Dengue feverBMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h4661 (Published 15 September 2015) Cite this as: BMJ 2015;351:h4661
All rapid responses
1.May I request the BMJ and the author to correct an error ? In the text, it mentions INCREASED liver function. A misprint no doubt. It should be DECREASED liver function.
2. The author mentions retroORBITAL pain. That implies intracranial pain, located behind the orbit. Surely the author meant retro-OPTIC pain? That is, pain behind the eye ball, but within the Orbit? .
I would be grateful for clarification.
3. Treatment. Considering the thousands of cases of Dengue in Sri Lanka, India and Pakistan, would the author not recommend a randomised controlled trial of Carica papaya? There are, in the literature, several reports of its value. Carica papaya is widely grown in the three countries, besides others such as the Phillipines.
Competing interests: No competing interests
Dengue is a viral disease. It is transmitted by the infective bite of the Aedes Aegypti mosquito. Man develops the disease after 5-6 days of being bitten by an infective mosquito. Though the fever can attack anybody, those with a weak immune system are at greater risk than others. Total cases and deaths in 2015 were 99913 and 220 respectively, and this year the death toll rose to 70 and cases rose to 36110 up to 11th September 2016. This number could increase rapidly in the next 1-2 months.
Communication campaigns about cleanliness, insecticide-laced mosquito nets and repellents are very important strategies in prevention. Dengue preventive plan mainly involves community people’s education, a uniform guideline to treat it, etc. People could be educated through behavior change communication. Tropical and sub-tropical areas are more prone to dengue outbreaks. Travelers from and across such regions can also carry the disease.
Do's and don'ts for Dengue fever
It is necessary to remove water from coolers and other small containers at least once in a week. Children should not be allowed to play in shorts and half sleeved clothes.
Antibiotics and steroids shouldn't be used because they do not show any benefit. It is necessary to avoid giving blood transfusion unless indicated, reduction in haematocrit or severe bleeding. Do not give aspirin or ibuprofen for treatment of fever.
Signs of recovery for Dengue fever
Various recovery signs of dengue fever or dengue hemorrhagic fever are stable pulse, normal blood pressure and breathing rate, normal temperature, no evidence of external or internal bleeding, normal appetite, no vomiting, good urinary output, stable haematocrit, etc.
 Report of Dengue Cases and Deaths in the Country since 2010 available at http://nvbdcp.gov.in/den-cd.html
Competing interests: No competing interests
Carica Papaya leaf extract is now being widely used as a treatment for Dengue fever in many countries (1) and in some with the approval of their health authorities (2). A large ampunt of biomedical research has been done on this subject, including three randomised control clinical trials (3,4,5,6,7,8,9,10,11,12,13). There were no reported significant adverse effects following this treatment (7) and toxicology studies ruled out any toxic effects even at higher doses (14).
This research has shown many beneficial effects, including reduction in the duration of fever, duration of illness, hospital stay, most importantly fluid leak and the conversion of Dengue fever to Dengue haemorrhagic fever, rapid elevation of white blood cells and platelet counts. This treatment can be initiated at primary care level after confirming the diagnosis with NS1 antigen from the first day of fever.
Based on my clinical experience and clinical research, I recommend that papaya leave extract to be given from the first day of Dengue fever concurrently with the usual dengue management. This will reduce morbidity and mortality.
Guidelines in using carica papaya leaf extract for Dengue fever patients
1. In anyone suffering from fever, headache or body pain, it is advisable to do Dengue NS1 antigen test as early as possible.
2. If the Dengue NS1 antigen test is positive, it is very likely that you are suffering from Dengue fever.
3. When you are diagnosed with Dengue fever you should immediately get treatment from an allopathic doctor. Papaya leaf extract should be used in addition to the usual Dengue management.
4. Papaya leaf extract could be given at any stage of the disease. But for best results it should be given from the first day of fever.
5. Papaya leaf extracts could be taken as syrup; 30ml three times a day before meals for an adult and 5-10ml three times a day for a child until you have fully recovered from the illness. It is advised not to stop the treatment halfway.
6. A few sips of cold water could be taken immediately after the Papaya leaf extract, to overcome the bitter taste.
7. Do not take Papaya leaf extract if you are allergic to Papaya.
8. Method of preparation
• Get fresh healthy mature papaya leaves from a fruit-bearing tree.
• Wash the leaves thoroughly with running tap water and chop the leaves in to small pieces excluding the main stem (not necessary to remove the small stems in the leaves).
• Weigh 50g of papaya leaves and put it into a mortar and pestle.
• Add 50ml of boiled cool water and 25g of sugar.
• Pound the above mixture well for 15 minutes till a uniform pulp is made.
• Mix this pulp well and keep for about 30 minutes.
• Squeeze this pulp by hand and get the papaya leaf extract (do not use a cotton sieve to extract the juice).
• You can store this preparation for 24 hours in the lower compartment of the refrigerator (+4 oC)
• Shake the bottle well before the preparation is given.
1. Hettige S .Carica papaya leaf extract in Dengue fever. IMPA Journal |December 2015|Volume 09|Number 01, IMPA Journal; pg 11-14. [Internet]. 2016 [cited 24February2016]; Available from: https://www.dropbox.com/s/b8zejo8r7nx3l6e/09%20Impa%20Journal%20-%20volu...
2. Free Malaysia Today. Ministry studies papaya leaves to treat dengue. [Internet]. 2015 [Cited30 September 2015];Available from: http://www.freemalaysiatoday.com/category/nation/2015/05/16/ministry-stu...
3. Hettige S. Salutary effects of carica papaya leaf extract in dengue fever patients – a pilot study [Internet]. Sri Lanka: Sri Lankan Family Physician; 2008 [Cited 30 September2015]; 2008,29,17-19. Available from: http://cgpsl.org/wp-content/uploads/2013/11/119.pdf
4. Hettige S. Dengue: an escalating problem., Papaya leaves for speedy rise of platelet count in Dengue. British Medical Journal [Internet]. 2002 [Cited 30 September 2015];324(7353):1563-1566. Available from: http://www.bmj.com/rapid-response/2011/11/03/repapaya-leaves-speedy-rise...
5. Paknikar S, Sarala N. Papaya extract to treat dengue: A novel therapeutic option?. Annals of Medical and Health Sciences Research [Internet]. 2014 [Cited 6 November 2015];4(3):320. Available from: http://www.amhsr.org/article.asp?issn=2141-9248;year=2014;volume=4;issue...
6. Kumar. N. Dengue: an escalating problem., Papaya leaves for speedy rise of platelet count in Dengue. British Medical Journal [Internet]. 2002 [Cited 30 September 2015];324(7353):1563-1566. Available from: http://www.bmj.com/rapid-response/2011/11/03/papaya-leaves-speedy-rise-p...
7. Subenthiran S, Choon T, Cheong K, Thayan R, Teck M, Muniandy P et al. Carica papaya Leaves Juice Significantly Accelerates the Rate of Increase in Platelet Count among Patients with Dengue Fever and Dengue Haemorrhagic Fever. Evidence-Based Complementary and Alternative Medicine [Internet]. 2013 [Cited 6 November 2015];2013:1-7.Available from: http://www.hindawi.com/journals/ecam/2013/616737/
8. Senthilvel P, Lavanya P, Kumar K, Swetha R, Anitha P, Bag S et al. Flavonoid from Carica papaya inhibits NS2B-NS3 protease and prevents Dengue 2 viral assembly [Internet]. India: Biomedical Informatics; 2013 [Cited 30 September 2015]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842573/
9. Otsuki N, Dang N, Kumagai E, Kondo A, Iwata S, Morimoto C. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects [Internet]. Japan: Elsevier Ireland Ltd., Journal of Ethnopharmacology; 2009 [Cited 30 September 2015]. Available from: http://herbalnet.healthrepository.org/bitstream/123456789/2193/1/sdartic...
10. Ranasinghe P, Ranasinghe P, Abeysekera W, Premakumara G, Perera Y, Gurugama P et al. In vitro erythrocyte membrane stabilization properties of Carica papaya L. leaf extracts [Internet]. Sri Lanka: Pharmacognosy Research; 2012 [Cited 30 September 2015]. Available from: http://www.phcogres.com/article.asp?issn=0974-8490;year=2012;volume=4;is...
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Competing interests: No competing interests
Manifestations of dengue in the eye, though rare in the past, are now more recently noted to be common in some outbreaks. The most common manifestation, besides the expected complication of bleeding on macula, seems to be foveolitis or maculopathy (1) Sometimes the maculopathy may resolve spontaneously (2) The prevalence may vary according to the subtype of the virus but it can be as high as 10% in some outbreaks (3) (4). Optical coherence tomography (OCT) patterns may be used to predict the visual outcomes of maculopathy (5) and function may be assessed with Electroretinography (6), and some authors have stressed the need to look at both structure and function (7). Some authors have correlated visual field changes with OCT (8) and others (9) have demonstrated a parafoveal retinal thickness and subfoveal chorioidal thickness. Dengue can have various manifestations in the eye, (10)(11) and more recently a newer terminology of “dengue eye disease” has emerged (12). Dengue may have presenting features of subconjunctival haemorrhage and ecchymosis (13). It may have unusual presentations like frosted branch angitis (14) or papillodema secondary to cerebral veinous thrombosis (15). It may cause a central retinal artery occlusion (16), a branch retinal artery occlusion (17) or subhyaloid haemorrhage (18). In severe, unusual cases it has been found to cause even proptosis and globe rupture, as seen by Nagaraj et al (19).
It can also cause symptomatic inflammatory manifestations like retinochoroiditis (20) vasculitis, choroidal neovascularisation (21) secondary to immune damage, and even panophthalmitis (22).
One needs to be aware that it has been known to cause both eye involvement with potential to make a person irreversibly bilaterally blind by causing bilateral vitreous haemorrhage (23), bilateral stellar neuroretinitis (24), bilateral choroidal effusion (25) and may be a suspect ethology even for bilateral acute angle closure glaucoma (26), oculomotor paralysis (27) and optic neuropathy (28). The " Seet Quek Lim triad" of flashes of light, floaters and blurring of vision (29) may now warrant an ophthalmic consult and if not requested may be construed as negligence if eventually the patient loses vision, because dengue vision loss can be irreversible and may be seen in up to 10 percent of cases and has potential to cause bilateral irreversible visual impairment or blindness as reported.
Besides this the patient may present with an opsoclonus which may point towards an encephalopathy (30) (31) and so the expected retinal and macular haemorrhages (32) (33) are not the only pathologies that dengue can cause in the eye.
One also needs to remember that in endemic areas recurrence of infection may mean recurrence of bilateral eye involvement (34).
If it is uveitis it may recover well with steroids like some reports suggest (35) but bilateral cases like vasculitis and macular oedema (36) one may need to use newer medications and even 66 years after eye manifestations of dengue were first reported (37) ,dengue continues to blind people and greater awareness and timely referral is important even today.
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2) Luk F, O, Chan C, K, Lai T, Y, A Case of Dengue Maculopathy with Spontaneous Recovery. Case Rep Ophthalmol 2013;4:28-33
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4) Chee E, Sims JL, Jap A, Tan BH, Oh H, Chee SP. Comparison of prevalence of dengue maculopathy during two epidemics with differing predominant serotypes. Am J Ophthalmol. 2009 Dec;148(6):910-3. doi: 10.1016/j.ajo.2009.06.030.
5) Teoh SC, Chee CK, Laude A, Goh KY, Barkham T, Ang BS; Eye Institute Dengue-related Ophthalmic Complications Workgroup. Optical coherence tomography patterns as predictors of visual outcome in dengue-related maculopathy. Retina. 2010 Mar;30(3):390-8. doi: 10.1097/IAE.0b013e3181bd2fc6.
6) Mendes TS, Sobrinho EF, Rosa AA, dos Anjos LM, da Costa GM, Souza Gda S, Gomes BD, Saito CA, da Silva Filho M, Silveira LC. Dengue maculopathy: visual electrophysiology and optical coherence tomography. Doc Ophthalmol. 2009 Oct;119(2):145-55. doi: 10.1007/s10633-009-9178-5.
7) Tan MH, Tan PE, Wong EN, Chen FK. Structure and function correlation in a patient with dengue-associated maculopathy. Clin Experiment Ophthalmol. 2014Jul;42(5):504-7. doi: 10.1111/ceo.12269.
8) Rhee TK, Han JI. Use of optical coherence tomography to evaluate visual acuity and visual field changes in dengue fever. Korean J Ophthalmol. 2014Feb;28(1):96-9. doi: 10.3341/kjo.2014.28.1.96.
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10) Chan, David P.L. et al. "Ophthalmic Complications of Dengue." Emerging Infectious Diseases 12.2 (2006): 285-289.
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12)Ng AW, Teoh SC. Dengue eye disease. Surv Ophthalmol. 2015 Mar-Apr;60(2):106-14. doi: 10.1016/j.survophthal.2014.07.003. Epub 2014 Aug 12.
13) Jain S, Goswami A, Singh N, Kaur S. Bilateral eyelid ecchymosis and sub conjunctival haemorrhage manifesting as presenting feature in a case of dengue haemorrhagic fever. Trop Doct. 2014 Dec 24. pii: 0049475514565429.
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16) Sadiq N, Naqaish T, Arif A, Mohammad K, Jalis M. Central retinal artery occlusion secondary to dengue fever. J Ayub Med Coll Abbottabad. 2014 Jan-Mar;26(1):98-9.
17) Kanungo S, Shukla D, Kim R. Branch retinal artery occlusion secondary to dengue fever. Indian J Ophthalmol. 2008 Jan-Feb;56(1):73-4.
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19) Nagaraj KB, Jayadev C, Yajmaan S, Prakash S. An unusual ocular emergency in severe dengue. Middle East Afr J Ophthalmol. 2014 Oct-Dec;21(4):347-9. doi:10.4103/0974-9233.142276.
20) Tabbara K. Dengue retinochoroiditis. Ann Saudi Med. 2012 Sep-Oct;32(5):530-3. doi: 10.5144/0256-4947.2012.30.4.1105.
21) Veloso CE, Schmidt-Erfurth U, Nehemy MB. Choroidal neovascularization induced by immunogenic alteration of the retinal pigment epithelium in dengue Fever. Case Rep Ophthalmol. 2015 Jan 17;6(1):18-23. doi: 10.1159/000371791.
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Competing interests: No competing interests