Convalescent Serology Research Articles

Serologic Testing for Rocky Mountain Spotted Fever in a Low-Incidence Region.

Tick-borne diseases have grown in incidence over recent decades. As a result, diagnostic testing has become more common, often performed as broad antibody-based panels for multiple tick-transmitted pathogens. Rocky Mountain spotted fever (RMSF) is rare in our region yet may cause severe morbidity, leading to diagnostic screening in low-risk patients. We sought to describe trends in RMSF diagnostic testing, rate of IgG seropositivity, and clinical features of those tested. We performed a retrospective chart review of patients ≤21 years old undergoing testing for RMSF and/or with an ICD-9/10 code for RMSF. Patients were categorized by infection likelihood based on clinical and laboratory criteria adapted from Centers for Disease Control and Prevention's (CDC) case definition of spotted fever rickettsioses. Clinical data were collected and analyzed with descriptive statistics. One hundred and seventy patients were included. 5.8% met CDC criteria for rickettsial infection, 6.5% had an elevated IgG titer but lacked suggestive symptoms, and 87.6% had a negative IgG titer. Many patients tested were unlikely to have RMSF, including 50% lacking fever, 20% lacking any RMSF "classic triad" symptoms, 13% without acute illness, and 22% tested during months with low tick activity. Convalescent serology was performed in 7.6% of patients and none underwent Rickettsia rickettsii polymerase chain reaction (PCR) testing. Diagnostic testing was frequently performed in patients unlikely to have RMSF. We identified many opportunities for improving test utilization. Reserving testing for those with higher pretest probability, performing convalescent serology, and utilizing PCR may improve the accuracy of RMSF diagnosis and reduce clinical challenges stemming from inappropriate testing.

“Leopards do not change their spots:” tick borne disease symptomology case report

BackgroundHuman Monocytic Ehrlichiosis is caused by infection with the bacteria Ehrlichia chaffeensis through the bite of an infected lone star tick (Amblyomma americanum). Patients infected with Human Monocytic Ehrlichiosis often present with symptoms including fever, headache, myalgia, and occasionally a macular rash. The presence of other endemic tick-borne diseases with similar symptoms, such as Rocky Mountain Spotted Fever, complicate the diagnosis of Human Monocytic Ehrlichiosis.Case presentationA patient developed a fever, diffuse myalgia, headache, and a non-productive cough 5 days after a fishing trip in late May in central North Carolina. Over the course of the illness the patient’s symptoms worsened, with arthralgia, bilateral lower extremity erythema and edema, and a developing bilateral rash on the palms. With testing that revealed elevated liver enzymes, a potential for recent tick exposure (e.g., fishing trip), presentation during tick season, and the development of a rash, Rocky Mountain Spotted Fever and Human Monocytic Ehrlichiosis were considered. The patient was prescribed a seven-day course of oral doxycycline and cefalexin, which would provide coverage from Rickettsia, Ehrlichia and gram-positive bacteria typically responsible for cellulitis. Many of the patient’s symptoms resolved or improved, although the right shoulder remained painful to active movement. The patient was prescribed another seven-day course of doxycycline due to his perceived incomplete response to the first course. Approximately 5 weeks after symptom onset (D0 + 36), the patient followed up with a provider for convalescent testing and counseling. Convalescent Ehrlichia and Rickettsia serological tests were ordered. The acute Ehrlichia serology and acute Rickettsia serology were originally non-reactive with both titers measured at < 1:64. Convalescent serology, ordered 28 days after the acute sample collection, showed a greater than four-fold increase in the Ehrlichia IgG titer (1:256), satisfying clinical and laboratory case definitions for ehrlichiosis. In follow-up, 3 weeks later (D0 + 57), the patient reported that most of his pain had subsided, though he still occasionally got shooting nerve pain when exercising.ConclusionThis case of Human Monocytic Ehrlichiosis in North Carolina exemplifies the need for a knowledge of spatial epidemiological patterns and clinical manifestations in the diagnosis of tick-borne diseases.

Plasma Rotavirus-specific IgA and Risk of Rotavirus Vaccine Failure in Infants in Malawi.

BackgroundRotavirus vaccine efficacy is reduced in low-income populations, but efforts to improve vaccine performance are limited by lack of clear correlates of protection. While plasma rotavirus (RV)-specific IgA appears strongly associated with protection against rotavirus gastroenteritis in high-income countries, weaker association has been observed in low-income countries. We tested the hypothesis that lower RV-specific IgA is associated with rotavirus vaccine failure in Malawian infants.MethodsIn a case-control study we recruited infants presenting with severe rotavirus gastroenteritis following monovalent oral rotavirus vaccination (RV1 vaccine failures). Conditional logistic regression was used to determine the odds of rotavirus seronegativity (RV-specific IgA<20 U/mL) in these cases compared 1:1 with age-matched, vaccinated, asymptomatic community controls. Plasma RV-specific IgA was determined by ELISA for all participants at recruitment, and for cases at 10 days post symptom onset. Rotavirus infection and genotype were determined by antigen testing and RT-PCR respectively.ResultsIn 116 age-matched pairs, infants with RV1 vaccine failure were more likely to be RV-specific IgA seronegative than controls: OR 3.1 (95%CI 1.6-5.9), p=0.001. In 60 infants with convalescent serology, 42/45 (93%, 95%CI 81-98%) infants seronegative at baseline became seropositive. Median rise in RV-specific IgA concentration following acute infection was 112.8 (IQR 19.1-380.6) fold.ConclusionsIn this vaccinated population with high residual burden of rotavirus disease, RV1 vaccine failure was associated with lower RV-specific IgA, providing further evidence of RV-specific IgA as a marker of protection. Robust convalescent RV-specific IgA response in vaccine failures suggests differences in wild-type and vaccine-induced immunity, which informs future vaccine development.

442. Common symptoms of outpatient COVID-19 compared to non-COVID-19 Cases: A prospective epidemiologic study in a major US metropolitan area

BackgroundThe majority of novel coronavirus 2019 (COVID-19) cases is comprised of non-critically ill adults. However, the medical epidemiology and clinical profile for mild COVID-19 is poorly described in the United States.MethodsWe prospectively recruited 151 mildly symptomatic adults from Emory Healthcare COVID-19 screening clinics in Atlanta, Georgia from March 18 to June 16, 2020. Interview-based questionnaires captured participants’ demographics, epidemiological history, and clinical features. Nasopharyngeal swabs were collected to test for SARS-CoV-2 by RT-PCR. Convalescent serum (13–74 days post symptom onset) from 19 participants was tested by an IgG ELISA. Descriptive and χ 2 analyses were performed to determine the characteristics of COVID-19 cases compared to patients who tested negative.ResultsA total of 151 patients were recruited. The majority were non-Hispanic white (51%), female (60%), middle-aged adults (46.3 y +/-15). Twenty-seven (17.9%) tested positive for SARS-CoV-2 and most frequently reported fever (63%), cough (67%), fatigue (56%), and myalgias (56%). See Table 1. Fever was statistically more common in positive cases vs negative (63% vs 34%, p = 0.005). Cases also experienced loss of taste (22%) and loss of smell (19%) more frequently than non-cases (p=0.01 and p=0.03). Diarrhea (22% vs 23%) and shortness of breath (33% vs 36%) did not differ significantly between groups. None of the 14 PCR-negative participants tested positive for SARS-CoV-2-specific IgG and 3 out of 5 COVID-19 cases tested positive for SARs-CoV-2-specific IgG. ConclusionMild COVID-19 cases reported fever, loss of smell and loss of taste significantly more than non-COVID-19 cases. Strong correlations between anosmia and ageusia with COVID-19 have been reported elsewhere, however these symptoms were only present in 19–22% of cases at the time of testing, limiting their utility for clinical diagnosis. Also, none of the PCR-negative participants tested positive for convalescent serology, supporting good sensitivity and negative predictive value of the RT-PCR test used in our clinic. Symptoms alone cannot differentiate COVID-19 from other illnesses, highlighting the critical need for widely available and highly sensitive and specific diagnostic tests.Disclosures All Authors: No reported disclosures

Searching and Finding the Hidden Treasure: A Retrospective Analysis of Rickettsial Disease Among Dutch International Travelers.

BackgroundRickettsial disease (RD) is a prevalent and underestimated cause of febrile illness worldwide, especially in the absence of an inoculation eschar. We attempted to quantify this underestimation at our clinic, by investigating past cases of febrile illness in travelers who had tested negative for leptospirosis, a disease that can initially present similarly to non-eschar RD, and which we routinely consider when other important causes of unspecified febrile illness have tested negative.MethodsWe performed a retrospective analysis in febrile returned travelers from Asia, Africa, or the Americas between 2010 and 2017, who had tested negative for leptospirosis. Serologic immunofluorescence assays were performed for Orientia tsutsugamushi (scrub typhus), typhus group, and spotted fever group RD. We performed a medical records review of all patients who tested positive. In case of a fitting medical history, cases were deemed either confirmed (based on convalescent serology) or suspected (based on single serology).ResultsAmong 97 patients, convalescent serology was available in 16 (16.5%) patients, and a single serology in 81 (83.5%) patients. RD was the likely diagnosis in 8 of 16 (50.0%) patients with convalescent serology, and in 8 of 81 (9.9%) with single serology. Of the 16 confirmed/suspected cases, 11 (69%) had been missed and 7 (44%) had not received adequate empiric antibiotic therapy.ConclusionsThis study shows that non-eschar RD is an important and poorly recognized cause of illness in travelers, even in a specialized travel clinic. A lower threshold to test and treat for RD is warranted in returning travelers with febrile illness.

An unusual presentation of a known condition: Q fever manifesting as an acute abdomen

Q fever is an endemic zoonotic infection in Australia cause by Coxiella burnetii. It has been recognised in other parts of the world, especially among livestock rearing occupations, stock yard and abattoir workers. Majority (65%) of patients infected with C.burnetti are asymptomatic while symptoms similar to those of respiratory and hepatitis are the most common making diagnosis difficult in the early stages. We report a case of a young man who was exposed to and infected with Q fever as an occupational hazard. He presented in an unusual way with the predominant initial symptoms of abdominal pain, fever, hepatitis and sterile peritonitis necessitating an emergency surgical procedure to explore a suspected surgical abdomen. Respiratory involvement ensued only several days later. The diagnosis of Q fever was confirmed with positive convalescent serology phase II IgM and IgG antibodies to Coxiella burnetii. A marked clinical response to doxycycline pending serological confirmation was supportive of this highly suspected diagnosis in an at-risk patient.

Serological response to influenza vaccination among adults hospitalized with community‐acquired pneumonia

Ninety‐five adults enrolled in the Etiology of Pneumonia in the Community study with negative admission influenza polymerase chain reaction (PCR) tests received influenza vaccination during hospitalization. Acute and convalescent influenza serology was performed. After vaccination, seropositive (≥1:40) hemagglutination antibody titers (HAI) were achieved in 55% to influenza A(H1N1)pdm09, 58% to influenza A(H3N2), 77% to influenza B (Victoria), and 74% to influenza B (Yamagata) viruses. Sixty‐six (69%) patients seroconverted (≥4‐fold HAI rise) to ≥1 strain. Failure to seroconvert was associated with diabetes, bacterial detection, baseline seropositive titers for influenza B (Yamagata), and influenza vaccination in the previous season.

Clinical evaluation and validation of laboratory methods for the diagnosis of Bordetella pertussis infection: Culture, polymerase chain reaction (PCR) and anti-pertussis toxin IgG serology (IgG-PT).

IntroductionThe appropriate use of clinically accurate diagnostic tests is essential for the detection of pertussis, a poorly controlled vaccine-preventable disease. The purpose of this study was to estimate the sensitivity and specificity of different diagnostic criteria including culture, multi-target polymerase chain reaction (PCR), anti-pertussis toxin IgG (IgG-PT) serology, and the use of a clinical case definition. An additional objective was to describe the optimal timing of specimen collection for the various tests.MethodsClinical specimens were collected from patients with cough illness at seven locations across the United States between 2007 and 2011. Nasopharyngeal and blood specimens were collected from each patient during the enrollment visit. Patients who had been coughing for ≤ 2 weeks were asked to return in 2–4 weeks for collection of a second, convalescent blood specimen. Sensitivity and specificity of each diagnostic test were estimated using three methods—pertussis culture as the “gold standard,” composite reference standard analysis (CRS), and latent class analysis (LCA).ResultsOverall, 868 patients were enrolled and 13.6% were B. pertussis positive by at least one diagnostic test. In a sample of 545 participants with non-missing data on all four diagnostic criteria, culture was 64.0% sensitive, PCR was 90.6% sensitive, and both were 100% specific by LCA. CRS and LCA methods increased the sensitivity estimates for convalescent serology and the clinical case definition over the culture-based estimates. Culture and PCR were most sensitive when performed during the first two weeks of cough; serology was optimally sensitive after the second week of cough.ConclusionsTiming of specimen collection in relation to onset of illness should be considered when ordering diagnostic tests for pertussis. Consideration should be given to including IgG-PT serology as a confirmatory test in the Council of State and Territorial Epidemiologists (CSTE) case definition for pertussis.

Use of Multiple Imputation to Estimate the Proportion of Respiratory Virus Detections Among Patients Hospitalized With Community-Acquired Pneumonia.

Real-time polymerase chain reaction (PCR) on respiratory specimens and serology on paired blood specimens are used to determine the etiology of respiratory illnesses for research studies. However, convalescent serology is often not collected. We used multiple imputation to assign values for missing serology results to estimate virus-specific prevalence among pediatric and adult community-acquired pneumonia hospitalizations using data from an active population-based surveillance study. Presence of adenoviruses, human metapneumovirus, influenza viruses, parainfluenza virus types 1-3, and respiratory syncytial virus was defined by positive PCR on nasopharyngeal/oropharyngeal specimens or a 4-fold rise in paired serology. We performed multiple imputation by developing a multivariable regression model for each virus using data from patients with available serology results. We calculated absolute and relative differences in the proportion of each virus detected comparing the imputed to observed (nonimputed) results. Among 2222 children and 2259 adults, 98.8% and 99.5% had nasopharyngeal/oropharyngeal specimens and 43.2% and 37.5% had paired serum specimens, respectively. Imputed results increased viral etiology assignments by an absolute difference of 1.6%-4.4% and 0.8%-2.8% in children and adults, respectively; relative differences were 1.1-3.0 times higher. Multiple imputation can be used when serology results are missing, to refine virus-specific prevalence estimates, and these will likely increase estimates.

Trichinella Nativa Outbreak With Rare Thrombotic Complications Associated With Meat From a Black Bear Hunted in Northern Ontario.

Although trichinellosis is known to cause thrombotic disease, serious thrombotic events are rare and have not been previously associated with Trichinella nativa infection. Patient interviews and medical chart reviews were conducted on 10 men who became ill following consumption of a common source of black bear meat. Trichinella serology on patient sera as well as polymerase chain reaction (PCR) and larval identification of the meat samples was conducted. All 10 exposed individuals developed an acute illness clinically compatible with trichinellosis, characterized by fever, abdominal pain, and diarrhea, along with eosinophilia ranging from 0.9 × 109/L to 6.1 × 109/L. Within 2 weeks of the diarrheal illness, systemic symptoms developed in all exposed individuals characterized by fever, myalgia, periorbital edema, and fatigue. ST-elevation myocardial infarction and sinus venous tract thrombosis occurred as a complication of trichinellosis in 2 patients. Acute serology was nonreactive in all patients, though convalescent serology was reactive in 6 of 8 (75%) patients for whom sera was available. Multiplex PCR identified T. nativa from the bear meat, and was corroborated by microscopic larval identification. We report a 100% attack rate of T. nativa from bear meat among those who were exposed, and demonstrate that this species can cause serious thrombotic complications of trichinellosis in humans. Education of hunters and the public regarding the importance of proper preparation of wild game prior to ingestion is warranted.

Bartonella-related multifocal bone marrow enhancement without osteolysis

Multifocal bone marrow disease due to Bartonella henselae is rare and is typically accompanied by osteolytic disease. A 10-year-old female presented with advanced disease, including prolonged fever, back pain, and radiographic multifocal pelvic bone marrow enhancement without osteolysis. Acute and convalescent serology supported the diagnosis of B. henselae infection. However, bone marrow aspirates lacked granulomas and inflammatory infiltrate. The patient fully recovered without specific antimicrobial therapy. B. henselae produces a fever and pain syndrome with multifocal bone marrow enhancement in the absence of osteolytic lesions.

Acute encephalitis with abnormal liver function tests: answer

Encephalopathy with fever has broad differentials including infectious, parainfectious, immune, paraneoplastic and metabolic causes. This Bartonella encephalitis patient demonstrates the importance of obtaining a complete environmental history, as the patient had five pet cats. Bartonella is a genus of gram negative bacteria, and the Bartonella henselae species is a causative agent of cat scratch disease, characterised by lymphadenopathy and fever. The serum testing was positive for B. henselae, with an immunoglobulin M (IgM) titre of 20 and an immunoglobulin G (IgG) titre of 512. The convalescent serology 6 months later, showed a fall in IgM titre to <20 and an IgG titre of 128. The patient was treated with acyclovir and ceftriaxone at presentation, with the addition of clarithromycin. She made a good functional recovery and was independent at discharge, with no new symptoms at the 24 month follow-up. A wide range of neurologic manifestations have been described in patients with Bartonella, including encephalopathy, transverse myelitis, polyradiculopathy, neuroretinitis, and cerebellar ataxia [1–4]. The patients with encephalopathy typically develop abrupt confusion and disorientation, which may progress to coma. Many of these patients will develop focal neurologic findings such as hemiparesis and seizures, due to the associated cerebral

Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: acute and convalescent serology among a prospective cohort of early Lyme disease patients.

Two-tier serology is often used to confirm a diagnosis of Lyme disease. One hundred and four patients with physician diagnosed erythema migrans rashes had blood samples taken before and after 3 weeks of doxycycline treatment for early Lyme disease. Acute and convalescent serologies for Borrelia burgdorferi were interpreted according to the 2-tier antibody testing criteria proposed by the Centers for Disease Control and Prevention. Serostatus was compared across several clinical and demographic variables both pre- and post-treatment. Forty-one patients (39.4%) were seronegative both before and after treatment. The majority of seropositive individuals on both acute and convalescent serology had a positive IgM western blot and a negative IgG western blot. IgG seroconversion on western blot was infrequent. Among the baseline variables included in the analysis, disseminated lesions (p < 0.0001), a longer duration of illness (p < 0.0001), and a higher number of reported symptoms (p = 0.004) were highly significantly associated with positive final serostatus, while male sex (p = 0.05) was borderline significant. This variability, and the lack of seroconversion in a subset of patients, highlights the limitations of using serology alone in identifying early Lyme disease. Furthermore, these findings underline the difficulty for rheumatologists in identifying a prior exposure to Lyme disease in caring for patients with medically unexplained symptoms or fibromyalgia-like syndromes.

Severe acute respiratory infections caused by 2009 pandemic influenza A (H1N1) among American Indians--southwestern United States, May 1-July 21, 2009.

During April-July 2009, U.S. hospitalization rates for 2009 pandemic influenza A (H1N1) virus (H1N1pdm09) infection were estimated at 4·5/100 000 persons. We describe rates and risk factors for H1N1pdm09 infection among American Indians (AIs) in four isolated southwestern U.S. communities served by the Indian Health Service (IHS). We reviewed clinical and demographic information from medical records of AIs hospitalized during May 1-July 21, 2009 with severe acute respiratory infection (SARI). Hospitalization rates were determined using denominator data provided by IHS. H1N1pdm09 infection was confirmed with polymerase chain reaction, rapid tests, or convalescent serology. Risk factors for more severe (SARI) versus milder [influenza-like illness (ILI)] illness were determined by comparing confirmed SARI patients with outpatients with ILI. Among 168 SARI-hospitalized patients, 52% had confirmed H1N1pdm09 infection and 93% had >1 high-risk condition for influenza complications. The H1N1pdm09 SARI hospitalization rate was 131/100 000 persons [95% confidence interval (CI), 102-160] and was highest among ages 0-4 years (353/100 000; 95% CI, 215-492). Among children, asthma (adjusted odds ratio [aOR] 3·2; 95% CI, 1·2-8·4) and age<2 years (aOR 3·8; 95% CI, 1·4-10·0) were associated with H1N1pdm09 SARI-associated hospitalization, compared with outpatient ILI. Among adults, diabetes (aOR 3·1; 95% CI, 1·5-6·4) was associated with hospitalization after controlling for obesity. H1N1pdm09 hospitalization rates among this isolated AI population were higher than reported for other U.S. populations. Almost all case patients had high-risk health conditions. Prevention strategies for future pandemics should prioritize AIs, particularly in isolated rural areas.

Low utilisation of diagnostic microbiology for community acquired pneumonia in regional Victoria

AimsDiagnostic microbiology for community acquired pneumonia (CAP) provides useful information for patient management, infection control and epidemiological surveillance. Newer techniques enhance that information and the time interval for obtaining results. An audit of diagnostic microbiology utilisation, microbiological aetiology, and influence of results on prescribing practices in CAP in a regional Australian hospital setting was performed.MethodsClinical, microbiological and outcome data were collected by medical record review of patients discharged from Ballarat Hospital with a diagnosis of CAP over a 12 month period.ResultsOf 184 identified CAP episodes, 47 (25.5%) had no diagnostic microbiology performed. Respiratory virus polymerase chain reaction (PCR) was rarely performed (2.7% of all episodes). Acute serology was frequently requested, however paired acute and convalescent serology was infrequently performed (5/75 testing episodes; 6.7%). CAP severity was not correlated with microbiological investigation intensity. The most common pathogens identified were Streptococcus pneumoniae and Mycoplasma pneumoniae (5.4% and 2.2%, respectively). Diagnostic testing appeared to rarely influence antimicrobial prescribing.ConclusionsIn this setting, diagnostic microbiological tests such as respiratory virus PCR and urinary antigen tests are under-utilised. In contrast, sputum and serological investigations are commonly requested, however rarely influence practice. Interventions to facilitate efficient usage of diagnostic microbiology are required.

Knowledge, Attitudes, and Practices for Diagnosing Breakthrough Varicella in the Outpatient Setting

We assessed provider knowledge, attitudes, and practices for the management of breakthrough varicella and identified barriers to implementation of laboratory testing and reporting. We surveyed 145 health-care providers (HCPs) from 30 pediatric practices in Philadelphia who did not have a history of laboratory testing for breakthrough varicella. The self-administered survey instrument collected information on clinicians' practices for management of children presenting with rash, infection-control strategies, reporting to public health agencies, and laboratory testing. Among the 144 HCPs who completed the survey, 73 (51%) had practiced for more than 10 years. While 115 HCPs (80%) would elect to evaluate a child with rash in the office, only 19 (13%) would submit diagnostics. When patients had a known recent exposure to varicella, 84 HCPs (58%) would use laboratory tests: 40% would use direct fluorescent antibody staining on a specimen from a cutaneous lesion, 24% would use polymerase chain reaction on a lesion specimen, 21% would use acute and convalescent serology, and 10% would use other tests. While waiting for test results, 82 HCPs (57%) would advise that the child be kept at home, 39 (27%) would notify the local health department, and 33 (23%) would inform the school nurse. As varicella becomes increasingly uncommon, laboratory confirmation becomes more critical for appropriate diagnosis, similar to poliomyelitis and measles. Our findings suggest that HCPs need further education regarding laboratory confirmation, containment, and reporting of breakthrough varicella.

Perimyocarditis Due to Yersinia enterocolitica in an Adult

We report an extremely rare case of perimyocarditis caused by Yersinia enterocolitica serotype 0:3 in a previously healthy young adult. To our knowledge, this is the first reported case of perimyocarditis in the Czech Republic and one of a limited number of reports of Y. enterocolitica carditis described globally. Upon admission to our institution, transient pericardial friction rub was audible. Electrocardiogram showed diffuse concave ST elevation, and PR segment depression was not observed. Increased cTnI (8.78 µg/L) and C-reactive protein levels (82 mg/mL) accompanied with elevated blood cell count (10.4 × 109/L) were also observed. A transthoracic echocardiography revealed a diffuse mild left ventricular hypokinesis. Anti-Y. enterocolitica serotype 0:3 antibodies were detected, and a treatment with cotrimoxazole (biseptol) was initiated. The IgM value was 112; IgG and IgE values were less than 10. The patient was discharged from the hospital in a hemodynamically stable condition after 9 days of treatment. Clinical and laboratory follow-up was performed 14 days after hospital discharge. The convalescent serology for Y. enterocolitica serotype 0:3 demonstrated conversion to positive IgG for Yersinia because the IgG value was more than 1000; IgM and IgA values were 116.8 and more than 50, respectively. Transthoracic echocardiography showed no remarkable changes compared with the previous study. C-reactive protein value decreased to 1.7 mg/L, the white blood cell count was 6.3 × 109/L, and the cTnI was less than 0.03 µg/L.

Acute Dengue Fever Causes False-Positive Reactivity in OraQuick Rapid HIV-1/2 Antibody Test

To the Editors: The OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, from OraSure Technologies Inc., detects antibodies to HIV-1 and HIV-2 in 20 minutes. This immunoassay can be performed on oral fluid, fingerstick whole blood, venipuncture whole blood, and plasma specimens. The manufacturer reports a sensitivity of 99.3% (95% confidence interval: = 98.4% to 99.7%) and specificity of 99.8% (95% confidence interval: = 99.6% to 99.9%) for use of the test with oral fluid specimens.1 However, false-positive results have been detected, including in test kits close to the expiration date. One study found a false-positive rate of 1.17% in test kits used with ≤1 month remaining until expiration.2 It is noted that these results came from an older version of the OraQuick ADVANCE test kit. Accuracy of both oral and blood HIV screening tests may also be affected by concomitant tropical infections. In sub-Saharan Africa, false-positive HIV enzyme-linked immunosorbent assay (ELISA) results were associated with a diagnosis of human African trypanosomiasis,3 urinary schistosomiasis,4 uncomplicated malaria,5 and visceral leishmaniasis.6 These false-positive results in HIV antibody detection testing have been attributed to polyclonal B-cell activation and/or high concentration of rheumatoid factor-like anti-immunoglobulin antibodies seen in these infections.3-6 In Colombia, 1 study postulated that parasitic proteins similar to the reverse transcriptase could be a possible cause of false positive HIV ELISA tests in patients infected by Trypanosoma cruzi.7 Since December 2008, we have been using the OraQuick test kit on oral fluid as part of a study in the Duke University Hospital Emergency Department to determine whether rapid HIV testing can be effectively offered and accepted as a routine screening test. Recently, a false-positive result occurred in a patient presenting with acute Dengue fever. The patient had just returned to the United States after traveling abroad to the island of Guadeloupe, French West Indies, for 3 weeks where she recalled receiving multiple mosquito bites. She was admitted to Duke University Hospital after presenting to the Emergency Department with acute HIV-like symptoms of recurrent fevers, night sweats, nausea, vomiting, headache, joint aches, and rash. Her initial temperature was 37.3°C, but she reported fevers up to 39.4°C at home. The patient had an erythematous, raised, nonpruritic maculopapular rash on her lower extremities. Upon presentation, her white blood cells was low at 1600 cells × 109/L with an absolute lymphocyte count of 500. Her platelets were low at 88 × 109/L and ultimately dropped to 47 during her hospitalization. Her aspartate aminotransferase was slightly elevated at 77 U/L. In Guadeloupe, she had serologies drawn, which were positive for Dengue. Acute and convalescent serologies drawn at Duke were sent to the North Carolina State Laboratory and also confirmed to be positive. As there are no reports of malaria in Guadeloupe,8 a blood smear was not performed. Her initial and repeat OraQuick oral swabs were positive. The patient denied any recent high-risk behaviors that would place her at risk for acute HIV infection and had tested negative for HIV 2 years ago. As part of our protocol for confirmation of a preliminary reactive test, a Western Blot was performed which was indeterminate with a faint band at p24. Further workup demonstrated a negative serum HIV ELISA and an undetectable HIV viral load. Although both OraQuick tests used had expiration dates ≤1 month from time of use, it is not clear if this was a contributing factor as we were using the newer version of the kit. More likely, the diagnosis of acute Dengue contributed to the false-positive result. There is only one other report documenting HIV-1 false-positive rapid ELISA tests in patients with Dengue fever.9 In this study, false-positive HIV screening tests on sera occurred in 4 of the 9 patients with Dengue, though there was no information on the mechanism by which Dengue infection triggered the false-positive reactivity. Our findings indicate that false positives may occur with rapid HIV assays, particularly in the case of concomitant infections. This may be a greater concern in resource-poor regions where diseases such as Dengue are most prevalent and as rapid HIV tests become more widely used. Alice Mao Chidera Obi-Gwacham Tamsey Hill, DMin Catherine Ryan, MSHSA Arthur Hendricks, MDiv Mehri McKellar, MD Division of Infectious Diseases and Department of Medicine, Duke University Durham, NC

Tularemia: Retrospective Review of 10 Years’ Experience in Arkansas

The purpose of this study is to review all cases of tularemia, a tick-borne illness, among inpatients at Arkansas Children's Hospital (ACH) from 1996-2006 to discuss clinical presentation, diagnosis and treatment. Records of the Infectious Disease Section were reviewed to identify cases of suspected or proven tularemia. Seventeen patients presented with ulceroglandular tularemia and thirteen with glandular disease. Most patients had been ill for 10-14 days prior to admission and were evaluated at least once by another physician. Serology was positive in 77% of patients, including several positive on convalescent testing alone. Most patients responded well to treatment with gentamicin. This series emphasizes the importance of tularemia as an early consideration among children with fever and lymphadenopathy in Arkansas. Convalescent serology is an important tool, as many patients will remain seronegative early in illness. Gentamicin remains effective treatment and should be considered first-line therapy for suspected tularemia.

The Role of β-Hemolytic Streptococci in Causing Diffuse, Nonculturable Cellulitis

Staphylococcus aureus and beta-hemolytic streptococci (BHS) are the 2 main types of bacteria causing soft-tissue infections. Historically, BHS were believed to be the primary cause of diffuse, nonculturable cellulitis. However, with the recent epidemic of community-associated methicillin-resistant S aureus (MRSA) causing culturable soft-tissue infections, it is currently unclear what role either of these bacteria has in cases where the cellulitis is diffuse and nonculturable. This uncertainty has led to broad-spectrum and haphazard use of antibiotics for this infection type, which has led to increased risk of adverse drug reactions, health care costs, and emergence of resistance in bacteria. To investigate this issue, we conducted a prospective investigation between December 2004 and June 2007, enrolling all adult patients admitted to the inpatient service at the Olive View-UCLA Medical Center, a county hospital of Los Angeles, with diffuse, nonculturable cellulitis. Acute and convalescent serologies for anti-streptolysin-O and anti-DNase-B antibodies were obtained. Patient data were analyzed for response to beta-lactam antibiotics. The primary outcome was the proportion of these cases caused by BHS, as diagnosed by serologies and/or blood cultures, and the secondary outcome was the response rate of patients to beta-lactam antibiotics. Of 248 patients enrolled, 69 were dropped from analysis because of loss to follow-up or exclusion criteria. Of the 179 remaining patients, 73% of nonculturable cellulitis cases were caused by BHS. Analysis of outcomes to beta-lactam antibiotic treatment revealed that patients diagnosed with BHS had a 97% (71/73) response, while those who did not have BHS had a 91% (21/23) response, with an overall response rate of 95.8% (116/121). Results of this large, prospective study show that diffuse, nonculturable cellulitis is still mainly caused by BHS, despite the MRSA epidemic, and that for this infection type, treatment with beta-lactam antibiotics is still effective. A cost-effective, evidence-based algorithm can be useful for the empiric management of uncomplicated soft-tissue infections based on the presence or absence of a culturable source.