Dengue and leptospirosis coinfection: a case series.

BACKGROUND: Both dengue and Leptospira infections are endemic to tropical and subtropical regions, with their prevalence increasing in recent decades. Coinfection with these pathogens presents significant diagnostic challenges for clinicians due to overlapping clinical manifestations and laboratory findings. This case report aims to elucidate two clinical scenarios where the coinfection of dengue and leptospirosis complicates the disease course, creating a diagnostic conundrum. CASE PRESENTATION: We present the clinical scenarios of two Bangladeshi males, aged 25 and 35 years, who were admitted to our hospital with acute febrile illness. The first patient exhibited hepatic and renal involvement, while the second presented with symptoms initially suggestive of meningoencephalitis. Both cases were initially managed under the presumption of dengue infection based on positive serology. However, further evaluation revealed coinfection with Leptospira, complicating the disease course. Both patients received appropriate treatment for dengue and antibacterial therapy for leptospirosis, ultimately resulting in their recovery. CONCLUSION: These case scenarios underscore the critical importance for clinicians in regions where dengue and Leptospira are endemic to consider both diseases when evaluating patients presenting with acute febrile illness.

New biomarkers for liver involvement by dengue infection in adult Vietnamese patients: a case-control study.

Liver injury with marked elevation of aspartate aminotransferase enzyme (AST) is commonly observed in dengue infection. To understand the pathogenesis of this liver damage, we compared the plasma levels of hepatic specific, centrilobular predominant enzymes (glutamate dehydrogenase, GLDH; glutathione S transferase-α, αGST), periportal enriched 4-hydroxyphenylpyruvate dioxygenase (HPPD), periportal predominant arginase-1 (ARG-1), and other non-specific biomarkers (paraoxonase-1, PON-1) in patients with different outcomes of dengue infection. This hospital-based study enrolled 87 adult dengue patients, stratified into three groups based on plasma AST levels (< 80, 80-400, > 400 U/L) in a 1:1:1 ratio (n = 40, n = 40, n = 40, respectively. The new liver enzymes in the blood samples from the 4th to 6th days of their illness were measured by commercial enzyme-linked immunosorbent assay (ELISA) or colorimetric kits. Based on the diagnosis at discharge days, our patients were classified as 40 (46%) dengue without warning signs (D), 35 (40.2%) dengue with warning signs (DWS), and 11 (12.6%) severe dengue (SD) with either shock (two patients) or AST level over 1000 U/L (nine patients), using the 2009 WHO classification. The group of high AST (> 400 U/L) also had higher ALT, GLDH, ARG-1, and HPPD than the other groups, while the high (> 400 U/L) and moderate (80-400 U/L) AST groups had higher ALT, αGST, ARG-1, and HPPD than the low AST group (< 80 U/L). There was a good correlation between AST, alanine aminotransferase enzyme (ALT), and the new liver biomarkers such as GLDH, αGST, ARG-1, and HPPD. Our findings suggest that dengue-induced liver damage initiates predominantly in the centrilobular area toward the portal area during the dengue progression. Moreover, these new biomarkers should be investigated further to explain the pathogenesis of dengue and to validate their prognostic utility.

Incidence of acute liver failure and its associated mortality in patients with dengue infection: A systematic review and meta-analysis.

Acute liver failure (ALF) is a devastating consequence of dengue infection. This systematic review and meta-analysis assessed the incidence of ALF in dengue infection and its associated mortality. We systematically searched the EMBASE and MEDLINE databases from inception to December 2023 for observational studies reporting ALF incidence and mortality in dengue patients. Twenty-one studies encompassing 26,839 dengue-infected patients were included. Meta-analysis revealed a pooled incidence of ALF in cases of general dengue infection of 2.0 % (95 % CI, 1.2-3.0 %), with 1.2 % (95 % CI, 0.6-2.1 %) in adults and 5.0 % (95 % CI, 1.5-10.2 %) in children. ALF incidence was 17.3 % (95 % CI, 6.5 %-31.5 %) in severe dengue and 7.4 % (95 % CI, 0.8-18.5 %) in dengue shock syndrome. The pooled mortality rate of dengue-associated ALF was 47.0 % (95 % CI, 32.9-61.2 %). These findings underscore the detrimental impact of dengue infection on the development of the relatively uncommon, albeit life-threatening, condition of ALF.

Risks of anxiety disorders, depressive disorders, and sleep disorders in patients with dengue fever: A nationwide, population-based cohort study.

BACKGROUND: Dengue virus (DENV) infection, a common mosquito-borne disease, has been linked to several mental disorders like depression and anxiety. However, the temporal risk of these disorders after DENV infection is not well studied. METHODS: This population-based cohort study encompassed 45,334 recently lab-confirmed dengue patients in Taiwan spanning 2002 to 2015, matched at a 1:5 ratio with non-dengue individuals based on age, gender, and residence (n = 226,670). Employing subdistribution hazard regression analysis, we assessed the immediate (<3 months), intermediate (3-12 months), and prolonged (>12 months) risks of anxiety disorders, depressive disorders, and sleep disorders post DENV infection. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure. RESULTS: A significant increase in depressive disorder risk across all timeframes post-infection was observed (<3 months [aSHR 1.90, 95% CI 1.20-2.99], 3-12 months [aSHR 1.68, 95% CI 1.32-2.14], and >12 months [aSHR 1.14, 95% CI 1.03-1.25]). Sleep disorder risk was higher only during 3-12 months (aSHR 1.55, 95% CI 1.18-2.04). No elevated anxiety disorder risk was found. Subgroup analysis of hospitalized dengue patients showed increased risk of anxiety disorders within 3 months (aSHR 2.14, 95% CI 1.19-3.85) and persistent risk of depressive disorders across all periods. Hospitalized dengue patients also had elevated sleep disorder risk within the first year. CONCLUSION: Dengue patients exhibited significantly elevated risks of depressive disorders in both the short and long term. However, dengue's impact on sleep disorders and anxiety seems to be short-lived. Further research is essential to elucidate the underlying mechanisms.

Mucocutaneous Manifestations in Patients with Dengue Fever: From the EPIDENGUE Cohort on Reunion Island.

Nearly 4 billion people live in a dengue risk area worldwide. The prevalence of dengue-related mucocutaneous manifestations and their association with severe dengue differ across studies. The aim of the study was to describe the characteristics of patients with dengue-related mucocutaneous manifestations and to investigate those were associated with severe dengue. A retrospective study was conducted in 2019 among patients with a positive RT-PCR for dengue at the University Hospital of Reunion, which has been experiencing a re-emergence of dengue since 2018. Of 847 patients with confirmed dengue, 283 (33.4%) developed mucocutaneous manifestations. Only manifestations of dehydration such as glossitis, dysgeusia, or conjunctivitis were associated with severe dengue, unlike pruritus and rash, in bivariate analysis but not in multivariate analysis. The rash and pruritus of dengue appear to be accompanied by a pronounced flu-like syndrome in younger people without comorbidity or severity, although careful examination of mucous membranes would better identify signs of dehydration and thus cases likely to worsen.

Dengue rhabdomyolysis successfully treated with hemoperfusion using CytoSorb® in combination with continuous renal replacement therapy: a case report.

BACKGROUND: Dengue fever is a mosquito-borne viral infection with a broad spectrum of clinical manifestations. Expanded dengue syndrome includes unusual manifestations that do not fall into the categories of dengue fever, dengue hemorrhagic fever, or dengue shock syndrome. Rhabdomyolysis causing acute renal failure in dengue is one such unusual manifestation, the pathophysiology of which is incompletely understood. CASE PRESENTATION: We describe a 21-year-old Sri Lankan man with dengue fever who developed severe rhabdomyolysis and acute kidney injury with extremely high creatinine phosphokinase levels (> 2 million U/L). Management of this patient was challenging as his creatinine phosphokinase kept rising with persistent anuria despite hydration, intermittent hemodialysis, and, later, continuous venovenous hemodiafiltration. Further therapeutic options were explored, and CytoSorb® adsorber was added as an adjunct to continuous venovenous hemodiafiltration, following which we observed a marked reduction in his creatinine phosphokinase and myoglobin levels over the next 12 hours and complete renal recovery over the next 5 weeks. CONCLUSION: We report a rare case of significant rhabdomyolysis secondary to dengue infection leading to acute kidney injury. Continuous venovenous hemodiafiltration performed with the hemofilter Pecopen 140 was ineffective, and the addition of CytoSorb® adsorber as an adjunct therapy to continuous venovenous hemodiafiltration may have a potential benefit in removing high-molecular-weight proteins such as myoglobin.

Common arboviruses and the kidney: a review.

Arboviruses are endemic in several countries and represent a worrying public health problem. The most important of these diseases is dengue fever, whose numbers continue to rise and have reached millions of annual cases in Brazil since the last decade. Other arboviruses of public health concern are chikungunya and Zika, both of which have caused recent epidemics, and yellow fever, which has also caused epidemic outbreaks in our country. Like most infectious diseases, arboviruses have the potential to affect the kidneys through several mechanisms. These include the direct action of the viruses, systemic inflammation, hemorrhagic phenomena and other complications, in addition to the toxicity of the drugs used in treatment. In this review article, the epidemiological aspects of the main arboviruses in Brazil and other countries where these diseases are endemic, clinical aspects and the main laboratory changes found, including changes in renal function, are addressed. It also describes how arboviruses behave in kidney transplant patients. The pathophysiological mechanisms of kidney injury associated with arboviruses are described and finally the recommended treatment for each disease and recommendations for kidney support in this context are given.

Is there an overestimation of dengue compared with that of other acute febrile syndromes in childhood?

A group of children with clinical suspicion of dengue were assessed to determine if there was an overestimation of dengue compared with that of leptospirosis and leishmaniasis. This descriptive and analytical cross-sectional study, based on the active search of participants with acute febrile illness, was conducted at two pediatric hospitals. The collection of clinical and epidemiological data was performed using questionnaires, and laboratory tests specific for dengue were performed using immunochromatographic, serological, and molecular methods. Dengue-negative samples were assessed for Leptospira and Leishmania spp. using molecular tests. Data were assessed using analysis of variance (ANOVA), the chi-square test, and Fisher's exact test. In total, 86 participants were evaluated, of whom 39 (45%) were positive for dengue fever, 4 (5%) for leptospirosis, and 1 (1%) for leishmaniasis. Forty-two participants (49%) presented dengue-like symptoms. The predominant age range for the virus was 3-10 years. Most clinical manifestations were nonspecific, with frequent concomitant gastrointestinal and respiratory symptoms. Furthermore, we found that the acute febrile syndrome in childhood persists as a challenge for health professionals, especially in the early days of the disease, due to a plurality of diagnostic hypotheses, associated with the difficulty of establishing well-defined symptoms in children, especially in infants. Dengue fever continues to be a frequent pathology with acute febrile infections in childhood; however, there is an overestimation of the disease, especially in endemic regions, when one considers only the clinical epidemiological diagnosis.

Liver involvement in dengue: A systematic review.

Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated liver involvement relies on an accurate description of its clinical and biological characteristics, its prognosis factors, its association with severe dengue and its clinical management. We conducted a systematic review by searching PubMed and Web of Science databases for original case reports, cohort and cross-sectional studies reporting the clinical and/or biological features of dengue-associated liver involvement. The study was registered in PROSPERO (CRD42021262657). Of the 2552 articles identified, 167 were included. Dengue-associated liver involvement was characterised by clinical features including abdominal pain, hepatomegaly, jaundice, nausea/vomiting, and an echogenic liver exhibiting hepatocellular necrosis and minimal inflammation. Elevated Aspartate Aminotransferase and Alanine Aminotransferase but also elevated bilirubin, Alkaline Phosphatase, gamma-glutamyl transferase, increased International Normalised Ratio, creatinine and creatine kinase, lower albumin and prolonged prothrombin and activated partial thromboplastin time were prevalent in dengue-associated liver involvement. Cardiovascular and haematological systems were frequently affected, translating in a strong association with severe dengue. Liver involvement was more common in males and older adults. It was associated with dengue virus serotype-2 and secondary infections. Early paracetamol intake increased the risk of liver involvement, which clinical management was mostly conservative. In conclusion, this systematic review demonstrates that early monitoring of transaminases, clinical assessment, and ultrasound examination allow an efficient diagnosis of dengue-associated liver involvement, enabling the early identification and management of severe dengue.

Postdengue Acute Disseminated Encephalomyelitis.

A 38-year-old gentleman, following an uncomplicated dengue fever 2 weeks back, developed acute onset bilateral lower limb weakness and numbness for 5 days, associated with bladder and bowel incontinence and a band-like sensation in T4 dermatome. On examination, he had paraparesis with normal cranial nerves except for left upper motor neuron-type 7th cranial nerve palsy and normal higher mental function. Magnetic resonance imaging (MRI) of the brain and spine detected multiple demyelinating lesions. A diagnosis of postdengue acute disseminated encephalomyelitis (ADEM) was made as part of postinfective inflammatory process after the fever had subsided. Cerebrospinal fluid study ruled out active infection. He was treated with intravenous steroids and is currently recovering. An interesting point in our case was that the patient had significant imaging findings in MRI of the brain with no symptoms or signs suggestive of intracranial involvement-ADEM without evidence of encephalitis.

Intravenous fluid therapy in hospitalized adult dengue patients without shock: Impact on subsequent severe dengue and potential adverse effects.

There is a lack of evidence on the optimal administration of intravenous (IV) fluids in hospitalized adult dengue patients without compensated and hypotensive shock. This study utilized a well-established cohort of dengue patients to compare risks of progressing to severe dengue (SD) over time for patients who were administered IV fluid versus others who were not. We included adult patients (n = 4781) who were hospitalized for dengue infection from 2005 to 2008. Cases were patients who developed SD (n = 689) and controls were patients who did not up until discharge (n = 4092). We estimated the hazard ratios (HRs) and risk of SD over time between groups administered different volumes of IV fluids versus the no IV fluid comparison group using Cox models with time-dependent covariates. The doubly-robust estimation approach was used to control for the propensity of fluid administration given clinical characteristics of patients. Subgroup analyses by age, sex, and dengue warning signs before IV fluid administration were conducted. High (>2000 mL/day) IV fluids volume was associated with a higher risk of development of SD for those who had warning signs (HR: 1.77 [1.05-2.97], p: 0.0713) and for those below 55 years old (HR: 1.53 [1.04-2.25], p: 0.0713). Low (<1000 mL/day) IV fluids volume was protective against SD for patients without warning signs (HR: 0.757 [0.578-0.990], p: 0.0883), no lethargy (HR: 0.770 [0.600-0.998], p: 0.0847), and females (HR: 0.711 [0.516-0.980], p: 0.0804). Over the course of hospitalization, there were no significant differences in IV fluid administration and SD risk in most subgroups, except in those who experienced lethargy and were administered IV fluid volume or quantity. Administering high volumes of IV fluids may be associated with an increased risk of SD during hospitalization for adult dengue patients without shock. Judicious use of IV fluids as supportive therapy is warranted.

Etiological spectrum and diagnostic challenges of short-duration fever in West Bengal (India). A cross-sectional tertiary care study.

INTRODUCTION: The scarcity of epidemiological data on acute febrile illnesses from South Asia impairs evidence-based clinical decision-making. Our study aimed to explore the etiological spectrum of short-duration fever in patients admitted to a tertiary care hospital in West Bengal, India. METHODS: We conducted a cross-sectional study from May 2021 to April 2022 involving 150 adult patients presenting with a fever lasting less than two weeks at Burdwan Medical College and Hospital (West Bengal, India). We performed comprehensive clinical assessments, including microbiological, serological, and other specific investigations, to identify the causes of the fever. RESULTS: The demographic profile predominantly included individuals aged 21-40 years, with a male-to-female ratio of 1.9:1; 60.7% of participants were from rural areas. The primary etiological agents identified were scrub typhus (25.3%), dengue (15.3%), and enteric fever (13.3%). Notably, 80% of patients presented with non-localizing symptoms, while 14.7% had respiratory symptoms. Blood cultures pinpointed Salmonella typhi and Staphylococcus aureus in a minority of cases (3.3%); malaria, primarily Plasmodium vivax, was diagnosed in 12% of the cases. CONCLUSION: Our findings highlight the complexity of diagnosing short-duration fevers, dominated by a wide range of etiological agents, with a notable prevalence of scrub typhus. These results underscore the urgent need for enhanced diagnostic facilities, including the availability of scrub typhus testing at primary healthcare centers. We recommend empirical doxycycline therapy for suspected cases and emphasize the need for further research to develop management guidelines for acute febrile illnesses. This study also highlights the importance of raising both community and clinician awareness to prevent irrational antibiotic use.

[Takotsubo syndrome in dengue patient]. / Síndrome de Takotsubo en paciente con dengue.

Takotsubo syndrome, was described in Japan in 1990, it is a stress cardiomyopathy, predominantly in women, usually postmenopausal. Cardiac hypokinesia occurs, with involvement of multiple coronary territories. In intensive care unit (ICU), it is considered underdiagnosed. Manifestations of severe dengue fever include cardiovascular involvement, mainly arrhythmias and systolic dysfunction. A case of a 72-year-old man is presented, who was hospitalized in ICU for dengue fever, with plateletopenia (15000 cells/mm3) and dehydration. After fluid management the patient reported respiratory discomfort, auscultating crackling rales. A pulmonary ultrasound was made where bilateral B lines were found with B7 pattern compatible with interstitial syndrome and pulmonary edema. Basal hyperkinesia, medial and apical hypokinesia with an image consistent with apical ballooning were observed in the transthoracic echocardiogram. The electrocardiogram showed complete right bundle branch block. Chagas serology was negative and quantitative troponin I was increased. In the context of severe dengue, a Takotsubo syndrome was diagnosed. The patient evolved favorably. After discharge, a normalization of the cardiac function was stated in ultrasound images. The case is of clinical importance due to the low association of these two diseases and the need to screen for cardiac involvement in severe dengue.

El síndrome de Takotsubo, fue descripto en Japón en 1990, se trata de una miocardiopatía por estrés, predominante en mujeres, generalmente postmenopáusicas. Se produce una hipoquinesia cardiaca, con compromiso de múltiples territorios coronarios. En las unidades de terapia intensiva (UTI), se considera subdiagnosticada. En las manifestaciones del dengue grave, se encuentra el compromiso cardiovascular, principalmente arritmias y disfunción sistólica. Se presenta el caso de un hombre de 72 años, internado en UTI por dengue, con plaquetopenia (15000 células/mm3) y deshidratación. Luego de la administración de fluidos refirió disconfort respiratorio, auscultándose estertores pulmonares. Se realizó ecografía pulmonar donde se apreció líneas B bilaterales con patrón B7 compatible con síndrome intersticial y edema pulmonar. En el ecocardiograma transtorácico se objetivó hiperquinesia basal, hipoquinesia medial y apical con imagen compatible con balonamiento apical. En el electrocardiograma se evidenció bloqueo completo de rama derecha. La serología para Chagas fue negativa y la troponina I cuantitativa se detectó aumentada. Se diagnosticó síndrome de Takotsubo en el contexto de dengue grave. El paciente evolucionó favorablemente. Posterior al alta, se constató normalización de la motilidad cardíaca, en las imágenes ecográficas. El caso es de importancia clínica por la baja asociación de las dos enfermedades y la necesidad de pesquisar el compromiso cardíaco en el dengue grave.

Neurological or Psychiatric Disorders After Dengue Fever.

This cohort study investigates the association between dengue fever and risk of neurological and psychiatric disorders among adults in Taiwan.

Duration of Fever in Patients with Dengue: A Systematic Review and Meta-Analysis.

Dengue is an acute febrile illness endemic to tropical countries and associated with high mortality rates. Despite being a viral infection, there is rampant misuse of antibiotics in patients with dengue because of perceived delay in defervescence and fear of secondary bacterial infections. Therefore, there is a need to establish the average fever duration with a confidence interval among patients with dengue. Studies up to October 21, 2022 from two databases (PubMed and Embase) were included using the search terms related to dengue and duration of fever. All retrieved articles were screened for eligibility by two independent reviewers. Studies where the average duration of fever was available were included for systematic review. Articles with at least more than 20 patients where a mean and standard deviation for the total duration of fever was available were included for meta-analysis. A total of 643 articles were included from the two databases after duplicate deletion. After two rounds of screening, 31 articles (n = 7,905) were finally included. The mean duration of fever in the 20 articles included for meta-analysis was 5.1 (95% CI: 4.7-5.5) days. Longer duration of fever was seen in those with a higher grade of fever, those with higher disease severity, and those with concurrent bacterial infections. In the absence of risk factors for concurrent bacteremia, antimicrobials may be unnecessary in those with dengue fever duration of less than 5.5 days.

Causes of Vision Loss Associated with Dengue Fever in Bihar, India - A Case Series.

The incidence and geographic distribution of dengue has increased dramatically in recent years across various parts of the world. Previously, ocular findings in dengue fever were considered rare. We report a spectrum of ocular manifestations presenting with vision loss in the last dengue epidemic in an eastern state of India. This is a retrospective interventional case series of patients with vision loss who were diagnosed with dengue eye disease in the 2022 epidemic. Systemic and ophthalmic examinations were completed on all patients and were analyzed. Fifteen patients had presented with vision loss. The mean age was 41.7 ± 10.8 years, and patients were mostly males. Three patients presented with panophthalmitis and orbital cellulitis. Eight patients were diagnosed with optic neuropathy. Four patients had macular involvement: macular chorioretinitis, macular subhyaloid hemorrhage, and macular hemorrhages in two patients. All patients with optic neuropathy gave a history of mild fever and had remained undiagnosed. The rest had been diagnosed with the more severe dengue hemorrhagic fever. Vision recovered partially or fully in patients with optic neuropathy and macular disease. No eye could be salvaged in any panophthalmitis patients. Thrombocytopenia (platelet count <100 × 109 per liter of blood) was significantly associated with ocular hemorrhage and panophthalmitis, but thrombocytopenia was not significantly seen in optic neuropathy. We conclude that optic neuropathy may be an underreported cause of vision loss in dengue fever. An eye examination is advocated in all patients with dengue eye disease.

First clinical reports of acute hantavirus and dengue infections among pregnant women in the Caribbean.

BACKGROUND: Hantavirus and dengue virus infections lead to diseases causing economic and public health concerns. Acute hantavirus infections can lead to similar clinical haemorrhagic signs as other endemic diseases including dengue and leptospirosis. METHODS: Using a retrospective case analysis of pregnant dengue and hantavirus disease patients with clinical reports and compatible clinical laboratory information during pregnancy, we report the first evidence of dengue and hantavirus infections and a case of dual dengue and hantavirus infection among pregnant women in the Caribbean. Laboratory testing by enzyme-linked immunosorbent assay (ELISA) and non-structural protein 1 (NS1) for DENV and for hantavirus infection pseudotype focus reduction neutralisation tests (pFRNT), ELISA and immunochromatographic (ICG) strips. RESULTS: Four pregnant cases with acute DENV infections were identified; however, only one out of the four cases (25%) had a detailed medical record to permit abstraction of clinical data. Six hantavirus infected pregnant cases were identified with gestation periods ranged from 36 to 39 weeks; none of the reported patients exhibited previous pregnancy complications prior to hospitalisation and infection. Acute liver damage was observed in three of the six cases (AST readings) who were subsequently diagnosed with hepatitis in pregnancy and variable clinical outcomes were observed with term and pre-term deliveries. CONCLUSIONS: Whilst hantavirus infection in pregnancy is rare, consideration should be given to differential diagnosis with fever, kidney involvement, liver involvement, haemorrhagic symptoms and thrombocytopenia in endemic areas with clinically similar diseases such as dengue and leptospirosis.HighlightsFirst recorded case of hantavirus and dengue co-infection in a pregnant woman.First detailed report of clinical hantavirus infection in pregnant women in the Caribbean.First published report of clinical dengue infection in pregnant woman in the Caribbean.Possible complications of pregnancy following hantavirus infection.Pre-term birth and low birth weights.Clinical course of hantavirus infection in a Caribbean population.