Acute Hemorrhagic Fever: Clinical, Epidemiological and Laboratory Aspects in São Toméand Príncipe

Background: In the last 6 months, cases of acute hemorrhagic fever (AHF) have been recorded in Sao Tome and Principe (STP). Objective: To identify the clinical, epidemiological and laboratory parameters associated with AHF cases found in patients hospitalized in STP. Methods: Descriptive and quantitative analysis of AHF cases hospitalized in STP in the period December 2021 to May 19, 2022 through the variables: demographic data;clinical data;laboratory data and clinical outcome. Results: Analyzed 18 of 22 AHF cases, 50% of them male, mean age 33.7 years, 85.7% residing in the 2 largest districts of the country, 66.7% rural workers, administrative near maritime areas, sailors and domestics. 66.7% were healthy individuals. ≥50% had a fever, asthenia/weakness, myalgia, headache, lethargy, nausea, vomiting, and diarrhea. 22.2% to 33.3% had retro-orbital pain, abdominal pain, decreased consciousness, dyspnea/hypoxia, and cough. In a smaller register (5.6% - 11.1%), exanthema, convulsion, arthralgia, low back pain, chills, and chest pain. Bleeding from the digestive tract was found in 72.2%, followed by vaginal (33.3%), urethral (27.8%), nasal (22.2%), and oral (16.7%). 50% had laboratory confirmation for dengue, and another 50% with suspected clinical diagnosis without laboratory confirmation of the etiologic agent. Despite hemorrhage, 66.7% of confirmed cases were hemodynamically non-severe, and 88.9% of suspected cases were severe. Coinfection with malaria is evidenced in 11.1% of cases. 72.2% recovered and 27.8% died (deaths in 55.5% of suspected cases). Case deaths were male (100%), resident foreigners (40%), tool store employees, sailors and students, healthy (80%), and residing in the largest district in the country (60%). All deaths were hospitalized in serious condition, 80% were hospitalized for hemorrhage and shock, with bleeding arising between day 4 - 5 of illness in 60% and hospitalization on day 5 of illness. 60% died within ≤24 hours of hospitalization. 80% died from shock and multi-organ dysfunction and 20% from respiratory failure. Deaths had thrombocytopenia (100%), renal dysfunction (100%) and significantly increased transaminases (100%), anemia (75%) and leukocytosis (66.7%). 20% had a radiological change of pulmonary infiltrates. Conclusion: Our data reveal the complexity of the pathogens causing AHF and suggest the possible presence of other human pathogens usually unknown in the Santomean geographical territory.

Crimean-Congo Hemorrhagic Fever: An Overview

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral infection that is a serious threat to humans. The disease is widely distributed in Africa, Asia, and Europe and has developed into a serious public health concern. Humans become infected through the bites of ticks, by contact with a patient with CCHF, or by contact with blood or tissues from viremic livestock. Microvascular instability and impaired hemostasis are the hallmarks of the infection. Infection in human begins with nonspecific febrile symptoms, but may progress to a serious hemorrhagic syndrome with high mortality rates. Enzyme-linked immunoassay (ELISA) and polymerase chain reaction (PCR) are the most used and specific tests for the diagnosis. The mainstay of treatment is supportive. Although definitive studies are not available, ribavirin is suggested to be effective especially at the earlier phase of the infection. Uses of universal protective measures are the best way to avoid the infection. In this review, all aspects of CCHF are overviewed in light of the current literature.

Hemorrhagic Fever with Renal Syndrome Associated with Acute Pancreatitis

Hemorrhagic fever with renal syndrome (HFRS) is a systemic infectious disease caused by Hantaviruses and characterized by fevers, bleeding tendencies, gastrointestinal symptoms and renal failure. It encompasses a broad spectrum of clinical presentations, ranging from unapparent or mild illnesses to fulminant hemorrhagic processes. Among the various complications of HFRS, acute pancreatitis is a rare find. In this report, based on clinical data, laboratory and radiologic examination findings, we describe a clinical case, with HFRS from Dobrava virus, associated with acute pancreatitis. The patient was successfully treated by supportive management. Clinicians should be alert to the possibility of HFRS when examining patients with epidemiological data and symptoms of acute pancreatitis.

Hemorrhagic fever with renal syndrome complicated with aortic dissection:A case report

BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection.Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically.Here,we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection.CASE SUMMARY A 56-year-old man complained of high fever and generalized body ache,with decreased platelet counts of 10×10^9/L and acute kidney injury.The enzymelinked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive.During the convalescent period,he complained sudden onset acute chest pain radiating to the back,and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery.He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection.The patient recovered completely after surgery with other support treatments.CONCLUSION Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition.Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment.A causal relationship has yet to be confirmed.

DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β_2-microglobulin (β_2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

A Retrospective Study of Continuous Renal Therapy and Anticoagulation in Patients with Hemorrhagic Fever with Renal Syndrome

Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-type patients(severe group) and 71 critical-type patients(critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. Results The frequency of CRRT in the critical group was higher than that in the severe group(P < 0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was significantly higher than that of the severe group(P = 0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.

Crimean-Congo hemorrhagic fever from the immunopathogenesis, clinical, diagnostic, and therapeutic perspective: A scoping review

Crimean-Congo hemorrhagic fever virus(CCHFV) is responsible for widespread tick-borne zoonotic viral disease CCHF in African, Middle Eastern, Asian, and European countries. CCHFV can be spread to humans through tick bites or contact with infected animals or humans, and it often progresses from asymptomatic to severe/lethal illness, with fatality rates ranging from 10% to 40% in humans. Today, CCHF is growing into a significant public health concern due to its very high prevalence, severity of the condition, and lack of available vaccines and specific treatments. Recent research has been drawn towards a more accurate study of CCHFV characteristics, including the structure, genetic diversity, mechanisms involved in pathogenesis and immunopathogenesis, and clinical features. In addition, the use of animal models(mouse and non-human primates) and advanced diagnostic tools in recent years has resulted in a significant advance in CCHF related studies. In this context, we summarized the latest findings about CCHF research, its health complications, animal models, current diagnosis, vaccination, and CCHF treatments, and therapeutic strategies. Furthermore, we discussed existing deficiencies and problems in CCHFV analysis, as well as areas that still need to yield conclusive answers.

Significance of IL-1Ra and IL-6 gene variants in Turkish patients with Crimean-Congo hemorrhagic fever

Objective: To investigate the association between IL-1 Ra variable number of tandem repeat(rs2234663), IL-6-597 GA(rs1800797), IL-6-572 GC(rs1800796) and the risk of CrimeanCongo hemorrhagic fever(CCHF) in the Turkish patients. Methods: This study included 50 patients infected with CCHF and 50 healthy controls. These variants were genotyped using polymerase chain reaction and/or restriction fragment length polymorphism method. Results: The distribution of the IL-6-572 GC genotypes and alleles varied significantly between the patients and the controls. The subjects carrying IL-6-572 GC GG genotype and G allele had increased risk of developing CCHF compared to the control group(P=0.006, P=0.014, respectively). IL-6-572 GC GC genotype was higher in the controls than the patients(P=0.006). For the triple genotype combinations, the 1/2-GC-GG genotype combination was detected more frequently in the control group than CCHF patients(P=0.016). IL-6(-572/-597) GG-GG genotype was significantly higher in the patient group(P=0.015), while the GC-GG genotype was significantly lower in the patient group(P=0.005). Additionally, the G-G haplotype was significantly higher in the patient group(P=0.042), whereas C-G was found to be significantly lower in the patients than the control group(P=0.037). Conclusions: The results of this study suggest the IL-6-572 GC variant might be genetic markers of sensitivity to CCHF in the Turkish population and may facilitate greater protection against the disease.

Determination of CD_(30) Expression on Peripheral Blood T Lymphocyte Subsets in Patients with Hemorrhagic Fever with Renal Syndrome by FCM

To determine the CD 30 expression on peripheral blood T lymphocyte subsets in patients with hemorrhagic fever with renal syndrome (HFRS) and its clinical implications, double immunofluorescence technique and flow cytometry were used. There was no significant difference among the severe group, mild-moderate group and normal control group in the CD + 4CD - 30 T lymphocyte subset. While the CD + 4CD + 30 T cells of HFRS patients were increased and the difference between severe group and mild-moderate group or normal control group were very significant (P<0.01) and the difference between the mild-moderate group and normal control group was also significant (P<0.05). The CD + 8CD - 30 T cells were increased while the CD + 8CD + 30 T cells decreased obviously in HFRS patients, and the differences among three groups in both subsets were very significant (P<0.01). The results showed that the humoral immunity and cellular immunity are overactive in HFRS patients during acute phase. The loss of balance between T lymphocyte subsets may play an important role in the pathophysiology of HFRS and is closely correlated with the severity of the HFRS.

Epidemic Hemorrhagic Fever in Hubei Frovince,The Peoples Repulic of China: A Clinical and Serological Study

Between July 1975 and April 1980, 71 patients were admitted to the 2ndAttached Hospital of Hubei Provincial Medical College in Wuchang withthe diagnosis of Epidemic Hemorrhagic Fever (EHF). The clinical courseamong these patients was similar to that described for patients with KoreanHemorrhagic Fever, Nephropathica Epidemica of Scandanavia and Hemor-rhagic Fever with Renal Syndrome of the U.S.S.R. The overall mortalitywas 11.2％. Sera obtaincd from some of these patients as well as frompatients admitted to the First Attached Hospital of Hubei Provincial Me-dical College were tested against an antigen associated with Korean He-morrhagic Fever and showed exceedingly high antibody titers. We concludethat EHF in Centfal China represents the same disease process as KoreanHemorrhagic Fever.

Dengue hemorrhagic fever and the liver

Dengue hemorrhagic fever(DHF)is one of the most rapidly emerging infections of tropical and subtropical regions worldwide.It affects more rural and urban areas due to many factors,including climate change.Although most people with dengue viral infection are asymptomatic,approximately 25%experience a selflimited febrile illness with mild to moderate biochemical abnormalities.Severe dengue diseases develop in a small proportion of these patients,and the common organ involvement is the liver.The hepatocellular injury was found in 60%-90%of DHF patients manifested as hepatomegaly,jaundice,elevated aminotransferase enzymes,and critical condition as an acute liver failure(ALF).Even the incidence of ALF in DHF is very low(0.31%-1.1%),but it is associated with a relatively high mortality rate(20%-68.3%).The pathophysiology of liver injury in DHF included the direct cytopathic effect of the DENV causing hepatocytes apoptosis,immunemediated hepatocyte injury induced hepatitis,and cytokine storm.Hepatic hypoperfusion is another contributing factor in dengue shock syndrome.The reduction of morbidity and mortality in DHF with liver involvement is dependent on the early detection of warning signs before the development of ALF.

STUDIES ON DYNAMIC CHANGES AND COMPARISONS OF SERUM SPECIFIC IGM AND IGG ANTIBODIES IN PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

The speciric IgM and IgG antibodies in serum samples from patients with hemorrhagic fever with renal syndrome (HFRS) were sequentially and simultaneously determined during the course of the disease. The results showed that the detectable days and the days reaching 100% positive rate after onset of illness in specific IgM antibodies were earlier than those in specific IgG antibodies. No significant differences were observed between the titers of specific IgM antibodies on different days after onset of the disease while the titers of specific IgG antibodies differed, significantly on different days after onset of illness (F'= 11. 72,P< 0. 01 ). The titers of specific IgM antibodies in different clinical types were not significantly different at the same illness day but the titers of specific IgG antibodies in various clinical types were significantly different from day 7 to day 8 after onset of disease (F' = 4. 004, P< 0. 05). The levels of specific IgM and IgG antibodies were more stable and the crossings of the IgM and IgG antibody curves presented later in patients with mild and middle clinical types than those in patients with severe and gravis types. These results suggest that the detection of specific IgM antibodies may be useful for the early laboratory diagnosis of HFRS,the excess Production of specific IgG antibodies may play a role in the formation of immune complexes and the exacerbation of pathologic damage in patients with severe and gravis types and the observations of the dynamic changes of specific IgM and IgG antibody curves may have some implications in evaluating the seventies of the disease and the prognosis of the patients with HFRS.

Study on Biologic Activity for Membrane of Normal Bone Marrow Cells with Infection of Epidemic Hemorrhagic Fever Virus

Using DPH fluorescence probe, the membrane of normal bone marrow cells with infection of epidemic hemorrhagic fever virus (EHFV) was labeled. The membrane lipid fluidity was obviously decreased from the membrane lipid fluorescence polarization. The membrane lipid fluidity of lympho- cyte, monocyte and neutrophilic granulocyte was dynamically observed. After culturing the cells for 1, 6, 24 and 72 h, it was found that all the membrane lipid fluidity of the infected cells was de- creased obviously with the longer the culturing time, the more obvious it. Compared with the normal control groups, there was a significant difference statistically (P<0. 05-0. 01). It was suggested that the decrease of the membrane lipid fluidity of normal bone marrow cell with infection of EHFV had correlation with the degree of virus invading and cellfunction injury.

Dengue hemorrhagic fever and cardiac involvement

Dengue viral infection(DVI)is one of the world’s most significant viral infections spreading.Most of the patients have been asymptomatic,with relatively benign clinical manifestations and outcomes.However,a small number of patients have progressed to severe dengue diseases,including hemorrhage,multi-organ impairment,and increased vascular leakage causing hypovolemic shock,which can cause cardiovascular collapse and death.Numerous lines of evidence have demonstrated that DVI could also cause cardiac dysfunction,arrhythmias,and severe myocarditis.The treatment for dengue hemorrhagic fever(DHF)patients remains symptomatic and supportive,with close monitoring of hemodynamic status.The contributory role of cardiac dysfunction in DHF patients has potentially critical implications on the management.This review will address the current knowledge of cardiac involvement in DHF patients and the management strategy to reduce the fatality outcome.

Modeling and Forecasting Malaria and Dengue Hemorrhagic Fever Incidence and Prevalence in Northern Thailand

Malaria and dengue hemorrhagic fever （DHF） are infectious diseases prevalent in many tropical countries, including Thailand. Thailand is located geographically in a tropical zone and the transmission of malaria and DHF is common, particularly in the upper Northern region of the country. The objective of this study is to identify the patterns of hospital-diagnosed Malaria and DHF incidences by using the previous monthly or quarterly periods of incidences occurring in the upper Northern region of Thailand. The authors use additive plus multiplicative regression models to describe these patterns. The models can be used to forecast malaria and DHF incidences, thus predicting where epidemics are likely to occur. This information can be used to prevent disease outbreaks occurring. Graphical displays showing district and period effects are presented. The results of this study show that historical malaria and DHF incidence rates can be used to provide a useful model for forecasting future epidemics. The graphical display shows the improvement of risk prediction brought about by model. The model, even if based purely on statistical data analysis, can provide a useful basis for allocation of resources for disease prevention.

The Risk of Severe Acute Kidney Injury Requiring Renal Replacement Therapy in Viral Hemorrhagic Fevers. A Review of Literature

Objective: It demonstrates the correlation of the viral hemorrhagic fever with kidney failure and the treatment as well as the outcome. Method: A PubMed search of the English literature from 1999 to 2019 was performed using “viral hemorrhagic fever, Case Report, Renal Failure” as the subject. The inclusion criteria were the following: 1) case report and case series of two or more patients;2) the report detailed the clinical presentation and reported the status of the renal system;3) the report described the management of renal failure if any;and 4) the etiology of the infection is known and is one of the known agents of viral hemorrhagic fever, listed on the centers of disease control website. We excluded infections related to vaccination related to viral hemorrhagic fever. Result: We found the mean age of these patients was 41.5. The male to female ratio was about 3.5:1. Dengue and Hantaviruses constituted 70.5% of patients. The overall mortality of the study cohort was 32.2%. Half of the patients had acute kidney injury and required renal replacement therapy. The chi-square statistic is 0.41;The p-value is 0.51;The chi-square statistic is 6.4254. Overall mortality was 32.3% in one cohort of 78 patients. The illness goes through several stages [1] [2] of clinical features and some viruses in the group have a high case fatality rate. Conclusions: Early diagnosis with aggressive supportive care is critical for improving clinical outcomes. Renal involvement is common. Amongst the cohort reviewed, of patients who had acute kidney injury, half of the patients required renal replacement support. However, some viruses cause greater kidney injury than others, for instance, kidney injury is more severe in Dengue hemorrhagic fevers when compared to Hantaviruses. Simultaneous management of public health by prevention and control of outbreaks is particularly important.

Sequencing, Expression and Diagnostic Application of the Nucleoprotein Gene of Xinjiang Hemorrhagic Fever Virus

In order to analyze the nucleoprotein (NP) gene of Crimean-Congo hemorrhagic fever virus (CCHFV), viral RNA was amplified by RT-PCR by using the proof-reading DNA polymerase to produce the complete NP gene. The PCR product was sequenced, analyzed for phylogenesis and cloned into the expression vector pET32a and the recombinant plasmid expressed in E.coli BL-21 with high yield. The primarily purified fused protein was used to coat ELISA plates for the detect antibodies. It was found the similarities between NP gene of BA88166 and other XHFVs in nucleotide level and amino acid contents were very significant, and the NP gene of BA88166 encoded a nucleoprotein with 482 amino acid and a deduced molecular weight (MW) of 54?kDa. Western blot assay showed that the fusion protein expressed in bacteria possessed good antigenicity. The results with ELISA for the detection of the human and animal sera collected in endemic areas were found to be in good accordance to the clinical diagnosis. It concluded that the relations of NP genes of XHFV BA88166 and other XHFVs appeared to be evolutionally close. The methodologies established in this study were accurate, specific, rapid and reproducible for the clinical examinations and epidemiological survey.

Effect of High-Quality Nursing on Patients with Hemorrhagic Fever with Renal Syndrome

Objective:To explore and analyze the effect of high-quality nursing on patients with epidemic hemorrhagic fever with renal syndrome.Methods:Ninety patients with epidemic hemorrhagic fever with renal syndrome treated in Huyi District People’s Hospital from October 2021 to January 2022 were randomly divided into an experimental group and a control group,with 45 cases in each group.The control group received routine nursing and the experimental group received high-quality nursing.The effect of routine nursing and high-quality nursing were compared and analyzed based on the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),the degree of satisfaction with nursing care,and the patients’quality of life.Results:Before nursing,there was no significant difference in the patients’psychological state between the two groups(P>0.05);after nursing,there was significant difference in the patients’psychological state between the two groups(P<0.05);the degree of satisfaction with nursing care of the experimental group was significantly higher than that of the control group(P<0.05);comparing the quality of life of the two groups,the quality-of-life score of the control group was significantly lower than that of the experimental group(P<0.05).Conclusion:For patients with epidemic hemorrhagic fever with renal syndrome,high-quality nursing can significantly and effectively improve their psychological state,level of satisfaction with nursing care,and quality of life.

Study on the Cytotoxic T Lymphocytes Clone Specific for the Nucleocapsid Protein of Hantaan Virus from Peripheral Blood in Patients with Hemorrhagic Fever with Renal Syndrome

In order to elucidate the molecular and immunological mechanisms as well as the pathogenesis of hemorrhagic fever with renal syndrome (HFRS), the CD8 + cytotoxic T lymphocytes (CTL) clone was established directly from peripheral blood mononuclear cells (PBMC) of patients with HFRS. The activities of CTL were detected as usual with EBV-transformed lymphoblastoid cell line (BLCL) as target cells. The results showed that the CTL clone could recognized and killed the target cells with specificity of nucleocapsid protein of Hantaan virus (HTNVNP) with the cytotoxicity percentages of 50.2%, 25.4% and 39.0% respectively. These results demonstrated that the antigenic epitopes of HTNVNP mainly located on the C-terminal of the viral nucleocapsid protein.

CLINICAL SIGNIFICANCE OF DETECTING SERUM ANTIBODIES TO NUCLEOPROTEIN AND GLYCOPROTEIN G_2 OF HANTAAN VIRUS IN PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

Antibody blocking enzyme linked immunosorbent assays, respectively detecting antibodies to Hantaan virus nucleoprotein (NPAb) and glycoprotein GZ (G,Ab), were developed using monoclonal antibody L133, L13r3, LV48A and LVZB28B NPAb and GZAb in 291 serum samples from 65 patientswith kemorrkagic fever with renal syudrome (HFRS) were detfrmlned by these methods. The positive rates or NPAb were 90N on day 2-3 and 100 % on day 8-9 arter onset of disease, respectively.NPAb titers Increased during fever period and reached Peak levels during kypotensive and oliguric periods of HFRS. It was suggested that NPAb might be an important component Involved in the immunopathogenlc lin'alrmeut of HFRS and the detection of NPAb might be useful for the early diagnosis or HFRS. The I,osltlve rates and titers of GZAh were very low during the rirst three periods,namely rever, hypoteuslve and ollgurlc periods, and reached high levels during the convalescent period. GRAb titers were negatively related to the I,rotelnurla levels during the course of HFRS. It wasIndicated that GZAb might be the main component or neutralizing autlhodles to Hantaan virus Infection and the efrlclent production or GZAb was a good marker ror predicting the recovery and betterprognosis of HFRS.