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Fulltext Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue Patients: A Retrospective Analysis

Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Jummaat F

PLoS One, 2015;10(9):e0138465.
PMID: 26421839 DOI: 10.1371/journal.pone.0138465

BACKGROUND: Dengue induced acute kidney injury (AKI) imposes heavy burden of illness in terms of morbidity and mortality. A retrospective study was conducted to investigate incidence, characteristics, risk factors and clinical outcomes of AKI among dengue patients.
METHODOLOGY: A total 667 dengue patients (2008-2013) were retrospectively evaluated and were stratified into AKI and non-AKI groups by using AKIN criteria. Two groups were compared by using appropriate statistical methods.
RESULTS: There were 95 patients (14.2%) who had AKI, with AKIN-I, AKIN-II and AKIN-III in 76.8%, 16.8% and 6.4% patients, respectively. Significant differences (P<0.05) in demographics and clinico-laboratory characteristics were observed between patients with and without AKI. Presence of dengue hemorrhagic fever [OR (95% CI): 8.0 (3.64–17.59), P<0.001],rhabdomyolysis [OR (95% CI): 7.9 (3.04–20.49)], multiple organ dysfunction OR (95% CI):17.9 (9.14–35.12), P<0.001], diabetes mellitus [OR (95% CI): 4.7 (1.12–19.86), P = 0.034], late hospitalization [OR (95% CI): 2.1 (1.12–19.86), P = 0.033] and use of nephrotoxic drugs [OR(95% CI): 2.9 (1.12–19.86), P = 0.006] were associated with AKI. Longer hospital stay (>3days) was also observed among AKI patients (OR = 1.3, P = 0.044) [corrected].Additionally, 48.4% AKI patients had renal insufficiencies at discharge that were signicantly associated with severe dengue, secondary infection and diabetes mellitus. Overall mortality was 1.2% and all fatal cases had AKI.
CONCLUSIONS: The incidence of AKI is high at 14.2% among dengue patients, and those with AKI portended significant morbidity, mortality, longer hospital stay and poor renal outcomes. Our findings suggest that AKI in dengue is likely to increase healthcare burden that underscores the need of clinicians' alertness to this highly morbid and potentially fatal complication for optimal prevention and management.

Matched MeSH terms: Dengue/complications*
Cost-utility analysis of an adjunctive recombinant activated factor VIIa for on-demand treatment of bleeding episodes in dengue haemorrhagic fever

Naing C, Poovorawan Y, Mak JW, Aung K, Kamolratankul P

Blood Coagul Fibrinolysis, 2015 Jun;26(4):403-7.
PMID: 25692521 DOI: 10.1097/MBC.0000000000000280

The present study aimed to assess the cost-utility analysis of using an adjunctive recombinant activated factor VIIa (rFVIIa) in children for controlling life-threatening bleeding in dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS). We constructed a decision-tree model, comparing a standard care and the use of an additional adjuvant rFVIIa for controlling life-threatening bleeding in children with DHF/DSS. Cost and utility benefit were estimated from the societal perspective. The outcome measure was cost per quality-adjusted life years (QALYs). Overall, treatment with adjuvant rFVIIa gained QALYs, but the total cost was higher. The incremental cost-utility ratio for the introduction of adjuvant rFVIIa was $4241.27 per additional QALY. Sensitivity analyses showed the utility value assigned for calculation of QALY was the most sensitive parameter. We concluded that despite high cost, there is a role for rFVIIa in the treatment of life-threatening bleeding in patients with DHF/DSS.

Matched MeSH terms: Severe Dengue/complications
Fulltext A case report: intracranial haemorrhage in a patient with probable dengue fever

Wafa SR, Jamsari S, Karis BM

Med J Malaysia, 1999 Jun;54(2):273-6.
PMID: 10972043

We present a rare case of a patient diagnosed with probable dengue fever sustaining an intracranial haemorrhage after a trivial motor vehicle accident. From the literature reviewed, it was noted that there have been no reports of dengue fever presenting with an intracranial haemorrhage, and the association is more common in patients diagnosed with dengue hemorrhagic fever and/or dengue shock syndrome.

Matched MeSH terms: Dengue/complications*; Severe Dengue/complications
Dengue-induced Acute Kidney Injury (DAKI): A Neglected and Fatal Complication of Dengue Viral Infection--A Systematic Review

Mallhi TH, Sarriff A, Adnan AS, Khan YH, Hamzah AA, Jummaat F, et al.

J Coll Physicians Surg Pak, 2015 Nov;25(11):828-34.
PMID: 26577971 DOI: 11.2015/JCPSP.828834

Dengue Viral Infection (DVI) imperils an estimated 2.5 billion people living in tropical and subtropical regions. World Health Organization (2011) guidelines also classified dengue as 'Expanded Dengue Syndrome' to incorporate wide spectrum of unusual manifestations of dengue infection affecting various organ systems - including liver, kidney, heart and brain. Renal involvements are least appreciated area of dengue infection, therefore, we systematically reviewed studies describing renal disorders in dengue infection, with emphasis on Acute Kidney Injury (AKI). The purpose of current review is to underscore clinicians’attention to this neglected intricacy of DVI. It suggests that dengue induced renal involvements vary from glomerulonephritis, nephrotic range proteinuria and AKI. We observed great disparity in incidence of AKI among dengue patients, based upon criteria used to define AKI. AKI among dengue patients was found to be associated with significant morbidity, mortality and longer hospitalization, adding financial burden to patients and healthcare system. Additionally, we identified several predictors of AKI in dengue patients including old age, obesity, severe dengue infection and concurrent bacterial or viral infection. Direct viral injury and deposition of antigen-antibody complex in glomerulus were found to be possible causes of renal disorders in dengue infection. Prior knowledge of clinico-laboratory characteristics and risk factors with early detection of AKI by using appropriate criteria would not only reduce morbidity and mortality but also decrease burden to patients and healthcare system.

Matched MeSH terms: Severe Dengue/complications*
Fulltext Dengue haemorrhagic fever with unusual prolonged thrombocytopaenia

Kamil SM, Mohamad NH, Narazah MY, Khan FA

Singapore Med J, 2006 Apr;47(4):332-4.
PMID: 16572249

We describe a case of dengue haemorrhagic fever with prolonged thrombocytopaenia. A 22-year-old Malay man with no prior illness presented with a history of fever and generalised macular rash of four days duration. Initial work-up suggested the diagnosis of dengue haemorrhagic fever based on thrombocytopaenia and positive dengue serology. Patient recovered from acute illness by day ten, and was discharged from the hospital with improving platelet count. He was then noted to have declining platelet count on follow-up and required another hospital admission on day 19 of his illness because of declining platelet count. The patient remained hospitalised till day 44 of his illness and managed with repeated platelet transfusion and supportive care till he recovered spontaneously.

Matched MeSH terms: Severe Dengue/complications*
Fulltext Association of Ward Acquired, On-admission, Progressive and Non-progressive AKI with Death among Dengue Patients: A Hidden Relationship

Mallhi TH, Khan AH, Sarriff A, Adnan AS, Khan YH

Acta Med Port, 2016 Feb;29(2):157-8.
PMID: 27234957 DOI: 10.20344/amp.6900
Matched MeSH terms: Dengue/complications*
Fulltext Determinants of mortality and prolonged hospital stay among dengue patients attending tertiary care hospital: a cross-sectional retrospective analysis

Mallhi TH, Khan AH, Sarriff A, Adnan AS, Khan YH

BMJ Open, 2017 Jul 10;7(7):e016805.
PMID: 28698348 DOI: 10.1136/bmjopen-2017-016805

OBJECTIVES: Dengue imposes substantial economic, societal and personal burden in terms of hospital stay, morbidity and mortality. Early identification of dengue cases with high propensity of increased hospital stay and death could be of value in isolating patients in need of early interventions. The current study was aimed to determine the significant factors associated with dengue-related prolonged hospitalisation and death.

DESIGN: Cross-sectional retrospective study.

SETTING: Tertiary care teaching hospital.

PARTICIPANTS: Patients with confirmed dengue diagnosis were stratified into two categories on the basis of prolonged hospitalisation (≤3 days and >3 days) and mortality (fatal cases and non-fatal cases). Clinico-laboratory characteristics between these categories were compared by using appropriate statistical methods.

RESULTS: Of 667 patients enrolled, 328 (49.2%) had prolonged hospitalisation. The mean hospital stay was 4.88±2.74 days. Multivariate analysis showed that dengue haemorrhagic fever (OR 2.3), elevated alkaline phosphatase (ALP) (OR 2.3), prolonged prothrombin time (PT) (OR 1.7), activated partial thromboplastin time (aPTT) (OR 1.9) and multiple-organ dysfunctions (OR 2.1) were independently associated with prolonged hospitalisation. Overall case fatality rate was 1.1%. Factors associated with dengue mortality were age >40 years (p=0.004), secondary infection (p=0.040), comorbidities (p<0.05), acute kidney injury (p<0.001), prolonged PT (p=0.022), multiple-organ dysfunctions (p<0.001), haematocrit >20% (p=0.001), rhabdomyolosis (p<0.001) and respiratory failure (p=0.007). Approximately half of the fatal cases in our study had prolonged hospital stay of greater than three days.

CONCLUSIONS: The results underscore the high proportion of dengue patients with prolonged hospital stay. Early identification of factors relating to prolonged hospitalisation and death will have obvious advantages in terms of appropriate decisions about treatment and management in high dependency units.

Study site: Hospital Universiti Sains Malaysia (HUSM), Kelantan

Matched MeSH terms: Severe Dengue/complications*
Fulltext Dengue Cerebellitis: A Case Report and Literature Review

Khoo CS

Am J Case Rep, 2018 Jul 24;19:864-867.
PMID: 30038209 DOI: 10.12659/AJCR.909884

BACKGROUND Dengue-associated neurological manifestations have recently been on the rise. Cerebellar syndrome complicating dengue fever has rarely been reported in the literature. We present a case report of dengue-associated cerebellar syndrome and performed a literature review to draw attention to this rare neurological complication. CASE REPORT A 60-year-old man presented with 4 days of fever, myalgia, arthralgia, headaches, and warning symptoms (persistent diarrhea and vomiting). He was admitted with serologically-confirmed dengue fever. He had been well until day 8 of illness, when he developed cerebellar signs and symptoms. The temporal relationship with the recent dengue fever suggested that he had dengue cerebellitis. He recovered well, with no neurological sequelae upon our clinic visit. CONCLUSIONS Dengue cerebellitis is a rare but recognized manifestation, which should be considered in patients from endemic areas of dengue fever who develop cerebellar syndrome.

Matched MeSH terms: Dengue/complications*
Cavity Forming Pneumonia Due to Staphylococcus aureus Following Dengue Fever

Miyata N, Yoshimura Y, Tachikawa N, Amano Y, Sakamoto Y, Kosuge Y

Am J Trop Med Hyg, 2015 Nov;93(5):1055-7.
PMID: 26304914 DOI: 10.4269/ajtmh.15-0045

While visiting Malaysia, a 22-year-old previously healthy Japanese man developed myalgia, headache, and fever, leading to a diagnosis of classical dengue fever. After improvement and returning to Japan after a five day hospitalization, he developed productive cough several days after defervescing from dengue. Computed tomography (CT) thorax scan showed multiple lung cavities. A sputum smear revealed leukocytes with phagocytized gram-positive cocci in clusters, and grew an isolate Staphylococcus aureus sensitive to semi-synthetic penicillin; he was treated successfully with ceftriaxone and cephalexin. This second reported case of pneumonia due to S. aureus occurring after dengue fever, was associated both with nosocomial exposure and might have been associated with dengue-associated immunosuppression. Clinicians should pay systematic attention to bacterial pneumonia following dengue fever to establish whether such a connection is causally associated.

Matched MeSH terms: Dengue/complications*
Fulltext Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever

Bandyopadhyay S, Lum LC, Kroeger A

Trop Med Int Health, 2006 Aug;11(8):1238-55.
PMID: 16903887 DOI: 10.1111/j.1365-3156.2006.01678.x

BACKGROUND: The current World Health Organisation (WHO) classification of dengue includes two distinct entities: dengue fever (DF) and dengue haemorrhagic fever (DHF)/dengue shock syndrome; it is largely based on pediatric cases in Southeast Asia. Dengue has extended to different tropical areas and older age groups. Variations from the original description of dengue manifestations are being reported.
OBJECTIVES: To analyse the experience of clinicians in using the dengue case classification and identify challenges in applying the criteria in routine clinical practice.
METHOD: Systematic literature review of post-1975 English-language publications on dengue classification.
RESULTS: Thirty-seven papers were reviewed. Several studies had strictly applied all four WHO criteria in DHF cases; however, most clinicians reported difficulties in meeting all four criteria and used a modified classification. The positive tourniquet test representing the minimum requirement of a haemorrhagic manifestation did not distinguish between DHF and DF. In cases of DHF thrombocytopenia was observed in 8.6-96%, plasma leakage in 6-95% and haemorrhagic manifestations in 22-93%. The low sensitivity of classifying DHF could be due to failure to repeat the tests or physical examinations at the appropriate time, early intravenous fluid therapy, and lack of adequate resources in an epidemic situation and perhaps a considerable overlap of clinical manifestations in the different dengue entities.
CONCLUSION: A prospective multi-centre study across dengue endemic regions, age groups and the health care system is required which describes the clinical presentation of dengue including simple laboratory parameters in order to review and if necessary modify the current dengue classification.

Matched MeSH terms: Dengue/complications; Severe Dengue/complications
Dengue fever complicated by pulmonary haemorrhage manifesting as haemoptysis

Liam CK, Yap BH, Lam SK

J Trop Med Hyg, 1993 Jun;96(3):197-200.
PMID: 8505777

A 17-year-old girl was admitted to hospital with dengue fever. On the ninth day of fever she developed haemoptysis and chest X-ray changes consistent with haemorrhage in her lungs. Thrombocytopaenia and mild coagulopathy were the most likely cause of this unusual haemoptysis in this patient. Investigations excluded other causes for the haemoptysis.

Matched MeSH terms: Dengue/complications*
Dengue-associated adult respiratory distress syndrome

Lum LC, Thong MK, Cheah YK, Lam SK

Ann Trop Paediatr, 1995 Dec;15(4):335-9.
PMID: 8687212 DOI: 10.1080/02724936.1995.11747794

In dengue shock syndrome, an acute increase in capillary permeability results in leakage of plasma into the interstitial space. Pleural effusion is commonly seen in dengue shock syndrome. We report three cases of dengue-associated adult respiratory distress syndrome (ARDS) in children, in all of whom dengue haemorrhagic fever, presenting with grade 3 or grade 4 dengue shock syndrome with disseminated intravascular coagulopathy, was confirmed. The criteria for the diagnosis of ARDS were based on the expanded definition of ARDS by Murray et al. Treatment consisted of fluid resuscitation, correction of coagulopathy and mechanical ventilation. All three children had multi-organ impairment, but it was more severe in the two who died. The one survivor was well at discharge.

Matched MeSH terms: Dengue/complications*
Preventive transfusion in Dengue shock syndrome-is it necessary?

Lum LC, Abdel-Latif Mel-A, Goh AY, Chan PW, Lam SK

J Pediatr, 2003 Nov;143(5):682-4.
PMID: 14615749

We compared 53 patients with Dengue shock syndrome (DSS) who received preventive transfusions with 53 who did not. Significant differences in the development of pulmonary edema and length of hospitalization (P

Matched MeSH terms: Severe Dengue/complications
Fever and rash in a returning traveller

Kumar N, Lewis DJ

BMJ, 2012;344:e2400.
PMID: 22496299 DOI: 10.1136/bmj.e2400
Matched MeSH terms: Dengue/complications*
Fulltext The dangers of accepting a single diagnosis: case report of concurrent Plasmodium knowlesi malaria and dengue infection

Chong SE, Mohamad Zaini RH, Suraiya S, Lee KT, Lim JA

Malar J, 2017 01 03;16(1):2.
PMID: 28049485 DOI: 10.1186/s12936-016-1666-y

BACKGROUND: Dengue and malaria are two common, mosquito-borne infections, which may lead to mortality if not managed properly. Concurrent infections of dengue and malaria are rare due to the different habitats of its vectors and activities of different carrier mosquitoes. The first case reported was in 2005. Since then, several concurrent infections have been reported between the dengue virus (DENV) and the malaria protozoans, Plasmodium falciparum and Plasmodium vivax. Symptoms of each infection may be masked by a simultaneous second infection, resulting in late treatment and severe complications. Plasmodium knowlesi is also a common cause of malaria in Malaysia with one of the highest rates of mortality. This report is one of the earliest in literature of concomitant infection between DENV and P. knowlesi in which a delay in diagnosis had placed a patient in a life-threatening situation.
CASE PRESENTATION: A 59-year old man staying near the Belum-Temengor rainforest at the Malaysia-Thailand border was admitted with fever for 6 days, with respiratory distress. His non-structural protein 1 antigen and Anti-DENV Immunoglobulin M tests were positive. He was treated for severe dengue with compensated shock. Treating the dengue had so distracted the clinicians that a blood film for the malaria parasite was not done. Despite aggressive supportive treatment in the intensive care unit (ICU), the patient had unresolved acidosis as well as multi-organ failure involving respiratory, renal, liver, and haematological systems. It was due to the presentation of shivering in the ICU, that a blood film was done on the second day that revealed the presence of P. knowlesi with a parasite count of 520,000/μL. The patient was subsequently treated with artesunate-doxycycline and made a good recovery after nine days in ICU.
CONCLUSIONS: This case contributes to the body of literature on co-infection between DENV and P. knowlesi and highlights the clinical consequences, which can be severe. Awareness should be raised among health-care workers on the possibility of dengue-malaria co-infection in this region. Further research is required to determine the real incidence and risk of co-infection in order to improve the management of acute febrile illness.

Matched MeSH terms: Dengue/complications*
Fulltext Dengue related maculopathy and foveolitis

Juanarita J, Azmi MN, Azhany Y, Liza-Sharmini AT

Asian Pac J Trop Biomed, 2012 Sep;2(9):755-6.
PMID: 23570008 DOI: 10.1016/S2221-1691(12)60223-8

A 24 year-old Malay lady presented with high grade fever, myalgia, generalized rashes, severe headache and was positive for dengue serology test. Her lowest platelet count was 45 × 10(9) cells/L. She complained of sudden onset of painlessness, profound loss of vision bilaterally 7 days after the onset of fever. On examination, her right eye best corrected vision was 6/30 and left eye was 6/120. Her anterior segment examination was unremarkable. Funduscopy revealed there were multiple retinal haemorrhages found at posterior pole of both fundi and elevation at fovea area with subretinal fluid. Systemic examination revealed normal findings except for residual petechial rashes. She was managed conservatively. Her vision improved tremendously after 2 months. The retinal hemorrhages and foveal elevation showed sign of resolving. Ocular manifestations following dengue fever is rare. However, bilateral visual loss can occur if both fovea are involved.

Matched MeSH terms: Dengue/complications*
Management of dengue haemorrhagic fever/dengue shock syndrome

Lum LC

Malays J Pathol, 1993 Jun;15(1):29-33.
PMID: 8277786
Matched MeSH terms: Dengue/complications*
Fulltext Atrial fibrillation as a complication of dengue hemorrhagic fever: non-self-limiting manifestation

Mahmod M, Mohd Darul ND, Mokhtar I, Md Nor N, Md Anshar F, Maskon O

Int J Infect Dis, 2009 Sep;13(5):e316-8.
PMID: 19541521 DOI: 10.1016/j.ijid.2009.01.017

While electrocardiogram (ECG) changes are common during viral dengue infection, atrial fibrillation (AF) is a very rare manifestation. It has previously been highlighted that cardiac complications during dengue infection are invariably transient and will spontaneously resolve following recovery from the illness. We present the case of a young patient with IgM- and IgG-positive dengue hemorrhagic fever complicated by AF. ECG revealed a structurally normal heart. The patient remained in AF despite resolution of the illness. Reversion to normal sinus rhythm was achieved after loading of oral amiodarone.

Matched MeSH terms: Severe Dengue/complications*
Concomitant dengue fever in Varicella zoster infection - A rare presentation

Shaiful Ehsan SM, Iskandar FO, Mohd Ashraf AR

Med J Malaysia, 2019 08;74(4):347-348.
PMID: 31424049

Varicella zoster infection is one of the self-limiting viral infections during childhood and dengue fever is an endemic infection in Malaysia, which commonly occurs in the form of nonspecific febrile illness at the initial stage. It is rare for the two viral infections to occur simultaneously. A case of dengue fever without warning sign in a five-year old girl was reported, with early symptoms of fever and vesicular rashes. She was clinically diagnosed with varicella zoster infection during the first visit. Surprisingly, she remained febrile even on day six of illness despite no new vesicular lesions on her skin. Due to suspicion of another infection, follow-up investigation was done and revealed isolated thrombocytopenia. This finding was confirmed with positive NS1Ag. A case of rare dengue fever concomitant with varicella zoster infection was reported.

Matched MeSH terms: Dengue/complications
Unusual, neurological and severe dengue manifestations during the outbreak in Sri Lanka, 2017

Ngwe Tun MM, Muthugala R, Nabeshima T, Rajamanthri L, Jayawardana D, Attanayake S, et al.

J Clin Virol, 2020 04;125:104304.
PMID: 32145478 DOI: 10.1016/j.jcv.2020.104304

BACKGROUND: Sri Lanka experienced its largest dengue outbreak in 2017 with more than 185,000 dengue cases including at least 250 fatalities.
OBJECTIVES: Our study aimed to characterize the clinical, immunological and virological features of confirmed dengue patients in Sri Lanka during the outbreak in 2017 when unusual manifestations of severe dengue were observed.
STUDY DESIGN: Sera from 295 patients who were admitted to Teaching Hospital Kandy, Kandy, Sri Lanka between March 2017- January 2018 were subjected to NS1 antigen, IgM and IgG ELISAs, virus isolation, conventional and real time RT-PCR and next generation sequencing.
RESULTS: Primary and secondary infections were detected in 48.5 % and 51.5 % of the study population, respectively. Two hundred twenty five DENV strains were isolated (219 DENV-2, one DENV-3, two DENV-4, two mixed infections of DENV-2 and -3 and one mixed infection of DENV-2 and -4). Unusual and severe manifestations such as encephalitis, encephalopathy, liver failure, kidney failure, myocarditis, Guillain-Barré syndrome and multi-organ failure were noted in 44 dengue patients with 11 deaths. The viraemia levels in patients with primary infection and unusual manifestations were significantly higher compared to those in patients with secondary infection. A new clade of DENV-2 Cosmopolitan genotype strains was observed with the strains closely related to those from China, Malaysia, Indonesia, Singapore and Taiwan.
CONCLUSIONS: The new clade of DENV-2 cosmopolitan genotype observed in Sri Lanka in 2017 caused an unprecedented, severe dengue outbreak. The emergence of DENV-3 and DENV-4 in the 2017 outbreak might cause future outbreaks in Sri Lanka.

Matched MeSH terms: Dengue/complications*

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