón Sandoval OC (2016) The Placenta in a Case of Pregnant Woman Infected by Chikungunya Virus. J Virol Retrovirol
2(1): 1-4.
The Placenta in a Case of Pregnant Woman Infected by Chikungunya Virus Copyright:
© 2016 Castejón Sandoval
consent and approval by the ethical committee of the hospitalary
institution for the realization of this investigation according to
the Helsinki declaration. Diagnostic was made by Micro-Elisa of
fourth generation, with equipment automatic AXSYM (Abbot,
of the maternal surface selected to the azar from the region
central parabasal in the vertical plane. Three slides by specimen
were prepared for light microscopic, 30 histological slides in total
which were stained with H&E for their observation.
Five small fragments in similar form were taken for Scanning
Electron Microscopy (SEM) according to conventional stains and
seen with a Hitachi S2300 scanning electron microscopy. Cross
sections of placental villi stained with H&E will be associated
with similar regions taken with SEM. The concepts of immaturity,
Edema, Fibrinoid deposition and chorangiosis are used as in
previous work [9] employing the same nomenclature of placental
villi.
Results
Numerous immature intermediate villi were seen. Some
placental villi were noted, in part, without the syncytiotrophoblast
surface of the villi showed interruptions or breaks. These villi
seen indicating necrosis of villous zone (Figure 2). Regions
of microinfarcts and placental villi showing a syncytium of
different thickness were found (Figure 3).The single, long,
mature intermediate villi showing the characteristic bends of its
longitudinal axis and multiple grape-like terminal villi were not
seen. There are not terminal villi arising from the convex side
of each bend as is seen in normality (Figure 4).The paucity of
mature intermediate villi associated with terminal villi is highly
terminal villi of minimum diameters with absence of capillary
branching were seen.
In some zone these types of villi are seen interlaced and
notorious stromal clear areas or empty are noted (Figure 5).
replaces villous stroma neath debris of trophoblastic cover
(Figure 6). These villi also showed severe damage in the blood
degenerating villi (Figure 7).
They are severely damaged with breaks at the level
of syncytium, with accented subtrophoblastic edema and
degenerative changes in stromal zone. Areas of prominent lysis
are observed (Figure 8).
of cytotrophoblast were observed with scarcity of chromatin and
occasionally placental villi that exhibits chorangiosis can be seen
suffering severe degenerative changes in their blood vessels.
a
b
Figure 1: a) A region of syncytiotrophoblast which has suffered necro-
sis showing stromal zone. b) Part of stem villi with collapsed vessels and
a
b
Figure 2: a) In the left upper angle interrumped syncytium or break is
H&E. 100X.
a
b
Figure 3: a) Two long mature intermediate villi and
a microinfart region are observed. b) Immature intermediate villi,
changes in the thickness of the syncytium and infarcts are exhibited.
H&E. 100X.
a
b
Figure 4: a) Long mature intermediate villi is noted without terminal
villi. b) Cross sectioned villi shows internal structure with Koilocytic
cell. H&E. 400X.
Discussion
Viruses cause disease directly affecting the physiology of the
cells they infect and the most dramatic effect that have on their
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Citation: Castejón Sandoval OC (2016) The Placenta in a Case of Pregnant Woman Infected by Chikungunya Virus. J Virol Retrovirol
2(1): 1-4.
The Placenta in a Case of Pregnant Woman Infected by Chikungunya Virus Copyright:
© 2016 Castejón Sandoval
plasma membrane permeability, fusion of cell membranes and
depolymerization of the cytoskeleton have been described [11].
Chikv was found in placenta but was not found in some samples
including maternal milk and synovial samples [12]. Ziegler et al
[13] found in 14 – day – old mice inoculated subcutaneously with
chikungunya virus histopathologic changes in skeletal muscle as
This offered a useful model for further study of the pathogenesis
reservoir or transformed cell organells by the viral activity. The
clear zones that were observed in the stromal region indicate that
the placental villi has suffered necrosis under the viral cytopathic
effect. Chikv can to provoke direct cytopathic effect on the
structure of the villi causing his destruction. These viruses have
RNA genome positive sense translationed directly by host tissue
and are very infectious. Extensive zones of the placenta with these
features can to produce growth retardation, low birth weight and
developmental anomalies as occurs with Rubella, CMV and HIV
villi. This technique exhibits a placental tree corresponding to
Although has been described that the rarity of placental
histologic lesions (in only 1 of 624 women with chikungunya
infection by the virus and explained the rarity of cases of fetal
chikungunya infection before birth [14]; however others factors as
lower education level [15], economic resources and nutrimental
problems could are contributing with these morphological
changes here observed
glioblastoma cells, meningeal and ependymal cells, kupffer cells,
[16]. This tropism so diverse add an aggressive character to these
viruses which can destroy all the structure of one placental villi
as seen in Figure 8.
Vertical contamination most probably occurs as consecuence
of passive transfer of maternal blood-borne free virus particles
through the placental barrier via the physiological breaches that
arise at term of pregnancy and during parturition by uterine
contractions and which are known to lead to maternal-fetal blood
exchanges [16].
It is possible that factors such as maternal immune status
and pre-term placental abruption may contribute to pre-partum
infection. The mechanisms that promote fetal infection remains
mother was highly viremic around the term of pregnancy [18].
Atrophy, necrosis, vacuolization and collagenosis were also
probably could be eliminated by a direct cytopathic effect [19].
Persistence bylong time of Chikv into macrophages as cellular
a
b
Figure 5: a) Interconnected long mature intermediate villi are noted.
b) Lytic changes in the stromal region of several villi are shown. H&E.
100X.
a
b
Figure 6: a) Notable damage is observed in the layers of blood vessels
-
ating villi. H&E. 100X.
a
b
Figure 7: a) Stem villi presents collapsed vessels H&E. 100X. b) At
the center debris of placental villi which presents stromal region
a
b
Figure 8: a) Stem villi is observed with interruptions of syncytium,
subtrophoblastic edema and severe degenerative changes in stromal
region. b) Placental villi presents disappearance of part of stromal zone,
H&E. 100X disintegration or lysis. H&E.100X.
host cells is lysis. They can directly damage cells stimulating
the cellular self-destructive- mechanism [10]. The host cells
that are infected by viruses undergo nuclear, cytoplasmic and
plasmalemmal degeneration. The plasmalemma disintegrates
focally but progressively, and the cell is lysed. Inhibition of vital
processes such as membranous vesicle accumulation, increased
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Citation: Castejón Sandoval OC (2016) The Placenta in a Case of Pregnant Woman Infected by Chikungunya Virus. J Virol Retrovirol
2(1): 1-4.
The Placenta in a Case of Pregnant Woman Infected by Chikungunya Virus Copyright:
© 2016 Castejón Sandoval
reservoirs during chikv infection in vivo potentially explains
long-lasting symptoms observed in humans [20].
In vitro studies using a panel of mammalian cell lines
showed rapid induction of cytopathic effects and cell death via
apoptosis in most adherent cell lines [21]. Aggregation of nucleus
with scarcity of chromatin represent a type of cytopathic effect
of Chikv on the placental structure known as cell fusion that
involves the fusion of the plasma membrane of four or more
cells to produce an enlarged cell with four or more nuclei [22].
Chorangiosis is a term of villous hipervascularization in response
villi [23,24]. The viral attack has deteriorate blood vessels and
the transference results impaired.
So, the vessels are damaged and the fetus will have problems
in the absorption of gases and nutrients. Lysis of the syncytial
plasma membrane by the viruses on it could produce holes
disorganize the stromal region.
In conclusion, an immature placental villous tree with
persistence of immature intermediate villi has been found.
development with accented degenerative changes. The viral
attack has transformed the placental villi in one structure which
is not in their better condition for the fetal transference of gases
and nutrients.
References
1. PAHO/CDC. Preparedness and response for chikungunya virus
introduction in the Americas. Washington, PAHO/CDC. 2011.
2. Caglioti C, Lalle E, Castilleti C, Carletti F, Capobianchi MR, Bordi L.
ChiKungunya virus infection: on overview. New Microbiol. 2013;
36(3):211-227.
3. Torres J, Gonzalez Y. Virus chikungunya. R Dominicana: Infección Neo-
natal;2014. https://es.noticias.yahoo.com/dominicana-m-100naci-
dos-con-chikungunya-164021896.html.
4. WHO, Center of Press (2015). Chikungunya. 327 Descriptive note.
5. Robinson MC. An epidemic of virus disease in Southern Province,
Tanganika Territory in 1952-1953. I Clinical features. Trans Royal
Society Trop Med Hyg. 1955; 49(1):28-32, doi:10.1016/0035-
9203(55)90080-8.
6. Touret Y, Randrianaivo H, Michault A, Schuffenecker I, Kauffmann E,
Lenglet Y, et al. Early maternal-fetal transmission of the chikungunya
virus Presse Med. 2006; 35:1656-1658.
7. Lumsden, WHR. An epidemic of virus disease in southern province,
Tanganika territory in 1952-1953 II. General description and
epidemiology. Trans Royal Society Trop Med Hyg. 1955; 49(1):33-57.
8. OPS/OMS. Aspectos generales sobre el virus chikungunya. Santo
Domingo: Ministerio de Salud Pública 2014.
9. Castejon S OC, Lopez G AJ. A light and scanning electron microscopy
study of placental villi associated with obesity and hypertension. Elect
J Biomed. 2013; 2013(2):29-36.
10. Ring, CJ. Cytolytic virus as potential anti-cancer agents. J Gen Virol.
2002; 83:491-502.
11. Flint SJ, Euquist LW, Krug RM, Racaniello VR, Skalka AM. Principles of
Virology: Molecular Biology, Pathogenesis and Control. Washington,
DC: American Society for Microbiology; 2000.
12. Grivard P, Le Roux K, Laurent P, Fianu A, Perrau J, Gigan J, et al.
Molecular and serological diagnosis of chikungunya virus infection.
Pathol Biol (Paris). 2007; 55(10):490-494.
13. Ziegler SA, Lu L, da Rosa AP, Xiao SY, Tesh RB.An animal Model for
studying the pathogenesis of chikungunya virus infection. Am J Trop
Med Hyg. 2008; 79:133-139.
14. Gerardin P, Barang G, Michault A, Bintner M, Randrianaivo H, Choker
G, et al. Multidisciplinary prospective study of mother to child
chikungunya virus infections on the island of La Reunion. Plos Med.
2008; 5(3):e60. doi: 10.1371/journal.pmed.0050060.
15. Fritel X, Rollet O, Gerardin P, Gaüzère BA, Bideault J, Lagarde L, et al.
Chikungunya virus infection during pregnancy, Reunion, France, 2006.
Emerg Infect Dis. 2010; 16:418-425.
16. Couderc T, Lecuit M. Focus on chikungunya pathophysiology in human
and animal models. Microbes and Infection II. 2009; 11(14-15): 1197-
1205, doi: 10.1016/j.micinf.2009.09.002.
17. Chen Ch I, Clark DC, Pesavento P, Lerche NW, Luciw PA, Reisen WK, et
al. Comparative pathogenesis of epidemic and enzootic chikungunya
viruses in a pregnant rhesus macaque model. Am J Trop Med Hyg.
2010; 83(6): 1249-1258, doi: 10.4269/ajtmh.2010.10-0290.
18. Haas H, Robin S, Ramful D, Houdon L, Minodier P, Gérardin P.
Chikungunya virus infections in children. Arch Pedriat. 2009;
16(2):572-579, doi: 10.1016/S0929-693X(09)75305-9.
19. Ozden S, Huerre M, Pierre Riviere J, Coffey LL, Afonso PV, Mouly V, et al.
Human muscle satellite cells as targets of chikungunya virus infection.
Plos one. 2007; 2:e527.
20. Labadie K, Larcher T, Jonbert C, Mannioui A, Delache B, Brochard P, et
al. Chikungunya disease in nonhuman primates involve long term viral
persistence in macrophages. J Clin Invest. 2010; 120(3):894-906, doi:
10.1172/JCI40104.
21. Suchman E, Blair C. Cytopathic effects of viruses protocols.
Washington: ASM Microbelibrary; 2013.
22. Suzuki k , Itoh H, Kimura S, Sugihara K, Yaguchi C, Kobayashi Y, et
al. Chorangiosis and placental oxygenation. Congenit Anom (Kyoto).
2009; 49(2):71-76. doi: 10.1111/j.1741-4520.2009.00226.x.
23. Sourisseau M, Schilte C, Casartelli N, Trouillet C, Guivel-Benhassine F,
Rudnicka D, et al. Characterization of remerging chikungunya virus.
Plos Pathog. 2007; 3:e89.
24. Benirschke K, Kaufmann P. Pathology of the human placenta. 4ed. New
York: Springer-Verlag, 2000.