Non-febrile Illness Research Articles

Emerging Zoonotic Diseases among Pastoral Communities of Caia and Búzi Districts, Sofala, Mozambique: Evidence of Antibodies against Brucella, Leptospira, Rickettsia, and Crimean-Congo Hemorrhagic Fever Virus.

Emerging zoonotic diseases are an increasing threat to public health. There is little data on the seroprevalence of zoonotic diseases among pastoralists in the country. We aim to carry out a cross-sectional study on the prevalence of major zoonotic diseases among pastoral communities in the Caia and Búzi districts. Between January and December 2018, a questionnaire was used to solicit socio-demographic data from consenting pastoralists with the collection of blood samples in the Caia and Búzi districts of the Sofala province. All samples were tested using ELISA commercial reagents for the detection of IgM antibodies against Brucella and Leptospira. Likewise, IgM and IgG antibodies against Rickettsia and CCHFV were determined using ELISA kits. A total of 218 samples were tested, of which 43.5% (95/218) were from the district of Caia and 56.4% (123/218) from the Búzi district. Results from both districts showed that the seroprevalence of IgM antibodies against Brucella and Leptospira was 2.7% (6/218) and 30.3% (67/218), respectively. Positivity rates for IgM and IgG anti-Rickettsia and CCHFV were 8.7% (19/218), 2.7% (6/218), 4.1% (9/218), and 0.9% (2/218), respectively. Results from our study showed evidence of antibodies due to exposure to Brucella, Leptospira, Rickettsia, and CCHFV with antibodies against Leptospira and Rickettsia being the most prevalent. Hence, laboratory diagnosis of zoonotic diseases is essential in the early detection of outbreaks, the identification of silent transmission, and the etiology of non-febrile illness in a pastoral community. There is a need to develop public health interventions that will reduce the risk of transmission.

Cumulative Antibiotic Exposure in the First 5 Years of Life: Estimates for 45 Low- and Middle-Income Countries From Demographic and Health Survey Data.

Estimates of the total cumulative exposure to antibiotics of children in low-resource settings, and the source of these treatments, are limited. We estimated the average number of antibiotic treatments children received in the first 5 years of life in 45 low- and middle-income countries (LMICs) using Demographic and Health Survey data. The 2-week point prevalence of fever, diarrhea, or cough and antibiotic treatment for these illnesses were estimated for ages 0-59 months and aggregated to estimate cumulative illness and antibiotic treatment for each country. We estimated treatment rates and contribution to total antibiotic use attributable to medical care, informal care, and self-medication. Forty-five countries contributed 438 140 child-observations. The proportion of illness episodes treated with antibiotics ranged from 10% (95% confidence interval [CI], 9%-12%]) in Niger to 72% (95% CI, 69%-75%) in Jordan. A mean of 42.7% (95% CI, 42.1%-43.3%) of febrile and 32.9% of nonfebrile (95% CI, 32.4%-33.5%) illness episodes received antibiotics. In their first 5 years, we estimate children received 18.5 antibiotic treatments on average (interquartile range [IQR], 11.6-24.6) in LMICs. Cumulative antibiotic exposure ranged from 3.7 treatments in Niger (95% CI, 2.8%-4.6%) to 38.6 treatments in the Democratic Republic of Congo (95% CI, 34.7%-42.4%). A median of 9.0% of antibiotic treatments was attributable to informal care (IQR, 5.9%-21.2%), and 16.9% to self-medication (IQR, 9.5%-26.2%). Childhood antibiotic exposure is high in some LMICs, with considerable variability. While access to antibiotics for children is still not universal, important opportunities for reducing excess use also exist, particularly with respect to the informal care sector and self-medication.

DENGUE FEVER

Background: Dengue is the most prevalent mosquito-born viral illness in theworld. Clinically dengue ranges from asymptomatic, non-febrile illness, classic dengue todengue hemorrhagic fever/dengue shock syndrome. Objective: Subjects & Methods: Thisstudy was included 79 patients conducted at Nawaz Sharif Social Sevurity Hospital, Lahoreduring the epidemic of dengue in Lahore from September 2011 to Dec 2011. Results: Twenty outof 79 patients suspected of dengue fever were dengue IgM positive. Male to female ratio was1.19: 1. Our study included 79 patients suspected of having dengue fever. Fever was the mostcommon symptom in these patients. Conclusions: Early identification of dengue with risk ofdeveloping hemorrhage is an important clinical objective. The morbidity and mortality can bereduced by appropriate and judicious treatment of dengue patients.

Lipid peroxidation, DNA damage, and apoptosis in dengue fever.

Interplay between the apoptosis, DNA damage, and oxidative stress as a host response to dengue viral infections remains unclear. Peripheral blood mononuclear cells (PBMCs) were isolated from 60 dengue infected patients, 20 patients with febrile illness other than dengue (OFI) and 10 non-febrile illness (NFI) patients. DNA damage in the PBMCs was assessed using single cell gel electrophoresis and stages of apoptosis underwent by the PBMCs were studied by Annexin-PI staining using flow cytometry. Plasma levels of malondialdehyde levels were estimated using thiobarbituric acid assay. Dengue infected individuals had showed increased DNA damage than NFI and OFI controls at the time of admission. Annexin-PI staining revealed increased frequency of apoptotic cells in dengue infected PBMCs than controls during the admission time. Similar pattern was observed in samples collected around defervescence. Within the dengue cases, percentage of live cells was higher in non-severe dengue than severe dengue at both the time points. Follow-up samples in dengue showed less number of live cells and higher percentage of apoptotic cells with respect to their baseline and this was reversed in case of OFI. Plasma malondialdehyde levels were found to be relatively higher in dengue cases than controls at admission and around defervescence. Significant positive correlation between DNA damage, apoptosis, and plasma malondialdehyde levels might pave a way for understanding the complex interactions between virus and hosts response thereby aids in identifying plausible immunopathological links contributing to disease pathogenesis. © 2018 IUBMB Life, 70(11):1133-1143, 2018.

Clinical consequences of submicroscopic malaria parasitaemia in Uganda

BackgroundSubmicroscopic malaria parasitaemia is common in both high- and low-endemicity settings, but its clinical consequences are unclear.MethodsA cohort of 364 children (0.5–10 years of age) and 106 adults was followed from 2011 to 2016 in Tororo District, Uganda using passive surveillance for malaria episodes and active surveillance for parasitaemia. Participants presented every 90 days for routine visits (n = 9075); a subset was followed every 30 days. Participants who presented with fever and a positive blood smear were treated for malaria. At all routine visits microscopy was performed and samples from subjects with a negative blood smear underwent loop-mediated isothermal amplification for detection of plasmodial DNA.ResultsSubmicroscopic parasitaemia was common; the proportion of visits with submicroscopic parasitemia was 25.8% in children and 39.2% in adults. For children 0.5–10 years of age, but not adults, having microscopic and submicroscopic parasitaemia at routine visits was significantly associated with both fever (adjusted risk ratios [95% CI], 2.64 [2.16–3.22], 1.67 [1.37–2.03]) and non-febrile illness (aRR [CI], 1.52 [1.30–1.78], 1.26 [1.09–1.47]), compared to not having parasitaemia. After stratifying by age, significant associations were seen between submicroscopic parasitaemia and fever in children aged 2–< 5 and 5–10 years (aRR [CI], 1.42 [1.03–1.98], 2.01 [1.49–2.71]), and submicroscopic parasitaemia and non-febrile illness in children aged 5–10 years (aRR [CI], 1.44 [1.17–1.78]). These associations were maintained after excluding individuals with a malaria episode within the preceding 14 or following 7 days, and after adjusting for household wealth.ConclusionsSubmicroscopic malaria infections were associated with fever and non-febrile illness in Ugandan children. These findings support malaria control strategies that target low-density infections.

Burden of Respiratory Syncytial Virus Infection in South African Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Pregnant and Postpartum Women: A Longitudinal Cohort Study.

Limited data exist on the burden of respiratory syncytial virus (RSV) illness among pregnant women, to determine their potential benefit from RSV vaccination. We evaluated the incidence of RSV illness from midpregnancy until 24 weeks postpartum in human immunodeficiency virus (HIV)-uninfected and HIV-infected women and their infants. Mother-infant dyads were enrolled in maternal influenza vaccine efficacy trials. These included 1060 and 1056 HIV-uninfected pregnant women in 2011 and 2012, respectively, 194 HIV-infected pregnant women in 2011, and their infants. Upper respiratory tract samples obtained at illness visits were tested for RSV. The incidence (per 1000 person-months) of RSV illness (n = 43 overall) among HIV-uninfected women was lower in 2011 (1.2; 95% confidence interval [CI], .6-2.2) than in 2012 (4.0; 95% CI, 2.8-5.6). The incidence of RSV illness (n = 5) in HIV-infected women was 3.4 (95% CI, 1.4-8.1). Maternal RSV infection was associated with respiratory symptoms including cough (72.1%), rhinorrhea (39.5%), sore throat (37.2%), and headache (42%), but fever was absent. RSV infection during pregnancy was not associated with adverse pregnancy outcomes. Postpartum, RSV infection in mothers (n = 27) was associated with concurrent infection among 51.9% of their infants and, conversely, 29.8% of mothers investigated within 7 days of their infants having an RSV illness also tested positive for RSV. RSV infection is associated with respiratory illness during pregnancy and postpartum. Vaccination of pregnant women against RSV could benefit the mother, albeit primarily against nonfebrile illness, and her infant. NCT01306669 and NCT01306682.

Guillain-Barré Syndrome Outbreak Associated With Zika Virus Infection in French Polynesia

Summary Background Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barre syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barre syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barre syndrome. Methods In this case-control study, cases were patients with Guillain-Barre syndrome diagnosed at the Centre Hospitalier de Polynesie Francaise (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barre syndrome using both ELISA and combinatorial microarrays. Findings 42 patients were diagnosed with Guillain-Barre syndrome during the study period. 41 (98%) patients with Guillain-Barre syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p Interpretation This is the first study providing evidence for Zika virus infection causing Guillain-Barre syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barre syndrome. Funding Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.

Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome. In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays. 42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively). This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome. Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.

Ferritin and iron in pediatric infections in the emergency department: A pilot study

We aimed to study ferritin as an acute phase marker in pediatric infections, and investigate its' clinical significance in the emergency department management of the febrile child. Multiple inflammatory markers, including C-reactive protein, procalcitonin, and serum ferritin, and other iron studies were measured in 37 children, from 3 months through 8 years of age, presenting to the emergency department with temperature of ≥ 39 degrees Celsius, and 38 patients in the same age group with non-febrile illness. Mean serum ferritin was significantly higher in the febrile group 71.4 ng/mL compared to the non-febrile group 45.1 ng/mL (p

Managing the Sick Child in the Era of Declining Malaria Transmission: Development of ALMANACH, an Electronic Algorithm for Appropriate Use of Antimicrobials.

ObjectiveTo review the available knowledge on epidemiology and diagnoses of acute infections in children aged 2 to 59 months in primary care setting and develop an electronic algorithm for the Integrated Management of Childhood Illness to reach optimal clinical outcome and rational use of medicines.MethodsA structured literature review in Medline, Embase and the Cochrane Database of Systematic Review (CDRS) looked for available estimations of diseases prevalence in outpatients aged 2-59 months, and for available evidence on i) accuracy of clinical predictors, and ii) performance of point-of-care tests for targeted diseases. A new algorithm for the management of childhood illness (ALMANACH) was designed based on evidence retrieved and results of a study on etiologies of fever in Tanzanian children outpatients.FindingsThe major changes in ALMANACH compared to IMCI (2008 version) are the following: i) assessment of 10 danger signs, ii) classification of non-severe children into febrile and non-febrile illness, the latter receiving no antibiotics, iii) classification of pneumonia based on a respiratory rate threshold of 50 assessed twice for febrile children 12-59 months; iv) malaria rapid diagnostic test performed for all febrile children. In the absence of identified source of fever at the end of the assessment, v) urine dipstick performed for febrile children <2years to consider urinary tract infection, vi) classification of ‘possible typhoid’ for febrile children >2 years with abdominal tenderness; and lastly vii) classification of ‘likely viral infection’ in case of negative results.ConclusionThis smartphone-run algorithm based on new evidence and two point-of-care tests should improve the quality of care of <5 year children and lead to more rational use of antimicrobials.

PO-0198 Ferritin And Serum Iron In Paediatric Febrile Illness

<h3>Introduction</h3> Ferritin is the major intracellular iron binding protein in the body. Serum ferritin is an inflammatory marker. Iron sequestration is one of the innate immune responses to infection. The goal of this research was to investigate the role of serum ferritin and serum iron as clinically useful markers of infection in the paediatric emergency department. <h3>Methods</h3> Multiple inflammatory markers, including C-reactive protein, procalcitonin, and serum ferritin, and other iron studies were measured in 37 children, from 3 months through 8 years of age, presenting to the emergency department with temperature of ≥39 degrees Celsius, and 38 patients in the same age group with non-febrile illness (controls). Patients with chronic inflammatory or rheumatologic conditions and those with renal or hepatic failure were excluded. <h3>Results</h3> Mean serum ferritin, and ferritin/iron ratio were significantly higher among febrile children when compared to controls. Mean serum iron levels were significantly lower among febrile patients and in the subgroup of children who had bacterial infections when compared with children who had viral infections and those who had a non-infectious illness. <h3>Conclusion</h3> Serum iron and ferritin/iron ratio may be clinically useful markers for the differentiation of bacterial from viral infection in the emergency department. Further studies are needed to confirm our findings and to further explore the role of iron metabolism in paediatric infections.

Nonfebrile Illness Seizures: A Unique Seizure Category?

To describe the clinical characteristics of children with a first-time nonfebrile seizure in the setting of mild illness and to test the hypothesis that these seizures are associated with illness characterized by diarrhea. This retrospective cohort study was performed in a pediatric emergency department. Patients ages 6 months to 6 years who were evaluated with first-time seizures were eligible for inclusion. Subjects were divided into three groups on the basis of symptoms accompanying their seizure: febrile (temperature, >38.0 degrees C with seizure), unprovoked (no symptoms of illness), and nonfebrile illness (no fever at the time of seizure, but other symptoms of illness present). Of the 323 children with first-time seizures, 247 (76%) had febrile seizure, 37 (12%) had unprovoked seizures, and 39 (12%) had nonfebrile illness seizures. Children with nonfebrile illness seizures were more likely than children with febrile seizures to have diarrheal illnesses accompanying their seizure (44 vs. 16%; p=0.001). Frequency of cough, rhinorrhea, and rash did not differ significantly between children with febrile and nonfebrile illness seizures. Diagnostic testing for infectious etiologies was not performed frequently in either group. Nonfebrile illness seizures may represent a distinct group of seizures with unique epidemiology. Further study to define this seizure group better is warranted.

Levels of Serum HDL-cholesterol and Total Cholestetol in Kawasaki Disease and Their Significance

Background:The value of serum lipid in children after recovery of Kawasaki disease may be important because of the predilection of this disease for the coronary artery. Methods:To determine the alterations in serum total cholesterol(TC) and high density lipoprotein (HDL)-cholesterol levels in Kawasaki disease(KD), we measured serum HDL-cholesterol and TC in 35 patients(mean age 36.8±22.0 months, range 6 to 93 months) with Kawasaki disease(KD) during 10 days or less after the onset(group A) and 2 months later after recovery. TC and HDL-cholesterol were also measured in an acute febrile respiratory illness group(group B) and a nonfebrile respiratory illness group(group C) to compare with those of KD. Results:HDL-cholesterol levels in group A were depressed(29.6±11.0mg/dl) compared with groups B and C(47.3±13.3mg/dl and 45.1±12.4mg/dl, respectively, p<0.01). TC levels in group A (145.1±33.1mg/dl) were not significantly different from those of group B(146.8±33.4mg/dl) and C (157.1±29.6mg/dl). Also the level of serum HDL-cholesterol in the acute phase of KD was significantly lower when compared with that after recovery(30.2±13.2mg/dl vs 50.0±10.2mg/dl, p<0.05). In KD patients, TC levels were not significantly different between the acute & recovery phases(145.0±26.6mg/dl, 153.4±32.6mg/dl). Echo-cardiography confirmed coronary artery aneurysms in 11 patients(31.4%) and otherwise, normal findings(n=24) in the KD group. There were no significant difference in TC level(140.7±27.6mg/dl vs. 146.9±35.4mg/dl, p=NS) and HDL cholesterol level(30.1±12.5mg/dl vs. 29.2±10.7mg/dl, p=NS) between patients with and without coronary aneurysms. Conclusions:HDL-cholesterol levels were significantly depressed only in the acute phase of KD but TC levels did not change significantly. Both levels were not related to coronary artery aneurysm.

Studies on the occurrence of bacteremia in rheumatic fever

1. 1. We have obtained 385 blood cultures from 185 patients with rheumatic fever in various stages. In patients who had received no therapy, a diplostreptococcus was found in 66 per cent in the acute stage, 22 per cent in the convalescent stage, and 10 per cent in the inactive stage. One hundred and twenty-four control cultures were drawn from 100 age-matched and untreated patients, half of whom had nonfebrile illness and half of whom had febrile illnesses of various types. The percentage of positive cultures, including staphylococcal contaminants, was 14 per cent in the febrile controls and 12 per cent in the nonfebrile controls. The high percentage of positive cultures in the rheumatic patients appeared to be related both to the acuteness of the disease and the absence of antibiotic or salicylate medication. 2. 2. The organism obtained has been identified as being most closely related to the “enterococcus” group of streptococci, most of the organisms belonging to Group D. 3. 3. The suggestion is made that the presence of these organisms in the blood stream may be an indication of their importance in the pathogenesis of the rheumatic process initiated by the Group A beta hemolytic streptococcus.