This study examined the relationship between atypical lymphocytes, large immature cells, platelet counts, and hematocrit in 79 patients with dengue virus infection. The results showed that increases in the percentage of atypical lymphocytes were associated with decreases in platelet count, suggesting atypical lymphocytes may play a role in platelet count fluctuations in dengue. A similar relationship was found between large immature cells and platelet count. The study supports the potential of atypical lymphocytes and large immature cells as predictive markers of the hematological changes seen in dengue, such as low platelet counts and increased hematocrit. However, limitations include the retrospective single-center design and lack of effective prognostic markers for vascular leakage in dengue.

1. UTILITY OF ATYPICAL LYMPHOCYTES
AND LARGE IMMATURE CELLS IN
PREDICTION OF DENGUE SEVERITY
MODERATOR :- DR. NAHIL NAJFI
SENIOR RESIDENT ,KIMS KOPPAL
STUDENT:- DR. SRINIVAS B J
POSTGRADUATE RESIDENT
KIMS KOPPAL

2. • PUBLISHED IN :- JOURNAL OF THE ASSOCIATION OF PHYSICIANS OF INDIA (2023)
• PUBLISHED ON :- NOVEMBER 2023
• AUTHORS AFFILATIONS; RAMADEVI PERAKA1*, ADITYA KOPPULA2 , BABY SHALINI MUPPALA3 , MANI M
PARSA 1 ASSOCIATE PROFESSOR, DEPARTMENT OF PATHOLOGY, APOLLO INSTITUTE OF MEDICAL SCIENCES &
RESEARCH, APOLLO HEALTH CITY CAMPUS; 2 RESEARCH SCHOLAR, DEPARTMENT OF BIOMEDICAL
ENGINEERING, INDIAN INSTITUTE OF TECHNOLOGY; 3 ASSOCIATE PROFESSOR, DEPARTMENT OF INTERNAL
MEDICINE; 4 PROFESSOR, DEPARTMENT OF PATHOLOGY, APOLLO INSTITUTE OF MEDICAL SCIENCES &
RESEARCH, APOLLO HEALTH CITY CAMPUS, HYDERABAD, TELANGANA, INDIA; * CORRESPONDING AUTHOR
• STUDY TYPE: SINGLE CENTRE RETROSPECTIVE STUDY
• STUDY DURATION ; OCTOBER 2019 TO 2022
• STUDY PLACE : APOLLO INSTITUTE OF MEDICAL SCIENCES & RESEARCH, APOLLO HEALTH CITY CAMPUS,
HYDERABAD, TELANGANA, INDIA

3.  INTRODUCTION
 NEED FOR THE STUDY
 METHODOLOGY
 RESULTS
 DISCUSSION
 LIMITATIONS
 STRENGTHS OF THE STUDY
 CONCLUSION
 CRITICAL ANALYSIS
 APPLICABILITY IN OUR SETUP

4. INTRODUCTION
 Dengue is a mosquito -borne viral hemorrhagic fever caused by the Dengue virus, a
flavivirus. It is transmitted by the bite of infected Aedes mosquitoes.
 390 million dengue virus infections globally every year, of which 96 million show
clinical manifestations and approximately 40,000 succumb to the disease annually.
 In India, 7,95,211 cases were reported, with 1,151 fatalities for 2017–2022,
 Four predominant serotypes (DEN-1, 2, 3, 4) The virus is endowed with three structural
proteins (capsid C, membrane M, and envelope E) and seven nonstructural (NS)
proteins.

5. • Primary infection induces lifelong immunity specific to the causal serotype
• Second infection by a different serotype is thought to increase the risk for severe dengue
• Virus thrives inside the cell, creating an inflammatory cascade that culminates in the cardinal
features of severe dengue, viz, vascular leakage, fluid accumulation, thrombocytopenia, shock,
MODS, DIC and potential death
• Crossreactive T cells, NS1 antigen, antidengue virus NS1 antibodies, and autoimmunity
contribute to the pathophysiology of dengue complications

6. • natural history of dengue fever has three stages/phases
(1) the acute febrile phase
(2) the critical phase following the defervescence
(3) the recovery phase
• Severe dengue with all attendant complications generally occurs after the febrile phase in the
critical stage when the hematocrit rises and the platelets fall

8. NEED FOR THE STUDY
(1) Determine time trends in hematological parameters
indicative of pathophysiological features of severe dengue,
viz, plasma leakage (rising hematocrit) and
thrombocytopenia,
(2) Determine the association of the longitudinal patterns in
atypical lymphocyte and large immature cell with time
trends in platelet counts and hematocrit.

9. METHODOLOGY
• STUDY DESIGN:
Retrospective data analysis was done on (n = 79) consecutive dengue patients
hospitalized between October 2019 to 2022

10. METHODOLOGY
STUDY POPULATION:-
NS1 antigen and immunoglobulin M antibody POSITIVE PATIENTS (Enzyme-linked
immunosorbent assay confirmed)
Inclusion criteria :-
 NS1 antigen and immunoglobulin M antibody POSITIVE PATIENTS (Enzyme-linked
immunosorbent assay confirmed)

11. EXCLUSION CRITERIA:-
 ELISA NEGATIVE NS1 antigen and immunoglobulin M antibody POSITIVE PATIENTS

13. RESULT
• Every 1% increase in atypical lymphocyte percentage is
associated with a decrease in platelet count by 16,963
cells/mm3 . This suggests that the ATY may play a causal role
in the platelet count fluctuations in dengue.
• A similar albeit weaker relation was found between platelet
count and LIC, with a platelet count fall by 6,680 cells/mm3
for every 1% rise in LICs

18. DISCUSSION
 To Explore the predictors of platelet counts, focusing on the ATY and large immature
cell fraction data from 79 patients
 Atypical lymphocytes fluctuated in lock-step with the platelet count but in an
anticorrelated manner with lower platelet counts whenever the atypical lymphocytes
increased and vice versa.
 Suggest that atypical lymphocytes play a potentially causal role in the decline of
platelet counts in dengue
 Jampangern et al. 2007 Sstudy suggested that significant positive correlation
between atypical lymphocytes and a cluster of differentiation 19 (CD19) + B cells.
 Liu TC et al study suggested that presence of T cell markers (CD2 and CD7) on
atypical lymphocytes.

19.  This study conjecture that atypical lymphocytosis reflects the heightened
and misdirected adaptive immune response to dengue characterized by
the triad of crossreacting B and T cells, cytokine storm, and
autoimmunity leading to tissue damage causing dengue pathophysiology

20. CONCLUSION
 Association between atypical lymphocytes and the pathognomonic
hematological changes of dengue, viz, platelet count and hematocrit.
 This study also supports the predictive potential of ATY and LIC in dengue

21. LIMITATIONS
There is a paucity of effective prognostic markers for the cardinal
pathophysiological feature of dengue, viz, vascular leakage and its severity

22. FUNDING
APOLLO INSTITUTE OF MEDICAL SCIENCES & RESEARCH, APOLLO HEALTH CITY

23. REFERENCES
1. World Health Organization (WHO) and the Special Programme for Research and Training in Tropical Diseases (TDR). Dengue Guidelines for
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2. World Health Organization. Dengue and severe dengue [Internet]. 2023. Available from: https://www. who.int/news-room/fact-
sheets/detail/dengue-andsevere-dengue.
3. National Centre for Vector Borne Diseases Control, Directorate General of Health Services, Ministry of Health & Family Welfare, Government of
India. DENGUE/DHF SITUATION IN INDIA [Internet]. 2023. Available from: https://ncvbdc.mohfw.gov.in/index4.
php?lang=1&level=0&linkid=431&lid=3715.
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5. Yip W. Dengue haemorrhagic fever: current approaches to management. Med Prog 1980.
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associated with death ≤7 days after illness onset and ≤3 days after presentation. J Clin Med 2018;7(11):1–15.
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Trop Dis 2021;15(10):1–25.
8. Huy BV, Toàn NV. Prognostic indicators associated with progresses of severe dengue. PLoS One. 2022;17(1):e0262096.
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24. REFERENCES(cont..)
10. Thisyakorn U, Nimmannitya S, Ningsanond V, et al. Atypical lymphocyte in dengue hemorrhagic fever: its value in diagnosis.
Southeast Asian J Trop Med Public Health 1984;15(1):32–36.
11. Hidayati L. Sensitivity and specificity of atypical lymphocyte for diagnosis of dengue virus infection at Mataram hospital, West
Nusa Tenggara. In: Strengthening Hospital Competitiveness to Improve Patient Satisfaction and Better Health Outcomes
2019:599–606.
12. Clarice CSH, Abeysuriya V, de Mel S, et al. Atypical lymphocyte count correlates with the severity of dengue infection. PLoS
One. 2019;14(5):e0215061.
13. Jampangern W, Vongthoung K, Jittmittraphap A, et al. Characterization of atypical lymphocytes and immunophenotypes of
lymphocytes in patients with dengue virus infection. Asian Pac J Allergy Immunol 2007;25(1):27–36.
14. Liu TC, Chan YC, Han P. Lymphocyte changes in secondary dengue fever: use of the Technicon H*1 to monitor progress of
infection. Southeast Asian J Trop Med Public Health 1991;22(3):332–336

25. CRITICAL ANALYSIS
 Title
 Materials & Methods
 Results
 Limitations
 Discussion & Conclusion
 Conflicts of interest; nil
 General considerations & implications

26. THANK YOU