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Leptospira is a bacterial genus that includes several pathogenic species related to leptospirosis. In Colombia, leptospirosis is a mandatorily reported disease, widely distributed across the country. In the Villeta municipality, leptospirosis has been identified as an important cause of febrile illness; however, to date, no studies have been performed to identify the circulating species. A genus-specific qualitative qPCR was performed on DNA extracted from febrile patients' acute-phase whole-blood samples targeting a fragment of the rrs gene. Positive qPCR samples were further amplified for the adk, icdA, LipL32, LipL41, rrs, and secY genes through conventional PCR for sequencing. All high-quality obtained sequences were further assessed through concatenated phylogenetic analysis. A total of 25% (14/56) of febrile patients' acute blood samples were positive for Leptospira spp. High-quality sequences were obtained for only five genes, and analysis through concatenated phylogeny identified that all sequences clustered within the P1/pathogenic clade; some of them formed a robustly supported clade with Leptospira santarosai, and others were closely related with other Leptospira species but exhibited considerable genetic divergence. We describe the presence of pathogenic Leptospira species among febrile patients from the Villeta municipality and identify L. santarosai and other Leptospira species as causative agents of leptospirosis in the region.

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One of India's predominant public health issues is acute undifferentiated fever illness (AUFI), a typical response to an infectious agent. Diagnosis becomes challenging when the disease has been reported with fever as the primary symptom. Among the cases presenting at a tertiary care hospital in central India, 88% had an acute undifferentiated fever, the most common being dengue infection. In India, rural communities are at more risk from AUFI than cities. Most of those in danger are those who reside in remote areas, and one of the most significant risks is for those who reside close to forests. AUFI is a complex condition for physicians to deal with and is one of the most frequent clinical conditions for which empirical treatment is required. Nowadays, AUFI can be managed by a syndromic approach with the judicial use of antibiotics. Symptoms of AUFI, along with myalgia, headache, and anorexia, can be caused by various illnesses. Patients are recommended to undertake a battery of investigations, which may delay the therapy and increase expenses because many diseases may present with the same symptoms. In the developed world, viral illness is the primary cause of AUFI. However, in developing countries like India, it can also be brought on by potentially curable but life-threatening conditions such as malaria, leptospirosis, hantavirus infection, and Japanese encephalitis. Lack of knowledge of the locally prevalent illnesses, which might be the cause of AUFI, and lack of preliminary screening and diagnostics at the point of care to identify the etiologies make it difficult to control these generally curable causes of the burden of AUFI, especially in tropical and subtropical countries. A deeper understanding of AUFI is required to develop better diagnostics and cures for various etiologies, especially scrub typhus.

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Scrub typhus and dengue fever are common infectious diseases in tropical regions, and both have overlapping clinico-epidemiological and laboratory features, which often pose a diagnostic challenge. This case report discusses a 15-year-old girl from the Indian subcontinent who presented with acute undifferentiated febrile illness (AUFI) without typical features of any of the common tropical infections. She was diagnosed with co-infection of scrub typhus and dengue fever using laboratory tests with good diagnostic accuracy. The patient was managed on an ambulatory basis, treated with oral doxycycline, and showed symptomatic improvement within 48 hours. Co-infections in endemic areas present a significant diagnostic and therapeutic challenge. This case report highlights the importance of considering co-infections in the differential diagnosis of AUFI, especially during the post-monsoon period, and the use of highly sensitive and specific tests for the diagnosis of co-infections.

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We assessed serum samples collected in Cauca Department, Colombia, from 486 persons for Orientia seroreactivity. Overall, 13.8% showed reactive IgG by indirect immunofluorescence antibody assay and ELISA. Of those samples, 30% (20/67) were confirmed to be positive by Western blot, showing >1 reactive band to Orientia 56-kD or 47-kD antigens.

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Acute undifferentiated febrile illness (AUFI) is the presenting symptom of various tropical and infectious diseases. Viral infection is generally the most common cause of AUFI, accounting for 8-11.8% of cases; thus, antibiotics might be unnecessary. Dengue and malaria are common tropical infectious diseases requiring effective supportive treatment and antimalarial agents, respectively. The uncertainty of early diagnosis results in widespread empirical antimicrobial treatment in high -income as well as in low-and middle-income countries. Although rapid diagnostic tests (RDTs) have been shown to limit antibiotic prescriptions in dengue and malaria, we observed a wide range of antibiotic prescriptions for 13-92.7% of cases in previous literature, particularly in RDT-negative malaria cases. Given several RDT limitations, antimicrobial stewardship (AMS) appears to be an effective strategy for controlling unnecessary antibiotic use and antimicrobial resistance (AMR) prevention. This program should be endorsed by a multidisciplinary team in tropical diseases to control collateral damage of inappropriate antimicrobial use. Empirical antibiotic treatment should be administered based on clinical judgement, microbiological evidence, and local epidemiological data. Rapid termination of antibiotic therapy, including disease control or elimination, is the mainstay of AMS in tropical diseases. Local and international sectors should implement an AMS programme to reduce AMR in the Tropics.

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CONTEXT: Acute undifferentiated febrile illness (AUFI) is characterized by a sudden onset of raised body temperature and is a common cause of hospital admission though not recognized as a disease state by the World Health Organization. Epstein-Barr virus (EBV) is reported to account for a significant occurrence of AUFI cases. AIM: To know the role of EBV infection as a cause of acute undifferentiated febrile illness (AUFI). SETTINGS AND DESIGN: We have used the combination of EBV serological assays to establish the role of the Epstein-Barr virus as the cause of acute undifferentiated febrile illness. METHODS AND MATERIAL: A total of 721 suspected cases of acute undifferentiated febrile illness which were tested negative for other common causes of acute febrile illness were selected for the study. Serum samples collected from these cases were tested for the presence of the EBV viral capsid antigen (VCA) IgM antibody. All positive serum samples were tested for the presence of EBV Epstein-Barr nuclear antigen (EBNA) IgG. STATISTICAL ANALYSIS USED:  Statistical analysis was performed with the help of Microsoft Excel software (Microsoft Corporation, Redmond, USA).  Results: Out of 721 suspected AUFI cases tested for EBV VCA IgM antibodies, 117 samples were positive and 604 were negative. All these 117 samples were tested for EBV EBNA IgG antibodies in which 88 were positive and 29 were negative. In our study, we found that around 4% (positive for VCA IgM and negative for EBNA IgG) of AUFI cases can be attributed to primary acute EBV infection. CONCLUSIONS: EBV infection should be considered particularly in AUFI cases of less than five years of age even in those who do not meet the typical presentation of fever, lymphadenopathy and sore throat. Our study should help to raise awareness regarding the possibility of EBV infection particularly in AUFI cases. A high index of suspicion and timely diagnosis will definitely help clinicians to avoid a battery of investigations and misuse of antibiotics in cases of AUFI.

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During the ongoing pandemic of coronavirus disease 2019 (COVID-19), it is crucial for clinicians to have an insight into the emerging co-infections. As the dengue virus (DENV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have related symptomatology, a high index of suspicion is required for prompt diagnosis of concurrent infections involving these two pathogens, especially in the areas endemic for tropical diseases, i.e., dengue fever (DF), malaria, enteric fever, chikungunya, leptospirosis, etc. In this report, we present the case of a middle-aged man from Northern India, who had DF with myocarditis, and was simultaneously found to have COVID-19 co-infection. The patient was managed as per the COVID-19 protocol and had a favorable outcome.

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BACKGROUND: In the absence of proper guidelines and algorithms, available rapid diagnostic tests (RDTs) for common acute undifferentiated febrile illnesses are often used inappropriately. METHODS: Using prevalence data of 5 common febrile illnesses from India and Cambodia, and performance characteristics (sensitivity and specificity) of relevant pathogen-specific RDTs, we used a mathematical model to predict the probability of correct identification of each disease when diagnostic testing occurs either simultaneously or sequentially in various algorithms. We developed a web-based application of the model so as to visualize and compare output diagnostic algorithms when different disease prevalence and test performance characteristics are introduced. RESULTS: Diagnostic algorithms with appropriate sequential testing predicted correct identification of etiology in 74% and 89% of patients in India and Cambodia, respectively, compared with 46% and 49% with simultaneous testing. The optimally performing sequential diagnostic algorithms differed in India and Cambodia due to varying disease prevalence. CONCLUSIONS: Simultaneous testing is not appropriate for the diagnosis of acute undifferentiated febrile illnesses with presently available tests, which should deter the unsupervised use of multiplex diagnostic tests. The implementation of adaptive algorithms can predict better diagnosis and add value to the available RDTs. The web application of the model can serve as a tool to identify the optimal diagnostic algorithm in different epidemiological settings, while taking into account the local epidemiological variables and accuracy of available tests.

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Acute undifferentiated febrile illness (AUFI) constitutes the predominant cause of healthcare seeking in Odisha. This prospective study was conducted to analyse the clinical, epidemiological and laboratory profile of scrub typhus patients presenting with AUFI from January to December 2017. Four hundred and thirty-two samples were tested for dengue, malaria, scrub typhus and enteric fever. Scrub typhus was overall the most common cause of AUFI (26.3%, 114/432) followed by dengue (19.2%, 83/432). Eschar was seen in 6.1% of cases. Aetiologies of 38.6% of AUFI remained unidentified. In the present study, there was no mortality attributed to scrub typhus.

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BACKGROUND: Acute undifferentiated febrile illness (AUFI) is caused by a multitude of diverse pathogens, with significant morbidity and mortality in the developing world. The objective of this review was to characterise the diversity and relative importance of common infectious aetiologies of AUFI in South and Southeast Asia. METHODS: We conducted a comprehensive literature review to identify common aetiologies of AUFI in Asian countries. Four medical and life sciences databases including PubMed, Medline, Embase and Cochrane Central, and Google Scholar were searched for articles published from January 1998 to March 2019. RESULTS: Forty-three studies met the inclusion criteria. Among AUFI cases, viral aetiologies at 18.5% (14888) were more common than bacterial aetiologies (12.9% [10384]). From 80,554 cases, dengue fever was the most common aetiology (11.8%, 9511), followed by leptospirosis (4.4%, 3549), typhoid (4.0%, 3258), scrub typhus (4.0%, 3243) and influenza other than H1N1 (3.1%, 2514). In both adults and children: dengue fever was the leading cause of AUFI with 16.6% (1928) and 18.7% (1281) of the total cases. In admitted patients, dengue fever was the main cause of AUFI at 16.4% (2377), however leptospirosis at 13.9% (2090) was the main cause of AUFI for outpatients. In South Asia, dengue fever was the main cause of AUFI, causing 12.0% (6821) of cases, whereas in Southeast Asia, leptospirosis was the main diagnosis, causing 12.1% (2861) of cases. CONCLUSIONS: In this study the most common causes of AUFI were viral, followed by bacterial and protozoal (malaria) infections. Dengue was the commonest virus that caused AUFI while leptospirosis and typhoid were important bacterial infectious causes. Therefore, it is imperative to maintain a sound epidemiological knowledge of AUFI so that evidence-based diagnostic criteria and treatment guidelines can be developed.

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CONTEXT: To the best of our knowledge, there are no reports of serological evidence of human leptospirosis from Uttarakhand state in India. AIMS: The aim of this study was to screen for serological evidence of leptospirosis in patients with acute undifferentiated febrile illness at a tertiary care teaching hospital in Uttarakhand. SETTINGS AND DESIGN: A pilot study was conducted from March to November 2017. SUBJECTS AND METHODS: Fifty-three adult patients who presented in Medicine outpatient Department with a history of fever of ≥7 up to 14 days duration with or without other associated symptoms such as a headache, rashes, myalgia, arthralgia, and conjunctival suffusion were enrolled in the study using convenience sampling technique. Blood samples of these patients were collected and subjected to peripheral smear examination for malaria parasites, dengue immunoglobulin M (IgM) immunochromatographic card test, IgM Typhidot, Leptospira and Scrub typhus IgM ELISA, respectively. Aerobic blood culture was performed in 24 cases. Relevant clinico-epidemiological details were obtained as per the pro forma formulated in accordance with the modified Faine's criteria. STATISTICAL ANALYSIS USED: Descriptive statistics. RESULTS: The study population consisted of 50.94% of males and 49.06% of females with a mean age ± standard deviation of 34.2 ± 15.2 years. Fifty febrile patients had additional symptoms of which myalgia was the most common (81.1%) followed by arthralgia (22.6%). Peripheral smears of all patients were negative for malaria parasites. Dengue and Typhidot IgM positivity was observed in two and eight patients, respectively. Six and five patients were tested positive by leptospira and scrub typhus IgM ELISA, respectively. Salmonella Typhi was isolated from blood sample of only one patient. Serum samples of two patients showed dual positivity. All six leptospira seropositive patients satisfied modified Faine's criteria. CONCLUSIONS: Leptospirosis is a seemingly unexplored infection in Uttarakhand and should be considered as a differential diagnosis in patients with acute undifferentiated febrile illness.

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Scrub typhus has struck back, albeit with renewed vigour, impacting areas with previously known endemicity as also impressing newer expanses. It is not surprising, therefore, that Scrub typhus has emerged as a leading cause of public health concern globally as well as in India, but are we ready to take on the challenge? Over the last decade, there has been a global increase in the number of outbreaks of Scrub typhus, be it the military occupied areas or the civil population at large. The innumerable outbreaks of Scrub typhus, although disconcerting, have nonetheless contributed phenomenally towards better understanding of the dynamics of scrub typhus. There have been significant contributions to awareness of the disease amongst medical professionals, scrub typhus as a cause of Acute Undifferentiated Febrile Illness (AUFI) and newer clinical manifestation - Acute Encephalitis Syndrome (AES), availability and advances in diagnostics and management, man-vector-pathogen interactions, new records of Leptotrombidium species, newer vectors and Orientia species. Antigenic diversity and the varied clinical presentation of scrub typhus, absence of scrub typhus surveillance system and a lack of political will to recognize the disease as one of the important reemerging public health problem are areas seeking concerted deliberations and actions so that the challenges posed by scrub typhus can be addressed.

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BACKGROUND: Acute undifferentiated febrile illness (AUFI) may have similar clinical presentation, and the etiology is varied and region specific. MATERIALS AND METHODS: This prospective observational study was conducted in a tertiary hospital in South India. All adult patients presenting with AUFI of 3-14 days duration were evaluated for etiology, and the differences in presentation and outcome were analyzed. RESULTS: The study cohort included 1258 patients. A microbiological cause was identified in 82.5% of our patients. Scrub typhus was the most common cause of AUFI (35.9%) followed by dengue (30.6%), malaria (10.4%), enteric fever (3.7%), and leptospirosis (0.6%). Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The mean time to presentation was longer in enteric fever (9.9 [4.7] days) and scrub typhus (8.2 [3.2] days). Bleeding manifestations were seen in 7.7% of patients, mostly associated with dengue (14%), scrub typhus (4.2%), and malaria (4.6%). The requirement of supplemental oxygen, invasive ventilation, and inotropes was higher in scrub typhus, leptospirosis, and malaria. The overall mortality rate was 3.3% and was highest with scrub typhus (4.6%) followed by dengue fever (2.3%). Significant clinical predictors of scrub typhus were breathlessness (odds ratio [OR]: 4.96; 95% confidence interval [CI]: 3.38-7.3), total whole blood cell count >10,000 cells/mm3 (OR: 2.31; 95% CI: 1.64-3.24), serum albumin <3.5 g % (OR: 2.32; 95% CI: 1.68-3.2). Overt bleeding manifestations (OR: 2.98; 95% CI: 1.84-4.84), and a platelet count of <150,000 cells/mm3 (OR: 2.09; 95% CI: 1.47-2.98) were independent predictors of dengue fever. CONCLUSION: The similarity in clinical presentation and diversity of etiological agents demonstrates the complexity of diagnosis and treatment of AUFI in South India. The etiological profile will be of use in the development of rational guidelines for control and treatment of AUFI.

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BACKGROUND: A single diagnostic test for acute undifferentiated febrile illnesses (AUFI) is elusive. This pilot study was undertaken on the premise that leucocytes, being the main cells of defence, undergo quantitative, structural and functional changes in AUFI. We evaluated the potential of volume, conductivity and scatter (VCS) parameters of leucocytes, generated with the haemogram report by the Coulter auto-analyzer, in differentiating the common etiologies of AUFI. METHODS: The haematological and VCS data obtained from 800 controls and 200 cases of AUFI (50 cases each of acute malaria, dengue, scrub typhus and enteric fever) were retrieved for analysis. RESULTS: The cases and controls differed significantly with respect to relative numbers and the VCS parameters of neutrophils, lymphocytes and monocytes (p<0.05). The neutrophil and lymphocyte were significantly voluminous in acute malaria and scrub typhus as compared to dengue and enteric fevers (p<0.05). Enteric fever significantly enhanced the conductivity of neutrophils as compared to other subgroups while lymphocyte conductivity significantly differed from dengue and scrub typhus. Lymphocyte and neutrophil scatter values in malaria and scrub typhus were comparable but differed significantly from that in enteric fever. CONCLUSIONS: Etiology-specific changes occur in leucocytes, both in numbers and their VCS properties which can be identified without additional cost.

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