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Thrombotic Thrombocytopenic Purpura in Dengue Fever

Tee TY, Cader RA

Acta Med Indones, 2021 Apr;53(2):208-212.

Thrombotic thrombocytopenic purpura is a rare but life threatening medical condition. Early recognition and treatment of thrombotic thrombocytopenic purpura is important especially in patients who do not present with the classic pentad to reduce the high mortality. Herein, we describe a case of a patient who does not fulfil the classic pentad features thrombotic thrombocytopenic purpura that was induced by dengue fever. The patients' initial full blood picture did not have all the typical features of microangiopathic haemolytic anaemia but there were fragmented red blood cells. However, even a small number of fragmented red blood cells in the peripheral blood should alert physicians of the possible diagnosis of thrombotic thrombocytopenic purpura together with other symptoms. Furthermore, signs and symptoms of thrombotic thrombocytopenic purpura and dengue fever can overlap such as fever, thrombocytopenia, neurological deficit mimicking dengue encephalopathy and dengue induced acute kidney injury.

Matched MeSH terms: 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*

Bleeding manifestations of dengue haemorrhagic fever in Malaysia

George R, Duraisamy G

Acta Trop, 1981 Mar;38(1):71-8.

PMID: 6111919

Analysis of the bleeding manifestations of 130 cases of dengue haemorrhagic fever admitted into the Children's ward of the General Hospital, Kuala Lumpur from May 1973 to September 1978 has been done. Petechial skin rash, epistaxis and gum bleeding were seen most commonly in mild and moderately severe cases. However, blood stained gastric aspirates, and severe haematemesis were seen in severe or very severe cases. Though with better vector control and preventive measures, a marked reduction in the incidence of the cases has been noted, severe cases were seen with symptoms of shock and gastrointestinal bleeding. These symptoms carried a bad prognosis. Among 15 children that died 10 had gastrointestinal bleeding and 2 had a disseminated intravascular coagulation defect. Lymphocytosis with atypical lymphocytes, low platelet count, low reticulocyte count and raised packed cell volume were the main haematological features seen in all these cases. All these features reverted to normal within a week. Mild evidence of disseminated intravascular coagulation was seen in a number of cases, but severe features were seen only in four. Two cases improved as a result of heparin therapy.

Matched MeSH terms: Dengue/complications*

Haemophagocytosis in dengue haemorrhagic fever: a case report

Ramanathan M, Duraisamy G

Ann Acad Med Singap, 1991 Nov;20(6):803-4.

PMID: 1803975

Virus associated haemophagocytic syndrome (VAHS), a distinct clinico-pathologic entity, is characterised by systemic proliferation of non-neoplastic histotiocytes showing haemophagocytosis resulting in blood cytopaenia. It has been described in relation to several viruses earlier. Here we describe a young girl who developed this reactive process during the course of dengue haemorrhagic fever (DHF).

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*

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*

A case of dengue-related osteonecrosis of the maxillary dentoalveolar bone

Al-Namnam NM, Nambiar P, Shanmuhasuntharam P, Harris M

Aust Dent J, 2017 Jun;62(2):228-232.

PMID: 27743399 DOI: 10.1111/adj.12472

Dengue is a mosquito transmitted flaviviral infection which can give rise to severe haemorrhage (dengue haemorrhagic fever) and with capillary leakage induces hypovolaemic shock (dengue shock syndrome). Although dengue symptoms and complications have been known for many decades, there has only been one documented case of osteonecrosis of the maxilla which was treated by excision of the necrotic bone. In this case of dengue infection, extensive maxillary osteonecrosis and minimal root resorption appeared to follow factitious injury with a toothpick but resolved with non-surgical management.

Matched MeSH terms: Dengue/complications*; Severe Dengue/complications*

Fulltext Post-dengue parkinsonism

Azmin S, Sahathevan R, Suehazlyn Z, Law ZK, Rabani R, Nafisah WY, et al.

BMC Infect Dis, 2013;13:179.

PMID: 23594500 DOI: 10.1186/1471-2334-13-179

BACKGROUND: Dengue is a common illness in the tropics. Equally common are neurological complications that stem from dengue infection. However, to date, parkinsonism following dengue has not been reported in medical literature.
CASE PRESENTATION: A previously well 18-year old man developed parkinsonism, in addition to other neurological symptoms following serologically confirmed dengue fever. Alternative etiologies were excluded by way of imaging and blood investigations.
CONCLUSIONS: The authors detail the first reported case of parkinsonism complicating dengue fever. Keeping rare presentations of common illnesses in mind, it behoves clinicians to consider parkinsonism as a complication following dengue infection. This would prevent injudicious treatment with L-dopa and dopamine agonists. Immunosuppression with steroids has been shown to be helpful in certain cases.

Matched MeSH terms: 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*

Haemolytic anaemia precipitated by dengue fever

Abdullah NH, Mohammad N, Ramli M, Wan Ghazali WS

BMJ Case Rep, 2019 Aug 28;12(8).

PMID: 31466966 DOI: 10.1136/bcr-2018-226760

We reported a case of a woman with no past medical illness who presented with a few days' history of fever, myalgia, arthralgia, hypochromic microcytic anaemia and thrombocytopaenia and who was nonstructural protein 1 antigen (NS1Ag)-positive. Haemolytic anaemia including full blood picture work-up revealed high reticulocyte count and haemolysis with positive direct Coombs test. She was started on prednisolone and was discharged well.

Matched MeSH terms: Dengue/complications*

Fulltext Severe Plasmodium knowlesi with dengue coinfection

Che Rahim MJ, Mohammad N, Besari AM, Wan Ghazali WS

BMJ Case Rep, 2017 Feb 20;2017.

PMID: 28219910 DOI: 10.1136/bcr-2016-218480

We report a case of severe Plasmodium knowlesi and dengue coinfection in a previously healthy 59-year-old Malay man who presented with worsening shortness of breath, high-grade fever with chills and rigors, dry cough, myalgia, arthralgia, chest discomfort and poor appetite of 1 week duration. There was a history mosquito fogging around his neighbourhood in his hometown. Further history revealed that he went to a forest in Jeli (northern part of Kelantan) 3 weeks prior to the event. Initially he was treated as severe dengue with plasma leakage complicated with type 1 respiratory failure as evidenced by positive serum NS1-antigen and thrombocytopenia. Blood for malarial parasite (BFMP) was sent for test as there was suspicion of malaria due to persistent thrombocytopenia despite recovering from dengue infection and the presence of a risk factor. The test revealed high count of malaria parasite. Confirmatory PCR identified the parasite to be Plasmodium knowlesi Intravenous artesunate was administered to the patient immediately after acquiring the BFMP result. Severe malaria was complicated with acute kidney injury and septicaemic shock. Fortunately the patient made full recovery and was discharged from the ward after 2 weeks of hospitalisation.

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*

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

Virus haemorrhagic fever

Reid HA

Bull Soc Pathol Exot Filiales, 1969;62(2):263-6.

PMID: 4397208

Matched MeSH terms: Dengue/complications*

Fulltext Posterior reversible encephalopathy syndrome secondary to dengue fever: a case report

Cheo SW, Wong HJ, Ng EK, Low QJ, Chia YK

Hong Kong Med J, 2021 02;27(1):55-57.

PMID: 33568560 DOI: 10.12809/hkmj208509

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*

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*

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) due to dengue virus

Fong CY, Khine MM, Peter AB, Lim WK, Rozalli FI, Rahmat K

J Clin Neurosci, 2017 Feb;36:73-75.

PMID: 27887978 DOI: 10.1016/j.jocn.2016.10.050

A 14-year-old girl presented with encephalopathy, delirium and ophthalmoplegia following a 3day history of high-grade fever. Brain MRI on day 6 of illness showed diffusion restricted ovoid lesion in the splenium of corpus callosum. Dengue virus encephalitis was diagnosed with positive PCR for dengue virus type-2 in both serum and cerebrospinal fluid. She made a complete recovery from day 10 of illness. Repeat brain MRI on day 12 of illness showed resolution of the splenial lesion. Serial diffusion tensor imaging (DTI) showed normal fractional anisotropy values on resolution of splenial lesion indicating that MERS was likely due to transient interstitial oedema with preservation of white matter tracts. This is the first reported case of MERS following dengue virus infection. It highlights the usefulness of performing serial DTI in understanding the underlying pathogenesis of MERS. Our case report widens the neurological manifestations associated with dengue infection and reiterates that patients with MERS should be managed supportively as the splenial white matter tracts are reversibly involved in MERS.

Matched MeSH terms: Dengue/complications*

Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome

Wan Jamaludin WF, Periyasamy P, Wan Mat WR, Abdul Wahid SF

J Clin Virol, 2015 Aug;69:91-5.

PMID: 26209387 DOI: 10.1016/j.jcv.2015.06.004

Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin.

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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