Search

Pathogens carried by insects, such as bunyaviruses, are frequently transmitted into human populations and cause diseases. Knowing which spillover events represent a public health threat remains a challenge. Metagenomic next-generation sequencing (mNGS) can support infectious disease diagnostics by enabling the detection of any pathogen from clinical specimens. mNGS was performed on blood samples to identify potential viral coinfections in human immunodeficiency virus (HIV)-positive individuals from Kinshasa, the Democratic Republic of the Congo (DRC), participating in an HIV diversity cohort study. Time-resolved phylogenetics and molecular assay development assisted in viral characterization. The nearly complete genome of a novel orthobunyavirus related to Nyangole virus, a virus previously identified in neighboring Uganda, was assembled from a hepatitis B virus-positive patient. A quantitative polymerase chain reaction assay was designed and used to screen >2,500 plasma samples from Cameroon, the DRC, and Uganda, failing to identify any additional cases. The recent sequencing of a US Center for Disease Control Arbovirus Reference Collection revealed that this same virus, now named Bangui virus, was first isolated in 1970 from an individual in the Central African Republic. Time-scaled phylogenetic analyses of Bangui with the related Anopheles and Tanga serogroup complexes indicate that this virus emerged nearly 10,000 years ago. Pervasive and episodic models further suggest that this virus is under purifying selection and that only distant common ancestors were subject to positive selection events. This study represents only the second identification of a Bangui virus infection in over 50 years. The presumed rarity of Bangui virus infections in humans can be explained by its constraint to an avian host and insect vector, precluding efficient transmission into the human population. Our results demonstrate that molecular phylogenetic analyses can provide insights into the threat posed by novel or re-emergent viruses identified by mNGS.

Abstract 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

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. [ABSTRACT FROM AUTHOR]

Background: Dengue is one of the most important emerging viral diseases of humans in the world afflicting humanity in terms of morbidity and mortality. All ages and both sexes are susceptible to dengue fever. Present study was aimed to study prevalence of dengue in different age groups and sex distribution at a tertiary hospital. Material and Methods: Present study was prospective, observational study, conducted in patients who were diagnosed as positive for Dengue NS1 antigen or Dengue Ig-M antibodies/IgG antibodies. Results: The maximum numbers of cases were in the age group of 11-20 years (36.80%), followed by in 21-30 years (21.80%). It was observed that the clinical data diagnosis of DF (77.20%) cases, DHF (18.64%) followed by DSS (4.20%). The mode of presentation in the present study was fever (100%), followed by headache (70.2%), myalgia (63%), arthralgia (48.2%), retro-orbital pain (46%), pain abdomen (21.2%), hepatomegaly (21.6%), rashes (17.4%), petechiae (13.8%), Splenomegaly (13.4%) and CNS manifestations (1.4%). Out of 500 cases (19.69%) showed positivity for NS1 antigen. The observation for individual markers IgG antibody were statistically significant with p-value of 0.001 and significant for IgM antibody with p-value of 0.03. The observations were statistically significant for combined NS1+IgM and NS1+IgM+IgG with a p-value of < 0.01. The maximum numbers of cases were recovered (93.6%), followed by discharged against medical advice or referred (4.6%). The patients expired were 9 (1.8%). The correlation of the clinical spectrum of dengue with died patients was significant with p-value was <0.05. Conclusion: Patients in the study presented commonly with fever, followed by headache, myalgia, arthralgia, retroorbital pain, rash and petechiae. Clinical findings of the cases included hepatomegaly, Splenomegaly, pleural effusion, ascites and shock. [ABSTRACT FROM AUTHOR]

Managing febrile illness is complicated due to the increasing involvement of non-malarial pathogens. This hospital-based cross-sectional study was conducted in Kiteto District Hospital in Northern Western, Tanzania, between January and February 2019. Out-patients with a temperature ≥38°C were consecutively enrolled until the sample size was reached. Whole blood samples were collected aseptically and tested for 36 pathogens using a multiplex PCR. Out of the 426 febrile patients, 184 (43.2%) had pathogens detected in their bloodstream. Brucella spp. was isolated in 61 (14.3%) patients, followed by Dengue virus 51 (12.0%), Salmonella Typhi 39 (9.2%), Plasmodium falciparum 37(8.7%), Coxiella burnetii 23 (5.4%) and Leptospira spp., 17 (4.0%). Forty patients (21.7%) had more than one pathogen, whereby co-infection with Brucella spp. and C. burnetii was frequent among study participants. Dengue virus was the most frequent in children aged below 14 years, whereas Brucella spp. was the dominant agent in adults. The cause of fever was not identified in 242 (56.8%) of these patients. Houses surrounded by long grasses were risk factors for febrile illness caused by P. falciparum, consuming untreated milk and consuming sour milk were risk factors for febrile illness caused by bacteria zoonoses while not washing hands after visiting the toilet was a risk factor for febrile illness by S. Typhi. Regarding management, 143 (34.8%) were given anti-malaria despite malaria rapid diagnostic test (MRDT) negative results, while 26.5% were given both anti-malaria and antibiotics for febrile illness. In this study, the majority of febrile illness cases were due to non-malarial pathogens, with P. falciparum accounting for only 8.7% of the cases. We found that about one-third of the cases were wrongly treated for malaria, and more than a quarter were wrongly given antibiotics. A review of the management of febrile illnesses is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Orientia tsutsugamushi causes acute febrile illness known as scrub typhus, which is spread by the bite of the trombiculid mite. Doxycycline is the first-line treatment for clinically diagnosed cases of scrub typhus. If not diagnosed and treated early, it can lead to complications such as acute renal failure, meningoencephalitis, gastrointestinal bleeding, and multiple organ failure. However, there have been no trials comparing the effectiveness of oral and Intravenous (i.v.) doxycycline for scrub typhus treatment. Aim: To assess the efficacy of intravenous versus oral doxycycline in managing uncomplicated scrub typhus. Materials and Methods: This prospective interventional research was conducted in the Paediatrics Department at Maharajah’s Institute of Medical Sciences, Vizianagaram, India, from June 2021 to July 2022. Out of a total of 178 children diagnosed with scrub typhus during the study period, 102 children who received either oral or intravenous doxycycline as monotherapy were included. The primary outcome measures studied were the incidence of delayed defervescence and the time of defervescence. The t-test or Mann-Whitney test was applied for continuous data, and the Chi-square test or Fischer’s-exact test was used to compare dichotomous variables. Results: The mean age of children treated with oral doxycycline was 9.5±2.7 years and with i.v. doxycycline was 8.2±2.4 years. Among the 178 children diagnosed with scrub typhus, 102 (57.3%) children treated with doxycycline alone were included in the study. Out of these, 78 (76.4%) cases received oral doxycycline, while 28 (27.4%) cases received intravenous doxycycline. There was no statistically significant difference in the response rate between the two groups. The p-value for time to defervescence was 0.672, and the p-value for the incidence of delayed defervescence was 0.9845. Conclusion: Both oral and intravenous forms of doxycycline demonstrated similar efficacy in the treatment of scrub typhus. Nearly all children in both groups became afebrile within 72 hours after starting treatment.

Purpose: Fever is a common cause for hospitalization among the pediatric population. The spectrum of causative agents is diverse. Human herpesvirus 6 (HHV-6) is a ubiquitous virus that often causes hospitalization of children in western countries. Previously, we investigated the cause of fever of 600 febrile hospitalized children in Gabon, and in 91 cases the causative pathogen was not determined. In this study, we assessed HHV-6 infection as potential cause of hospitalization in this group. Methods: Blood samples were assessed for HHV-6 using real-time quantitative PCR. Three groups were investigated: (1) group of interest: 91 hospitalized children with febrile illness without a diagnosed causing pathogen; (2) hospitalized control: 91 age-matched children hospitalized with febrile illness with a potentially disease-causing pathogen identified; both groups were recruited at the Albert Schweitzer Hospital in Lambaréné, Gabon and (3) healthy control: 91 healthy children from the same area. Results: Samples from 273 children were assessed. Age range was two months to 14 years, median (IQR) age was 36 (12–71) months; 52% were female. HHV-6 was detected in 64% (58/91), 41% (37/91), and 26% (24/91) of the samples from groups 1, 2, and 3, respectively; with statistically significant odds of being infected with HHV-6 in group 1 (OR = 4.62, 95% CI [2.46, 8.90]). Only HHV-6B was detected. Conclusions: Although tropical diseases account for a large proportion of children's hospitalizations, considering common childhood diseases such as HHV-6 when diagnosing febrile illnesses in pediatric populations in tropical countries is of importance. [ABSTRACT FROM AUTHOR]

This article discusses the temporal trends and spatial distribution of Brazilian spotted fever (BSF) in Brazil. BSF is an acute febrile infectious disease caused by the bacterium Rickettsia rickettsii and primarily transmitted through tick bites. The study analyzed data from 2012 to 2020 and found that the incidence and mortality rates of BSF remained stable over the study period, while the fatality rate showed a decreasing trend in the last five years. The disease had a heterogeneous geographical distribution, with well-defined spatial clusters. The findings highlight the need for improved surveillance, preventive measures, and targeted interventions in high-risk areas to reduce the impact of BSF on public health. [Extracted from the article]

Introduction: Anaemia is one of the major public health concerns in many developing countries including Zambia. Unless it is acute, the consequences of anaemia are not immediate but have long-term debilitating effects such as growth and intellectual retardation and as such it does not receive the necessary attention it deserves. This study set out to assess the prevalence and associated factors of anaemia in under-five children in Zambia. Methods: This study was a secondary analysis of the 2021 Malaria Indicator Survey. We extracted data from the datasets at the National Malaria Elimination Centre after obtaining permission from the Ministry of Health. The extracted data was analysed in STATA 14, summarised in frequencies, cross-tabulations between independent variables and the outcome and multivariable logistic regression was used to assess the associations between variables and anaemia. Findings: The prevalence of anaemia was found to be 53.8%. Anaemia was found to be associated more with children below one year compared to older children, children whose household heads had no or only have primary education compared to those with secondary or tertiary education and in the northern parts of the country such as Luapula and Northern provinces compared to the southern province. Further anaemia was more common in those with malaria than those without malaria and those with febrile illnesses than those without febrile illnesses. In addition, anaemia was less common in those who slept under insecticide-treated nets. Conclusion: Anaemia in Zambia has been found to be higher than the average in Southern Africa, it is associated with younger age groups, poverty conditions and where diseases like malaria and other febrile illnesses are more common than where they are not. The use of interventions like insecticidetreated nets is associated with reduced prevalence of anaemia. [ABSTRACT FROM AUTHOR]

Introduction: Orientia tsutsugamushi causes acute febrile illness known as scrub typhus, which is spread by the bite of the trombiculid mite. Doxycycline is the first-line treatment for clinically diagnosed cases of scrub typhus. If not diagnosed and treated early, it can lead to complications such as acute renal failure, meningoencephalitis, gastrointestinal bleeding, and multiple organ failure. However, there have been no trials comparing the effectiveness of oral and Intravenous (i.v.) doxycycline for scrub typhus treatment. Aim: To assess the efficacy of intravenous versus oral doxycycline in managing uncomplicated scrub typhus. Materials and Methods: This prospective interventional research was conducted in the Paediatrics Department at Maharajah's Institute of Medical Sciences, Vizianagaram, India, from June 2021 to July 2022. Out of a total of 178 children diagnosed with scrub typhus during the study period, 102 children who received either oral or intravenous doxycycline as monotherapy were included. The primary outcome measures studied were the incidence of delayed defervescence and the time of defervescence. The t-test or Mann-Whitney test was applied for continuous data, and the Chi-square test or Fischer's-exact test was used to compare dichotomous variables. Results: The mean age of children treated with oral doxycycline was 9.5±2.7 years and with i.v. doxycycline was 8.2±2.4 years. Among the 178 children diagnosed with scrub typhus, 102 (57.3%) children treated with doxycycline alone were included in the study. Out of these, 78 (76.4%) cases received oral doxycycline, while 28 (27.4%) cases received intravenous doxycycline. There was no statistically significant difference in the response rate between the two groups. The p-value for time to defervescence was 0.672, and the p-value for the incidence of delayed defervescence was 0.9845. Conclusion: Both oral and intravenous forms of doxycycline demonstrated similar efficacy in the treatment of scrub typhus. Nearly all children in both groups became afebrile within 72 hours after starting treatment. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Understanding the circumstances, leading to unmasking of hidden Brugada syndrome is essential for the practicing clinician and the patients so that they are informed adequately to seek prompt medical attention. Brugada syndrome is a genetic arrhythmia syndrome characterized by a coved type of ST‐segment elevation in the ECG. The patients are usually asymptomatic, with unmasking of the disease under certain conditions. We are reporting the case of a patient diagnosed with Brugada syndrome, which was unmasked during an attack of dengue fever. [ABSTRACT FROM AUTHOR]

Objective: Acute 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. Methods: This 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. Results: A 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). Conclusion: This 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.

BackgroundKawasaki disease (KD) is the leading cause of acquired heart disease in children. The major challenge in KD diagnosis is that it shares clinical signs with other childhood febrile control (FC) subjects. We sought to determine if our algorithmic approach applied to a Taiwan cohort.MethodsA single center (Chang Gung Memorial Hospital in Taiwan) cohort of patients suspected with acute KD were prospectively enrolled by local KD specialists for KD analysis. Our previously single-center developed computer-based two-step algorithm was further tested by a five-center validation in US. This first blinded multi-center trial validated our approach, with sufficient sensitivity and positive predictive value, to identify most patients with KD diagnosed at centers across the US. This study involved 418 KDs and 259 FCs from the Chang Gung Memorial Hospital in Taiwan.FindingsOur diagnostic algorithm retained sensitivity (379 of 418; 90.7%), specificity (223 of 259; 86.1%), PPV (379 of 409; 92.7%), and NPV (223 of 247; 90.3%) comparable to previous US 2016 single center and US 2020 fiver center results. Only 4.7% (15 of 418) of KD and 2.3% (6 of 259) of FC patients were identified as indeterminate. The algorithm identified 18 of 50 (36%) KD patients who presented 2 or 3 principal criteria. Of 418 KD patients, 157 were infants younger than one year and 89.2% (140 of 157) were classified correctly. Of the 44 patients with KD who had coronary artery abnormalities, our diagnostic algorithm correctly identified 43 (97.7%) including all patients with dilated coronary artery but one who found to resolve in 8 weeks.InterpretationThis work demonstrates the applicability of our algorithmic approach and diagnostic portability in Taiwan.

Abstract Background Fever is a common reason to seek healthcare in Southeast Asia, and the decline of malaria has complexified how is perceived, and what actions are taken towards it. We investigated the concept of fever and the determinants influencing health-seeking behaviours among migrants on the Thai-Myanmar border, where rapid economic development collides with precarious political and socio-economic conditions. Methods We implemented a mixed-methods study between August to December 2019. Phase I used a qualitative approach, with in-depth interviews and focus group discussions. Phase II used a quantitative approach with a close-ended questionnaire based on Phase I findings. A conditional inference tree (CIT) model first identified geographic and socio-demographic determinants, which were then tested using a logistic regression model. Results Fever corresponded to a high diversity of conceptions, symptoms and believed causes. Self-medication was the commonest behaviour at fever onset. If fever persisted, migrants primarily sought care in humanitarian cost-free clinics (45.5%, 92/202), followed by private clinics (43.1%, 87/202), health posts (36.1%, 73/202), public hospitals (33.7%, 68/202) and primary care units (30, 14.9%). The qualitative analysis identified distance and legal status as key barriers for accessing health care. The quantitative analysis further investigated determinants influencing health-seeking behaviour: living near a town where a cost-free clinic operated was inversely associated with seeking care at health posts (adjusted odds ratio [aOR], 0.40, 95% confidence interval [95% CI] [0.19–0.86]), and public hospital attendance (aOR 0.31, 95% CI [0.14–0.67]). Living further away from the nearest town was associated with health posts attendance (aOR 1.05, 95% CI [1.00–1.10] per 1 km). Having legal status was inversely associated with cost-free clinics attendance (aOR 0.27, 95% CI [0.10–0.71]), and positively associated with private clinic and public hospital attendance (aOR 2.56, 95% CI [1.00–6.54] and 5.15, 95% CI [1.80–14.71], respectively). Conclusions Fever conception and believed causes are context-specific and should be investigated prior to any intervention. Distance to care and legal status were key determinants influencing health-seeking behaviour. Current economic upheavals are accelerating the unregulated flow of undocumented migrants from Myanmar to Thailand, warranting further inclusiveness and investments in the public health system.

Introduction: Febrile Seizures (FS) are the most common neurological disorders among infants and young children, occurring in 2%-5% of children younger than five years of age. Iron deficiency is reported as a commonest micronutrient deficiency, that has been associated with FS. Aim: To find out the cause of fever and the role of Iron Deficiency Anaemia (IDA) and its outcome in first FS in six months to six years of age. Materials and Methods: This was a hospital-based prospective observationa study, conducted in the Department of Paediatrics at King George Hospital, Visakhapatnam, Andhra Pradesh, India. The duration of the study was one year and seven months, from December 2019 to July 2021. A total of 130 children (six months- six years) were included in the study. A total of 65 cases had a febrile seizure and the rest 65 controls had a history of Febrile Illness (FI) without seizures. Anaemia was defined as the decrease of Haemoglobin (Hb)450 µg/ dL, transferrin

Abstract Background Evidence on the relative importance of various factors associated with febrile illness in children and their heterogeneity across countries can inform the prevention, identification, and management of communicable diseases in resource-limited countries. The objective of the study is to assess the relative significance of factors associated with childhood febrile illness in 27 sub-Saharan African countries. Methods This cross-sectional study of 298,327 children aged 0 to 59 months assessed the strengths of associations of 18 factors with childhood fevers, using Demographic and Health Surveys (2010-2018) from 27 sub-Saharan African countries. A total of 7 child level factors (i.e., respiratory illness, diarrhea, breastfeeding initiation; vitamin A supplements; child's age; full vaccination; sex), 5 maternal factors (maternal education; maternal unemployment; antenatal care; maternal age, and maternal marriage status) and 6 household factors (household wealth; water source; indoor pollution, stool disposal; family planning needs and rural residence) were assessed. Febrile illness was defined as the presence of fever in 2 weeks preceding the survey. Results Among the 298,327 children aged 0 to 59 months included in the analysis, the weighted prevalence of fever was 22.65% (95% CI, 22.31%-22.91%). In the pooled sample, respiratory illness was the strongest factor associated with fever in children (adjusted odds ratio [aOR], 5.46; 95% CI, 5.26-5.67; P < .0001), followed by diarrhea (aOR, 2.96; 95% CI, 2.85-3.08; P < .0001), poorest households (aOR, 1.33; 95% CI,1.23-1.44; P < .0001), lack of maternal education (aOR, 1.25; 95% CI, 1.10-1.41; P < .0001), and delayed breastfeeding (aOR, 1.18; 95% CI, 1.14-1.22; P < .0001. Febrile illnesses were more prevalent in children older than >6 months compared to those 6 months and younger. Unsafe water, unsafe stool disposal, and indoor pollution were not associated with child fever in the pooled analysis but had a large country-level heterogeneity. Conclusions Major causes of fevers in sub-Saharan Africa could be attributed to respiratory infections and possibly viral infections, which should not be treated by antimalarial drugs or antibiotics. Point-of-care diagnostics are needed to identify the pathogenic causes of respiratory infections to guide the clinical management of fevers in limited-resource countries.

Abstract Background Primary health care settings and hospitals of low- and middle-income countries have few accessible diagnostic tools and limited laboratory and human resources capacity to identify multiple pathogens with high accuracy. In addition, there is a paucity of information on fever and its underlying aetiology in the adolescent and adult population in East Africa. The purpose of this study was to estimate the pooled prevalence of fever of unidentified aetiology among adolescent and adult febrile patients seeking health care in East Africa. Methods We pursued a systematic review using readily available electronic databases (i.e. PubMed, Cumulative Index to Nursing & Allied Health Literature, Scopus, Cochrane Library and Web of Science) without language restriction from inception date of the respective databases to October 31, 2022. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were screened for relevance. Further analyses based on pre-set eligibility criteria were carried out for final inclusion. Two reviewers independently screened and extracted data. Risk of study bias was assessed. Meta-analysis of the prevalence of fever of unidentified aetiology was performed. Results We identified 14,029 articles of which 25 were eligible for inclusion, reporting data from 8538 participants. The pooled prevalence of febrile cases with unidentified aetiology was 64% [95% confidence interval (CI): 51–77%, I 2 = 99.6%] among febrile adolescents and adults in East Africa. For the proportion of patients with identified aetiology, the studies documented bacterial pathogens (human bloodstream infections), bacterial zoonotic pathogens and arboviruses as the main non-malarial causative agents in East Africa. Conclusions Our study provides evidence that almost two-thirds of adolescent and adult febrile patients attending health care facilities in East Africa might receive inappropriate treatments due to unidentified potential life-threatening fever aetiology. Hence, we call for a comprehensive fever syndromic surveillance to broaden a consequential differential diagnosis of syndromic fever and to considerably improve the course of patients’ disease and treatment outcomes.

Key Clinical Message Understanding the circumstances, leading to unmasking of hidden Brugada syndrome is essential for the practicing clinician and the patients so that they are informed adequately to seek prompt medical attention. Abstract Brugada syndrome is a genetic arrhythmia syndrome characterized by a coved type of ST‐segment elevation in the ECG. The patients are usually asymptomatic, with unmasking of the disease under certain conditions. We are reporting the case of a patient diagnosed with Brugada syndrome, which was unmasked during an attack of dengue fever.

Background: Fever is a common reason to seek healthcare in Southeast Asia, and the decline of malaria has complexified how is perceived, and what actions are taken towards it. We investigated the concept of fever and the determinants influencing health-seeking behaviours among migrants on the Thai-Myanmar border, where rapid economic development collides with precarious political and socio-economic conditions. Methods: We implemented a mixed-methods study between August to December 2019. Phase I used a qualitative approach, with in-depth interviews and focus group discussions. Phase II used a quantitative approach with a close-ended questionnaire based on Phase I findings. A conditional inference tree (CIT) model first identified geographic and socio-demographic determinants, which were then tested using a logistic regression model. Results: Fever corresponded to a high diversity of conceptions, symptoms and believed causes. Self-medication was the commonest behaviour at fever onset. If fever persisted, migrants primarily sought care in humanitarian cost-free clinics (45.5%, 92/202), followed by private clinics (43.1%, 87/202), health posts (36.1%, 73/202), public hospitals (33.7%, 68/202) and primary care units (30, 14.9%). The qualitative analysis identified distance and legal status as key barriers for accessing health care. The quantitative analysis further investigated determinants influencing health-seeking behaviour: living near a town where a cost-free clinic operated was inversely associated with seeking care at health posts (adjusted odds ratio [aOR], 0.40, 95% confidence interval [95% CI] [0.19–0.86]), and public hospital attendance (aOR 0.31, 95% CI [0.14–0.67]). Living further away from the nearest town was associated with health posts attendance (aOR 1.05, 95% CI [1.00–1.10] per 1 km). Having legal status was inversely associated with cost-free clinics attendance (aOR 0.27, 95% CI [0.10–0.71]), and positively associated with private clinic and public hospital attendance (aOR 2.56, 95% CI [1.00–6.54] and 5.15, 95% CI [1.80–14.71], respectively). Conclusions: Fever conception and believed causes are context-specific and should be investigated prior to any intervention. Distance to care and legal status were key determinants influencing health-seeking behaviour. Current economic upheavals are accelerating the unregulated flow of undocumented migrants from Myanmar to Thailand, warranting further inclusiveness and investments in the public health system. [ABSTRACT FROM AUTHOR]

Introduction: Febrile Seizures (FS) are the most common neurological disorders among infants and young children, occurring in 2%-5% of children younger than five years of age. Iron deficiency is reported as a commonest micronutrient deficiency, that has been associated with FS. Aim: To find out the cause of fever and the role of Iron Deficiency Anaemia (IDA) and its outcome in first FS in six months to six years of age. Materials and Methods: This was a hospital-based prospective observationa study, conducted in the Department of Paediatrics at King George Hospital, Visakhapatnam, Andhra Pradesh, India. The duration of the study was one year and seven months, from December 2019 to July 2021. A total of 130 children (six months-six years) were included in the study. A total of 65 cases had a febrile seizure and the rest 65 controls had a history of Febrile Illness (FI) without seizures. Anaemia was defined as the decrease of Haemoglobin (Hb)<11 gm%. Among the Red Blood Cells (RBC) indices Mean Corpuscular Volume (MCV) <70 femtoliters (fl), Mean Corpuscular Haemoglobin (MCH) <27 picograms (pg), plasma ferritin<12 µg/dL, and serum ferrous<60 µg/dL, Total Iron Binding Capacity (TIBC) >450 µg/dL, transferrin<250 mg. Discrete variables are expressed as counts (%) and compared using the Chi-square test, quantitative variables were expressed as mean and Standard Deviation (SD) and compared using t-test. and Statistical significance was set at p-value<0.05. Analysis was done using Statistical Package for Social Sciences (SPSS) version 22.0. Results: The mean age of the study participants (cases) was 2.57±1.5 years for cases and 2.56±1.35 years for controls. In the present study, male:female ratio was 1.24:1. In the present study, positive family history of seizures is an important risk factor for FS. The observations came 43 (66.2%) cases were IDA with FS 22 (33.8%) cases, were, with only FS 23 (35.4%) of controls were, with IDA and FI 42 (64.6%) of controls with the FI, which is statistically significant, p-value=0.001. Conclusion: IDA is one of the major risk factors for FS in the paediatric age group. Early identification and treatment of iron deficiency may prove helpful in preventing FS in paediatric patient. [ABSTRACT FROM AUTHOR]

Summary: Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.

Summary: Background: Children in Africa carry a disproportionate burden of malnutrition and infectious disease. Together, malnutrition and infection are major contributors to global child mortality; however, their collective impact on immune activation are not well described. Methods: This was a secondary analysis of a prospective cohort study of children hospitalized with acute febrile illness at a single centre in Uganda. We investigated the association between malnutrition (determined using the mid-upper arm circumference, MUAC), immune activation (as measured by inflammatory markers IL-6, IL-8, CXCL10, CHI3L1, sTNFR1, Cystatin C, granzyme B, and sTREM-1), and mortality. Findings: Of the 1850 children eligible for this secondary analysis, 71 (3.8%) and 145 (11.7%) presented with severe acute malnutrition (SAM, MUAC

Background: Evidence on the relative importance of various factors associated with febrile illness in children and their heterogeneity across countries can inform the prevention, identification, and management of communicable diseases in resource-limited countries. The objective of the study is to assess the relative significance of factors associated with childhood febrile illness in 27 sub-Saharan African countries. Methods: This cross-sectional study of 298,327 children aged 0 to 59 months assessed the strengths of associations of 18 factors with childhood fevers, using Demographic and Health Surveys (2010-2018) from 27 sub-Saharan African countries. A total of 7 child level factors (i.e., respiratory illness, diarrhea, breastfeeding initiation; vitamin A supplements; child's age; full vaccination; sex), 5 maternal factors (maternal education; maternal unemployment; antenatal care; maternal age, and maternal marriage status) and 6 household factors (household wealth; water source; indoor pollution, stool disposal; family planning needs and rural residence) were assessed. Febrile illness was defined as the presence of fever in 2 weeks preceding the survey. Results: Among the 298,327 children aged 0 to 59 months included in the analysis, the weighted prevalence of fever was 22.65% (95% CI, 22.31%-22.91%). In the pooled sample, respiratory illness was the strongest factor associated with fever in children (adjusted odds ratio [aOR], 5.46; 95% CI, 5.26-5.67; P <.0001), followed by diarrhea (aOR, 2.96; 95% CI, 2.85-3.08; P <.0001), poorest households (aOR, 1.33; 95% CI,1.23-1.44; P <.0001), lack of maternal education (aOR, 1.25; 95% CI, 1.10-1.41; P <.0001), and delayed breastfeeding (aOR, 1.18; 95% CI, 1.14-1.22; P <.0001. Febrile illnesses were more prevalent in children older than >6 months compared to those 6 months and younger. Unsafe water, unsafe stool disposal, and indoor pollution were not associated with child fever in the pooled analysis but had a large country-level heterogeneity. Conclusions: Major causes of fevers in sub-Saharan Africa could be attributed to respiratory infections and possibly viral infections, which should not be treated by antimalarial drugs or antibiotics. Point-of-care diagnostics are needed to identify the pathogenic causes of respiratory infections to guide the clinical management of fevers in limited-resource countries. [ABSTRACT FROM AUTHOR]

Background: Primary health care settings and hospitals of low- and middle-income countries have few accessible diagnostic tools and limited laboratory and human resources capacity to identify multiple pathogens with high accuracy. In addition, there is a paucity of information on fever and its underlying aetiology in the adolescent and adult population in East Africa. The purpose of this study was to estimate the pooled prevalence of fever of unidentified aetiology among adolescent and adult febrile patients seeking health care in East Africa. Methods: We pursued a systematic review using readily available electronic databases (i.e. PubMed, Cumulative Index to Nursing & Allied Health Literature, Scopus, Cochrane Library and Web of Science) without language restriction from inception date of the respective databases to October 31, 2022. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were screened for relevance. Further analyses based on pre-set eligibility criteria were carried out for final inclusion. Two reviewers independently screened and extracted data. Risk of study bias was assessed. Meta-analysis of the prevalence of fever of unidentified aetiology was performed. Results: We identified 14,029 articles of which 25 were eligible for inclusion, reporting data from 8538 participants. The pooled prevalence of febrile cases with unidentified aetiology was 64% [95% confidence interval (CI): 51–77%, I2 = 99.6%] among febrile adolescents and adults in East Africa. For the proportion of patients with identified aetiology, the studies documented bacterial pathogens (human bloodstream infections), bacterial zoonotic pathogens and arboviruses as the main non-malarial causative agents in East Africa. Conclusions: Our study provides evidence that almost two-thirds of adolescent and adult febrile patients attending health care facilities in East Africa might receive inappropriate treatments due to unidentified potential life-threatening fever aetiology. Hence, we call for a comprehensive fever syndromic surveillance to broaden a consequential differential diagnosis of syndromic fever and to considerably improve the course of patients' disease and treatment outcomes. [ABSTRACT FROM AUTHOR]

Aim: This study investigated febrile children with petechial rashes who presented to European emergency departments (EDs) and investigated the role that mechanical causes played in diagnoses. Methods: Consecutive patients with fever presenting to EDs in 11 European emergency departments in 2017–2018 were enrolled. The cause and focus of infection were identified and a detailed analysis was performed on children with petechial rashes. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: We found that 453/34010 (1.3%) febrile children had petechial rashes. The focus of the infection included sepsis (10/453, 2.2%) and meningitis (14/453, 3.1%). Children with a petechial rash were more likely than other febrile children to have sepsis or meningitis (OR 8.5, 95% CI 5.3–13.1) and bacterial infections (OR 1.4, 95% CI 1.0–1.8) as well as need for immediate life‐saving interventions (OR 6.6, 95% CI 4.4–9.5) and intensive care unit admissions (OR 6.5, 95% CI 3.0–12.5). Conclusion: The combination of fever and petechial rash is still an important warning sign for childhood sepsis and meningitis. Ruling out coughing and/or vomiting was insufficient to safely identify low‐risk patients. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is the causal agent of dengue fever. The symptoms and signs of dengue vary from febrile illness to hemorrhagic syndrome. IFITM3 and TNFA are genes of the innate immune system. Variants IFITM3 (rs12252 T>C) and TNFA (rs1800629 G > A and rs361525 G>A) might alter gene expression and change the course of the disease. Our first objective was to determine whether these variants were associated with the susceptibility and severity of dengue. The second was to assess the association of these variants with each symptom. We studied 272 cases with suspected dengue infection, of which 102 were confirmed dengue cases (DENV+) and 170 were dengue-like cases without DENV infection (DENV−). Samples of 201 individuals from the general population of Mexico were included as a reference. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique. Odds ratios and confidence intervals were calculated using Pearson's chi-square test and later adjusted for age and sex with a binary logistic regression model. Haldane correction is applied when necessary. We found a significantly higher frequency of the A allele of TNFA rs361525 in both the DENV+ and DENV− groups compared with the general population. Focusing on DENV+ and DENV−, the frequency of the A allele of TNFA rs361525 was higher in the DENV+ group. A broad spectrum of symptoms was related to the A allele of both TNFA variants. We conclude that TNFA rs361525 increases the susceptibility to symptomatic dengue but can also be associated with susceptibility to other dengue-like symptoms from unknown causes. [ABSTRACT FROM AUTHOR]

BackgroundWhile health providers consistently use malaria rapid diagnostic tests to rule out malaria, they often lack tools to guide treatment for those febrile patients who test negative. Without the tools to provide an alternative diagnosis, providers may prescribe unnecessary antibiotics or miss a more serious condition, potentially contributing to antibiotic resistance and/or poor patient outcomes.MethodsThis study ascertained which diagnoses and treatments might be associated with poor outcomes in adults who test negative for malaria. Adult patients for rapid diagnostic test of malaria seen in mobile health clinics in Mulanje and Phalombe districts were followed for 14 days. Participants were interviewed on sociodemographic characteristics, health-seeking behaviour, diagnosis, treatment and access to care. Mobile clinic medical charts were reviewed. Two weeks (±2 days) following clinic visit, follow-up interviews were conducted to assess whether symptoms had resolved.ResultsInitially, 115 adult patients were enrolled and 1 (0.88%) was lost to follow-up. Of the 114 adult patients remaining in the study, 55 (48%) were seen during the dry season and 59 (52%) during the wet season. Symptoms resolved in 90 (80%) patients at the 14-day follow-up visit (n=90) with the rest (n=24) reporting no change in symptoms. None of the patients in the study died or were referred for further care. Almost all patients received some type of medication during their clinic visit (98.2%). Antibiotics were given to 38.6% of patients, and virtually all patients received pain or fever relief (96.5%). However, no anti-malarials were prescribed.ConclusionsMobile clinics provide important health care where access to care is limited. Although rapid tests have guided appropriate treatment, challenges remain when a patient's presenting complaint is less well defined. In rural areas of southern Malawi, simple diagnostics are needed to guide treatment decisions.

BackgroundHow people respond to febrile illness is critical to malaria prevention, control, and ultimately elimination. This article explores factors affecting treatment-seeking behaviour for febrile illnesses in a remote area of Lao PDR.MethodsHousehold heads or their representatives (n = 281) were interviewed using a structured questionnaire. A total of twelve focus group discussions (FGDs) each with eight to ten participants were conducted in four villages. In addition, observations were recorded as field notes (n = 130) and were used to collect information on the local context, including the treatment seeking behaviour and the health services.ResultsAlmost three-quarters (201/281) of respondents reported fever in past two months. Most (92%, 185/201) sought treatment of which 80% (149/185) sought treatment at a health centre. Geographic proximity to a health centre (AOR = 6.5; CI = 1.74-24.25; for those  3.6 km) and previous experience of attending a health centre (AOR = 4.7; CI = 1.2-19.1) were strong predictors of visiting a health centre for febrile symptoms. During FGDs, respondents described seeking treatment from traditional healers and at health centre for mild to moderate illnesses. Respondents also explained how if symptoms, including fever, were severe or persisted after receiving treatment elsewhere, they sought assistance at health centres. Access to local health centres/hospitals was often constrained by a lack of transportation and an ability to meet the direct and indirect costs of a visit.ConclusionIn Nong District, a rural area bordering Vietnam, people seek care from health centres offering allopathic medicine and from spiritual healers. Decisions about where and when to attend health care depended on their economic status, mobility (distance to the health centre, road conditions, availability of transport), symptoms severity and illness recognition. Current and future malaria control/elimination programmes could benefit from greater collaboration with the locally accessible sources of treatments, such as health volunteers and traditional healers.

Abstract Background In Myanmar, malaria still poses a significant burden for vulnerable populations particularly forest goers even though impressive progress has been made over the past decade. Limited evidence existed related to forest goers’ health-seeking behaviour and factors that drive decision making for providers’ choice to support national malaria programmes towards elimination. In response to that, this research is conducted to identify who they preferred and what are the factors associated with providers’ choice in malaria febrile illness and Rapid Diagnostic Testing (RDT). Methods A cross-sectional study applying quantitative household survey was completed with 479 forest goer households in 20 malaria endemic townships across Myanmar. The household data was collected with the types of providers that they consulted for recent and previous febrile episodes. To identify the factors associated with providers’ choices, univariate and multivariate multinomial logistic regressions were done using Stata version 14.1. Statistical significance was set as p = 0.05. Results A total of 307 individuals experienced fever within one month and 72.3% sought care from providers. Also, a total of 509 forest goers reported that they had a previous febrile episode and 62.6% received care from a provider. Furthermore, 56.2% said that they had RDT testing during these previous febrile illnesses. They consulted public facilities and public health staff, private facilities, private and semi-private providers, community health volunteers or workers in their residing village and those located outside their villages but majority preferred those within their villages. On multivariate analyses, second richest quintile (public, RRR = 12.9) (semi-private, RRR = 17.9), (outside, RRR = 8.4) and access to 4 and above nearby providers (public, RRR = 30.3) (semi-private, RRR = 1.5) (outside, RRR = 0.5) were found to be significantly associated with provider choice for recent fever episode. Similar findings were also found for previous febrile illness and RDT testing among forest goers. Conclusions It was highlighted in this study that in forest goer households, they preferred nearby providers and the decision to choose providers seemed to be influenced by their access to number of nearby providers and socio-economic status when they sought care from a provider regardless of fever occurrence location. It was important that the national programmes considere involving these nearby providers in elimination efforts.

Abstract Background Urban malaria has received insufficient attention in the literature. The prevalence and clinical characteristics of Plasmodium falciparum infection amongst patients presenting with suspected malaria were investigated at a major urban hospital in Douala, Cameroon with a particular focus on anaemia. Methods A cross-sectional, 18-week demographic and clinical survey was conducted of patients presenting to the Emergency Department of Douala Military Hospital with suspected malaria, largely defined by the presence or recent history of fever. Venous samples were tested for P. falciparum using rapid diagnostic tests and PCR, and anaemia was defined by haemoglobin level according to WHO definitions. Likelihood ratios (LR), odds ratios (OR), and population attributable risk percent (PARP) were calculated. Results Participants were ages 8 months to 86 years, 51% were women (257/503), and all districts of Douala were represented. Overall, 38.0% (n = 189/497) were anaemic, including 5.2% (n = 26/497) with severe anaemia. Anaemia prevalence was significantly higher (OR: 2.20, 95% CI 1.41–3.45) among children 40 °C at presentation (positive LR: 4.83). Among all participants, 8.7% of anaemia was associated with P. falciparum infection, while the PARP was 33.2% among those

Abstract Background Predictors associated with the decision of blood culture ordering among hospitalized patients with abnormal body temperature are still underexplored, particularly non-clinical factors. In this study, we evaluated the factors affecting blood culture ordering in febrile and hypothermic inpatients. Methods We performed a retrospective study of 15,788 adult inpatients with fever (≥ 38.3℃) or hypothermia (

Abstract Background We aimed to assess the prevalence of Salmonella Typhi through DNA and IgM-antibody detection methods as a prelude to extended surveillance activities at sites in Ghana, Madagascar, and Ethiopia. Methods We performed species-specific real-time polymerase reaction (RT-PCR) to identify bacterial nucleic acid, and enzyme-linked immunosorbent assay (ELISA) for detecting HlyE/STY1498-, CdtB/STY1886-, pilL/STY4539- and Vi-antigens in blood and biopsy specimens of febrile and non-febrile subjects. We generated antigen-specific ELISA proxy cut-offs by change-point analyses, and utilized cumulative sum as detection method coupled with 1000 repetitive bootstrap analyses. We computed prevalence rates in addition to odds ratios to assess correlations between ELISA outcomes and participant characteristics. Results Definitive positive RT-PCR results were obtained from samples of febrile subjects originating from Adama Zuria/Ethiopia (1.9%, 2/104), Wolayita Sodo/Ethiopia (1.0%, 1/100), Diego/Madagascar (1.0%, 1/100), and Kintampo/Ghana (1.0%, 1/100), and from samples of non-febrile subjects from Wolayita Sodo/Ethiopia (1%, 2/201). While IgM antibodies against all antigens were identified across all sites, prevalence rates were highest at all Ethiopian sites, albeit in non-febrile populations. Significant correlations in febrile subjects aged

Objective: In this study, we aimed to conduct a systematic review to characterize antimicrobial resistance (AMR) patterns for bacterial causes of febrile illness in Africa and Asia. Methods: We included published literature from 1980-2015 based on data extracted from two recent systematic reviews of nonmalarial febrile illness from Africa, South Asia, and Southeast Asia. Selection criteria included articles with full bacterial identification and antimicrobial susceptibility testing (AST) results for key normally sterile site pathogen-drug combinations. Pooled proportions of resistant isolates were combined using random effects meta-analysis. Study data quality was graded using the Microbiology Investigation Criteria for Reporting Objectively (MICRO) framework. Results: Of 3475 unique articles included in the previous reviews, 371 included the target pathogen-drug combinations. Salmonella enterica tested against ceftriaxone and ciprofloxacin were the two highest reported combinations (30,509 and 22,056 isolates, respectively). Pooled proportions of resistant isolates were high for third-generation cephalosporins for Klebsiella pneumoniae and Escherichia coli in all regions. The MICRO grading showed an overall lack of standardization. Conclusion: This review highlights a general increase in AMR reporting and in resistance over time. However, there were substantial problems with diagnostic microbiological data quality. Urgent strengthening of laboratory capacity, standardized testing, and reporting of AST results is required to improve AMR surveillance.