Cause Of Arboviral Disease Research Articles

The phenuivirus Toscana virus makes an atypical use of vacuolar acidity to enter host cells.

Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons and cell lines, we found that virus binding to the cell surface was specific, and 50% of bound virions were endocytosed within 10 min. Virions entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomal compartments. Penetration required intact late endosomes and occurred within 30 min following internalization. Virus entry relied on vacuolar acidification, with an optimal pH for viral membrane fusion at pH 5.5. The pH threshold increased to 5.8 with longer pre-exposure of virions to the slightly acidic pH in early endosomes. Strikingly, the particles remained infectious after entering late endosomes with a pH below the fusion threshold. Overall, our study establishes Toscana virus as a late-penetrating virus and reveals an atypical use of vacuolar acidity by this virus to enter host cells.

Comparing the performance of dengue virus IgG and IgG-capture enzyme-linked immunosorbent assays in seroprevalence study

BackgroundDengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. Currently Dengvaxia, the first dengue vaccine licensed in 20 countries, was recommended for DENV seropositive individuals aged 9–45 years. Studying dengue seroprevalence can improve our understanding of the epidemiology and transmission dynamics of DENV, and facilitate future intervention strategies and assessment of vaccine efficacy. Several DENV envelope protein-based serological tests including IgG and IgG-capture enzyme-linked immunosorbent assays (ELISAs) have been employed in seroprevalence studies. Previously DENV IgG-capture ELISA was reported to distinguish primary and secondary DENV infections during early convalescence, however, its performance over time and in seroprevalence study remains understudied.MethodsIn this study, we used well-documented neutralization test- or reverse-transcription-polymerase-chain reaction-confirmed serum/plasma samples including DENV-naïve, primary and secondary DENV, primary West Nile virus, primary Zika virus, and Zika with previous DENV infection panels to compare the performance of three ELISAs.ResultsThe sensitivity of the InBios IgG ELISA was higher than that of InBios IgG-capture and SD IgG-capture ELISAs. The sensitivity of IgG-capture ELISAs was higher for secondary than primary DENV infection panel. Within the secondary DENV infection panel, the sensitivity of InBios IgG-capture ELISA decreased from 77.8% at < 6 months to 41.7% at 1–1.5 years, 28.6% at 2–15 years and 0% at > 20 years (p < 0.001, Cochran-Armitage test for trend), whereas that of IgG ELISA remains 100%. A similar trend was observed for SD IgG-capture ELISA.ConclusionsOur findings demonstrate higher sensitivity of DENV IgG ELISA than IgG-capture ELISA in seroprevalence study and interpretation of DENV IgG-capture ELISA should take sampling time and primary or secondary DENV infection into consideration.

West Nile Virus Surveillance in Sentinel Chickens and Mosquitoes in Panama City Beach, Florida, from 2014 To 2020.

Over 20 years since its introduction, the West Nile virus (WNV) continues to be the leading cause of arboviral disease in the USA. In Panama City Beach (Bay County, FL), WNV transmission is monitored using sentinel chickens and testing mosquito pools for presence of viral RNA. In the current work, we monitored WNV transmission from 2014 to 2020 through weekly serology sampling of sentinel chickens; mosquito populations through biweekly mosquito collections by suction traps (1 m and 9 m) and weekly gravid trap collections; and mosquito infection rates using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Samples were sent to the Bureau of Public Health Laboratories (Tampa, FL) for testing presence/absence of WNV via RT-PCR assay. Our results indicated that canopy surveillance could augment ground collections, providing greater proportions of Culex mosquitoes with less bycatch compared with ground collections. Serology indicated 94 seroconversions to WNV in the study area from 2014 to 2020. The most active year was 2016, which accounted for 32% (n = 30) of all seroconversions reported during the study period. We detected 20 WNV-positive mosquito pools from Culex quinquefasciatus during 2014-17; mosquito infection rates ranged from 2.02 to 23.81 per thousand (95% CI). Climate data indicated anomalously high precipitation in 2014-19 preceding WNV transmission. Data analyzed herein indicate utility in year-round continuous and diversified surveillance methodologies. This information is needed to properly calibrate future models that could assist with predicting transmission events of WNV in Panama City Beach, FL.

Assess the changes in hematological parameters in dengue and malaria fever

Introduction: Dengue fever is the most common cause of arboviral disease. Dengue fever presents with confusing clinical profile and dengue is diagnosed by reverse transcription polymerase chain reaction. Hematological parameters like platelet count, hematocrit, leucocyte count and peripheral smear findings will aid in the diagnosis of dengue fever whereas malaria which is responsible for Leukemia, anemia and thrombocytopenia. Method: Total number of cases was 138. Out of which 121 Dengue IgM positive cases and for Malaria 107 rapid card test positive and smear positive cases were selected. period of 1 year. Jan 2020 to Sep 2021. Result: dengue incidence is 66.10% up to 30yrs of age group, where as in Malaria incidence is 60.90%. Dengue is more common in females(64.50)% than Males(35.50%) as compared to malaria. Reduction in RBC count less than 4 million is more common in malaria (48.76) than dengue (48.76%). anemia is more common in malaria(74.76%) compared to dengue(46.23%). Conclusion: Raised hematocrit, thrombocytopenia, leucopenia, and atypical lymphocytes in the peripheral smear will aid in the early diagnosis of dengue infection. Hematological changes and their diagnostic values in malaria infected patients found out that hemoglobin levels, white blood cell counts, and platelet counts were significantly reduced.

Obtention of Dengue Virus Membrane Proteins and Role for Virus Assembly.

The four serotypes of dengue virus (DENV), belonging to the genus Flavivirus in the family Flaviviridae, are the leading cause of arboviral diseases in humans. The clinical presentations range from dengue fever to dengue hemorrhagic fever and dengue shock syndrome. Despite decades of efforts on developing intervention strategies against DENV, there is no licensed antiviral, and safe and effective vaccines remain challenging. Similar to other flaviviruses, the assembly of DENV particles occurs in the membranes derived from endoplasmic reticulum; immature virions bud into the lumen followed by maturation in the trans-Golgi and transport through the secretary pathway. A unique feature of flavivirus replication is the production of small and slowly sedimenting subviral particles, known as virus-like particles (VLPs). Co-expression of premembrane (prM) and envelope (E) proteins can generate recombinant VLPs, which are biophysically and antigenically similar to infectious virions and have been employed to study the function of prM and E proteins, assembly, serodiagnostic antigens, and vaccine candidates. Previously, we have developed several assays including sucrose cushion ultracentrifugation, sucrose gradient ultracentrifugation, membrane flotation, subcellular fractionation, and glycosidase digestion assay to exploit the interaction between DENV prM and E proteins, membrane association, subcellular localization, glycosylation pattern, and assembly of VLPs and replicon particles. The information derived from these assays have implications to further our understanding of DENV assembly, replication cycle, intervention strategies, and pathogenesis.

Cost-Effectiveness and Impact of a Targeted Age- and Incidence-based West Nile Virus Vaccine Strategy.

West Nile virus (WNV) is the leading cause of arboviral disease in the United States and is associated with significant morbidity and mortality. A previous analysis found that a vaccination program targeting persons aged ≥60 years was more cost-effective than universal vaccination, but costs remained high. We used a mathematical Markov model to evaluate cost-effectiveness of an age- and incidence-based WNV vaccination program. We grouped states and large counties (≥100 000 persons aged ≥60 years) by median annual WNV incidence rates from 2004 to 2017 for persons aged ≥60 years. We defined WNV incidence thresholds, in increments of 0.5 cases per 100 000 persons ≥60 years. We calculated potential cost per WNV vaccine-prevented case and per quality adjusted life-years (QALYs) saved. Vaccinating persons aged ≥60 years in states with an annual incidence of WNV neuroinvasive disease of ≥0.5 per 100 000 resulted in approximately half the cost per health outcome averted compared to vaccinating persons aged ≥60 years in the contiguous United States. This approach could potentially prevent 37% of all neuroinvasive disease cases and 63% of WNV-related deaths nationally. Employing such a threshold at a county level further improved cost-effectiveness ratios while preventing 19% and 30% of WNV-related neuroinvasive disease cases and deaths, respectively. An age- and incidence-based WNV vaccination program could be a more cost-effective strategy than an age-based program while still having a substantial impact on lowering WNV-related morbidity and mortality.

Ross River Virus Provokes Differentially Expressed MicroRNA and RNA Interference Responses in Aedes aegypti Mosquitoes.

Alphaviruses are globally distributed and predominately transmitted by mosquitoes. Aedes species are common vectors for the clinically important alphaviruses—Chikungunya, Sindbis, and Ross River (RRV) viruses—with Aedes aegypti also being a vector for the flaviviruses dengue, Yellow Fever, and Zika viruses. Ae. aegypti was putatively implicated in the large 1979–1980 South Pacific Islands outbreak of RRV—the leading cause of arboviral disease in Australia today. The RNA interference (RNAi) defense response in mosquitoes involves a number of small RNAs, with their kinetics induced by alphaviruses being poorly understood, particularly at the tissue level. We compared the small RNA profiles between RRV-infected and non-infected Ae. aegypti midgut and fat body tissues at 2, 6, and 12 days post-inoculation (dpi). RRV induced an incremental RNAi response, yielding short interfering and P-element-induced-wimpy-testis (PIWI)-interacting RNAs. Fourteen host microRNAs were differentially expressed due to RRV with the majority in the fat body at 2 dpi. The largely congruent pattern of microRNA regulation with previous reports for alphaviruses and divergence from those for flaviviruses suggests a degree of conservation, whereas patterns of microRNA expression unique to this study provide novel insights into the tissue-specific host-virus attributes of Ae. aegypti responses to this previously unexplored old-world alphavirus.

Hematological parameters in dengue fever: A study in tertiary care hospital

Dengue fever has been known for more than a century in the tropical countries. Dengue fever is now the most common cause of arboviral disease in the world, with an estimated annual occurrence of 100 million cases of dengue fever and 250,000 cases of dengue hemorrhagic fever and a mortality rate of 25,000 per year. Most cases of dengue hemorrhagic fever are reported from Asia, where it is a leading cause of hospitalization and death among children. Dengue fever presents with confusing clinical profile and has to be differentiated from other febrile illnesses like malaria, typhoid, leptospirosis etc. Dengue is diagnosed by reverse transcription polymerase chain reaction (RT-PCR) and detection of NS1 antigen with corresponding IgM, IgG antibodies by Enzyme immunoassay &amp; Immunochromatographic test. These tests may not be available in the periphery. So the hematological parameters like platelet count, hematocrit, lecocyte count and peripheral smear findings will aid in the diagnosis of Dengue Fever.100 cases with proven diagnosis of dengue by serology were taken. Detailed history, physical examination and investigations including Complete blood count, coagulation profile, Liver function tests were done. Their stay in hospital and outcome were observed.Dengue infection was more common in adult age group with slight male preponderance. It presented commonly as dengue fever with other constitutional symtoms. Petechial ecchymosis was the most common sign elicited clinically. Hematological findings like raised hemotocrit, platelet count and atypical lymphocytes were seen in majority of the cases. Supportive treatment was the mainstay mode of management. Overall mortality was seen in 2% of the cases.Raised hematocrit, thrombocytopenia, leucopenia and atypical lymphocytes in the peripheral smear will aid in early diagnosis of Dengue infection. Early recognition and prevention rather than treatment of complications is most important for favourable outcome of the disease.

Seroprevalence of dengue virus in two districts of Kaohsiung City after the largest dengue outbreak in Taiwan since World War II.

Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. In this study, we investigated the seroprevalence of DENV infection in two districts of Kaohsiung City, a metropolis in southern Taiwan, where major dengue outbreaks have occurred in the past three decades. We enrolled 1,088 participants from the Sanmin and Nanzih districts after the dengue outbreak of 2015, the largest in Taiwan since World War II, and found an overall DENV seroprevalence of 12.4% (95% confidence interval: 10.5–13.4%) based on the InBios DENV IgG ELISA kit. The ratios of clinically inapparent to symptomatic infections were 2.86 and 4.76 in Sanmin and Nanzih districts, respectively. Consistent with higher case numbers during recent outbreaks, the DENV seroprevalence was higher in Sanmin district (16.4%) than in Nanzih district (6.9%), suggesting district differences in seroprevalence and highlighting the importance of screening the DENV immune status of each individual before using the currently available DENV vaccine, Dengvaxia. In the two districts, the seroprevalence rates increased from 2.1% (in the 30–39-year age group) to 17.1% (60–69) and 50% (70–79). The pattern of a sharp and significant increase in seroprevalence in the 70–79-year age group correlated with a dramatic increase in the proportion of clinically severe DENV infections among total dengue cases in that age group. This differed from observations in the Americas and Southeast Asia and suggested that a large proportion of monotypically immune individuals together with other risk factors may contribute to clinically severe dengue among the elderly in Taiwan.

Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development.

The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

Effects of an In-Frame Deletion of the 6k Gene Locus from the Genome of Ross River Virus.

The alphaviral6kgene region encodes the two structural proteins 6K protein and, due to a ribosomal frameshift event, the transframe protein (TF). Here, we characterized the role of the6kproteins in the arthritogenic alphavirus Ross River virus (RRV) in infected cells and in mice, using a novel6kin-frame deletion mutant. Comprehensive microscopic analysis revealed that the6kproteins were predominantly localized at the endoplasmic reticulum of RRV-infected cells. RRV virions that lack the6kproteins 6K and TF [RRV-(Δ6K)] were more vulnerable to changes in pH, and the corresponding virus had increased sensitivity to a higher temperature. While the6kdeletion did not reduce RRV particle production in BHK-21 cells, it affected virion release from the host cell. Subsequentin vivostudies demonstrated that RRV-(Δ6K) caused a milder disease than wild-type virus, with viral titers being reduced in infected mice. Immunization of mice with RRV-(Δ6K) resulted in a reduced viral load and accelerated viral elimination upon secondary infection with wild-type RRV or another alphavirus, chikungunya virus (CHIKV). Our results show that the6kproteins may contribute to alphaviral disease manifestations and suggest that manipulation of the6kgene may be a potential strategy to facilitate viral vaccine development. Arthritogenic alphaviruses, such as chikungunya virus (CHIKV) and Ross River virus (RRV), cause epidemics of debilitating rheumatic disease in areas where they are endemic and can emerge in new regions worldwide. RRV is of considerable medical significance in Australia, where it is the leading cause of arboviral disease. The mechanisms by which alphaviruses persist and cause disease in the host are ill defined. This paper describes the phenotypic properties of an RRV6kdeletion mutant. The absence of the6kgene reduced virion release from infected cells and also reduced the severity of disease and viral titers in infected mice. Immunization with the mutant virus protected mice against viremia not only upon exposure to RRV but also upon challenge with CHIKV. These findings could lead to the development of safer and more immunogenic alphavirus vectors for vaccine delivery.

West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2014.

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States (1). However, several other arboviruses also cause sporadic cases and seasonal outbreaks. This report summarizes surveillance data reported to CDC in 2014 for WNV and other nationally notifiable arboviruses, excluding dengue. Forty-two states and the District of Columbia (DC) reported 2,205 cases of WNV disease. Of these, 1,347 (61%) were classified as WNV neuroinvasive disease (e.g., meningitis, encephalitis, or acute flaccid paralysis), for a national incidence of 0.42 cases per 100,000 population. After WNV, the next most commonly reported cause of arboviral disease was La Crosse virus (80 cases), followed by Jamestown Canyon virus (11), St. Louis encephalitis virus (10), Powassan virus (8), and Eastern equine encephalitis virus (8). WNV and other arboviruses cause serious illness in substantial numbers of persons each year. Maintaining surveillance programs is important to help direct prevention activities.

Complexity of Neutralizing Antibodies against Multiple Dengue Virus Serotypes after Heterotypic Immunization and Secondary Infection Revealed by In-Depth Analysis of Cross-Reactive Antibodies.

The four serotypes of dengue virus (DENV) cause the most important and rapidly emerging arboviral diseases in humans. The recent phase 2b and 3 studies of a tetravalent dengue vaccine reported a moderate efficacy despite the presence of neutralizing antibodies, highlighting the need for a better understanding of neutralizing antibodies in polyclonal human sera. Certain type-specific (TS) antibodies were recently discovered to account for the monotypic neutralizing activity and protection after primary DENV infection. The nature of neutralizing antibodies after secondary DENV infection remains largely unknown. In this study, we examined sera from 10 vaccinees with well-documented exposure to first and second DENV serotypes through heterotypic immunization with live-attenuated vaccines. Higher serum IgG avidities to both exposed and nonexposed serotypes were found after secondary immunization than after primary immunization. Using a two-step depletion protocol to remove different anti-envelope antibodies, including group-reactive (GR) and complex-reactive (CR) antibodies separately, we found GR and CR antibodies together contributed to more than 50% of neutralizing activities against multiple serotypes after secondary immunization. Similar findings were demonstrated in patients after secondary infection. Anti-envelope antibodies recognizing previously exposed serotypes consisted of a large proportion of GR antibodies, CR antibodies, and a small proportion of TS antibodies, whereas those recognizing nonexposed serotypes consisted of GRand CR antibodies. These findings have implications for sequential heterotypic immunization or primary immunization of DENV-primed individuals as alternative strategies for DENV vaccination. The complexity of neutralizing antibodies after secondary infection provides new insights into the difficulty of their application as surrogates of protection. The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Despite the presence of neutralizing antibodies, a moderate efficacy was recently reported in phase 2b and 3 trials of a dengue vaccine; a better understanding of neutralizing antibodies in polyclonal human sera is urgently needed.We studied vaccinees who received heterotypic immunization of live-attenuated vaccines, as they were known to have received the first and second DENV serotype exposures.We found anti-envelope antibodies consist of group-reactive (GR), complex-reactive (CR), and type-specific (TS) antibodies, and that both GR and CR antibodies contribute significantly to multitypic neutralizing activities after secondary DENV immunization. These findings have implications for alternative strategies for DENV vaccination. Certain TS antibodies were recently discovered to contribute to the monotypic neutralizing activity and protection after primary DENV infection; our findings of the complexity of neutralizing activities after secondary immunization/infection provide new insights for neutralizing antibodies as surrogates of protection.

West Nile Virus: an overview.

West Nile Virus is the most frequent cause of arboviral disease in the United States. It was first identified in the United States in 1999. Since that time, each of the 48 contiguous states in the United States has seen the disease, and it has been found in 96% of the U.S. counties in infected humans, mosquitoes, birds, horses, or other mammals. Although most often the disease resolves on its own, patients can develop serious and life-threatening complications, and may need further monitoring and treatment. This article reviews the prevalence, transmission, signs and symptoms, complications, treatment, surveillance, and prevention of the disease.

Study of binding characteristics of human monoclonal antibodies to differentially matured dengue virus particles (VIR2P.1172)

Abstract Dengue virus (DENV) is the leading cause of arboviral disease. The ectodomain of envelope protein, containing three domains, DI, DII and DIII, is the major target of DENV vaccine. Studies on monoclonal antibodies (mAbs) showed that DIII mAbs are more potent neutralizing (NT) than those mAbs binding DII fusion-loop (FL). Due to the inefficiency of furin protease activity, produced DENV is a mixture of mature, immature and partially immature virions. It remains unknown regarding the epitope accessibility, avidity and NT potency of different mAbs on different maturation status of DENV. Immature and mature virions were generated from DENV1 infected BHK cells with treatment of NH4Cl and transfected with furin, respectively. Capture ELISA were performed to examine human anti-FL and anti-DIII mAbs (kindly provided by Dr. J. Mongkolsapaya and Dr. F. Sallusto). Anti-FL mAbs had higher maximum binding (Bmax) to immature than mature virions (P=0.0015) and no difference in dissociation constant (Kd) to both virions, suggesting that they have more accessible epitopes on immature virions and bind both with similar avidity. Anti-DIII mAbs showed no difference in Bmax or Kd to both virions but had lower Kd to mature virions than Anti-FL mAbs (P=0.04). Considering the greater infectivity of mature than immature virions, our findings of higher avidity of Anti-DIII mAbs to mature virions compared with Anti-FL mAbs provide a mechanistically explanation for stronger NT potency of Anti-DIII mAbs.

Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults.

The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic. NCT01072786 and NCT01436422.

Dengue Fever outbreak in delhi, north India: a clinico-epidemiological study.

Background:Dengue viruses, single-stranded positive polarity ribonucleic acid (RNA) viruses of the family Flaviviridae, are the most common cause of arboviral disease in the world. We report a clinico-epidemiological study of the dengue fever outbreak of 2010 from a tertiary care hospital in Delhi, North India.Objectives:Objectives of the study were to know the incidence of laboratory-confirmed dengue cases among the clinically suspected patients; to study the clinical profile of dengue-positive cases; and to co-relate the above with the prevalent serotype and environmental conditions.Materials and Methods:Four thousand three hundred and seventy serum samples from clinically suspected cases of dengue infection were subjected to μ-capture enzyme-linked immunosorbent assay (ELISA) for detection of dengue-virus-specific IgM antibodies. Virus isolation was done in 55 samples on C6/36 cell mono-layers. Clinical and demographic details of the patients were obtained from requisition forms of the patients or from treating clinicians.Results:Out of the 4,370 serum samples, 1,700 were positive for dengue-virus-specific IgM antibodies (38.9%). Prevalent serotype was dengue virus type-1. Thrombocytopenia and myalgia was seen in 23.1% and 18.3% of the 1,700 dengue IgM-positive patients, respectively. Also, 10.3% of 1,700 were dengue hemorrhagic fever (DHF) patients; and the mortality in serologically confirmed dengue fever cases was 0.06%.Conclusions:A change in the predominant circulating serotype, unprecedented rains, enormous infrastructure development, and increased reporting due to improved diagnostic facilities were the factors responsible for the unexpected number of dengue fever cases confronted in 2010.

West Nile Virus and Other Arboviral Diseases—United States, 2013

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States. However, several other arboviruses also cause sporadic cases and seasonal outbreaks of neuroinvasive disease (i.e., meningitis, encephalitis, and acute flaccid paralysis). This report summarizes surveillance data reported to CDC in 2013 for WNV and other nationally notifiable arboviruses, excluding dengue. Forty-seven states and the District of Columbia reported 2,469 cases of WNV disease. Of these, 1,267 (51%) were classified as WNV neuroinvasive disease, for a national incidence of 0.40 per 100,000 population. After WNV, the next most commonly reported cause of arboviral disease was La Crosse virus (LACV) (85 cases), followed by Jamestown Canyon virus (JCV), Powassan virus (POWV), and eastern equine encephalitis virus (EEEV) (eight). WNV and other arboviruses continue to cause serious illness in substantial numbers of persons annually. Maintaining surveillance remains important to help direct and promote prevention activities.

Analysis of Cross-Reactive Antibodies Recognizing the Fusion Loop of Envelope Protein and Correlation with Neutralizing Antibody Titers in Nicaraguan Dengue Cases

Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. The envelope (E) protein of DENV is the major target of neutralizing antibodies (Abs). Previous studies have shown that a significant proportion of anti-E Abs in human serum after DENV infection recognize the highly conserved fusion loop (FL) of E protein. The role of anti-FL Abs in protection against subsequent DENV infection versus pathogenesis remains unclear. A human anti-E monoclonal Ab was used as a standard in a virion-capture ELISA to measure the concentration of anti-E Abs, [anti-E Abs], in dengue-immune sera from Nicaraguan patients collected 3, 6, 12 and 18 months post-infection. The proportion of anti-FL Abs was determined by capture ELISA using virus-like particles containing mutations in FL, and the concentration of anti-FL Abs, [anti-FL Abs], was calculated. Neutralization titers (NT50) were determined using a previously described flow cytometry-based assay. Analysis of sequential samples from 10 dengue patients revealed [anti-E Abs] and [anti-FL Abs] were higher in secondary than in primary DENV infections. While [anti-FL Abs] did not correlate with NT50 against the current infecting serotype, it correlated with NT50 against the serotypes to which patients had likely not yet been exposed (“non-exposed” serotypes) in 14 secondary DENV3 and 15 secondary DENV2 cases. These findings demonstrate the kinetics of anti-FL Abs and provide evidence that anti-FL Abs play a protective role against “non-exposed” serotypes after secondary DENV infection.

DENGUE HEMORRHAGIC FEVER IN THE STATE OF CEARÁ, BRAZIL, 2005

Dengue is the most common cause of arboviral disease in the world. The aim of this study was to evaluate the clinical manifestations, laboratory features and outcome of dengue hemorrhagic fever. This is a retrospective study including 49 consecutive patients with dengue hemorrhagic fever in Fortaleza, Brazil, between February and August 2005. Statistical analysis was performed through the software SPSS 10.0 for windows. Patients’ mean age was 34.8±16.8 years; 59.2% were female. The main clinical signs and symptoms at admission were: fever (95.9%), headache (91.8%), myalgia (87.8%), abdominal pain (77.5%) and asthenia (73.5%). Hemorrhagic manifestations were present in 29 (59.2%) patients, including petechia (32.7%), gingival bleeding (18.4%), epistaxis (12.2%), echimosis (12.2%) and melena (12.2%). The tourniquet test was positive in 3 of 11 patients (27.2%). Platelets count at admission was 82,644±53,147/mm³. All patients presented platelets < 100,000/mm 3 . There was significant difference between admission and hospital discharge platelets count (82,644±53,147 vs. 146,081±88,999/mm³, p < 0.001). There was significant decrease between admission and hospital discharge haemoglobin and hematocrit (13.5±1.9 vs. 12.7±1.5/mm³, P = 0.002 and 41.0±5.9% vs. 38.6±4.8%, p = 0.001, respectively). All patients received venous hydration with saline solution. The mean infusion used was 2,513±1,065 mL daily. Four patients (8.1%) received blood transfusions and 9 (18.3%) platelets transfusions. Two patients died (4.1%) due to hypovolemic shock. Dengue is an endemic disease in emergent countries, with potential fatal outcome. Signs and symptoms suggestive of dengue hemorrhagic fever must be known by any physician in order to institute early adequate treatment. DOI: http://dx.doi.org/10.17525/vrrjournal.v15i1.37