Homoeopathy in the treatment of dengue: a literature review

Dr S Mithra

ABSTRACT:
Dengue fevers is an arthropod born febrile illness which is transmitted through the vector Aedes aegypti. It can also lead to Dengue hemorrhagic fever and Dengue shock syndrome. The tropical areas like Asia, Africa, Caribbeans and South America have majority of cases. Dengue fever is characterized by biphasic fever, myalgia, arthralgia, rash, leukopenia, and lymphadenopathy. Dengue hemorrhagic fever is severe and most often fatal. It is characterized by increased capillary permeability, abnormalities of haemostasis, and, in severe cases, it can progress to a protein-losing shock syndrome (dengue shock syndrome).

KEYWORDS: Dengue fever, dengue hemorrhagic fever, dengue shock syndrome, homoeopathy

INTRODUCTION:
Dengue is a tropical disease transmitted by mosquito. Vector that transmits dengue most commonly is Aedes aegypti. It is caused by dengue virus. Dengue viruses (DENV) belongs to the genus Flavivirus in the family Flaviviridae. There are four antigenically distinct dengue viruses (DENV)designated as DEN-1, DEN-2, DEN-3, and DEN-4. If  Aedes aegypti mosquito bites a person with dengue, during febrile viraemic stage it may become infected and subsequently transmit the virus to other uninfected persons¹.

Along with the dengue virus, this genus includes a number of other viruses transmitted by mosquitoes and ticks that includes the Yellow Fever, West Nile, Japanese Encephalitis, And Tickborne Encephalitis Viruses ².

Dengue is a single stranded RNA virus with a lipid envelope. The viral genome encodes three structural proteins and seven non-structural proteins.  The three structural proteins are capsid –  C protein ,membrane -M glycoprotein and envelope- E protein .The seven non-structural proteins are NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5. NS1 is the only non-structural protein in a soluble form that can be detected in circulation¹.

Infection with one dengue serotype provides lifelong immunity to that serotype only, but it also provides protection against other serotypes for initial few months. Neutralizing antibodies to DENV are responsible for specific protection ¹.

EPIDEMIOLOGY:
Dengue has caused significant increase in mortality, morbidity and economic burden in different regions across the world. Dengue is a life-threatening condition in Southeast Asia, where it is the leading cause of deaths in children. In last few decades, we can see overwhelming increase in dengue infections around the world and it is estimated that two fifths of the world’s population is now at risk with the mortality rate of about 5%.Dengue epidemics occur during the warm, humid and rainy seasons, which favour abundant mosquito growth. Aedes aegypti is a daytime biting mosquito which is the principal vector, and all four virus types have been recovered from it. Its  highly domesticated tropical mosquito that prefers to breed in water stored for drinking or bathing and in rainwater collected in any container ^3,4.

PATHOGENESIS :
When an Aedes aegypti feeds on the human and injects the virus into the blood stream. The target cells for the viruses are immature Langerhans cells and keratinocytes. The infected cells migrate to lymph nodes and it attacks monocytes and macrophages. Consequently, viral replication takes place and migrates to various parts through the lymphatic system. When the virus enters the blood stream it causes viremia. As a result of the viremia, many other cells like blood-derived monocytes, myeloid dendritic cells, and splenic and liver macrophages gets infected. Viremia occurs between two to six days of infection⁴.

There are infection-enhancing antibodies formed as a result of first infection, which on second exposure cause higher degree of viraemia and consequently a more severe disease⁵. In the early stage of secondary dengue infections, there is rapid activation of the complement system. Shortly before or during shock, blood levels of soluble tumour necrosis factor receptor, interferon-γ, and interleukin-2 are elevated. Circulating viral non-structural protein 1 (NS1) is a viral toxin that activates myeloid cells to release cytokines by attaching to toll receptor 4. Which also contributes to increased vascular permeability by activating complement, interacting with and damaging endothelial cells, blood clotting factors and platelets. The mechanism of bleeding in dengue hemorrhagic fever is not known fully. But , mild degree of disseminated intravascular coagulopathy, liver damage, and thrombocytopenia together may be responsible for bleeding. Capillary damage allows fluid, electrolytes, small proteins, red blood cells to leak into extravascular spaces. This internal redistribution of fluid, together with deficits caused by fasting, thirsting, and vomiting, results in haemoconcentration, hypovolemia, increased cardiac work, tissue hypoxia, metabolic acidosis, and hyponatremia ³.

Studies done reported that there is high level of viremia in DHF. The characteristic features of DHF is plasma leakage into the abdominal and pleural cavities. Plasma leakage in DHF causes low platelet counts that is below 100,000/mm3 within 1-2 days of infection and it mainly remains low for 3-5 days in most cases. The platelets count in DSS cases is around 20,000/mm³, however in severe cases the platelet counts have frequently been seen below 50,000/mm³. Bleeding is commonly seen in both DHF and DF. Elevated levels of  liver enzymes are commonly observed in both DF and DHF but are more severe in DHF. Microvascular permeability has been reported in both the cases of DHF and DSS⁴.

CLINICAL MANIFESTATION:

Dengue fever:
The incubation period is 1-7 days.

In infants and young children, the disease may be undifferentiated or characterized by fever for 1-5 days with flu-like symptom.

Majority of older children and adults experience sudden onset of fever, with temperature ranging from 39.4-41.1°C (103-106°F),

Accompanied by following symptom :

• Day 1-2:
• Severe back pain precedes the fever.
• Muscle: Myalgia
• Joint : arthralgia
• frontal or retroorbital pain (particularly when pressure is applied to the eyes).
• Skin: transient, macular, generalized rash that blanches under pressure(first 24-48 hr of fever)
• pulse rate : slow relative to the degree of fever.
• Day 2-6:
• Fever
• GIT: nausea ,vomiting ,taste aberrations, and pronounced anorexia.
• Lymph nodes: generalized lymphadenopathy
• Cutaneous hyperesthesia or hyperalgesia
• Approximately 1-2 days after defervescence:
• A generalized, morbilliform, maculopapular rash appears that spares the palms and soles which disappears in 1-5 days and desquamation with intense itching may occur. Rarely there is oedema of the palms and soles.
• When the rash appears for the second time, the body temperature, which has previously decreased to normal, may become slightly raise and may show the characteristic biphasic temperature pattern(saddle back fever).

Dengue Hemorrhagic Fever:

The first phase will be followed by second phase after 2-5 days by rapid clinical deterioration and collapse.

In this phase the patient usually experiences following symptoms:

• Cold and clammy extremities
• Warm trunk
• Flushed face
• Diaphoresis
• Restlessness and irritability
• Mid epigastric pain
• Decreased urinary output
• Skin: petechiae, ecchymoses ,bruising ,bleeding at the sites of venipuncture ,macular or maculopapular rash ,circumoral and peripheral cyanosis.
• Laboured breathing.
• Pulse: weak, rapid, and thready
• Heart sounds: faint.
• Liver : may enlarge to 4-6 cm below the costal margin and is usually firm and tender.

Dengue shock syndrome:

Approximately 20–30% of cases of dengue hemorrhagic fever are complicated by dengue shock syndrome.

shock like state is due to the accompanying hypovolaemia (Leaky capillaries) and also bleeding.

Dengue shock can be accompanied by:

• Increased peripheral vascular resistance.
• Raised diastolic blood pressure rises toward the systolic level.
• Pulse pressure narrows.
• Shock is not from congestive cardiac failure but its due to venous pooling.
• Extravasation of fluid: pleural effusion and ascites.
• Gross ecchymosis or gastrointestinal bleeding(fewer than 10%).
• Temperature : may return back to normal before or during the stage of shock.
• Heart rate and sounds :Bradycardia and ventricular extrasystoles are common during convalescence.

Convalescence phase :

• Temperature, blood pressure and pulse may return to normal.
• Reabsorption of the intravascular fluid.
• During this phase, careful attention to fluid intake is required as patient may develop congestive heart failure.

WHO Criteria for DHF/DSS

Dengue Hemorrhagic Fever:

• Fever
• Minor/major haemorrhagic manifestations
• Thrombocytopenia <100,000/ cu.mm
• Increased capillary permeability (increase in haematocrit of >20%)
• Pleural effusion (X-ray chest)
• Hypoalbuminemia

Dengue shock syndrome:

• DHF criteria Plus
• Hypotension
• Pulse pressure <20 mmHg⁵

DIAGNOSIS : Diagnosis can be made with virological and serological tests. Complete blood counts (haematocrit and platelets)thrombocytopenia and leukopenia and repeated on alternate days or even every day to check for platelet levels². RT-PCR from clinical samples can detect NS1 antigen (virus- produced protein)⁶.Non-structural protein 1 (NS1) preferably the test is done within the first 2 days of infection to get a quick diagnosis².Liver function test may show elevation of ALT/AST, hypoproteinaemia and prolonged prothrombin time². Chest radiographs show pleural effusion² . Serological test ELISA will detect IgM and IgG antibodies⁶.IgM is found during the 4th or the 5th day after the onset of symptom the IgM antibodies are detectable. These antibodies continue to remain in the blood and can be detected for the next 12 weeks. After this, the IgG antibody takes over².

TREATMENT :  There is no specific treatment for dengue in modern medicine. Paracetamol is given every six to eight hours to reduce fevers. The use of painkillers or non-steroidal anti-inflammatory drugs (NSAID) brings the platelet count further down. This can further cause difficult to breath. Antibiotics are useless as the fever is viral. Hospitalization is essential if the platelet count falls to 50,000/mm3 with bleeding and low blood pressure. Platelet transfusion is required only when platelets falls less than 20,000/mm3 with bleeding².

HOMOEOPATHIC MANAGEMENT:

1. ACONITE

• AILMENTS FROM: Dry and cold winds; hot days and cool nights; getting wet ;suppressed perspiration; by fright.

• CHILLS : Starts from extremities to head and face

When uncovered or even touched, slightest movement

One cheek red and hot and the other cheek cold and pale

Face hot, hands and feet cold.

• HEAT: Great thirst for large quantities of water

Dry burning heat which extends from head and face

Great fear; nervous excitability; restlessness and anxious tossing about.

Cough during heat, with palpitation and pleuritic  stitches in the chest

Likes to be uncovered

• SWEAT:
• Must be covered as soon as sweat begins; covered or affected parts sweats perspiration only on side on which he lies.
• TONGUE:
• “Strawberry tongue.”
• Everything else tastes bitter except water
• PULSE:

during chill: intermittent, thread-like

during heat: quick, full, hard, bounding.

2. Belladona

• CHILLS: Begins in both arms at once.
• Hot and red face

Dread of light and noise

Pale face, when lying down; red face when sitting up

Not relieved by heat of stove.

• HEAT: Great thirst and desire for cold water

External coldness of the body and internal burning heat.

Extreme distension of the superficial blood-vessels, the distended veins lie like   cords on the skin.

Violent, bursting headache, with strong pulsations of arteries, especially throbbing of the carotids

Averse to uncovering.

Sensitive to light and noise.

• SWEAT:
• On covered parts only.
• Sweat stains the linen yellow.
• Sweat of empyreumatic ,smoky odour.
• TONGUE:

Red, dry, “scarlatina-like”.

Offensive, putrid taste

• PULSE:

During chills: strong, full, large and frequent

During heat : small, wiry and hard

3. BRYONIA

• AILMENTS FROM:  Getting wet ; in dry weather, together hot or cold.

• CHILLS: Begins on lips, tips of fingers and toes

With great thirst for large quantities of cold water

Violent and dry cough during chills

Pleuritic stitching pains in chest and region of  the spleen

Chills on right side of the body

< warm room ;from moving.

• HEAT
• Headache and vertigo
• Dry, burning, internal heat as if  molten lead was running through the blood-vessels .
• With desire to uncovered
• Wants to be quiet
• Thirst less than in cold stage

SWEAT

• Profuse, sour, oily
• Sweat on single parts .
• Sweat on side on which he lies
• TONGUE
• Thick, yellow coating on the tongue

Dryness of mouth and lips 

Everything tastes bitter.

• PULSE
• Full, hard and tense.

4. EUPATORIUM PERFOLIATUM

• CHILL
• With intense thirst; but drinking water causes the nausea and bitter vomiting.
• Chilliness in the morning, heat throughout the whole day, but no perspiration.
• Pain in back and bones of extremities, moaning with pain.

Yawning and stretching.

Must be warmly covered.

Begins in or may spread from the back or runs up the back.

• HEAT
• Preceded by thirst ,“A swallow of water will make him shiver”

Cephalalgia and bone pains are increased; cannot raise the head while fever lasts

Seldom any nausea during this stage, but bitter vomiting

Much shivering even during heat.

• SWEAT
• Generally scanty, or absent
• It brings relief of all pains except cephalalgia, which is increased.
• TONGUE
• Coated white or yellow.
• Taste, insipid, bitter; food has no taste.
• Desire for ice cream.
• Canine hunger after Quinine.

5. GELSEMIUM :

• CHILL
• Without thirst.
• Chill commences in the hands and feet
• Chill running up the back from sacrum to occiput.
• Child wants to be held so that he will not shake so hard.
• HEAT

Without thirst; intense burning.

• General heat, mostly about the head and face.
• After chills comes a flying heat and pricking in the skin which is rapidly followed by perspiration.
• Sleepy, stupid, besotted, with half-waking, muttering delirium.
• Wants to lie still
• Sensitive to light or noise

SWEAT

• Profuse, which relieves the pain.

TONGUE

• Coated yellowish-white, or nearly clean, or with white centre and red margins.
• Taste: bitter, foul, with blood-coloured saliva.
• PULSE
• Irregular, intermitting, yet full.
• Small, weak, feeble, almost imperceptible.

6. IPECACUANHA

• AILMENTS FROM:

Irregularities and indiscretions in diet.

Cases drugged with quinine and arsenic.

• CHILL
• Without thirst.
• Chilliness is worse when in a warm place and lessened by drinking and in the open air .
• External coldness with external heat.
• The hands and feet are icy-cold, and wet with cold sweat
• Chill with or without nausea and vomiting.
• HEAT

With thirst

With alternate coldness and paleness of face

           Oppressed breathing, dry, hacking cough which often exciting

           nausea and vomiting

External heat without internal heat

           One hand cold and  the other one hot

• SWEAT
• Sudden attacks of sweat in a room; on upper parts of body; increased by motion and in the open air .
• Always worse during sweat; better after it
• TONGUE
• At first clean; then coated yellowish or white; pale in all cases.
• Taste bitter, sweetish, like rancid oil.

Desire for sweets

7. RHUS TOXICODENDRON

• CAUSE
• Especially getting wet when overheated; after a drenching from rain and neglecting the precaution of changing the wet clothes, living in damp rooms
• CHILLS

Begins on only one side, the right by preference .

Severe chills as though dashed with ice-cold water or as if the blood were running    cold through the vessels; cold when  he moves; increased by eating and drinking;  became hot by lying down and covering .

Pain between the shoulders and stretching of the limbs during fever at night.

Dry, teasing, fatiguing cough during chill.

Great restlessness during chill.

• HEAT
• With thirst.
• As if dashed with hot water; excessive heat, as from hot water running through the blood -vessels, without thirst, but with throbbing, dull, headache, pressure and  swelling at pit of stomach, and diarrhoea with cutting pain in abdomen.
• Urticaria breaks out over entire body with violent itching, increased by rubbing.
• Hot internally and chilly externally.
• SWEAT
• Profuse sweat, odourless and not exhausting.
• Urticaria, with violent itching, which passes off with the sweat.
• Sweat does not relieve all pains.
• TONGUE
• Coated white, often on one side only; takes imprint of teeth with red, dry, triangular tip⁷.

REFERENCES:

1. Parthasarathy A. IAP Textbook of Pediatrics. JP Medical Ltd; 2016.
2. Tripathy T, Das S, Singh DP, Pandey SN, Tripathy S, Tripathy A, et al. Role of homoeopathy of Ayush in dengue fever. International journal of community medicine and public health/International journal of community medicine and public health. 2023 Dec 30;11(1):577–81. Role_of_homoeopathy_of_Ayush_in_dengue_fever.pdf
3. Kliegman RM. Nelson Textbook of Pediatrics. 21st ed. Philadelphia: Elsevier; 2020.
4. Hussain T, Jamal M, Tayyab ur Rehman, Saadia Andleeb. Dengue: pathogenesis, prevention and treatment – A mini review. 2015 May 25;2(3):110–4. https://www.researchgate.net/publication/277197294_Dengue_pathogenesis_prevention_and_treatment_-_A_mini_review
5. Goel KM, Gupta DK. Hutchison’s Paediatrics. New Delhi: Jaypee Brothers Pvt. Ltd.; 2012.
6. Kannan C, N. Nirubanraj, Jane P. Dengue Fever Cured by Homeopathy– Two Case Series. Asian Pacific journal of health sciences. 2022 Jun 20;9(4):61–5. https://www.researchgate.net/publication/369742534_Dengue_Fever_Cured_by_Homeopathy-_Two_Case_Series
7. ‌Henry Clay Allen. The Therapeutics of intermittent fever. 1884.

Dr S Mithra. _BHMS
PG Scholar Department of Pediatrics
Government Homoeopathic Medical College and Hospital,Bengaluru-560079
drsmithra@gmail.com
Under The Guidance of Dr. Muddassir M Mulla. _{MD, Hom}
Associate Professor, Department Of Pediatrics, Government Homoeopathic Medical College and Hospital Bengaluru-560079