The Ulutas Medical Journal p-ISSN 2149-0430 e-ISSN 2149-388X

The Ulutas Medical Journal · ISSN 2149-0430 (print), 2149-388X (online) · https://www.ulutasmedicaljournal.com/?mno=268883

Review Article · Open access

Dengue Viral Infection and Necessity for Screening Patients Having Pyrexia of Unknown Origin

  • Humaira Zafar1
  • Kiran Tauseef Bukhari2
  • Sadaf Humayoun3
  • Nouman Noor4
  • Noor Khan Lakhnana5
  1. Pathology Consultant Microbiologist, Al Nafees Med College Isra University, Islamabad Campus, Pakistan ROR
  2. Pathology Consultant Haematologist, Al Nafees Med College Isra University, Islamabad Campus, Pakistan ROR
  3. Rawal Dental College, Rawal Institute of Health Sciences, Islamabad, Pakistan ROR
  4. Operative Dentistry, Rawal Dental College Rawal Institute of Health Sciences, Islamabad, Pakistan ROR
  5. Pathology Consultant Histopathologist, Al Nafees Med College Isra University, Islamabad Campus, Pakistan
Download PDF (257.2 KB) How to cite doi:10.5455/umj.20170608022332

Abstract

Dengue Viral Infection (DVI) is an emerging global health problem infecting about 50-100 million people annually worldwide. More than 2.5 million people have dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Aedesaegypti is the principal vector for disease transmission while humans are the main reservoir. The clinical manifestations range from self-limited Dengue fever (DF) to complicated and fatal outcomes, DHF and DSS. DF is prevalent in more than 100 countries of the world. More than 2.5 billion people of the World's population are residents of Dengue endemic area. According to one reported study, the prevalence of DF in Pakistan is 29%. Similarly, one study result carried out in India has shown 78% prevalence of DF. In Mexico, the one published seroprevalence study showed 79.6% prevalence of DF. A review/analysis report of the Gynecological and Obstetrical survey from 30 published studies has shown 64% transmission rate of DF from a mother to a child. The study results carried out in Jamaica has shown an increase in the prevalence of DF in seen in less than 1year and more than 60 years. The mortality rate with DHF is 33%. While in less than 15 years of it is 5%. This can be only reduced with early/accurate diagnosis and the prompt management of the condition. The absence of specific vaccine and antiviral is responsible for making this infection as a global health problem. The US government has spent 15 million US dollars for the establishment and discovery of specific DF treatment. The study carried out in India has shown the median cost for treatment per patient about 432.2 US dollars. It is 4 times in case of private health sectors. The proposed review article will highlight the incidence of dengue infection in patients having PUO (pyrexia of unknown origin). It will be a guide for the clinicians to consider DVI in their list of differential diagnosis of PUO. Moreover, it will be helpful in establishing the screening policies for DVI in PUO. The resultant of all of this will improve the life quality of PUO sufferers. It will be useful to reduce the increased financial burden due to PUO missed diagnosis and management in underdeveloped countries like one of ours.

Keywords

Full text

Introduction

Break Bone Fever

The word dengue has been derived from a Spanish word meaning Fastidious or Careful. An American physician Benjaman Rush first gave Dengue fever a name Break Bone fever or Bone Crush Disease. This is attributed to the major complications of disease i.e. myalgias and arthralgias (1–3). Dengue virus belongs to genus flavivirus (4). According to the WHO report it is amongst the most common causes of arboviral diseases worldwide (5, 6).

Vector of Disease

Aedesaegypti is the principle vector in the transmission of disease. This special mosquito is well adapted to humans and prefers to live in clean surroundings in close proximity to humans. Aedesaegypti is the small sized mosquito in comparison to the other mosquitoes. It is black colored with white stripes on head and body. There are specific white rings on the legs. Male Aedesaegypti population is harmless to humans and usually lives on fruits. Female Aedesaegypti are the ones responsible for disease transmission. It sucks blood from one person and transmits to another by biting.The infection develops within 24-30 hours of biting. This pathway between man-vector-man makes a triad of disease (5). Aedesalbopictus is a lesser vector of dengue viral infection. Few cases with this vector have

Dengue Virus Genotype And Virulence

In Malaysia DEN 4 serotype is the most common disease causing one (9). While in Pakistan DEN 2 serotypes predominates followed by DEN 3 serotype (10). The infection with any one serotype provides the immunity against that specific serotype (11). Ab produced in result of infection with any serotype usually provides the homotypic immunity (12).

LITERATURE REVIEW

Dengue In Pakistan

In 1994 first outbreak of DHF occurred at Karachi, Pakistan. In 1995, second outbreak occurred in Baluchistan. In 2002, educational programmes for Aedesaegypti mosquitoes were established (13). In Rawalpindi, from September to November 2008, 49 positive cases were detected. Out of which 23 reported at Benazir Bhutto Hospital and 26 at Holy Family Hospital (14).

been recorded in Pakistasn and USA (5). Predisposing Factors

Pathogenesis of Dengue Infection

Dr.Albert Sabin in1944 isolated and detected four serotypes of DV. DEN 1, 2, 3 and 4 are the well known ones for DVI. These serotypes are responsible for the production of serotype specific IgG Ab mediated protective immunity following the first infection(7). Extrinsic Incubation Period: During these period mosquitoes acquire virus while feeding on the viremic humans. Viral replication starts in the salivary glands of Aedes. This is called as Extrinsic I/P. The mosquitoes remain infected until 65 days of their lifespan. Intrinsic Incubation Period: There are two types of serological responses seen in DVI patient i.e primary and the secondary one. A primary response is seen in those who are not immune to the Flaviviruses. While secondary response is seen in those who had previous flaviviral infection. Thus responsible for pathogenesis of DF, DHF and DSS (5, 8). The immune status, age of patient, type of virus infecting, climatic change, unplanned urbanization, increase in the international trade and increase in air travel. All of these provide an ideal way of transporting virus to new areas (15). Moreover lack of awareness and knowledge especially in low socioeconomic class contributes to the spread of disease (16). The WHO report of the year 2007 had highlighted DF a great threat for travelers (17). The appropriate education to the travelers can be helpful to reduce arthropod borne diseases (18).

Dengue A Global Health Problem

DF is prevalent in more than 100 countries of the world (19). More than 2.5 billion people of the World’s population are residents of Dengue endemic area (20). Currently there is no vaccine or specific anti viral drugs/ injections available for the treatment of DF. Thus, making it a global health problem (21, 22).

Commonly Affected Age Groups

A study report on Jamaican population has shown that DF usually affects less than 1 year and more than 60 years of age group (23). A study in Bangladesh concluded that adults are frequently infected by DV (24). WHO report has shown that DF is a febrile illness which mostly affects the infants, young children and the adults (25).

Vertical Transmission of DVI

A case report in Bangkok has shown that DVI can be vertically transmitted from a mother to 1 day old infant (26). Another study carried out in Kuala Lumpur has shown that vertical transmission rate of DF is 1.6% (27). A systematic review report of 30 published studies by gynecological and obstetric survey2010 has shown vertical transmission rate of 64% (28).

Clinical Manifestations of DVI

These ranges from self limited DF to DHF and DSS (29). DF/DHF are amongst important differential diagnosis in an undifferentiated febrile illneses (30). The fever could be of biphasic pattern (31). WHO definition of DHF requires filling of criteria: a;fever,bladder problem, constant severe headache, dizziness and loss of appetite. b; Haemorrhagic tendency, i.e. positive tourniquet test, spontaneous bruising, bleeding from mucosa, gingival, injection site etc, menorrhagia, bloody vomiting, malena or bloody diarrhea. c; Thrombocytopenia i.e. less than 100,000/mm3 platelets. d; Hemoconcen-teration i.e. evidence of plasma leakage and hematocrit >20% of expected following I/V fluids, pleural effusion, ascities or hypoproteinemia (32, 33, 35). DSS is defined as DHF plus weak and rapid pulse, narrow pulse pressure <20 mmHg, cold and clammy skin and restlessness (1–3).

Mortality Rate of DHF/ DSS

It is 5% in less than 15 year of age group (34). While the estimated overall mortality rate with this infection is 33% (35). The mortality rates can be decreased by early diagnosis and prompt management of the condition (36). A study carried out on the citizens residing in Puerto Rico, United States, has shown that the infants and 10 to19 years of age group are amongst those who usually harbor the severe outcomes of DF (37).

DVI and PUO

A study result carried out in Singapore on Chinese migrant workers hospitalized due to febrile illness since a month. The serological results have shown the prevalence of acute Dengue in 10% of patients. The most common serotype was DEN 2 (38). Another study results carried out in United Kingdom had shown that DVI can present as undifferentiated fever (39). A study carried out on children between 6 months to 12 years in Lucknow, India has shown that DVI can cause undifferentiated febrile illness (40). The Cuban Government had declared two Dengue outbreaks showing the presence of febrile illness as initial presentation in 3.2% of the total diagnosed cases (41). In Thailand population the estimated prevalence of DF in patients having PUO is 40.8% (42).

Diagnosis of DVI and ELISA

Serologiacal tests, viral isolation and molecular level detection are the three options for DV detection (44). ELISA is considered to be 99.2% sensitive and 96.2% specific for DF virus IgG detection (45). The Dengue virus IgG antibodies in the serum are not affected by the duration of storage (46).

Cross Reacting Antibodies Formation

The high degree of cross reactivity between flaviviruses can result in false positive serological results. The booster for Yellow fever immunization is 10 years, for Tick borne encephalitis is 3 years and for Japanese encephalitis is 2 years (41, 47, 48).

Dengue Prevention

The laboratory based surveillance and daily correspondence between epidemiologists and infectious disease units will provide a proactive approach for the prevention and control of disease in specific regions of the world (49).

Conclusion

One of the early presentations of primary dengue viral infection is PUO especially in less than 18 years of age. So that the Government should mainly focus on the particular age group. This study will be helpful for the clinicians to consider DVI in their list of differential diagnosis of PUO.

Recommendations

Screening of Dengue viral infection should be done in patients having pyrexia of unknown origin.

Declarations

Author contributions (CRediT)
All authors contributed equally to all 14 CRediT roles (Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing).
Funding

Funding information was not reported in the published version of this article.

Conflicts of interest
A conflict of interest statement was not reported in the published version of this article.
Ethics approval
Ethics committee approval was not required for this article, as it is based on previously published literature and does not involve human participants, patient data or animals.
Data availability
Data sharing is not applicable to this article as no new data were created or analysed in this study.

References (49)

14 of 49 references are linked to their DOI.

  1. Stephen JP. Dengue ‘Break Bone’ Fever: Will it spread like West Nile Virus? EEM. 2008; 30(3): 14-16. PubMed Google Scholar
  2. Reed W. New U.S army mosquito control technology licensed for deployment against dengue.Website:www. medicalnewstoday.com/articles/130061.php. Retrieved on th April 2011. PubMed Google Scholar
  3. Gubler DJ. WHO Dengue Bulletin [homepage on Internet]. Dengue/Dengue Hemorrhagic Fever.1997; 21. Website: http://www.searo.who.int/Section10/Section332/section51 9_2380.htm. PubMed Google Scholar
  4. Smith AW, Chen LH, Massuda E, Wilson ME. Threat of Dengue to blood safety in Dengue endemic country. Web site:http://www.medscape.com/viewarticle/586772. Retriev on 14 th July 2009. PubMed Google Scholar
  5. Heyman D, Chakarborty T. Deadly diseases and epidemics. Dengue Fever and other hemorrhagic viruses. WHO 2008 (InfoBase Publishing. PubMed Google Scholar
  6. Osman O, Fong MY, Sekaran SD. Genetic characterization of Dengue virus type 1 isolated in Brunei in 2005-6. J Gen Virol. 2009; 90: 678-86. DOI Crossref PubMed Google Scholar
  7. Egger JR, Ooi EE, Kelly DW, Woolhouse MK, Davies CR, Coleman PG. Reconstructing historical changes in the force of infection of DF in Singapore: Implications for surveillance and control. WHO Bull. 2008; 86(3): 161-240. DOI Crossref PubMed Google Scholar
  8. Shu PY, Huang JH. Curent advances in Dengue diagnosis. Clin and Diagnos Lab Immunol. 2004; 11(4): 642-50. PubMed Google Scholar
  9. Bakar SA, Wong PF, Chan YF. Emergence of Dengue virus type 4 genotype in Malaysia. J Gen Virol. 2002;83:2437-42. PubMed Google Scholar
  10. Khan E, Hassan R, Mehraj V, Nasr A, Siddiqui J,Hewson R. Co circulation of two genotypes of Dengue virus in 2006 out break of DHF in Karachi, Pakistan. J ClinVirol. 2006; 43(2): 176-9. PubMed Google Scholar
  11. Jacquelin L, Harris E, Wills B, Balmaseda A, Nadia S, Rocha C et al.The WHO Dengue classification and case definitions: Time for reassessment. The Lancet. 2006; 368: 170-3. PubMed Google Scholar
  12. Schieffelin JS, Costin JM, Nicholson CO, OrgeronNM, Fontaine KA, Isern S et al. Neutralizing and non neutralizing monoclonal antibodies against Dengue virus E protein derived from a naturally infected patient. Virol J. 2010; 7: 28. DOI Crossref PubMed Google Scholar
  13. Almani SA, Rahpoto MQ, Shah MI, Shaiku M, Memon AI. Dengue fever at Liaquat University Jamshoro, Sindh, Pakistan. Med Channel. 2008; 14: 2. PubMed Google Scholar
  14. Muhammad Qasim. 49 DF cases reported in Rawalpindi 5 expired. THE NEWS. Saturday 1st Nov 2008. PubMed Google Scholar
  15. Smith AW, Schwuartz AW. Dengue in travelers. N Eng J 2005; 353: 924-32. PubMed Google Scholar
  16. Madiha S, Syeda UR, Habiba M, Zahid R, Bashir A, Rabbani M, et al. Knowledge, attitudes and practices regarding DF among adults of high and low socioeconomic groups. JPMA. 2010; 60: 243. PubMed Google Scholar
  17. Wichmannn O, Gascon J, Schmunk M, Velez RL, Clerinx J, Kern P, et al. Severe DVI in travelers. J Infect Dis. 2007; 195: 1089-96. PubMed Google Scholar
  18. Christine e, Waasdorp. Preparing children for travel in Asia. WMS. 18(3): 222-9. DOI Crossref PubMed Google Scholar
  19. Pandey BD, Morita K, Raj S, Tomo K, Ogawa MT, Inobu S, et al. Dengue virus, Nepal. EmergInfect Dis.2008;14 (3): 514-15. DOI Crossref PubMed Google Scholar
  20. Saone NS. Sanofi Aventis builds Dengue fever vaccine plant. Website: http: //www.pr- inside.com/sanofi-aventis-builds-dengue-fever-vaccine r1246621.htm. Retrieved on 12th May 2010. PubMed Google Scholar
  21. Rathor HR. The role of vector in emerging and re-emerging infectious diseases in the Eastern Mediterranean region. Med East Health J. 1996; 2(1): 61-7. PubMed Google Scholar
  22. Hapugoda MD, Barta G, Abeewickreme W, Swaminathan S, Khanna N. Single Antign detects both immunoglobulin M and IgG antibodies elicited by all four dengue virus serotypes. Clin Vaccine Immunol.2007;14(11):1505-14. DOI Crossref PubMed Google Scholar
  23. Brown MG, Vickers IE, Salas RA, Smikla MF. Patterns of dengue virus IgM and IgG antibodies in suspected cases of dengue infection, Jamaica, 2003-2006. Human Ab J. 2009; 18(1-2):29-34. DOI Crossref PubMed Google Scholar
  24. First outbreak of DHF, Bangladesh: Conclusion. Website: http://medscape.com/view article/4374373. Retrieved on th March 2010. PubMed Google Scholar
  25. WHO, Dengue. Website:http:// who.int/topics/dengue/en]. Retrieved on 3 rd March 2010. PubMed Google Scholar
  26. Petdachai W, Sila OJ, Ninimannitya S, Nisalak A. neonatal dengue infection: report of DF in aone day old infant.Obstet and Gyne. 2004; 35(2). PubMed Google Scholar
  27. Chiong TP, Geetha R, Shamala D, Zawiash OS. Dengue infection in pregnancy. Prevalence, Vertical transmission and pregnancy outcome. Obstet and Gyne. 2008; 111(5): 1111-7. PubMed Google Scholar
  28. Sawyer HP, Xiong XU, Emily H, Valerie PS, Kay MT, Gerard B. Maternal dengue and pregnancy outcomes: A systemic review. Obstet and Gyne. 2010; 65(2): 107-18. Dengue Viral Infection and Necessisty for Screening Humaira Zafar, et al. PubMed Google Scholar
  29. Khanna S, Vij JC, Kumar A, Singal D, Tandon R. Dengue fever is a differential diagnosis in patients with fever and abdominal pain in an endemic area. Trop Med and Parasitol. 2004; 98(7): 757-60. DOI Crossref PubMed Google Scholar
  30. Itoda I, Masuda G, Suganuma A, Imamura A, Ajisawa A, Yamada KI etal. Clinical features of 62 imported cases of Dengue fever in Japan. Am J Trop med Hyg. 2006; 75(3): 470-4. DOI Crossref PubMed Google Scholar
  31. Dengue Fever. Website: http://www.symptoms101.com/ med/archives/2005/05/denguefever.php. Retrieved on 20 th March 2010. PubMed Google Scholar
  32. eMedicine. Dengue fever. Pennsylvania. Shepherd SM. Retrieved on 20 th March 2010. PubMed Google Scholar
  33. Siqueira JB, Maria C, Martelli T, Coelho GE. Dengue and dengue hemorrhagic fever. Brazil, 1981-2002. Emerg Infect Dis. 2005: 11(1). DOI Crossref PubMed Google Scholar
  34. Noisakran S, Perng GC. Alternate hypothesis on the pathogenesis of DHF/ DSS and Dengue viral infection. ExpBiol Med. 2008; 233(4): 40-8. PubMed Google Scholar
  35. Kabra SK, Verma IC, Arora NK, Jain Y, Kalra V. Dengue hemorrhagic fever in children in Delhi. WHO Bull.1992; 70 (1): 105-8. PubMed Google Scholar
  36. Trantracheewathorn T, Trantracheewathorn S. risk factors for Dengue shock syndrome in children. J Med Assoc Thai. 2007; 90(2): 272-7. PubMed Google Scholar
  37. Tomashek KM, Rivera A, Jordan JL, Hunsperger E, Santiago L, Padro O. Description of a large island-wide outbreak of Dengue in Puerto Rico, 2007. Am J Trop Med Hyg. 2009; 81(3): 467-74. DOI Crossref PubMed Google Scholar
  38. Seet SC, OoiEE,Wong HB, Paton NI. An outbreak of primary dengue infection amongst migrant Chinese workers in Singapore characterized by prominent GI symptoms and ahigh proportion of symptomatic cases. J ClinVirol. 2005; 33(4): 336-40. DOI Crossref PubMed Google Scholar
  39. Malavige GN, Fernando S, Fernando DJ, Seviratne SL. Dengue viral infection. Postgrad Med J. 2004; 80: 588-601. PubMed Google Scholar
  40. Kumar R, Tripathi P, Tripathi S, Kanodia A, Pant S, Venkatesh V. Prevalence and clinical differentiation of DF in children in Northern India. Infect. 2008; 36(5): 444-9. PubMed Google Scholar
  41. Virology online. Flaviviruses. Website: http://virology. online.com/viruses/Arboviruses 4 htm]. Retrieved on 15 th April 2010. PubMed Google Scholar
  42. Mundy LM. Cuban study. Prior Dengue infection means risk for symptomatic reinfection. J Watch Infect Dis. 2001; 1. Available from: http://infectious -diseases.jwatch.org/cgi/ content/full/2001/111/3. PubMed Google Scholar
  43. Jitana P, Sukone P, Marisa K, Kamkarn S. The etiology of acute pyrexia of unknown origin in children after a flood. Southeast Asian J Trop Med and Public Health. 2003; 34(1): 175-8. PubMed Google Scholar
  44. Wichmann O, Stark K, Shu PY, Niedrig M, Frank C, Huang JH. Clinical features and pitfalls in the laboratory diagnosis of Dengue in travelers. BMC Infect Dis. 2006; 6: 120. DOI Crossref PubMed Google Scholar
  45. Smith AW, Foo W, Earnest A, Sremulanathan S, Nicholas I. Seroepidemiology of Dengue in the adult population of Singapore. Trop Med and Int Health. 2004; 9(2): 305-8. PubMed Google Scholar
  46. Tran TN, Vries PJ, Hoang LP, Phan GT, Le HQ, Tran BQ et al. Enzyme Linked Immunoassay for Dengue virus IgM and IgG antibodies in serum and filter paper blood. BMC Infect Dis. 2006; 6: 13. DOI Crossref PubMed Google Scholar
  47. Patient UK.Tick borne encephalitis vaccination. Website: http://www.patient.co.uk/doctor/Tick.borne.EncephalitisVa ccination.htm. Retrieved on 4th April 2010. PubMed Google Scholar
  48. Travel and Health VaccClin. Information on Japanese encephalitis. Vancouver Canada. Website: http://www. doctortravel. Ca/index.php? Page = Japanese encephalitis. Retrieved on 4 th April 2010. PubMed Google Scholar
  49. Fisher D. The vector borne, mosquito transmitted diseases in Singapore. Singapore Med J. 2005; 46 (11): 596. PubMed Google Scholar

Respond to this article

Comments on a published article are welcome as a Letter to the Editor.

Write a letter to the editor

Get an e-mail when new articles in your fields are published

Questions to the authors

Questions are moderated: an editor approves each question, the authors answer, and an editor approves the answer before both appear here.

No answered questions yet.

Ask the authors a question

Discussion

Comments are moderated: they appear after the writer confirms the e-mail address and an editor approves them. Each comment carries a conflict-of-interest statement.

No comments yet.

Write a comment

Read the full text

Open the PDF here

Loading the PDF…

If the PDF does not show here, use the download button above.

How to cite this article

Zafar H, Bukhari KT, Humayoun S, Noor N, Lakhnana NK. Dengue Viral Infection and Necessity for Screening Patients Having Pyrexia of Unknown Origin. Ulutas Med J. 2017;3(3):49-53. doi:10.5455/umj.20170608022332

Zafar, H., Bukhari, K. T., Humayoun, S., Noor, N., & Lakhnana, N. K. (2017). Dengue Viral Infection and Necessity for Screening Patients Having Pyrexia of Unknown Origin. The Ulutas Medical Journal, 3(3), 49–53. https://doi.org/10.5455/umj.20170608022332

Zafar, H. et al. (2017) 'Dengue Viral Infection and Necessity for Screening Patients Having Pyrexia of Unknown Origin', The Ulutas Medical Journal, 3(3), pp. 49–53. doi: 10.5455/umj.20170608022332.

RIS (EndNote, Zotero) BibTeX JATS XML
Embed this article on your site

Paste this code into your page. The card shows the title, authors and DOI and links back to the article.

WhatsApp Tell the Editor
Submit manuscript Contact