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[This corrects the article DOI: 10.3389/fped.2023.1240242.].

The impact of the COVID-19 pandemic on new diagnoses of recurrent fevers and autoinflammatory diseases is largely unknown. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA/AID Working Group aimed to investigate the impact of the COVID-19 pandemic on the number of pediatric patients evaluated for recurrent fevers and autoinflammatory diseases in North America. The absolute number of new outpatient visits and the proportion of these visits attributed to recurrent fever diagnoses during the pre-pandemic period (1 March 2019-29 February 2020) and the first year of the COVID-19 pandemic (1 March 2020-28 February 2021) were examined. Data were collected from 27 sites in the United States and Canada. Our results showed an increase in the absolute number of new visits for recurrent fever evaluations in 21 of 27 sites during the COVID-19 pandemic compared to the pre-pandemic period. The increase was observed across different geographic regions in North America. Additionally, the proportion of new visits to these centers for recurrent fever in relation to all new patient evaluations was significantly higher during the first year of the pandemic, increasing from 7.8% before the pandemic to 10.9% during the pandemic year (p

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Wenzel Trnka von Krzowitz’s Study Historia febrium intermittentium on Malaria in the Habsburg Monarchy. Wenzel Trnka von Krzowitz was born in 1739 in Tabor. He graduated from the University of Vienna, where after studying philosophy he studied at the Faculty of Medicine. His personality and systematic work attracted the attention of Gerard van Swieten, who in 1769 made a significant contribution to the institutional establishment of the first medical faculty in the Hungarian Lands. Trnka thus became one of the founding members of this faculty, where he was appointed professor of anatomy. The Faculty of Medicine was the last part of the Pázmany University to be established in Trnava, which could not meet the needs of a growing university, especially of the medical faculty itself, and so in 1777 the entire campus was moved to Buda. While still in Trnava, in 1775, Trnka published one of his most important works, Historia febrium intermittentium, in which he discusses intermittent fevers. These fevers were a relatively common and unpleasant phenomenon in Europe, especially in certain regions. They are caused by protozoa of the genus Plasmodium, discovered in the 19th century, which cause several types of malaria, all of them being characterised by periodic bouts of fever. In his work, Trnka discusses in detail both the actual course of the disease and the treatment, emphasizing the use of quinine bark. The work contains several historically valuable chapters. It describes views and treat- ments of malaria in the 18th century, focusing also on those areas in the Habsburg Monarchy where the disease was widespread. Through Trnka’s work, the article provides an insight into life with this now exotic disease, which is today of little concern in our part of the world.

The impact of the COVID-19 pandemic on new diagnoses of recurrent fevers and autoinflammatory diseases is largely unknown. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA/AID Working Group aimed to investigate the impact of the COVID-19 pandemic on the number of pediatric patients evaluated for recurrent fevers and autoinflammatory diseases in North America. The absolute number of new outpatient visits and the proportion of these visits attributed to recurrent fever diagnoses during the pre-pandemic period (1 March 2019–29 February 2020) and the first year of the COVID-19 pandemic (1 March 2020–28 February 2021) were examined. Data were collected from 27 sites in the United States and Canada. Our results showed an increase in the absolute number of new visits for recurrent fever evaluations in 21 of 27 sites during the COVID-19 pandemic compared to the pre-pandemic period. The increase was observed across different geographic regions in North America. Additionally, the proportion of new visits to these centers for recurrent fever in relation to all new patient evaluations was significantly higher during the first year of the pandemic, increasing from 7.8% before the pandemic to 10.9% during the pandemic year (p

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En este artículo se abordará la llegada de la epidemia de 1813 a Tlalnepantla y sus pueblos sujetos, mismos que se ubicaban en el camino hacia Querétaro. Como sucedió en otras zonas de la Nueva España, las llamadas “fiebres misteriosas” o “epidemia de fiebres” provocaron una catástrofe demográfica de grandes dimensiones. Se pretende demostrar que el paso de tropas por el camino hacia el norte fue un factor determinante para la llegada del tifo a esta zona. Las fuentes con que se contó para hacer este estudio son de dos tipos: la información generada por las autoridades militares leales a la Corona, que reflejaban su gran preocupación ante el aumento de los contagios en esta zona, y los archivos parroquiales de Tlalnepantla.

Introduction: Sierra Leone has one of the highest burdens of febrile illnesses in the world. As the incidence of malaria diminishes, a better understanding of the spectrum of etiological agents was important for accurate diagnosis and empirical treatment of febrile illness. Methods: Blood, nasopharyngeal, and fecal specimens were collected from febrile patients for serological, molecular detection, and microbiologic culture to identify potential pathogens. Results: For this prospective study, 142 febrile patients were enrolled. The prevalence of malaria was higher in children aged 5–15 years old (P = 0.185) and adults (P = 0.018). Acute respiratory infection (ARI) presented more commonly in the under 5 years old group (P = 0.009). For diarrhea, all children groups (P = 0.024) were predominant. A total of 22.5% of the febrile patients had malaria infection, 19.7% had typhoid infection, and 2.8% were coinfected with malaria and typhoid. ARI was the most common causes of fever, accounting for 31.7% of patients, influenza A virus, Mycoplasma pneumoniae, and five other respiratory pathogens were found. Diarrhea accounted for 16.2%, and seven kinds of diarrhea bacteria were isolated. Hepatitis B accounted for 8.5%, including five cases of spontaneous bacterial peritonitis, and ascites smear staining were both Gram-negative bacteria. Tuberculous encephalitis, parasitic diseases (ascaris and filariasis), and skin infection caused by Staphylococcus aureus accounted for 0.7%, 2.1%, and 0.7%, respectively. Conclusions: Evidence of a wide spectrum of febrile etiological agents other than malaria was identified. The spread of malaria rapid diagnostic tests (RDTs) out of hospital and establishment of a national standard for Widal test will reduce the misdiagnosis of febrile diseases. Antibiotics against Gram-negative bacteria are helpful for empirical treatment. Plain Language Summary: Sierra Leone has one of the highest burdens of febrile illnesses in the world. Evidence of a wide spectrum of febrile pathogens other than malaria has been proven in this study. We considered that the etiology of febrile patients was closely related to local geography, heredity, immune features, economic industry, living habits, air pollution, medical and health conditions, and this was fully analyzed and discussed. The screening process used in this study can further simplify and identify the etiological agents of fever in more than 70% of the study population. This laid the foundation for the establishment of a more simplified and efficient diagnosis and treatment process in the local area. We also found the characteristics of age distribution of different febrile diseases. Children were an important susceptible population to fever. This study indicated the importance of reliable diagnostic tests for febrile pathogens and provided the necessary information for RDT requirements. The spread of malaria RDTs out of hospital and establishment of a national standard for Widal test will reduce the misdiagnosis of febrile diseases. For empirical treatment, antimalarial treatment was still targeted at falciparum malaria in Sierra Leone. Antibiotics against Gram-negative bacteria contributed to the empirical treatment of febrile diseases. For patients with acute respiratory tract infection, Gram-positive coccal antibiotics could be candidates for treatment. In addition, systematic and professional treatment of liver diseases should be promoted to reduce infection complications. [ABSTRACT FROM AUTHOR]

Medical reports on fevers and epidemics are an interesting research field for investigating eighteenth-century medical language. The works under scrutiny here are focused on epidemic outbreaks which were widespread especially in large and medium towns. They provide linguistic evidence for the many processes of denomination and lexicalisation of diseases, and the lexicalisation of related notions (e.g. contagion and infection), ideas (e.g. environment and social groups), and values (e.g. public health, prevention, poverty and wealth). Starting from the two keywords fever/s and epidemic/s, the aim of this study is to analyse a set of texts published in the British Isles in the last thirty years of the century and referring to contemporary events (from the middle 1760s to the end of the century), in order to discuss the processes of lexicalisation and their impact and function at discourse level. Data were collected quantitatively and qualitatively: the analysis was first carried out on a corpus-based software (focus on occurrence, frequency, collocates, patterns); whereas close reading of concordances and manual selection of extracts represent the qualitative approach and examination for interpretation and discussion of preliminary quantitative results. Medical writing often becomes the background for introducing social issues and contemporary needs and values. The study will confirm this relevant function in the changing late eighteenth-century British society. [ABSTRACT FROM AUTHOR]

We present a case of a 94-year-old female who presented to the emergency room with a fever and generalized weakness without an initial obvious source of infection. Throughout admission, she continued to be febrile despite broad-spectrum antibiotics. Several days into admission, the patient complained of severe back pain, necessitating magnetic resonance imaging (MRI) of the entire spine. The imaging revealed an extensive epidural fluid collection consistent with a spinal epidural abscess. Fortunately, she did not have any neurological deficits and was treated conservatively with IV antibiotics with improvement. This case highlights this rare presentation and the importance of early diagnosis and management of spinal epidural abscesses., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yadav et al.)

In early modern Scandinavia, the population's sensitivity to disease and food supply shortages was great. Researchers have long been interested in the crises caused by these conditions, and the dominant causes of death have been well documented in Sweden since the late eighteenth century. But for the seventeenth and early eighteenth century, in the mortality regime preceding the initial stage of the demographic transition, our understanding of the infectious diseases is significantly limited. Through an analysis of causes of death and tithe levels, this article gives new insight regarding mortality rates, harvests and, above all, diseases in a parish located in a Swedish forested area during the mid- and late seventeenth century and first half of the eighteenth century. It presents new research about which diagnoses were most common, how often the more prevalent diseases of fevers, smallpox, and dysentery broke out, and the varying role of diseases on mortality rates during bad harvest years. The inhabitants in this parish presumably had a food supply buffer in their summer farm system, yet they remained vulnerable to bad harvests, and people in the area were just as susceptible to the common infectious diseases as the inhabitants in more tightly populated areas. [ABSTRACT FROM AUTHOR]

In the early- to mid-nineteenth century, European mortality rates in West Africa were the highest in the world. Mortality estimates included nine missionaries sent from the Basel Mission (established in what is now Switzerland) to the Gold Coast (present-day Ghana), eight of whom died between 1828 and 1840, mostly from "fevers." In response to high mortality rates, the Basel Mission recruited several Afro-West Indians to work as Christian missionaries in the Gold Coast, mostly based on the presumption that individuals of African descent would better survive the environment. The decision to recruit Afro-West Indians to evangelize on the Gold Coast seemed to the mission to be a rational decision, one not in need of further justification or an overarching theory of race, environment, and disease. Surprisingly, the Basel Mission did not justify this position Biblically either. Once arrived, the West Indian Christian missionaries mostly lived in the Akwapem hills above Accra at an elevation that would have provided some protection against malaria; subsequently, their mortality rates were significantly lower than the European missionaries. After quinine came to be used as a prophylactic against malaria after 1850, thus lowering European missionary mortality rates, no more Afro-West Indians were recruited by the Basel Mission., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Though exclusive breastfeeding (EBF) for the first six months is recommended, it remains a debatable issue in both developed and developing countries. Thus, this study investigated the effect of EBF cessation time on childhood morbidity and adverse nutritional outcome in Ethiopia. Methods: We used the 2011 and 2016 Ethiopian Demographic and Health Surveys. The study involved 2,433 children under six months of age. Logistic regression model was applied to determine the effect of EBF cessation time on outcome variables. Population Attributable Fraction was calculated to evaluate the public health impacts of EBF termination in the population. Results: Discontinuing EBF at 0–3 months (adjusted odds ratio (AOR): 1.95, 95% confidence interval (CI): 1.08, 3.53)) and 4–6 months (AOR: 3.57, 95% CI: 2.19, 5.83) increased diarrhea occurrence compared to children who continued EBF up to 6 months. Children who had terminated EBF at 4–6 months had increased odds of fever (AOR: 1.73, 95% CI: 1.11, 2.68) and acute respiratory illnesses (ARIs) (AOR: 2.74, 95% CI: 1.61, 4.65). Cessation of EBF earlier than 4 months or between 4–6 months was associated with increased odds of having at least one childhood morbidity. Termination of EBF at 0–3 months and at 4–6 months were associated with increased occurrence of wasting (AOR: 2.32, 95% CI: 1.45, 3.74) and underweight (AOR: 2.30, 95% CI: 1.36, 3.91), respectively. Exclusive breastfeeding can avert 42% of diarrhea, 27% of ARI, 21% of fever, 26% of wasting and 23% of underweight burden among children under six months of age. Conclusions: Termination of EBF before six months was associated with increased occurrence of diarrhea, fever and ARIs. It was also linked with increased occurrence of childhood wasting and underweight. The finding emphasized EBF for the first six months to reduce childhood morbidity and adverse nutritional outcomes. [ABSTRACT FROM AUTHOR]

Background: Fascioliasis is a neglected zoonosis with major public health implications in humans. Although triclabendazole (TCBZ) is the drug of choice, there are records of TCBZ failure worldwide. TCBZ-resistant fascioliasis is treated with alternative approved drugs including nitazoxanide (NTZ), with varying levels of efficacy. Data on NTZ efficacy after TCBZ failure in Egypt is scarce. This study evaluated the efficacy of NTZ in cases of TCBZ failure during an outbreak of fascioliasis in Assiut governorate of Upper Egypt. Methodology/Principal findings: This prospective study included 67 patients from the outpatient clinic in Manfalout locality of Assiut governorate with clinical manifestations of acute fascioliasis. These included high eosinophilia (> 6% eosinophils in peripheral blood), positive anti-Fasciola antibodies, and hepatic focal lesions (HFL) or ascites on abdominal ultrasound or computed tomography. All patients initially received TCBZ at recommended doses. Patients were followed up after 1 month to assess response. According to the responses, patients were categorized as non-responders and responders. The non-responders received a trial of NTZ and were re-assessed for response based on clinical manifestations, eosinophil count, and abdominal ultrasound. Patients not responding to NTZ received additional doses of TCBZ. One month after initial TCBZ treatment, 37 patients responded well to TCBZ, while 30 patients failed to respond with persistence of fever, abdominal pain, high eosinophilia, and HFL. Most non-responders were male (56.7%); females predominated among TCBZ responders (62.2%). The mean age of the non-responders was relatively lower, at 20.57 ± 14.47 years (p = 0.004). Following NTZ therapy, HFL disappeared in 9/30 (30%) patients and eosinophil counts normalized in only 2 (6.7%) patients, indicating an overall efficacy of 36.6%. The remaining cases received additional doses of TCBZ with complete clinical, pathological, and radiological resolution. Conclusions/Significance: Nitazoxanide was partially effective in TCBZ failure in acute human fascioliasis in Upper Egypt. Further studies with larger samples are highly encouraged and further research is urgently needed to find new therapeutic alternatives to TCBZ. [ABSTRACT FROM AUTHOR]

Swine influenza virus (SIVs) infections cause a significant economic impact to the pork industry. Moreover, pigs may act as mixing vessel favoring genome reassortment of diverse influenza viruses. Such an example is the pandemic H1N1 (pH1N1) virus that appeared in 2009, harboring a combination of gene segments from avian, pig and human lineages, which rapidly reached pandemic proportions. In order to confront and prevent these possible emergences as well as antigenic drift phenomena, vaccination remains of vital importance. The present work aimed to evaluate a new DNA influenza vaccine based on distinct conserved HA-peptides fused with flagellin and applied together with Diluvac Forte as adjuvant using a needle-free device (IntraDermal Application of Liquids, IDAL®). Two experimental pig studies were performed to test DNA-vaccine efficacy against SIVs in pigs. In the first experiment, SIV-seronegative pigs were vaccinated with VC4-flagellin DNA and intranasally challenged with a pH1N1. In the second study, VC4-flagellin DNA vaccine was employed in SIV-seropositive animals and challenged intranasally with an H3N2 SIV-isolate. Both experiments demonstrated a reduction in the viral shedding after challenge, suggesting vaccine efficacy against both the H1 and H3 influenza virus subtypes. In addition, the results proved that maternally derived antibodies (MDA) did not constitute an obstacle to the vaccine approach used. Moreover, elevated titers in antibodies both against H1 and H3 proteins in serum and in bronchoalveolar lavage fluids (BALFs) was detected in the vaccinated animals along with a markedly increased mucosal IgA response. Additionally, vaccinated animals developed stronger neutralizing antibodies in BALFs and higher inhibiting hemagglutination titers in sera against both the pH1N1 and H3N2 influenza viruses compared to unvaccinated, challenged-pigs. It is proposed that the described DNA-vaccine formulation could potentially be used as a multivalent vaccine against SIV infections. [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection of CCHF virus (CCHFV) with mycobacterial infection has not been assessed nor has the ability of virus to persist and cause long-term sequela in a primate model. In this study, we compared the disease progression of two diverse strains of CCHFV in the recently described cynomolgus macaque model. All animals demonstrated signs of clinical illness, viremia, significant changes in clinical chemistry and hematology values, and serum cytokine profiles consistent with CCHF in humans. The European and Asian CCHFV strains caused very similar disease profiles in monkeys, which demonstrates that medical countermeasures can be evaluated in this animal model against multiple CCHFV strains. We identified evidence of CCHFV persistence in the testes of three male monkeys that survived infection. Furthermore, the histopathology unexpectedly revealed that six additional animals had evidence of a latent mycobacterial infection with granulomatous lesions. Interestingly, CCHFV persisted within the granulomas of two animals. This study is the first to demonstrate the persistence of CCHFV in the testes and within the granulomas of non-human primates with concurrent latent tuberculosis. Our results have important public health implications in overlapping endemic regions for these emerging pathogens. [ABSTRACT FROM AUTHOR]

In 2014, the World Health Organization (WHO) proposed a new severe influenza surveillance case definition, which has not been evaluated in a high human immunodeficiency virus (HIV) prevalence setting. Our study aimed to assess the performance of this proposed case definition in identifying influenza among HIV-uninfected and HIV-infected children aged <5 years in South Africa. We prospectively enrolled children aged <5 years hospitalised with physician-diagnosed lower respiratory tract infection (LRTI) at two surveillance sites from January 2011 to December 2015. Epidemiologic and clinical data were collected. We tested nasopharyngeal aspirates for influenza using reverse transcription polymerase chain reaction. We used logistic regression to assess factors associated with influenza positivity among HIV-infected and HIV-uninfected children. We calculated sensitivity and specificity for different signs and symptoms and combinations of these for laboratory-confirmed influenza. We enrolled 2,582 children <5 years of age with LRTI of whom 87% (2,257) had influenza and HIV results, of these 14% (318) were HIV-infected. The influenza detection rate was 5% (104/1,939) in HIV-uninfected and 5% (16/318) in HIV-infected children. Children with measured fever (≥38°C) were two times more likely to test positive for influenza than those without measured fever among the HIV-uninfected (OR 2.2, 95% Confidence Interval (CI) 1.5–3.4; p<0.001). No significant association was observed between fever and influenza infection among HIV-infected children. Cough alone had sensitivity of 95% (95% CI 89–98%) in HIV-uninfected and of 100% (95% CI 79–100%) in HIV-infected children but low specificity: 7% (95% CI 6–8%) and 6% (95% CI 3–9%) in HIV-uninfected and HIV-infected children, respectively. The WHO post-2014 case definition for severe acute respiratory illness (SARI—an acute respiratory infection with history of fever or measured fever of ≥ 38°C and cough; with onset within the last ten days and requires hospitalization), had a sensitivity of 66% (95% CI 56–76%) and specificity of 46% (95% CI 44–48%) among HIV-uninfected and a sensitivity of 63% (95% CI 35–84%) and a specificity of 42% (95% CI 36–48%) among HIV-infected children. The sensitivity and specificity of the WHO post-2014 case definition for SARI were similar among HIV-uninfected and HIV-infected children. Our findings support the adoption of the 2014 WHO case definition for children aged <5 years irrespective of HIV infection status. [ABSTRACT FROM AUTHOR]

Symptomatic acute CHIKV infection is mainly characterized by high fever and severe joint pain (arthralgia) that can compromise daily life activities [[2]]. CHIKV infection and its complications can be the underlying cause of death or trigger a decompensation of preexisting medical conditions leading to a fatal outcome. Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Reunion. A major epidemic of chikungunya virus infection on Reunion Island, France, 2005-2006. [Extracted from the article]

Introduction: While parents’ construction of and actions around child growth are embedded in their cultural framework, the discourse on child growth monitoring (CGM) has been using indicators grounded in the biomedical model. We believe that for CGM to be effective, it should also incorporate other relevant socio-cultural constructs. To contribute to the further development of CGM to ensure that it reflects the local context, we report on the cultural conceptualization of healthy child growth in rural Tanzania. Specifically, we examine how caregivers describe and recognize healthy growth in young children, and the meanings they attach to these cultural markers of healthy growth. Methods: Caregivers of under-five children, including mothers, fathers, elderly women, and community health workers, were recruited from a rural community in Kilosa District, Southeastern Tanzania. Using an ethnographic approach and the cultural schemas theory, data for the study were collected through 19 focus group discussions, 30 in-depth interviews, and five key informant interviews. Both inductive and deductive approaches were used in the data analysis. Results: Participants reported using multiple markers for ascertaining healthy growth. These include ‘being bonge’ (chubby), ‘being free of illness’, ‘eating well’, ‘growing in height’, as well as ‘having good kilos’ (weight). Despite the integration of some biomedical concepts into the local conceptualization of growth, the meanings attached to these concepts are largely rooted in the participants’ cultural framework. For instance, a child’s weight is ascribed to the parents’ adherence to postpartum sex taboos and to the nature of a child’s bones. The study noted conceptual differences between the meanings attached to height from a biomedical and a local perspective. Whereas from a biomedical perspective the height increment is considered an outcome of growth, the participants did not see height as linked to nutrition, and did not believe that they have control over their child’s height. Conclusions: To provide context-sensitive advice to mothers during CGM appointments, health workers should use a tool that takes into account the mothers’ constructs derived from their cultural framework of healthy growth. The use of this approach should facilitate communication between health professionals and caregivers during CGM activities, increase the uptake and utilization of CGM services, and, eventually, contribute to reduced levels of childhood malnutrition in the community. [ABSTRACT FROM AUTHOR]

Unsustainable wildlife trade is a pervasive issue affecting wildlife globally. To address this issue, a plethora of demand reduction efforts have been carried out. These necessitate consumer research which provides crucial knowledge for designing and evaluating targeted interventions. We implemented a rigorous consumer survey on saiga (Saiga tatarica) horn use in Singapore, where usage is legal and widely sold. Saiga are Critically Endangered antelopes from Central Asia with horns (often marketed as ling yang) used in traditional Chinese medicine (TCM). Few past studies have assessed saiga horn consumers. This work is the most extensive consumer research to date specifically characterising saiga horn consumers and usage. We conducted 2294 in-person surveys on saiga horn use with Chinese Singaporeans, employing neutral questioning approaches. We found 19% of individuals reported saiga horn as a product they choose most often for themselves and/or others when treating fever and/or heatiness (a TCM state of illness), indicating a minimum estimate of high-frequency usage, not including possible low-frequency users. Overall saiga users were most characterised as middle-aged Buddhists and Taoists. However, saiga users were found in a range of demographic groups. Women preferred saiga shavings (the more traditional form), while men preferred saiga cooling water (the more modern form). About 53% of individuals who used saiga horn themselves also bought it for someone else. Buyers for others were most likely to be female middle-aged Buddhists or Taoists. Key motivating reasons for usage were “it works” and “someone recommended it to me.” The top two reported recommenders were family and TCM shopkeepers. Saiga users were more likely than non-saiga users to perceive saiga as a common species in the wild. This research holds significance for interventions targeting saiga horn consumption within Singapore and throughout Asia, by identifying potential target audiences, product types, non-desirable alternatives, and motivations for use. [ABSTRACT FROM AUTHOR]

Background: Brazilian spotted fever (BSF), caused by the bacterium Rickettsia rickettsii, has been associated with the transmission by the tick Amblyomma sculptum, and one of its main hosts, the capybara (Hydrochoerus hydrochaeris). Methods: During 2015–2019, we captured capybaras and ticks in seven highly anthropic areas of São Paulo state (three endemic and four nonendemic for BSF) and in two natural areas of the Pantanal biome, all with established populations of capybaras. Results: The BSF-endemic areas were characterized by much higher tick burdens on both capybaras and in the environment, when compared to the BSF-nonendemic areas. Only two tick species (A. sculptum and Amblyomma dubitatum) were found in the anthropic areas; however, with a great predominance of A. sculptum (≈90% of all ticks) in the endemic areas, in contrast to a slight predominance of A. dubitatum (≈60%) in the nonendemic areas. Tick species richness was higher in the natural areas, where six species were found, albeit with a predominance of A. sculptum (≈95% of all ticks) and environmental tick burdens much lower than in the anthropic areas. The BSF-endemic areas were characterized by overgrowth populations of A. sculptum that were sustained chiefly by capybaras, and decreased populations of A. dubitatum. In contrast, the BSF-nonendemic areas with landscape similar to the endemic areas differed by having lower tick burdens and a slight predominance of A. dubitatum over A.sculptum, both sustained chiefly by capybaras. While multiple medium- to large-sized mammals have been incriminated as important hosts for A. sculptum in the natural areas, the capybara was the only important host for this tick in the anthropic areas. Conclusions: The uneven distribution of R. rickettsii infection among A. sculptum populations in highly anthropic areas of São Paulo state could be related to the tick population size and its proportion to sympatric A. dubitatum populations. [ABSTRACT FROM AUTHOR]

Background: Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis. Methodology: We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections. Results: Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue–caused by DENV-1 and/or DENV-2 –and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment. Discussion: Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will–ultimately and hopefully–improve the clinical care of outpatients in low-resource settings. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Introduction: Malaria is a public health emergency in India and Odisha. The national malaria elimination programme aims to expedite early identification, treatment and follow-up of malaria cases in hot-spots through a robust health system, besides focusing on efficient vector control. This study, a result of mass screening conducted in a hot-spot in Odisha, aimed to assess prevalence, identify and estimate the risks and develop a management tool for malaria elimination. Methods: Through a cross-sectional study and using WHO recommended Rapid Diagnostic Test (RDT), 13221 individuals were screened. Information about age, gender, education and health practices were collected along with blood sample (5 μl) for malaria testing. Altitude, forestation, availability of a village health worker and distance from secondary health center were captured using panel technique. A multi-level poisson regression model was used to analyze association between risk factors and prevalence of malaria, and to estimate risk scores. Results: The prevalence of malaria was 5.8% and afebrile malaria accounted for 79 percent of all confirmed cases. Higher proportion of Pv infections were afebrile (81%). We found the prevalence to be 1.38 (1.1664–1.6457) times higher in villages where the Accredited Social Health Activist (ASHA) didn’t stay; the risk increased by 1.38 (1.0428–1.8272) and 1.92 (1.4428–2.5764) times in mid- and high-altitude tertiles. With regard to forest coverage, villages falling under mid- and highest-tertiles were 2.01 times (1.6194–2.5129) and 2.03 times (1.5477–2.6809), respectively, more likely affected by malaria. Similarly, villages of mid tertile and lowest tertile of education had 1.73 times (1.3392–2.2586) and 2.50 times (2.009–3.1244) higher prevalence of malaria. Conclusion: Presence of ASHA worker in villages, altitude, forestation, and education emerged as principal predictors of malaria infection in the study area. An easy-to-use risk-scoring system for ranking villages based on these risk factors could facilitate resource prioritization for malaria elimination. [ABSTRACT FROM AUTHOR]

Introduction: Childhood morbidities are common in Ghana. The present study sought to geospatially analyze morbidities among children (0–23 months of age) using five different survey datasets (1993–2014) from the Ghana Demographic and Health Survey. Methods: Logistic regression was used to examine childhood morbidity within a place of residence. Then three spatial statistical tools were applied to analyze morbidities among children (0–23 months of age). These tools were: spatial autocorrelation (Global Moran’s I)—used to examine clustering or dispersion patterns; cluster and outlier analysis (Anselin’s local Moran’s I)—to ascertain geographic composition of childhood morbidity clusters and outliers; and hot spot analysis (Getis-Ord G)—to identify clusters of high values (hot spots) and low values (cold spots). Results: Children in rural areas were much burdened with the occurrence of childhood morbidity. The study revealed positive spatial autocorrelation for childhood morbidity in Ghana. Childhood morbidity (diarrhoea, ARI, anaemia, and fever) clusters were identified within districts in the country. Children in rural areas were more likely to be morbid with diarrhoea, anaemia, and fever compared to those in urban areas. Hot spot districts for diarrhoea, anaemia and fever were mainly situated in semi-arid areas and those with ARI were located both at the semi-arid areas and coastal portions of Ghana. Conclusion: Rural children are much exposed to have higher burden of a childhood morbidity compared to their urban counterparts. Most semi-arid districts in Ghana are burdened with diarrhoea, ARI, anaemia, and fever. To minimize the occurrence of childhood morbidity in Ghana, designing of more context-based interventions to target hot spots districts of these morbidities are required in order to use scarce resources judiciously. [ABSTRACT FROM AUTHOR]

As a result of migrations and globalization, people may face a possible increase in the incidence of central nervous system rickettsial infections (CNS R). These diseases, caused by Rickettsia species and transmitted to humans by arthropod bites, are putatively lethal. However, the diagnosis of CNS R is challenging and often delayed due to their nonspecific clinical presentation and the strict intracellular nature of rickettsiae. Furthermore, transfer of rickettsiae to the brain parenchyma is not yet understood. The aim of this review is to analyze and summarize the features and correlated findings of CNS R in order to focus attention on these intriguing but frequently neglected illnesses. We also incorporated data on CNS infections caused by Rickettsia-related microorganisms. [ABSTRACT FROM AUTHOR]

Background: Radiologic evaluation of children with Mycoplasma pneumoniae is important for diagnosis and management. Objective: To investigate the correlation between chest radiographic findings and the clinical features in children with Mycoplasma pneumoniae pneumonia. Materials and methods: This study included 393 hospitalized children diagnosed with M. pneumoniae pneumonia between January 2000 and August 2016. Their clinical features and chest radiographs were reviewed. Radiographic findings were categorized and grouped as consolidation group (lobar or segmental consolidation) and non-consolidation group (patchy infiltration, localized reticulonodular infiltration, or parahilar peribronchial infiltration). Results: Lobar or segmental consolidation (37%) was the most common finding, followed by parahilar or peribronchial infiltration (27%), localized reticulonodular infiltration (21%) and patchy infiltration (15%). The consolidation group was more frequently accompanied by pleural effusions (63%), compared to the non-consolidation group (16%). Compared with patients in the non-consolidation group, those in the consolidation group were associated with a significantly higher rate of hypoxia, tachypnea, tachycardia, extrapulmonary manifestations, prolonged fever, and longer periods of anti-mycoplasma therapy and hospitalization. Lobar or segmental consolidation was significantly more frequent in children ≥5 years old (44%) compared with children 2–5 years old (34%) and <2 years old (13%). Parahilar peribronchial infiltration was significantly more frequent in children <2 years old (56%) compared with children 2–5 years old (32%) and ≥5 years old (18%). Conclusion: The chest radiographic findings of children with M. pneumoniae pneumonia correlate well with the clinical features. Consolidative lesions were frequently observed in older children and were associated with more severe clinical features. [ABSTRACT FROM AUTHOR]

Background: The aim of our study is to describe the FDG-PET/CT findings in patients with tuberculosis and to correlate them with the patient’s prognosis. Methods: We retrospectively collected data from patients with tuberculosis, who had an FDG-PET/CT performed prior to treatment initiation from 2010 to 2015. Results: Forty-seven out of 504 patients with active tuberculosis diagnosis (9.33%) underwent an FDG-PET/CT. The reasons for performing the FDG-PET/CT were: characterization of a pulmonary nodule (24; 51.1%), study of fever of unknown origin (12; 25.5%), study of lymph node enlargement (5; 10.6%) and others (6; 12.8%). Median age was 64 (IQR 50–74) years and 31 (66%) patients were male. Twenty-six (55.3%) patients had an immunosuppressant condition. According to the FDG-PET/CT, 48.6% of the patients had more than 1 organ affected and 46.8% had lymph node involvement. Median SUVmax of the main lesion was 5 (IQR 0.28–11.85). We found an association between the FDG accumulation and the size of the main lesion with a correlation coefficient of 0.54 (p<0.002). Patients with an unsuccessful outcome had a higher ratio SUVmax main lesion / SUVmean liver (1.92 vs 7.67, p<0.02). Conclusions: In our cohort, almost half of the patients had more than 1 organ affected and 46.8% of them had lymph node involvement. FDG uptake was associated with the size of the main lesion and seems to be related to the treatment outcome. The extent of its potential to be used as an early predictor of treatment success still needs to be defined. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus, an important cause of unexplained fever, is grossly neglected and often misdiagnosed in low and middle income countries like Nepal. The main aim of this study was to report on the clinical profile and complications of scrub typhus and its outcome in Nepalese children. Methods: A prospective observational study was carried out in children aged 1–16 years, admitted to a tertiary care hospital of central Nepal in between July 2016- Aug 2017. Scrub typhus was diagnosed with IgM ELISA. Results: All cases of scrub typhus (n = 76) presented with fever and commonly had other symptoms such as headache (75%), myalgia (68.4%), vomiting (64.5%), nausea (59.2%), abdominal pain (57.9%), cough (35.5%), shortness of breath (22.4%), altered sensorium (14.5%), rashes (13.2%) and seizures (11.8%). Important clinical signs noticed were lymphadenopathy (60.5%), hepatomegaly (47.4%), edema (26.3%), jaundice (26.3%), and splenomegaly (15.8%). About 12% (n = 9) had necrotic eschar. Similarly, thrombocytopenia, raised liver enzymes and raised creatinine values were seen in 36.9%, 34.2% and 65.8% respectively. The most common complications were myocarditis (72.4%), hypoalbuminemia (71.1%), severe thrombocytopenia (22.4%), renal impairment (65.8%), hyponatremia (48.7%) and hepatitis (34.2%). Over two-thirds (69.70%) of the cases were treated with doxycycline followed by combination with azithromycin in the remaining 18.4%. Overall, mortality rate in this group was 3.9%. Conclusions: Scrub typhus should be considered as a differential in any community acquired acute undifferentiated febrile illness regardless of the presence of an eschar. Myocarditis and acute kidney injury are important complications which when addressed early can prevent mortality. Use of doxycycline showed a favorable outcome. [ABSTRACT FROM AUTHOR]

Background: Public health responses to outbreaks of dengue, chikungunya, and Zika virus have been stymied by the inability to control the primary vector, Aedes aegypti mosquitos. Consequently, the need for novel approaches to Aedes vector control is urgent. Placement of three autocidal gravid ovitraps (AGO traps) in ~85% of homes in a community was previously shown to sustainably reduce the density of female Ae. aegypti by >80%. Following the introduction of chikungunya virus (CHIKV) to Puerto Rico, we conducted a seroprevalence survey to estimate the prevalence of CHIKV infection in communities with and without AGO traps and evaluate their effect on reducing CHIKV transmission. Methods and findings: Multivariate models that calculated adjusted prevalence ratios (aPR) showed that among 175 and 152 residents of communities with and without AGO traps, respectively, an estimated 26.1% and 43.8% had been infected with CHIKV (aPR = 0.50, 95% CI: 0.37–0.91). After stratification by time spent in their community, protection from CHIKV infection was strongest among residents who reported spending many or all weekly daytime hours in their community:10.3% seropositive in communities with AGO traps vs. 48.7% in communities without (PR = 0.21, 95% CI: 0.11–0.41). The age-adjusted rate of fever with arthralgia attributable to CHIKV infection was 58% (95% CI: 46–66%). The monthly number of CHIKV-infected mosquitos and symptomatic residents were diminished in communities with AGO traps compared to those without. Conclusions: These findings indicate that AGO traps are an effective tool that protects humans from infection with a virus transmitted by Ae. aegypti mosquitos. Future studies should evaluate their protective effectiveness in large, urban communities. [ABSTRACT FROM AUTHOR]

Severe-febrile-illness (SFI) is a common cause of morbidity and mortality across sub-Saharan Africa (SSA). The burden of SFI in SSA is currently unknown and its estimation is fraught with challenges. This is due to a lack of diagnostic capacity for SFI in SSA, and thus a dearth of baseline data on the underlying etiology of SFI cases and scant SFI-specific causative-agent prevalence data. To highlight the public health significance of SFI in SSA, we developed a Bayesian model to quantify the incidence of SFI hospital admissions in SSA. Our estimates indicate a mean population-weighted SFI-inpatient-admission incidence rate of 18.4 (6.8–31.1, 68% CrI) per 1000 people for the year 2014, across all ages within areas of SSA with stable Plasmodium falciparum transmission. We further estimated a total of 16,200,337 (5,993,249–27,321,779, 68% CrI) SFI hospital admissions. This analysis reveals the significant burden of SFI in hospitals in SSA, but also highlights the paucity of pathogen-specific prevalence and incidence data for SFI in SSA. Future improvements in pathogen-specific diagnostics for causative agents of SFI will increase the abundance of SFI-specific prevalence and incidence data, aid future estimations of SFI burden, and enable clinicians to identify SFI-specific pathogens, administer appropriate treatment and management, and facilitate appropriate antibiotic use. [ABSTRACT FROM AUTHOR]

Background: Rickettsial infections are a common cause of hospitalization in tropical settings, although early diagnosis is challenging in the rural locations where these infections are usually seen. Methods: This retrospective, clinical audit of microbiologically-confirmed cases of scrub typhus or spotted fever group (SFG) rickettsial infection between 1997 and 2016 was performed a tertiary referral hospital in tropical Australia. Clinical, laboratory and radiological findings at presentation were correlated with the patients’ subsequent clinical course. Results: There were 135 locally-acquired cases (95 scrub typhus, 37 SFG, 3 undifferentiated). There were nine hospitalizations during the first 5 years of the study period and 81 in the last 5 years (p for trend = 0.003). Eighteen (13%) of the 135 cases required ICU admission, all of whom were adults. A greater proportion of patients with SFG infection required ICU support (8/37 (22%) compared with 10/95 (11%) scrub typhus cases), although this difference did not reach statistical significance (p = 0.10). Three (8%) of the 37 patients with SFG infection had severe disease (1 died, 2 developed permanent disability) versus 0/95 scrub typhus patients (p = 0.02). Adults with a high admission qSOFA score (≥2) had an odds ratio (OR) of 19 (95% CI:4.8–74.5) for subsequent ICU admission (p<0.001); adults with a high NEWS2 score (≥7) had an OR of 14.3 (95% CI:4.5–45.32) for ICU admission (p<0.001). A patient’s respiratory rate at presentation had strong prognostic utility: if an adult had an admission respiratory rate <22 breaths/minute, the negative predictive value for subsequent ICU admission was 95% (95% CI 88–99). Conclusions: In the well-resourced Australian health system outcomes are excellent, but the local burden of rickettsial disease appears to be increasing and the clinical phenotype of SFG infections may be more severe than previously believed. Simple, clinical assessment on admission has prognostic utility and may be used to guide management. [ABSTRACT FROM AUTHOR]

Background: To evaluate the impact of macrophage activation syndrome (MAS) on clinical features in patients with Kikuchi-Fujimoto disease (KFD) and to compare the features of MAS in KFD with those of adult-onset Still’s disease (AOSD) and systemic lupus erythematosus (SLE). Methods: The medical records of febrile patients hospitalised with KFD between November 2005 and April 2017 were reviewed. Patients fulfilling the 2016 classification criteria for MAS were classified as having MAS. Clinical and laboratory features of patients with KFD with and without MAS were evaluated. Poor hospitalisation outcomes were defined as intensive care unit admission or in-hospital mortality. The treatment outcomes of MAS in KFD, AOSD, and SLE were also compared. Results: Among 78 patients hospitalised with KFD, 24 (30.8%) patients had MAS during admission. Patients with KFD and MAS more frequently required glucocorticoid treatment (66.7% vs 40.7%, p = 0.036) and had longer hospital stays than patients with KFD without MAS (12.5 vs 8.5 days, p<0.001). In addition, patients with MAS had worse hospitalisation outcomes than patients without MAS (29.2% vs. 0.0%, p<0.001). Among patients with MAS in KFD, AOSD, and SLE, the number of patients requiring glucocorticoid treatment after 3 months was significantly lower among patients with MAS and KFD (KFD 33.3%, AOSD 88.9%, SLE 100%, p<0.001). Conclusions: The presence of MAS in KFD was associated with adverse clinical outcomes including higher steroid usage and worse hospitalisation outcomes. However, compared to those with AOSD and SLE, patients with MAS and KFD were less likely to require long-term glucocorticoid treatment. [ABSTRACT FROM AUTHOR]

Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blood culture to improve typhoid case detection. We carried out a prospective diagnostic cohort study and enrolled children (aged 0–4 years) with non-specific febrile disease admitted to a tertiary hospital in Blantyre, Malawi from August 2014 to July 2016. Blood was collected for culture (BC) and real-time PCR after a pre-enrichment culture in tryptone soy broth and ox-bile. DNA was subjected to PCR for invA (Pan-Salmonella), staG (S. Typhi), and fliC (S. Typhimurium) genes. A positive PCR was defined as invA plus either staG or fliC (CT<29). IgM and IgG ELISA against four S. Typhi antigens was also performed. In total, 643 children (median age 1.3 years) with nonspecific febrile disease were enrolled; 31 (4.8%) were BC positive for Salmonella (n = 13 S. Typhi, n = 16 S. Typhimurium, and n = 2 S. Enteritidis). Pre-enrichment culture of blood followed by PCR identified a further 8 S. Typhi and 15 S. Typhimurium positive children. IgM and IgG titres to the S. Typhi antigen STY1498 (haemolysin) were significantly higher in children that were PCR positive but blood culture negative compared to febrile children with all other non-typhoid illnesses. The addition of pre-enrichment culture and PCR increased the case ascertainment of invasive Salmonella disease in children by 62–94%. These data support recent burden estimates that highlight the insensitivity of blood cultures and support the targeting of pre-school children for typhoid vaccine prevention in Africa. Blood culture with real-time PCR following pre-enrichment should be used to further refine estimates of vaccine effectiveness in typhoid vaccine trials. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate an interactive nomogram to predict healthcare-associated infections (HCAIs) in the intensive care unit (ICU). Methods: A multicenter retrospective study was conducted to review 2017 data from six hospitals in Guizhou Province, China. A total of 1,782 ICU inpatients were divided into either a training set (n = 1,189) or a validation set (n = 593). The patients’ demographic characteristics, basic clinical features from the previous admission, and their need for bacterial culture during the current admission were extracted from electronic medical records of the hospitals to predict HCAI. Univariate and multivariable analyses were used to identify independent risk factors of HCAI in the training set. The multivariable model’s performance was evaluated in both the training set and the validation set, and an interactive nomogram was constructed according to multivariable regression model. Moreover, the interactive nomogram was used to predict the possibility of a patient developing an HCAI based on their prior admission data. Finally, the clinical usefulness of the interactive nomogram was estimated by decision analysis using the entire dataset. Results: The nomogram model included factor development (local economic development levels), length of stay (LOS; days of hospital stay), fever (days of persistent fever), diabetes (history of diabetes), cancer (history of cancer) and culture (the need for bacterial culture). The model showed good calibration and discrimination in the training set [area under the curve (AUC), 0.871; 95% confidence interval (CI), 0.848–0.894] and in the validation set (AUC, 0.862; 95% CI, 0.829–0.895). The decision curve demonstrated the clinical usefulness of our interactive nomogram. Conclusions: The developed interactive nomogram is a simple and practical instrument for quantifying the individual risk of HCAI and promptly identifying high-risk patients. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the prevalence rate of vaso-occlusive crisis (VOC) episodes, rates of uncomplicated and complicated VOC episodes, and the primary reasons for emergency room (ER) visits and inpatient admissions for sickle cell disease (SCD) patients. Methods: The Medicaid Analytic extracts database was used to identify adult SCD patients using claims from 01JUL2009-31DEC2012. The date of the first observed SCD claim was designated as the index date. Patients were required to have continuous medical and pharmacy benefits for ≥6 months baseline and ≥12 months follow-up period. Patient demographics, baseline clinical characteristics, the rate of uncomplicated and complicated VOC (VOC with concomitant SCD complications) episodes, and reasons for ER visits and inpatient stays were analyzed descriptively. Results: A total of 8,521 patients were included in the analysis, with a median age of 30 years. The average follow-up period was 2.7 years. The rate of VOC episodes anytime in the follow-up was 3.31 in person-years. During the first-year follow-up period, an average of 2.79 VOC episodes were identified per SCD patients, with 1.06 VOC episodes treated in inpatient setting and 0.90 VOC episodes in ER without admission. A total of 76,154 VOC episodes were identified during the entire follow-up period for the overall SCD patients. Most of the VOC episodes (70.3% [n = 53,523]) were uncomplicated episodes, and 29.7% were complicated episodes. Using primary diagnosis claims only, the most frequent complications during the VOC episode were infectious diseases (25.9%), fever (21.8%), and pulmonary disorders (16.2%). Among ER and hospitalizations related to VOC or SCD complication, ~85.0% had VOCs as the primary reason for admission; 15.0% had SCD complications as the primary reason. Conclusion: In summary, SCD and its related comorbidities and complications result in high acute health care utilization. In addition, VOC remains the primary reason for SCD patients’ ER visits and inpatient admissions. [ABSTRACT FROM AUTHOR]

Introduction: Diagnosis and treatment for visceral leishmaniasis (VL) is considered to be delayed amongst poor, rural women in highly endemic districts of Bihar and Jharkhand. The objective of this study was to assess and understand barriers to VL diagnosis and treatment for women in endemic districts with a high burden of VL. Methods: The study used a stratified and purposive sample of 33 female patients with VL, 11 health staff, 11 local (unqualified) health providers and 12 groups of community elders drawn from ten districts in Bihar and four in Jharkhand with high burdens of VL. The study was conducted within an exploratory and inductive framework, using semi-structured in-depth interviews and discussions. Results: Women accessing treatment more quickly tended to move faster from treating their symptoms on their own to seeking care from local providers. Perception among female patients of the illness being not serious (owing to initially non-specific and mild symptoms), lack of money, prioritisation of household chores over their need to seek care and the absence of a male guardian to accompany them in seeking care at facilities worked together to drive these choices. Most patients and their families did not suspect VL as the cause for their non-specific symptoms, but when VL was suspected, treatment shopping ended. Lack of prioritization of women’s health issues appears to be a pervasive underlying factor. Public health facilities were not an early treatment choice for the majority, but where it was, the diagnosis of VL was often not considered when presenting with under 2 weeks of symptoms, nor were appropriate follow-up plans instituted. Conclusion: The insidious presentation of VL and the low prioritisation of women’s health need to be jointly addressed through messages that emphasise the importance of early diagnosis and treatment of disease, which is low-cost in time and money when managed in public health facilities. Clear messages that project prioritising women’s care-seeking over household work as a smart choice and the need for rallying male support are needed. Additionally, efforts to reduce missed opportunities through early case suspicion and engaging private providers to better counsel women with suspected VL could close critical gaps in the continuum of care. [ABSTRACT FROM AUTHOR]

Introduction: Asymptomatic carriage of P. falciparum is frequent in areas endemic for malaria and individual diagnosis of clinical malaria attacks is still difficult. We investigated the impact of changes in malaria endemicity on the diagnostic criteria for malaria attacks in an area of seasonal malaria transmission. Methods: We analyzed the longitudinal data collected over 20 years from a daily survey of all inhabitants of Ndiop, a rural community in central Senegal, in a logistic regression model to investigate the relationship between the level of Plasmodium falciparum parasitemia and the risk of fever, with the aim of determining the best parasitemia thresholds for attributing to malaria a fever episode. Results: A total of 34,136 observations recorded from July 1993 to December 2013 from 850 individuals aged from 1 day to 87 years were included. P. falciparum asymptomatic carriage declined from 36% to 1% between 1993 and 2013. A total of 9,819 fever episodes were associated with a positive blood film for P. falciparum. Using age-dependent parasitemia thresholds for attributing to malaria a fever episode, we recorded 6,006 malaria attacks during the study period. Parasitemia thresholds seemed to be lower during the low-to-zero transmission season and tended to decrease with changes in control policies. The number of clinical malaria attacks was overestimated for all age groups throughout the study when all fever episodes associated with P. falciparum parasitemia were defined as malaria attacks. Conclusion: Pyrogenic thresholds are particularly sensitive to changes in malaria epidemiology and are therefore an interesting tool to accurately assess the burden of malaria in the context of declining transmission. [ABSTRACT FROM AUTHOR]

Background: Dengue virus infection (DVI) among children is a leading cause of hospitalization in endemic areas. Hospitalized patients are at risk of receiving unnecessary antibiotics. Methods: A retrospective medical review analysis study was conducted to evaluate the prevalence, indication, and choice of antibiotics given to hospitalized patients less than 15 years of age with DVI in two different hospital settings (teaching and private hospitals) in the Municipality of Bandung. Epidemiological, clinical, and laboratory data were obtained using a pre-tested standardized questionnaire from patients’ medical records admitted from January 1 to December 31, 2015. Results: There were 537 (17.5%) out of 3078 cases who received antibiotics. Among 176 cases admitted to the teaching hospitals, presumed bacterial upper respiratory tract infection (URTI) and typhoid fever were found in 1 (0.6%) case and 6 (0.3%) cases. In private hospitals among 2902 cases, presumed bacterial URTI was found in 324 (11.2%) cases, typhoid fever in 188 (6.5%) cases and urinary tract infection (UTI) in 18 (0.6%) cases. The prevalence of URTI and typhoid fever were significantly lower in the teaching hospitals compared to the private hospitals (p<0.0001 and p<0.05 respectively). The diagnosis of URTI in both teaching and private hospitals was merely based on clinical findings. Amoxicillin was given to 1 patient in the teaching hospitals; the 3rd generation of cephalosporins, mostly intravenous, were given in 247 (67%) cases in private hospitals. The diagnosis of typhoid fever in the teaching hospitals was based on culture in 1 (16.7%) and reactive IgM anti-Salmonella in 5 (83.3%) cases while in the private hospitals, they were based on reactive IgM anti-Salmonella in 13 (6.5%) cases, single Widal test in 61 (32.5%), and without laboratory confirmation in 114 (60.6%) cases. Most of the cases in both hospital settings were treated mostly with 3rd generation cephalosporin. The diagnosis of UTI was based on positive leucocyte esterase and nitrite in urine dipstick test in 7 (38.9%) and leucocyturia alone in 11 (61.1%) cases and was treated with 3rd generation in 15 (83.3%) cases, amoxicillin, chloramphenicol and clarithromycin, each in 1 (5.6%) case. Conclusion: The use of antibiotics in private hospitals was inappropriate in most cases while the use of antibiotics in the teaching hospital was more accountable. This study indicated that interventions, such as the implementation of the antibiotics stewardship program, are needed especially in private hospitals to reduce inappropriate use of antibiotics. [ABSTRACT FROM AUTHOR]

Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2–54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children. [ABSTRACT FROM AUTHOR]

Introduction: Child health remains an important public health concern at the global level, with preventable diseases such as diarrheal disease, acute respiratory infection (ARI) and fever posing a large public health burden in low- and middle-income countries including Bangladesh. Improvements in socio-economic conditions have tended to benefit advantaged groups in societies, which has resulted in widespread inequalities in health outcomes. This study examined how socioeconomic inequality is associated with childhood morbidity in Bangladesh, and identified the factors affecting three illnesses: diarrhea, ARI and fever. Materials and methods: A total of 43,860 sample observations from the Bangladesh Demographic and Health Survey, spanning a 22-year period (1993–2014), were analysed. Concentration curve and concentration index methods were used to evaluate changes in the degree of household wealth-related inequalities and related trends in childhood morbidity. Regression-based decomposition analyses were used to attribute the inequality disparities to individual determinants for the three selected causes of childhood morbidity. Results: The overall magnitude of inequality in relation to childhood morbidity has been declining slowly over the 22-year period. The magnitude of socio-economic inequality as a cause of childhood morbidity varied during the period. Decomposition analyses attributed the inequalities to poor maternal education attainment, inadequate pre-delivery care, adverse chronic undernutrition status and low immunisation coverage. Conclusions: High rates of childhood morbidity were observed, although these have declined over time. Socio-economic inequality is strongly associated with childhood morbidity. Socio-economically disadvantaged communities need to be assisted and interventions should emphasise improvements of, and easier access to, health care services. These will be key to improving the health status of children in Bangladesh and should reduce economic inequality through improved health over time. [ABSTRACT FROM AUTHOR]

Background: Although there is mounting evidence demonstrating beneficial effects of community health workers (CHWs), few studies have examined the impact of CHW programs focused on preventing infectious diseases in children through behavior changes. We assessed the preventive effects of community health volunteers (CHVs), who receive no financial incentive, on child diarrhea and fever prevalence in Ghana.Methods and Findings: We conducted a cluster-randomized controlled trial in 40 communities in the Volta Region, Ghana. Twenty communities were randomly allocated to the intervention arm, and 20 to the control arm, using a computer-generated block randomization list. In the intervention arm, CHVs were deployed in their own community with the key task of conducting home visits for health education and community mobilization. The primary outcomes of the trial were diarrhea and fever prevalence at 6 and 12 months among under-5 children based on caregivers' recall. Secondary outcomes included oral rehydration treatment and rapid diagnostic testing for malaria among under-5 children, and family planning practices of caregivers. Generalized estimating equations (GEEs) with a log link and exchangeable correlation matrix were used to determine the relative risk (RR) and 95% confidence intervals (CIs) for diarrhea, fever, and secondary outcomes adjusted for clustering and stratification. Between April 18 and May 4, 2015, 1,956 children were recruited and followed up until September 20, 2016. At 6 and 12 months post-randomization, 1,660 (85%) and 1,609 (82%) participants, respectively, had outcomes assessed. CHVs' home visits had no statistically significant effect on diarrhea or fever prevalence at either time point. After a follow-up of 12 months, the prevalence of diarrhea and fever was 7.0% (55/784) and 18.4% (144/784), respectively, in the control communities and 4.5% (37/825) and 14.7% (121/825), respectively, in the intervention communities (12-month RR adjusted for clustering and stratification: diarrhea, RR 0.73, 95% CI 0.37-1.45, p = 0.37; fever, RR 0.76, 95% CI 0.51-1.14, p = 0.20). However, the following were observed: improved hand hygiene practices, increased utilization of insecticide-treated bed nets, and greater participation in community outreach programs (p-values < 0.05) in the intervention group. In a post hoc subgroup analysis, the prevalence of diarrhea and fever at 6 months was 3.2% (2/62) and 17.7% (11/62), respectively, in the intervention communities with ≥70% coverage and a ≥30-minute visit duration, and 14.4% (116/806) and 30.2% (243/806) in the control communities (RR adjusted for clustering, stratification, baseline prevalence, and covariates: diarrhea, RR 0.23, 95% CI 0.09-0.60, p = 0.003; fever, RR 0.69, 95% CI 0.52-0.92, p = 0.01). The main limitations were the following: We were unable to investigate the longer-term effects of CHVs; the trial may have been underpowered to detect small to moderate effects due to the large decline in diarrheal and fever prevalence in both the intervention and control group; and caregivers' practices were based on self-report, and the possibility of caregivers providing socially desirable responses cannot be excluded.Conclusions: We found no effect of CHVs' home visits on the prevalence of child diarrhea or fever. However, CHV programs with high community coverage and regular household contacts of effective duration may reduce childhood infectious disease prevalence.Trial Registration: International Standard Randomised Controlled Trial Registry, ISRCTN49236178. [ABSTRACT FROM AUTHOR]

Objectives: During winter, after excluding obvious sites of infection, the most important diagnoses of isolated fever or influenza-like illness (ILI) to rule out are listeriosis and influenza, because of their severe potential outcomes and the straightforward management available for each. While awaiting laboratory results, the recommended management strategy is usually hospitalization for intravenous antibiotic therapy against potential listeria. This study sought to assess the effect of the use of a rapid test on hospitalization and antibiotic therapy rates. Methods: The study included all pregnant women who consulted for ILI or isolated fever after clinical and laboratory investigations and had a molecular diagnostic assay for influenza during two time periods, both during influenza epidemics: before introduction of the rapid molecular assay use (period 1) and after this (period 2). Results: The study included 38 women during period 1 and 124 during period 2. The influenza diagnosis was confirmed for 24 of 38 (63.2%) women during period 1 and 65 of 124 (52.4%) women during period 2 (P = 0.24). The hospitalization rate fell significantly from period 1 to period 2, both in the total population (71.0% versus 44.3%, P = 0.004) and among women with confirmed influenza (83.3% versus 38.5%, P<0.001), as did the antibiotic therapy rate in both groups (respectively, 86.8% versus 56.1%, P = 0.001 and 91.7% versus 44.7%, P<0.001). Conclusion: The use of a rapid molecular assay for the diagnosis of influenza improved the management of pregnant women with an isolated fever or ILI by reducing the rates of unnecessary hospitalization and antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background: Non-malarial febrile illnesses comprise of almost half of all fever presenting morbidities, among under-five children in sub-Saharan Africa. Studies have reported cases of prescription of antimalarial medications to these febrile under-fives who were negative for malaria. The treatment of these children with antimalarial medications increases incidences of antimalarial drug resistance as well as further morbidities and mortalities, due to failure to treat the actual underlying causes of fever. Aim: To identify clinical and demographic factors associated with treatment type (malarial/non-malarial) of non-malarial febrile illnesses (NMFI) in children aged ≤5 at the Kenyatta National Hospital in Nairobi, Kenya. Methods: A positivist epistemological approach, cross sectional descriptive study design was used. A structured questionnaire was used on a sample of 341 medical records of children aged ≤5 years to extract data on clinical examinations (recorded as yes or no), diagnostic test results, and demographic data on the child’s sex and age. Descriptive and inferential analysis was applied to the data. Results: Prescription of antimalarial drugs despite negative microscopy results was found in 44 (12.9%) of the children, with mortality reported in 48 (14.1%). Assessment of respiratory distress was 0.13 (0.03,0.58) times associated with less likelihood of prescribing an antimalarial in those with a negative microscopy. A male patient was 0.21 (0.05,0.89) times less likely to receive an intravenous antimalarial after a negative microscopy. Patients aged ˂1 with a negative microscopy result were more likely to receive an antimalarial than older children. Conclusion: There is a need to eliminate incorrect treatment of NMFI with antimalarial medication, while ensuring correct diagnosis and treatment of the specific illness occurs. This requires strengthening and adherence to diagnostic and treatment guidelines of febrile illnesses in under-fives, consequently reducing morbidities and mortalities associated with inadequate management of NMFIs. [ABSTRACT FROM AUTHOR]

Objectives: Pneumonia is the most common bacterial infection in children at the emergency department (ED). Clinical prediction models for childhood pneumonia have been developed (using chest x-ray as their reference standard), but without implementation in clinical practice. Given current insights in the diagnostic limitations of chest x-ray, this study aims to validate these prediction models for a clinical diagnosis of pneumonia, and to explore their potential to guide decisions on antibiotic treatment at the ED. Methods: We systematically identified clinical prediction models for childhood pneumonia and assessed their quality. We evaluated the validity of these models in two populations, using a clinical reference standard (1. definite/probable bacterial, 2. bacterial syndrome, 3. unknown bacterial/viral, 4. viral syndrome, 5. definite/probable viral), measuring performance by the ordinal c-statistic (ORC). Validation populations included prospectively collected data of children aged 1 month to 5 years attending the ED of Rotterdam (2012–2013) or Coventry (2005–2006) with fever and cough or dyspnoea. Results: We identified eight prediction models and could evaluate the validity of seven, with original good performance. In the Dutch population 22/248 (9%) had a bacterial infection, in Coventry 53/301 (17%), antibiotic prescription was 21% and 35% respectively. Three models predicted a higher risk in children with bacterial infections than in those with viral disease (ORC ≥0.55) and could identify children at low risk of bacterial infection. Conclusions: Three clinical prediction models for childhood pneumonia could discriminate fairly well between a clinical reference standard of bacterial versus viral infection. However, they all require the measurement of biomarkers, raising questions on the exact target population when implementing these models in clinical practice. Moreover, choosing optimal thresholds to guide antibiotic prescription is challenging and requires careful consideration of potential harms and benefits. [ABSTRACT FROM AUTHOR]

Introduction: A large proportion of children with uncomplicated malaria receive appropriate treatment late, contributing to progression of illness to severe disease. We explored contexts of caregiver delays in seeking appropriate care for children with severe malaria. Methods: This qualitative study was conducted at the Children’s Ward of Jinja Hospital, where children with severe malaria were hospitalized. A total of 22in-depth interviews were conducted with caregivers of children hospitalized with severe malaria. Issues explored were formulated based on the Partners for Applied Social Sciences (PASS) model, focusing on facilitators and barriersto caregivers’promptseeking and accessing ofappropriate care. The data were coded deductively using ATLAS.ti (version 7.5). Codes were then grouped into families based on emerging themes. Results: Caregivers’ rating of initial symptoms as mild illness lead to delays in response. Use of home initiated interventions with presumably ineffective herbs or medicines was common, leading to further delay. When care was sought outside the home, drug shops were preferred over public health facilities for reasons of convenience. Drug shops often provided sub-optimal care, and thus contributed to delays in access to appropriate care. Public facilities were often a last resort when illness was perceived to be progressing to severe disease. Further delays occurred at health facilities due to inadequate referral systems. Conclusion: Communities living in endemic areas need to be sensitized about the significance of fever, even if mild, as an indicator of malaria. Additionally, amidst ongoing efforts at bringing antimalarial treatment services closer to communities, the value of drug shops as providers ofrationalantimalarialtreatment needs to be reviewed. [ABSTRACT FROM AUTHOR]