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BACKGROUND: Rapid point-of-care tests for malaria are now widely used in many countries to guide the initial clinical management of patients presenting with febrile illness. With China having recently achieved malaria elimination, better understanding regarding the identity and distribution of major non-malarial causes of febrile illnesses is of particular importance to inform evidence-based empirical treatment policy. METHODS: A systematic review of published literature was undertaken to characterise the spectrum of pathogens causing non-malaria febrile illness in China (1980-2015). Literature searches were conducted in English and Chinese languages in six databases: Ovid MEDLINE, Global Health, EMBASE, Web of Science™ - Chinese Science Citation Database SM, The China National Knowledge Infrastructure (CNKI), and WanFang Med Online. Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection. The number of published articles, reporting a given pathogen were presented, rather than incidence or prevalence of infection. RESULTS: A total of 57,181 records from 13 provinces of China where malaria used to be endemic were screened, of which 392 met selection criteria and were included in this review. The review includes 60 (15.3%) records published from 1980 to 2000, 211 (53.8%) from 2001 to 2010 and 121 (30.9%) from 2011 to 2015;. Of the 392 records, 166 (42.3%) were from the eastern region of China, 120 (30.6%) were from the south-west, 102 (26.0%) from south-central, and four (1.0%) were multi-regional studies. Bacterial infections were reported in 154 (39.3%) records, viral infections in 219 (55.9%), parasitic infections in four (1.0%), fungal infections in one (0.3%), and 14 (3.6%) publications reported more than one pathogen group. Participants of all ages were included in 136 (34.7%) studies, only adults in 75 (19.1%), only children in 17 (4.3%), only neonates in two (0.5%) and the age distribution was not specified in 162 (41.3%) records. The most commonly reported bacterial pathogens included Typhoidal Salmonella (n = 30), Orientia/ Rickettsia tsutsugamushi (n = 31), Coxiella burnetii (n = 17), Leptospira spp. (n = 15) and Brucella spp. (n = 15). The most commonly reported viral pathogens included Hantavirus/Hantaan virus (n = 89), dengue virus (DENV) (n = 76 including those with unknown serovars), Japanese encephalitis virus (n = 21), and measles virus (n = 15). The relative lack of data in the western region of the country, as well as in in neonates and children, represented major gaps in the understanding of the aetiology of fever in China. CONCLUSIONS: This review presents a landscape of non-malaria pathogens causing febrile illness in China over 36 years as the country progressed toward malaria elimination. These findings can inform guidelines for clinical management of fever cases and infection surveillance and prevention, and highlight the need to standardize operational and reporting protocols for better understanding of fever aetiology in the country.
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Fiebre , Humanos , China/epidemiología , Fiebre/epidemiología , Fiebre/etiología , Malaria/epidemiologíaRESUMEN
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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PURPOSE: The consequent use of malaria rapid diagnostic tests (RDTs) preceding a treatment decision has improved the global management of malaria. A combination RDT, including an inflammation marker to potentially guide antibiotic prescription, could improve the management of acute febrile illness (AFI). METHODS: We performed a prospective, cross-sectional study in Gabon evaluating the STANDARD Malaria/CRP DUO (S-DUO) RDT. Participants aged 2 to 17 years with fever at presentation and/or a history of fever < 7 days were enrolled. Expert microscopy, SD Bioline Malaria Ag P.f/Pan test for malaria detection, and NycoCard CRP device for CRP were used as comparators. AFI cases were classified on a spectrum encompassing bacterial vs. non-bacterial infection. RESULTS: 415 participants with AFI were enrolled. S-DUO RDT sensitivity and specificity for malaria detection vs. microscopy were 99·1% (95·2-100%) and 72·7% (64·3-80·1%); and for CRP detection (20 mg/L and above) 86·9% (80-92%) and 87% (79·2-92·7%), respectively. The difference in CRP levels between bacterial infection (mean = 41·2 mg/L) and other causes of fever, measured from our study population using the Nycocard device, was statistically significant (p < 0·01); CRP precision-recall AUC to distinguish bacterial infection class vs. non-bacterial classifications was 0·79. CONCLUSION: S-DUO RDT is suitable for malaria detection in moderate-to-high malaria transmission settings such as in Lambaréné; however, a CRP band detection limit > 40 mg/L is more adequate for indication of antibiotic prescription for AFI cases in Gabon.
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Infectious disease (ID) cohorts are key to advancing public health surveillance, public policies, and pandemic responses. Unfortunately, ID cohorts often lack funding to store and share clinical-epidemiological (CE) data and high-dimensional laboratory (HDL) data long term, which is evident when the link between these data elements is not kept up to date. This becomes particularly apparent when smaller cohorts fail to successfully address the initial scientific objectives due to limited case numbers, which also limits the potential to pool these studies to monitor long-term cross-disease interactions within and across populations. CE data from 9 arbovirus (arthropod-borne viruses) cohorts in Latin America were retrospectively harmonized using the Maelstrom Research methodology and standardized to Clinical Data Interchange Standards Consortium (CDISC). We created a harmonized and standardized meta-cohort that contains CE and HDL data from 9 arbovirus studies from Latin America. To facilitate advancements in cross-population inference and reuse of cohort data, the Reconciliation of Cohort Data for Infectious Diseases (ReCoDID) Consortium harmonized and standardized CE and HDL from 9 arbovirus cohorts into 1 meta-cohort. Interested parties will be able to access data dictionaries that include information on variables across the data sets via Bio Studies. After consultation with each cohort, linked harmonized and curated human cohort data (CE and HDL) will be made accessible through the European Genome-phenome Archive platform to data users after their requests are evaluated by the ReCoDID Data Access Committee. This meta-cohort can facilitate various joint research projects (eg, on immunological interactions between sequential flavivirus infections and for the evaluation of potential biomarkers for severe arboviral disease).
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Infecciones por Arbovirus , Humanos , Infecciones por Arbovirus/epidemiología , Estudios de Cohortes , América Latina/epidemiología , Masculino , Femenino , Niño , Arbovirus , Estudios Retrospectivos , Adolescente , Preescolar , AdultoRESUMEN
Introduction: Mayaro Fever (MF) is a tropical disease caused by the Mayaro virus (MAYV), with outbreaks documented in Latin America. Methods: A hospital-based fever surveillance in Leticia, Colombian Amazon, collected sera from 1,460 patients aged 5-89 between December 2020 and April 2023. Results: Dengue and malaria were the main diagnoses (19.4 and 5.8%, respectively), leaving 71.4% of cases unidentified after testing. Metagenomic sequencing and real-time RT-qPCR testing identified MAYV in two patients (25-year-old male and an 80-year-old female) exhibiting typical symptoms, of MF including rash, joint pain, and fever. Phylogenetics analysis of these two viruses revealed a close relationship to Peruvian strains within the MAYV D genotype. Discussion: The study of AFI in Leticia, Colombia, identified dengue as prevalent, with malaria, COVID-19, Influenza, and Zika viruses also detected. Despite extensive testing, most cases remained unexplained until metagenomic sequencing revealed MAYV, previously unseen in Colombia but known in neighboring countries. Conclusion: This study presents the first near full-length genomes of MAYV in Colombia, highlighting the need for further seroprevalence studies and enhanced surveillance to understand and control the spread of the virus in the region.
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Background: Sickle cell disease (SCD) is a disorder marked by a single-point mutation in the beta-globin gene. Hydroxyurea is a globally accepted disease-modifying agent that sounds to be effective in managing clinically and probably preventing complications of SCD. The current study aims to document the morbidity pattern and impact of Hydroxyurea therapy in the Outpatient Department of Sickle Cell Institute, Raipur. Materials and Methods: This cross-sectional study was conducted among randomly selected sixty-five patients (adults and children above six years). After obtaining informed consent, relevant data were collected in a predesigned pretested questionnaire. The appropriate statistical exercise was applied for the interpretation of results and inferences. Results: Acute febrile illness 54 (83%) and 53 (81.5%) reported pain crisis observed to have the most common morbidity among the study subjects, followed by 55.4% (36), 33 (50.8%) jaundice and difficulty breathing, respectively. Joint pain was the most commonly observed complaint, particularly at the knee joint (76.9%). Other complaints such as hand-foot syndrome (24.6%), epistaxis (27.7%), and acute chest syndrome (21.5%). Vaso-occlusive crisis (72.4%), difficulty in walking (60.0%) and eyesight (35.4%), leg ulcers (9.2%), and dactylitis (3.1%) were also documented as clinical manifestations among study participants. Less than half (44.46%) had an awareness about SCD. Hydroxyurea therapy was highly significant in improving the patient's clinical picture (P < 0.01), especially following the frequency of hospitalization and the requirement for blood transfusion. Conclusion: Pain crisis is the most common morbidity among study participants with a low level of knowledge about SCD with febrile illness. Hydroxyurea therapy was found to be quite effective as a disease-modifying therapy, especially for reducing the frequency of blood transfusion and lowering hospitalization rates among SCD patients.
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Acute febrile illness (AFI) and severe neurological disorders (SNDs) often present diagnostic challenges due to their potential origins from a wide range of infectious agents. Nanopore metagenomics is emerging as a powerful tool for identifying the microorganisms potentially responsible for these undiagnosed clinical cases. In this study, we aim to shed light on the etiological agents underlying AFI and SND cases that conventional diagnostic methods have not been able to fully elucidate. Our approach involved analyzing samples from fourteen hospitalized patients using a comprehensive nanopore metagenomic approach. This process included RNA extraction and enrichment using the SMART-9N protocol, followed by nanopore sequencing. Subsequent steps involved quality control, host DNA/cDNA removal, de novo genome assembly, and taxonomic classification. Our findings in AFI cases revealed a spectrum of disease-associated microbes, including Escherichia coli, Streptococcus sp., Human Immunodeficiency Virus 1 (Subtype B), and Human Pegivirus. Similarly, SND cases revealed the presence of pathogens such as Escherichia coli, Clostridium sp., and Dengue virus type 2 (Genotype-II lineage). This study employed a metagenomic analysis method, demonstrating its efficiency and adaptability in pathogen identification. Our investigation successfully identified pathogens likely associated with AFI and SNDs, underscoring the feasibility of retrieving near-complete genomes from RNA viruses. These findings offer promising prospects for advancing our understanding and control of infectious diseases, by facilitating detailed genomic analysis which is critical for developing targeted interventions and therapeutic strategies.
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Metagenómica , Secuenciación de Nanoporos , Humanos , Metagenómica/métodos , Secuenciación de Nanoporos/métodos , Masculino , Femenino , Enfermedades del Sistema Nervioso/microbiología , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/virología , Adulto , Persona de Mediana Edad , Nanoporos , Anciano , Metagenoma/genética , Fiebre/microbiología , Fiebre/virología , Escherichia coli/genéticaRESUMEN
Acute febrile illness (AFI) in pregnancy is a neglected cause of maternal and foetal mortality and morbidity in low-and middle-income countries. This prospective cohort studied antenatal and postpartum women admitted with acute fever to a tertiary care university teaching hospital from July 2014 to March 2015 for aetiology, maternal and foetal complications, and the impact on maternal mortality ratio (MMR) and perinatal mortality rate. Among the 180 women admitted with AFI, urinary tract infection 54(30%) was the commonest cause, followed by airborne infections (67; 37.2%), peripartum or wound infections (25; 13.8%) and vector-borne diseases (21; 11.6%). Maternal deaths were 4 (2%) and foetal deaths 9 (5%). Post-operative gram-negative sepsis was the most common cause of maternal mortality. The MMR was ten times higher with AFI 2778 against 197 (p < 0.0001) among the other hospital deliveries during the same period. Screening for asymptomatic bacteriuria , maintaining aseptic precautions, and vaccination may impact maternal and foetal morbidity significantly.
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We report on the complete coding sequence of Rift Valley Fever Virus inadvertently identified through metagenomics in a child with undifferentiated fever at Marigat sub-county hospital, Kenya. On phylogeny, the genome clustered with sequences obtained during the 2017 human outbreak in Uganda and the 2021 cattle outbreak in Kiambu, Kenya.
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At 3 severe infection cohort sites in Uganda, Orientia seropositivity was common. We identified 4 seroconversion cases and 1 PCR-positive case. These results provide serologic and molecular support for Orientia spp. circulating in sub-Saharan Africa, possibly expanding its endemic range. Orientia infections could cause severe illness and hospitalizations in this region.
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Enfermedades Endémicas , Humanos , Uganda/epidemiología , Masculino , Femenino , Adulto , Estudios de Cohortes , Persona de Mediana Edad , Adolescente , Adulto JovenRESUMEN
Background Tribal populations constitute a major portion of India's total population, especially in the eastern and northeastern states. We lack comprehensive information on the community burden of general morbidity and febrile illness in tribal population-dominated areas, which is quite essential for the microplanning of healthcare expenditure and implementation. This study aimed to provide evidence on the prevalence and pattern of general morbidity and febrile illness at the community level as well as the treatment-seeking behaviour in a tribal-dominated area. Methods The study was undertaken as an observational study in the community setting; looking into seasonal cross-sectional evidence on period prevalence (two weeks) of morbidity and qualitative/semiquantitative information on treatment-seeking behaviour of the selected community during 2012 and 2013. Result This study involved 5541, 5482, and 5638 individuals during the rainy season 2012, winter 2012-13, and rainy season 2013 seasons, respectively, from 25 tribal villages of Odisha, India. A period prevalence (two weeks) of overall morbidities was shown to be 27.28% and 28.9% during the rainy seasons of 2012 and 2013, respectively, of which 13% and 11.5%, respectively, were febrile, with low prevalence (6.44% overall morbidity and 1.81% febrile illness) in the winter of 2012-13. It indicated inadequacy in skills of the village-level health staff, monitoring of supplies/logistics, and population awareness for early reporting of fever to healthcare providers at the community level. Conclusion The evidence provided by the study would be helpful in making public health plans in tribal settings and also highlighted the opportunity to improve tribal health status through community awareness, especially in areas and populations with limited health access.
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Background Pediatric febrile illnesses are a major cause of hospital admissions and are often associated with significant morbidity and mortality. These illnesses pose a diagnostic challenge to both clinicians and laboratories. This study aims to explore the clinical characteristics of acute febrile illness in children and examine the effectiveness of various diagnostic techniques. Methods This prospective study was carried out at the Mahatma Gandhi Memorial Hospital, Warangal, India, from January 2020 to October 2022. It included children aged one month to 12 years. Results Out of 245 identified cases, 195 met the inclusion criteria. This study found that 18 patients (9.23%) suffered from serious bacterial infections (SBIs). In 63 patients (32.20%), the source of infection remained unidentified. Among those with SBI, UTIs were the most frequent. Bacteremia was identified in 2.5% of the patients. Conclusion SBIs were identified in 18 hospitalized children (9.23%), with UTIs being the most common SBI in children aged one to 36 months. Children in this age group presenting with toxic symptoms should be thoroughly evaluated for SBIs. The study also observed a higher prevalence of Gram-negative bacteremia compared to Gram-positive cases.
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Objectives: Acute febrile illness (AFI) causes significant health-seeking, morbidity, and mortality in Southeast Asia. This pilot study aimed to describe presentation, etiology, treatment, and outcomes of patients with AFI at one hospital in Timor-Leste and assessing the feasibility of conducting larger studies in this setting. Methods: Patients attending Hospital Nacional Guido Valadares with tympanic or axillary temperature ≥37.5°C in whom a blood culture was taken as part of routine clinical care were eligible. Participants were followed up daily for 10 days and again after 30 days. Whole blood was analyzed using a real-time quantitative polymerase chain reaction assay detecting dengue virus serotypes 1-4 and other arthropod-borne infections. Results: A total of 82 participants were recruited. Polymerase chain reaction testing was positive for dengue in 14 of 82 (17.1%) participants and blood culture identified a bacterial pathogen in three of 82 (3.7%) participants. Follow-up was completed by 75 of 82 (91.5%) participants. High rates of hospital admission (58 of 82, 70.7%), broad-spectrum antimicrobial treatment (34 of 82, 41.5%), and mortality (9 of 82, 11.0%) were observed. Conclusions: Patients with AFI experience poor clinical outcomes. Prospective observational and interventional studies assessing interventions, such as enhanced diagnostic testing, clinical decision support tools, or antimicrobial stewardship interventions, are required and would be feasible to conduct in this setting.
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Background: With growing use of parasitological tests to detect malaria and decreasing incidence of the disease in Africa; it becomes necessary to increase the understanding of causes of non-malaria acute febrile illness (NMAFI) towards providing appropriate case management. This research investigates causes of NMAFI in pediatric out-patients in rural Guinea-Bissau. Methods: Children 0-5 years presenting acute fever (≥38°) or history of fever, negative malaria rapid diagnostic test (mRDT) and no signs of specific disease were recruited at the out-patient clinic of 3 health facilities in Bafatá province during 54 consecutive weeks (dry and rainy season). Medical history was recorded and blood, nasopharyngeal, stool and urine samples were collected and tested for the presence of 38 different potential aetiological causes of fever. Results: Samples from 741 children were analysed, the protocol was successful in determining a probable aetiological cause of acute fever in 544 (73.61%) cases. Respiratory viruses were the most frequently identified pathogens, present in the nasopharynx samples of 435 (58.86%) cases, followed by bacteria detected in 167 (22.60%) samples. Despite presenting negative mRDTs, P. falciparum was identified in samples of 24 (3.25%) patients. Conclusions: This research provides a description of the aetiological causes of NMAFI in West African context. Evidence of viral infections were more commonly found than bacteria or parasites.
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Introduction: Acute febrile illnesses (AFI) in developing tropical and sub-tropical nations are challenging to diagnose due to the numerous causes and non-specific symptoms. The proliferation of rapid diagnostic testing and successful control campaigns against malaria have revealed that non-Plasmodium pathogens still contribute significantly to AFI burden. Thus, a more complete understanding of local trends and potential causes is important for selecting the correct treatment course, which in turn will reduce morbidity and mortality. Next-generation sequencing (NGS) in a laboratory setting can be used to identify known and novel pathogens in individuals with AFI. Methods: In this study, plasma was collected from 228 febrile patients tested negative for malaria at clinics across Senegal from 2020-2022. Total nucleic acids were extracted and converted to metagenomic NGS libraries. To identify viral pathogens, especially those present at low concentration, an aliquot of each library was processed with a viral enrichment panel and sequenced. Corresponding metagenomic libraries were also sequenced to identify non-viral pathogens. Results and Discussion: Sequencing reads for pathogens with a possible link to febrile illness were identified in 51/228 specimens, including (but not limited to): Borrelia crocidurae (N = 7), West Nile virus (N = 3), Rickettsia felis (N = 2), Bartonella quintana (N = 1), human herpesvirus 8 (N = 1), and Saffold virus (N = 1). Reads corresponding to Plasmodium falciparum were detected in 19 specimens, though their presence in the cohort was likely due to user error of rapid diagnostic testing or incorrect specimen segregation at the clinics. Mosquito-borne pathogens were typically detected just after the conclusion of the rainy season, while tick-borne pathogens were mostly detected before the rainy season. The three West Nile virus strains were phylogenetically characterized and shown to be related to both European and North American clades. Surveys such as this will increase the understanding of the potential causes of non-malarial AFI, which may help inform diagnostic and treatment options for clinicians who provide care to patients in Senegal.
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BACKGROUND: Leptospirosis presents with highly variable clinical manifestations affecting different organ systems in different individuals. The presentation ranges from an asymptomatic or mild disease to a severe disease associated with multiorgan failure and higher mortality. Leptospirosis is highly underreported due to a lack of diagnostic modalities and less suspicion among clinicians. METHODOLOGY: We present this single-center retrospective case series of 12 cases, which include various common and uncommon scenarios by which the disease can present and can be missed due to lack of suspicion. The study contains individual patient characteristics including demographic, laboratory, clinical, and treatment data. The association between these variables and mortality was analyzed using p-values and results were described. A p-value of<0.05 was considered statistically significant. RESULTS: A total of 12 cases were included in the study. The male-to-female ratio was 3:1. The mean age was higher (37.75±9.81 years) in cases who died than those who recovered (34.25±14.09). Factors like history of alcoholism, presence of chronic liver disease (CLD), jaundice, acute renal failure, requirement of dialysis, and requirement of intensive care were significantly associated with increased risk of death (odds ratio >1, p-value <0.05). The most common symptom of presentation was fever in 11 (91.66%) cases. Jaundice and renal failure were significantly associated with death (odds ratio 1.2, p-value 0.04). The requirement of intensive care treatment (odds ratio 2.1, p-value 0.05) and dialysis (odds ratio 39.66, p-value 0.03) were also significantly associated with death. The percentage of death was lower in the group of patients who received combination antibiotic therapy. CONCLUSION: Leptospirosis has varied presentations in different individuals and the diagnosis can be missed due to lack of specific signs and symptoms. Severe diseases involving multiple organs and preexisting comorbidities are associated with higher mortality rates. Timely diagnosis and treatment are necessary to reduce mortality and increase survival.
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Longitudinally extensive transverse myelitis (LETM) is a rapidly progressing demyelinating disease affecting the spinal cord over three or more vertebral segments. Most causes are idiopathic, while others include infections, autoimmune causes, central nervous system demyelinating diseases, and post vaccination. Here, we report a 37-year-old male who presented with a fever for six days with no source of infection and complained of pain and weakness in the bilateral lower limbs eight hours after admission. Though the neurological examination of the lower limbs was normal at that time, reduced power was detected 16 hours later, with loss of proprioception and sensation of pain with a sensory level at T4 vertebrae. Then, the patient became unable to vocalize, and the chest X-ray showed an elevated left hemidiaphragm. Thirty hours after admission, the patient went into type 2 respiratory arrest and was intubated. The magnetic resonance imaging (MRI) showed a longitudinally extensive transverse myelitis extending from the C2 vertebrae to the conus medullaris. Febrile illness is common in the medical setting in Sri Lanka, but its association with LETM is unusual. Since LETM is very rare and is a rapidly progressive disease, a high degree of clinical suspicion is crucial for early diagnosis and the initiation of treatment. This case underscores the importance of early diagnosis, which would require timely MRI, and prompt treatment with intravenous (IV) glucocorticoids or plasma exchange to reduce morbidity and mortality.
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Background and Objectives: Scrub typhus is an acute febrile illness transmitted by the bite of trombiculid mite in the larval stage. Scrub typhus is rare in pregnancy and there is paucity of data on the clinical outcome of scrub typhus during pregnancy. Material and Methods: We present five cases of scrub typhus complicating pregnancy who were admitted in the obstetric ward at AIIMS Rishikesh, India during the antenatal period for management. Results: The first patient presented at term pregnancy in semiconscious state while the rest were preterm between 31 and 34 weeks period of gestation. The age at presentation was 21-31 years. All five had febrile illness of >5 days' duration along with cough. Fever investigations like blood culture, peripheral smear for malarial parasite, dengue serology, widal test, and urine culture were negative. Serology for scrub typhus was positive in all. Once diagnosis was confirmed for scrub typhus, patients were given the drug of choice azithromycin 500 mg twice daily for five days. Scrub typhus complicating pregnancy led to maternal mortality in one patient. It resulted in one preterm delivery, one intrauterine fetal death, and rest three were delivered at term with good perinatal outcome. Conclusion: Scrub typhus is common in endemic areas like Uttarakhand, India. It has a poor fetal outcome. If diagnosed early and treatment started, maternal and fetal prognosis can be favorable. As large case series are unavailable in literature, it is difficult to predict the course of disease which at times may be fulminant.
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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.
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Dengue , Fiebre , Humanos , Tailandia/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Dengue/virología , Dengue/epidemiología , Fiebre/virología , Adulto Joven , Adolescente , Filogenia , Anciano , Niño , Tifus por Ácaros/microbiología , Tifus por Ácaros/epidemiología , Tifus por Ácaros/virología , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Preescolar , Coinfección/virología , Coinfección/microbiología , Coinfección/epidemiología , Virus/genética , Virus/clasificación , Virus/aislamiento & purificación , Culicidae/virología , Culicidae/microbiología , Animales , Virus del Dengue/genética , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Infecciones por Rickettsia/epidemiología , Infecciones por Rickettsia/microbiología , Infecciones por Rickettsia/virologíaRESUMEN
BACKGROUND: Metagenomic next-generation sequencing (mNGS) could improve the diagnosed efficiency of pathogens in bloodstream infections or sepsis. Little is known about the clinical impact of mNGS test when used for the early diagnosis of suspected infections. Herein, our main objective was to assess the clinical efficacy of utilizing blood samples to perform mNGS for early diagnosis of suspected infections, as well as to evaluate its potential in guiding antimicrobial therapy decisions. METHODS: In this study, 212 adult hospitalized patients who underwent blood mNGS test in the early stage of suspected infections were enrolled. Diagnostic efficacy of mNGS test and blood culture was compared, and the clinical impact of mNGS on clinical care was analyzed. RESULTS: In our study, the total detection rate of blood mNGS was significantly higher than that of culture method (74.4% vs. 12.1%, P < 0.001) in the paired mNGS test and blood culture. Blood stream infection (107, 67.3%) comprised the largest component of all the diseases in our patients, and the detection rate of single blood sample subgroup was similar with that of multiple type of samples subgroup. Among the 187 patients complained with fever, there was no difference in the diagnostic efficacy of mNGS when blood specimens or additional other specimens were used in cases presenting only with fever. While, when patients had other symptoms except fever, the performance of mNGS was superior in cases with specimens of suspected infected sites and blood collected at the same time. Guided by mNGS results, therapeutic regimens for 70.3% cases (149/212) were changed, and the average hospitalized days were significantly shortened in cases with the earlier sampling time of admission. CONCLUSION: In this study, we emphasized the importance of blood mNGS in early infectious patients with mild and non-specific symptoms. Blood mNGS can be used as a supplement to conventional laboratory examination, and should be performed as soon as possible to guide clinicians to perform appropriate anti-infection treatment timely and effectively. Additionally, combining the contemporaneous samples from suspected infection sites could improve disease diagnosis and prognoses. Further research needs to be better validated in large-scale clinical trials to optimize diagnostic protocol, and the cost-utility analysis should be performed.