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High Dose Intravenous Vitamin C Treatment for Zika Fever

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High Dose Intravenous Vitamin C Treatment for Zika Fever JOM Volume 31, Number 1, 2016 Case Report 19 High Dose Intravenous Vitamin C Treatment for Zika Fever Michael J. Gonzalez, NMD, DSc, PhD, FACN;1 Miguel J. Berdie,l MD;2 Jorgé R. Miranda- Massari, PharmD;2 Jorgé Duconge, PhD;1 Joshua L. Rodríguez-López, BS;3 Pedro A. Adrover-López, BS 3 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 o"cial treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol) and non-steroidal anti-in#ammatory 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 e$ects 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 (European Center for Disease Prevention and Zika virus (ZIKV) is a member of the Control, 2015). As of February 2016, there are virus family Flaviviridae and the genus three reported cases indicating that Zika virus Flavivirus (Knipe et al, 2007). Like other could possibly be sexually transmitted (World !aviviruses, Zika virus is enveloped and Health Organization, 2016a). icosahedral and has a nonsegmented, single- #e infection, known as Zika fever, often stranded, positive-sense RNA genome. It causes none or only mild symptoms, simi- is spread by daytime active Aedes mosqui- lar to a mild form of dengue fever (Knipe toes, such as A. Aegypti and A. Albopictus et al, 2007). #e illness cannot be prevented (Knipe et al, 2007). Its name comes from by medications or vaccines and is treated the Zika Forest of Uganda, where the virus mainly by rest (Chen et al, 2016). Zika fe- was "rst isolated in 1947 (European Center ver in pregnant women is associated with for Disease Prevention and Control, 2015). microcephaly but it is unclear whether the Zika virus is related to dengue, yellow fever, virus is the cause (Knipe et al, 2007; Cable Japanese encephalitis, and West Nile viruses News Network, 2015; Centers for Disease High Dose Intravenous Vitamin C for Zika Fever 20 Control and Prevention, 2016a). !ere is a Commercial assays for Zika antibodies are link between Zika fever and neurologic con- now available but have not yet been FDA ditions in infected adults, including cases approved (Centers for Disease Control and of the Guillain–Barré syndrome (World Prevention, 2016). During the $rst seven Health Organization, 2016b; Oehler et al, days of these illnesses, viral RNA can often 2014; Cao-Lormeau et al, 2016). Common be identi$ed in serum, and RTPCR is the symptoms of infection with the virus in- preferred test for Zika, chikungunya, and clude mild headaches, maculopapular rash, dengue viruses. fever, malaise, conjunctivitis, and joint pains. For many years, it has been widely known Within two days, the rash may start fading, that ascorbic acid (vitamin C) has a variety and within three days, the fever is generally of physiological functions with clinical e#- resolved and only the rash remains. cacy. Vitamin C is a water-soluble vitamin, As of 2016, no vaccine or preventive and has been used to prevent many diseases drug is available. Symptoms can be treated and/or infections like the common cold and with rest, "uids, and paracetamol (acetamin- other viral infections (Mikirova et al, 2012; ophen), while aspirin and other nonsteroi- Padayatty et al, 2010; Byun et al, 2011; Har- dal anti-in"ammatory drugs should be used akek et al, 1990; Zhang et al, 2014). Ascor- only when dengue has been ruled out to re- bic acid scavenges reactive oxygen species duce the risk of bleeding (Sikka et al, 2016). (ROS), increases vascular and connective It is di#cult to diagnose Zika virus infec- tissue integrity, improves immune function tion based on clinical signs and symptoms (increases interferon) and assists in leuko- alone due to overlaps with other arboviruses cyte phagocytic functions (increases hydro- that are endemic to similar areas (Centers gen peroxide, number and aggressiveness of for Disease Control and Prevention, 2016b). white blood cells) (Gonzalez et al, 2014). In small case series, routine chemistry and Vitamin C supplemented orally has its complete blood counts have been normal in limitations in achieving high blood (i.e., most patients. A few have been reported to plasma) levels, whereas the use of intravenous have mild leukopenia, thrombocytopenia, vitamin C (IVC) can reach blood levels that and elevated liver transaminases (Centers possess distinct clinical and pharmacologi- for Disease Control and Prevention, 2016c; cal advantages. Oral vitamin C is absorbed Waggoner et al, 2016). in the gastrointestinal tract, where the body Zika virus can be identi$ed by reverse metabolizes a limited amount and the rest transcriptase PCR (RT-PCR) in acutely ill is excreted through the kidneys. However, if patients. However, the period of viremia can the vitamin is administered intravenously it be short and the World Health Organiza- can reach plasma concentrations that are 30 tion (WHO) recommends RT-PCR testing to 70 times higher than the oral route, which be done on serum collected within 1 to 3 seems necessary for the antiviral activity days of symptom onset or on saliva or urine (Chen et al, 2016). samples collected during the $rst 3 to 5 days Ascorbic acid is also a nutrient for the (Waggoner et al, 2016; Faye et al, 2008; Ay- immune system. Treatment of ascorbic acid ers et al, 2006). in vitro resulted in an increase in T-cells and Later on, serology for the detection of natural killer (NK)-cells, which constitute one speci$c IgM and IgG antibodies to Zika of the main components of the adaptive im- virus can be used. IgM antibodies can be mune system, which $ghts against viruses and detectable within three days of the onset of intracellular bacteria (World Health Organi- illness (Waggoner et al, 2016). Serological zation, 2016). It has been suggested the same cross-reactions with closely related "avivi- e%ect can be achieved by IVC administration. ruses such as dengue and West Nile virus as Here we report a case of Zika fever, treated well as vaccines to "aviviruses are possible with high doses of IVC in a period of three (Waggoner et al, 2016; Faye et al, 2008). days without any negative side e%ects. High Dose Intravenous Vitamin C for Zika Fever 21 Case Report Presentation leased into the extracellular medium (Smith, !ree days after su%ering several mos- 1994; Kim et al, 2013). quito bites the patient noted the onset of Vitamin C is an e#cient antioxidant intermittent periods of fever and chills (day and possesses anti-viral activity. For ex- one). Two days later, her mouth became sore ample, it has been shown that vitamin C is and oral blisters developed. On day $ve, a an essential factor in the production of the papular rash developed, which spread to her anti-viral immune response during the early extremities. !e rash lasted three days, and phase of viral infection through the produc- in conjunction with a retro-orbital headache tion of type I interferons, which up-regulates and fever and mild non-purulent conjunc- NK cell and cytotoxic T-lymphocyte activity tivitis, signi$cant joint and muscle tender- (Madhusudana et al, 2004). Also, studies have ness developed which prompted a visit to the indicated that ascorbic acid can be used as an physician. inactivating agent for both RNA and DNA Blood, nasopharyngeal swab, and urine viruses, impacting viral infectivity (Byun et samples were collected for investigation of al, 2011). In addition, ascorbic acid can de- measles and/or other possible infectious toxify viral products that produce pain and causes as the di%erential work-up. Initial in"ammation (Harakek et al, 1990). All this laboratory investigations showed a hemo- evidence con$rms the e%ectiveness of ascor- globin level, leukocyte count, platelet count bic acid against viral infections, and against and levels of creatinine, electrolytes, alanine Zika fever, as suggested by the patient’s swift aminotransferase, and alkaline phosphatase response to IVC. Furthermore, no negative were all within reference ranges. side e%ects resulted during or after the treat- A reverse transcription polymerase ment. Based on the positive outcome in this chain reaction (RT-PCR) described by was case, we propose that IVC should be studied performed resulting positive for "aviviruses. further as a potential treatment for acute vi- Since the clinical signs and symptoms of ral infections. infection with Zika virus can be easily con- fused with dengue and/or Chikungunya, References mainly because of the fever, headache, and Ayers, M., Adachi, D., Johnson, G., Andonova, M., generalized rash-like presentation this test Drebot, M., & Tellier, R. (2006). A single tube RT- was relevant to diagnosis. PCR assay for the detection of mosquito-borne Vitamin C was applied after a G6PD "aviviruses.
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