Acute Kidney Injury (AKI) in the Setting of Multi-Organ Dysfunction Syndrome (MODS) Secondary to Yellow Fever Infection (YFI) in a 19-Year-Old Woman

Background: Outbreak of yellow fever infection (YFI), a mosquito-borne disease, occurs sporadically worldwide especially in tropical nations. Acute kidney injury (AKI) commonly results from YFI and could be associated with a poor prognosis for victims even under intensive care unit (ICU). Pathophysiologic mechanisms for AKI include hypovolemic shut down, cytotoxicity, acute tubular necrosis (ATN), hemolysis, or coagulopathy. Early diagnosis, prompt and effective treatment modalities including dialysis improve treatment outcome. Aim: We report the case management of a 19-year-old woman who had yellow fever infection complicated by acute kidney injury in the setting of multi-organ dysfunction syndrome (MODS). Case Presentation: A 19-year-old woman who presented with fever, headache and vomiting for 2 weeks. In the course of the illness, urine volume became reduced and coke colored, followed by body swelling, yellowness of the eyes bleeding from the orifices. Examination revealed an acutely ill looking woman, icteric, and with pedal edema. Her pulse was 100/min and blood pressure was 120/80 mmHg. Liver was enlarged, soft and tender. She had proteinuria 3+ and polymerase chain reaction (PCR) confirmed yellow fever infection. She had markedly deranged serum biochemical parameters for which she had a three-hour session of hemodialysis with Heparin anticoagulation. The urea reduction ratio (URR) was 46.9%. Barrier nursing was commenced. She had 7 units of whole blood and a pint of fresh frozen plasma (FFP) with antibiotics, Rabeprazole, Tranexamic acid, Vitamin K and Frusemide. She had the second dialysis session of HD and entered into the recovering phase of AKI and was subsequently discharged after 18th days on admission. Conclusion: Yellow fever infection occurs sporadically and could lead to MODS involving the kidneys, liver and hematologic system. Prompt initiation of dialysis, correction of coagulopathy, and antibiotics use are measures needed to arrest progression and death. Vaccination, destruction of the natural habitat of the carrier and infective organisms are necessary particularly in endemic regions of the world.

Epidemiological, prevention and control updates of yellow fever outbreak in Brazil

Yellow fever is an acute viral disease endemic to tropical countries, like Brazil, where, since the 1940 s, has no significant documented outbreaks similar to that observed between 2016/2018(2 045 confirmed cases and 677 deaths; caused by the sylvatic form).The principal manipulating factors inciting this change were absence of appropriate vaccination campaigns and increased urbanization & population growth in forest areas, with prevalence of the virus in the species inhabiting of these areas.The 2016/2018 outbreaks exhibited incidence in areas with historically low or no yellow fever virus activity, triggering a surge in recorded deaths-mainly in the Southeastern states of Brazil.The Brazilian government aggressively responded, reforming the countries' prophylactic measures, including vaccine implementation-as of March, 2018, switching from the former double dose regimen of the vaccine, to a single dose protocol, deemed as adequate.Moreover, some states appropriated the fractionated dosage(1/5 of the standard dose), in foresight of potential vaccine shortages.To prevent the uprising of new sylvatic yellow fever cases in Brazil, it's obligatory the development of effective combative plans, including adaptation of prophylactic measures individually(use of repellents, protective clothing etc.), applicable vaccination campaigns in every endemic region, to raise awareness to locals and visitors alike.Notwithstanding these preventative strategies, the persistence of cases and the recent outbreaks in Brazil, highlight the possible ineffectiveness of combative measures.Based on these considerations, the objective of this review was to raise more awareness of the epidemiological impact of the disease in Brazil.

Socio-Demographic Determinant of Yellow Fever Patient: A Retrospective Study (2020), Federal Medical Center, Asaba

Background: Yellow fever is transmitted primarily to humans and non-human primates through the bite of an infected female mosquito Aedes Spp. It is prevented mainly by vaccination. Method: This retrospective observational study at the Center for Communicable Disease Control and Research (CCDCR) Federal Medical Center Asaba (F.M.C) was conducted on all patients diagnosed and managed with yellow fever in the year 2020. We studied a total number of 57 patients’ case files seen within the period. A chi-square test was done to test the null and alternative hypotheses. Result: About 48 (84.2%) males and female 9 (15.8%) females were mostly affected and gender was significant with a chi-squared value of 26.6 and p-value of 0.00. Conclusion: To eradicate this virus, vaccination and health promotions should be encouraged by the health care workers supported by the government. This is to ensure that a greater proportion of the affected community can be immunized.

Yellow Fever: A Re-Emerging Threat

Yellow fever (YF) is arguably one of the most notorious infectious diseases in the world. The disease is not only fatal to the human but also several primate species many of which are endangered by now. YF is caused by the yellow fever virus (YFV). While YFV was one of the most feared infectious diseases in the 18th and 19th century, the overall disease burden has been greatly reduced through an effective vector (mosquito) control and the development of the live-attenuated vaccine, YFV-17D. However, recent outbreaks in previously non-endemic areas have risen intense awareness among scientists and the public and remind us that YFV cannot be forgotten and containing it needs to remain a global health priority. Notably, the 11 imported yellow fever cases to China;hence the whole Asia-Pacific region, in 2016 alone, highlight that YFV may pose a threat to a large population which is intensified by increasing human migration and an extremely low vaccination rate. This paper assesses the possibility of a new round of epidemics of YFV, indicating that the virus should indeed be recognized as a re-emerging threat, and offers suggestions on how to prevent it. Stricter vaccine regulation and border check should be applied, as well as further research into alternative vaccines. More attention and efforts should be paid to fighting against the disease.

Management Problems of Trans-Frontier Yellow Fever Cases in Burkina Faso 2010

This last decade, Burkina Faso has been confronted with yellow fever confirmed cases, mainly from Western part of the country. In 2010, National Reference laboratory of yellow fever received 970 sera of suspected cases from the 65 Health Districts of the country. We found 11 positive results by ELISA test researching specific IgM against yellow fever. An aliquot of these eleven positive sera were sent to Dakar for confirmation by sero neutralization and RT-PCR. Eight have been confirmed by regional laboratory of Pasteur Institute of Dakar and three were classified as doubtful. Confirmed cases were manly notified by Sindou (4/8) and Mangodara (3/8) Health Districts and the last one came from Nongr-masson health District situated in the central part of the country. Three out of the four confirmed cases in Sindou Health District were resident from neighboring village in Ivory Cost. Conformed cases coming from neighboring villages of Ivory Cost were difficult to manage because of the relative lack of coordination between the two health centers responsible in two different countries. The three cases were not notified to Ivory Cost Health authorities and, in addition, they didn’t benefit from the Burkina Faso response plan. The goal of this work is to present results from National Reference yellow fever laboratory in 2010 in Burkina Faso and stressing trans-frontier cases management problems in order to suggest a multinational mechanism of response to fight against this disease more effectively.

King's College criteria and the Clichy-Villejuif criteria require adjustments for assessing acute liver failure due to yellow fever

BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver disease.Liver transplantation(LT)is the most impactful treatment.Yellow fever(YF)is an infectious disease that primarily affects the liver and has a high mortality rate.However,LT can be a viable option for treating rare cases with extensive liver involvement.However,the criteria for assessing the severity of ALF and determining the indications for transplantation have not been specifically validated for cases caused by YF.AIM To present necessary adjustments to established scoring systems for ALF secondary to YF.METHODS This was an observational,retrospective,single-center study.Fourteen consecutive patients with confirmed ALF due to YF were monitored in the intensive care unit by a specialized liver transplant team during a three-month epidemic outbreak in Brazil.During hospitalization,general supportive therapeutic measures were implemented,and the patients were regularly assessed using the King's College criteria and the Clichy-Villejuif criteria to determine the severity of liver failure.LT is considered a viable measure for patients with signs of end-stage liver failure.RESULTS Eight of 14(57%)patients developed severe neurological alterations within the first 96 hours after hospital admission.Four patients underwent emergency LT,and despite a moderate viral infection of the graft after transplantation,the 5-year survival rate was 50%.Although the King's College criteria and the Clichy-Villejuif criteria are the main scoring systems for ALF,they are insufficient for predicting the risk of mortality in this context,primarily because of low serum bilirubin levels in the final stage of the disease and significant disparities between coagulation abnormalities and patient severity.CONCLUSION To ensure good applicability in cases of YF-induced ALF,the authors suggest adaptations to the King's College and Clichy-Villejuif criteria.

Crystal structure of the C-terminal fragment of NS1 protein from yellow fever virus

Dear Editor,Yellow fever（YF）,a mosquito-borne flavivirus disease,is endemic in tropical areas of Africa and Central and South America.YF is transmitted via the bite of infected Aedes aegypti or Haemogogus mosquitoes and mainly affects humans and nonhuman primates.

Guiding dengue vaccine development using knowledge gained from the success of the yellow fever vaccine

Flaviviruses comprise approximately 70 closely related RNA viruses. These include several mosquito-borne pathogens, such as yellow fever virus （YFV）, dengue virus （DENV）, and Japanese encephalitis virus （JEV）, which can cause significant human diseases and thus are of great medical importance. Vaccines against both YFV and JEV have been used successfully in humans for decades; however, the development of a DENV vaccine has encountered considerable obstacles. Here, we review the protective immune responses elicited by the vaccine against YFV to provide some insights into the development of a protective DENV vaccine.

Generation and Application of a Luciferase Reporter Virus Based on Yellow Fever Virus 17D

Yellow fever virus(YFV) is a re-emerging virus that can cause life-threatening yellow fever disease in humans.Despite the availability of an effective vaccine,little is known about the replication mechanism of YFV,and there are still no available specific anti-YFV medicines.Herein,by introducing the Renilla luciferase gene(Rluc) into an infectious clone of YFV vaccine strain 17 D,we generated a recombinant virus 17 D-Rluc.2 A via reverse genetics approaches.The 17 D-Rluc.2 A had similar plaque morphology and comparable in vitro growth characteristics with its parental strain.Importantly,the reporter luciferase was efficiently expressed in 17 D-Rluc.2 A-infected mammalian and mosquito cells,and there was a good linear correlation between intracellular luciferase expression and extracellular infectious virion reproduction.Furthermore,by a combination of the 17 D-Rluc.2 A reporter virus and selective 2’-hydroxyl acylation analyzed by primer extension(SHAPE)technology,the conserved 5’-SLA element was shown to be essential for YFV replication,highlighting the capability of17 D-R1 uc.2 A in the investigation of YFV replication.At last,we demonstrated that two compounds with distinct anti-viral mechanisms can effectively inhibit the viral propagation in 17 D-Rluc.2 A-infected cells,demonstrating its potential application in the evaluation of anti-viral medicines.Taken together,the 17 D-Rluc.2 A serves as a useful tool for the study of YFV replication and anti-YFV medicine development.

Yellow fever and Hajj： with all eyes on Zika, a familiar flavivirus remains a threat

Hajj is among the world＇s largest mass gatherings, drawing between 2 and 3.5 million Muslims from 183 nations annually to perform pilgrimage in Mecca, Saudi Arabia. Infectious disease outbreaks can be imported both into the Hajj population and exported internationally by returning pilgrims. The domestic Saudi population can also be at risk of outbreaks traveling amid this mass migration. With yellow fever reported for the first time in China following the infection of expatriate Chinese workers in Angola and a full blown outbreak underway in wider West Africa, the prospect of yellow fever outbreaks in Asia threatens to impact Saudi Arabia, both during and beyond the Hajj season. With global focus trained on Zika, the rising threat of yellow fever cannot be overlooked. Strategies to mitigate risk to Saudi Arabia and the global population are thereby suggested.

Yellow fever virus outbreak in Brazil under current and future climate

Introduction:Yellow fever(YF)is primarily transmitted by Haemagogus species of mosquitoes.Under climate change,mosquitoes and the pathogens that they carry are expected to develop faster,potentially impacting the case count and duration of YF outbreaks.The aim of this study was to determine how YF virus outbreaks in Brazil may change under future climate,using ensemble simulations from regional climate models under RCP4.5 and RCP8.5 scenarios for three time periods:2011-2040(short-term),2041-2070(mid-term),and 2071-2100(long-term).Methods:A compartmental model was developed to fit the 2017/18 YF outbreak data in Brazil using least squares optimization.To explore the impact of climate change,temperature-sensitive mosquito parameters were set to change over projected time periods using polynomial equations fitted to their relationship with temperature according to the average temperature for years 2011-2040,2041-2070,and 2071-2100 for climate change scenarios using RCP4.5 and RCP8.5,where RCP4.5/RCP8.5 corresponds to intermediate/high radiative forcing values and to moderate/higher warming trends.A sensitivity analysis was conducted to determine how the temperature-sensitive parameters impacted model results,and to determine how vaccination could play a role in reducing YF in Brazil.Results:Yellow fever case projections for Brazil from the models varied when climate change scenarios were applied,including the peak clinical case incidence,cumulative clinical case incidence,time to peak incidence,and the outbreak duration.Overall,a decrease in YF cases and outbreak duration was observed.Comparing the observed incidence in 2017/18 to the projected incidence in 2070-2100,for RCP4.5,the cumulative case incidence decreased from 184 to 161,and the outbreak duration decreased from 21 to 20 weeks.For RCP8.5,the peak case incidence decreased from 184 to 147,and the outbreak duration decreased from 21 to 17 weeks.The observed decrease was primarily due to temperature increasing beyond that suitable for Haemagogus mosquito survival.Conclusions:Climate change is anticipated to have an impact on mosquito-borne diseases.We found outbreaks of YF may reduce in intensity as temperatures increase in Brazil;however,temperature is not the only factor involved with disease transmission.Other factors must be explored to determine the attributable impact of climate change on mosquito-borne diseases.

Estimating the size of Aedes aegypti populations from dengue incidence data: Implications for the risk of yellow fever outbreaks

In this paper we present a model to estimate the density of aedes mosquitoes in a community affected by dengue.The method consists in fitting a continuous function to the incidence of dengue infections,from which the density of infected mosquitoes is derived straightforwardly.Further derivations allow the calculation of the latent and susceptible mosquitoes'densities,the sum of the three equals the total mosquitoes'density.The method is illustrated with the case of the risk of urban yellow fever resurgence in dengue infested areas but the same procedures apply for other aedes-transmitted infections like Zika and chikungunya viruses.

The Yellow FeverPandemic and the Establishment of a Transatlantic Knowledge Network for Epidemic Prevention in the Late 18th and Early 19th Centuries

During the late 18th and early 19th centuries,a series of conflicts erupted in the Caribbean,leading to the spread of yellow fever to North America and Europe.This yellow fever epidemic was aggravated by war,migration,trade,and other human behaviors,resulting in a decadelong transatlantic pandemic.Groups of physicians in Europe and the United States established a transatlantic network focused on epidemic prevention,to investigate the pathology,causes,and treatments of yellow fever Subsequently,some consular officers were also concerned about the yellow fever epidemic,which led to the expansion of this network.The formation and expansion of the transatlantic knowledge network profoundly demonstrated the spirit of transnationalism and promotes progress in international public health.It sets a precedent for international health cooperation.However,this network was dominated by the so-called"white elite",with European and American countries holding the knowledge hegemony,it had a clear racist and colonialism feature.

A Study of the Personal Reactivity after Taking Cholera or Yellow Fever Vaccine

BACKGROUND: In recent years the diseases of cholera and yellow fever are rampant,many health authorities have asked the international travelers who will enter the infected area to take these two vaccines to prevent the diseases. The purpose of this study was to identify associations between the personal reactivities after vaccination and some relative factors,which will offer advices for the routine international traveling vaccination.METHOD: The subjects were 289 people who took cholera vaccine, and 57 of them also took yellow fever vaccine simultaneously. Twelve variables were identified for study: sex, age, occupation, vaccinating frequency, vaccinating history, alcoholic drink, irritant food, strenuous exercises, pain in the vaccinated arm, redness and swelling on the arm, fever,tiredness. Stratfied chi-square test was done among the ranked variables.RESULTS: There were few personal reactivities after taking yellow fever vaccine,while the main reactivities after taking cholera vaccine were redness and swelling in the vaccinated arms pain in the arm, fever and tiredness. For people who took cholera vaccine, pain in the arm, fever and tiredness. For people who took cholera vaccine, the high rate of redness and swelling on the arm was significantly associated with the long vaccinating history, high vaccination frequency,taking alcoholic drink within 3 days after vaccination the high rate of pain in the arm was significantly associated with doing strenuous exercises, heavy labour work, taking alcoholic drink and irritant food within 3 days after vaccination; the rate of fever rises in people with long vaccinating history,high vaccinating frequency, taking these two vaccines simultaneously;the rate of tiredness significantly rises in people having taken cholera vaccine before, more than 40 years old, doing heavy labour work wthin 3 days after vaccination.CONCLUSION: It is recommended for people who takes cholera vaccine not to take yellow fever vaccine simultaneously, within 3 days after vaccination not to take any irritant food or alcoholic drink, not to do any heavy labour work or strenubus exercises, which are especially important for elder people, people with the long vaccinating history and high vaccinating frequency.

野口英世黄热病研究与科研范式的批判性刍议

日本著名微生物学家野口英世的黄热病研究一度举世瞩目,但其研究不久便遭到质疑。基于科赫法则,野口认为类黄疸性钩端螺旋体为黄热病病原体,然而泰勒尔在条件不具备的情况下没有盲从科赫法则,批判性地证明了黄热病病原体为滤过性病毒,否证了野口的结论。面对泰勒尔的质疑野口没有及时反省,最终逝于前往非洲研究黄热病的途中。由野口黄热病研究的失败可见,科学研究中不应预设结果,要做到大胆假设、批判性求证。深入分析类似于野口的科学家在科研活动中的思维路径,有助于认识科研范式在应用中遇到的真实问题。

流行性乙型脑炎病毒、西尼罗病毒、黄热病毒和寨卡病毒四重LuminexxTAG检测方法的建立与应用

【目的】黄病毒科虫媒病毒引起的人畜共患传染病对我国畜牧业及公共卫生造成严重影响。虫媒病毒种类多且感染症状相似,临床监测工作繁重,建立4种危害严重的黄病毒科虫媒病毒快速、高通量检测技术为其诊断和流行病学监测提供技术支撑。【方法】利用Luminex xTAG技术,针对流行性乙型脑炎病毒(JEV)5'UTR、西尼罗病毒(WNV)5'UTR及部分C基因、黄热病毒(YFV)5'UTR和寨卡病毒(ZIKV)NS5基因保守区,设计4对特异性引物并对引物进行TAG和Biotin修饰,以标准毒株为模板,进行多重PCR扩增;将扩增产物与带有反向TAG序列的不同编号荧光MagTAG磁珠、链霉亲和素R-藻红蛋白进行核酸杂交反应,利用Luminex 200系统检测磁珠荧光信号和藻红蛋白荧光信号,对病原进行分类和定量检测。【结果】建立了能特异性检测JEV、WNV、YFV和ZIKV的四重Luminex xTAG方法,其最优引物工作浓度为0.5、0.5、0.75、0.5µmol/L;杂交工作体系为磁珠工作液20μL、PCR扩增产物5μL、SAPE报告缓冲液75μL;杂交温度为37℃,杂交时间为30 min,pH值为8.0;该检测方法特异性好且不与登革病毒等其他虫媒病毒发生交叉反应。重复性试验结果表明,Luminex xTAG方法的批内变异系数为2.50%~5.63%,批间变异系数为3.61%~12.50%。四重Luminex xTAG方法对JEV和ZIKV的检测限为1×10^(4) copies/μL,对WNV和YFV的检测限为1×10^(3)copies/μL,其检测WNV、YFV和ZIKV的灵敏度较常规PCR高10~100倍。用Luminex xTAG方法和RT-qPCR方法检测209份临床样品和模拟样品,JEV、WNV、YFV、ZIKV符合率为100%。【结论】建立的四重Luminex xTAG方法具有高通量、高特异性和灵敏度、成本效益高的优点,可为虫媒病毒临床诊断和流行病学监测提供一种高通量技术手段。

赴非洲、南美洲出入境人群预防黄热病措施分析研究

目的通过对2018—2023年赴非洲、南美洲出入境人群在沈阳国际旅行卫生保健中心门诊进行预防黄热病情况的综合分析,给国际旅行卫生保健机构提供预防黄热病措施的有效指导建议。方法根据研究对象(2018—2023年共计9548人)赴非洲、南美洲的具体情况,结合国际疫情流行特点,进行身体健康状况评估,核查黄热病疫苗的接种禁忌症及慎用症,搜集相关预防接种资料,进行统计分析研究。结果得出研究对象根据出入境各方面的差异,人群的特点具有不同的分布,针对不同人群提供有效的预防黄热病措施。结论赴非洲、南美洲人群应根据自身特点及出入境状况针对性采取预防黄热病措施,同时国际旅行卫生保健门诊应加强预防接种风险排查,做到安全有效预防黄热病。

黄热病疫情及防控对策

世界卫生组织称安哥拉黄热病疫情或将对全世界构成威胁,我国已报告多例黄热病输入性病例。为加强我国黄热病的防控工作,本文介绍了黄热病的病原学和临床学特征、流行病学特征和疫情分布情况,分析了黄热病疫情对我国的威胁,提出我国应对黄热病疫情的预防与控制措施。

黄热病毒的一步RT-PCR法检测

自不同稀释度的乳鼠脑病毒悬液中制备总RNA,在自制缓冲液条件下,进行一步RT-PCR法检测.对一步RT-PCR法与常规RT-PCR的敏感性进行比较,并且以基孔肯亚病毒和登革1-4型病毒RNA为模板进行特异性观察.结果表明,本研究建立的一步RT-PCR法可检出2.8×103PFU的病毒,敏感性比常规RT-PCR法高10倍,且与基孔肯亚病毒、登革病毒1-4型无交叉反应,具有良好的特异性和敏感性,适用于黄热病毒的病原学检测.

黄热病病毒检测基因芯片的研究制备

目的制备黄热病病毒寡核苷酸检测芯片。方法根据黄热病病毒基因组序列,并应用生物信息学软件设计出22条寡核苷酸探针用于制备基因芯片。克隆于质粒上的黄热病病毒全长基因经限制性显示技术完成扩增并标记,杂交清洗后对芯片进行扫描和数据分析。结果大部分黄热病病毒寡核苷酸探针检测出阳性信号,阴性对照和空白对照检出阴性信号。结论基因芯片技术为黄热病病毒检测提供了一种早期、快速、可靠的方法。