ArticlePDF Available

Abstract

The Zika Fever is a viral disease caused by a single-stranded RNA virus from the Flavivirus genus, Flaviviridae family, from the Spondweni group. Its transmission occurs through mosquito vectors, principally Aedes aegypti. The most common symptoms of Zika are fever, rash, joint pain, conjunctivitis (red eyes). Other common symptoms include muscle pain and headache. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol) and non-steroidal anti-inflammatory drugs. This is a case report of a 54 year old Hispanic female that arrived at the clinic with symptomatology congruent with the Zika fever. The patient was treated with high doses of intravenous vitamin C over three days. The symptoms resolved after the infusions without any side effects at day 4. Recovery from this viral infection takes normally around 2 weeks. Based on the positive outcome in this case, and both its documented effect as antimicrobial and the good safety tract record we propose that intravenous vitamin C should be studied further as a potential treatment for acute viral infections.
Case Report
JOM Volume 31, Number 1, 2016 1
High Dose Intravenous Vitamin C
Treatment for Zika Fever
Michael J. Gonzalez, NMD, DSc, PhD, FACN;1 Miguel J. Berdie,l MD;2 Jorge R. Miran-
da-Massari, PharmD;2 Jorge Duconge, PhD;1 Joshua L. Rodríguez-López, BS;3 Pedro
A. Adrover-López, BS;
¹University of Puerto Rico, Medical Sciences Campus, Schools of Public Health and Pharmacy, San Juan, PR, 00936-5067
²Berdiel Clinic, Ponce, PR, 00716
3Ponce Health Sciences University, School of Medicine, Ponce, PR, 00716
Abstract e Zika Fever is a viral disease caused by a single-stranded RNA virus from the Fla-
vivirus genus, Flaviviridae family, from the Spondweni group. Its transmission occurs through
mosquito vectors, principally Aedes Aegypti. e most common symptoms of Zika are fever, rash, joint
pain, and conjunctivitis (red eyes). Other common symptoms include muscle pain and headache. As of
now, no vaccine exists for the virus and no official treatment has been developed aside from standard
procedures of the use of acetaminophen (paracetamol) and non-steroidal anti-inflammatory drugs.
is is a case report of a 54 year-old Hispanic female who arrived at the clinic with symptomatology
congruent with the Zika fever. e patient was treated with high doses of intravenous vitamin C
over three days. e symptoms resolved after the infusions without any side effects at day four. Re-
covery from this viral infection takes normally around two weeks. Based on the positive outcome in
this case, we propose that intravenous vitamin C should be studied further as a potential treatment
for acute viral infections.
Introduction
Zika virus (ZIKV ) is a member of the
virus family Flaviviridae and the genus
Flavivirus (Knipe et al, 2007). Like other
flaviviruses, Zika virus is enveloped and
icosahedral and has a nonsegmented, single-
stranded, positive-sense RNA genome. It
is spread by daytime active Aedes mosqui-
toes, such as A. Aegypti and A. Albopictus
(Knipe et al, 2007). Its name comes from
the Zika Forest of Uganda, where the virus
was first isolated in 1947 (European Center
for Disease Prevention and Control, 2015).
Zika virus is related to dengue, yellow fever,
Japanese encephalitis, and West Nile viruses
(European Center for Disease Prevention and
Control, 2015). As of February 2016, there are
three reported cases indicating that Zika virus
could possibly be sexually transmitted (World
Health Organization, 2016a).
e infection, known as Zika fever, often
causes none or only mild symptoms, simi-
lar to a mild form of dengue fever (Knipe
et al, 2007). e illness cannot be prevented
by medications or vaccines and is treated
mainly by rest (Chen et al, 2016). Zika fe-
ver in pregnant women is associated with
microcephaly but it is unclear whether the
virus is the cause (Knipe et al, 2007; Cable
News Network, 2015; Centers for Disease
2
High Dose Intravenous Vitamin C for Zika Fever
Control and Prevention, 2016a). ere is a
link between Zika fever and neurologic con-
ditions in infected adults, including cases
of the Guillain–Barré syndrome (World
Health Organization, 2016b; Oehler et al,
2014; Cao-Lormeau et al, 2016). Common
symptoms of infection with the virus in-
clude mild headaches, maculopapular rash,
fever, malaise, conjunctivitis, and joint pains.
Within two days, the rash may start fading,
and within three days, the fever is generally
resolved and only the rash remains.
As of 2016, no vaccine or preventive
drug is available. Symptoms can be treated
with rest, fluids, and paracetamol (acetamin-
ophen), while aspirin and other nonsteroi-
dal anti-inflammatory drugs should be used
only when dengue has been ruled out to re-
duce the risk of bleeding (Sikka et al, 2016).
It is difficult to diagnose Zika virus infec-
tion based on clinical signs and symptoms
alone due to overlaps with other arboviruses
that are endemic to similar areas (Centers
for Disease Control and Prevention, 2016b).
In small case series, routine chemistry and
complete blood counts have been normal in
most patients. A few have been reported to
have mild leukopenia, thrombocytopenia,
and elevated liver transaminases (Centers
for Disease Control and Prevention, 2016c;
Waggoner et al, 2016).
Zika virus can be identified by reverse
transcriptase PCR (RT-PCR) in acutely ill
patients. However, the period of viremia can
be short and the World Health Organiza-
tion (WHO) recommends RT-PCR testing
be done on serum collected within 1 to 3
days of symptom onset or on saliva or urine
samples collected during the first 3 to 5 days
(Waggoner et al, 2016; Faye et al, 2008; Ay-
ers et al, 2006).
Later on, serology for the detection of
specific IgM and IgG antibodies to Zika
virus can be used. IgM antibodies can be
detectable within three days of the onset of
illness (Waggoner et al, 2016). Serological
cross-reactions with closely related flavivi-
ruses such as dengue and West Nile virus as
well as vaccines to flaviviruses are possible
(Waggoner et al, 2016; Faye et al, 2008).
Commercial assays for Zika antibodies are
now available but have not yet been FDA
approved (Centers for Disease Control and
Prevention, 2016). During the first seven
days of these illnesses, viral RNA can often
be identified in serum, and RTPCR is the
preferred test for Zika, chikungunya, and
dengue viruses.
For many years, it has been widely known
that ascorbic acid (vitamin C) has a variety
of physiological functions with clinical effi-
cacy. Vitamin C is a water-soluble vitamin,
and has been used to prevent many diseases
and/or infections like the common cold and
other viral infections (Mikirova et al, 2012;
Padayatty et al, 2010; Byun et al, 2011; Har-
akek et al, 1990; Zhang et al, 2014). Ascor-
bic acid scavenges reactive oxygen species
(ROS), increases vascular and connective
tissue integrity, improves immune function
(increases interferon) and assists in leuko-
cyte phagocytic functions (increases hydro-
gen peroxide, number and aggressiveness of
white blood cells) (Gonzalez et al, 2014).
Vitamin C supplemented orally has its
limitations in achieving high blood (i.e.,
plasma) levels, whereas the use of intravenous
vitamin C (IVC) can reach blood levels that
possess distinct clinical and pharmacologi-
cal advantages. Oral vitamin C is absorbed
in the gastrointestinal tract, where the body
metabolizes a limited amount and the rest
is excreted through the kidneys. However, if
the vitamin is administered intravenously it
can reach plasma concentrations that are 30
to 70 times higher than the oral route, which
seems necessary for the antiviral activity
(Chen et al, 2016).
Ascorbic acid is also a nutrient for the
immune system. Treatment of ascorbic acid
in vitro resulted in an increase in T-cells and
natural killer (NK)-cells, which constitute one
of the main components of the adaptive im-
mune system, which fights against viruses and
intracellular bacteria (World Health Organi-
zation, 2016). It has been suggested the same
effect can be achieved by IVC administration.
Here we report a case of Zika fever, treated
with high doses of IVC in a period of three
days without any negative side effects.
3
High Dose Intravenous Vitamin C for Zika Fever
Case Report Presentation
ree days after suffering several mos-
quito bites the patient noted the onset of
intermittent periods of fever and chills (day
one). Two days later, her mouth became sore
and oral blisters developed. On day five, a
papular rash developed, which spread to her
extremities. e rash lasted three days, and
in conjunction with a retro-orbital headache
and fever and mild non-purulent conjunc-
tivitis, significant joint and muscle tender-
ness developed which prompted a visit to the
physician.
Blood, nasopharyngeal swab, and urine
samples were collected for investigation of
measles and/or other possible infectious
causes as the differential work-up. Initial
laboratory investigations showed a hemo-
globin level, leukocyte count, platelet count
and levels of creatinine, electrolytes, alanine
aminotransferase, and alkaline phosphatase
were all within reference ranges.
A reverse transcription polymerase
chain reaction (RT-PCR) described by was
performed resulting positive for flaviviruses.
Since the clinical signs and symptoms of
infection with Zika virus can be easily con-
fused with dengue and/or Chikungunya,
mainly because of the fever, headache, and
generalized rash-like presentation this test
was relevant to diagnosis.
Vitamin C was applied after a G6PD
test in escalating doses of 25g (Day 1 of
Treatment), 50 g (Day 2 of Treatment) and
75 g (Day 3 of Treatment). e symptoms
improved substantially in 24 hours and were
absent by the third day.
Discussion
Mounting evidence has suggested a close
correlation between oxidative stress and viral
infectious disease. e elevated oxidants in-
duced by viral infection include nitric oxide
radicals, superoxide anions, hydroxyl radicals
and their by-products, which may all con-
tribute to viral pathogenesis, the modulation
of cellular responses, the regulation of viral
replication and the host defense (Epstein &
Weiss, 1989). Many of these oxidants may
be harmful to the host cells if they are re-
leased into the extracellular medium (Smith,
1994; Kim et al, 2013).
Vitamin C is an efficient antioxidant
and possesses anti-viral activity. For ex-
ample, it has been shown that vitamin C is
an essential factor in the production of the
anti-viral immune response during the early
phase of viral infection through the produc-
tion of type I interferons, which up-regulates
NK cell and cytotoxic T-lymphocyte activity
(Madhusudana et al, 2004). Also, studies have
indicated that ascorbic acid can be used as an
inactivating agent for both RNA and DNA
viruses, impacting viral infectivity (Byun et
al, 2011). In addition, ascorbic acid can de-
toxify viral products that produce pain and
inflammation (Harakek et al, 1990). All this
evidence confirms the effectiveness of ascor-
bic acid against viral infections, and against
Zika fever, as suggested by the patient’s swift
response to IVC. Furthermore, no negative
side effects resulted during or after the treat-
ment. Based on the positive outcome in this
case, we propose that IVC should be studied
further as a potential treatment for acute vi-
ral infections.
References
Ayers, M., Adachi, D., Johnson, G., Andonova, M.,
Drebot, M., & Tellier, R. (2006). A single tube RT-
PCR assay for the detection of mosquito-borne
flaviviruses. Journal of Virological Methods,135(2),
235-239.
Byun, S. H., & Jeon, Y. (2011). Administration of
vitamin C in a patient with herpes zoster-a case
report. e Korean Journal of Pain, 24(2), 108-111.
Cable News Network. Brazil warns against pregnancy
due to spreading virus. (2015, December 23). Re-
trieved from http://edition.cnn.com/2015/12/23/
health/brazil-zika-pregnancy-warning/.
Cao-Lormeau, V., Blake, A., Mons, S., Lastère,
S., Roche, C., Vanhomwegen, J., et al. (2016).
Guillain-Barré Syndrome outbreak associated
with Zika virus infection in French Polynesia: a
case-control study. e Lancet, 387(10027), 1531-
1539.
Centers for Disease Control and Prevention. Zika
virus. Zika and pregnancy. (2016a, January 14).
Retrieved f rom Centers for Disease Control and
Prevention. Zika virus. Symptoms, diagnosis,
& treatment. (2016b, March 3). Retrieved from
http://www.cdc.gov/zika/symptoms/.
Centers for Disease Control and Prevention. Revised
diagnostic testing for Zika, chikungunya, and
4
High Dose Intravenous Vitamin C for Zika Fever
dengue viruses in US Public Health Laboratories.
Division of Vector-Borne Diseases. (2016c, Feb-
ruary 7). Retrieved from http://www.cdc.gov/zika/
pdfs/denvchikvzikv-testing-algorithm.pdf.
Chen, L.H., Hamer, D.H. (2016). Zika Virus: Rapid
Spread in the Western Hemisphere. Annals of In-
ternal Medicine, 164(9), 613-616.
Epstein, F.H., & Weiss, S.J. (1989). Tissue destruction
by neutrophils. New England Journal of Medicine,
320(6), 365–376.
European Centre for Disease Prevention and Con-
trol. Factsheet for health professionals. Zika virus
infection. 2015, December 22. Retrieved from
http://ecdc.europa.eu/en/healthtopics/zika_virus_in-
fection/factsheet-health-professionals/Pages/fact-
sheet_health_professionals.aspx.
Faye, O., Faye, O., Dupressoir, A., Weidmann, M.,
Ndiaye, M., & Sall, A. A. (2008). One-step RT-
PCR for detection of Zika virus. Journal of Clini-
cal Virology, 43(1), 96-101.
Gonzalez, M.J., Miranda-Massari, J.R., Berdiel, M.J.,
et al. (2014). High dose intravenous vitamin C
and Chikungunya Fever: A case report. Journal of
Orthomolecular Medicine, 29(4), 154–156.
Harakeh, S., Jariwalla, R. J., & Pauling, L. (1990). Sup-
pression of human immunodeficiency virus rep-
lication by ascorbate in chronically and acutely
infected cells. Proceedings of the National Academy
of Sciences, 87(18), 7245-7249.
Kim, Y., Kim, H., Bae, S., et al. (2013). Vitamin C is an
essential factor on the anti-viral immune responses
through the production of interferon- alpha/beta
at the initial stage of influenza A virus (H3N2)
infection. Immune Network, 13(2), 70–74.
Knipe, D.M., & Howley, P.M. (2007). Fields’ Virology
(5th ed, pp. 1156-1199). Lippincott Williams &
Wilkins.
Madhusudana, S. N., Shamsundar, R., & Seetharaman,
S. (2004). In vitro inactivation of the rabies virus
by ascorbic acid. International Journal of Infectious
Diseases, 8(1), 21-25.
Mikirova, N., Casciari, J., Rogers, A., & Taylor, P.
(2012). Effect of high-dose intravenous vitamin
C on inflammation in cancer patients. Journal of
Translational Medicine, 10(1), 189.
Oehler, E., Watrin, L., Larre, P., Leparc-Goffart, I.,
Lastere, S., Valour, F., et al. (2014). Zika virus in-
fection complicated by Guillain-Barre syndrome-
-case report, French Polynesia, December 2013.
Eurosurveillance, 19(9), 20720.
Padayatty, S. J., Sun, A. Y., Chen, Q., Espey, M. G.,
Drisko, J., & Levine, M. (2010). Vitamin C: in-
travenous use by complementary and alternative
medicine practitioners and adverse effects. PLoS
One, 5(7), e11414.
Sikka, V., Chattu, V.K., Popli, R.K., et al. (2016).e
emergence of zika virus as a global health security
threat: A review and a consensus statement of the
INDUSEM Joint working Group ( JWG). Jour-
nal of Global Infectious Diseases, 8(1), 3-15.
Smith, J.A. (1994). Neutrophils, host defence, and
inflammation. Journal of Leukocyte Biology, 56(6),
672–686.
Waggoner, J.J., & Benjamin, A. P. (2016). Zika virus:
diagnostics for an emerging pandemic threat.
Journal of Clinical Microbiology, 54(4), 860-867.
World Health Organization. Zika virus and compli-
cations. (2016a, January). Retrieved from http://
www.who.int/emergencies/zika-virus/en/.
World Health Organization. WHO Director-General
summarizes the outcome of the Emergency Com-
mittee regarding clusters of microcephaly and
Guillain-Barré syndrome. Media Center. (2016b,
February 1). Retrieved from http://www.who.int/
mediacentre/news/statements/2016/emergency-com-
mittee-zika-microcephaly/en/.
Zhang, Y., Zehua, W., Chen, H., et al. (2014). Anti-
oxidants: potential antiviral agents for Japanese
encephalitis virus infection. International Journal
of Infectious Diseases, 24, 30–36.
... Several mosquito transmitted viruses have been successfully treated using high doses of IV vitamin C. For example, Gonzalez et al. [11] presented a case report on a 54-year-old Hispanic female who had Zika like symptoms. Some of the symptoms may include mild headaches, fever, joint pain, malaise, and conjunctivitis. ...
... Within 24 hours the symptoms had substantially improved and by the third day were gone. From this case it was established that IV vitamin C should be investigated further, as a possible treatment for acute viral infections [11]. Marcial-Vega et al. [12] used IV vitamin C from 25-50 grams with a 3cc of a 3% hydrogen peroxide solution on 56 patients with the chikungunya viral infection. ...
Article
Full-text available
The controversy between pharmaceutical drugs and supplements is ever present in global society, especially now, in the media during the current Covid-19 virus. One of the most important, yet, provocative supplements is vitamin C. While historically, its positive benefits have long been known, during the last decades the push for pharmaceutical drugs, instead of supplements like vitamin C, has created a heated debate against this, and other very affordable supplements.
... Vitamin C contributes to immune defense by supporting and directly stimulating various cellular functions of both the innate and adaptive immune system. Consistent with this documented ability of vitamin C to upregulate the immune system, the scientific literature has abundant documentation of the ability of vitamin C to cure a number of viruses (Klenner, 1951;Stone, 1972;Levy, 2002, Gonzalez, 2014, Gonzalez, 2016. In this particular case report, the viral infection had reached the point of being life-threatening, even though it was afflicting a young man who previously had always been in exemplary good health. ...
... In addition, ascorbic acid can detoxify viral products that produce pain and inflammation (Harakek et al .1990). High dose IV Vitamin C has been shown to be effective against viral infections such as the common cold rhinovirus (Hemila and Herman,1995); avian virus H1N1 (Ely,2007;) Chikungunya (Gonzalez et al. 2014;Marcial-Vega et al,2015); Zika (Gonzalez et al 2016) and influenza (Zarubaeva et al.2017). Also oral supplementation with vitamin C (doses over 3g) appears to be able to both prevent and treat respiratory and systemic infections (Carr and Maggini, 2017). ...
... Clinical evidence exists that shows vitamin C's potent antiviral effect. Studies in which very large amounts of vitamin C have been used to treat different viral infections have been published (Gonzalez et al. 2014;Marcial-Vega et al. 2017;Gonzalez et al. 2016;Gonzalez et al. 2018a;Gonzalez et al. 2018b). Frequent oral doses with vitamin C sufficient to reach a bowel tolerance limit will work as antiviral therapy for most people (Cathcart, 1981). ...
Article
Full-text available
Currently, there is no vaccine or specific antiviral medication for COVID-19. An accessible, effective and safe treatment is urgently needed to save lives and curtail the spreading of this disease. Acute respiratory distress syndrome (ARDS) is a key factor in the fatality outcome of COVID-19. Significantly increased oxidative stress due to rapid release of free radicals and cytokines (cytokine storm) are the hallmark of ARDS, which leads to cellular injury, organ failure and possible death. We report a case in which early use of high dose intravenous vitamin C (HDIVC) along to other nutrients and medications produced a positive outcome in this patient.
... Finally, there is evidence to suggest that high dose IV Vit C inhibits the replication of rhinoviruses (Hemilä and Herman, 1995), H1N1 (Cai et al. , 2015), Chikungunya (Gonzalez et al. , 2016), Zika (J. González et al. , 2016) and seasonal influenza (Zarubaev et al. , 2017). ...
Article
Background COVID-19-associated acute respiratory distress syndrome (ARDS) is associated with significant morbidity and high levels of mortality. This paper describes the processes involved in the pathophysiology of COVID-19 from the initial infection and subsequent destruction of type II alveolar epithelial cells by SARS-CoV-2 and culminating in the development of ARDS. Main body The activation of alveolar cells and alveolar macrophages leads to the release of large quantities of proinflammatory cytokines and chemokines and their translocation into the pulmonary vasculature. The presence of these inflammatory mediators in the vascular compartment leads to the activation of vascular endothelial cells platelets and neutrophils and the subsequent formation of platelet neutrophil complexes. These complexes in concert with activated endothelial cells interact to create a state of immunothrombosis. The consequence of immunothrombosis include hypercoagulation, accelerating inflammation, fibrin deposition, migration of NET producing neutrophils into the alveolar apace, activation of the NLRP3 inflammazome, increased alveolar macrophage destruction and massive tissue damage by pyroptosis and necroptosis Therapeutic combinations aimed at ameliorating immunothrombosis and preventing the development of severe COVID19 are discussed in detail.
... We have published a series of case reports on high dose intravenous vitamin C and different viral infections (Gonzalez et al., 2014;Gonzalez et al., 2016;Marcial-Vega, Gonzalez-Terron & Levy, 2017;, showing a potent antiviral effect of vitamin C. Neither intravenous nor oral administration of high dose Vitamin C is associated with significant side effects. ...
Article
Full-text available
Currently, there is no vaccine or specific antiviral medication for COVID-19. An accessible, effective and safe treatment is urgently needed to save lives and curtail the spreading of this disease. Acute respiratory distress syndrome (ARDS) is a key factor in the fatality outcome of COVID-19. Significantly increased oxidative stress due to rapid release of free radicals and cytokines (cytokine storm) are the hallmark of ARDS, which leads to cellular injury, organ failure and possible death. We report a case in which early use of high dose intravenous vitamin C (HDIVC) along to other nutrients and medications produced a positive outcome in this patient.
... In a case report, high doses of intravenous vitamin C given over 2 days may have resolved symptoms of a patient with Chikungunya [54]. In addition, vitamin C given over 3 days in increment doses up to 75 g substantially improved symptoms of a patient with ZIKV infection [55]. The mechanism of action of antioxidant vitamin C remains controversial. ...
Article
Full-text available
Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/β and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1β, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.
Article
Full-text available
The new coronavirus (2019-nCoV) and its pulmonary and systemic complications have caused worldwide concern and emergency. There is a lack of effective targeted antiviral drugs and symptomatic supportive treatment. Ascorbic acid (AA) is an essential nutrient with important and diverse physiological effects that has demonstrated at high doses a variety of pharmacological actions, including decreasing inflammation, enhancement of the immune system and a direct antiviral effect. Recently, a randomized study in septic patients with severe acute respiratory failure using intravenous ascorbic acid in 167 patients demonstrated a significant reduction in mortality in the ascorbic acid group when compared to placebo (p = 0.023) Furthermore, a report from Shanghai (2020) showed that 50 CoVid19 complicated patients treated with intravenous ascorbic acid and resulted in zero mortality and few minor side effects. Intravenous ascorbate has a remarkable record of safety and has a diversity of favorable physiological and pharmacological actions in the management of viral infections and sepsis that supports its use. There are several ongoing studies on the use intravenous ascorbic acid in CoVid19 that should further clarify this matter. In the meantime, the benefits of intravenous ascorbate supports its use for COVID-19.
Article
Full-text available
The Zika virus (ZIKV), first discovered in 1947, has emerged as a global public health threat over the last decade, with the accelerated geographic spread of the virus noted during the last 5 years. The World Health Organization (WHO) predicts that millions of cases of ZIKV are likely to occur in the Americas during the next 12 months. These projections, in conjunction with suspected Zika-associated increase in newborn microcephaly cases, prompted WHO to declare public health emergency of international concern. ZIKV-associated illness is characterized by an incubation period of 3-12 days. Most patients remain asymptomatic (i.e., ~80%) after contracting the virus. When symptomatic, clinical presentation is usually mild and consists of a self-limiting febrile illness that lasts approximately 2-7 days. Among common clinical manifestations are fever, arthralgia, conjunctivitis, myalgia, headache, and maculopapular rash. Hospitalization and complication rates are low, with fatalities being extremely rare. Newborn microcephaly, the most devastating and insidious complication associated with the ZIKV, has been described in the offspring of women who became infected while pregnant. Much remains to be elucidated about the timing of ZIKV infection in the context of the temporal progression of pregnancy, the corresponding in utero fetal development stage(s), and the risk of microcephaly. Without further knowledge of the pathophysiology involved, the true risk of ZIKV to the unborn remains difficult to quantify and remediate. Accurate, portable, and inexpensive point-of-care testing is required to better identify cases and manage the current and future outbreaks of ZIKV, including optimization of preventive approaches and the identification of more effective risk reduction strategies. In addition, much more work needs to be done to produce an effective vaccine. Given the rapid geographic spread of ZIKV in recent years, a coordinated local, regional, and global effort is needed to generate sufficient resources and political traction to effectively halt and contain further expansion of the current outbreak.
Article
Full-text available
The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human transmission cycle. It is associated with severe arthritis/arthralgias, myalgias, high fever, headache, and maculopapular rash. Joint ache appears to be symmetrical. The virus has an incubation period of 2 to 7 days, where the high fever is typically presented. It is followed by arthralgias and myalgias, and rashes, which last for 3 to 5 days. However, the arthralgias can persist for months after the infection, which can contribute to severe arthritis. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol), and non-steroidal anti-inflammatory drugs. This is a case report of a 54-year old Hispanic individual that reported left shoulder pain, left knee pain and fever. The symptoms started on a Saturday in September 2014 in middle of the night. The patient was treated with high doses of intravenous vitamin C over two days. The symptoms resolved after the infusions without any side effects. Based on the positive outcome in this case, we propose that intravenous vitamin C should be studied further as a potential treatment for acute viral infections.
Article
Full-text available
Japanese encephalitis (JE) is prevalent throughout eastern and southern Asia and the Pacific Rim. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. Despite the importance of JE, little is known about its pathogenesis. The role of oxidative stress in the pathogenesis of viral infections has led to increased interest in its role in JEV infections. This review focuses mainly on the role of oxidative stress in the pathogenesis of JEV infection and the antiviral effect of antioxidant agents in inhibiting JEV production. First, this review summarizes the pathogenesis of JE. The pathological changes include neuronal death, astrocyte activation, and microglial proliferation. Second, the relationship between oxidative stress and JEV infection is explored. JEV infection induces the generation of oxidants and exhausts the supply of antioxidants, which activates specific signaling pathways. Finally, the therapeutic efficacy of a variety of antioxidants as antiviral agents, including minocycline, arctigenin, fenofibrate, and curcumin, was studied. In conclusion, antioxidants are likely to be developed into antiviral agents for the treatment of JE.
Article
Full-text available
Zika fever, considered as an emerging disease of arbo-viral origin, because of its expanding geographic area, is known as a benign infection usually presenting as an influenza-like illness with cutaneous rash. So far, Zika virus infection has never led to hospitalisation. We describe the first case of Guillain-Barre syndrome (GBS) occurring immediately after a Zika virus infection, during the current Zika and type 1 and 3 dengue fever co-epidemics in French Polynesia. We report on a French Polynesian patient presenting a Zika virus (ZIKA) infection complicated by Guillain-Barre syndrome GBS).
Article
Full-text available
L-ascorbic acid (vitamin C) is one of the well-known anti-viral agents, especially to influenza virus. Since the in vivo anti-viral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-α/β, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-α/β, were increased in the lung. Taken together, vitamin C shows in vivo anti-viral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-α/β.
Article
Full-text available
An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer.Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels.Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods.CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment.There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein.Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels.In summary, our data support the hypothesis that high dose intravenous ascorbate treatments may reduce inflammation in cancer patients. Our results suggest that further investigations into the use of IVC to reduce inflammation in diseases where inflammation is relevant are warranted.
Article
To the Editor: In the excellent article by Weiss on tissue destruction by neutrophils (Feb. 9 issue),¹ there is an implicit assumption that neutrophils lack endogenous reducing substances that could quench intracellular or extracellular oxidants. We would therefore like to emphasize that ascorbic acid is present in human neutrophils, in concentrations 20 to 30 times higher than in plasma.² Although the function of ascorbic acid in neutrophils is unknown, it has been proposed that it quenches free radicals,³ either within or perhaps outside neutrophils. However, before this or other functions of neutrophil ascorbic acid can be addressed, it is of…
Article
Background: Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome. Methods: In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays. Findings: 42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively). Interpretation: This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome. Funding: Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.
Article
Zika virus (ZIKV) is an Aedes mosquito-borne flavivirus that emerged in Brazil in 2015 and then rapidly spread throughout the tropical and subtropical Americas. Based on clinical criteria alone, ZIKV cannot be reliably distinguished from infections with other pathogens that cause an undifferentiated systemic febrile illness, including infections with two common arboviruses, dengue virus and chikungunya virus. This minireview details the methods that are available to diagnose ZIKV infection. © Copyright 2016, American Society for Microbiology. All Rights Reserved.
Article
Zika virus, a mosquito-borne flavivirus that causes febrile illness associated with rash, has been rapidly emerging in the Western Hemisphere over the past few months. The virus was rarely identified until outbreaks occurred on Yap Island in the Federated States of Micronesia in 2007, French Polynesia in 2013, and Easter Island in 2014. It was initially detected in Brazil in 2015, in the northeast, and was subsequently identified in other states and several South American countries, including Colombia, Ecuador, Suriname, Venezuela, French Guyana, and Paraguay (1). Local transmission has been documented in Central America (Panama, El Salvador, Honduras, and Guatemala), the Caribbean (Martinique, Puerto Rico, Dominican Republic, and Haiti), and Mexico. Transmission has also occurred in travelers returning from the infected regions to nonendemic countries, including the United States, Canada, Japan, and Western Europe. As of 22 January 2016, a total of 20 countries and territories in the Americas have Zika virus circulation (1). The explosive spread mirrors the emergence of chikungunya, which was first detected in the Americas (St. Martin) in 2013 and rapidly disseminated throughout the region (2).