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Background: In 2014, an outbreak of adenoviral pneumonia occurred in the Korean military training center. However, there are limited data on the characteristics of the fever and its response to antipyretic therapy in immunocompetent adults with adenovirus-positive community-acquired pneumonia (CAP)., Methods: The medical records of the patients who were admitted to the Armed Forces Chuncheon Hospital for the treatment of CAP between January 2014 and December 2016 were retrospectively analyzed. The patients were divided into three groups, namely, the adenovirus-positive (Adv) group, the adenovirus-negative (Non-Adv) group and the unknown pathogen group, according to the results of a polymerase chain reaction (PCR) test and sputum culture used to measure adenovirus and other bacteria or viruses in respiratory specimens. We evaluated and compared the demographics, clinicolaboratory findings and radiological findings upon admission between the two groups., Results: Out of the 251 military personnel with CAP during the study periods, 67 were classified into the Adv group, while 134 were classified into the Non-Adv group and 50 were classified into the unknown pathogen group. The patients in the Adv group had a longer duration of fever after admission (3.2 ± 1.6 vs. 1.9 ± 1.2 vs. 2.2 ± 1.5 days, P = 0.018) and symptom onset (5.8 ± 2.2 vs. 3.9 ± 2.5 vs. 3.7 ± 2.0 days, P = 0.006) than patients in the Non-Adv and unknown pathogen groups, respectively. The patients in the Adv group had a higher mean temperature at admission (37.8 ± 0.3 vs. 37.3 ± 0.3 vs. 37.3 ± 0.3, P = 0.005), and more patients were observed over 40 and 39 to 40(14.9% vs. 2.2% vs. 4.0%, 35.8% vs. 3.7% vs. 6.0%, P <  0.001) than those in the Non-Adv and unknown pathogen groups, respectively. The Adv group more commonly had no response or exhibited adverse events after antipyretic treatment compared to the Non-Adv group (17.9% vs. 1.5%, 35.0% vs. 4.3%, P <  0.001, P = 0.05, respectively). In addition, the time from admission to overall clinical stabilization was significantly longer in the patients in the Adv group than in those in the Non-Adv group (4.3 ± 2.8 vs. 2.9 ± 1.8 days, P = 0.034, respectively). Furthermore, no significant difference in the length of hospital stay was observed between the two groups, and no patient died in either group., Conclusion: In this study, Adv-positive CAP in immunocompetent military personnel patients had distinct fever characteristics and responses to antipyretic treatment.

Fever is a common symptom of many diseases. Fever temporal patterns can be different depending on the specific pathology. Differentiation of diseases based on multiple mathematical features and visual observations has been recently studied in the scientific literature. However, the classification of diseases using a single mathematical feature has not been tried yet. The aim of the present study is to assess the feasibility of classifying diseases based on fever patterns using a single mathematical feature, specifically an entropy measure, Sample Entropy. This was an observational study. Analysis was carried out using 103 patients, 24 hour continuous tympanic temperature data. Sample Entropy feature was extracted from temperature data of patients. Grouping of diseases (infectious, tuberculosis, non-tuberculosis, and dengue fever) was made based on physicians diagnosis and laboratory findings. The quantitative results confirm the feasibility of the approach proposed, with an overall classification accuracy close to 70%, and the capability of finding significant differences for all the classes studied.

Introduction: With the ability to diagnose malaria with rapid diagnostic tests (mRDT), interest in improving diagnostics for non-malarial fevers has increased. Understanding how health providers diagnose and treat fevers is important for identifying additional tools to improve outcomes and reduce unnecessary antibiotic prescribing, particularly in areas where access to laboratory diagnostics is limited. This study aimed to understand rural health providers' practice patterns, both quantitatively and qualitatively, and influences on diagnostic and treatment decision-making., Methods: A mixed-methods study was conducted in Mulanje and Phalombe districts in southern Malawi. Retrospective data on diagnoses and treatments of febrile illness from seven mobile clinic logbooks were collected for a 2-month period in both the dry and wet seasons. Mobile health clinics visited remote villages in southern Malawi once every 7 days. Records from all patients with a recorded axillary temperature of 37.5&ordm;C or higher or reported history of fever within 48 hours, and a negative mRDT, were included in the analysis. Key informant interviews were conducted with 31 mobile clinic health workers who triage, diagnose, and treat patients as well as dispense medication., Results: In total, 30 672 febrile patients were seen during the study period. Of those, 9924 (32%) tested negative for malaria by mRDT. Acute respiratory infection was the most common diagnosis for mRDT-negative patients (44.6%), and this number increased in the rainy season as compared to the dry season (odds ratio=2.18, 95% confidence interval=2.01-2.36). Over half (60%) of mRDT-negative patients received antibiotics as a treatment. Almost all the health providers in this study reported limited training in non-malarial fever management, despite the fact that roughly 30% of all patients with fever seen at the mobile clinics tested negative by mRDT. Without diagnostic tools beyond mRDTs, providers relied heavily on patient history to guide treatment decisions., Conclusion: Additional simple-to-use diagnostic tests as well as additional training in patient examination and clinical assessment are needed in rural settings where health providers risk over-prescribing antibiotics or missing a potentially dangerous infection in febrile patients who test negative for malaria.

Background: Fever remains a major public health problem. In Burkina Faso, more than half of febrile children are considered not to be infected by malaria. This study prospectively assessed probable (treatable) causes of fever in Burkinabe children., Methods: A prospective study was conducted among febrile children (≥37.5 °C) under 5 years of age presenting at four health facilities and one referral hospital in rural Burkina Faso. From each participant, blood was collected for malaria microscopy and culture, urine for dipstick testing and culturing if tested positive for leucocytes and nitrite, stool for rotavirus/adenovirus testing, culture and parasitology, and a nasopharyngeal swab for culture., Results: In total 684 febrile children were included in the study. Plasmodium falciparum malaria was found in 49.7% (340/684) of the participants and non-malaria infections in 49.1% (336/684) of children. The non-nalaria infections included gastro-intestinal infections (37.0%), common bacterial pathogens of nasopharynx (24.3%), bacterial bloodstream infections (6.0%) and urinary tract infections (1.8%). Nearly 45% (154/340) of the malaria infected children were co-infected with non-nalaria infections, but only 3.2% (11/340) of these co-infections could be considered as a possible alternative cause of fever. In contrast, in the malaria microscopy negative children 18.0% (62/344) of the infections could be the probable cause of the fever. Pathogens were not isolated from 23.7% (162/684) of the febrile cases., Conclusions: Malaria remains the most common pathogen found in febrile children in Burkina Faso. However, a relative high number of febrile children had non-malaria infections. The correct diagnosis of these non-malaria fevers is a major concern, and there is an urgent need to develop more point-of-care diagnostic tests and capacities to identify and treat the causes of these fevers.

Background: Dengue is a leading cause of fever and mimics other acute febrile illnesses (AFI). In 2009, the World Health Organization (WHO) revised criteria for clinical diagnosis of dengue., Methodology/principal Findings: The new WHO 2009 classification of dengue divides suspected cases into three categories: dengue without warning signs, dengue with warning signs and severe dengue. We evaluated the WHO 2009 classification vs physicians' subjective clinical diagnosis (gestalt clinical impression) in a large cohort of patients presenting to a tertiary care center in southern Sri Lanka hospitalized with acute febrile illness. We confirmed acute dengue in 388 patients (305 adults ≥ 18 years and 83 children), including 103 primary and 245 secondary cases, of 976 patients prospectively enrolled with AFI. At presentation, both adults and children with acute dengue were more likely than those with other AFI to have leukopenia and thrombocytopenia. Additionally, adults were more likely than those with other AFI to have joint pain, higher temperatures, and absence of crackles on examination whereas children with dengue were more likely than others to have sore throat, fatigue, oliguria, and elevated hematocrit and transaminases. Similarly, presence of joint pain, thrombocytopenia, and absence of cough were independently associated with secondary vs primary dengue in adults whereas no variables were different in children. The 2009 WHO dengue classification was more sensitive than physicians' clinical diagnosis for identification of acute dengue (71.5% vs 67.1%), but was less specific. However, despite the absence of on-site diagnostic confirmation of dengue, clinical diagnosis was more sensitive on discharge (75.2%). The 2009 WHO criteria classified almost 75% as having warning signs, even though only 9 (2.3%) patients had evidence of plasma leakage and 16 (4.1%) had evidence of bleeding., Conclusions/significance: In a large cohort with AFI, we identified features predictive of dengue vs other AFI and secondary vs primary dengue in adults versus children. The 2009 WHO dengue classification criteria had high sensitivity but low specificity compared to physicians' gestaldt diagnosis. Large cohort studies will be needed to validate the diagnostic yield of clinical impression and specific features for dengue relative to the 2009 WHO classification criteria.

Diagnosis of undifferentiated fever is a major challenging task to the physician which often remains undiagnosed and delays the treatment. The aim of the study was to record and analyze a 24-hour continuous tympanic temperature and evaluate its utility in the diagnosis of undifferentiated fevers. This was an observational study conducted in the Kasturba Medical College and Hospitals, Mangaluru, India. A total of ninety-six ( n = 96) patients were presented with undifferentiated fever. Their tympanic temperature was recorded continuously for 24 hours. Temperature data were preprocessed and various signal characteristic features were extracted and trained in classification machine learning algorithms using MATLAB software. The quadratic support vector machine algorithm yielded an overall accuracy of 71.9% in differentiating the fevers into four major categories, namely, tuberculosis, intracellular bacterial infections, dengue fever, and noninfectious diseases. The area under ROC curve for tuberculosis, intracellular bacterial infections, dengue fever, and noninfectious diseases was found to be 0.961, 0.801, 0.815, and 0.818, respectively. Good agreement was observed [kappa = 0.618 ( p < 0.001, 95% CI (0.498-0.737))] between the actual diagnosis of cases and the quadratic support vector machine learning algorithm. The 24-hour continuous tympanic temperature recording with supervised machine learning algorithm appears to be a promising noninvasive and reliable diagnostic tool.

Background: Universal access to, and community uptake of malaria prevention and treatment strategies are critical to achieving current targets for malaria reduction. Each step in the treatment-seeking pathway must be considered in order to establish where opportunities for successful engagement and treatment occur. We describe local classifications of childhood febrile illnesses, present an overview of treatment-seeking, beginning with recognition of illness, and suggest how interventions could be used to target the barriers experienced., Methods: Qualitative data were collected between September 2010 and February 2011. A total of 12 Focus Group Discussions and 22 Critical Incident Interviews were conducted with primary caregivers who had reported a recent febrile episode for one of their children., Findings and Conclusion: The phrase 'kutentha thupi', or 'hot body' was used to describe fever, the most frequently mentioned causes of which were malungo (translated as 'malaria'), mauka, nyankhwa and (m)tsempho. Differentiating the cause was challenging because these illnesses were described as having many similar non-specific symptoms, despite considerable differences in the perceived mechanisms of illness. Malungo was widely understood to be caused by mosquitoes. Commonly described symptoms included: fever, weakness, vomiting, diarrhoea and coughing. These symptoms matched well with the biomedical definition of malaria, although they also overlapped with symptoms of other illnesses in both the biomedical model and local illness classifications. In addition, malungo was used interchangeably to describe malaria and fever in general. Caregivers engaged in a three-phased approach to treatment seeking. Phase 1-Assessment; Phase 2-Seeking care outside the home; Phase 3-Evaluation of treatment response. Within this paper, the three-phased approach is explored to identify potential interventions to target barriers to appropriate treatment. Community engagement and health promotion, the provision of antimalarials at community level and better training health workers in the causes and treatment of non-malarial febrile illnesses may improve access to appropriate treatment and outcomes.

Introduction: The development of simple clinical tools to identify children at risk of death would enable rapid and rational implementation of lifesaving measures to reduce childhood mortality globally., Methods: We evaluated the ability of three clinical scoring systems to predict in-hospital mortality in a prospective observational study of Ugandan children with fever. We computed the Lambaréné Organ Dysfunction Score (LODS), Signs of Inflammation in Children that Kill (SICK), and the Pediatric Early Death Index for Africa (PEDIA). Model discrimination was evaluated by comparing areas under receiver operating characteristic curves (AUCs) and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Sub-analyses were performed in malaria versus non-malaria febrile illness (NMFI), and in early (≤48 hours) versus late (>48 hours) deaths., Results: In total, 2089 children with known outcomes were included in the study (99 deaths, 4.7% mortality). All three scoring systems yielded good discrimination (AUCs, 95% confidence interval (CI): LODS, 0.90, 0.88 to 0.91; SICK, 0.85, 0.83 to 0.86; PEDIA, 0.90, 0.88 to 0.91). Using the Youden index to identify the best cut-offs, LODS had the highest positive likelihood ratio (+LR, 95% CI: LODS, 6.5, 5.6 to 7.6; SICK, 4.4, 3.9 to 5.0; PEDIA, 4.4, 3.9 to 5.0), whereas PEDIA had the lowest negative likelihood ratio (-LR, 95% CI: LODS, 0.21, 0.1 to 0.3; SICK, 0.22, 0.1 to 0.3; PEDIA, 0.16, 0.1 to 0.3), LODS and PEDIA were well calibrated (P = 0.79 and P = 0.21 respectively), and had higher AUCs than SICK in discriminating between survivors and non-survivors in malaria (AUCs, 95% CI: LODS, 0.92, 0.90 to 0.93; SICK, 0.86, 0.84 to 0.87; PEDIA, 0.92, 0.90 to 0.93), but comparable AUCs in NMFI (AUCs, 95% CI: LODS, 0.86, 0.83 to 0.89; SICK, 0.82, 0.79 to 0.86; PEDIA, 0.87, 0.83 to 0.893). The majority of deaths in the study occurred early (n = 85, 85.9%) where LODS and PEDIA had good discrimination., Conclusions: All three scoring systems predicted outcome, but LODS holds the most promise as a clinical prognostic score based on its simplicity to compute, requirement for no equipment, and good discrimination.

Although oral health care has a preventive effect against ventilator-associated pneumonia (VAP), the most effective method of oral health care in this respect remains to be established. The objective of this single-center, randomized, controlled trial was to investigate the relationship between VAP and various methods of oral health care. All patients included in the study (n=142) were on mechanical ventilation with oral intubation at the intensive care unit of the Tokyo Dental College Ichikawa General Hospital. They were divided into two groups, one receiving standard oral health care (Standard group), and the other receiving oral health care using an oral moisture gel instead of water (Gel group). After removal of the intubation tube, biofilm on cuff of the tube was stained with a disclosing agent to determine the contamination level. Factors investigated included sex, age, number of remaining teeth, intubation time, fever ≥38.5°C, VAP, cuff contamination level, and time required for one oral health care session. No VAP occurred in either group during the study period. The level of cuff contamination was significantly lower in the Gel group than the Standard group, and the time required for one session of oral health care was shorter (p<0.001). Multivariate analysis revealed use of the oral moisture gel as a factor affecting cuff contamination level. Use of an oral moisture gel decreased invasion of the pharynx by bacteria and contaminants together with biofilm formation on the intubation tube cuff. These results suggest that oral health care using an oral moisture gel is effective in preventing cuff contamination.

Background: Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated., Methods: Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive "gold standard" (ANC <1.0×10(9)/L, and body temperature ≥38.3°C or receipt of antibiotics) and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity., Results: Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24-45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78-95) and sensitivity was 57% (46-68). For the definition including neutropenia in any position (n=71), PPV was 77% (68-87) and sensitivity was 67% (56-77)., Conclusions: Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

Community-acquired pneumonia (CAP) is now most frequent in elderly patients. CAP in the younger patient has attracted much less attention. Therefore, we compared patients with CAP aged 18 to <65 yrs with those aged ≥ 65 yrs. Data from the prospective multicentre Competence Network for Community Acquired Pneumonia Study Group (CAPNETZ) database were analysed for potential differences in baseline characteristics, comorbidities, clinical presentation, microbial investigations, aetiologies, antimicrobial treatment and outcomes. Overall, 7,803 patients were studied. The proportion of younger patients (aged <65 yrs) was 52.3% (18 to <30 yrs 6.4%; <40 yrs 17.1%; <50 yrs 29.4%). Comorbidity was present in only half of the younger patients (46.6% versus 88.2%). Fever and chest pain were more common. Most younger patients presented with mild CAP (74.0% had a CRB-65 [corrected] score of 0 (confusion of new onset, [corrected] respiratory rate of ≥ 30 breaths · min(-1), blood pressure <90 mmHg or diastolic blood pressure ≤ 60 mmHg, age ≥ 65 yrs)). Overall, Streptococcus pneumoniae and Mycoplasma pneumoniae were the most frequent pathogens in the younger patients. Short-term mortality was very low (1.7% versus 8.2%) and even lower in patients without comorbidity (0.3% versus 2.4%). Long-term mortality was 3.2% versus 15.9%, also lower in patients without comorbidity (0.8% versus 6.1%). Most of the differences found clearly arise after the fifth or within the middle of the sixth decade. CAP in the younger patient is a clinically distinct entity.

Background: Community clinics offer potential for timelier outbreak detection and monitoring than emergency departments. However, the accuracy of syndrome definitions used in surveillance has never been evaluated in community settings. This study's objective was to assess the accuracy of syndrome definitions based on diagnostic codes in physician claims for identifying 5 syndromes (fever, gastrointestinal, neurological, rash, and respiratory including influenza-like illness) in community clinics., Methods: We selected a random sample of 3,600 community-based primary care physicians who practiced in the fee-for-service system in the province of Quebec, Canada in 2005-2007. We randomly selected 10 visits per physician from their claims, stratifying on syndrome type and presence, diagnosis, and month. Double-blinded chart reviews were conducted by telephone with consenting physicians to obtain information on patient diagnoses for each sampled visit. The sensitivity, specificity, and positive predictive value (PPV) of physician claims were estimated by comparison to chart review., Results: 1,098 (30.5%) physicians completed the chart review. A chart entry on the date of the corresponding claim was found for 10,529 (95.9%) visits. The sensitivity of syndrome definitions based on diagnostic codes in physician claims was low, ranging from 0.11 (fever) to 0.44 (respiratory), the specificity was high, and the PPV was moderate to high, ranging from 0.59 (fever) to 0.85 (respiratory). We found that rarely used diagnostic codes had a higher probability of being false-positives, and that more commonly used diagnostic codes had a higher PPV., Conclusions: Future research should identify physician, patient, and encounter characteristics associated with the accuracy of diagnostic codes in physician claims. This would enable public health to improve syndromic surveillance, either by focusing on physician claims whose diagnostic code is more likely to be accurate, or by using all physician claims and weighing each according to the likelihood that its diagnostic code is accurate.

Objective: The Paediatric Canadian Triage and Acuity Scale (PaedCTAS) stipulates that febrile patients who are 3 to 36 months old should be triaged to the PaedCTAS 3 "urgent" category. To optimize resource use, we implemented a protocol enabling these children to be down-triaged to the PaedCTAS 4 "less urgent" category if there was no sign of toxicity. Our objective was to evaluate the safety of this triage protocol modification., Methods: This retrospective cohort study evaluated all patients triaged in an urban tertiary pediatric hospital during a 6-month period between November 22, 2005, and May 22, 2006. Data were retrieved from the emergency department (ED) database and rates of hospitalization and intensive care unit (ICU) admission were compared for 4 groups: all patients triaged as urgent (level 3), all febrile patients from 3 to 36 months old triaged as urgent (level 3), all patients triaged as less urgent (level 4) and all febrile patients aged 3 to 36 months old who were down-triaged to less urgent (level 4)., Results: There were 36,285 total ED visits during the study period, including 3477 febrile children who were 3 to 36 months old. Nurses down-triaged 1869 febrile children (54%) to the level-4 (less urgent) category and left 1322 (38%) in the level-3 (urgent) category. Hospitalization rate for down-triaged febrile patients was similar to that seen for all PaedCTAS 4 patients (2.4% v. 2.8%, 95% confidence interval for difference -0.3% to 1.1%). Down-triaged patients had significantly lower admission rates than those remaining in the level-3 (urgent) category (absolute risk reduction 10.7% standard deviation 1.9%, p<0.001). No down-triaged patient died or required ICU admission., Conclusion: Febrile children aged 6 to 36 months who have no signs of toxicity can safely be down-triaged, based on triage nurse clinical judgement, to the less urgent PaedCTAS 4 category. This modification would affect the triage level of approximately 5% of all pediatric ED visits.

Objectives: Febrile neutropenia (FN) in patients with cancer treated with chemotherapy has traditionally been managed with inpatient broad-spectrum antibiotics until the infection and neutropenia have resolved. A newer strategy is outpatient oral or intravenous antibiotics in selected patients after an initial hospitalization. We sought to determine these costs, both overall and relative to those of traditional management, and the optimal role of prophylactic colony-stimulating factor (CSF) in patients at greatest risk for FN., Methods: Existing economic decision models were modified by incorporating a treatment strategy for FN in which patients are classified as high- and low-risk according to criteria described by Talcott. Low-risk patients were assumed to be treated as outpatients. Overall costs with the revised economic model were assessed and sensitivity analyses were performed., Results: The costs of an episode of FN were estimated as 1) no CSF: dollar 13,355; 2) CSF with hospitalization for FN: dollar 8677; and 3) CSF with risk stratification and outpatient management in low-risk patients: dollar 8188. The risk threshold for the cost-effective use of CSF was only slightly lower with outpatient treatment. When all patients with FN are treated as inpatients and the cost of hospitalization is dollar 1750/day the risk threshold for FN at which prophylactic CSF becomes cost-effective is 16%. It is 15% when low-risk patients are treated as outpatients., Conclusions: Outpatient treatment slightly decreases the risk threshold for FN at which prophylactic CSF becomes cost-effective. The limited economic effect of this strategy may be because the patients who were at greatest risk of complications had significantly longer lengths of stay and accounted for most of the hospitalization costs.

Background: The Ugandan Ministry of Health has adopted the WHO Home Based Fever Management strategy (HBM) to improve access to antimalarial drugs for prompt (<24 h) presumptive treatment of all fevers in children under 5 years. Village volunteers will distribute pre-packed antimalarials free of charge to caretakers of febrile children 2 months to 5 years ('Homapaks')., Objective: To explore the local understanding and treatment practices for childhood fever illnesses and discuss implications for the HBM strategy., Methods: Focus Group Discussions were held with child caretakers in three rural communities in Kasese district, West Uganda, and analysed for content in respect to local illness classifications and associated treatments for childhood fevers., Results: Local understanding of fever illnesses and associated treatments was complex. Some fever illness classifications were more commonly mentioned, including 'Fever of Mosquito', 'Chest Problem', 'the Disease', 'Stomach Wounds' and 'Jerks', all of which could be biomedical malaria. Although caretakers refer to all these classifications as 'fever' treatment differed; some were seen as requiring urgent professional western treatment and others were considered severe but 'non-western' and would preferentially be treated with traditional remedies., Conclusions: The HBM strategy does not address local community understanding of 'fever' and its influence on treatment. While HBM improves drug access, Homapaks are likely to be used for only those fevers where 'western' treatment is perceived appropriate, implying continued delayed and under-treatment of potential malaria. Hence, HBM strategies also need to address local perceptions of febrile illness and adapt information and training material accordingly.

Hereditary amyloidoses with renal involvement are classified in two groups. The first group is a growing family of autoinflammatory disorders characterized by recurrent fever attacks. Amyloidosis is caused by the deposition of amyloid A (AA) protein, which is a degradation product of a normal serum acute-phase protein: serum amyloid A (SAA). The prototype is familial Mediterranean fever (FMF). TNF Receptor Associated Periodic Syndrome (TRAPS) is a recently recognized periodic fever syndrome, differing from FMF in several characteristics: autosomal-dominant transmission, longer duration of attacks, and lack of response to colchicine prophylaxis. The second group comprises a variety of disorders, each characterized by the deposition of a specific mutant protein. The prototype is transthyretin amyloidosis (TTR). Identification of the form of amyloidosis has clinical implications. Therefore, in a patient with a history of recurrent fever attacks and AA amyloidosis, a diagnosis of FMF or TRAPS dictates appropriate genetic counseling and management. In patients with renal amyloidosis without a history of fever, identification of the mutant protein is therapeutically crucial; therefore, when the cell type that produces the precursor is (exclusively or mainly) the hepatocyte, a liver transplantation is to be considered.

The differential diagnosis for febrile patients with a rash is extensive. Diseases that present with fever and rash are usually classified according to the morphology of the primary lesion. Rashes can be categorized as maculopapular (centrally and peripherally distributed), petechial, diffusely erythematous with desquamation, vesiculobullous-pustular and nodular. Potential causes include viruses, bacteria, spirochetes, rickettsiae, medications and rheumatologic diseases. A thorough history and a careful physical examination are essential to making a correct diagnosis. Although laboratory studies can be useful in confirming the diagnosis, test results often are not available immediately. Because the severity of these illnesses can vary from minor (roseola) to life-threatening (meningococcemia), the family physician must make prompt management decisions regarding empiric therapy. Hospitalization, isolation and antimicrobial therapy often must be considered when a patient presents with fever and a rash.

The recently proposed Duke criteria were confirmed to be more sensitive than the former Beth Israel criteria for the diagnosis of infective endocarditis (IE). To assess the specificity of the Duke criteria, we reviewed the records of 100 patients admitted to two internal medicine wards because of acute fever or fever of unknown origin (FUO). IE was considered a possible diagnosis for all patients who had had at least two blood cultures performed and one transthoracic echocardiogram obtained. The diagnosis of IE was rejected in all cases in accordance with the Duke criteria (i.e., a firm alternate diagnosis [n = 23], resolution of symptoms with no antibiotics [n = 39], or both reasons [n = 38]). To calculate the specificity of the Duke criteria, all 100 cases were then reclassified according to these criteria as if the diagnosis of IE had not been rejected. Only one patient, who probably did not have IE, was reclassified as having clinically definite IE. The specificity of the Duke criteria could therefore be calculated to 0.99 (95% confidence interval, 0.97-1). Although the design of the study may have resulted in a slight overestimation of the specificity rate, we conclude that the Duke criteria are highly specific for ruling out IE in patients with acute fever or FUO who are at low risk for IE.

While 46 percent of febrile children, aged 3 months to 24 months, will be well without treatment within 24 to 48 hours, and another 12 percent well within 72 to 96 hours, approximately 6 percent will have serious bacterial infections. The incidence of such infections tends to increase with decreasing age and increasing degree of fever. Physicians, who make specific observations of the child's color, hydration, social response, consolability, and degree of alertness after the child has been made comfortable, can identify about two thirds of those with benign illness and the one tenth who require inpatient evaluation. Of the remaining patients, those with serious illness can be further identified if their white blood count is greater than 15,000/microL, neutrophils are greater than 10,000/microL, band cells are greater than 500/microL, or sedimentation rate is more than 30 mm/h. Children with these laboratory findings should then have a chest film and blood culture and, if the former is negative, should be considered for a lumbar puncture and urine culture. Whether further observation or treatment at this point can be done as an outpatient depends on physician judgment.