INTRODUCTION
In the recent years, the global incidence of dengue fever has considerably increased which lead to an imminent need to engage in a research study of the same. According to the reports of World Health Organization (WHO), there are about 390 million cases of dengue fever being reported worldwide, and of the total number of cases, 96 million require medical treatment. India also has witnessed a doubling up of cases of dengue from 2014 to 2015;
among that the worst hit city was Delhi with more than 1800 cases of the fever. Significantly, this challenge continues to affect societies and communities and has become a major cause of concern across the country in the contemporary.According to NVBDCP,number of dengue cases reported in Tamilnadu were 12826,6122,2804 in 2012,2013,2014 respectively[1].The number of deaths reported were 66,0,3 in 2012,2013,2014 respectively.[1] It is in this context that this study on dengue fever assumes relevance and significance as a research engagement.
First of all, it is important to survey some of the basic details related to Dengue.
Dengue was classified as a neglected tropical disease and its occurrence has got a historical precedence across the globe. Dengue has become a global problem since the Second World War[2] and is now prevailing in more than 110 countries. It has been reported that each year between 50 and 528 million people are getting infected out of which approximately 10,000 to 20,000 die[3]. As one of the recent studies, an estimated 50 million dengue infections now occuring annually, particularly in South-East Asia[4], the Americas, and the Western Pacific islands[5]. In the year 2002 alone around 19000 dengue-related deaths were reported and these figures are really alarming.
The earliest descriptions of an outbreak dates back to 18th century, approximately in the year 1779 ,when it was not diagnosed properly. However, its viral etiology and spread were understood by early 20th century only. Between 250 000 and 500 000 people develop severe dengue each year.[8]
Dengue is spread by several species of mosquitoes of the Aedes type, mainly- A. aegypti. The virus has five different serotypes; infection with one serotype of virus usually gives lifelong immunity to that type, but only short-term immunity to other serotypes. Subsequent infection with a different serotype leads to the risk of severe complications. Currently, there are a number of tests available to confirm the diagnosis including detecting antibodies to the culprit virus or its RNA. In addition to that, a novel treatment and vaccine for dengue has been approved and is commercially available in various countries. Other methods of prevention are by reducing habitat of mosquito and limiting one’s exposure to mosquito bites.
This may be done in different ways - by getting rid of or covering the stagnant water reservoirs and also by wearing clothing that covers much of the body.[6] However, it is not just enough to reduce the exposure to mosquitoes. Apart from all these, major research work is going on for medication targeted directly at the virus.
Treatment of acute dengue fever is supportive and includes giving fluid either by mouth or intravenously for mild or moderate disease. For more severe cases blood transfusion may be required. It is also estimated that about half a million people require admission to hospital a year. During the treatment it is important to note that NSAIDs such as ibuprofen,diclofenac should not be used.
Arguably, dengue is the most rapidly spreading arboviral disease in the tropical and subtropical areas. Over the last three decades the global burden of dengue has increased to at least four-fold;
therefore, almost half of the world’s population is estimated to be at risk of this infection[2].It is a fact that the dengue is accepted as an important public health problem in the WHO South-East Asia Region (SEAR), Western Pacific Region (WPR) and Americas Region (AMR), without a proper reliable data about the burden of disease in the African Region (AFR) and the Eastern Mediterranean Region (EMR), no detailed documentation of the real burden of dengue does exist.
This can be considered as the greatest challenge and hindrance as far the research work on dengue is concerned. Quantifying the epidemiological and economic burden of dengue is key to formulating policy decisions on research priorities, prevention programmes, clinical training for management of the disease, and the introduction of new technology.[9]Reliable diagnosis, testing, and reporting of dengue cases would allow better understanding of the true burden of dengue in a world of competing public health issues. Reports should capture the seasonal and cyclical (annual) variations in disease incidence[11] Such reports can be used for various purposes. Firstly, they would provide the basis for comparisons of the burden of dengue in different geographical locations and time periods. Secondly, they would help country-level, regional, and global public health authorities to make decisions on resource allocations. Decisions can be based on the comparison of the burden of dengue with that of other health issue.[9] Accurate estimates of the magnitude of dengue can serve to justify donor funding, setting priorities for research, and accelerating the development of dengue vaccines[12]. Thirdly, such reports would have to serve as important baselines for assessing the impact of any intervention (e.g. a larvicide campaign or vaccine) that could alter the burden of dengue fevere, and would also have to provide a key ingredient in cost–effectiveness analyses of a single or multiple interventions and technologies.
Although improvements are being made, the current gaps in epidemiological data and surveillance mean that the burden of dengue in India is uncertain. However, dengue is recognized as one of the leading causes of death and hospitalization among children in India[10]. The burden
of illness caused by dengue is measured by epidemiological indicators like the number of clinical cases classified by severity (DF, DHF, DSS), duration of illness episode, quality of life during dengue illness, case-fatality rate and absolute number of deaths in a given period of time. All these epidemiological indicators are combined into a single indicator, as disability-adjusted life years (DALYs).
AIMS AND OBJECTIVES OF THE STUDY
1. TO COMPARATIVELY ANALYSE THE CLINICAL PROFILE OF
CASES OF DENGUE ADMITTED IN KAPV MEDICAL COLLEGE
2. TO EVALUATE HEMATOLOGICAL CHANGES IN PATIENTS
SUFFERING FROM CLINICAL MANIFESTATIONS OF DENGUE WITH SEROLOGICAL CONFIRMATION.
3. TO STUDY THE AGE AND SEX DISTRIBUTION, AND CLINICAL FEATURES OF DENGUE ILLNESS
4. TO CORRELATE WHETHER GENDER HAS ANY BINDING ON THE CLINICAL OUTCOME
MATERIALS AND METHODS OF THE STUDY SOURCE OF DATA
Primary Data
The data bank of medical records present in the Mahatma Gandhi Memorial Govt..Hospital attached to KAPV Medical College,Tiruchirappalli, along with the Lab observation report is being used for collecting the primary data. The sample will be selected using the simple random sampling method and the analysis of the data will be done with the help of SPSS.
Secondary Data
Secondary data were collected from the published materials including books, periodicals, print and e-journals and various internet sites.
ETHICAL COMMITTEE APPROVAL
The study was initiated only after getting the ethical approval from Ethics Committee, KAPV Medical College & Hospital, Trichy.
STUDY DESIGN
Retrospective analytical study
The researcher used descriptive statistics for calculation of quantitative & qualitative variables. And chi-square test was used to find out the association between different demographic features & outcome of dengue cases.
INCLUSION CRITERIA
Patients more than 13 yrs of age
Serologically Confirmed dengue cases.
Cases that were followed in our institute so that at least two
CBC results available.
No other confounding factors such as co-infection that may
alter the clinical and/or the laboratory results.
EXCLUSION CRITERIA
Negative cases for dengue serology.
Patients with less than two CBC readings.
Pregnant women
patients less than 13yrs of age HYPOTHESIS
H0 : There is no significant influence of Gender with the Symptoms, Clinical Manisfestations and Lab Observations of Seropositive Dengue patients.
SELECTION OF SAMPLE SIZE
For the present study, a convenience sampling in non-probability has been adopted. The study, being a three year one, has been done on 50 patients from the years–2012, 2013&2014.
DATA ANALYSIS AND STATISTICAL TOOL USED
After primary data are collected, the data are coded, filtered and entered in SPSS (Statistical Package for Social Science) version 20. Finally50 cases were retained for analysis to get out put. The data are presented in tables and pictographic format for the easy interpretation and understanding.
SAMPLE SIZE – 150 (50 each from 2012, 2013& 2014)
REVIEW OF LITERATURE History of Dengue
The study of any occurrence would be complete only by the inclusion of a historical background and survey. Dengue virus was first isolated in Japan in 1943 by the inoculation of serum of patients into the suckling mice[13]. In an year inCalcutta (the now Kolkata) ,in 1944 ,based on the serum samples of soldiers of US army, it was again identified and isolated.[14] The first epidemic of clinical dengue fever-like illness was recorded in Madras ( now Chennai) in 1780 and the first virologically proved epidemic of DF in India had occurred in Calcutta and Eastern Coast of India in 1963-1964[18-20]. The first major epidemic of Dengue Haemorrhagic Fever had occurred in 1953-1954 in Philippines which was followed by a quick global spread of epidemics of DF/DHF.
This was rather as remarkable as DHF was occurring in the adjoining countries of India but it was absent in India for unknown reasons inspite of the presence of all the risk factors. As per the available data and records, the DHF started simmering in various areas of India since 1988[16]. The first major wide spread epidemic of DHF/DSS occurred in India in 1996 in and around the areas of Delhiand Lucknow.[15] It didn’t take much long for the virus to then spread to different parts of the country. Now dengue is seen as one of the most important medical challenges faced by our country.
Epidemiology of dengue
A history of symptoms compatible with dengue fever can be traced back to the Chin Dynasty of 265–420 AD.[17]The epidemiology of dengue fever in the Indian subcontinent has been quite complex.This has substantially changed over past six decades in terms of the prevalence of the strains,the affected geographical areas and the severity of disease. The very first report of dengue fever in India was back in 1946.[21] Thereafter, for the next 18 years,there was no significant dengue virus activity reported anywhere in the country. An initial epidemic of dengue fever was
reported on the Eastern Coast of India[22-26], during 1963-1964. As per research data, it then spread north wards until it hit Delhi in 1967 and Kanpur in 1968[27,28]. Simultaneously it affected the southern parts of the country and gradually the whole country was involved with wide spread epidemics followed by endemic/hyperendemic prevalence of all the four serotypes of dengue virus.
It can be said that the epidemiology of dengue virus and its prevalent serotypes has been ever changing. The epidemic at Kanpur during 1968 was due to DV-4 and during 1969 epidemic, both DV-2 and DV-4 were isolated[29]. However, it was completely superseded by DV-2 during 1970 epidemic in the neighbouring city of Hardoi[30]. Myers et al [31,32]had reported the presence of DV-3 in patients and in mosquitoes at Vellore during the epidemic of 1966 while during the epidemic of 1968, the four serotypes of viruses were isolated from patients and mosquitoes[33]. In another study ,Myers & Varkey[34] recounted the instance of a third attack of DV in an individual.
DV-2 was isolated during the epidemics of dengue fever in urban and rural areas of Gujarat during 1988 and 1989.[35]Occurrences of dengue in Rajasthan by DV- 1 and DV-3[36] and DV- 2[37];Madhya Pradesh by DV-3[38]; Gujarat by DV-2 and in Haryana by DV-2[39]. DV-2 was thought to be the principal serotype circulating in northern India, including Delhi, Lucknow and Gwalior while DV-1 was isolated during the epidemic of 1997 at Delhi[40]. The phylogenetic examination by the Molecular Evolutionary Genetics Analysis programme has suggested that the 1996 Delhi isolates of DV-2 were mostly of the genotype IV[41]. The 1967 isolate was related to the 1957 isolate of DV-2, from India, and was catalogued as genotype V. This analysis indicates that earlier DV-2 strains of genotype V has been replaced by genotype IV[42]. The Gwalior DV-2 viruses were classified into genotype-IV, and was closely related to Delhi 1996 DV-2 viruses and FJ 10/11 strains prevalent in the Fujian State of China. However, two earlier Indian isolates of DV-2 were classified into genotype-V. Genotype V of DV-2 has been replaced by genotype IV
during epidemic in the last decade, which has continued to circulate silently in north India, and has the potential to re-emerge and trigger major epidemics of DF and DHF[43]. DV-2 has also been reported from southern parts of India - in Kerala along with DV-3.[44]
DV-3 has also been isolated during the epidemics at Vellore in 1966[45], at Calcutta in the year 1983and in 1990[46,47], at Jalore city, state of Rajasthan in 1985 ,at Gwalior in 2003 and 2004 and at Tirupur, Tamil Nadu in 2010[48]. The Madurai isolates were closely related to Gwalior and Delhi isolates as suggested by the Phylogenetic analysis. The emergence of DV-4 has been reported in the states of Andhra Pradesh[49] and Pune, Maharashtra[50], which was also implicated in increased severity of the disease.At Delhi, till 2003, the predominant serotype was DV-2 (genotype IV) but in 2003 for the first time all four dengue virus subtypes were found to co- circulate in Delhi and thus changing to a hyperendemic state[51] which was followed by complete predominance of DV serotype 3 in 2005[52]. However, thus a sudden shift and dominance of the DV serotype-3 (subtype III) occurred in northern parts of India .During the 2004 epidemic of DHF/DSS; in this case the earlier circulating serotype-2 (subtype IV) and it was replaced. Co- circulation of DV serotypes in Delhi in 2003-2004 has been identified. These, it has been reported, may have implications for increased DHF/DSS. Emergence of a distinct lineage of DV- 1, having similarity with the Comoros/Singapore 1993 and Delhi 1982 strains has also been reported[53]. But this was considered quite different from the Delhi 2005 lineage and microevolution of the pre-circulating DV-3. Co-circulation of different serotypes of dengue viruses has resulted in concurrent infection in some patients with multiple serotypes of the virus[54]. Further, replacement of DV-2 and 3 with DV-1 as the predominant serotype in Delhi over a period of three years (2007-2009) has been reported[55]. Interestingly and significantly, yet another instance of concurrent infection by Chikungunya and DV-2 was reported from Vellore[56]
and Delhi[57] – from the South and the North India.
Due to our time constraints and unavailablility and inaccessibility of data this study plans to focus only on the state of Tamil Nadu. In fact, it is also interesting to note that all the four serotypes of the virus have been in circulation and documented in Tamil Nadu which is also the state within which this current study gets situated.
Dengue virus and its serotypes
Dengue fever virus (DENV) is an RNA virus of the family Flaviviridae; genus Flavivirus. Other members of the same genus include yellow fever virus, West Nile virus, St. Louis encephalitis virus, Japanese encephalitis virus, tick-borne encephalitis virus, Kyasanur forest disease virus, and Omsk hemorrhagic fever virus. Most are transmitted by arthropods (mosquitoes or ticks), and are therefore also referred to as arboviruses (arthropod-borne viruses). It is composed of three structural protein genes, one of which encode the nucleocapsid or core (C) protein, second one ecodes for a membrane-associated (M) protein,and the third one for an enveloped (E) glycoprotein and seven non-structural (NS) proteins molecules (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5) that are found in infected host cells only and are required for replication of the virus.
The very first structure of a flavivirus was determined by using a combination of cryoelectron microscopy and fitting of the glycoprotein E into the electron density map. The virus core, which is within a lipid bilayer, has a less-ordered structure than the external, icosahedral scaffold of 90 glycoprotein E dimers. The three E monomers present per icosahedral asymmetric unit do not have quasiequivalent symmetric environments. Difference in maps indicate the location of the small membrane protein M relative to the overlaying scaffold of E dimers. The structure suggests that flaviviruses, and also by analogy alphaviruses, employs a fusion mechanism in which the distal β barrels of domain II of the glycoprotein E are inserted into the cellular membrane.[60]
Available and reliable research data indicates that DV-1 was isolated in 1956 at Vellore,Tamilnadu. This also leads us to assume that all the Indian DV-1 isolates belong to the American Africa genotype. It is important to further understand these classifications. The Indian DV-1 isolates are primarily distributed into four lineages, India I, II, III and the Africa lineage[58]. Of these, India III is the oldest and perhaps also considered as the extinct lineage; the Afro-India is a transient lineage while India I is imported from Singapore and India II, evolving in situ, are the circulating lineages. The American genotype of DV-2 which circulated predominantly in India during the pre-1971 period, was subsequently replaced by the Cosmopolitan genotype.
Post-1971 Indian isolates formed a separate subclade within the Cosmopolitan genotype. DV-2 strains were isolated in India over a time span of more than 50 years (1956-2011). The re- emergence of an epidemic strain of DV type-3 in Delhi in 2003 and its persistence in subsequent years marked a changing trend in DV circulation in this part of India[59]. Occasional reports of circulation of DV-4 are also seen, though it is not the predominant type in India. . The five strains of the virus, called serotypes, of which the first four are referred to as DENV-1, DENV-2, DENV-3 and DENV-4. The fifth type was announced in 2013. The distinctions between the serotypes are based on their antigenicity.
Transmission
Transmission of dengue viruses occur in three cycles:
(1) Enzootic cycle:This primitive sylvatic cycle maintained by monkey-Aedes-monkey cycle as reported from South Asia and Africa. Viruses are not pathogenic to monkeys and viraemia lasts 2–3 days [70]
(2) Epizootic cycle:The dengue virus crosses over to non-human primates from adjoining human epidemic cycles by bridge vectors. In Sri Lanka, the epizootic cycle was observed
among touqe macaques (Macaca sinica) during 1986-1987,within the study area (three kilometres), 94% macaques were affected [71]
(3) Epidemic cycle:The epidemic cycle is maintained by human-Aedes aegypti-humancycle with periodic epidemics. The persistence of dengue virus, depends on the high viral titres in the human host to ensure transmission in mosquitoes[72]
Dengue virus is primarily transmitted by Aedes mosquitoes, particularly A. aegypti. These mosquitoes usually live between the latitudes of 35° North and 35° South below an elevation of 1,000 metres (3,300 ft). Its eggs are somewhat resistant to sub-freezing temperatures.They typically bite during the early morning and in the evening, but they may bite and thus spread infection at any time of day. Because of the species’ high degree of domestication and strong affinity for human blood, it has achieved high vectorial capacity for transmission of DF/DHF in all the areas where it prevailed.Other species that transmit the disease include A. albopictus, A.
polynesiensis and A.scutellaris. Aedes (Stegomyia) albopictus belongs to the scutellaris group of
subgenus Stegomyia. It is an Asian species belonging to South-East Asia and islands of the Western Pacific and Indian Ocean.Humans are the primary host of the virus, but it also circulates in nonhuman primates. An infection can be acquired via a single bite.
A female mosquito that takes a blood meal from a person infected with dengue fever, during the initial 2- to 10-day febrile period, becomes itself infected with the virus in the cells lining its gut.
About 8–10 days later, the virus spreads to other tissues including the mosquito's salivary glands and is subsequently released into its saliva. The virus seems to have no detrimental effect on the mosquito, which remains infected for life. Aedes aegypti is particularly involved, as it prefers to lay its eggs in artificial water containers, to live in close proximity to humans, and to feed on people rather than other vertebrates.[61]
Both aegypti and albopictus have high vectorial competency for Dengue viruses.
Ae. aegypti bites more than one host to complete one blood meal-nervous feeder and needs more
than one feed for the completion of the gonotropic cycle-discordant species. These habits epidemiologically can result in the generation of multiple cases and the clustering of dengue cases in urban areas. But, Ae.albopictus still maintains feral moorings and partly invades peripheral areas of urban cities, and it feeds on both humans and animals; an aggressive feeder and a concordant species, i.e. the species can complete its blood meal in one go on one person and does not require a second blood meal for the gonotropic cycle completion. Hence,Ae.
albopictus carries poor vectorial capacity in an urban epidemic cycle[64]
Dengue can also be transmitted via infected blood products and through organ donation. In countries such as Singapore, where dengue is endemic, the risk is estimated to be between 1.6 and 6 per 10,000 transfusions.. Vertical transmission (from mother to child) during pregnancy or at birth has been reported. Though unusual, other person-to-person modes of transmission have also been reported. The genetic variation in dengue viruses is region specific, suggestive that
establishment into new territories is relatively infrequent despite dengue emerging in new regions in recent decades.
Predisposition
In contrast to many other infections,the disease is more severe in babies and young children who are relatively well nourished. The other risk factors for severe disease include pregnant female, high body mass index, peptic ulcer disease,women abnormal vaginal bleeding and those on mensturation and viral load. While each serotype can cause the full spectrum of disease, virus strain is a risk factor. Infection with one serotype is thought to produce lifelong immunity to that type, but only short-term protection against the other three. The risk of severe disease from secondary infection increases if someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or DENV-3, or if someone previously exposed to DENV-3 acquires DENV-2.
Dengue can be life-threatening in people with chronic diseases such as diabetes,brochial asthma,systemic hypertension,ischaemic heart disease,liver cirrhosis and chronic renal failure .Patients on steroids or NSAIDs are also in the high risk category[64].
Polymorphisms (normal variations) in particular genes have been linked with an increased risk of severe dengue complications. Examples include the genes coding for the proteins known as TNFα, mannan-binding lectin, CTLA4, TGFβ, DC-SIGN, PLCE1, and particular forms of human leukocyte antigen from gene variations of HLA-B. A common genetic abnormality, especially in Africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk.
Polymorphisms in the genes for the vitamin D receptor and FcγR seem to offer protection against severe disease in secondary dengue infection.
Other risk factors common to all include
A.uncontrolled urbanization putting severe constraints on civic amenities like water supply and solid waste disposal and thereby increasing breeding potential of the vectors
B. Inadequate water distribution .
C. Inefficient waste collection and disposal D.Lack of vector control infrastructure.
E.Introduction of consumerism,plastics,paper bags,cups,tyres where water can remain stagnant and increase the chance of passive spread of the disease[62].
F.Increased air travel and globalization of trade.
G.Microevolution of viruses[63]
Dengue and its symptoms
The word “dengue” is derived from the Swahili phrase Ka-dinga pepo, meaning “cramp-like seizure”.Dengue (pronounced as “daen-gay”).Talking about its symptoms, Dr Mukesh Mehra, Senior Consultant, Internal Medicine, Max Super Specialty Hospital, Patparganj says, "Typically people infected with dengue virus are asymptomatic (80 per cent) and only only 5 per cent have severe illness."
Early signs of dengue may include high fever, joint pains, headache, nausea, appetite loss, vomiting, dip in blood pressure and would perpetuate with a characteristic skin rash. Though mostly the fever doesn't last beyond a week, some cases may develop more critical and pose life threatening danger. The latter situation is characterized by a drop in the level of blood platelets, blood plasma leakage or a severely low blood pressure.
The rare case when dengue develops into a life threatening disease is referred to as Dengue Hemorrhagic Fever or Dengue Shock Syndrome. The former is characterized by Haemorrhage (severe bleeding), blood plasma leakage, and an exceptionally low platelet count. While, the latter occurs due to dangerously low blood pressure, which may lead to a circulatory collapse.The
alternative name for dengue, "breakbone fever", comes from the associated muscle and joint pains.The course of infection is divided into three phases: febrile, critical, and recovery.
The febrile phase involves high fever, potentially over 40 °C (104 °F), and is associated with generalized pain and a headache; this usually lasts two to seven days(average 3-14days)[64]
Nausea and vomiting may also occur. A rash occurs in 50–80% of those with symptomsin the first or second day of symptoms as flushed skin or face [65]or later in the course of illness (days 4–
7), as a measles-like rash. A rash described as "islands of white in a sea of red" has also been observed. Some petechiae (small red spots that do not disappear when the skin is pressed, which are caused by broken capillaries) can appear at this point, as may some mild bleeding from the mucous membranes of the mouth and nose. The fever itself is classically biphasic or saddleback in nature, breaking and then returning for one or two days.
In certain cases, the disease proceeds to a critical phase as fever resolves. During this period, there is leakage of plasma from the blood vessels, typically lasting one to two days. This may result in fluid accumulation in the chest(pleural effusion) and abdominal cavity(as free fliud or ascites) as well as depletion of fluid from the circulation and decreased blood supply to vital organs. There may also be organ dysfunction and severe bleeding, typically from the gastrointestinal tract.Shock(dengue shock syndrome) and hemorrhage (dengue hemorrhagic fever) occur in less than 5% of all cases of dengue, however those who have previously been infected with other serotypes of dengue virus ("secondary infection") are at an increased risk.
This critically serious phase, while rare, occurs relatively more commonly in children and young adults.
The recovery phase occurs next, with resorption of the leaked fluid into the bloodstream. This usually lasts two to three days. The improvement is often striking, and can be accompanied with
severe itching and a slow heart rate(bradycardia). Another rash may occur with either a maculopapular or a vasculitic appearance, which is followed by peeling of the skin.
Classification; Dengue virus infection
Symptomatic Asymptomatic Undifferentiated Fever(viral syndrome)
Denguefever(DF) Without Haemorrhage With unusual haemorrhage
Dengue haemorrheagic fever (DHF) (with plasma leakage) Expanded dengue syndrome/Isolated organopathy
DHF (non-shock) DHF withDSS (unusual manifestation) Newer classification includes 1.Probable Dengue 2.Dengue with warning signs 3.Severe Dengue Clinical manifestations
The clinical manifestation depends on different factors like the virus strain and host factors such as age, immune status, etc
a.Undifferentiated fever-Those who have been infected with dengue virus, especially for the first time - primary dengue infection,may develop a simple fever which cannot be distinguishable from other viral infections.Maculopapular rashes may occur during the fever or during defervescence. Upper respiratory signs and gastrointestinal symptoms are common.
b.Dengue fever-Dengue fever (DF) is most commonly occur in older children, adolescents and adults. It generally manifest an acute febrile illness, and sometimes as biphasic fever with severe headache, myalgia,arthralgia, rashes, leucopenia and thrombocytopenia. Although DF can be
benign, it could sometimes be an incapacitating disease with severe headache, muscle and joint and bone pains (break-bone fever), mostly in adults. Occasionally unusual haemorrhage such as gastrointestinal bleeding, hypermenorrhea and massive epistaxis occur. In dengue endemic areas, outbreaks of DF seldom occur among local inhabitants.
c. Dengue haemorrhagic fever and Dengue shock syndrome
Dengue haemorrhagic fever (DHF) is common in children less than 15 years of age residing in hyperendemic areas, in association with repeated dengue infections. However, the incidence of DHF in adults is also in increasing trend. DHF is characterized by the acute onset of high grade fever and is associated with signs and symptoms similar to that of DF in the early febrile phase of infection. Typical cases are characterized by high grade fever, haemorrhagic phenomena, hepatomegaly, and often circulatory disturbance and shock[69]. Thrombocytopenia with concurrent haemoconcentration are distinctive laboratory findings to be seen with.The major pathophysiological changes that determine the severity of DHF and differentiate it from DF and other viral haemorrhagic fevers are abnormal haemostasis and leakage of plasma selectively in pleural and abdominal cavities..By the end of the febrile phase of infection,there is a tendency to develop hypovolemic shock (dengue shock syndrome) due to plasma leakage through capillaries.The presence of warning signs such as persistent vomiting, abdominal pain(epigastric tenderness), lethargy or restlessness, or irritability and oliguria are quite important for intervention to prevent progression to shock.Abnormal haemostasis and plasma leakage are the main pathophysiological hall marks in case of DHF. Thrombocytopenia and rising trend in haematocrit/haemoconcentration are constant findings before the disppearance of fever or onset of shock.DHF occurs commonly in children with secondary dengue infection.It has also been documented in primary infections with DENV-1 and DENV-3 and in infants.
Dengue fever with haemorrhagic manifestations has to be differentiated from dengue haemorrhagic fever (DHF).
A positive tourniquet test (≥10 spots/square inch), is the most common haemorrhagic phenomenon, that may be observed in the early febrile phase. Easy bruising and bleeding and ecchymotic pathces in venipuncture sites are present in most cases. Fine petechiae scattered on the extremities, axillae, and face and soft palate can also be seen during the early febrile phase of infection. A confluent petechial rash with small, round areas of normal skin is seen during convalescence, as in dengue fever. A maculopapular or rubelliform rash may be observed either early or late in the course of illness. Epistaxis and gum bleeding are less common. Mild gastrointestinal haemorrhage is occasionally observed, however, this can be be severe in pre- existing active peptic ulcer disease. Haematuria is usually rare.
The liver is usually palpable early in the febrile phase, varying from just palpable to 2–4 cm, below the right costal margin with soft to firm consistency. Liver size is not correlated with disease severity, but hepatomegaly is more common in shock cases. The liver is tender on palpation, but jaundice not usually observed but the incidence of hepatomegaly is observer dependent. Splenomegaly is seen in infants under twelve months and by radiology examination.
A lateral decubitus chest X-ray demonstrating mostly right sided pleural effusion, is a constant finding. The extent of pleural effusion is positively correlated with severity of the illness.
Ultrasound detects pleural effusion and ascites. Gall bladder oedema is found to precede plasma leakage.
The critical phase of DHF-the period of plasma leakage, usually begins around the transition from the febrile to the afebrile phase. Evidence of plasma leakage, may not always be detectable by physical examination in the early phase of plasma leakage or in mild cases of DHF. A rising haematocrit,( 10% to 15% above baseline), is the earliest evidence.
Significant plasma leakage leads to hypovolemic shock. Even in shock cases, prior to intravenous fluid therapy, pleural effusion and ascites may not be detected clinically. Plasma leakage will be detected as the disease progresses or after fluid therapy. Radiographic and ultrasound evidence of plasma leakage precedes clinical detection. A right lateral decubitus chest radiography increases the sensitivity in detecting minimal pleural effusion. Gall bladder wall oedema may precede the clinical detection. A significantly low serum albumin >0.5 gm/dl from the baseline or <3.5 gm%
is an indirect evidence of plasma leakage.
In mild cases of DHF, the signs and symptoms subsides after the fever subsides. Fever lysis may be accompanied by diaphoresis and mild changes in pulse rate and blood pressure. These changes reflect mild and transient circulatory disturbances as a result of mild degrees of plasma leakage.
Patients recover either spontaneously or after fluid and electrolyte therapy.
In moderate to severe cases of DHF, the patient’s condition deteriorates a few days after the onset of fever. There will be warning signs such as persistent vomiting, abdominal pain, refusal of oral intake,lethargy or restlessness or irritability, postural hypotension and oliguria.At the end of the febrile phase, by the time or shortly after the temperature drops or between 3–7 days after the fever onset, there will be signs of circulatory failure: the skin becomes cool, blotchy and congested, circum-oral cyanosiscan be frequently observed, and the pulse becomes weak and rapid.Though some patients appear lethargic, they become restless and then rapidly fall into a critical stage of shock. Acute abdominal pain is a frequent and common complaint before the onset of shock.
The shock is characterized by a rapid and weak pulse with narrow, pulse pressure ≤20 mmHg with an increased diastolic pressure, e.g. 100/90 mmHg, or hypotension. Signs of reduced tissue perfusion are: delayed capillary refilling time (>3 seconds), cold and clammy skin and restlessness. Patients in shock may succumb to death within 12 to 24 hours if no prompt and
appropriate treatment is given. Patients may pass into a stage of profound shock with blood pressure and/or pulse becoming imperceptible(Grade4 DHF). It is noteworthy that most patients remain conscious almost to the terminal stage. Shock is reversible and of short duration if in time adequate treatment with volume-replacement is administered.. Patients with prolonged shock or uncorrected shock may develop metabolic acidosis and electrolyte imbalance,multiorgan dysfunction and severe bleeding from various organs and have poor prognosis and high mortality. Hepatic failure and renal failure are commonly seen in prolonged shock.
Encephalopathy can also occur in association with multiorgan failure,metabolic and electrolyte disturbances. Intracranial haemorrhage is very rare and may be a late event.
In cases with shock, a rising haematocrit and marked thrombocytopenia support the
diagnosis of DSS. A low ESR (<10 mm/first hour) during shock differentiates DengueShock Syndrome from septic shock.
GRADING ACCORDING TO SEVERITY
DF/DHF GRADE SIGNS AND SYMPTOMS LABORATORY FINDINGS
DF Fever with two of the following:
Headache.
Retro-orbital pain.
Myalgia.
Arthtralgia/bone pain.
Rash.
Haemorrhagic manifestations.
No evidence of plasma
Leucopenia (wbc ≤5000 cells/mm3).
Thrombocytopenia (Platelet count
<150 000 cells/mm3).
Rising haematocrit (5% – 10% ).
No evidence of plasma loss
leakage.
DHF I Fever and haemorrhagic
manifestation
(positive tourniquet test) and evidence of plasma leakage
Thrombocytopenia <100 000 cells/
mm3; HCT rise ≥20%
DHF II As in Grade I plus spontaneous bleeding
Thrombocytopenia
<100 000 cells/mm3; HCT rise
≥20%.
DHF(DSS) III As in Grade I or II plus circulatory failure
(weak pulse, narrow pulse pressure (≤20 mmHg), hypotension,
restlessness).
Thrombocytopenia
<100 000 cells/mm3; HCT rise
≥20%.
DHF(DSS) IV As in Grade III plus profound shock with undetectable BP and pulse
Thrombocytopenia
< 100 000 cells/mm3; HCT rise
≥20%.
c. Expanded dengue syndrome
Unusual manifestations of patients with severe organ involvement such as liver, kidneys, brain or heart associated with dengue infection is being increasingly reported in DHF and also in dengue patients who do not have any evidence of plasma leakage. These unusual manifestations may be accompanied with co-infections, co-morbidities or complications of prolonged shock.Several investigations should be done.Most DHF patients who have unusual manifestations are as a result of prolonged shock with organ failure or patients with co-morbidities or co-infections.
SYSTEM INVOLVED ATYPICAL MANIFESTATIONS
NEUROLOGICAL Febrile seizures in young children.
Encephalopathy.
Encephalitis/aseptic meningitis.
Intracranial haemorrhages/thrombosis.
Subdural effusions.
Mononeuropathies/polyneuropathies/Guillane-Barre Syndrome.
Transverse myelitis
GIT/HEPATIC Hepatitis/fulminant hepatic failure.
Acalculous cholecystitis.
Acute pancreatitis.
Hyperplasia of Peyer’s patches.
Acute parotitis.
RENAL Acute renal failure.
Hemolytic uremic syndrome
CARDIAC Conduction abnormalities-arrythmias
Myocarditis.
Pericarditis
RESPIRATORY Acute respiratory distress syndrome.
Pulmonary haemorrhage.
MUSCULOSKELETAL Myositis with raised creatine phosphokinase (CPK).
Rhabdomyolysis
LYMPHORETICULAR/BONEMARROW Infection associated haemophagocytic syndrome.
IAHS or Haemophagocytic lymphohistiocytosis
d. Convalescence in DHF
Diuresis and return of the appetite are signs of recovery and are indications to stop intravenous volume replacement. Common findings in convalescence include sinus bradycardia or arrhythmia and the characteristic dengue confluent petechial rash. Convalescence in patients with or without shock is usually short and uneventful. Even in cases with profound shock, once the shock is overcome with proper treatment the survivors will recover within 2 – 3 days but those who had prolonged shock and multiorgan dysfunction require specific treatment and experience a longer convalescence.
Clinical laboratory findings
Positive tourniquet test and leukopenia (WBC ≤5000 cells/mm3) help in making early diagnosis of with a positive predictive value of 70%–80%.[66,67]
• Total WBC which is usually normal at the onset of fever; then leucopenia develops especially neutropenia and it lasts throughout the febrile period of infection. Relative lymphocytosis with increased atypical lymphocytes is commonly seen by the end of the febrile phase and during convalescence.
thrombocytopenic purura (ITP).
Spontaneous splenic rupture.
Lymph node infarction.
EYE Macular haemorrhage.
Impaired visual acuity.
Optic neuritis
OTHERS Post-infectious fatigue syndrome, depression,
hallucinations, psychosis, alopecia
• Platelet counts are usually normal,
Mild thrombocytopenia (100 000 to 150 000 cells/mm3) is common
About half of all the DF patients have platelet count less than 100 000 cells/mm3 Severe thrombocytopenia(<50 000 cells/mm3) is rare.[68].
In addition there is impairment of platelet function
• Mild haematocrit rise (≈10%) can be seen as a result of dehydration along with high grade fever, vomiting, anorexia and poor oral intake
A sudden rise in haematocrit observed simultaneouslyor shortly after thrombocytopenia development. Haemoconcentration by 20% from the baseline is objective evidence of plasma leakage.
• Hypoproteinemia/albuminaemia (as a consequence of plasma
leakage), hyponatremia, and mildly elevated serum aspartate aminotransferase levels (≤200U/L) with the ratio of AST:ALT>2.
• A transient mild albuminuria is sometimes observed.
• Occult blood is often found in the stool.
In most cases, Reductions in fibrinogen,Prothrombin,Factor VIII, Factor XII, and Antithrombin III.A reduction in antiplasmin (plasmin inhibitor) hasseen in some cases.
In severe cases with marked liver dysfunction,reduction in the vitamin K-dependent prothrombin co-factors, such as V, VII, IX and X.
• Partial thromboplastin time and prothrombin time are prolonged in about half and one third of DHF cases respectively. Thrombin time is also prolonged in severe cases.
• Hyponatremia is frequent in DHF and is more severe in shock.
• Hypocalcemia (corrected for hypoalbuminemia)is observed in almost all cases of DHF, the level is lower in Grade 3 and 4.
• Metabolic acidosis is frequently found in those with prolonged shock.
Blood urea nitrogen is elevated in prolonged shock.
Pathophysiology:When a mosquito carrying dengue virus bites a human, the virus enters the skin along with the mosquito's saliva. Although DHF occur in patients having dengue virus infection for the first time, mostly DHF cases occur in secondary infection[77,78]
The association between occurrence of DHF/DSS and secondary dengue
Infections indicates the immune system role in the pathogenesis of DHF. Innate immunity such as the complement system and NK cells as well as the adaptive immunity including humoral and cell mediated immunity are involved in this process.[79,80]. It has been established that DHF is caused by a “Cytokine Tsunami” but despite extensive studies for more than four decades, its genesis is not fully understood. The mechanisms that have been considered to cause DHF include antibody-dependent enhancement (ADE), T cell response[73,74,75] and a shift from Th-1 to Th-2 response[76].
In severe infection, the virus production inside the body is greatly increased, and many organs like the liver and the bone marrow can be affected. Fluid from the bloodstream leaks through the wall of small blood vessels into body cavities due to increased capillary permeability followed by hypovolemia and decreased perfusion. The period of leakage is short(24–48 hours). Rapid recovery of shock without sequelae and the absence of inflammation of pleura and peritoneum indicate functional changes in vascular integrity rather than structural damage of the endothelium.
Elevated levels of complement fragments have been documented in DHF[84]. C3a and C5a are known to have permeability enhancingeffects. In recent studies, the NS1 antigen of dengue virus has shown to regulate complement system activation and may play a role in the pathogenesis of DHF[81-83] Furthermore, dysfunction of the bone marrow due to infection of the stromal cells leads to reduced numbers of platelets, which are needed for effective blood clotting; thus
increasing the risk of bleeding. Severe disease is marked by the problems of capillary permeability (an allowance of fluid and protein normally contained within blood to pass) and disordered blood clotting. Viral products such as NS1 may play a role in regulating complement activation and vascular permeability. The initial reaction of infected cells is to produce IFN- Gamma augments the production of a large group of proteins mediated by the JAK-STAT pathway. Some serotypes of dengue virus have mechanisms to slow down this process. Interferon activates the adaptive immune system also, leading to the generation of antibodies against the virus as well as T cells that directly attack any cell infected with the virus. Some of the antibodies generated bind closely to the viral proteins and target them for phagocytosis, but some bind the virus less well and appear instead to deliver the virus into a part of the phagocytes where it is not destroyed but is able to replicate further. The degrees of viral load is proportional to the disease severity such as the amount of2pleural effusions and thrombocytopenia, suggesting that the viral burden may be a key determinant of
disease severity.
Laboratory diagnosis : The following laboratory tests are available to diagnose dengue fever and DHF:
1.Virus isolation in tissue culture and sequencing[85]
Specimens for virus isolation include: acute phase serum, plasma or washed buffy coat from the patient, autopsy tissues from fatal cases (especially liver, spleen, lymph nodes and thymus), and the mosquitoes collected from the affected areas.
2. Viral nucleic acid detection
A BSL2 laboratory with equipment for molecular biology and skilled professionals are needed for RT-PCR.(a)A single tube nested PCR for detection and serotyping of DV was developed and used for detection of co-infection by two viruses[86].(b)one- step multiplex RT-
PCR.(c)real- time RT-PCR .(d) Isothermal amplification-The NASBA (nucleic acid sequence-based amplification) assay is an isothermal RNA-specific
amplification assay that does not require thermal cycling instrumentation.(e) loop mediated amplification (LAMP) PCR method has been developed, which promises
an easy-to-do and less expensive instrumentation alternative for RT-PCR and real-time PCR assays[88]
3.Viral antigen detection- NS1 is a glycoprotein gene product produced by all flaviviruses and is essential for replication and viability of the virus. The protein is secreted by mammalian cells but never by insect cells. NS1 antigen appears first day after the onset of the fever and becomes undetectable levels by 5–6 days.
ELISA and dot blot assays directed against the envelope/membrane (EM) antigens and NS1 demonstrated that this antigen is present in high concentrations in the sera of the dengue virus- infected patients during the early clinical phase of the disease and can be detected in primary and secondary dengue infections for up to six days after the onset of
the illness. Commercial kits for the detection of NS1 antigens do not differentiate between the serotypes. Besides providing an early diagnostic marker for clinical
management, it may also improve of epidemiological surveys of dengue infection.
4.Immunological response based tests[70,72]- Haemagglutination-inhibition (HI), complement fixation (CF), neutralization test (NT), IgM capture enzyme-linked immunosorbent assay (MAC- ELISA), and indirect IgG ELISA. ELISA kits prepared by National Institute of Virology, Pune and commercial kits are available[87]
.
Interpretation of dengue diagnostic test[89]
HIGHLY SUGGESTIVE CONFIRMED
One of the following:
(1) IgM+ve in a single serum sample.
(2) IgG+ve in a single serum sample with a HI titre of 1280 or greater
One of the following:
(1) RT-PCR+ve.
(2) Virus culture+ve.
(3) IgM seroconversion in paired sera.
(4) IgG seroconversion in paired sera or fourfold IgG titre increase in paired sera.
Dengue viremia exists 2 to 3 days before onset of fever to 4 to 7 days during the illness.
During this period the dengue virus, its nucleic acid and circulating viral antigen can be detected in the blood.IgM antibodies are detectable by 3–5days after the onset of illness, rise quickly by about two weeks and decline to undetectable levels after about 2–3 months.IgG antibodies are detectable at low level by the end of the first week, increase gradually and remain for many years. Because of the late appearance of IgM antibody, serological tests
based on this antibody done during the first five days of clinical illness will usually turn out to be negative.
In secondary infection ,IgG levels will be much higher and IgM levels will be lower.The ratio between IgG/IgM is is commonly used to differentiate between primary and secondary infections.
5.Analysis for haematological parameters
Thrombocytopenia, a drop in platelet count below 100 000 per μl, may be occasionally observed in dengue fever but is a constant feature in DHF. Thrombocytopenia is commonly found between the third and eighth day of illness often before or simultaneously with changes in haematocrit.Haemoconcentration with an increase in the haematocrit of 20% or more (for the same patient or for a patient of the same age and sex) is considered to be a definitive evidence of increased vascular permeability and plasma leakage
Management of dengue cases
The management of dengue cases is supportive and symptomatic. According to the severity of presentation, patients can be treated on OPD basis or as in patients.
A detailed history of illness, vital signs, Tourniquet test with CBC is to be carrued out in all patients arriving at the OPD.Decision for observation and treatment and if needed admission is for patients in high risk category,those with warning signs,severe dengue and those with shock.
Advice for home management includes
• adequate bed rest.
• Adequate intake of fluids (no plain water) such as milk, fruit juice, isotonic electrolyte solution, oral rehydration solution (ORS) and barley/rice water. Beware of overhydrationin infants and young children.
• Keep body temperature below 39 °C. If the temperature beyond 39 °C, giv paracetamol. The recommended dose is 10 mg/kg/dose and should be administered in frequencies of not less than six hours.The maximum dose for adults is 4 gm/day. Avoid too much paracetamol, and aspirin or NSAID is not recommended.
• Tepid sponging of forehead, armpits and extremities. A lukewarm shower or bath for adults.
Seek medical attention if
• No clinical improvement or worsening just before or during the transition to a febrile phase or as the disease progresses.
• Persistent vomiting, inadequate water intake.
• Severe abdominal pain.
• Lethargy and/or restlessness,giddiness, sudden behavioural changes.
• Bleeding: Epistaxis, black coloured stools, haematemesis, excessive menstrual bleeding,dark- coloured urine (haemoglobinuria) or haematuria.
• Pale, cold and clammy extremities
• Less/no urine output for 4–6 hours.
Follow up with CBC is essential to detect early danger signs
such as leucopenia, thrombocytopenia, and/or haematocrit rise during critical/afebrile phase.
Daily follow-up is required for all except those who have resumed normal activities or are normal in afebrile period.
In-patient management can be done by (1) monitoring the following;
General condition, appetite, vomiting, bleeding and other signs and symptoms.
Vital signs should be every 2–4 hours in non-shock patients and 1–2 hours in shock patients,peripheral perfusion
Serial haematocrit at least every four to six hours in stable cases and more frequently in unstable patients or those with suspected bleeding. Haematocrit should be done before fluid resuscitation. If not possible,it should be done after the fluid bolus but not during the infusion of the bolus.
Urine output (amount of urine) at least every 8 to 12 hours in uncomplicated cases and hourly basis in patients with profound/prolonged shock orthose with fluid overload
Additional tests-Blood glucoseBlood gas analysis, lactate,Serum electrolytes and BUN, creatinine, Serum calcium,Liver function test, Coagulation profile, Right lateral decubitus chest radiograph (optional),Group and match for fresh whole blood or fresh packed red cells,Cardiac enzymes or ECG if indicated, especially in adults,Serum amylase and ultrasound if abdominal pain does not resolve with
fluid therapy.Any other test, if indicated.
(2)Intravenous fluid therapy and supportive measures Management in DHF during the critical period Indications for IV fluid in the patients are;
• when the patient is not able to have adequate oral fluid intake or is having vomiting episodes.
• when haematocrit continues to rise 10%–20% despite oral rehydration.
• impending shock/shock.
Isotonic crystalloid solutions should be used throughout the critical period except in infants <6 months of age in whom 0.45% sodium chloride is used.
Hyper-oncotic colloid, such as dextran 40 or starch solutions can be used in patients with massive plasma leakage, and those not responding to the minimum volume of crystalloid (as recommended below). Iso-oncotic colloid solutions such as plasma or hemaccel may not be effective. A volume of about maintenance +5% dehydration to be given to maintain a “just
adequate” intravascular volume and circulation. The duration of intravenous fluid therapy should never exceed 24 to 48 hours for those with shock. However, for those patients who are not in shock, the duration of intravenous fluid therapy may be longer but never more than 60 to 72 hours because the latter group of patients has just entered the plasma leakage period while shock patients had a longer duration of plasma leakage before intravenous therapy is begun.
Requirement of fluid based on ideal body weight
IDEAL BODY WEIGH T (Kgs)
MAINTENANCE (ml)
M+5%
DEFICIT(ml)
IDEAL BODY WEIGHT(Kgs)
MAINTENANCE (ml)
M+5% DEFICIT(ml)
5 500 750 35 1800 3550
10 1000 1500 40 1900 3900
15 1250 2000 45 2000 4250
20 1500 2500 50 2100 4600
25 1600 2850 55 2200 4950
30 1700 3200 60 2300 5300
Rate of IV fluid in adults and children
NOTE CHILDREN RATE(mg/kg/hr) ADULT RATE(ml/hr)
Half the maintenance M/2 1.5 40-50
Maintenance (M) 3 80-100
M+5% DEFICIT 5 100-120
M+7% DEFICIT 7 120-150
M+10% DEFICIT 10 300-500
Management of patients with warning signs
It is important to verify if the warning signs are due to other causes such as acute gastroenteritis, vasovagal reflex, hypoglycemia, etc. IV fluids and supportive and symptomatic treatment should be given while these patients are under observation in hospital.
Theycan be sent home within 8 to 24 hours if they show rapid recovery and are not in the critical period(i.e. when their platelet count is >100 000 cells/mm3).
Fluid management in critical phase in haemodynamically stable patients is given in graph below
Management of DHF-grade 1 and 2 is given in the table below
Management of severe haemorrhage
Source of bleeding should be stopped immediately. If the amount of blood lost is known,replace it else aliquots of 10 ml/kg of fresh whole blood or 5 ml/kg of freshly packed red cells should be transfused and response evaluated. The patient may require one or more aliquot
In gastrointestinal bleeding, H-2 antagonists and proton pump inhibitors have been used, but no proper study is there to show its efficacy.
No evidence to support the use of blood components such as platelet concentrates, fresh frozen plasma or cryoprecipitate. Its use could contribute to fluid overload.
Recombinant Factor 7 might be helpful in some without organ failure, but it is quite expensive and not available easily
Management of high-risk patients
Avoid excessive IV fluid infusion in obese patients, Infants, Cardiac patients
Amount and rate of IV fluid for pregnant women is similar to those for non-pregnant woman using pre-pregnant weight for calculation. Combined management of multiple specialities is essential in case of pregnant women.
Antocoagulant therapy should be stopped temporarily in critical period
In diabetics, IV insulin for glycaemic control,non sugar containing IV fluids to be given The baseline blood pressure of patients with hypertension who are on anti-hypertensive therapy that masks the cardiovascular response in shock has to be considered for fluid infusion.
Patients with Haemolytic diseases and haemoglobinopathies are at risk of haemolysis and will require blood transfusion. Caution should accompany hyperhydration and alkalinization therapy, which can cause fluid overload and hypocalcemia.
Those on steroid can continue the therapy but in a different route Management of convalescence
• Intravenous fluid should be discontinued.
• In those with massive effusion and ascites, hypervolemia may occur and diuretic therapy may be necessary to prevent pulmonary oedema.
• Hypokalemia due to stress and diuresis and should be corrected with potassium-rich fruits or supplements.
• Bradycardia is commonly found and requires intense monitoring for possible rare complications such as heart block or ventricular premature contraction (VPC).
• Convalescence rash is found in 20%–30% of patients Management of complications
(1). Volume overload
In the early stage of fluid overload, switch from crystalloid to colloid solutions as bolus fluids. Dextran 40 may be used with the dose restricted to 30 ml/kg/day because of its renal effects.
In the late stage of fluid overload or those with frank pulmonary oedema but in shock colloid at the rate of 10ml/kg/h of colloid can be given. When the blood pressure is stable, usually within 10 to 30 minutes of infusion, administer IV 1 mg/kg/dose of furosemide and continue with dextran infusion until completion with continuous monitoring of vitals. Intravenous fluid has to be reduced to as low as 1 ml/kg/h until discontinuation when the haematocrit
decreases to baseline or below along with clinical improvement. In cases with no improvement with furosemide (no urine obtained), repeated doses of furosemide and doubling of the dose can be attempted. If oliguric renal failure is established, renal replacement therapy is to be done as soon as possible. These cases carry poor prognosis.
• Therapeutic thoracocentesis or parecentesis may be indicated and can be life-saving in cases withsevere respiratory distress and failure of the above management but with caution
(2). Encephalopathy
Usually encephalopathy manifest as convulsions or coma and may be due to hyponatremia, Intracranial haemorrhage or occlusion associated with DIC.
In those with encephalopathy,
a.Maintain adequate airway oxygenation with oxygen therapy Prevent/reduce ICP b. Decreae ammonia production by giving lactulose to promote osmotic diarrhea c. Maintain blood sugar level at 80–100 mg/dl per cent
d. Correct acid-base and electrolyte imbalance
e. Vitamin K1 IV administration; 3 mg for <1-year-old, 5 mg for <5-year-old and 10 mg for>5-year-old and adult patients
f. Anticonvulsants g. H2 blockers
h. Transfuse blood, preferably freshly packed red cells, as indicated. Platelets and fresh frozen plasma transfusion may not be given because the fluid overload and may cause increased ICP.
i. Empiric antibiotics to be given if there are suspected superimposed bacterial infections.
j.Plasmapheresis or h aemodialysis or renal replacement therapy in cases with
clinical deterioration.
Criteria for discharging patients
• Absence of fever for at least 24 hours without the use of antipyretic therapy
• Return of appetite.
• Visible clinical improvement.
• Satisfactory urine output.
• A minimum of 2–3 days have elapsed after recovery from shock.
• No respiratory distress from pleural effusion and no ascites.
• Platelet count of more than 50 000/mm3. If not, patients can be recommended to avoid traumatic activities for at least 1–2 weeks for platelet count to become normal. In mostcases, platelet rises to normal within 3–5days
Preventive measures
1.VECTOR SURVEILLANCE
Larval survey- Four indices commonly used to monitor Ae aegypti infection levels are:
a.House index (Hl): percentage of houses infected with larvae and/or pupae HI = Number of Houses infected Number of Houses inspected X100
b.Container Index (Cl): percentage of water holding containers infected with larvae or pupae.
Cl = Number of positive containers Number of containers inspected X100 c.Breteau Index (Bl): number of positive containers per 100 houses inspected
Bl: Number of positive containers Number of houses inspected X100 d.Pupae Index (Pl): number of pupae per 100 houses
Pl = Number of pupae Number of houses inspected X100
Adult surveys: i) Landing/biting collection.ii) Resting collection iii) Oviposition traps
Vector management:
ENVIRONMENTAL MANAGEMENT
(i) Environmental modification: improved water supply, mosquito proofing of overhead tanks, cisterns or underground reservoirs.
(ii) Environmental manipulation: management of ìessentialî and ìnon-essentialî containers and management of or removal of ìnaturalî breeding sites.
(iii) Changes in human habitations: reduce man-virus contact by mosquito proofing of houses with screens on doors/windows
PERSONAL PROTECTION
Protective clothing and repellents against mosquitoes and other biting insects.
