Unexplained Febrile Illness Research Articles

Characteristics of Kawasaki Disease in Infants Younger than Six Months of Age

Kawasaki disease is the leading cause of acquired heart disease in childhood. However, there are only a few reports in infants younger than 6 months. The objective of this study is to investigate the clinical and laboratory characteristics of Kawasaki disease in infants younger than 6 months. From 1994 to 2003, 120 patients with Kawasaki disease diagnosed at our institution were included. Group 1 consisted of 20 (17%) patients younger than 6 months, and group 2 consisted of 100 (83%) patients older than 6 months. Clinical manifestations, laboratory results, echocardiographic findings, treatment and outcome were compared between these 2 groups. Clinical manifestations (hydrops of gallbladder: 0% versus 16%, P < 0.001) and laboratory results (white blood cell count 21,740 +/- 11,706 versus 11,830 +/- 4390/mm3, P < 0.001; hemoglobin 9.98 +/- 1.25 versus 10.8 +/- 1.37 g/dL, P = 0.015; platelet 483 +/- 393 versus 355 +/- 138 x 1000/mm3, P = 0.011; triglyceride 138 +/- 77.5 versus 107 +/- 17 mg/dL, P < 0.001) were different between patients with Kawasaki disease younger and older than 6 months, respectively. Younger infants were more likely to have incomplete presentation (35% versus 12%, P = 0.025), coronary involvement (65% versus 19%, P < 0.001), late intravenous immunoglobulin treatment and relatively poor outcome. Infants younger than 6 months with prolonged unexplained febrile illnesses should be suspected as having Kawasaki disease, despite the incomplete clinical presentation. Because early diagnosis and timely treatment are difficult in younger infants with Kawasaki disease because of delayed and incomplete clinical presentations, echocardiogram becomes an important implement for diagnosis. Early intravenous immunoglobulin treatment is required in view of the highest risk of coronary involvement in them.

Congenital Pulmonary Tuberculosis Associated With Maternal Cerebral Tuberculosis—Florida, 2002

In 2002, congenital tuberculosis (TB), a rare disease with nonspecific signs and symptoms, was diagnosed in an infant in Florida. If untreated, congenital TB is fatal, which underscores the importance of suspecting congenital TB in newborns and infants who are at risk and who have unexplained febrile illnesses. This report summarizes the investigation of the case in Florida. Health-care practitioners should administer a tuberculin skin test to women who have risks for Mycobacterium tuberculosis infection and treat those who have latent TB infection (LTBI) to prevent maternal and congenital TB disease.

Standardized Infection Surveillance in Long-Term Care Interfacility Comparisons From a Regional Cohort of Facilities

To measure infection rates in a regional cohort of long-term-care facilities (LTCFs) using standard surveillance methods and to analyze different methods for interfacility comparisons. Seventeen LTCFs in Idaho. Prospective, active surveillance for LTCF-acquired infections using standard definitions and case-finding methods was conducted from July 2001 to June 2002. All surveillance data were combined and individual facility performance was compared with the aggregate employing a variety of statistical and graphic methods. The surveillance data set consisted of 472,019 resident-days of care with 1717 total infections for a pooled mean rate of 3.64 infections per 1000 resident-days. Specific infections included respiratory (828; rate, 1.75), skin and soft tissue (520; rate, 1.10), urinary tract (282; rate, 0.60), gastrointestinal (77; rate, 0.16), unexplained febrile illnesses (6; rate, 0.01), and bloodstream (4; rate, 0.01). Initially, methods adopted from the National Nosocomial Infections Surveillance System were used comparing individual rates with pooled means and percentiles of distribution. A more sensitive method appeared to be detecting statistically significant deviations (based on chi-square analysis) of the individual facility rates from the aggregate of all other facilities. One promising method employed statistical process control charts (U charts) adjusted to compare individual rates with aggregate monthly rates, providing simultaneous visual and statistical comparisons. Small multiples graphs were useful in providing images valid for rapid concurrent comparison of all facilities. Interfacility comparisons have been demonstrated to be valuable for hospital infection control programs, but have not been studied extensively in LTCFs.

Tuberculosis Associated With Blocking Agents Against Tumor Necrosis Factor-Alpha—California, 2002-2003

The Food and Drug Administration (FDA) has determined that tuberculosis (TB) disease is a potential adverse reaction from treatment with the tumor necrosis factor-alpha (TNF-alpha) antagonists infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira); the three products are labeled accordingly. These products work by blocking TNF-alpha, an inflammatory cytokine, and are approved for treating rheumatoid arthritis and other selected autoimmune diseases. TNF-alpha is associated with the immunology and pathophysiology of certain infectious diseases, notably TB; blocking TNF-alphacan allow TB disease to emerge from latent Mycobacterium tuberculosis infection. In 2002, a California county health department reported three cases of TB disease occurring in association with infliximab therapy. This report summarizes those cases and nine subsequently reported cases and provides interim recommendations for TB prevention and management in recipients of these blocking agents. Health-care providers should take steps to prevent TB in immunocompromised patients and remain vigilant for TB as a cause of unexplained febrile illness.

Coxiella burnetii infection of an aortic graft: surgical view and a word of caution

A 30-year-old-man presented with an aortic graft infection. Polymerase chain reaction study identified the infectious organism as Coxiella burnetii, a strictly intracellular pathogen that causes Q fever in humans. The patient was successfully treated by removal of the infected graft, implantation of homograft aortic tube, and specific antibiotic therapy. He is doing well after 6 months, with no evidence of recurrent homograft infection on transthoracic echocardiography. C. burnetii vascular graft infections may be underdiagnosed because of lack of recognition. We suggest that serologic tests for C. burnetii be routinely performed in the presence of unexplained febrile illness or pain in patients with a history of underlying vascular disease.

Approach to the child with prolonged fever in the pediatric emergency department

Children with prolonged fever represent diagnostic challenges. Although prolonged fever has been variously defined, the most widely accepted definition of fever of unknown origin in a child is an unexplained febrile illness lasting at least 8 days. Other term, fever without localizing signs, and fever without source refer to children with fever of shorter duration, generally less than 5 days. This review focuses on children with fever greater than 5 days duration. In each case, the practitioner of pediatric emergency medicine must be systematic and highly organized. He or she must first carefully review the child's history and physical examination for overlooked clinical clues, and then must make use of a focused set of laboratory and radiological tests. A “shotgun” approach must be avoided. Hospital admission may occasionally be warranted for die extremely ill child or to facilitate further evaluation, Extensive family counseling and close clinical follow-up are crucial. Repetition of the history and physical examination, is well is serial careful observations, may yield important leads that less rigorous physicians failed to see. Compared with adults, children have fewer life-threatening and chronic conditions that present as prolonged fever. Occult infections acocunt for nearly 50% of cases anti the overall mortality is low.

Regional data set of infection rates for long-term care facilities: Description of a valuable benchmarking tool

Background: Surveillance for nosocomial infections has been clearly established as a key element of all infection control programs. Surveillance programs in long-term care facilities (LTCFs) have been described, but published infection rates vary widely depending on the type of facility studied, nature of resident population, definitions used for LTCF-acquired infections, and type of data analysis. The aim of this initial study was to create a standardized regional data set of infection rates that could provide an external benchmark for interfacility comparison. Methods: The study included 6 LTCFs in close geographic proximity with similar patient populations. Surveillance in each facility was conducted by a licensed nurse supervised by an infectious diseases physician. Standard definitions for infections and uniform reporting forms were used. Data were pooled in an aggregate cumulative fashion, and data analysis was patterned after the National Nosocomial Infection Surveillance System. Results: The data set consisted of 328,065 resident-days of care during 30 months, with a total of 1252 infections for a pooled mean rate of 3.82 infections per 1000 resident-days of care. Infections for specific categories were 496 urinary tract infections (rate 1.51), 376 respiratory tract infections (rate 1.15), 88 gastroenteritis infections (rate 0.27), 283 skin and soft tissue infections (rate 0.86), 2 bloodstream infections (rate 0.06), and 3 unexplained febrile illnesses (rate 0.09). Data analysis for comparison included interfacility means ±2 standard deviations and percentiles of distribution. Conclusions: A regional data set of infection rates for LTCFs allowed for meaningful interfacility comparison of overall and specific endemic rates and is a valuable benchmarking tool for participating facilities. (AJIC Am J Infect Control 1999;27:20-6)

Update: Leptospirosis and Unexplained Acute Febrile Illness Among Athletes Participating in Triathlons—Illinois and Wisconsin, 1998

Update: Leptospirosis and Unexplained Acute Febrile Illness Among Athletes Participating in Triathlons—Illinois and Wisconsin, 1998

Update: Leptospirosis and Unexplained Acute Febrile Illness Among Athletes Participating in Triathlons--Illinois and Wisconsin, 1998

Since July 14, 1998, the Illinois Department of Health, the Wisconsin Department of Health, the U.S. Department of Agriculture (USDA), and CDC, in collaboration with other state and local health departments, have been investigating an outbreak of acute febrile illness among athletes from 44 states and seven countries who participated in triathlons in Springfield, Illinois, on June 21, 1998, and in Madison, Wisconsin, on July 5, 1998. Initial testing at CDC of specimens from four athletes identified leptospirosis as the illness in all four. This report updates the ongoing investigation of this outbreak through August 13, which indicates that Leptospira was the etiologic agent for illness in athletes and in persons with occupational or recreational exposure to Lake Springfield, where the event was held in Illinois.

Evaluation of the pathogenic potential of Rickettsia canada and Rickettsia prowazekii organisms in dogs

Summary An unusual pattern of seroreactivity to antigens of rickettsial organisms (Rickettsia rickettsii, R rhipicephali, R montana, and R bellii), particularly to R bellii antigen, was detected in 3 dogs during a 2-month period. Thus, studies were initiated to clarify the pathogenic potential of the more distantly related rickettsial organisms (R canada and R prowazekii) in dogs. Because R bellii are nonpathogenic rickettsiae that share numerous common properties with spotted fever-group and typhus-group rickettsiae, and because closely related pathogenic relatives of R bellii have not been identified, we examined the pathogenic potential of these typhus-group rickettsiae by testing stored serum samples, by attempting rickettsial isolation from febrile dogs, and by experimentally inoculating dogs with R canada and R prowazekii. Evaluation of results of a serosurvey of acute and convalescent serum samples from 80 dogs in which Rocky Mountain spotted fever had been considered as a differential diagnosis, but seroconversion to R rickettsii had not been documented, identified 1 dog with a fourfold increase in antibody titer to R rhipicephali and 3 dogs with fourfold increases in antibody titer to 1 or more antigens of typhus-group rickettsial organisms. A study of 15 dogs that were febrile during summer months failed to identify serologic or tissue culture evidence of typhus-group rickettsial infection or typhus-group rickettsemia, but did result in isolation of R rickettsii and Ehrlichia canis, respectively, from 1 dog each. In our final study, after experimentally inoculating 6 dogs with R canada and R prowazekii, all dogs seroconverted to the respective rickettsiae, but rickettsemia or clinical and hematologic evidence of disease was not observed. Collectively, our results did not provide convincing evidence to support a pathogenic role for R canada and R prowazekii organisms in dogs. Our findings supported the conclusion that an unidentified microorganism, which results in production of antibodies against R bellii and antigens of typhus-group rickettsial organisms, contributed to an unexplained febrile illness of dogs in the southeastern United States. In an effort to identify dogs in which serologic evidence supports this conclusion, we recommend the use of selected spotted fever-group, typhus-group, and R bellii antigens for serodiagnostic purposes. We also recommend that diagnosticians attempt tissue culturing to isolate organisms when a rickettsial agent is suspected.

Infective Endocarditis

A high level of suspicion is of utmost importance in the diagnosis of endocarditis, particularly in the patient at risk who may have received antibiotic treatment for the prodrome. Treatment with adequate levels of a bactericidal drug based on an identified organism will give the highest percentage of cures. Early treatment may prevent damage to cardiac structures and lessen further complications related to emboli or progressively enlarging vegetations. The combination of a high-risk patient with either resistant bacterial endocarditis or fungal [See table in the PDF file] endocarditis carries a higher morbidity and will account for most of the mortality. Although not an ideal answer, SBE prophylaxis is justified from observations in animals and should be recommended strongly to the parents and to the patient as she or he gets older. Because an increasing number of children survive their congenital heart defects but remain at risk for acquiring SBE and because an increasing number of preterm infants and neonates are exposed to indwelling catheters, the pediatrician will continue to see IE presenting as both a diagnostic dilemma and an acute treatment problem. The emergence of children who are human immunodeficiency virus-positive or who have acquired immunodeficiency syndrome has increased the group at immunologic risk, as has an increasing population of children surviving organ transplants. These children can present more often with infections caused by nosocomial, resistant agents because of their frequent hospitalizations, and they may have a variety of opportunistic infections from organisms that normally are not pathogens. Unfortunately, a higher mortality rate can be expected among these children. The diagnosis of IE is made even more of a challenge because it accounts for only about 1/1000 to 1/4500 hospital admissions to pediatric services. In tertiary care hospitals that have an active pediatric cardiac service, the numbers may be higher. The most important element in diagnosing endocarditis remains its early consideration as a possibility in any child who has a persistent unexplained febrile illness and its being the first consideration in a high-risk child.

Human Herpesvirus-6 (HHV-6) Infection in Allogeneic Bone Marrow Transplant Recipients: Evidence of a Marrow-Suppressive Role for HHV-6 In Vivo

Sixteen adults were studied for the first 100 days after allogeneic bone marrow transplant to assess the pathogenic role of human herpesvirus-6 (HHV-6) infection in patients with unexplained febrile illnesses. HHV-6 was directly isolated from the blood of 6 patients. Analysis of the clinical courses of these 16 patients revealed otherwise unexplained posttransplant marrow suppression in 5 patients. Idiopathic marrow suppression occurred more frequently in patients with concurrent HHV-6 viremia (4/6) than in those from whom HHV-6 was not isolated from peripheral blood (1/10, P < .05). An etiologic role for the virus was also supported by isolation of HHV-6 from the bone marrow of all 4 patients at the time of marrow suppression and by in vitro colony-forming unit (cfu) assays that demonstrated that HHV-6 could inhibit cfu-granulocyte-macrophage and burst-forming unit-erythroid growth from human bone marrow. By restriction enzyme mapping, all clinical isolates were type B, suggesting that bone marrow transplant recipients may be preferentially infected with and reactivate this HHV-6 subtype. This study implicates HHV-6 as a novel cause of bone marrow suppression in marrow transplant recipients.

Disseminated granulomatous disease (BCGosis) following chemoimmunotherapy for ovarian carcinoma

The use of BCG (bacille Calmette Guérin) in conjunction with cytotoxic chemotherapeutic agents has been advocated in patients with ovarian carcinoma. We describe a patient with stage III, grade I, endometrioid carcinoma of the ovary treated with cisplatin, doxorubicin, cyclophosphamide, and BCG. Following one course of therapy she presented with an elevated temperature, purpuric skin rash, abnormal liver function tests and hematological indices, and multiple organ failure resulting in sepsis and death. At autopsy, disseminated noncaseating granulomas were found in the lungs, hilar lymph nodes, liver, and spleen. Metastatic carcinoma was not present in these organs. This report describes the rapid onset of a disseminated BCG infection (BCGosis) in a patient with ovarian carcinoma receiving chemoimmunotherapy. Clinical recognition of BCGosis in immunocompromised patients is difficult but should be considered in the differential diagnosis of patients presenting with unexplained febrile illness, functional abnormalities in multiple organ systems, and a history of immunotherapy with BCG. Appropriate specimen collection is emphasized.

Syndromes of Vibrio vulnificus infections. Clinical and epidemiologic features in Florida cases, 1981-1987.

To describe the clinical and epidemiologic features of Vibrio vulnificus infections. Case series based on notifiable disease report forms and patient medical records. Cases reported to the Florida Department of Health and Rehabilitative Services from 1981 to 1987. Sixty-two patients with V. vulnificus infection. The three clinical syndromes found were primary septicemia (38 patients), wound infections (17 patients), and gastrointestinal illness without septicemia or wound infections (7 patients). Mortality rate was highest for patients with primary septicemia (55%; 95% CI, 38 to 71) and intermediate for wound infections (24%; 95% CI, 8 to 51): no deaths occurred in those with gastrointestinal illness. Common characteristics and exposures in patients with these syndromes included recent history of raw oyster consumption for primary septicemia and gastrointestinal illness, liver disease for primary septicemia, and either having a preexisting wound or sustaining a wound in contact with seawater for wound infections. Clinicians should ask about marine exposures in patients with underlying medical conditions, especially liver disease, who present with unexplained febrile illness, and should start appropriate therapy promptly.

Colorado Tick Fever or Ehrlichiosis

<h3>To the Editor.—</h3> I read with interest the recent article by Fishbein et al¹entitled "Unexplained Febrile Illnesses After Exposure to Ticks: Infection With an<i>Ehrlichia?</i>" Although the serological data are very supportive of disease due to<i>Ehrlichia</i>, I would also note that virological and serological studies were apparently not performed for Colorado tick fever (CTF). This latter infection caused by an orbivirus has many similar clinical features to the illness described by Fishbein et al, with fever, chills, headache, myalgias, and abdominal complaints occurring commonly.²A biphasic course is characteristic, but occurs in only half the cases. In addition the major laboratory abnormality of CTF is leukopenia, and lymphopenia is also frequently present.³Both thrombocytopenia and liver function abnormalities have been described.⁴ Despite its name, CTF is endemic throughout the mountainous regions of the western United States and Canada in the distribution of<i>Dermacentor andersoni</i>

Unexplained febrile illnesses after exposure to ticks. Infection with an Ehrlichia?

Unexplained febrile illnesses after exposure to ticks. Infection with an Ehrlichia?

Unexplained Febrile Illnesses After Exposure to Ticks

The Ehrlichia are tick-borne rickettsial organisms that cause disease in animals throughout the world but that have been previously recognized as human pathogens only in Asia. We have identified six patients with serological evidence of recent infection with an Ehrlichia: a fourfold or greater rise or fall in titer to Ehrlichia canis. All of the patients reported recent tick bites. Rigors, myalgia, headache, nausea, and anorexia were each reported by five patients. Fever was present in all patients and was accompanied by relative bradycardia and leukopenia in five patients, thrombocytopenia and abnormal liver function test results in four, and anemia in three. Five of the six patients were treated with tetracycline hydrochloride, and all recovered. Infection with Ehrlichia should be considered in patients with unexplained febrile illnesses after tick exposure.

Incomplete Kawasaki disease with coronary artery involvement

We report four patients with Kawasaki disease in whom characteristic coronary artery abnormalities developed after illnesses that did not meet diagnostic criteria. An additional patient lacked a history of acute manifestations of Kawasaki disease, but severe Kawasaki-like arterial changes were noted at autopsy. Fever was present in four of the five patients, in three lasting from 7 to 14 days. Despite manifestation of few classic acute clinical features of Kawasaki disease, three of four patients had desquamation of the fingers and toes 10 to 14 days after onset of illness, and the fifth had desquamation several months prior to death. These patients were seen over a 2-year period during which 22 other children were seen with Kawasaki disease with coronary artery abnormalities. Thus, strict adherence to currently accepted criteria for diagnosis of Kawasaki disease may lead to failure to recognize incomplete forms of this illness, with potential sequelae of myocardial infarction or sudden death. This finding suggests that children with prolonged unexplained febrile illnesses, especially those associated with subsequent peripheral desquamation, should undergo echocardiography 3 to 4 weeks after onset of the illness. This practice would help to identify those patients with illnesses characterized by incomplete diagnostic criteria but in whom significant coronary abnormalities develop.

Transfusion malaria in the United States, 1972-1981.

Twenty-six cases of transfusion-induced malaria were reported in the United States from 1972 through 1981. In nine patients malaria was due to Plasmodium malariae; eight, P. falciparum; eight, P. vivax; and one, P. ovale. Four patients died. The estimated rate of transfusion malaria for this period was 0.25 cases per million donor units collected. Of the 18 cases in which a specific infective blood donor could be identified, at least nine of the donors should have been rejected for blood donation because of recent residence or travel to a malarious area. Among 17 patients for whom the national origin of the implicated blood donor was reported, 12 were born in malarious countries. We propose minor changes in donor procedures and standards, including stricter criteria for donors born in malarious countries. Potential donors should be deferred for 3 years after an unexplained febrile illness occurring 1 year after exposure to malaria.

HLA-B27-associated spondyloarthritis and enthesopathy in childhood: Clinical, pathologic, and radiographic observations in 58 patients

HLA-B27 typing of all arthritic children helped to identify and focus attention on a subset whose disease was pathogenetically related to and demonstrated clinical features of ankylosing spondylitis and Reiter syndrome, but only rarely fulfilled current diagnostic criteria for those disorders (spondyloarthritis). In contrast to other forms of childhood arthritis, enthesopathy (inflammation at the sites of attachment of ligaments and tendons to bone) was a prominent feature in 75%; a family history of similar arthritis was obtained from 60%; boys were more frequently affected (2:1); urethritis, acute iritis, conjunctivitis, or keratoderma blennorrhagicum occurred at some time in 42%; and the initial attack followed an unexplained febrile illness, known dysentery or urethritis, or severe musculoskeletal trauma in 41%. The arthritis was generally pauciarticular, asymmetric, and primarily in the feet and large joints of the lower extremities. Distinctive radiographic features included periostitis, severe osteopenia, calcaneal erosions, and heel spurs; three of 58 had rapid destruction of a single joint. Only ten patients (all boys) were found to have radiographic sacroiliitis after an average of five years of disease, and only three had the Reiter triad. The lifetime risk of sacroiliitis and spinal ankylosis can only be determined by long-term follow-up of such prospectively identified groups of spondyloarthritic children.