Epidemiology Of Fever Research Articles

Mosquito species associated with horses in Madagascar: a review of their vector status with regard to the epidemiology of West Nile fever.

In Madagascar, the high West Nile virus (WNV) antibody prevalence reported in horse populations suggests a high level of vector-horse contact. This study aims to characterize the mosquito species usually involved in WNV transmission in horse stables in Madagascar. Five horse stables were investigated in October and November 2016 in five distinct inland areas. Mosquitoes were collected using double net traps baited with human, poultry or horse as well as light traps. Blood meal identification from engorged females was performed using host-specific PCRs. A total of 2898 adult mosquitoes were collected with Culex (Culex) antennatus (Becker) (40.7%), and Cx. (Cux.) quinquefasciatus Say (14.9%), being the most abundant species. The mosquito abundance varied between horse stables (P < 10-7 ) and depending on the bait used in the double net traps (P < 0.003). Among the 190 tested blood meals, 119 consisted of single blood meals with 85 from horse, 17 from human, 16 from chicken, one from cattle and 71 consisted of mixed blood meals. The mosquito species collected during this study exhibited a generalist feeding behaviour allowing them to act as bridge vectors between different vertebrate hosts involved in WNV transmission cycle. Their vector status with regard to West Nile fever epidemiology is reviewed.

The changing epidemiology of hemorrhagic fever with renal syndrome in Southeastern China during 1963-2020: A retrospective analysis of surveillance data.

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantavirus which was endemic Zhejiang Province, China. In this study, we aim to explore the changing epidemiology of HFRS in Zhejiang, identify high-risk areas and populations, and evaluate relevant policies and interventions to better improve HFRS control and prevention. Surveillance data on HFRS during 1963-2020 in Zhejiang Province were extracted from Zhejiang Provincial Center for Disease Control and Prevention archives and the Chinese Notifiable Disease Reporting System. The changing epidemiological characteristics of HFRS including seasonal distribution, geographical distribution, and demographic features, were analyzed using joinpoint regression, autoregressive integrated moving average model, descriptive statistical methods, and Spatio-temporal cluster analysis. From 1963 to 2020, 114 071 HFRS cases and 1269 deaths were reported in Zhejiang Province. The incidence increased sharply from 1973 and peaked in 1986, then decreased steadily and maintained a stable incidence from 2004. HFRS cases were reported in all 11 prefecture-level cities of Zhejiang Province from 1963 to 2020. The joint region (Shengzhou, Xinchang, Tiantai, and surrounding areas), and Kaihua County are the most seriously affected regions throughout time. After 1990, the first HFRS incidence peak was in May-June, with another one from November to January. Most HFRS cases occurred in 21- (26.48%) and 30- years group (24.25%) from 1991 to 2004, but 41- (25.75%) and 51-years (23.30%) had the highest proportion from 2005 to 2020. Farmers accounted for most cases (78.10%), and cases are predominantly males with a male-to-female ratio of 2.6:1. It was found that the median time from onset to diagnosis was 6.5 days (IQR 3.75-10.42), and the time from diagnosis to disease report was significantly shortened after 2011. We observed dynamic changes in the seasonal distribution, geographical distribution, and demographic features of HFRS, which should be well considered in the development of control and prevention strategies in future. Additional researches are warranted to elucidate the environmental, meteorological, and social factors associated with HFRS incidence in different decades.

Epidemiology of African Swine Fever and Its Risk in Nepal

African swine fever (ASF) is a highly contagious viral infection of domestic and wild pigs with high mortality. First reported in East Africa in the early 1900s, ASF was largely controlled in domestic pigs in many countries. However, in recent years ASF outbreaks have been reported in several countries in Europe and Asia. The occurrence of ASF in China, the largest pork producer in the world, in 2018 and in India, the country that surrounds and shares open borders with Nepal, has increased the risk of ASF transmission to Nepal. Lately, the pork industry has been growing in Nepal, overcoming traditional religious and cultural biases against it. However, the emergence of viral infections such as ASF could severely affect the industry’s growth and sustainability. Because there are no effective vaccines available to prevent ASF, the government should focus on preventing entry of the virus through strict quarantine measures at the borders, controls on illegal trade, and effective management practices, including biosecurity measures.

Climate Variability, Dengue Vector Abundance and Dengue Fever Cases in Dhaka, Bangladesh: A Time-Series Study

Numerous studies on climate change and variability have revealed that these phenomena have noticeable influence on the epidemiology of dengue fever, and such relationships are complex due to the role of the vector—the Aedes mosquitoes. By undertaking a step-by-step approach, the present study examined the effects of climatic factors on vector abundance and subsequent effects on dengue cases of Dhaka city, Bangladesh. Here, we first analyzed the time-series of Stegomyia indices for Aedes mosquitoes in relation to temperature, rainfall and relative humidity for 2002–2013, and then in relation to reported dengue cases in Dhaka. These data were analyzed at three sequential stages using the generalized linear model (GLM) and generalized additive model (GAM). Results revealed strong evidence that an increase in Aedes abundance is associated with the rise in temperature, relative humidity, and rainfall during the monsoon months, that turns into subsequent increases in dengue incidence. Further we found that (i) the mean rainfall and the lag mean rainfall were significantly related to Container Index, and (ii) the Breteau Index was significantly related to the mean relative humidity and mean rainfall. The relationships of dengue cases with Stegomyia indices and with the mean relative humidity, and the lag mean rainfall were highly significant. In examining longitudinal (2001–2013) data, we found significant evidence of time lag between mean rainfall and dengue cases.

Modeling the dynamics of Lassa fever in Nigeria

Lassa fever is a zoonotic disease spread by infected rodents known as multimammate rats. The disease has posed a significant and major health challenge in West African countries, including Nigeria. To have a deeper understanding of Lassa fever epidemiology in Nigeria, we present a deterministic dynamical model to study its dynamical transmission behavior in the population. To mimic the disease’s biological history, we divide the population into two groups: humans and rodents. We established the quantity known as reproduction number {mathcal {R}}_{0}. The results show that if {mathcal {R}}_{0} <1 then the system is stable, otherwise it is unstable. The model fitting was performed using the nonlinear least square method on cumulative reported cases from Nigeria between 2018 and 2020 to obtain the best fit that describes the dynamics of this disease in Nigeria. In addition, sensitivity analysis was performed, and the numerical solution of the system was derived using an iterative scheme, the fifth-order Runge–Kutta method. Using different numeric values for each parameter, we investigate the effect of all highest sensitivity indices’ parameters on the population of infected humans and infected rodents. Our findings indicate that any control strategies and methods that reduce rodent populations and the risk of transmission from rodents to humans and rodents would aid in the population’s control of Lassa fever.

Epidemiology of hemorrhagic fever with renal syndrome in Tai\u2019an area

Hemorrhagic fever with renal syndrome (HFRS), a serious threat to human health, is mainly transmitted by rodents in Eurasia. The risk of disease differs according to sex, age, and occupation. Further, temperature and rainfall have some lagging effects on the occurrence of the disease. The quantitative data for these factors in the Tai’an region of China are still unknown. We used a forest map to calculate the risk of HFRS in different populations and used four different mathematical models to explain the relationship between time factors, meteorological factors, and the disease. The results showed that compared with the whole population, the relative risk in rural medical staff and farmers was 5.05 and 2.00, respectively (p < 0.05). Joinpoint models showed that the number of cases decreased by 33.32% per year from 2005 to 2008 (p < 0.05). The generalized additive model showed that air temperature was positively correlated with disease risk from January to June, and that relative humidity was negatively correlated with risk from July to December. From January to June, with an increase in temperature, after 15 lags, the cumulative risk of disease increased at low temperatures. From July to December, the cumulative risk decreased with an increase in the relative humidity. Rural medical staff, farmers, men, and middle-aged individuals were at a high risk of HFRS. Moreover, air temperature and relative humidity are important factors that affect disease occurrence. These associations show lagged and differing effects according to the season.

Research priorities to fill knowledge gaps in wild boar management measures that could improve the control of African swine fever in wild boar populations

The European Commission asked EFSA to provide study designs for the investigation of four research domains (RDs) according to major gaps in knowledge identified by EFSA in a report published in 2019: (RD 1) African swine fever (ASF) epidemiology in wild boar; (RD 2) ASF transmission by vectors; (RD 3) African swine fever virus (ASFV) survival in the environment, and (RD 4) the patterns of seasonality of ASF in wild boar and domestic pigs in the EU. In this Scientific Opinion, the second RD on ASF epidemiology in wild boar is addressed. Twenty‐nine research objectives were proposed by the working group and broader ASF expert networks and 23 of these research objectives met a prespecified inclusion criterion. Fourteen of these 23 research objectives met the predefined threshold for selection and so were prioritised based on the following set of criteria: (1) the impact on ASF management; (2) the feasibility or practicality to carry out the study; (3) the potential implementation of study results in practice; (4) a possible short time‐frame study (< 1 year); (5) the novelty of the study; and (6) if it was a priority for risk managers. Finally, after further elimination of three of the proposed research objectives due to overlapping scope of studies published during the development of this opinion, 11 research priorities were elaborated into short research proposals, considering the potential impact on ASF management and the period of one year for the research activities.

Q Fever: A Troubling Disease and a Challenging Diagnosis

Q fever is a disease caused by the bacterial pathogen Coxiella burnetii. This hardy organism can easily spread long distances in the wind, and only a few infectious aerosolized particles are necessary to cause serious illness. Presentations of Q fever disease can be wide ranging, allowing it to masquerade as other illnesses, highlighting the importance of laboratory testing for diagnosis and treatment. This review summarizes Q fever's epidemiology and clinical presentations and presents classical laboratory diagnostic assays and novel approaches to detecting this troubling disease.

Paradigm Shift in Socio-Demographic Profile of Dengue Infection: A Hospital Based Cross-Sectional Study.

Background:Dengue is the most rapidly spreading mosquito borne viral disease in the world with increasing geographical expansion to new countries and from urban to rural settings due to combination of urbanisation, population growth, increased international travel and trade and global warming. The epidemiology of dengue fever in India has been very complex with a seasonal pattern. The first outbreak in Odisha was in 2010 and is now spreading to different districts of the state.Materials and Methods:A hospital based cross-sectional study was carried out between 2017 to 2018 in the dengue ward of a teaching hospital in Berhampur, Ganjam district of Odisha.Results:The prevalence of admitted dengue patients was 4.32%. Majority of the patients were males (81.9%) and ≥15 years old (91.7%). About 68.5% were from rural areas and belonged to low socio-economic status (53.2%). Cases were reported mostly in peri-monsoon periods and 65.7% of them came directly to the hospital.Conclusion:The study highlights the need to curb the rural spread of the disease through activities in creating awareness among all section of people to promote control measures and early reporting of all fever cases, capacity building of rural doctors for early detection, treatment and early referral of high-risk patients and availability of ELISA based tests in sub-district hospitals along with Rapid Diagnostic Kits (RDKs). Emphasis for preventive and control measures to be increased during peri-monsoon periods and also to be instituted in offices, educational institutes and other indoor activity areas.

Estimating the Impact of Vaccination on Antimicrobial-Resistant Typhoid Fever in Gavi-73 Countries

Background: Multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) are major concerns for the epidemiology and treatment of typhoid fever. The recent development and licensure of typhoid conjugate vaccines (TCVs) provide an opportunity to limit the transmission and burden of antimicrobial-resistant (AMR) typhoid fever. Methods: We combined output from mathematical models of typhoid transmission with estimates of antimicrobial resistance to predict the burden of AMR typhoid fever across Gavi-73 countries. We considered FQNS and MDR separately. The impact of vaccination was predicted based on forecasts of vaccine coverage. We explored how the potential impact of vaccination on the proportion of cases that were AMR varied depending on key model parameters. Findings: The introduction of routine immunization with TCV at 9 months of age with a catch-up campaign to 15 years of age was predicted to avert 46-74% of all typhoid fever cases in Gavi-73 countries. Vaccination was predicted to reduce the relative prevalence of AMR typhoid fever by 16% (95% prediction interval (PI): 0-49%). TCV introduction with a catch-up campaign was predicted to avert 42.5 million (95% PI: 24.8-62.8 million) cases and 506,000 (95% PI: 187,000-1.9 million) deaths due to FQNS typhoid fever and 21.2 million (95% PI: 16.4-26.5 million) cases and 342,000 (95% PI: 135,000-1.5 million) deaths from MDR typhoid fever over 10 years following introduction. Interpretation: Our results indicate the benefits of prioritizing TCV introduction for countries with a high avertable burden of FQNS and MDR typhoid fever. Funding: The Bill & Melinda Gates Foundation. Declaration of Interest: AJP chairs the UK Department of Health’s (DoH) Joint Committee on Vaccination and Immunisation (JCVI) and and is a member of the World Health Organization’s (WHO) Strategic Advisory Group of Experts. VEP has received reimbursement from Merck and Pfizer for travel expenses to Scientific Input Engagements unrelated to the subject of this manuscript and is a member of the World Health Organization’s (WHO) Immunization and Vaccine-related Implementation Research Advisory Committee. The views expressed in this manuscript are those of the authors and do not necessarily reflect the views of the JCVI, the DoH, or the WHO.

Changing epidemiology of hemorrhagic fever with renal syndrome in Jiangsu Province, China, 1963–2017

Hemorrhagic fever with renal syndrome (HFRS) remains a serious public health problem in China. Although the number of cases has been decreasing, its incidence shows geographical variability, and risk regions change over time. The aim of this study was to observe temporal and geographic dynamics of HFRS in Jiangsu Province and the impact of demographic characteristics. Surveillance data of HFRS in Jiangsu Province for the period of 1963–2017 were retrieved and analyzed. We first plotted the overall incidence and created a heat map of the annual incidence rate to visualize the long-term change over the 55-year period by county. The HFRS incidence map was then depicted to show its spatial and geographic distributions. Changes of demographic characteristics, including gender, age, occupation, and region of patients’ residence were considered. A total of 73,305 confirmed cases of HFRS were reported during the study period and the peak years were in 1964 (13.7 cases/million), 1977 (31.4 cases/million), 1983 (150.9 cases/million), and 1991 (40.1 cases/ million) historically. HFRS affected the southern region of Jiangsu Province first (incidence relatively scattered), then northern regions (relatively high in 1983–1986, 1990–1995), and finally, other parts of the province. Extensive spreading and expanded spatial distribution of risk areas were seen over the past several decades. Most cases occurred in people 16–60 years of age, males, and farmers. Cases involving people over 60 years of age showed a trend of increasing risk. The risk to females over 60 years of age is higher than that of males. HFRS incidence showed substantial geographical and temporal variations, which may be associated with rodent migration and urbanization. The detected hotspots of HFRS for future control emphasis are Guanyun, Dafeng, Gaochun, and Sihong Counties. The focus should be on young adult males, farmers, and the elderly.

Epidemiology of dengue fever in Gabon: Results from a health facility-based fever surveillance in Lambaréné and its surroundings.

BackgroundIn Africa, information on dengue is limited to outbreak reports and focused on some countries with continuing transmission in West and East Africa. To estimate the proportion of dengue-positive cases among febrile patients and identify clinical indicators of dengue cases, we conducted passive facility-based fever surveillance in a catchment area population of 70,000 residents of Lambaréné and its surroundings in Gabon.MethodsNon-malarial febrile patients with current fever or history of fever (≤7 days) between 1 and 55 years of age, were enrolled at Albert Schweitzer Hospital (ASH). Acute (visit 1, day of enrollment) and convalescent blood samples were collected between 10 and 21 days after enrollment. Acute/convalescent samples were tested with IgM/IgG ELISA, and a selected subset of acute samples with RT-PCR.ResultsAmong 682 non-malarial febrile patients enrolled, 119 (17.4%) were identified as dengue-positive (94 dengue-confirmed and 25 dengue-probable cases). Of these dengue-positive cases, 14 were confirmed with PCR, and based on serotyping, two infections were identified to be DENV-2 and two were DENV-3. The majority of our enrolled patients were <25 years of age and close to 80% of our dengue-positive cases were <15 years of age. In adjusted analyses, retro-orbital pain and abdominal pain were 2.7 and 1.6 times more frequently found among dengue-positive cases, compared to non-dengue cases.ConclusionLambaréné is not considered dengue-endemic. However, one in six non-malarial febrile episodes was found to be dengue-positive in the study period. Dengue should be considered more frequently in clinicians’ diagnosis among non-malarial febrile patients in Lambaréné. Given the lack of data on dengue in Gabon, additional prospective and longitudinal studies would help to further define the burden and patterns of dengue for improved case detection.

Predictive Performance of Rapid Diagnostic Tests for Falciparum Malaria and Its Modeled Impact on Integrated Community Case Management of Malaria in Sub-Saharan African Febrile Children.

BackgroundIntegrated community case management (iCCM) of malaria complements public health services to improve access to timely diagnosis and treatment of malaria. ICCM relies on standardized test-and-treat algorithms implemented by community health workers using malaria rapid diagnostic tests (RDTs). However, due to a changing epidemiology of fever causes in Africa, positive RDT results might not correctly reflect malaria. In this study, we modeled diagnostic predictive values for all malaria-endemic African regions as an indicator of the programmatic usefulness of RDTs in iCCM campaigns on malaria.MethodsPositive predictive values (PPVs) and negative predictive values (NPVs) of RDTs for clinical malaria were modeled. Assay-specific performance characteristics stem from the Cochrane Library and data on the proportion of malaria-attributable fevers among African febrile children aged <5 years were used as prevalence matrix.ResultsAverage country-level PPVs vary considerably. Ethiopia had the lowest PPVs (histidine-rich protein II [HRP2] assay, 17.35%; parasite lactate dehydrogenase [pLDH] assay, 39.73%), and Guinea had the highest PPVs (HRP2 assay, 95.32%; pLDH assay, 98.46%). On the contrary, NPVs were above 90% in all countries (HRP2 assay, ≥94.87%; pLDH assay, ≥93.36%).ConclusionsPPVs differed considerably within Africa when used to screen febrile children, indicating unfavorable performance of RDT-based test-and-treat algorithms in low-PPV settings. This suggests that the administration of antimalarials alone may not constitute causal treatment in the presence of a positive RDT result for a substantial proportion of patients, particularly in low-PPV settings. Therefore, current iCCM algorithms should be complemented by information on other setting-specific major causes of fever.

Epidemiology of Viral Hemorrhagic Fever in Africa

A variety of viral hemorrhagic fevers such as Ebola virus disease exist in Africa and impose a great threat in public health due to their high fatality. It is considered to be difficult to eradicate the etiological agents of viral hemorrhagic fever because they have non-human natural hosts. Therefore, the importance of public health measures remains high in addition to the urgent need for the development of medicines for treatment and prevention. Furthermore, public health measures directly lead to the accumulation of epidemiological knowledge about the diseases. As an infectious disease consultant for the World Health Organization, I have been involved with public health activities including the development of clinical guidelines, the establishment of laboratory diagnostic systems, the training for infection, prevention and control, the planning of budget for outbreak response, and the analysis of epidemiological data. On the last point, I reported the situation of Ebola virus disease outbreak in Liberia, 2014-2015 and Lassa fever outbreak in Nigeria, 2018-2019 describing the risk factors, morbidity, and mortality of the diseases.

Electronic data capture for large scale typhoid surveillance, household contact tracing, and health utilisation survey: Strategic Typhoid Alliance across Africa and Asia.

Electronic data capture systems (EDCs) have the potential to achieve efficiency and quality in collection of multisite data. We quantify the volume, time, accuracy and costs of an EDC using large-scale census data from the STRATAA consortium, a comprehensive programme assessing population dynamics and epidemiology of typhoid fever in Malawi, Nepal and Bangladesh to inform vaccine and public health interventions. A census form was developed through a structured iterative process and implemented using Open Data Kit Collect running on Android-based tablets. Data were uploaded to Open Data Kit Aggregate, then auto-synced to MySQL-defined database nightly. Data were backed-up daily from three sites centrally, and auto-reported weekly. Pre-census materials' costs were estimated. Demographics of 308,348 individuals from 80,851 households were recorded within an average of 14.7 weeks range (13-16) using 65 fieldworkers. Overall, 21.7 errors (95% confidence interval: 21.4, 22.0) per 10,000 data points were found: 13.0 (95% confidence interval: 12.6, 13.5) and 24.5 (95% confidence interval: 24.1, 24.9) errors on numeric and text fields respectively. These values meet standard quality threshold of 50 errors per 10,000 data points. The EDC's total variable cost was estimated at US$13,791.82 per site. In conclusion, the EDC is robust, allowing for timely and high-volume accurate data collection, and could be adopted in similar epidemiological settings.

Electronic data capture for large scale typhoid surveillance, household contact tracing, and health utilisation survey: Strategic Typhoid Alliance across Africa and Asia

Electronic data capture systems (EDCs) have the potential to achieve efficiency and quality in collection of multisite data. We quantify the volume, time, accuracy and costs of an EDC using large-scale census data from the STRATAA consortium, a comprehensive programme assessing population dynamics and epidemiology of typhoid fever in Malawi, Nepal and Bangladesh to inform vaccine and public health interventions. A census form was developed through a structured iterative process and implemented using Open Data Kit Collect running on Android-based tablets. Data were uploaded to Open Data Kit Aggregate, then auto-synced to MySQL-defined database nightly. Data were backed-up daily from three sites centrally, and auto-reported weekly. Pre-census materials’ costs were estimated. Demographics of 308,348 individuals from 80,851 households were recorded within an average of 14.7 weeks range (13-16) using 65 fieldworkers. Overall, 21.7 errors (95% confidence interval: 21.4, 22.0) per 10,000 data points were found: 13.0 (95% confidence interval: 12.6, 13.5) and 24.5 (95% confidence interval: 24.1, 24.9) errors on numeric and text fields respectively. These values meet standard quality threshold of 50 errors per 10,000 data points. The EDC’s total variable cost was estimated at US$13,791.82 per site. In conclusion, the EDC is robust, allowing for timely and high-volume accurate data collection, and could be adopted in similar epidemiological settings.

The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study.

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV—Sanofi Pasteur) and DENVax (TAK 003—Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

Detection and characterisation of sheep-associated malignant catarrhal fever infection from ruminants by using tegument and gB gene sequences of OvHV-2

In this study, positive blood and organ samples were obtained from different mixed herds of sheep and cattle against ovine herpesvirus 2 (OvHV-2) infection. Target-positive DNA was sequenced and compared with worldwide distributed OvHV-2 sequences. Tegument gene (422 base pairs) and glycoprotein B (gB) gene (2800 base pairs) amplicons of OvHV-2 genome were used for understanding of epidemiology of malignant catarrhal fever (MCF) infection in Turkey. The results of nucleotide sequencing of polymerase chain reaction (PCR) products indicated presence of sheep-associated form for MCF infection in Turkey. Although the obtained sequences were genetically different from each other, it was found that genetic variations were limited.

Vaccination and Therapeutics: Responding to the Changing Epidemiology of Yellow Fever.

At the turn of the nineteenth century, yellow fever (YF) was considered the most dangerous infectious disease with high case fatality. Subsequent, mass vaccination campaigns coupled with widespread elimination of the YF mosquito vector significantly decreased YF cases and reduced outbreaks to the tropical and subtropical forested regions of Africa and South America. However, recent (2016) large outbreaks in Angola, Democratic Republic of Congo (DRC), and South-Eastern Brazil, where previously had been demarcated as low-risk regions, have highlighted the possibility of a rapidly changing epidemiology and the potential re-emergence of yellow fever virus (YFV). Furthermore, the first-ever importation of YFV into Asia has highlighted the potential fear of YFV emerging as a global threat. In this review, we describe the changing epidemiology of YF outbreaks, and highlight the use of public health policies, therapeutics, and vaccination as tools to help eliminate future YFV outbreaks.

Gallbladder carriage generates genetic variation and genome degradation in Salmonella Typhi.

Despite recent advances in typhoid fever control, asymptomatic carriage of Salmonella Typhi in the gallbladder remains poorly understood. Aiming to understand if S. Typhi becomes genetically adapted for long-term colonisation in the gallbladder, we performed whole genome sequencing on a collection of S. Typhi isolated from the gallbladders of typhoid carriers. These sequences were compared to contemporaneously sampled sequences from organisms isolated from the blood of acute patients within the same population. We found that S. Typhi carriage was not restricted to any particular genotype or conformation of antimicrobial resistance genes, but was largely reflective of S. Typhi circulating in the general population. However, gallbladder isolates showed a higher genetic variability than acute isolates, with median pairwise SNP distances of 21 and 13 SNPs (p = 2.8x10-9), respectively. Within gallbladder isolates of the predominant H58 genotype, variation was associated with a higher prevalence of nonsense mutations. Notably, gallbladder isolates displayed a higher frequency of non-synonymous mutations in genes encoding hypothetical proteins, membrane lipoproteins, transport/binding proteins, surface antigens, and carbohydrate degradation. Specifically, we identified several gallbladder-specific non-synonymous mutations involved in LPS synthesis and modification, with some isolates lacking the Vi capsular polysaccharide vaccine target due to the 134Kb deletion of SPI-7. S. Typhi is under strong selective pressure in the human gallbladder, which may be reflected phylogenetically by long terminal branches that may distinguish organisms from chronic and acute infections. Our work shows that selective pressures asserted by the hostile environment of the human gallbladder generate new antigenic variants and raises questions regarding the role of carriage in the epidemiology of typhoid fever.