Undifferentiated Febrile Illness Research Articles

Sentinel Enhanced Dengue Surveillance System - Puerto Rico, 2012-2022.

Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated febrile illness to hemorrhagic manifestations, shock, multiorgan failure, and death in severe cases. The disease presentation is nonspecific; therefore, various other illnesses (e.g., arboviral and respiratory pathogens) can cause similar clinical symptoms. Enhanced surveillance is necessary to determine disease prevalence, to characterize the epidemiology of severe disease, and to evaluate diagnostic and treatment practices to improve patient outcomes. The Sentinel Enhanced Dengue Surveillance System (SEDSS) was established to monitor trends of dengue and dengue-like acute febrile illnesses (AFIs), characterize the clinical course of disease, and serve as an early warning system for viral infections with epidemic potential. May 2012-December 2022. SEDSS conducts enhanced surveillance for dengue and other relevant AFIs in Puerto Rico. This report includes aggregated data collected from May 2012 through December 2022. SEDSS was launched in May 2012 with patients with AFIs from five health care facilities enrolled. The facilities included two emergency departments in tertiary acute care hospitals in the San Juan-Caguas-Guaynabo metropolitan area and Ponce, two secondary acute care hospitals in Carolina and Guayama, and one outpatient acute care clinic in Ponce. Patients arriving at any SEDSS site were eligible for enrollment if they reported having fever within the past 7 days. During the Zika epidemic (June 2016-June 2018), patients were eligible for enrollment if they had either rash and conjunctivitis, rash and arthralgia, or fever. Eligibility was expanded in April 2020 to include reported cough or shortness of breath within the past 14 days. Blood, urine, nasopharyngeal, and oropharyngeal specimens were collected at enrollment from all participants who consented. Diagnostic testing for dengue virus (DENV) serotypes 1-4, chikungunya virus, Zika virus, influenza A and B viruses, SARS-CoV-2, and five other respiratory viruses was performed by the CDC laboratory in San Juan. During May 2012-December 2022, a total of 43,608 participants with diagnosed AFI were enrolled in SEDSS; a majority of participants (45.0%) were from Ponce. During the surveillance period, there were 1,432 confirmed or probable cases of dengue, 2,293 confirmed or probable cases of chikungunya, and 1,918 confirmed or probable cases of Zika. The epidemic curves of the three arboviruses indicate dengue is endemic; outbreaks of chikungunya and Zika were sporadic, with case counts peaking in late 2014 and 2016, respectively. The majority of commonly identified respiratory pathogens were influenza A virus (3,756), SARS-CoV-2 (1,586), human adenovirus (1,550), respiratory syncytial virus (1,489), influenza B virus (1,430), and human parainfluenza virus type 1 or 3 (1,401). A total of 5,502 participants had confirmed or probable arbovirus infection, 11,922 had confirmed respiratory virus infection, and 26,503 had AFI without any of the arboviruses or respiratory viruses examined. Dengue is endemic in Puerto Rico; however, incidence rates varied widely during the reporting period, with the last notable outbreak occurring during 2012-2013. DENV-1 was the predominant virus during the surveillance period; sporadic cases of DENV-4 also were reported. Puerto Rico experienced large outbreaks of chikungunya that peaked in 2014 and of Zika that peaked in 2016; few cases of both viruses have been reported since. Influenza A and respiratory syncytial virus seasonality patterns are distinct, with respiratory syncytial virus incidence typically reaching its annual peak a few weeks before influenza A. The emergence of SARS-CoV-2 led to a reduction in the circulation of other acute respiratory viruses. SEDSS is the only site-based enhanced surveillance system designed to gather information on AFI cases in Puerto Rico. This report illustrates that SEDSS can be adapted to detect dengue, Zika, chikungunya, COVID-19, and influenza outbreaks, along with other seasonal acute respiratory viruses, underscoring the importance of recognizing signs and symptoms of relevant diseases and understanding transmission dynamics among these viruses. This report also describes fluctuations in disease incidence, highlighting the value of active surveillance, testing for a panel of acute respiratory viruses, and the importance of flexible and responsive surveillance systems in addressing evolving public health challenges. Various vector control strategies and vaccines are being considered or implemented in Puerto Rico, and data from ongoing trials and SEDSS might be integrated to better understand epidemiologic factors underlying transmission and risk mitigation approaches. Data from SEDSS might guide sampling strategies and implementation of future trials to prevent arbovirus transmission, particularly during the expansion of SEDSS throughout the island to improve geographic representation.

Identification of Bacteria and Viruses Associated with Patients with Acute Febrile Illness in Khon Kaen Province, Thailand.

The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we conducted molecular pathogen screening and serological analyses in patients who sought treatment in Chum Phae Hospital, Khon Kaen province, during the period from 2015 to 2016. Through integrated approaches, we successfully identified the etiology in 25.5% of cases, with dengue virus infection being the most common cause, noted in 17% of the study population, followed by scrub typhus in 3.8% and rickettsioses in 6.8%. Further investigations targeting viruses in patients revealed the presence of Guadeloupe mosquito virus (GMV) in four patients without other pathogen co-infections. The characterization of four complete genome sequences of GMV amplified from AFI patients showed a 93-97% nucleotide sequence identity with GMV previously reported in mosquitoes. Nucleotide substitutions resulted in amino acid differences between GMV amplified from AFI patients and mosquitoes, observed in 37 positions. However, these changes had undergone purifying selection pressure and potentially had a minimal impact on protein function. Our study suggests that the GMV strains identified in the AFI patients are relatively similar to those previously reported in mosquitoes, highlighting their potential role associated with febrile illness.

Scrub Typhus During Pregnancy: A Study from Northeast India

Introduction: Scrub typhus is a crucial underrecognized cause of undifferentiated febrile illness in Northeastern India. Scrub typhus in pregnancy is an uncommon entity. In such cases, not initiating effective and safe antibiotics leads to maternal and fetal complications. To reduce complications, it is a must to keep a high index of clinical suspicion. Methodology: The present study was conducted to find the various disease manifestations of scrub typhus during pregnancy from January 2014 to December 2018. It was a retrospective study that included hospitalized patients with a diagnosis of scrub typhus during pregnancy. The scrub typhus was diagnosed based on the clinical presentation and serological test with Weil-Felix test titer for OXK more or equal to 1:160 or immunochromatographic test positive for scrub typhus IgM antibody. Result: During the study period, complete data were obtained from nine patients. The mean age of the patient was 26.5 years. A maximum of five patients presented in the third trimester, and two presented each in the first and second trimesters. Adverse fetal outcome was found in 33.3% of cases. Two patients had multiorgan dysfunction syndrome, and hepatitis was found to be a common occurrence. Conclusion: Scrub typhus during pregnancy presents a unique problem that is associated with high fetal loss and maternal complications. Keeping a high index of suspicion for diagnosis in endemic regions is essential, as prompt initiation of safe and effective antibiotics can prevent complications.

Evaluation of serological tests in the diagnosis of scrub typhus

Scrub typhus is a leading cause of acute undifferentiated febrile illness in India. Overlapping clinical presentation and very low incidence of characteristic eschar makes serology the main stay of diagnosis. IgM ELISA is the most common test performed in tertiary care centres along with rapid diagnostic tests (RDT) and Weil Felix with varying sensitivity and specificityThe present study was conducted to compare the RDT’s and Weil Felix with IgM ELISA and analyse the demographic and clinical profile of scrub positive patientsSerum samples from clinically suspected scrub typhus patients admitted in a tertiary care hospital were tested by Weil Felix, RDT and IgM ELISA. Scrub typhus was confirmed in 38 of the 100 clinically suspected patients by IgM ELISA. Fever was the most common presenting symptom with significant proportion of patients being exposed to vegetation (p=0.0001).Sensitivity of Weil Felix and RDT was 42.1% and 84.2% respectively. Acute Kidney injury was the most common complication and mortality rate was 7.9%.Weil Felix is not a reliable test for scrub typhus diagnosis due to low sensitivity. Results of positive RDT’s can used for early initiation of specific treatment and IgM ELISA can be used as a confirmatory test in highly suspected cases.

Scrub typhus among patients with acute febrile illness in a tertiary health care centre

Scrub typhus, caused by Orientia tsutsugamushi and transmitted by bite of larval trombiculid mite of the Leptotrombidium genus and is a vector borne zoonotic disease. It has been predominantly reported from Southeast Asia, the Asian Pacific Rim, and Australia. The incidence of this disease is increased in India. These patients show an acute undifferentiated febrile illness and laboratory confirmation is essential. Delay in diagnosis may be fatal. : To assess the Scrub typhus burden among acute febrile illness patients. This Cross-sectional study, conducted in Dept. of Microbiology, Basaveshwara Medical College & Hospital, Chitradurga, Karnataka, India. Study duration was from August 2020 to January 2021. In this study, a total of 100 febrile illness patients were involved. Among them, 66 were males and 34 females. Under aseptic conditions, venous blood samples were collected from all subjects. Serum was separated by centrifugation, aliquoted, and stored at −20°C for further testing. The serum sample was tested for scrub typhus IgM ELISA using the INBIOS kit. Samples were also checked for dengue fever, typhoid fever, leptospirosis, and malaria. The serum samples that tested positive for any other infectious disease mentioned above (with or without detectable rickettsial antibodies) were excluded from the study. Data was represented in numbers and percentages. : In this study, out of 100 samples 30 were seropositive. Of the 30 seropositive scrub typhus cases, women were 11 (37%) and men were 19 (63%), suggesting that seropositivity was more in men than women. Among the seropositive cases, maximum number of the cases were in 16-30 years (33%) of age, followed by 31–45 years (23%). In this study, more number of positive cases 17 (56.6%) were found during the post-monsoon season i.e., October and November 2020. Fever, the most common symptom (100%). Headache, reported in (70 %) of cases, myalgia (40%), abdominal pain (37%), cough (23%), vomiting (20%), lymphadenopathy (17%), rashes (13%), hepato-spleenomegaly (10%), eschar (3%). The study results may conclude that Scrub typhus seropositivity rate was higher in males than females and also to be included in differential diagnosis of fever of unknown origin.

Development of a clinical scoring system to make a presumptive diagnosis of Kyasanur Forest Disease: a case-control study from South India.

Kyasanur Forest Disease (KFD) is a viral haemorrhagic fever endemic in South India. Based on clinical presentation alone, it is challenging to distinguish KFD from other febrile illnesses in the region. The study aimed to develop a clinical scoring system for early presumptive diagnosis of KFD. This retrospective case-control study included microbiologically diagnosed KFD patients (n=186) with other undifferentiated febrile illnesses as controls (n=203). The clinical and laboratory features between cases and controls were compared. A logistic regression analysis included those variables found to be significantly associated with KFD on univariate analysis. The adjusted odds ratio for the significant variables was calculated and converted into logarithmic scales. These numbers were rounded off to the nearest integer to find the score assigned to each variable. A receiver operating characteristics curve was created to find the best cut-off for the scoring system that predicted the diagnosis of KFD. A total of 186 anonymised cases and 203 anonymised controls were recruited from the records for this study. Myalgia, headache, lymphadenopathy, bleeding manifestations, Central Nervous System (CNS) involvement, raised haematocrit, leukopenia, and raised transaminases were more common in patients with KFD. Except for lymphadenopathy and raised transaminases, all the other variables were independent predictors of making a diagnosis of KFD. Since raised transaminases tended towards significance, it was included in the scoring system with other independent predictors. A scoring system was created with a maximum score of 12. The receiver operating characteristic curve showed an Area Under Curve of 0.912 (95%CI: 0.88-0.94). A score of 4 or more was found to have a sensitivity and specificity of 83% and 87%, respectively. The presence of specific features should alert primary care physicians working in endemic areas about the possibility of KFD. This diagnostic scoring system can be used to make a presumptive diagnosis of KFD after undergoing a prospective validation study.

Clinical Presentation, Risk Factors, and Comparison of Laboratory Diagnostics for Seasonal Influenza Virus Among Cambodians From 2007 to 2020.

Despite its global significance, challenges associated with understanding the epidemiology and accurately detecting, measuring, and characterizing the true burden of seasonal influenza remain in many resource-poor settings. A prospective observational study was conducted in Cambodia at 28 health facilities between 2007 and 2020 utilizing passive surveillance data of patients presenting with acute undifferentiated febrile illness (AUFI) to describe the prevalence of influenza A and B and characterize associated risk factors and symptoms using a questionnaire. A comparison of rapid influenza diagnostic tests (RIDTs) and real-time reverse transcription polymerase chain reaction (rRT-PCR) results was also conducted. Of 30 586 total participants, 5634 (18.4%) tested positive for either influenza A or B, with 3557 (11.6%) positive for influenza A and 2288 (7.5%) positive for influenza B during the study. Influenza A and B were strongly associated with the rainy season (odds ratio [OR], 2.30; P < .001) and being from an urban area (OR, 1.45; P < .001). Analysis of individual symptoms identified cough (OR, 2.8; P < .001), chills (OR, 1.4; P < .001), and sore throat (OR, 1.4; P < .001) as having the strongest positive associations with influenza among patients with AUFI. Analysis comparing RIDTs and rRT-PCR calculated the overall sensitivity of rapid tests to be 0.492 (95% CI, 0.479-0.505) and specificity to be 0.993 (95% CI, 0.992-0.994) for both influenza type A and B. Findings from this 14-year study include describing the epidemiology of seasonal influenza over a prolonged time period and identifying key risk factors and clinical symptoms associated with infection; we also demonstrate the poor sensitivity of RIDTs in Cambodia.

Incidence of acute undifferentiated febrile illnesses in an urban slum of Delhi: A longitudinal cohort study

ObjectiveAcute undifferentiated febrile illness (AUFI) is a neglected topic in health care. It has considerable morbidity and mortality worldwide. Slum dwellers are at high risk due to poor living conditions. This longitudinal cohort study estimated the incidence of AUFI in urban slum dwellers in Delhi. MethodsThis study was conducted on urban slum dwellers in Delhi. Data were collected using a structured interviewer-administered questionnaire over a period of 18 months. Adjusted incidence rates (IR) and incidence rate ratios (IRR) were calculated using Poisson regression models. Kaplan-Meier survival curves were used to estimate survival from fever. ResultsA total of 1497 population were studied. Incidence rate of AUFI was 47.43 per 1000 person-months (95% CI: 44.88; 50.08). The incidence was highest among the 50–59 year age group (54.18 per 1000 person months; 95% CI: 43.19; 67.17). Significant seasonal variation was observed with IR high in winter (IR: 32.80 per 1000 person month; adjusted IRR: 1.44 (95% CI: 1.26; 1.66) and monsoon (IR:19.89 per 1000 person month; adjusted IRR: 0.44 (95% CI: 0.36; 0.53). ConclusionThis study has shown a high incidence rate of AUFI amongst the slum dwellers in Delhi. This calls for awareness about clinical investigation and management among patients and healthcare providers. The findings from this study may sensitize policymakers and healthcare stakeholders to draw a road map with insightful consideration of the environmental factors that bring health burdens to the slum population. Further, comparative studies between slum and non-slum dwellers may be undertaken to evaluate the incidence of AUFI.

From fever to action: diagnosis, treatment, and prevention of acute undifferentiated febrile illnesses.

Acute Undifferentiated Febrile Illness (AUFI) presents a clinical challenge, often characterized by sudden fever, non-specific symptoms, and potential life-threatening implications. This review highlights the global prevalence, types, challenges, and implications of AUFI, especially in tropical and subtropical regions where infectious diseases thrive. It delves into the difficulties in diagnosis, prevalence rates, regional variations, and potential causes, ranging from bacterial and viral infections to zoonotic diseases. Furthermore, it explores treatment strategies, preventive measures, and the critical role of the One Health approach in addressing AUFI. The paper also addresses the emerging zoonotic risks and ongoing outbreaks, including COVID-19, Rickettsia spp., and other novel pathogens, emphasizing their impact on AUFI diagnosis and management. Challenges in resource-limited settings are analyzed, highlighting the need for bolstered healthcare infrastructure, enhanced diagnostics, and collaborative One Health strategies. Amidst the complexity of emerging zoonotic threats, this review underscores the urgency for a multifaceted approach to mitigate the growing burden of AUFI, ensuring early diagnosis, appropriate treatment, and effective prevention strategies.

First Molecular Identification of Rickettsia aeschlimannii and Rickettsia africae in Ticks from Ghana.

The threats from vector-borne pathogens transmitted by ticks place people (including deployed troops) at increased risk for infection, frequently contributing to undifferentiated febrile illness syndromes. Wild and domesticated animals are critical to the transmission cycle of many tick-borne diseases. Livestock can be infected by ticks, and serve as hosts to tick-borne diseases such as rickettsiosis. Thus, it is necessary to identify the tick species and determine their potential to transmit pathogens. A total of 1,493 adult ticks from three genera-Amblyomma, Hyalomma, and Rhipicephalus-were identified using available morphological keys and were pooled (n = 541) by sex and species. Rickettsia species were detected in 308 of 541 (56.9%) pools by genus-specific quantitative polymerase chain reaction assay (Rick17b). Furthermore, sequencing of the outer membrane protein A and B genes (ompA and ompB) of random samples of Rickettsia-positive samples led to the identification of Rickettsia aeschlimannii and Rickettsia africae with most R. africae DNA (80.2%) detected in pools of Amblyomma variegatum. We report the first molecular detection and identification of the rickettsial pathogens R. africae and R. aeschlimannii in ticks from Ghana. Our findings suggest there is a need to use control measures to prevent infections from occurring among human populations in endemic areas in Ghana. This study underscores the importance of determining which vector-borne pathogens are in circulation in Ghana. Further clinical and prevalence studies are needed to understand more comprehensively the clinical impact of these rickettsial pathogens contributing to human disease and morbidity in Ghana.

Challenges and epidemiological implications of the first outbreak of dengue and chikungunya in Sudan.

Dengue and chikungunya are mosquito-borne infections that are spreading rapidly worldwide. The highest burden lies in tropical and subtropical countries. In 2022 Sudan encountered the most widespread infection of both diseases. To describe the magnitude of the first outbreak of dengue and chikungunya infections in Tandalti Town, White Nile State, southern part of Sudan. Following the report of a high number of undifferentiated febrile illnesses in 32 health clinics in Tandalti Town, an area with high densities of Aedes aegypti, we collected blood samples from symptomatic suspected cases. The samples were tested for major arboviral infections using arboviral-specific enzyme-linked immunosorbent assays (IgM capture ELISA), and serologically positive samples were confirmed using commercially available Real Time RT-PCR Kits. Out of 773 suspected cases, 63 (8.15%) were confirmed. Eleven (17.46%) of the confirmed cases were DENV, 49 (77.77%) were CHIKV, and 3 (4.76%) were DENV and CHIKV co-infections. The outbreak started at the beginning of October and ended by mid December 2022. Both dengue and chikungunya infection was higher (41(65.08%)) among young females than males (22 (34.92%)). White Nile State may experience larger outbreaks of dengue and chikungunya in the future, there is, therefore, an urgent need for proper vector control interventions in the state and nearby states.

Scrub Typhus Diagnostics: The Present and the Future

Scrub typhus, caused by Orientia tsutsugamushi, is a vector-borne, zoonotic disease commonly occurring in a geographic region known as the ‘tsutsugamushi triangle’. Scrub typhus causes acute undifferentiated febrile illness (AUFI) with non-specific clinical features and is difficult to diagnose when a highly characteristic but not pathognomonic eschar is absent. Because the eschar is not always present, laboratory tests are required for diagnosis. Serological assays have been the mainstay of laboratory diagnosis of scrub typhus to date. Here, we present the major clinical features and clinical algorithms suggestive of this disease, to aid in better selection of diagnostic methods. The advantages and disadvantages of various scrub typhus assays are also discussed. Furthermore, we describe diagnostics, including serological and molecular assays, that may be available in the near future.

Typhoid fever.

Typhoid fever is an invasive bacterial disease associated with bloodstream infection that causes a high burden of disease in Africa and Asia. Typhoid primarily affects individuals ranging from infants through to young adults. The causative organism, Salmonella enterica subsp. entericaserovar Typhi is transmitted via the faecal-oral route, crossing the intestinal epithelium and disseminating to systemic and intracellular sites, causing an undifferentiated febrile illness. Blood culture remains the practical reference standard for diagnosis of typhoid fever, where culture testing is available, but novel diagnostic modalities are an important priority under investigation. Since 2017, remarkable progress has been made in defining the global burden of both typhoid fever and antimicrobial resistance; in understanding disease pathogenesis and immunological protection through the use of controlled human infection; and in advancing effective vaccination programmes through strategic multipartner collaboration and targeted clinical trials in multiple high-incidence priority settings. This Primer thus offers a timely update of progress and perspective on future priorities for the global scientific community.

The Chikungunya virus: A reemerging cause of acute febrile illness in the high jungle of northern Peru

Background The Chikungunya virus (CHIKV) is an emerging arthropod-borne virus (arbovirus) that causes undifferentiated acute febrile illness. Cases of CHIKV may be under-reported in Peru, given the various difficulties in diagnosing it, such as lack of diagnostic tests in remote areas, the passive nature of epidemiological surveillance, and co-circulation of other arthropod-borne pathogens. Therefore, a study was conducted in the high jungle of northern Peru to determine the prevalence of CHIKV among febrile patients and describe their clinical characteristics. Methods A cross-sectional study was conducted in the province of Jaen, Cajamarca, located in the high jungle of northern Peru. Patients attending primary healthcare centers within Cajamarca’s Regional Health Directorate were enrolled. The study took place from June 2020 through June 2021. Patients were eligible if they sought outpatient healthcare for a clinical diagnosis of acute febrile illness (AFI). Serum samples were collected from all patients, and the diagnosis of CHIKV was determined using real-time RT-PCR, as well as the detection of IgM antibodies by ELISA. A logistic regression model was employed to identify the risk factors for CHIKV, and the odds ratios (ORs) were calculated, along with their corresponding 95% confidence intervals (95% CI). Results A total of 1 047 patients with AFI were included during the study period. CHIKV was identified in 130 patients of 1 047 (12.4%). Among the CHIKV positive cases, 84 of 130 (64.6%) were diagnosed by RT-PCR, 42 of 130 (32.3%) by IgM ELISA detection, and 4 of 130 (3.1%) by both assays. The majority of patients with CHIKV infection fell within the 18–39 years age group (50.0%), followed by the 40–59 years age group (23.9%) and those with 60 years or older (10.8%). The most common clinical symptoms observed in patients with CHIKV infection were headache (85.4%), myalgias (72.3%), and arthralgias (64.6%). The highest number of positive CHIKV cases occurred in May (23.1%), followed by March (20.0%) and February (13.8%) of 2021. Conclusion The study reports a considerable frequency of CHIKV infections among patients with AFI from the high jungle of northern Peru. These findings highlight the importance of recognizing CHIKV as an ongoing pathogen with continuous transmission in various areas of Peru. It is crucial to enhance epidemiological surveillance by implementing reliable diagnostic techniques, as the clinical symptoms of CHIKV infection can be nonspecific.

Scrub typhus in Northeast India: epidemiology, clinical presentations, and diagnostic approaches.

Scrub typhus is one of the most neglected tropical diseases, a leading cause of acute undifferentiated febrile illness in areas of the 'tsutsugamushi triangle', diagnosed frequently in South Asian countries. The bacteria Orientia tsutsugamushi is the causative agent of the disease, which enters the human body through the bite of trombiculid mites (also known as chiggers) of the genus Leptotrombidium deliense. Diagnosis of the disease is challenging, as its early symptoms mimic other febrile illnesses like dengue, influenza and corona viruses. Lack of rapid, reliable and cost-effective diagnostic methods further complicates the identification process. Northeast India, a mountainous region with a predominantly rural tribal population, has witnessed a resurgence of scrub typhus cases in recent years. Various ecological factors, including rodent populations, habitat characteristics and climatic conditions, influence its prevalence. Entomological investigations have confirmed the abundance of vector mites, highlighting the importance of understanding their distribution and the probability of transmission of scrub typhus in the region. Proper diagnosis, awareness campaigns and behavioural interventions are essential for controlling scrub typhus outbreaks and reducing its impact on public health in Northeast India. Further research and community-based studies are necessary to accurately assess the disease burden and implement effective prevention strategies.

Murine Typhus: A Review of a Reemerging Flea-Borne Rickettsiosis with Potential for Neurologic Manifestations and Sequalae.

Murine typhus is an acute febrile illness caused by Rickettsia typhi, an obligately intracellular Gram-negative coccobacillus. Rats (Rattus species) and their fleas (Xenopsylla cheopis) serve as the reservoir and vector of R. typhi, respectively. Humans become infected when R. typhi-infected flea feces are rubbed into flea bite wounds or onto mucous membranes. The disease is endemic throughout much of the world, especially in tropical and subtropical seaboard regions where rats are common. Murine typhus is reemerging as an important cause of febrile illness in Texas and Southern California, where an alternate transmission cycle likely involves opossums (Didelphis virginiana) and cat fleas (Ctenocephalides felis). Although primarily an undifferentiated febrile illness, a range of neurologic manifestations may occur, especially when treatment is delayed. Serology is the mainstay of diagnostic testing, but confirmation usually requires demonstrating seroconversion or a fourfold increase in antibody titer from acute- and convalescent-phase sera (antibodies are seldom detectable in the first week of illness). Thus, early empiric treatment with doxycycline, the drug of choice, is imperative. The purpose of this review is to highlight murine typhus as an important emerging and reemerging infectious disease, review its neurologic manifestations, and discuss areas in need of further study.

Fatal acute undifferentiated febrile illness among clinically suspected leptospirosis cases in Colombia, 2016-2019.

Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019. We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92). This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.

Severe fever with thrombocytopenia syndrome virus genotype B in Thailand.

Severe fever with thrombocytopenia syndrome virus (SFTSV) has been reported in many countries in Southeast Asia, which expands the original geographic range of China, Korea, and Japan. Here, we report the complete genome sequences of two Thai SFTSV strains previously identified in patients with undifferentiated febrile illness in 2020. Phylogenetically, both clustered with SFTSV genotype B strains and were most closely related to those previously reported in central China (≥99.0% nucleotide sequence identity) in the L, M, and S gene segments. Nine amino acid residues encoded by one or more Thai SFTSV genomes differed from those found in global strains. Interestingly, the observed differences in numerous residues between the Thai strains suggest possible separate introductions of different variants into the region.

Increasing prevalence of malaria and acute dengue virus coinfection in Africa: a meta-analysis and meta-regression of cross-sectional studies

BackgroundMalaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario. Through a systematic review of the published literature, this study seeks to estimate the prevalence of dengue and malaria coinfection among acute undifferentiated febrile diseases in Africa.MethodsRelevant publications were systematically searched in the PubMed, Cochrane Library, and Google Scholar until May 19, 2023. A random-effects meta-analysis and meta-regression were used to summarize and examine the prevalence estimates.ResultsTwenty-two studies with 22,803 acute undifferentiated febrile patients from 10 countries in Africa were included. The meta-analysis findings revealed a pooled prevalence of malaria and dengue coinfection of 4.2%, with Central Africa having the highest rate (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). Continent-wide, Plasmodium falciparum and acute dengue virus coinfection prevalence increased significantly from 0.9% during 2008–2013 to 3.8% during 2014–2017 and to 5.5% during 2018–2021 (p = 0.0414).ConclusionThere was a high and increasing prevalence of malaria and acute dengue virus coinfection in Africa. Healthcare workers should bear in mind the possibility of dengue infection as a differential diagnosis for acute febrile illness, as well as the possibility of coexisting malaria and dengue in endemic areas. In addition, high-quality multicentre studies are required to verify the above conclusions.Protocol registration number: CRD42022311301.

Epidemiology, clinical characteristics, diagnosis, and complications of scrub typhus infection in Nepal: a systematic review.

Scrub typhus (ST) is a neglected tropical disease of serious concern in Nepal. This systematic review aims to describe the burden of disease, clinical presentation, and complications of ST infection in Nepal. A systematic search of PubMed, EMBASE, Google Scholar, and national databases was conducted for any literature published in English between January 2000 and January 2023. Any type of study design (observational studies, case series, and interventional studies) that reported laboratory-confirmed ST and was conducted in Nepal among patients of all age groups was included. The seroprevalence of ST among acute undifferentiated febrile illness (AUFI) cases, geographical distribution, monthly distribution, clinical presentations, complications, and treatment were assessed by the study. A total of 15 studies with 10,977 participants were included in the review. The seroprevalence of ST among the AUFI cases in Nepal was 19.31%. Young people at or below 20 years of age were mostly affected. The maximum number of cases were reported from Bagmati province (59.46%) and in the month of August (26.33%). Fever, headache, cough, shortness of breath, nausea, and abdominal pain were the clinical characteristics in decreasing order of occurrence. The most common complication was acute kidney injury, followed by respiratory problems, cardiac issues, and neurological manifestations. The case fatality rate of ST in Nepal was 2.56%. The authors findings showed a significant burden of ST among AUFI cases in Nepal. Improved surveillance, general public awareness, and early detection post-calamities could help reduce the disease burden and improve patient outcomes.