Zika virus outbreak – overview on homoeopathic management, therapeutics and prevention

Dr Arun S Raj

Zika virus (ZIKV) infection is a new emerging threat around the globe which might be responsible for microcephaly and Guillain–Barre syndrome in the infants. Recently, ZIKV outbreak has caused a public health crisis in Brazil after being linked to a sharp increase in birth defects. ZIKV is ssRNA virus belongs to the family Flaviviridae. It is mainly transmitted by mosquito bite specifically Aedes species and disease symptoms include fever, joint pain, muscle pain, rash, conjunctivitis, and headache.

The reservoir of ZIKV is still not known. Protection at personal level by avoiding mosquito bite would help to reduce the incidence of the disease. Control of ZIKV infection by vaccination or antiviral drug either from modern, complementary and alternative medicines may be considered to be one of the most effective strategies in the long run. Large scale immunization of susceptible human population is highly required to prevent this deadly disease. Attempts should be made as soon as possible to develop effective vaccines or antiviral to prevent ZIKV infection. This article provides a current overview of the experimental therapeutics and treatment options based on modern, complementary and alternative medicines.

UPDATES OF ZIKKA VIRUS:
Recently, first case of ZIKV infection was reported in Brazil in May 2015. Subsequently, outbreaks were reported throughout the country with high number of congenital malformations including 3500 cases of microcephaly. After 9 months of arrival of ZIKV, microcephaly cases in newborns has been tremendously increased in South America. Additionally, the number of infected patients is increasing as the time moving on; hence, there is an urgent need to find the remedy for the eradication of ZIKV infection for maintaining the heath of the human beings around the globe.

In spite of the fact that the mechanism of infection of ZIKV is not studied in detail so far, although, it belongs to the Flaviviridae family which is well studied Flavivirus group. Therefore, the replication cycle may be similar like other Flaviviruses (Fig. 1). However, further research is essential to ascertain the same. Flaviviruses contain three structure proteins; the capsid protein C, pre-membrane protein prM, and the envelope protein E. RNA genome of the virus is encapsulated in multiple copies of the C protein to frame the viral nucleocapsid. Virus entry into the cell is mediated by the envelope proteins in three relatively discrete steps. The first step involves the attachment of the virus particle to the cell. Second step is the collisions between virus and target cells and third step is the attachment factors which promote infection by increasing the duration of contact between the virus and cell surface. Flaviviruses are internalized via clathrin-mediated endocytosis and after virus entry into the cell, uncoating of the nucleocapsid take place and RNA molecule is translated as a single polyprotein.

What is Zika Fever?
Zika fever is a disease caused by Zika virus that is spread through mosquito bites. Its name comes from the Ziika Forest of Uganda, where the virus was first isolated in 1947. The Zika virus belongs to the family Flaviviridae family and the genus Flavivirus, thus is related to the dengue, yellow fever, Japanese encephalitis, and West Nile viruses.

How does Zika virus spread?
Zika virus spreads through the bite of Aedes aegypti mosquito, which is also responsible for spreading Dengue and Chikungunya. It can also spread through unprotected sexual contact (vaginal, oral or anal) and from a pregnant woman to the foetus.

SYMPTOMS OF ZIKA FEVER?
The symptoms of ZIKV virus infection are that about 1 in 5 people infected with ZIKV become ill. The clinical presentation includes rash, fever, conjunctivitis and joint pain. Additional symptoms include headache and muscle pain. The incubation period for ZIKV disease is still not clear, but is likely to be 2–7 days with usually mild symptoms of illness. Amid substantial outbreaks in Brazil and French Polynesia in 2015 and 2013 individually, health authorities reported potential auto-immune and neurological entanglements which might be due to ZIKV illness.

Recently Brazilian local health authorities have watched an expansion of ZIKV infection in overall population and additionally an increment of microcephaly in infants in northeast Brazil. Offices examining ZIKV episodes are searching an expanding assemblage of confirmation of the association between ZIKV infection and microcephaly. Nonetheless, more examination is required before we appreciate the relationship between microcephaly in babies and the ZIKV infection. Other potential causes are in like manner being explored. Researchers have associated the ZIKV infection with microcephaly, however, the connection between ZIKV and brain abnormalities isn’t completely understood, but it may be possible that the virus attacks stem cells during early brain development while also causing the general destruction of other brain tissue. The early loss of stem cells may keep a fetal brain from forming the correct architecture.

Eighty percent of the infected with Zika virus do not develop any symptoms. Those having symptoms complain of fever, skin rash of maculopapular nature, joint pains, headache and conjunctivitis. In December 2015 an association was found between serious birth defect called as microcephaly (small heads) in babies born in a mother having Zika infection during pregnancy due to transplacental crossing of virus. Microcephaly leads to developmental issues in children. Ongoing Researches are also trying to find out if any relation exists  between this virus and Guillain –Barre syndrome where life threatening paralysis appears.

In a few cases, Zika can trigger paralysis (Guillain-Barré Syndrome). Zika can spread from a pregnant woman to her baby. This can result in microcephaly, severe brain malformations, and other birth defects. It can also lead to abortions.

When present, symptoms are mild and last less than a week. They include fever, rash, joint pain and red eyes.

Zika infection can have no symptoms, but people may experience:

• Pain areas: in the back of the eyes, joints, or muscles
• Whole body: fatigue, fever, chills, loss of appetite, or sweating
• Also common: eye redness, headache, skin rash, or vomiting

TRANSMISSION:
ZIKV is transmitted to people through the infected mosquito bite belongs to Aedes family, basically Aedes aegypti in tropical locales.

What is the treatment for Zika fever?
There’s no vaccine or specific treatment in conventional medicine for Zika virus treatment. Instead, the focus is on relieving symptoms and includes rest, rehydration and acetaminophen for fever and pain. Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen should be avoided.

Prospective Homeopathic Approach for Zika Fever?
Homoeopathic prescriptions Eupatorium perfoliatum, Atropa belladonna, Rhus tox may be securely utilized as a part of ZIKV treatment. These medications come the nearest in treating the symptoms of ZIKV infection disease. Homeopathy has been very effective in treating epidemic diseases such as cholera, dengue fever, yellow fever typhus, and conjunctivitis. In an epidemic when an immense number of individuals are assaulted by acute and similar sufferings from similar cause, homeopathy may be an excellent prophylactic help. Records demonstrate that during epidemics, homeopathic pharmaceuticals are of great help in diminishing the mortality when contrasted with those put under conventional system of medicines.

Atropa belladonna or Belladonna is a medicinal plant categorized under Solanaceae family. This plant has great commercial importance as it is a major source of pharmaceutical bioactive compounds like alkaloids mainly scopolamine and hyoscyamine and is native to Western Asia Europe and North Africa. Although, all alkaloids in Atropa belladonna are distributed in the entire plant, but the majority of the alkaloid content is found in green leaves and ripe fruit. It has long been used in human medicine for the treatment of inflammation, headache, peptic ulcer, menstrual symptoms and histaminic reaction. In our studies Belladonna treatment successfully reduced the Japanese encephalitis virus infection [Saxena and Gadugu. Pers. Comm.

This may be attempted in case of ZIKV after proper consultation with the physician, since they both belong to same family. In homeopathy, ultra-diluted concentration like 3, 6, 30, and 200 of above mention drugs are prescribed for the treatment of all infectious diseases. Therefore, homeopathy may have a huge role to play as prophylactic when disease spreads suddenly over a substantial region. Additionally, homeopathic pharmaceutical Eupatorium perfoliatum may be utilized as prophylactic as a part of ZIKV, as this drug has the nearest match to the symptoms displayed in ZIKV disease.

Homeopathy is a holistic system of medicine, which treats on the basis of symptom similarity. While individualistic therapy is preferred in most cases, in epidemic cases, one or two remedies may be found indicated in most patients. Such a homeopathic medicine is called Genus Epidemicus.

Homeopathy treatment for zika fever is also based on following philosophy, so let us try to figure out the possible genus epidemicus and a larger group of indicated remedies for Zika virus fever, based on the currently known symptoms.

• The first thing to note is that FOR MOST PEOPLE who get infected by the Zika virus, either there are NO SYMPTOMS or MILD SYMPTOMS.

That means we need remedies that can produce mild illness. It rules out homeopathic remedies like Aconite, Belladonna, Lac caninum, Lachesis, Merc sol, Phytolacca, Stramonium etc, which are known to produce  violent/intense symptoms. It indicates remedies that have mildness of symptoms and nature. Remedies like Calcarea carb, Acid phos, Pulsatilla, Ignatia, Gelsemium, Arnica, Arsenic alb, Lycopodium, Natrum mur, Rhus-tox, Silicea, Sepia etc.

• Although Zika virus infection is often clinically labelled as a mild form of Dengue but the homeopathic remedies that are commonly indicated for Dengue will not work for it because it neither has the severe bone pains of Eupatorium, not has the hemorrhagic complications that indicate Phosphorus, Crotalus etc.
• There are two characteristic symptoms that we can add to filter remedies:
  • Fever often comes with a mild rash.
  • Fever often has redness of eyes with it.

After this filtering, we are left with 8 remedies: Rhus-tox, Arsenic alb, Natrum mur, Sepia, Pulsatilla, Lycopodium, Sulphur, Calcarea carb.

So these are some group of homeopathic remedies that can prove helpful in Zika virus fever.

• Other complications of zika fever are:
  • Guillain-Barré Syndrome
  • Microcephaly / Congenital defects
  • Abortion

For Guillain-Barré Syndrome, we can use the rubric:

• Paralysis, Fever after: NAT MUR, Arn, Ars, Lach, Nux vom, Gels, Arn, Vinc-m
• Head, Microcephaly  – only has Syphilinium and Tuberculinum and they might help the children born to the Zika infected mother.
• Miscarriage, Fever with has Baptisia, Pulsatilla, Hammamelis and Ruta.
• So now we are left with Natrum mur, Pulsatilla and Arsenic alb that cover the possible complications too. These three remedies are likely to help in most cases of Zika Fever.
• Since Arsenic album has prostration which is out of proportion to illness (which is usually not present in Zika fever), I believe the most indicated homeopathy remedies for zika virus infection will be Natrum mur and Pulsatilla.

It is very easy to differentiate between these two homeopathy remedies:
PULSATILLA and NATRUM MUR with:

• Thirstless and Thirsty
• Consolation Amel Consolation Agg
• Company desires Company averse to
• Desires Fat Desires Salt etc.

PREVENTION:
Mosquitoes and their reproducing locales represent a critical danger component for ZIKV. Preventive measure and control depends on reducing the source of mosquitoes and by decreasing the encounter between humans and mosquitoes. This could be possible by utilizing mosquito repellent, using mosquito nets, shutting off screens, entryways and windows. It is likewise critical to look at the places where mosquitoes can breed. Insecticide sprays suggested by the WHO Pesticide Evaluation Scheme might likewise be utilized as larvicides to treat generally extensive water compartments.

Rapid test for ZIKV infection should be taken into the consideration during blood transfusion. Before travelling to a new place, a complete record of the diseases endemic to that particular place may also aid in preventing risk. Vector control program should be initiated to prevent the quick spreading of the ZIKV infection. If symptoms of the disease experienced, consultation of certified doctor should be immediately taken Instead of self medication. Women who are planning to conceive the child should require taking extra precautions as microcephaly may be somehow associated with ZIKV infection. Pregnancy may be decisively avoided till the eradication of ZIKV infection.

FUTURE PROSPECTIVE AND CONCLUSIONS:
As the number of cases of ZIKV infection is increasing dramatically, some necessary steps should be taken to eradicate this deadly infection and to inhibit the entry of it in future as well. There is an urgent need of a rapid molecular diagnostics specific for ZIKV so that the infection may be detected in a short period of time and necessary action can be taken before the situation gets out of control. After the development of the diagnostic tools, effective specific therapeutics needs to be developed, for the treatment of ZIKV infection.

ZIKV specific vaccine is the need of the hour, which may be developed using modern molecular biology techniques. Apart from the development of diagnostic and therapeutic, researchers and policy makers should come on the same table to discuss the detailed information about the ZIKV outbreak, which may be helpful in the better understanding of the ZIKV infection, prevention and for the development of effective future diagnosis and treatment. We need to proceed with a sense of urgency in this context.

REFERENCES

• 1. Dr. Manish Bhatia, Homeopathy for Zika Fever Treatment, Disease Index , Homeopathy Papers, October 19, 2018.
  2. Dr. Vikas Sharma MD, Homoeopathic medicinesfor zikavirus treatment and prevention, dr homeo article
  3. Bandyopadhyay B, Das S, Sengupta M, Saha C, Das KC, Sarkar D, Nayak C. Decreased intensity of Japanese encephalitis virus infection in chick chorioallantoic membrane under influence of ultradiluted Belladonna extract. [CrossRef] [Google Scholar]
  4. Bearcroft WG. Zika virus infection experimentally induced in a human volunteer. [PubMed] [CrossRef] [Google Scholar]
  5. Bousta D, Soulimani R, Jarmouni I, Belon P, Falla J, Froment N, Younos C. Neurotropic, immunological and gastric effects of low doses of Atropa belladonna L., Gelsemium sempervirens L. and Poumon histamine in stressed mice. J Ethnopharmacol. 2001; 74:205–215. [PubMed] [CrossRef] [Google Scholar]
  6. Bryant JE, Calvert AE, Mesesan K, Crabtree MB, Volpe KE, Silengo S, Kinney RM, Huang CY, Miller BR, Roehrig JT. Glycosylation of the dengue 2 virus E protein at N67 is critical for virus growth in vitro but not for growth in intrathoracicallyinoculated Aedes aegypti mosquitoes. Virology. 2007;366:415–423. [PubMed] [CrossRef] [Google Scholar]
  7. Clyde K, Kyle JL, Harris E. Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis. J Virol. 2006;80:11418–11431. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  8. Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev. 1999;12:564–582. [PMC free article] [PubMed] [Google Scholar]
  9. Dick GW. Zika virus pathogenicity and physical properties. Trans R Soc Trop Med Hyg. 1952;46:521–534. [PubMed] [CrossRef] [Google Scholar]
  10. Dick GW, Kitchen SF, Haddow AJ. Zika virus isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46:509–520. [PubMed] [CrossRef] [Google Scholar]
  11. Dyer O. Zika virus spreads across Americas as concerns mount over birth defects. BMJ. 2015;351:h6983.[PubMed] [CrossRef] [Google Scholar]
  12. Fagbami AH. Zika virus infections in Nigeria: virological and seroepidemiological investigations in Oyo State. J Hyg (Lond). 1979;83:213–219. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  13. Haddow AJ, Williams MC, Woodall JP, Simpson DIH, Goma LK. Twelve isolations of Zika virus from Aedes (Stegomyia) africanus (Theobald) taken in and above a Ugandan forest. Bull World Health Organ. 1964;31:57–69. [PMC free article] [PubMed] [Google Scholar]
  14. Jayasurriya H, Koonchanok MK, Geahlen RL, Mclanghlin JL, Chang CJ. Emodine, a protein kinase inhibitor from polygonum Cuspidatum. J Nat Pro. 1991;55:696–698. [PubMed] [CrossRef] [Google Scholar]
  15. Marchette NJ, Garcia R, Rudnick A. Isolation of Zika virus from Aedes aegypti mosquitoes in Malaysia. Am J Trop Med Hyg. 1969;18:411–415. [PubMed] [Google Scholar]
  16. Mittal J, Sharma MM, Batra A. Tinospora cordifolia: a multipurpose medicinal plant- A review. J Med Plant Stud. 2014;2:32–47. [Google Scholar]
  17. Moore DL, Causey OR, Carey DE, Reddy S, Cooke AR, Akinkugbe FM, David-West TS, Kemp GE. Arthropod-borne viral infection of man in Nigeria, 1964–1970. Ann Trop Med Parasitol. 1975;69:49–64. [PubMed] [CrossRef] [Google Scholar]
  18. Olson JG, Ksiazek TG. Suhandiman, Triwibowo. Zika virus, a cause of fever in Central Java, Indonesia. Trans R Soc Trop Med Hyg. 1981;75:389–393. [PubMed] [CrossRef] [Google Scholar]
  19. Rita P, Animesh DK. An updated overview on Atropa belladonna L. Int Res J Pharm. 2011;2:11–17. [Google Scholar]
  20. Rodenhuis-Zybert IA, Wilschut J, Smit JM. Dengue virus life cycle: viral and host factors modulating infectivity. Cell Mol Life Sci. 2010;67:2773–2786. [PubMed] [CrossRef] [Google Scholar]
  21. Simpson DIH. Zika virus infection in man. Trans R Soc Trop Med Hyg. 1964;58:335–338. [PubMed] [CrossRef] [Google Scholar]
  22. US Centers for Disease Control and Prevention (CDC) (2016) National center for emerging and zoonotic infectious diseases (NCEZID), Division of vector-borne diseases (DVBD). Zika virus. http://www.cdc.gov/zika. Accessed 4 Feb 2016.
  23. Weinbren MP, Williams MC. Zika virus: further isolations in the Zika area and some studies on the strains isolated. Trans R Soc Trop Med Hyg. 1958;52:263–268. [PubMed] [CrossRef] [Google Scholar]
  24. World Health Organization (2016) Zika virus: Fact sheet (Jan 2016) http://www.who.int/mediacentre/factsheets/zika/en/. Accessed 3 Feb 2016.
  25. Shailendra K. Saxena, Asif Elahi, Srinivasulu Gadugu, and Anil K. Prasad, Virusdisease, Zika virus outbreak: an overview of the experimental therapeutics and treatment 2016 Jun; 27(2): 111–115. Published online 2016 Feb 20.

Dr Arun S Raj
PGT (Organon)
Under the Guidance Of Dr, Manoj Naryan  M D. (Hom.)
SKHMC, Kulasekharam.