Medical Officers’Handbook for Clinical

Management of Dengue& Malaria

Department of Health & Family WelfareGovernment of West Bengal

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ANIL VERMA, I.A.S.Principal Secretary

FOREWORD

Over the last decade, dengue has emerged globally as a critical threat to health of people. The WorldHealth Organization (WHO) estimates that 50-100 million dengue infections occur each year and almosthalf the world’s population lives in countries where dengue is endemic. Dengue also ranks as one of themost challenging mosquito-borne viral diseases in the world including malaria. While dengue is a globalconcern, West Bengal is not untouched.

To work upon these concerns, the training of Medical Officers at health facility levels will be undertakenwith the aim to reduce Dengue mortality & Malaria Mortality by improved clinical management of patients.We already have worked on Vector Borne Diseases Surveillance Joint Action Plan to tackle and take measureson outbreak prediction, epidemiological and entomological surveillance and develop locally-adapted vectorcontrol programme.

The Guidelines – “Medical Officers Handbook for Clinical Management of Dengue & Malaria” will providecritical inputs to Medical Officers to enhance the quality of patient management at the point of health caredelivery. Such management practices with timely intervention will also ensure early recovery and restrictunnecessary referral.

I express my gratitude to the experts, WHO-NTD Division and compliment the Public Health Division ofthe Directorate of Health Services, WB on this initiative. I wish all success to the programme.

(Anil Verma)

Government of West BengalHealth & Family Welfare DepartmentSwasthya Bhavan, 3rd Floor, Wing ‘B’

GN-29, Sector-V, Salt Lake,Kolkata-700091

Ph. : (033) 2357-5899, Fax : (033) 2357-7907

No. HS-352/2018 Dated : 23/05/2018

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Dr. Ajoy Kumar Chakraborty Government of West BengalDirector of Health Service Department of Health and Family Welfare

Swasthya Bhawan, Wing- “A” 4th Floor, GN-29Sector-V, Salt Lake City, Kolkata-700091

PREFACE

Dengue & Malaria both are major public health challenges among vector borne diseases in West Bengal.There has been a recent upsurge of fever cases. Dengue cases are reported but the proportionate mortalityis less in our State. This can be further reduced with timely case management specially maintaining thecritical fluid balance even in the primary tier set up. More alarming is Malaria situation where at Nationallevel we have less Falciparum cases but higher case fatality in the country and also single largest contributorof malaria deaths in the country. This needs further focus since prompt diagnosis and intervention canprevent many of such deaths.

An urgent need was felt to sensitize the Medical Officers on Dengue and Malaria so that all of them aresensitized on recent updates of treatment guideline, have a clear clarification on approaches to be adoptedand provide timely best possible treatment available at that facility, even in a primary setting.

“Medical Officers Handbook for Clinical Management of Dengue & Malaria” developed by Health & FamilyWelfare Department, Govt of West Bengal is not intended to replace national treatment training materialsand guidelines but is developed based upon that to give practical contextual information and helpful tobuild up confidence of Medical Officers in our State.

This handbook has been produced and made widely available to health-care practitioners at all levels. Thisdeals with different aspects of management even severe cases of dengue & malaria at different levels ofhealth care. The focus is to build up the confidence of Medical Officers and bring uniformity in casemanagement of dengue & malaria in West Bengal. I hope, with help of this training there will be a greatimprovement of quality of management of both the cases and many lives will be saved in future.

We are most grateful to all the contributors without whose active support it was not possible to prepare thismodule in such a short time.

DATE : 23.05.2018 (Dr. A.K. Chakraborty)

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CONTENTS

Chapter Page No

Foreword iii

Preface v

Clinical Management of Dengue

Introduction 3

Dengue virus 3

Understanding dengue fever 3

Febrile phase of dengue 4

Critical phase 5

Recovery phase 6

Worsening hypovolemic shock 6

Prolonged hypotensive shock 6

Medical complications seen in the febrile, critical and recovery phases of dengue. 7

Risk factors associated with severe disease of dengue 7

Clinical evaluation 7

History taking 7

Clinical examination 8

Investigations 8

Diagnosis and assessment of disease phase and severity 9

Undifferentiated dengue Fever (UDF) 9

Severe dengue Fever 10

Grading of DF/ DHF 10

Expanded dengue Syndrome (EDS) 11

Clinical Criteria for DF/ DHF/ DSS 11

Differential Diagnosis of DF/ DHF 11

Clinical Management 12

General Management of Dengue Fever (DF) 13

Management of DHF Grade I and II 14

Management of Shock (DHF Grade III/IV) 15

Flow diagrams 15

When to start and stop intravenous fluid therapy 17

Choice of intravenous fluids for resuscitation 17

Summary of IV fluid therapy in Dengue 19

Management of severe bleeding 21

Management of DF/ DHF with co-morbid illness. 22

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Chapter Page NoManagement of DF with co-infections 24

Management of dengue in pregnancy 24

Management of dengue in infants 26

Suggested Admission & Discharge criteria 27

Nursing advice in admitted patient 27

Practices to be kept in mind 28

Annexure 28

References 31

Clinical Management of Malaria

What is Malaria? 34

Clinical features 34

Diagnosis 34

Treatment of Vivax Malaria 36

Treatment of Falciparum Malaria 36

Management in specific situation

Treatment of uncomplicated P. falciparum cases in pregnancy: 36

Treatment of mixed infections (P. vivax + P. falciparum) cases: 37

Antimalarials for severe malaria cases: 37

Treatment of patients co-infected with HIV: 38

Additional consideration for clinical management: 38

Points to Note –

Pre-referral treatment options 38

Initiation of treatment and advice to the patient/caretaker 38

General recommendations for the management of uncomplicated malaria 39

Primaquine therapy: Caution 39

Clinical observation of admitted cases 39

Dont’s in severe malaria 40

Annexure 41

Clinical Management of Dengue

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Medical Officers Handbook for Clinical Management of Dengue

Introduction

Dengue is a major public health concerns globally, a common cause of illness seen in primary care settingsin tropical and subtropical countries. It is endemic in more than 100 countries of Africa, America, EasternMediterranean, South-East Asia and Western Pacific. It is the most rapidly spreading mosquito-borne viraldisease of mankind, with a 30-fold increase in global incidence over the last five decades. According toWorld Health Organization (WHO), about 50-100 million new dengue infections are estimated to occurannually in more than 100 endemic countries, with a steady increase in the number of countries reportingthe disease.

Every year, during the period July - November, an upsurge in the cases of dengue/DHF has been observedin India. The disease has a seasonal pattern; the cases peak after the monsoons. It is transmitted by Aedesaegypti and Aedes albopictus.

Literature shows that case fatality in Dengue can be minimized by early treatment attention. Medical Officersplay a pivotal role in the early recognition and management of dengue fever when patients progress throughthe different phases of illness.

Dengue virus

The agent of dengue,i.e. dengue viruses, are categorized under the genus Flaviviridae. They are singlestranded RNA virus. The dengue virus genome is composed of three structural protein genes encoding thenucleocapsid of core protein(C), a membrane associated protein (M), an envelope protein (E) and sevennon-structural (NS) proteins — NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5. The functions for all theindividual NS-proteins are not well characterized. However,NS1 protein has been shown to interact withthe host immune system, and known to evoke T cell responses. In dengue virus infection, patients havemeasurable levels of NS1 protein in the blood, which are utilized as a diagnostic marker of the infection.Thereare four dengue virus serotypes which are designated as DENV-1, DENV-2, DENV-3 and DENV- 4. Theseserotypes can co-exist in the endemic areas because the immunity to one serotype does not afford protectionfrom the infection by a heterotopous serotype. Although all four serotypes are antigenically similar, they aredifferent enough to elicit cross- protection only for a few months after infection by any one of them. Infectionwith any one serotype confers lifelong immunity to that virus serotype. The ability of all DENV serotypes toutilize pre-existing heterotypic flavivirus antibody to enhance antigen antibody reaction, a unique feature ofDENV, distinguishes it from all other flaviviruses and is considered to be the primary basis of DENVpathogenesis.Individual variations occur in antibody responses to the dengue virus. Secondary infectionsare associated with elevated risks of severe disease outcomes. Primary and secondary infections aredistinguishable based on their antibody responses.

Understanding dengue fever

Dengue viruses cause symptomatic infections or asymptomatic seroconversion. Patients with asymptomaticinfection are viraemic and thus may be a source of infection. Symptomatic dengue infection is a systemicand dynamic disease. The incubation period lasts for 5 to 7 days and the onset of the illness is abrupt. It hasa wide clinical spectrum, which includes both severe and non-severe clinical manifestations.

Common presenting symptoms include high-grade fever, headache, retro-orbital pain, myalgia, arthralgia,nausea, vomiting and rash. The symptoms usually last for 2-7 days. As the symptoms are relatively nonspecificin early stages, other differential diagnoses need to be considered in the first 72 hours. In patients withmoderate-to-severe disease, the course of the illness follows three phases: febrile, critical and recovery.

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The severity of the disease usually becomes apparent during defervescence, that is, during transition fromthe febrile to the afebrile phase. This often coincides with the onset of the critical phase, usually occurs ondays 3 to 8 of illness. The critical phase is distinguished by the pathophysiological phenomenon of increasedcapillary permeability, which lasts approximately for 24 to 48 hours and is more common in secondarydengue infections. This phase is followed by the recovery phase. The key to achieve a good clinical outcomeis to have an understanding of the different phases of the disease and be alert to the clinical problems thatcould arise during these phases.

Figure 1: Course of Dengue illness

Febrile phase of dengue

After the incubation period, the illness starts abruptly with high fever accompanied by non-specific symptomssuch as facial flushing, skin erythema, generalised body aches and headache. This febrile or viraemia phaseusually lasts for 2 to 7 days. It can be clinically difficult to distinguish dengue from other viral febrileillnesses in the early febrile phase.

In addition to a recent history of dengue within the family or neighborhood, the three early clinical predictorsof dengue at 72 hours of fever were nausea and/or vomiting, postural dizziness and lower total whitecell count compared to patients with other febrile illnesses (OFI). Symptoms such as headache, myalgia,arthralgia and retro-orbital pain that were frequently reported by patients with dengue fever were alsoobserved in patients with OFI with no significant differences. Similarly, children with dengue were morelikely to report anorexia, nausea and vomiting. They had a positive tourniquet test, lower total white cellcounts, absolute neutrophil and monocyte counts and higher plasma ALT and AST than the children withOFI. Symptoms of upper respiratory tract infections such as injected pharynx and enlarged tonsils did notexclude dengue.

After 2 to 3 days of high fever, anorexia and nausea, most patients may have varying degrees of dehydrationand lethargy. The quality of life decreases to approximately 40% to 50% at the onset of fever with experiencesof somatic pain and discomfort and difficulties in cognition, sleep, mobility, self-care and anxiety or depression.Mild haemorrhagic manifestations such as petechiae and mucosal membrane bleeding (e.g., nose and gums)may be seen. Easy bruising and bleeding at venipuncture sites are present in some cases. Massive vaginalbleeding (in women of childbearing age) and gastrointestinal bleeding may occur during this phase, althoughthis is not common. The liver may be enlarged and tender after a few days of fever. The earliest change inthe full blood count is a progressive decrease in white blood cell count, which should alert the physician toa high probability of dengue. This leucopenia is most likely due to a virus-induced down-regulation ofhaematopoiesis.

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Critical phase

During the transition from febrile to afebrile phase, usually after day 3 or as late as day 7 of fever, patientswithout an increase in capillary permeability improve without going through the critical phase. Their appetitesimprove and they feel better. Patients with increased capillary permeability, however, experience worseningof symptoms with the subsidence of high fever. Defervescence usually occurs on days 3 to 8 of illness whentemperature drops to 38°C or less and remains below this level. Patients may have warning signs, mostly asa result of plasma leakage. Warning signs usually precede the manifestations of shock and appear towardsthe end of the febrile phase, usually between days 3 and 7 of illness.

Warning and danger signs and symptoms of dengue fever

Bleeding: epistaxis, scanty haemoptysis, haematemesis, gum bleeding, black coloured stools,excessive menstrual bleeding, dark-coloured urine or haematuria.

Lethargy and/or restlessness, sudden behavioural changes.

Convulsions.

Difficulty in breathing or palpitation or breathlessness.

Persistent vomiting >3 times a day.

Severe abdominal pain

Enlarged and/or tender liver

Clinical fluid accumulation.

Postural hypotension-dizziness.

Pale, cold clammy hands and feet.

Not able to drink and no urine output for 4-6 h/ urine output less than 0.5 ml/kg/h.

Rising HCT (>45%)together with rapid fall in platelet count.

Metabolic acidosis.

Derangement of liver/ kidney function tests.

Pleural effusion/ ascites/ gall bladder oedema on imaging.

It is important to note that the warning signs should not be randomly applied without making a clinicaldiagnosis of dengue.

In the full blood count picture, progressive leucopenia followed by a rapid decrease in platelet countusually precedes plasma leakage. An increasing haematocrit (HCT) above the baseline is another earlysign. The period of clinically significant plasma leakage usually lasts 24-48 h. The degree of plasma leakagevaries. A rising haematocrit precedes changes in blood pressure (BP) and pulse volume. The degree ofhaemoconcentration above the baseline haematocrit reflects the severity of plasma leakage; however, thiscan be masked by early intravenous fluid therapy. Usually pleural effusion and ascites are clinically detectableonly after an intravenous fluid therapy unless the plasma leakage is significant, which is a case of patient ina state of shock. A right lateral decubitus chest radiograph, ultrasound detection of free fluid in the chest orabdomen or gall bladder wall oedema may precede clinical detection. In addition to the plasma leakage,haemorrhagic manifestations such as easy bruising and bleeding at venepuncture sites occur frequently.Shock occurs when a critical volume of plasma is lost through leakage; it is often preceded by warningsigns. Some patients progress to the critical phase of plasma leakage and shock before defervescence. Inthese patients, a rising haematocrit and rapid onset of thrombocytopenia or the warning signs indicate theonset of plasma leakage. Most patients with dengue having warning signs recover from intravenousrehydration, although some will deteriorate to severe dengue.

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Recovery phase

As the patient survives the 24- to 48-hour critical phase, a gradual reabsorption of extravascular compartmentfluid takes place in the following 48 to 72 hours. During this time, patient’s general well-being improves,appetite returns, gastrointestinal symptoms abate, haemodynamic status stabilizes and diuresis ensues.Some patients may exhibit a confluent erythematous or petechial rash in small areas of normal skin describedas “isles of white in the sea of red”. Some may experience generalised pruritus. Bradycardia andelectrocardiographic changes are common during this stage. The hematocrit stabilizes or may becomelower due to the dilutional effect of reabsorbed fluid. The white blood cell count usually starts to rise soonafter defervescence but the recovery of the platelet count is typically later than that of the white blood cellcount. Respiratory distress from massive pleural effusion and ascites, pulmonary oedema or congestiveheart failure may occur during the critical and/or recovery phases if excessive intravenous fluids have beenadministered.

Worsening hypovolemic shock

Worsening hypovolemic shock manifests as increasing tachycardia and peripheral vasoconstriction. Notonly are the extremities cold and cyanosed but the limbs become mottled, cold and clammy. By this stagethe breathing becomes more rapid and increases in depth, a compensation for the metabolic acidosis(Kussmaul’s breathing). Finally, there is decompensation, both systolic and diastolic BPs decrease suddenlyand dramatically, and the patient is said to have hypotensive or decompensated shock.

At this time the peripheral pulses disappear while the central pulse (femoral) will be weak. Hypotensiondevelops when physiologic attempts to maintain systolic BP and perfusion are no longer effective.

One key clinical sign of this deterioration is a change in mental state as brain perfusion declines. The patientbecomes restless, confused and extremely lethargic. Seizures may occur and agitation may alternate withlethargy. On the other hand, children and young adults have been known to have a clear mental status evenin profound shock. Adults have been known to be able to work until the stage of profound shock is reached.

The failure of infants and children to recognize, focus or make eye contact with parents may be an earlyominous sign of cortical hypo perfusion, as is the failure to respond to painful stimuli such as venepuncture.Parents may be the first to recognize these signs, but they may be unable to describe them, other than to saysomething is wrong. Listen to parents! Hypotension is a late finding and signals an imminent totalcardiorespiratory collapse.

Prolonged hypotensive shock

Prolonged hypotensive shock and hypoxia lead to severe metabolic acidosis, multiple organ failure and anextremely difficult clinical situation. It may take a few hours for patients to progress from warning signs tocompensated shock and another few hours for compensated shock to progress to hypotensive shock, butonly minutes for hypotensive shock to progress to cardiorespiratory collapse and cardiac arrest.

Hypotension is associated with prolonged shock which is often complicated by major bleeding. Patientswith severe dengue have varying degrees of coagulation abnormalities, but these are usually not sufficientto cause major bleeding. When major bleeding does occur, it is almost always associated with profoundshock since this, in combination with thrombocytopenia, hypoxia and acidosis, can lead to multiple organfailure and advanced disseminated intravascular coagulation.

Massive bleeding may occur without prolonged shock in instances when acetylsalicylic acid(aspirin),ibuprofen, or corticosteroids have been taken. Bleeding may occur in patients with previous peptic orduodenal ulcers. Acute liver and renal failure and encephalopathy may be present in severe shock; thesehave been described even in the absence of severe plasma leakage or shock. Cardiomyopathy and encephalitis

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have also been reported in a few dengue case series. However, most deaths from dengue occur in patientswith profound and prolonged shock resulting from plasma leakage and complicated by bleeding and/orfluid overload.

Table 1

Medical complications seen in the febrile, critical and recovery phases of dengue.

Phase Complication

Febrile phase Dehydration: High fever may cause neurological disturbances andfebrile seizures in young children

Critical phase Shock from plasma leakage: Severe haemorrhage and organimpairment

Recovery phase Hypervolemia (only if intravenous fluid therapy has been excessive and/or has extended into this period) and acute pulmonary oedema

The various risk factors associated with severe disease of dengue are listed as below :

Infants.

Young children.

Pregnant women.

Diabetes mellitus.

Hypertension.

Haemolytic conditions.

Older persons.

Obese patients

Clinical evaluation

Clinical evaluation of the patients involves four steps-

1. History taking,

2. Clinical examination,

3. Investigations and

4. Diagnosis and assessment of disease phase and severity.

Step 1 : A patient’s history should include-Ask

Date of onset of fever (date is preferable to the number of days of fever)

Other symptoms and severity

Ask the 3 three golden questions:

Oral fluid intake-quantity and types of fluids

Urine output-quantify in terms of frequency and estimated volume and time of most recentvoiding

Types of activities performed during this illness (e.g., can the patient go to school, work,market, etc?)

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These questions, though not specific to dengue, give a good indication of patient’s hydration status and howwell the patient copes with his illness.

Other fluid losses-such as vomiting or diarrhoea

Presence of warning signs, particularly after the first 72 hr of fever

Family or neighbor having dengue or travel to dengue-endemic areas

Medications (including non-prescription or traditional medicine) in use

List of medications and the time they were last taken

Risk factors

Step 2 : Clinical examination - Assess :

Mental state

Hydration status

Peripheral perfusion done by holding the patient’s hand, assessing the colour, capillary refill time,temperature of the extremities, pulse volume and pulse rate (CCTVR)

Haemodynamic status

Tachypnoea/acidotic breathing/pleural effusion

Abdominal tenderness/hepatomegaly/ ascites

Rash and bleeding manifestations

Tourniquet test (repeat if previously negative or if there is no bleeding manifestation)

Step 3 : Investigation

For confirmation of dengue infection, Government of India (Gol) recommends use of ELISA—based antigendetection test (NS1) for diagnosing the cases from the first day of fever onwards and antibody detection testlgM capture ELISA (MAC-ELISA) for diagnosing the cases after the fifth day of onset of disease.

(NS1 for samples collected from day-1 to day-5 and IgM after day-5)

Directorate of National Vector Borne Disease Control Programme (NVBDCP), Gol has identified a networkof laboratories (sentinel surveillance hospitals and apex referral laboratories) for surveillance of denguefever cases across the country. These laboratories are also meant to augment the diagnostic facilities in allendemic areas. They are linked with Apex Referral Laboratories (ARLs) with advanced diagnostic facilitiesfor backup support and serotyping of dengue samples. For details, please refer to NVBDCP websitewww.nvbdcp.gov.in.

If facilities are available, a full blood count (FBC) should be done at the first visit to establish thebaseline haematocrit. However, a normal FBC during the first 72 hours of illness does not excludedengue infection. The haematocrit in the early febrile phase can be used as the patient’s ownbaseline. This should be repeated after the 3rd day of illness and in those with warning signs andwith risk factors for severe disease.

In the absence of the patient’s baseline haematocrit, age-specific population haematocrit levelscan be used as a surrogate during the critical phase. In the absence of a baseline HCT level, a HCTvalue of >40% in female adults and children aged <12 years and >46% in male adults shouldraise the suspicion of plasma leakage

Leucopenia usually precedes the onset of the critical phase and has been associated with severedisease. A rapid decrease in platelet count, concomitant with a rising haematocrit compared tothe baseline, is suggestive of progress in the plasma leakage/critical phase of the disease. Thesechanges are usually preceded by leucopenia (5000 cells/mm3).

A decreasing white blood cell and platelet count makes the diagnosis of dengue very likely.

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Additional tests such as liver function test, glucose, serum electrolytes, urea and creatinine,bicarbonate or lactate, cardiac enzymes, electrocardiogram (ECG) and urine-specific gravity shouldbe considered in patients with co-morbidities or in patients with clinically severe disease asindicated.Aspartate aminotransferase (AST) levels were higher compared to the levels of alanineaminotransferase (ALT). The degree of rise of AST and ALT was significantly more in DHF andDSS, as compared to DF

Interpretation of Haematocrit

Haemodynamic state should be the principal driver of IV fluid therapy. Haematocrit level should only bea guide.

Interpretation of rising or persistently high haematocrit

Haematocrit Vitals Interpretation Action

A rising or + Unstable vital = Active plasma Need for furtherpersistently high signs leakage fluid replacement

haematocrit

A rising or + Stable = Does not require Continue to monitorpersistently high haemodynamic extra intravenous closely.

haematocrit status fluid HCT should start tofall within next 24 hoursas plasma leakage stops.

Interpretation of a decrease in haematocrit

Haematocrit Vitals Interpretation Action

A decrease in + Unstable vital = Major haemorrhage Need for urgenthaematocrit signs transfusion

A decrease in + Stable = Haemodilution and/ IV fluids should behaematocrit haemodynamic or reabsorption of reduced in step-wise

status extravasated fluids manner or discontinuedimmediately to avoidpulmonary oedema

Step 4 : Diagnosis, assessment of disease phase and severity

Based on the evaluation of history, physical examination and/or FBC and haematocrit, one could clinicallydetermine the diagnosis of dengue, the phase patient is in, the presence or absence of warning signs, thehydration and haemodynamic state of the patient and whether the patient requires admission.

Dengue viral infected person may be asymptomatic or symptomatic and clinical manifestations vary fromundifferentiated fever to florid haemorrhage and shock.

The clinical presentations depend on various factors such as age, immune status of the host, the virus strainand primary or secondary infection. Infection with one dengue serotype gives lifelong immunity to thatparticular serotype.

Undifferentiated dengue Fever (UDF)

In primary dengue infection patient may develop mild to moderate fever and it is often difficult to distinguishfrom other viral infections. Maculopapular rash may or may not appear during fever or defervescence. Thesymptoms of DF may not be very distinguished and signs of bleeding or capillary leakage may be absent.

The rash associated with measles and rubella has a particular distribution from the head to the trunk andextremities, but in dengue the rash usually first appears on the trunk and later extends to the face andextremities.

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Figure 2

Severe dengue Fever

Majority of the dengue virus infected persons are asymptomatic but symptomatic patients may present withundifferentiated fever, non-severe and severe manifestation. Some patients with dengue virus infection presentwith severe manifestations like shock, plasma leakage, bleeding and organ involvement.

DHF has been divided into four grades based on i> thrombocyte count, ii> haematocrit, iii> evidenceof capillary leakage, iv> bleeding and v> hypotension.

Non severe cases may be DF and DHF grade I and II without significant bleeding. Severe dengue may beDHF III and IV with or without significant bleeding. DHF grade I and II may be severe when they presentwith significant bleeding or with metabolic and electrolyte abnormalities. Sometimes DF may present withlife threatening significant bleeding without evidence of capillary leakage or haemoconcentration. SomeDengue Fever patients may also present with multiple organ involvement without bleeding and shock. Insome patient there may be unusual atypical presentation also.

It is also reported in various literatures that high morbidity and mortality in DF/DHF is due to involvementof the following organs during illness:

- Hepatic- Renal- Cardiac- Pulmonary- CNS

Grading of DF/ DHF

DF: Fever of 2-7 days with two or more of following- Headache, Retro orbital pain, Myalgia, Arthralgiawith or without leukopenia, thrombocytopenia and no evidence of plasma leakage.

DHF I: Above criteria plus positive tourniquet test and evidence of plasma leakage.Thrombocytopeniawith platelet count less than 1,00,000/ cu.mm and Hct rise more than 20% over baseline or Fall in Hematocritby 20% after Fluid replacement.

DHF II: Above plus some evidence of spontaneous bleeding in skin or other organs (black tarry stool,epistaxis, gum bleeds) and abdominal pain.

DHF III (DSS): Above plus circulatory failure (weak rapid pulse, narrow pulse pressure < 20 mm Hg,Hypotension, cold clammy skin, restlessness).

DHF IV (DSS): Profound shock with undetectable blood pressure or pulse.

Dengue patient withMaculopapular rash

Finger impression on skinof a dengue patient

Rounded stetho impression onskin of a dengue patient

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Expanded dengue Syndrome (EDS)

Mild or Severe organ involvement may be found in DF/DHF. Unusual manifestations of DF/DHF arecommonly associated with co-morbidities and with various other co-infections.

Clinical manifestations observed in EDS are as follows:

Table 2

System Unusual or atypical manifestations

CNS involvement Encephalopathy, encephalitis, febrile seizures, intra-cranial bleedG. l. involvement Acute Hepatitis/ fulminant hepatic failure, cholecystitis, cholangitis acute

pancreatitisRenal involvement Acute renal failure, haemolytic uremic syndrome, acute tubular necrosisCardiac involvement Cardiac arrhythmia, cardiomyopathy, myocarditis, pericardial effusionRespiratory Pulmonary oedema, ARDS, pulmonary haemorrhage, pleural effusionEye Conjunctival bleed, macular haemorrhage, visual impairment, optic neuritis

Clinical Criteria for DF/ DHF/ DSS

Clinical Features of DF :An acute febrile illness of 2-7 days duration with two or more of the following manifestations:Headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations.Dengue Haemorrhagic Fever (DHF) :

a) A case with clinical criteria of dengue fever;plus

b) Haemorrhagic tendencies evidenced by one or more of the following1. Positive tourniquet test2. Petechiae, echymoses or purpura3. Bleeding from mucosa, gastrointestinal tract, injection sites or other sites;

plusc) Thrombocytopenia (<100 000 per cumm)

plusd) Evidence of plasma leakage due to increased vascular permeability, manifested by one or more of

the following1. A rise in average haematocrit for age & sex 20%2. A more than 20% drop in haematocrit following volume replacement treatment compared

to baseline3. Signs of plasma leakage (pleural effusion, ascites, hypoproteinemia)

Dengue Shock Syndrome (DSS) :All the above criteria for DHF with evidence of circulatory failure manifested by rapid and weak pulse andnarrow pulse pressure ( 20% mm Hg) or hypotension for age, cold and clammy skin and restlessness.

Differential Diagnosis of DF/ DHFConditions that mimic the febrile phase of dengue infectionFlu-like syndromes

Influenza, measles, chikungunya, infectious mononucleosis, HIV seroconversion illnessIllnesses with a rash

Rubella, measles, scarlet fever, meningococcal infection, chikungunya, drug reactions

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Diarrhoeal diseasesRotavirus, other enteric infections

Illnesses with neurological manifestationsMeningoencephalitisFebrile seizures

Conditions that mimic the critical phase of dengue infectionInfectious

Acute gastroenteritis, malaria, leptospirosis, typhoid fever, typhus, viral hepatitis, Acute HIV-seroconversion illness, bacterial sepsis, septic shock

MalignanciesAcute leukaemia and other malignancies

Other clinical picturesAcute abdomen

Acute appendicitisAcute cholecystitisPerforated viscus

Diabetic ketoacidosisKawasaki syndromeLactic acidosisLeukopenia, thrombocytopenia and bleedingPlatelet disordersRenal failureRespiratory distress (Kussmaul’s breathing)Systemic lupus erythematosus

CLINICAL MANAGEMENT

Mild DF Moderate DF Severe DF

DF with high risk /co-morbid conditions

DF with warning signs & symptoms /DHF Gr I & II with / without minorbleeding

InfantsOld ageDiabetesHypertensionPregnancyCADHemoglobinopathies Immunocompromized patientPatient on steroids, anticoagutants or immuunosuppresants

A. DF with warming signs andsymptomsRecurrent vomitingAbdominal pain/tenderness General weakness/lethargy/ restlessMinor bleedingMild pleural eflusion/ascitesHepatomegalyIncreased HctB. DHF Gr I & II with / without minor bleeds

A. DF with significant Hemor-rhageB. (i) DHF with significanthemorrhage with or withoutshock(ii) DHF III & IV (DSS) withshock with or without signifi-cant hemorrhageC. Severe organ involvement(Expanded Dengue Syndroms)D. Metabolic and electrolyteabnormalities

Home Management

Close Monitoring and possibly Hospitalizasion Tertiary level care

A. Undifferentiated DFB. Fever without complicationlike bleeding, hypotensionand organ involvementC. Without evidence ofcapillary leakage

Dengue Viral Infection

Symptomatic Asymptomatic

Dengue case classification

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MANAGEMENT OF DENGUE CASES AT PRIMARY HEALTH CARE LEVEL AND REFERRAL

General Management of Dengue Fever (DF)

i. Management of dengue fever is symptomatic and supportive

ii. Bed rest is advisable during the acute phase.

iii. Use cold/tepid sponging to keep temperature below 38.5° C.

iv. Antipyretics may be used to lower the body temperature. Aspirin/NSAIDs like ibuprofen, etcshould be avoided since it may cause gastritis, vomiting, acidosis,platelet dysfunction and severebleeding. Do not even use combination of paracetamol plus above mentioned drugs.

Paracetamol is preferable in the doses given below :

1-2 years: 60 -125 mg/dose 3-6 years: 125 mg/dose

7-12 years: 250 mg/dose Adult : 500 mg/dose

v. Encourage oral intake to replace fluid loss from fever and vomiting. Small amounts of oral fluidsshould be given frequently for those with nausea and anorexia. The choice of fluids should bebased on the local culture: coconut water, rice water or barley water. Oral rehydration solution orsoup and fruit juices may be given to prevent electrolyte imbalance and are preferable to plainwater. Commercial carbonated drinks (cold drinks)/ drinks that exceed the isotonic level (5%sugar) should be avoided. They may exacerbate hyperglycaemia related to physiological stressfrom dengue and diabetes mellitus. Sufficient oral fluid intake should result in a urinary frequencyof at least 4 to 6 times per day. A record of oral fluid and urine output could be maintained andreviewed daily in the ambulatory setting.

vi. Patients should be monitored for 24 to 48 hours after they become afebrile for development ofcomplications.

[Note: In children the dose of paracetamol is calculated as per 10-15 mg/Kg body weight per dose. Paracetamoldose can be repeated at intervals of 6 hrs depending upon fever and body ache.]

Management ofDF/DHF

6ml/kg/hr for 2 hours crystallold.Repeal Hct

Maintenance fluids (IV)Hct: Normal

Hb & HctBP & pulse pressure - Normal.

Stable.Orally accepting.Hct: Normal

Hb & Hct Signs of clrculatory falilureSignificant bleeding

20ml/kg crystalloid in 15 min bolusMoist O2

No Improvement

20 ml/kg/hr crystalloid: HctBleeding++

Persistent hypotention, oliguriaaltered sensorium, activebleeding, rapidly falling Hct

TRANSFER TOHIGHER CENTER

During referal 5ml/kg/hr;continue over 2 hours

No ImprovementHome Management/Discharge Improvement

Advise increased intakeof fluid. PCM sos &explain warning signsand symptorns

Improvement

Improvement

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Advice in patient’s card

What should be done?

Adequate bed rest

Adequate fluid intake : at least 5 glasses of other fluids (with electrolytes) in addition to normaldaily intake of plain water e.g. milk, fruit juice (caution with diabetic patient), oral rehydrationsolution (ORS) or barley/rice water/coconut water

Note: Plain water alone may cause electrolyte imbalance

Take paracetamol (as per doctors’ advice; not more than 3 to 4 times in 24 hours in children)

Tepid sponging

Look for mosquito breeding places in and around the home and eliminate them

What should be avoided?

Do not take acetylsalicylic acid (aspirin), mefenamic acid, ibuprofen or other NSAIDs or steroids.If you are already taking these medications please consult your doctor

Do not take combination of paracetamol with above mentioned drugs

Antibiotics are not necessary

If any of following is observed, the patient should be immediately taken to the nearest hospital; these arewarning signs for dengue:

Bleeding :

red spots or patches on the skin

bleeding from nose or gums

vomiting blood

black-coloured stools

heavy menstruation/vaginal bleeding

Frequent vomiting or not able to drink

Severe abdominal pain

Drowsiness, mental confusion or seizures

Pale, cold or clammy hands and feet

Difficulty in breathing

Dizziness

No urination for 4–6 hours

Management of DHF Grade I and II

Any person who has dengue fever with thrombocytopenia, high haemoconcentration and presents withabdominal pain, black tarry stools, epistaxis, bleeding from the gums etc.needs to be hospitalized. All thesepatients should be observed for signs of shock. The critical period for development of shock is duringtransition from febrile to afebrile phase of illness, which usually occurs after third day of illness. Rise ofhaemoconcentration indicates plasma leakage and loss of volume for which proper fluid management playsan important role. Despite the treatment, if the patient develops fall in BP, decrease in urine output or otherfeatures of shock, the management for Grade III/ IV DHF-DSS should be instituted.

Oral rehydration should be given along with antipyretics like Paracetamol, sponging, etc. as describedabove. The algorithm for fluid replacement therapy in case of DHF Grade I and II is given in Chart 1

15

Management of Shock (DHF Grade III/IV)

Immediately after hospitalization, the haematocrit, platelet count and vital signs should be examined toassess the patient’s condition and intravenous fluid therapy should be started.The patient requires regularand continuous monitoring. If the patient has already received about 1000 ml of intravenous fluid, it shouldbe changed to colloidal solution preferably Dextran 40 or if haematocrit further decreases fresh wholeblood transfusion 10-20ml/kg/dose should be given.

However, in case of persistent shock even after initial fluid replacement and resuscitation with plasma orplasma expanders, the haematocrit continues to decline, internal bleeding should be suspected. It may bedifficult to recognize and estimate the degree of internal blood loss in the presence of haemoconcentration.It is thus recommended to give whole blood in small volumes of 10ml/kg/hour for all patients in shock as aprecaution.

Oxygen should be given to all patients in shock.

Treatment algorithm for patients with DHF Grades III and IV is given in Chart 2.

Chart 1: Management of DHF Grade I and II

Initiate IV therapy @ 6 ml/kg/hr Crystalloid solution (0.9% NS/RL) for 1-2 hrs

Improverment No improvement

IV therapy with Crystalloid,successively reducing from6 to 3 ml/kg/hr

Further improvement

Discontinue IV fluid after24 hrs

Increase IV fluid to 10 ml/kg/hr crystalloid for 2 hrs

Improverment No improvement.Unstable vital signs

Hct falls (Suspectinternal hemorrhage)

Reduce IV to 6 ml/kg/hrCrystalloid with laterreduction to 3 ml/kg/hr anddiscontinue after 24-48 hrs.

IV Colloid Dextran(40y Hydroxyethyl starch@

10 ml/kg/hr for 1 hr.

Blood transfusion10ml/kg/hr

IV therapy with Crystalloid, successivelyreducing the flow from 10 to 6 and laterto 3 ml/kg/hr. Discontinue after 24-48 hrs.

Improverment

Improvement : Hematocrit falls, pulse rate and blood pressure stable, urine output risesNo Improvement : Hematocrit or pulse rate rises, pulse pressure falls below 20 mm/Hg. Urine output fallsUnstable Vital signs : Urine output falls, signs of shock

Hct rises

Hemorrhagic (bleeding) tendencies, Thrombocytopenia,Heamatocrit (Hct) rise

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Chart 2 : Management of Shock (DHF Grade III / IV)

Chart 3 : Management of compensated shock in children

UNSTABLE VITAL SIGNS (VS)Urine output falls, signs of shock, Hypotension (SBP<90mmHg),

reduced pulse pressure, High Hematocrit (Hct)

Oxygen

Immediate rapid volume replacement : give 20 ml/kg crystalloidsolution as rapid bolus over 15 min

Improvement in VS & fall in HCt No improvement in VS

IV Crystalloid infusion successively reducing from20 to 10, then 10 to 6 and 6 to 3 ml/kg/hr.

Repeat 20 ml/kg crystalloid bolusover 15 mins.

Further improvement in VS

Discontinue IV after 24 hrs.Hct Rises or > 45 Hct Falls

Suspect bleedingIV Colloid (Dextran 40/

Hemaccel or plasma 10 ml/kg/hras intravenous bolus over 30 min

(repeat if necessary)

Blood transfusion (10 ml/kg/hr)

Refractoryhypotension

No Improvement in VS

IV Inotropes withcrystalloid

Improvement in VS

Start IV therapy by crystalloid successively reducingthe flow from 10 to 6 and 6 to 3 ml/kg/hr.

Discontinue after 24-28 hrs

Compensated shock in Children : Normal BP, tachypnea, tachycardia

Ringer’s Lactate (RL)/ NS 10 ml/kg/hour

Assess after every hours byChecking vital signs and PVC

No improvement Improvement

RL 10ml/kg/hr

Assessment at 2 hours

No improvement

RL 15ml/kg/hr

Assessment at 3 hours

Colloids 10ml/kg/hr

No improvement

Look for anemia, acidosis, myocardialdysfunction and treat accordingly

RL 5-7ml/kg/ 1-2hr

Further improvement

RL 3-5ml/kg/hr 2-4 hrs

Continue IV fluids tillstable for 24 hours

Discharge when stablefor 28-48 hours

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Chart 4 : Management of hypotensive shock in children

When to start and stop intravenous fluid therapy

Febrile phase

Limit IV fluids.

Early IV therapy may lead to fluid overload especially with non-isotonic IV fluid

Critical phase

IV fluids are usually required for 24–48 hours

NOTE: For patients who present with shock, IV therapy should be <48 hours

Recovery phase

IV fluids should be stopped so that extravasated fluids can be reabsorbed

Choice of intravenous fluids for resuscitation

Replacement of plasma lost because of increased vascular permeability is a mainstay of severe denguemanagement, particularly during the critical stage. Two main types of volume expander are used to replacelost fluid in the management of dengue fever: crystalloids and colloids. Crystalloids are aqueous solutionsof mineral salts or other water-soluble molecules, whereas colloids contain larger insoluble moleculessuch as gelatin, dextrans or starches.

There is no clear advantage of the use of colloids over crystalloids in terms of the overall outcome. However,colloids may be the preferred choice if the blood pressure has to be restored quickly. Colloids have beenshown to restore the cardiac index and reduce the level of haematocrit faster than crystalloids in patientswith intractable shock and pulse pressure less than 10 mm Hg.One of the greatest concerns regardingcolloid use is the impact on coagulation.

Crystalloids

Normal plasma chloride ranges from 95 to 105 mmol/L. Saline 0.9% is a suitable option for initial fluidresuscitation, but repeated large volumes of 0.9% saline may lead to hyperchloremic acidosis.Hyperchloraemic acidosis may aggravate or be confused with lactic acidosis from prolonged shock.Monitoring the chloride and lactate levels will help to identify this problem. When serum chloride levelexceeds the normal range, it is advisable to change to other alternatives such as Ringer’s Lactate.

Hypotensive shock in children

Improvement No improvement

Gradually decrease infusion rate10 ml/kg/hr 1-2 hr7 ml/kg for 2-3 hrs5 ml/kg for 2-4 hrs3ml/kg for 2-4 hrsStop at 48 hours

Improvement No Improvement

Look for blood loss, acidosis, cardiacdysfunction & treat accordingly

20 ml /kg crystalloids or colloids over 15-20 minutes

Assessment of Shock

PCV increased PCV decreased

Colloids10-20 ml/kg

BloodTransfusion

Assessment

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Ringer’s Lactate

Ringer’s Lactate has lower sodium (131 mmol/L) and chloride (115 mmol/L) contents and an osmolality of273 mOsm/L. It may not be suitable for resuscitation of patients with severe hyponatremia. However, it isa suitable solution after 0.9% Saline has been given and the serum chloride level has exceeded the normalrange. Ringer’s Lactate should preferably be avoided in liver failure and in patients taking metforminwhere lactate metabolism may be impaired.

Colloids

The types of colloids are gelatin-based, dextran-based and starch-based solutions. One of the biggestconcerns regarding their use is their impact on coagulation. Theoretically, dextrans bind to von Willebrandfactor/Factor VIII complex and impair coagulation the most. However, this was not observed to haveclinical significance in fluid resuscitation in dengue shock. Of all the colloids, gelatin has the least effect oncoagulation but the highest risk of allergic reactions. Allergic reactions such as fever, chills and rigors havealso been observed in Dextran 70. Dextran 40 can potentially cause an osmotic renal injury in hypovolaemicpatients.

What type of intravenous fluid therapy should we use ?

Use isotonic solutions (normal saline, Ringer’s lactate)

Colloids are preferred if the blood pressure has to be restored urgently

When are colloids given?

Hypotensive shock

Repeated shock – 2nd or 3rd shock and onwards

After >20 to 30 ml/kg of crystalloids

If Hct does not decrease after crystalloid administration in shock state

DOSE: Limited to 30 to 50 ml/kg/day

What intravenous fluids should not be used?

Hypotonic solution, e.g. 0.45% saline, even during the febrile phase.

Dextrose solutions should be limited to avoid hyperglycaemia, but may be used in hypoglycaemia withclose blood glucose monitoring

Albumin solutions

HOW MUCH & HOW FAST to run intravenous fluid? Give the minimum IVF required to maintain good perfusion and urine output of about 0.5 ml/kg/hr. Volume based on ideal body weight if overweight. Titrate to haemodynamic state and age

What does “titrate IVF rate to haemodynamic state” mean?Reassess haemodynamic responses immediately after every IV bolus.AFTER correction of shock:

Reduce IV infusion rate in step-wise manner whenever:• Haemodynamic state is stable• Rate of plasma leakage decreases towards end of critical phase indicated by:

Improving haemodynamic signs Increasing urine output Adequate oral fluid intake Haematocrit decreases below baseline value in a stable patient

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Table 3: Ideal body weight (IBW) for overweight/obese adults can be estimated based on the followingformula

Female Male

45.5 kg + 0.91(height – 152.4cm) or 50.0 kg + 0.91(height – 152.4 cm) or45.5 kg + 2.3 kg for each inch over 5 ft 50 kg + 2.3 kg for each inch over 5 ft

Calculation of fluid

Required amount of fluid should be calculated on the basis of body weight and charted on a 1-3 hourlybasis, or even more frequently in the case of shock. For obese and overweight patients calculation of fluidshould be done on the basis of ideal body weight. The regimen of the flow of fluid and the time of infusionare dependent on the severity of DHF. The schedule given below is recommended as a guideline. It iscalculated for dehydration of about 5% deficit (plus maintenance).

Table 4:

The maintenance fluid should be calculated using the Holliday-Segar formula as follows:

Body weight in kg Maintenance volume for 24 hours

<10kg 100ml/kg

10-20 1000+50 ml / kg body weight exceeding 10 kg

More than 20 kg 1500+20 ml / kg body weight exceeding 20 kg

For intravenous fluid therapy of patients with DHF, following regimens of fluid are suggested: 1.5/ml/kg/hr,3ml/kg/hr; 6ml/kg/hr; 10ml/kg/hr, and 20ml/kg/hr. For ready reference, the calculated fluid requirements,based on body weight and rate of flow of fluid volume for the five regimens are given in Table 5.

Summary of IV fluid therapy in dengue

Inadequate Adequate Excessive

Hypovolaemia

Compensated shock

Hypotensive shock

Bleeding

DIC

Multi-organ failure

Improved circulationand tissue perfusion

Capillary refill 2 seconds

Normal heart rate

Normal blood pressure

Normal pulse pressure

Urine 0.5 ml/kg/hr

HCT to normal

Improving acid-base

Fluid overload:

Pulmonary oedema

Respiratory distress

Worsening pleural effusionand ascites

Clinical deterioration

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R-1 R-2 R-3 R-4 R-5

(in kgs)

(in kgs) (in kgs)(

)(

)

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Remember !!!

The fluid volumes mentioned are approximate.

The fluid replacement should be just sufficient to maintain effective circulation during the periodof plasma leakage.

The recommended intravenous fluids are Normal saline, Ringers Lactate or 5% DNS.

One should keep a watch for urine output, liver size and signs of pulmonary oedema. Hypervolemiais a common complication.

Normally intravenous fluids are not required beyond 36 to 48 hrs.

Normally change should not be drastic. Do not jump from R-3 to R-5 since this can overload thepatient with fluid. Similarly, reduce the volume of fluid from R-5 to R-4, from R-4 to R-3, and fromR-3 to R-2 in a stepwise manner.

Remember that ONE ML is equal to 15 DROPS. In case of micro drip system, one ml is equal to60 drops. (If needed, adjust fluid speed in drops according to equipment used).

It is advised to start with one bottle of 500 ml initially, and order more as and when required. Thedecision about the speed of IV fluid should be reviewed every 1-3 hours. The frequency of monitoringshould be determined on the basis of the condition of the patient.

Management of severe bleeding

In case of severe bleeding, patient should be admitted in the hospital and investigated to look for the causeand site of bleeding and immediate attempt should be made to stop the bleeding. Internal bleeding like GIbleeding may be sometime severe and difficult to locate.

Patients may also have severe epistaxis and haemoptysis and may present with profound shock. Urgentblood transfusion is life saving in this condition. However, if blood is not available shock may be managedwith proper IV fluid or plasma expander. If the patient has thrombocytopenia with active bleeding, it shouldbe treated with blood transfusion and then if required platelet transfusion. In case of massive haemorrhageblood should be tested to rule out coagulopathy by testing for prothrombin time (PT ) and APTT. Patients ofsevere bleeding may have liver dysfunction and in such case, liver function test should also be performed.In rare circumstances, intracranial bleed may also occur in some patients who have severe thrombocytopeniaand abnormality in coagulation profile.

Indications for platelet transfusion

Platelet transfusion is not the mainstay of treatment in patients with DF. In general, there is noneed to give prophylactic platelets even if at platelet count <40 000/mm3.

Prophylactic platelet transfusion may be given at levels of <10 000/mm3 in the absence of bleedingmanifestations.

Haemorrhage with or without thrombocytopenia.

Prolonged shock with coagulopathy and abnormal coagulogram.

In case of systemic bleeding, platelet transfusion may be needed in addition to red cell transfusion.Whole fresh blood transfusion doesn’t have any role in managing thrombocytopenia.

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Indications for blood transfusion

Loss of blood (overt blood)—10% or more of total blood volume

Refractory shock despite adequate fluid administration, and declining Hct

Replacement volume should be 10 ml/kg body weight at a time and coagulogram should be done

If fluid overload is present, packed cell transfusion is to be given.

Use of whole blood/ fresh frozen plasma/ cryoprecipitate in coagulopathy

Use of whole blood/ fresh frozen plasma/cryoprecipitate is to be done in coagulopathy with bleeding as

per advice of the treating physician and the patient’s condition.

Management of DF/ DHF with co-morbid illness

Dengue viral hepatitis:

Some patient may have impairment of liver function test due to dengue viral infection. In some DF patients

the AST/ALT level may be very high and PT may be prolonged. Hepatic involvement is commonly associated

with pre-existing conditions like chronic viral hepatitis, cirrhosis of liver and haepatomegaly due to some

other cause. Patient may also develop hepatic encephalopathy due to acute liver failure.

Liver involvement also sometimes associates with DF in pregnancy. Low albumin due to chronic liver

disease may be associated with severe DHF and bleeding. GI bleeding is common in this condition and

patient may go to severe DSS. These patients should be managed carefully with hepatic failure regimen with

appropriate fluid and blood transfusion.If PT is prolonged, intravenous vitamin K1 may be initiated in such

conditions.

Dengue myocarditis:

Dengue infection may rarely cause acute myocarditis which also may contribute for the development of

DSS. Cardiac complications may be seen in presence of CAD, hypertension, diabetic and valvular heart

disease. Management of shock with IV fluid in such cases is sometime difficult due to myocardial dysfunction.

Patient may develop pulmonary oedema due to improper fluid management. Some CAD patient may be

already taking Aspirin and other anti-platelet agent which may also contribute for severe bleeding unless

these are stopped during dengue infection. Cardiac ischemia or electrolyte disturbances should be frequently

reassessed. Patient may develop congestive or biventricular failure and therefore should be treated properly

for better morbidity and mortality outcome.

DF in Hypertension:

Hypotension is a late sign of shock. However, a BP reading that is considered normal for age may, in reality,

be low for patients with uncontrolled hypertension. Similarly, what is considered as “mild”hypotension

may in fact be profound.

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ß-blockers, a common anti-hypertensive medication, cause bradycardia and may block the tachycardic

response in shock. The heart rate should not be used as an assessment of perfusion in patients on ß-blockers.

Anti-hypertensive agents such as calcium channel blockers may cause tachycardia.Tachycardia in these

patients may not indicate hypovolemia. Knowing the baseline heart rate before the dengue illness is helpful

in the haemodynamic assessment.

DF in Diabetes:

Sometimes diabetic patients may present with severe complication in DF when target organs are involved

like diabetic retinopathy, neuropathy, nephropathy,vasculopathy, cardiomyopathy and hypertension. Due

to dengue infection in diabetes the blood sugar may become uncontrolled which may sometimes require

insulin therapy for better management.

Hypoglycaemia may occur in those patients taking oral hypoglycaemic agents (e.g.long-acting sulphonylurea),

but who had poor oral intake. Hypoglycaemia could be aggravated by severe hepatitis from dengue.

Gastrointestinal absorption of oral hypoglycaemic agents is unreliable because of vomiting and diarrhoea

during the dengue illness. Some hypoglycaemic agents such as metformin may aggravate lactic acidosis,

particularly in dengue shock. These agents should be avoided or discontinued during dengue shock and

also in those with severe hepatitis.

Renal involvement in DF:

Acute Tubular Necrosis (ATN) may develop during DHF and may complicate to acute kidney injury (AKI) if

fluid therapy is not initiated in time. Renal function may be reversible, if shock is corrected within a short

span of time. If the shock persists for long time patient may develop renal complications. Urine output

monitoring in dengue infection is very important to assess renal involvement. Microscopic/macroscopic

haematuria should be examined in DHF patients. Other investigations like blood urea,creatinine, electrolytes,

GFR, ABG should be performed in patients with severe dengue/DHF. Fluid intake should be closely monitored

in case of AKI to avoid fluid overload and pulmonary oedema. Dengue patient may develop severe DHF in

presence of diabetic nephropathy, hypertensive nephropathy, connective tissue disorders (SLE) and other

pre-existing chronic diseases.

CNS involvement in DF :

Altered sensorium may develop in dengue patient due to various conditions like shock (DSS), electrolyte

imbalance (due to persistent vomiting), fluid overload (dilutional hyponatremia or other electrolyte imbalance),

hypoglycemia, hepatic encephalopathy and also due to involvement of CNS by dengue virus. Acute

encephalopathy or encephalitis may be seen in some patients with severe dengue. Sometimes it may be

difficult to clinically exclude cerebral Malaria and enteric encephalopathy which may also appear during

same period (epidemic). Dengue serology (IgM) in CSF may help to confirm dengue encephalopathy or

encephalitis.

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Management of DF with co-infections

TB:

Patients may develop breathlessness and massive haemoptysis in PulmonaryTuberculosis. These patientsmay also develop moderate to massive pleural effusion and ARDS. If patient has DF in presence of TB andis on ATD, then should be closely monitored for further development of respiratory/pulmonary complicationsto prevent morbidity and mortality.

HIV:

Dengue may cause severe complications like DHF, DSS, significant bleeding and organ involvement amongHIV and AIDS patients. Outcome of DF is poor amongst severely immune compromised patients thosewho have opportunistic infection and very low CD4 count. Multi-organ involvement may be common inDF and responsible for high mortality. Management of DF with HIV and AIDS should be undertaken withHIV specialist consultation.

Malaria:

Malaria is also a common co-infection in dengue as it is prevalent across India and transmission alsocoincides during the same period/season. Malaria should be excluded in the beginning without loss ofmuch time as it has its specific management.Antimalarial treatment should be started as soon as possible toprevent complication and give better outcome during co-infection.

Chikungunya:

It is also reported that in some geographical areas both the infections are prevalent at the same time. Acutecomplications are sometimes severe in DF in presence of Chikungunya. In case of predominant jointinvolvement in a DF patient, Chikungunya should be investigated and proper management to be carried outaccordingly.

Enteric Fever:

Water borne diseases like Typhoid fever and gastroenteritis are also common during monsoon seasonwhen dengue infection is also reported in large number. In the initial phase DF patient may be morecomplicated with Typhoid if antibiotic treatment is started late. In highly suspected cases blood culture forTyphoid fever should be sent to confirm the diagnosis as Widal test may not be positive before 2 weeks offever.

Management of dengue in pregnancy

DF infection in pregnancy carries the risk of more bleeding, foetal complications, low birth weight andpremature birth. Risk of vertical transmission also increases during pregnancy. Severe bleeding may complicatedelivery and/or surgical procedures performed on pregnant patients with dengue during the critical phase,i.e. the period coinciding with marked thrombocytopenia with or without coagulopathy andvasculopathy.Pleural effusion, ascites, hypotension are commonly associated with DF in pregnancy.Involvement of lungs and liver is also common in pregnancy. Patients may have respiratory symptom due tomassive pleural effusion and high SGOT/SGPT due to liver involvement.Complications of DF depend onthe different stages of pregnancy like early, late, peri-partum and post partum periods.

25

However, it is to be kept in mind that

The lower BP and tachycardia of normal pregnancy could be misinterpreted as hypotensive shock.

The lower baseline haematocrit after the second trimester of pregnancy should be noted. Establishingthe baseline haematocrit during the first 2–3 days of fever is essential for early recognition ofplasma leakage.

Clinical signs of plasma leakage such as pleural effusion and ascites could be difficult to elicit inthe presence of a gravid uterus.

Management of dengue infection in pregnancy should be taken seriously to reduce morbidity and mortalityin mother as well as foetus.

Pregnancy is a state of hyper dynamic circulation and fluid replacement should be carefully done to preventpulmonary oedema. Regular BP monitoring should be performed during DF in pregnancy. Fulminant hepaticfailure, ARDS and acute renal failure in pregnancy may be associated with dengue infection.There is nodifference in fluid therapy compared with the non-pregnant state. However it is important to note that thegrowing gravid uterus may result in narrower tolerance of fluid accumulation in the peritoneal and pleuralcavity

The presence of wounds or trauma during the critical phase of dengue with marked thrombocytopenia,coagulopathy and vasculopathy creates a substantial risk of severe haemorrhage.If severe haemorrhageoccurs, replacement with transfusion of fresh whole blood/fresh packed red cells should be promptlyinstituted.Frequent platelet count and coagulation profile testing should be performed during DF in pregnancy.

Delivery should take place in a hospital where blood/blood components and a team of skilled obstetriciansand a neonatologist are available.Prophylactic platelet transfusion is not recommended unless obstetricallyindicated.

Post-delivery– ( Keep in mind)

Newborns with mothers who had dengue just before or at delivery, should be closely monitored inhospital after birth in view of the risk of vertical transmission. Severe foetal or neonatal dengue illnessand death may occur when there is insufficient time for the production of protective maternalantibodies.

Vertical dengue infection transmission from pregnant women to their foetus has been reported indifferent studies from 1.6 -64%. Clinical manifestations of vertically infected neonates vary from mildillness such as fever with petechial rash, thrombocytopenia and hepatomegaly, to severe illness withpleural effusion, gastric bleeding, circulatory failure and massive intracerebral haemorrhage.

Clinicians should be aware that presentation of either maternal or neonatal disease may be atypicaland confound diagnosis.Congenital infection could eventually be suspected on clinical grounds andthen confirmed in the laboratory.

Inevitable delivery during critical phase - what to do?

If delivery is inevitable, bleeding should be anticipated and closely monitored.

Blood and blood products should be cross-matched and saved in preparation for delivery.

Trauma or injury should be kept to the minimum if possible.

It is essential to check for complete removal of the placenta after delivery.

26

Transfusion of platelet concentrates should be initiated during or at delivery but not too far aheadof delivery, as the platelet count is sustained by platelet transfusion for only a few hours duringthe critical phase.

Fresh whole blood/fresh packed red cell transfusion should be administered as soon as possibleif significant bleeding occurs. If blood loss can be quantified, it should be replaced immediately.Do not wait for blood loss to exceed 500 ml before replacement, as in postpartum haemorrhage.Do not wait for the haematocrit to decrease to low levels.

Ergotamine and or oxytocin infusion as per standard obstetrical practice should be commencedto contract the uterus after delivery to prevent postpartum haemorrhage.

Management of dengue in infants

Dengue virus can cause a spectrum of outcomes in infants, ranging from asymptomatic infection to mild orclinically significant severe disease similar to older children and adults.Compared to older children upperrespiratory tract symptoms (cough, nasal congestion, runny nose, dyspnoea), gastrointestinal symptoms(vomiting, diarrhoea), and febrile convulsions are more common in infants with dengue.The burden ofsevere dengue lies predominantly in infants 4—9 months of age.

The degree of increase above the baseline haematocrit often reflects the severity of plasma leakage. However,rise of haematocrit may not be sometimes detectable because the normal value of haematocrit in infants 2-12 months of age is relatively low and may be even lower in iron deficiency anaemia. Thrombocytopeniaand leukopenia are often observed in this phase. Liver involvement is found more frequently in infantscompared to children. Progression of infants with dengue is the same as that of children and adults duringthe recovery phase.

Management of dengue among infants without warning signs

Oral rehydration should be encouraged with oral rehydration solution (OHS), fruit juice and other fluidscontaining electrolytes and sugar, together with breast feeding or formula feeding. Parents or caregiversshould be instructed about fever control with antipyretics and tepid sponging. They should be advised tobring the infant back to the nearest hospital immediately if the infant has any of the warning signs.

Management of dengue among infants with warning signs

When the infant has dengue with warning signs intravenous fluid therapy is indicated. In the early stage,judicious volume replacement by intravenous fluid therapy may modify the course and severity of the illness.Initially isotonic crystalloid solutions such as Ringer’s Lactate (RL), Ringer’s Acetate (RA), or 0.9% salinesolution should be used. The capillary leak resolves spontaneously after 24-48 hours in most of the patients.

Management of infants with severe dengue: Treatment of shock

Volume replacement in infants with dengue shock is very challenging and it should be done promptlyduring the period of defervescence. Each and every case should be critically analyzed separately.

Management of neonatal dengue

After delivery, the new born may go into shock which may be confused with septic shock or birth trauma.In this case, history of febrile illness during pregnancy is important which may help to diagnose DengueShock Syndrome among neonates and infants. Close observation, symptomatic and supportive treatmentare the mainstay of management.

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Suggested Admission & Discharge criteria

Admission criteria

Warning signs Persistent high grade fever (38.5o C and above) Any of the warning signs includingsudden drop of temperature

Signs and symptoms Dehydrated patient, unable to tolerate oral fluidsrelated to hypotension Dizziness or postural hypotension(possible plasma Profuse perspiration, fainting, prostration during defervescenceleakage) Hypotension or cold extremities Difficulty in breathing/shortness of breath

(deep sighing breaths)

Bleeding Spontaneous bleeding, independent of the platelet count

Organ impairment Renal, hepatic, neurological or cardiac– enlarged, tender liver, although not yet in shock– chest pain or respiratory distress, cyanosis

Findings through Rising haematocritfurther Investigations Pleural effusion, ascites or asymptomatic gall-bladder thickening

Co-existing conditions Pregnancy, Co-morbid conditions, such as diabetes mellitus, hypertension,peptic ulcer,haemolytic anemias and others. Overweight or obese (rapid venousaccess difficult in emergency). Infancy or old age

Social circumstances Living alone; Living far from health facility; Without reliable means of transport

Discharge criteria The admitted patients who have recovered from acute dengue infection withvisible clinical improvement having no fever for at least 24 - 48 hours, normal bloodpressure, no respiratory distress from pleural effusion or ascites, improvement inclinical status (general well-being, return of appetite, adequate urine output, norespiratory distress),persistent platelet count >50,000/cu.mm may be dischargedfrom hospital.

N.B. This is suggestive only & MO should judge on case to case basis and decide.

Nursing advice in admitted patient

High-grade fever: Record & note temperature 6 hourly & as asked. Tepid sponging/paracetamol. Encourageintake of plenty of oral fluids.Abdominal pain: Severe abdominal pain may be a sign of severe complication, so remain vigilant andinform the treating doctor.Bleeding : Estimate and record the amount of blood loss, monitor vitals and inform the doctor.Plasma leakage: Monitor vitals, Hct and input/output. Encourage oral intake if possible and start IV fluid asper instructions. Strictly follow type of fluid & fluid rate.Shock/impending shock : Monitor vitals, input/output, Hct and sensorium. Start IV fluids/inotropes as perinstructions.Decreased urine output : First rule out catheter blockade by palpating the bladder.Flush the catheter ifblocked. Continue monitoring vitals, input/output and inform the doctor.Respiratory distress : Check oxygen saturation and administer oxygen via face mask or nasal catheter ifSpO2 <90%. Look for cardiac involvement and inform the doctor.Convulsions/encephalopathy : Pay attention to maintenance of airway, breathing and circulation (ABC).Be ready with resuscitation set for emergency intubation and mechanical ventilation.Fluid overload : It may develop during recovery phase of the illness due to fluid shifts. Closely observe forpedal oedema, neck vein engorgement and respiratory distress. Continue strict input/output monitoringduring the recovery phase.

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Practices to be kept in mind

In summary, training in the clinical management of dengue is essential if the clinician is to be able tonavigate the patient through the three phases of the illness.Training is needed, first, to understand the disease course and second, to be alert to the physiologicalproblems.Intravenous fluid therapy is life-saving in dengue shock. However, there is a “narrow therapeutic index”.In other words, fluids have to be given timely, at the appropriate volume, rate, of the appropriate type(crystalloids, colloid and/or blood) and for the appropriate duration. Therein lies the challenge to physiciansfor the important practice of fluid titration through frequent and meticulous assessment. Progression of thedisease through the critical phase should be tracked in hours of plasma leakage.Recognizing the cues to discontinue intravenous fluid therapy is just as important as knowing when tostart it. Given time and haemodynamic stability, other issues such as thrombocytopenia, coagulopathy andraised liver enzymes will recover spontaneously or with supportive care.

Annexure 1:

Tourniquet test:

The tourniquet test is part of the new WHO case definition for dengue. The test is a marker of capillaryfragility and it can be used as a triage tool to differentiate patients with acute gastroenteritis, for example,from those with dengue.

How to do a Tourniquet Test

1. Take the patient’s blood pressure and record it, for example, 100/70.

2. Inflate the cuff to a point midway between SBP and DBP and maintain for 5 minutes. (100 + 70) ÷ 2 =85 mm Hg

3. Reduce and wait 2 minutes.

4. Count petechiae below antecubital fossa.

A positive test is 10 or more petechiae per square inch. The test is considered positive when 10 or morepetechiae per square inch area over forearm are observed. In DHF, the test usually gives a definite positive testwith 20 petechiae or more. The test may be negative or only mildly positive during the phase of profound shock.

29

Annexure 2 : PLATELET PRODUCTS

1. Random donor platelets (RDP).

The platelets are prepared from whole blood. Depending upon the method of preparation, they can be classified

as PRP platelets or buffy coat reduced platelets. Either of these platelet products have a volume of 40—50 ml,

platelet content of 4.5x1010 per pack and shelf life of 5 days. These whole-blood derived platelet concentrates

are expected to raise the platelet count by 5—7 thousand in adults and 20 thousand in paediatric patients.

2. Buffy coat pooled platelets (BCPP).

Pooled buffy coat platelet concentrates are derived from four donations of whole blood (obtained from the

buffy coat of ABO identical donors re-suspended in plasma or additive solutions). BCPP has a volume of

160—200 ml, with platelet content ranging from 2.5 to 4.4x1011 per product.

3. Single donor apheresis (SDP).

These are collected by a variety of apheresis systems using different protocols. A single donation procedure

may yield one to three therapeutic doses and the donation may be split between two or three bags, depending

on counts. SDP are leukocyte reduced; however, in some apheresis systems, filtration may be required for

leucocyte depletion. For SDP collection, donors are tested for platelet count, transfusion transmitted infection

(‘TTT) markers and blood group before collection. The average volume for SDP is 200—300 ml, yield or

platelet content is 3x1011 per bag and is thus equal to 5—6RDP. Thus, it also often regarded as the jumbo

pack. SDPs are expected to increase a patient’s platelet count by 30—50 000/ul. BCPP serves as an alternative

choice of SDP in case of emergency.

a. Compatibility testing is not required for platelet concentrates. Platelet concentrates from donors of

the identical ABO group are given and the patient can have the components of choice and should be

used as far as is possible. However, administrations of ABO non-identical platelet transfusions are

also an acceptable transfusion practice; in particular, when platelet concentrates are in short supply.

b. Similarly, RhD-negative platelet concentrates should be given, where possible, to RhD-negative

patients, particularly to women who have not reached menopause. If RhD-positive platelets are

transfused to an RhD-negative woman of child bearing potential, it is recommended that anti-D

should be given. A dose of 300 IU of anti-D should be sufficient to cover six SDP or 30 RDP

RhD-positive platelets within a 6-week period.

c. Platelets with WBC counts of <8.3x105 in RDP and <5x106 in SDP or BCPP are regarded as

leuco-reduced platelets. Leuco-reduced platelets offer the advantage of decreased CMV transmission,

febrile non-haemolytic transfusion reaction and all immunization. Irradiated platelet or blood

products are used for patients at risk of TA-GVHD.

d. The standard dose for adults is 5—6 units of random donor platelets or one unit of apheresis

platelets or one unit of BCPP, equivalent to 3x1 011 platelets. For neonates/infants, the dose of the

platelets should be 10—15ml/kg of body weight.

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Annexure 3

RDTs

A number of commercial RDT kits for anti-dengue IgM/IgG antibodies and NS1 antigen are commerciallyavailable, which give the results within 15 to 25 minutes. However, the accuracy of most of these tests isnot known since they have not yet been properly validated. Some of the RDTs have been independentlyevaluated. The results showed a high rate of false positives compared to standard tests, while someothers have agreed closely with standard tests. The sensitivity and specificity of some RDTs are alsofound to vary from batch to batch.

According to WHO guidelines, these kits should not be used in clinical settings to guide management ofDF/DHF cases. Use of RDT is not recommended also under the disease control programme.

Interpretation for Primary and secondary infection

In a primary infection (i.e. when an individual is infected for the first time with a flavivirus), viraemia develops from 1–2 days before the onset of fever until 4–5 days after. Accordingly, anti-dengue IgM specific antibodies can be detected3-6 days after fever onset. On average, IgM is detected in 50% of cases by days 3–5 after the onset of illness, this figureincreasing to 95–98% for days 6-10. Thereafter low levels of IgM are detectable around one to three months after fever.In addition, the primary infection is characterized by slowly increasing but low levels of dengue-specific IgG, becomingelevated at days 9-10. Low IgG levels persist for decades, an indication of a past dengue infection.

A totally different picture is observed during a secondary infection, with a rapid and higher increase ofanti-dengue specific IgG antibodies and slower and lower levels of IgM. High IgG levels remain for30–40 days. A short-lasting but higher viremia level characterizes the secondary infection compared tothe primary infection. Primary infections are characterized by high levels of IgM and low levels of IgG,while low levels of IgM with high levels of IgG characterize secondary infections.

IgG + immunoglobulin G; IgM= immunoglobulin M

ViremiaIgM

Primary Infection Second Infection

Viremia

IgG

31

References:1. National Guidelines for Clinical Management of Dengue Fever. NVBDCP. GoI. 2014

2. Handbook for clinical management of dengue. ISBN 978 92 4 150471 3 (NLM classification: WC528) © World Health Organization 2012

3. Lum L, Ng C, Khoo E. Managing dengue fever in primary care: A practical approach. Malaysian FamilyPhysician/: the Official Journal of the Academy of Family Physicians of Malaysia. 2014;9(2):2-10.

4. MODULE 8A: IV Fluid Principles. Dengue Clinical Management. WHO Western Pacific Region

5. Clinical Assessment. Tourniquet Test handout. https://www.cdc.gov/dengue/training/cme/ccm/page73112.html

6. Hung NT. Fluid management for dengue in children. Paediatrics and International Child Health.2012;32(s1):39-42.

32

NOTES

33

Clinical Management of Malaria

34

MALARIAWhat is Malaria?

Malaria is a potentially life threatening parasitic disease caused by parasites known as Plasmodiumviviax (P.vivax), Plasmodium falciparum (P.falciparum), Plasmodium malariae (P.malariae), Plasmodiumovale (P.ovale) and Plasmodium knowlesi (P. knowlesi)

It is transmitted by the infective bite of female Anopheles mosquito

Man develops disease after 10 to 14 days of being bitten by an infective mosquito

There are two types of parasites of human malaria, Plasmodium vivax & P. falciparum, which arecommonly reported from India.

The parasite completes life cycle in liver cells (pre-erythrocytic schizogony) and red blood cells(erythrocytic schizogony).

Clinical features

Fever is the cardinal symptom of malaria. It can be intermittent with or without periodicity or continuous.Many cases have chills and rigors.

The fever is often accompanied by

headache,

myalgia,

arthralgia,

anorexia,

nausea and vomiting.

The symptoms of malaria can be non-specific and mimic other diseases like viral infections, enteric feveretc.

Malaria should be suspected in patients presenting with above features. Malaria is known to mimic thesigns and symptoms of many common infectious diseases. The other causes of fever should also be suspectedand investigated in the presence of manifestations like running nose, cough and other signs of respiratoryinfection, diarrhoea/dysentery, burning micturition and/or lower abdominal pain, skin rash/infections, abscess,painful swelling of joints, ear discharge, lymphadenopathy, etc.

All clinically suspected malaria cases should be investigated immediately by microscopy and/or RapidDiagnostic Test (RDT).

Diagnosis

Microscopy: Microscopy of stained thick and thin blood smears remains the gold standard for confirmationof diagnosis of malaria. The advantages of microscopy are:

The sensitivity is high. It is possible to detect malaria parasites at low densities. It also helps to quantifythe parasite load.

It is possible to distinguish different species of malaria parasites and their different stages.

Rapid Diagnostic Test: Rapid Diagnostic Tests are based on the detection of circulating parasite antigens.Several types of RDTs are available (http:// www.wpro.who.int/sites/rdt). The NVBDCP has rolled outbivalent RDTs (for detecting P. falciparum and P. vivax) for use in the public health sector.

RDTs are produced by different manufacturers, so there may be differences in the contents and in themanner in which the test is done. The user manual should always be read properly and instructions followedmeticulously. The results should be read at the specified time. It is the responsibility of the health carepersonnel doing a rapid test for malaria to ensure that the kit is within its expiry date and has been transportedand stored under recommended conditions. Ensure that correct buffer is always used and not done withbuffer for other kits or with normal saline/ distilled water. Failure to observe these criteria can lead toincorrect results.

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It should be noted that Pf HRP-2 based kits may show positive result up to three weeks after successfultreatment and parasite clearance.

In these cases, results should be correlated with microscopic diagnosis.

Diagnosis of severe malaria cases negative on microscopy

Microscopic evidence may be negative for asexual parasites in patients with severe infections due tosequestration and partial treatment. Efforts should be made to confirm these cases by RDT or repeatmicroscopy. However, if clinical presentation indicates severe malaria and there is no alternative explanation,these patients should be treated accordingly.

Severe malaria due to P. vivax

In recent years, increased attention has been drawn to severe malaria caused by P. vivax. Some cases havebeen reported in India along with deaths, and there is reason to fear that this problem may become morecommon in the coming years. Severe malaria caused by P. vivax should be treated like severe P. falciparummalaria, however, primaquine should be given for 14 days for preventing relapse as per guidelines after thepatient recovers from acute illness and can tolerate primaquine.

Severe malaria : Clinical features

Clinical features of severe manifestations can develop in P. falciparum infection over a span of time asshort as 12–24 hours and may lead to death, if not treated promptly and adequately. Severe malaria ischaracterized by one or more of the following features:

Impaired consciousness/coma [A Glasgow coma score <11 in adults or a Blantyre coma score <3 inchildren.]

Repeated generalized convulsions [ >2 episodes within 24 hours]

Prostration: Generalized weakness so that the person is unable to sit, stand or walk without assistance

Renal failure (Serum Creatinine >3 mg/dl.)

Jaundice (Serum Bilirubin >3 mg/dl)

Severe anaemia (Hb <5 g/dl)

Pulmonary oedema/acute respiratory distress syndrome [Radiologically confirmed or oxygensaturation <92% in room air with a respiratory rate >30/min, often with chest indrawing andcrepitations on auscultation.]

Hypoglycaemia [Plasma Glucose <40 mg/dl ]

Metabolic acidosis [A base deficit of >8 mEq/L or, if not available, a plasma bicarbonate level of <15mmol/L or venous plasma lactate of <15 mmol/L. Severe acidosis manifests clinically as respiratorydistress (rapid, deep, labored breathing)]

Circulatory collapse/shock [Systolic BP <80 mm Hg, <50 mm Hg in children with evidence ofimpaired perfusion (cold peripheries or prolonged capillary refill).]

Abnormal bleeding and Disseminated intravascular coagulation (DIC) [Significant bleeding includingrecurrent or prolonged bleeding from the nose, gums or venepuncture sites; hematemesis or melaena.]

Haemoglobinuria

Hyperpyrexia (Temperature >106°F or >42°C)

Hyperparasitaemia (>5% parasitized RBCs ).

Foetal and maternal complications are more common in pregnancy with severe malaria; therefore,those need prompt attention.

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EXCERPTS FROM GUIDELINES FOR DIAGNOSIS & TREATMENT OF MALARIA IN INDIA

(Based on National Drug Policy on Malaria, 2013)

Treatment of Vivax Malaria

Note: CQ (chloroquine) 250mg tablet contains 150mg base.

PQ (primaquine) is used to prevent relapse but is contraindicated in pregnant women, infants and individualswith known G6PD deficiency. Test for G6PD level is not mandatory for giving PQ to a patient.

Note : Patients should be instructed to report back in case of haematuria or high colored urine/cyanosisor blue coloration of lips and Primaquine should be stopped in such cases. Care should be taken inpatients with anemia.

CQ & PQ should be taken after a meal and not on an empty stomach.

Treatment of Falciparum Malaria

It is imperative to start the treatment for falciparum malaria immediately on diagnosis.

(A) Treatment of uncomplicated P. falciparum cases :

All tablets for a particular day should be taken together, swallowed with water.

AS = artesunate; SP = sulphadoxine-pyrimethamine.

PQ = primaquine; prevents transmission of Pf malaria to others by killing the gametocytes.

*SP is not to be prescribed for children <5 months of age, who should be treated with alternate ACT.

Day1 Day2 Day3 Day4 to 14

CQ PQ CQ PQ CQ PQAge (150 (2.5 (150 (2.5 (150 (2.5 PQ (2.5mg)mg) mg) mg) mg) mg) mg)

Less than 1yr ½ 0 ½ 0 ¼ 0 0

1-4 years 1 1 1 1 ½ 1 1

5-8 years 2 2 2 2 1 2 2

9-14 years 3 4 3 4 1½ 4 4

15 yrs or more 4 6 4 6 2 6 6

Pregnancy 4 0 4 0 2 0 0

Age Group 1st day 2nd day 3rd day(Years) AS SP AS PQ AS

0-1* (25mg) (250+12.5 mg) (25mg) Nil (25mg)

1-4 (50 mg) (500+25 mg) (50mg) 1 (7.5 mg base) (50mg)

5-8 (100mg) (750+37.5 mg) (100mg) 2 (7.5mg (100mg)base each)

9-14 (150mg) 2 (500+25 mg each) (150mg) 4 (7.5mg (150mg)base each)

15 & above (200mg) 2 (750+37.5 mg each) (200mg) 6 (7.5mg (200mg)base each

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(B) Treatment of uncomplicated P. falciparum cases in pregnancy:

1st trimester : Quinine salt 10mg/kg 3 times daily for 7days.

Quinine may induce hypoglycemia. Pregnant women should not start taking quinine on an empty stomachand should eat regularly, while on quinine treatment.

In severe malaria in first trimester of pregnancy, parenteral quinine is the drug of choice. However, ifquinine is not available, artemisinin derivatives may be given to save the life of mother.

2nd and 3rd trimester: ACT-SP.[Primaquine is contraindicated in pregnancy].

In severe malaria during second or third trimester, parenteral artemisinin derivatives are preferred.

(C) Treatment of mixed infections (P. vivax +P. falciparum) cases:

Mixed infections should be treated with full course of ACT (like falciparum malaria) and Primaquine 0.25mgper kg body weight daily for 14 days (like vivax malaria).

(D) Antimalarials for severe malaria cases:

CHOOSE ONE of following four options Follow-up treatment, when patient cantake oral medication following parenteral Rx

Artesunate: 2.4 mg/kg i.v. or i.m. given onadmission (time=0), then at 12 hr and 24 hr,then once a day Full oral course of Area-specific ACT is to be given(most preferred among artemisinin derivatives). after parenteral therapy.Or Artemether: 3.2mg/kg bw i.m. given onadmission, then1.6mg/kg per day. Treat with ACT-SP for 3 days+PQ single dose (asOr Arteether: 150mg daily i.m. for 3 days in mentioned above).adults only (not recommended for children).

Quinine: 20mg quinine salt/kg body weight on Quinine :admission (IV infusion or divided IM inj) -10mg/kg orally three times a dayfollowed by maintenance dose of 10mg/kg with doxycycline100mg once a day or clindamycin8 hourly; infusion rate should not exceed (doxycycline is contraindicated in pregnant &5mg/kg per hour. Loading dose of 20mg/kg lactating women and children< 8 years of age)should not be given, if patient has already - Complete 7 days of treatment.received quinine.

Rapid intravenous administration of quinine is dangerous.

Each dose of parenteral quinine must be administered as a slow, rate-controlled infusion (usually diluted in5% dextrose and infused over 4 hr). The infusion rate should not exceed 5 mg salt/ kg bw per hour. It maycause hypotension if administered rapidly.

If intramuscular quinine is to be given, give it to anterior thigh; and should not be given in buttock in orderto avoid sciatic nerve injury. The first dose should be split, with 10mg/ kg bw into each thigh.

The parenteral treatment in severe malaria cases should be given for minimum of 24 hours once started,irrespective of patient’s ability to take oral medication earlier than 24 hour. [In parenteral treatment withquinine it should be minimum 48 hours].

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After parenteral artemisinin therapy, start within 8-12 hours a full course of area-specific oral ACT for 3days. After parenteral Quinine therapy a patient should receive oral Quinine10 mg/kg bw three times a dayfor 7 days (including the days when parenteral dose was given) plus Doxycycline 3mg/kg bw once a day orClindamycin 10mg/kg bw 12-hourly for 7 days or ACT as described. [Contraindication of Doxycycline: seetable above].

Revised dose recommendation for parenteral artesunate in young children [Annex 1]

Children weighing <20 kg should receive a higher dose of artesunate (3 mg/ kg bw per dose) than largerchildren and adults ( 2.4 mg/ kg bw per dose) to ensure equivalent exposure to the drug.

(D) Treatment of patients co-infected with HIV:

In people who have HIV/ AIDS and uncomplicated P. falciparum malaria, avoid artesunate + SP if they arebeing treated with co-trimoxazole, and avoid artesunate + amodiaquine if they are being treated with efavirenzor zidovudine.

(E) Additional consideration for clinical management:

I. Use of Antipyretics: Antipyretics should be used if the core temperature is > 38.5 0C. Paracetamolat a dose of 15 mg/kg bw every 4 hr. Aspirin & other NSAIDs is no longer recommended becauseof the risk of gastrointestinal bleeding, renal impairment and Reye’s syndrome.

II. Use of anti-emetics: Antiemetics like domperidone or 5 HT3 antagonists like ondansetron can be used.

III. Management of seizures: If the seizure continues, the airways should be maintained andanticonvulsants given (inj valproate @20 mg/kg loading followed by maintenance @ 10 mg/kg 12hrly). There is no evidence that prophylactic anticonvulsants are beneficial.

IV. Fluid therapy: Fluid requirements should be assessed individually. Adults with severe malaria arevery vulnerable to fluid overload, while children are more likely to be dehydrated. The fluid regimenmust also be adapted to the infusion of antimalarial drugs. Rapid bolus infusion of colloid orcrystalloids is contraindicated.

Points to Note –

Pre-referral treatment options

Where complete treatment of severe malaria is not possible but injections are available, give adults andchildren a single dose of artesunate injection and then refer to an appropriate facility for further care.

Every 24 × 7 govt. health facility must have at least 2 doses of injection artesunate as a reserve stock as pera govt. circular.

Initiation of treatment and advice to the patient/caretaker

Once a suspected case is diagnosed positive by RDT or microscopy, treatment is started. The first dose isalways taken in the presence of the health volunteer/worker. The blister pack with remaining tablets is givento the patient/caretaker to take home with clear instructions.

That if the treatment is not completed as prescribed, the disease may manifest again with moreserious features and may be more difficult to treat.

To come back immediately, if there is no improvement after 24 hours, if the situation gets worse orthe fever comes back.

That regular use of a mosquito net (preferably insecticide treated net) is the best way to preventmalaria.

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Caution: If the patient is a child under 5 years or pregnant, ask the patient to wait for 15 minutes after takingthe first dose. If it is vomited within this period, let the patient rest for 15 minutes, and then give the firstdose again i.e. open a new blister-pack and discard what remains of the old. If the patient vomits the firstdose again, it is considered a case of severe malaria, refer the patient immediately to the nearest Block PHC/RH/Hospital.

General recommendations for the management of uncomplicated malaria

Avoid starting treatment on an empty stomach. The first dose should be given under observation.

Dose should be repeated if vomiting occurs within half an hour of antimalarial intake afterantiemetics.

The patient should be asked to report back, if there is no improvement after 48 hours or if thesituation deteriorates.

The patient should also be examined and investigated for concomitant illnesses.

Primaquine therapy: Caution

Caution should be exercised before administering primaquine in areas known to have high prevalence ofG6PD deficiency. Patient should be advised to stop primaquine immediately if he/she develops any of thefollowing symptoms and should report to the doctor immediately: (i) dark coloured urine (ii) yellow conjunctiva(iii) bluish discolouration of lips (iv) abdominal pain (v) nausea (vi) vomiting (vii) breathlessness, etc.

Considering the varying relapse rates, G6PD deficiency and facilities for G6PD testing, individual cliniciansshould weigh risks versus benefits while prescribing primaquine.

Clinical observation of admitted cases

Vitals signs with temperature recording

Urine output

Coma score

Blood glucose in comatose/ unconscious patient every 4 hourly

Other points

If a suspected malaria patient has a negative RDT, it can be assumed that the patient does not havemalaria and another cause of the symptoms should be sought for. If no other cause can be foundand the clinical suspicion is high for Malaria (e.g. intermittent fever with rigors and sweats), thetest should be repeated after about 24 hours and special efforts should be made to obtain themicroscopy result rapidly.

If the tests for malaria (both RDT & microscopy) are negative, but history & examination findingsclearly point to Malaria (uncomplicated/severe) and there is no alternative explanation, such acase should only be treated accordingly (full course of chloroquine/ inj antimalarial respectively).Also, tests for malaria should be repeated. It is to be re-emphasized that there is no presumptivetreatment of Malaria under current Guideline.

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Don’ts in severe malaria :

Do not use

adrenaline·

corticosteroids·

intravenous mannitol·

heparin (as anticoagulant)

Do not overhydrate the patient.

MONOTHERAPY OF ORAL ARTEMISININ DERIVATIVES IS BANNED IN INDIA

Injectable artemisinin derivatives should be used only in severe malaria, followed byoral combination therapy.

The presently recommended ACT for the North-Eastern States is fixed dose combinationof Artemether-Lumefantrine (AL). Adult dose: 4 tablets twice daily for 3 days

(80 mg/ 480 mgper dose). It may be required in case of malaria imported from the NE States.For age-wise schedule of AL please go through National Drug Policy on Malaria, 2013.

In a case of uncomplicated falciparum malaria, resistance should be suspected if in spite of full treatmentwith no history of vomiting or diarrhoea, patient does not respond within 72 hours, clinically andparasitologically; or if danger signs of severe malaria develops even after one day of therapy. Such casesnot responding to ACT, should be treated with oral quinine with Tetracycline / Doxycycline, or in the lineof severe Malaria if signs of severe Malaria have appeared. These instances should be reported to theconcerned Dy.CMOH-II / DDHS (Malaria).

41

Annexure: Guideline for administration of injectable Artesunate for Severe Malaria

42

43

NOTES