A Q fever case mimicking crimean-congo haemorrhagic fever

Coxiella burnetii is the bacterium that causes Q fever. Human infection is mainly transmitted from cattle, goats and sheep. The disease is usually self-limited. Pneumonia and hepatitis are the most common clinical manifestations. In this study, we present a case of Q fever from the western part of Turkey mimicking Crimean-Congo haemorrhagic fever (CCHF) in terms of clinical and laboratory findings.     

Profile of transforming growth factor-beta 1 in patients with dengue haemorrhagic fever

The pathogenesis of dengue haemorrhagic fever (DHF) is incompletely understood but it has been suggested that various cytokines may have a role in the process. In this study the profile of the cytokine Transforming Growth Factor-beta 1 (TGF-beta1) was investigated in the sera of 79 patients with various grades of dengue illness and in 21 normal healthy controls. Also, TGF-beta1-specific mRNA was examined in their peripheral blood mononuclear cells (PBMC). The results showed that neither TGF-beta1 protein nor its mRNA were detected in healthy controls. In dengue patients, the TGF-beta1 protein and its mRNA were detected in 96%. However, among the patient groups, the levels of TGF-beta1 were lowest in patients with dengue fever (DF; mean value 315 +/- 95 pg/ml) and were highest in patients with DHF grade IV (mean value 1350 +/- 280 pg/ml; P = < 0. 001). The cytokine appeared during the first four days of illness (304 +/- 90 pg/ml) and gradually increased, reaching peak levels (1050 +/- 215 pg/ml) after the 9th day of the illness. Thus TGF-beta1 in the sera and TGF-beta1-mRNA in the PBMC were present in most of the patients with dengue (96%) but the cytokine levels were highest during the later periods of illness and in patients with DHF grade IV, suggesting a possible role of TGF-beta1 in the pathogenesis of DHF.     

Study of anti-dengue NS1 antibody by Western blot

The presence of anti-nonstructural protein (NS1) antibody in natural dengue infections has been suspected to be associated with development of dengue haemorrhagic fever (DHF). The Western blot technique was used to study the dynamics of the immune response to NS1 and to determine the frequency of anti-NS1 antibody among confirmed dengue patients in Indonesia, where DHF is common, and in Puerto Rico, where DHF is less frequently observed. Anti-NS1 antibody was rarely found in those with primary infections in either group. The antibody occurred at a significantly higher frequency in acute-phase serum samples from secondary infections in Indonesia than in those from Puerto Rico. No difference was observed, however, in Indonesian patients with secondary infection who had dengue fever or DHF.     

Emergence of Crimean–Congo haemorrhagic fever in Greece

In the summer of 2008, the first case of Crimean–Congo haemorrhagic fever (CCHF) was observed in Greece. The laboratory diagnosis was established using nested RT-PCR and quantitative real-time RT-PCR. A high viral load and increased levels of cytokines were detected on the third day of illness and the patient died 7 days after the onset of symptoms. Nucleotide sequence analysis revealed that the Greek CCHF virus strain had high sequence identity with other Balkan CCHF virus strains.     

Pregnancy and Crimean-Congo haemorrhagic fever

Crimean-Congo Hemorrhagic fever (CCHF) is a potentially fatal viral infection with reported case fatality rates of 5–30%. Humans become infected through tick bites, by contact with a patient with CCHF during the acute phase of infection, or by contact with blood or tissues from viraemic livestock. In this first report in the literature, we present the characteristics of three pregnant women with CCHF infection and the outcome of their babies. Transmission of the CCHF infection could be either intrauterine or perinatal. In endemic regions, CCHF infection should be considered in the differential diagnosis of HELLP syndrome (haemolytic anaemia, elevated liver enzymes, low platelet count), and obstetricians should be familiar with the characteristics of CCHF infection. In the aetiology of necrotising enterocolitis, CCHF should be considered.     

Seroepidemiological study of Crimean-Congo haemorrhagic fever in Greece, 2009-2010

To estimate endemic areas for Crimean-Congo haemorrhagic fever (CCHF) in Greece, a country-wide seroepidemiological study was conducted, and 1611 human sera were prospectively collected along with data regarding possible risk factors for acquisition of infection, and tested for CCHF virus IgG antibodies by ELISA. The overall seroprevalence was 4.2%, with significant differences among prefectures, ranging from 0 to 27.5%. Multivariate analysis revealed that slaughtering and agricultural activities were significant risk factors for CCHFV seropositivity. The significantly high seroprevalence in specific prefectures, together with the extremely low number of CCHF cases, suggest that this phenomenon might be strain-related.     

Crimean-Congo haemorrhagic fever presenting as epididymo-orchitis

BackgroundCrimean-Congo haemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus.ObjectivesA 53-year-old man presented with fever and acute painful scrotal swelling simulating acute epididymo-orchitis.Study designBased on the clinical and epidemiological findings, CCHF virus infection and epididymo-orchitis were suspected. This symptom, rarely reported in viral haemorrhagic fevers, was observed in this case.ResultsThe diagnosis was confirmed by detection of the IgM antibody to CCHF virus and positive RT-PCR.ConclusionWe report the first case of imported CCHF presenting as epididymo-orchitis. This symptom is a rare complication of CCHF, and the clinician should consider this entity in the differential diagnosis of adults with epididymo-orchitis.     

Serum cytokine/chemokine profiles in patients with dengue fever (DF) and dengue hemorrhagic fever (FHD) by using protein array

BackgroundDENV infection can induce different clinical manifestations varying from mild forms to dengue fever (DF) or the severe hemorrhagic fever (DHF). Several factors are involved in the progression from DF to DHF. No marker is available to predict this progression. Such biomarker could allow a suitable medical care at the beginning of the infection, improving patient prognosis.ObjectivesThe aim of this study was to compare the serum expression levels of acute phase proteins in a well-established cohort of dengue fever (DF) and dengue hemorrhagic fever (DHF) patients, in order to individuate a prognostic marker of diseases severity.Study designThe serum levels of 36 cytokines, chemokines and acute phase proteins were determined in DF and DHF patients and compared to healthy volunteers using a multiplex protein array and near-infrared (NIR) fluorescence detection. Serum levels of IL-1ra, IL-23, MIF, sCD40 ligand, IP-10 and GRO-α were also determined by ELISA.ResultsAt the early stages of infection, GRO-α and IP-10 expression levels were different in DF compared to DHF patients. Besides, GRO-α was positively correlated with platelet counts and IP-10 was negatively correlated with total protein levels.ConclusionsThese findings suggest that high levels of GRO-α during acute DENV infection may be associated with a good prognosis, while high levels of IP-10 may be a warning sign of infection severity.     

Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections

Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue haemorrhagic fever (DHF). To develop a better understanding of the roles of platelet-associated IgG (PAIgG) and IgM (PAIgM) in inducing thrombocytopenia and its severity of disease in patients with secondary dengue virus infection, the relationship between the PAIgG or PAIgM levels and disease severity as well as thrombocytopenia was examined in 78 patients with acute phase secondary infection in a prospective hospital-based study. The decrease in platelet count during the acute phase recovered significantly during the convalescent phase. In contrast, the increased levels of PAIgG or PAIgM that occurred during the acute phase of these patients decreased significantly during the convalescent phase. An inverse correlation between platelet count and PAIgG or PAIgM levels was found in these patients. Anti-dengue virus IgG and IgM activity was found in platelet eluates from 10 patients in an acute phase of secondary infection. Increased levels of PAIgG or PAIgM were significantly higher in DHF than those in dengue fever (DF). An increased level of PAIgM was associated independently with the development of DHF, representing a possible predictor of DHF with a high specificity. Our present data suggest that platelet-associated immunoglobulins involving antidengue virus activity play a pivotal role in the induction of thrombocytopenia and the severity of the disease in secondary dengue virus infections.     

A prospective prediction tool for understanding Crimean–Congo haemorrhagic fever dynamics in Turkey

ObjectivesWe aimed to develop a prospective prediction tool on Crimean–Congo haemorrhagic fever (CCHF) to identify geographic regions at risk. The tool could support public health decision-makers in implementation of an effective control strategy in a timely manner.MethodsWe used monthly surveillance data between 2004 and 2015 to predict case counts between 2016 and 2017 prospectively. The Turkish nationwide surveillance data set collected by the Ministry of Health contained 10 411 confirmed CCHF cases. We collected potential explanatory covariates about climate, land use, and animal and human populations at risk to capture spatiotemporal transmission dynamics. We developed a structured Gaussian process algorithm and prospectively tested this tool predicting the future year's cases given past years' cases.ResultsWe predicted the annual cases in 2016 and 2017 as 438 and 341, whereas the observed cases were 432 and 343, respectively. Pearson's correlation coefficient and normalized root mean squared error values for 2016 and 2017 predictions were (0.83; 0.58) and (0.87; 0.52), respectively. The most important covariates were found to be the number of settlements with fewer than 25 000 inhabitants, latitude, longitude and potential evapotranspiration (evaporation and transpiration).ConclusionsMain driving factors of CCHF dynamics were human population at risk in rural areas, geographical dependency and climate effect on ticks. Our model was able to prospectively predict the numbers of CCHF cases. Our proof-of-concept study also provided insight for understanding possible mechanisms of infectious diseases and found important directions for practice and policy to combat against emerging infectious diseases.     

Dengue hemorrhagic fever – A systemic literature review of current perspectives on pathogenesis,prevention and control

BackgroundDengue is an arboviral disease caused by dengue virus. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to potentially fatal disease, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). We conducted a literature review to analyze the risks of DHF and current perspectives for DHF prevention and control.MethodsAccording to the PRISMA guidelines, the references were selected from PubMed, Web of Science and Google Scholar database using search strings containing a combination of terms that included dengue hemorrhagic fever, pathogenesis, prevention and control. Quality of references were evaluated by independent reviewers.ResultsDHF was first reported in the Philippines in 1953 and further transmitted to the countries in the region of South-East Asia and Western Pacific. Plasma leakages is the main pathophysiological hallmark that distinguishes DHF from DF. Severe plasma leakage can result in hypovolemic shock. Various factors are thought to impact disease presentation and severity. Virus virulence, preexisting dengue antibodies, immune dysregulation, lipid change and host genetic susceptibility are factors reported to be correlated with the development of DHF. However, the exact reasons and mechanisms that triggers DHF remains controversial. Currently, no specific drugs and licensed vaccines are available to treat dengue disease in any of its clinical presentations.ConclusionThis study concludes that antibody-dependent enhancement, cytokine dysregulation and variation of lipid profiles are correlated with DHF occurrence. Prompt diagnosis, appropriate treatment, active and continuous surveillance of cases and vectors are the essential determinants for dengue prevention and control.     

Analysis of risk-factors among patients with Crimean-Congo haemorrhagic fever virus infection: severity criteria revisited

The aim of this study was to determine the predictors of mortality among patients infected with Crimean-Congo haemorrhagic fever (CCHF) virus. Among patients with acute febrile syndrome, characterised by malaise, bleeding, leukopenia and thrombocytopenia, who were admitted to hospital during the spring and summer of 2002-2004, 54 had positive IgM and/or PCR results for CCHF virus in blood or tissue. The overall case fatality rate was 7.4%. Among the fatalities, haematemesis (p 0.009), melaena (p 0.001) and somnolence (p 0.022) were more common, the median platelet count was significantly lower (10,600/mL vs. 20,000/mL; p 0.038), the mean prothrombin time (27 s vs. 16 s; p 0.002) and mean activated partial thromboplastin time (73 s vs. 44 s; p < 0.001) were longer, and the mean alanine transferase (ALT) level (1,125 vs. 331; p < 0.001), the mean aspartate transferase (AST) level (3,118 vs. 913; p 0.004) and the mean fibrinogen level (119 vs. 340; p 0.012) were higher. Serum IgM and IgG against CCHF virus was detected in 25% and 0%, respectively, of fatal cases, compared with 94% and 62%, respectively, of cases with favourable outcomes. Oral ribavirin was prescribed to 22 (41%) patients. Of the four fatal cases, it was the intention to prescribe ribavirin to three patients, but this was not possible because of haematemesis and melaena. Higher levels of AST (>or= 700 U/L) and ALT (>or= 900 U/L) are suggested for use as severity criteria. Oral ribavirin was not effective for patients with haematemesis, and intravenous ribavirin is necessary for treatment of CCHF.     

Elevated levels of IL-8 in dengue hemorrhagic fever

Dengue virus causes dengue fever, a mild febrile illness, and at times dengue hemorrhagic fever (DHF), a severe illness the pathogenesis of which is not fully understood. Given the crucial roles played by interleukin-8 (IL-8) as a chemoattractant cytokine and in inflammatory processes, levels of circulating IL-8 in the sera and IL-8 mRNA in the peripheral blood mononuclear cells (PBMC) were measured in 99 patients of a recent dengue epidemic that occurred in India in 1996 and in 21 normal healthy controls. Twenty-six of the patients had dengue fever (DF) and the remaining 73 were diagnosed as having different grades of DHF. All the control normal sera were negative for IL-8, so were their PBMC for IL-8 mRNA. Increased levels of IL-8 in the sera and IL-8 mRNA in their PBMC were observed in patients with severe illness of DHF grades III and IV. Only two out of 26 patients of DF and one out of 10 DHF grade I patient were positive for IL-8 and all three deteriorated to DHF grade IV within 24 hr. All six patients of DHF grade IV who died had higher serum level of IL-8 above 200 pg/ml, the highest being 5,568 pg/ml in one patient; the presence of mRNA for IL-8 was very high in all patients. A striking correlation was observed between increased levels of IL-8 and severe DHF, with greater levels in patients with increased grade of the disease and death. These results suggest that IL-8 may have an important role and may be an indicator of increasing severity of the disease and death. J. Med. Virol. 56:280–285, 1998. © 1998 Wiley-Liss, Inc.     

阳江市一起基孔肯雅热暴发疫情流行病学调查

目的了解基孔肯雅热的流行特征,探索有效的防控策略,为今后防控工作提供依据。方法根据病例定义进行病例搜索,对符合病例定义的病例进行流行病学调查;采用酶联免疫吸附试验方法检测登革热病毒IgM和IgG抗体;采用实时荧光定量逆转录聚合酶链反应方法检测登革热病毒核酸和基孔肯雅热病毒核酸。结果 2010年9月12日至10月21日,阳江市某建筑工地发生基孔肯雅热病27例,总罹患率为11.07%（27/244）;其中男性17例,占62.96%,女性10例,占37.04%;检测15份恢复期病例血样登革热病毒IgM和IgG抗体,其中2份病例血样IgM抗体阳性,其余13份为阴性,15份病例血样IgG抗体均为阴性;检测5份现症病例血样,登革热病毒核酸均为阴性,2份基孔肯雅热病毒核酸阳性。结论这是一起基孔肯雅热暴发疫情,加强出入境检疫、开展医疗机构症状监测和控制传播疾病的媒介密度是预防控制孔肯雅热的重要措施。     

Fulminant hepatitis in dengue haemorrhagic fever.

Dengue virus is estimated to cause over 100 million infections throughout the world annually. While dengue infections can have a wide range of infections, atypical manifestations have been described. These involve the central nervous system, cardiac alterations and hepatitis. Here, we highlight a case of dengue haemorrhagic fever (DHF) with fulminant hepatitis. A 55-year-old male was admitted for 16 days, developing severe thrombocytopenia as low as 6x10(9)/L, haematocrit of 48% with transaminitis: ALT: 3,515 U/L, AST: 12,541 U/L, GGT: 1,094 U/L. Subsequent investigations excluded any occult liver lesions, hepatitis A, B and C, Wilson's disease, Epstein-Barr virus and Cytomegalo virus as possible causes. His dengue PCR was positive. His condition subsequently improved with supportive treatment. Liver injury from dengue virus is mediated by its direct infection of hepatocytes and kupffer cells. While mild to moderate elevations of serum aminotransferases (ALT and AST<5X normal) are common in dengue virus infection, liver failure rarely dominate the clinical picture. Liver dysfunction was commoner in DHF, with case reports indicating that severe hepatic dysfunction (ALT and AST>10X normal) was seen with DHF associated with spontaneous bleeding tendencies. Overall prognosis depends on age and other concomitant co-morbidities. We seek to review the literature on dengue infections with hepatitis and discuss issues pertaining to pathophysiology of liver impairment in dengue, the frequency of transaminitis associated with DHF and the overall prognosis.     

The immunopathogenesis of dengue haemorrhagic fever

Over the past 20 years, dengue haemorrhagic fever (DHF) has been the subject of intensive epidemiological, clinical, virological and immunological investigations. Considerable debate and controversy have surrounded its causation and the probable role of immunological mechanisms in its pathogenesis. The exact cause of DHF is still uncertain and this article reviews current thinking about the problem.     

Seroepidemiology and active surveillance of dengue fever/dengue haemorrhagic fever in Delhi

The aims of the present study were to carry out surveillance for dengue virus infection in adults with short-duration fever, and serological study of dengue virus infection in persons without fever. Patients were divided into two groups. Group 1 included patients above 12 years of age with fever of 2-12 days duration without any apparent cause. Of these, patients who presented with fever for 2-5 days were included for virus isolation (group 1a) while those who presented within 6-12 days of the onset of fever were included for the dengue-specific IgM serology (group 1b). Group 2 included a sample of population belonging to all age groups but without pyrexia and blood was collected for dengue-specific IgG serology. Twenty-six patients were enrolled in group 1a over a period of 4 months (September to December, 1997). Of these, DEN1 was isolated in 5 cases. Group 1b included 182 patients, out of which 34 (18.68%) were positive for dengue-specific IgM antibodies. Significantly, all the positive cases were detected during the months of September to November. Retro-orbital pain was present in a significantly more number of IgM-positive cases as compared to IgM-negative cases. Group 2 included 125 cases without fever. The overall positivity for dengue-specific IgG antibodies was 77.6%, with the highest positivity of 100% in the age group of 31-40 years. It was concluded that dengue virus infection is endemic in and around Delhi with peak incidence between September and Novemver. The prevalent serotype during September and December 1997 was DEN1. Since previous epidemic of DHF was due to DEN2 type, isolation of DEN1 serotype indicates changes of another epidemic of DHF due to DEN1 serotype. The stresses the urgent need for implementation of measures to control the transmission of dengue infection.     

Dengue fever and dengue haemorrhagic fever: challenges of controlling an enemy still at large

Dengue virus infections are a serious cause of morbidity and mortality in most tropical and subtropical areas of the world: mainly Southeast and South Asia, Central and South America, and the Caribbean. Understanding the pathogenesis of dengue haemorrhagic fever (DHF), the severe form of dengue illness, is a very important and challenging research subject. Viral virulence and immune responses have been considered as two major factors responsible for the pathogenesis. Virological studies are attempting to define the molecular basis of viral virulence. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators apparently plays a key role in inducing plasma leakage, shock and haemorrhagic manifestations. It is likely that the entire process is initiated by infection with a so-called virulent dengue virus, often with the help of enhancing antibodies in secondary infection, and then triggered by rapidly elevated cytokines and chemical mediators produced by intense immune activation. However, understanding of the DHF pathogenesis is not complete. We still have a long way to go.     

Serodiagnosis of dengue virus infection in patients presenting to a tertiary care hospital

Dengue is an acute infectious disease of viral etiology. It is probably one of the most important arthropod borne viral disease in terms of human morbidity and mortality. The spectrum of disease ranges from self-limited dengue fever to more severe forms of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Laboratory diagnosis of dengue virus infection mainly depends on detection of virus specific antibodies. The aim of the study was to correlate the serological results with clinical presentation in patients with a diagnosis of dengue. Eleven out of 15 (73.3%) patients with DHF and DSS had secondary antibody response and mortality was 100% in these patients.     

A study on gender-related differences in laboratory characteristics of dengue fever

Studies have reported significant gender-related differences in serological tests for detection of NS1 antigen and IgM antibody used for diagnosing dengue fever. However, no such study has been undertaken in India though dengue fever is endemic in this country. Therefore, this study was planned to study the association of serological findings with gender in 700 patients suspected to be suffering from dengue fever in the Indian setting. Haematological parameters of seropositive patients were also studied. Seropositivity and haemorrhagic findings were significantly associated with the female gender. Positive NS1 antigen and IgM antibody results were significantly associated with females and males, respectively.