Fourfold Increase In Antibody Titer Research Articles

Seroconversion, genotyping, and potential mosquito vector identification of Japanese encephalitis virus in pig sentinel settings in Bali, Indonesia.

Despite the endemicity of Japanese encephalitis virus (JEV) in humans and animals in the Province of Bali, Indonesia, there is little data on whether seroconversion to the virus occurs in pigs, JEV genotypes circulating, and it's potential mosquito vectors in the area. The aims of this study were to (i) Determine whether JEV infection in Balinese pigs occurs before reaching their sexual maturity, (ii) identify the genotypes of circulating JEV, and (iii) identify potential JEV mosquito vectors at the study sites in urban and peri-urban areas of Bali. Sixteen 1-week-old Landrace piglets from two different sows were housed in Denpasar. Similarly, 18 one-week-old mixed-breed piglets of two different sows were housed in Badung Regency. The piglets were bled every 1 to 4 weeks for up to 24 weeks. Serum samples from the 11 piglets were tested for antibodies against JEV, and seroconversion-suspected sera were titrated using an enzyme-linked immunosorbent assay. Blood of seroconverted sera from pigs were tested using polymerase chain reaction (PCR) to detect the genetic sequence of JEV. The mosquitoes in the sentinels were trapped throughout the study period to identify the potential mosquito vectors of JEV. Antibodies were detected in most of the selected piglets' sera from weeks 1 to 24 of their age. However, sera of pig B9 collected from the sentinel setting in Badung Regency showed a four-fold increase in antibody titer from week 4 to week 8, indicating seroconversion. PCR testing of blood from B9 (pooled blood sample collected from week 5 to week 8) identified JEV nucleic acids, which were phylogenetically classified as belonging to the JEV genotype III. Meanwhile, 1271 of two genera of mosquitoes, Anopheles spp. and Culex spp. were trapped in the pig sentinels. JEV seroconversion likely occurs before the pig reaches sexual maturity in Badung Regency. Sequence data indicate that JEV genotype III is circulating in the pig sentinel setting in the regency; however, circulating genotypes need to be clarified through increased surveillance. Meanwhile, Culex spp. and most likely Culex quinquefasciatus and Anopheles spp. were the dominant mosquitoes present in the study sites set in the urban area of Denpasar and peri-urban areas of Badung, Bali, indicating that these are likely vectors in spread of JEV in the region.

Murine Typhus: A Review of a Reemerging Flea-Borne Rickettsiosis with Potential for Neurologic Manifestations and Sequalae.

Murine typhus is an acute febrile illness caused by Rickettsia typhi, an obligately intracellular Gram-negative coccobacillus. Rats (Rattus species) and their fleas (Xenopsylla cheopis) serve as the reservoir and vector of R. typhi, respectively. Humans become infected when R. typhi-infected flea feces are rubbed into flea bite wounds or onto mucous membranes. The disease is endemic throughout much of the world, especially in tropical and subtropical seaboard regions where rats are common. Murine typhus is reemerging as an important cause of febrile illness in Texas and Southern California, where an alternate transmission cycle likely involves opossums (Didelphis virginiana) and cat fleas (Ctenocephalides felis). Although primarily an undifferentiated febrile illness, a range of neurologic manifestations may occur, especially when treatment is delayed. Serology is the mainstay of diagnostic testing, but confirmation usually requires demonstrating seroconversion or a fourfold increase in antibody titer from acute- and convalescent-phase sera (antibodies are seldom detectable in the first week of illness). Thus, early empiric treatment with doxycycline, the drug of choice, is imperative. The purpose of this review is to highlight murine typhus as an important emerging and reemerging infectious disease, review its neurologic manifestations, and discuss areas in need of further study.

Evaluation Of Antibody Response To Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination In Patients With Lymphoid And Solid Organ Malignancies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. There is emerging evidence regarding suboptimal response to vaccination against COVID-19 in patients with hematologic and solid organ malignancies. We conducted a single-center prospective study assessing seroconversion in response to vaccination against COVID-19 in 53 patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), and solid organ malignancies. A quantitative immunoassay of IgG antibodies to SARS-CoV-2 Spike (S) protein was measured prior to vaccination and at 2 weeks after completion of two-dose vaccination series. A fourfold increase in antibody titers was considered positive seroconversion. Through a predesigned survey, patients also self-reported side effects from each dose of vaccination. Seroconversion on vaccination was seen in 6/12 (50%) patients with CLL, 7/11 (63.6%) patients with NHL, 9/10 (90%) patients with MM, and 17/20 (85%) patients with solid organ malignancy. Only 6 of the 14 (42.8%) patients currently on or with previous history of rituximab use seroconverted. Injection site soreness was the most reported side effect. The only severe side effect occurred in a patient with solid organ malignancy who developed Parsonage-Turner syndrome. Patients with CLL and NHL appear less likely to respond to vaccination against COVID-19 in contrast to patients with MM or solid organ malignancies. Previous treatment with rituximab is a possible risk factor for suboptimal response to vaccination. These data highlight the importance of continuing risk mitigation strategies against COVID-19 in individuals with hematologic malignancy, particularly those with CLL or on treatment with rituximab.

Manifestations and Management of Flea-Borne Rickettsioses.

Murine typhus and flea-borne spotted fever are undifferentiated febrile illnesses caused by Rickettsia typhi and Rickettsia felis, respectively. These organisms are small obligately intracellular bacteria and are transmitted to humans by fleas. Murine typhus is endemic to coastal areas of the tropics and subtropics (especially port cities), where rats are the primary mammalian host and rat fleas (Xenopsylla cheopis) are the vector. In the United States, a cycle of transmission involving opossums and cat fleas (Ctenocephalides felis) are the presumed reservoir and vector, respectively. The incidence and distribution of murine typhus appear to be increasing in endemic areas of the US. Rickettsia felis has also been reported throughout the world and is found within the ubiquitous cat flea. Flea-borne rickettsioses manifest as an undifferentiated febrile illness. Headache, malaise, and myalgia are frequent symptoms that accompany fever. The incidence of rash is variable, so its absence should not dissuade the clinician to consider a rickettsial illness as part of the differential diagnosis. When present, the rash is usually macular or papular. Although not a feature of murine typhus, eschar has been found in 12% of those with flea-borne spotted fever. Confirmatory laboratory diagnosis is usually obtained by serology; the indirect immunofluorescence assay is the serologic test of choice. Antibodies are seldom present during the first few days of illness. Thus, the diagnosis requires acute- and convalescent-phase specimens to document seroconversion or a four-fold increase in antibody titer. Since laboratory diagnosis is usually retrospective, when a flea-borne rickettsiosis is considered, empiric treatment should be initiated. The treatment of choice for both children and adults is doxycycline, which results in a swift and effective response. The following review is aimed to summarize the key clinical, epidemiological, ecological, diagnostic, and treatment aspects of flea-borne rickettsioses.

Immunogenicity and Safety of Ebola Virus Vaccines in Healthy Adults’ Volunteers: A Systematic Review and Network Meta-Analysis

Background: Clinical development of Ebola virus vaccines was accelerated by the West African Ebola virus epidemic which remain the deadliest in history ever witnessed. We aimed to compare and rank Ebola virus vaccines according to their immunogenicity and safety. Methods: We conducted a network meta-analysis using random-effect model within a frequentist setting to obtain direct and indirect comparison of trials. We searched Medline, Embase, and the Cochrane library (CENTRAL) until March 31, 2019, for published phase I or II randomized controlled trials (RCTs) vaccine against Ebola virus in healthy adult’s volunteers. We used the Cochrane Risk of Bias Tools to evaluate RCTs methods, and we extracted the proportion or number of participants who seroconverted and reported adverse events. The primary outcome was immunogenicity assessed by the seroconversion rates, defined as number of participants in each group who showed at least a four-fold increase in antibody titer for enzyme-linked immunosorbent assay (ELISA) 28 days after vaccination. Findings: A total of 18 RCTs, which assessed 18 different treatments involving 58 comparisons and 3,633 participants were included in the analysis. The mean age of participants was between 18 and 65 years, and 59% of them were male. The overall quality of evidence was rated as moderate to low. For immunogenicity, 2,198 (61%) participants had seroconversion at 28-days post-vaccination, and the recombinant vesicular virus-based vaccine expressing a Zaire Ebolavirus glycoprotein (rVSVΔ-ZEBOV-GP) at dose of 2 × 107 was significantly the better vaccine (P-score 0·78). Among the 4,746 reported adverse event (AEs), 97 were severe. For the injection-site pain, a total of 1,222 AEs was reported, and Placebo was associated with few events (P-score 0·93). For fatigue (805 reported AEs) and for headache (1,103 reported AEs), the DNA-EBOV vaccine at dose of ≤ 4 mg was the best one with a P-score of 0·96 and 0·85 respectively. For myalgia, 759 AEs were reported, and the ChAd3 vaccine at dose of 1010 was associated with a lower risk (P-score 0·95). Among the 760 AEs reported for fever, the rVSV-ZEBOV vaccine at dose of ≤ 5 × 105 was ranked as the best one (P-score 0·78). Except for the fatigue AEs, no significant global heterogeneity was found. Interpretation: To prevent the next outbreak of Ebola virus disease, the rVSVΔ-ZEBOV-GP vaccine at dose of 2 × 107 appears as the best available option for sufficiently high immunogenicity. Ad5.ZEBOV (1·6 × 1011) might be a possible alternative for immunogenicity. For AEs, no evidence of the best one vaccine is emerged· Larger RCTs are need to clarify the best candidate vaccine in terms of immunogenicity and safety. Funding Statement: None. Declaration of Interests: The authors declare no competing interests in relation with this work. Ethics Approval Statement: The study protocol number registered in the International Register of Systematic Reviews (PROSPERO) was: CRD42018109473.

Infection with influenza A(H1N1)pdm09 during the first wave of the 2009 pandemic: Evidence from a longitudinal seroepidemiologic study in Dhaka, Bangladesh

BackgroundWe determined influenza A(H1N1)pdm09 antibody levels before and after the first wave of the pandemic in an urban community in Dhaka, Bangladesh.MethodsWe identified a cohort of households by stratified random sampling. We collected baseline serum specimens during July‐August 2009, just prior to the initial wave of the 2009 pandemic in this community and a second specimen during November 2009, after the pandemic peak. Paired sera were tested for antibodies against A(H1N1)pdm09 virus using microneutralization assay and hemagglutinin inhibition (HI) assay. A fourfold increase in antibody titer by either assay with a titer of ≥40 in the convalescent sera was considered a seroconversion. At baseline, an HI titer of ≥40 was considered seropositive. We collected information on clinical illness from weekly home visits.ResultsWe tested 779 paired sera from the participants. At baseline, before the pandemic wave, 1% overall and 3% of persons >60 years old were seropositive. After the first wave of the pandemic, 211 (27%) individuals seroconverted against A(H1N1)pdm09. Children aged 5‐17 years had the highest proportion (37%) of seroconversion. Among 264 (34%) persons with information on clinical illness, 191 (72%) had illness >3 weeks prior to collection of the follow‐up sera and 73 (38%) seroconverted. Sixteen (22%) of these 73 seroconverted participants reported no clinical illness.ConclusionAfter the first pandemic wave in Dhaka, one in four persons were infected by A(H1N1)pdm09 virus and the highest burden of infection was among the school‐aged children. Seroprevalence studies supplement traditional surveillance systems to estimate infection burden.

A Survey of Acute Q Fever among Patients with Brucellosis-Like and Atypical Pneumonia Symptoms Who Are Referred to Qaemshahr Razi Hospital in Northern Iran (2014-2015)

<p><strong>INTRODUCTION</strong><strong>:</strong> Coxiella burnetii is the etiologic agent of the zoonotic disease of Q fever which causes lots of morbidities and mortalities every year. The main route of human infection is inhalation of contaminated aerosols; however, consumption of contaminated dairy products is the second cause. Mazandaran province is one of the main livestock centers of the country and consumption of raw dairy in the region is quite common. There isn’t any data about Q fever incidence in this region. It seems that most cases are undiagnosed. Our main target is to prove existence of Q fever human cases in Mazandaran province. We evaluated suspect Q fever cases to demonstrate its incidence and identify the risk factors.</p><p><strong>MATERIAL </strong><strong>& METHODS</strong>: In this cross-sectional study, 56 Patients including 36 patients with brucellosis-like systemic symptoms identified by negative Wright, Coomb's Wright and 2-mercaptoethanol tests as well as 20 patients with symptoms of atypical pneumonia who did not respond to conventional therapy were enrolled. At the beginning of hospitalization and 3-4 weeks later, 10cc blood was obtained from each of 56 patients who referred for a second blood sampling. Demographic, epidemiological, and clinical manifestations of Q fever and clinical changes were completed for each patient. The samples were evaluated quantitatively in terms of the presence of phase II IgG antibodies against Coxiella burnetii by ELISA method. Acute Q fever was confirmed by line-sero conversion (change of antibody from negative to positive) or fourfold antibody rising titer in each patient. The presence of primary and secondary seropositive samples and absence of line-sero conversion (change of antibody from negative to positive) or fourfold increase in antibody titer was considered as previous infection.</p><p><strong>RESULTS</strong><strong>:</strong> The prevalence rate of acute Q fever in 56 patients with 2nd blood sample was 5.3%. There was no history of tick bite, while in 100% of cases there were risk factors such as a history of residence near animal care centers as well as a history of consumption of raw dairy products (P = 0/001). 23.2% had a previous history of Q fever infection, out of which 25.8% lived in rural areas. Among people with risk factors of keeping domestic animals, living close to animal care centers and animal abortion, the prevalence rate of previous infection was higher compared to those who did not have these risk factors.</p><p><strong>CONCLUSION</strong><strong>: </strong>Since most of the patients with acute Q fever have no specific symptom, health care providers do not suspect acute Q fever disease. In this study, it was demonstrated that infection is either directly or indirectly associated with increase in environmental risk factors including contact with livestock and its products. Our study proved that Q fever is endemic in Mazandaran province. In order to have an accurate diagnosis and proper management, clinicians should be aware of existence of this disease in the region. Because of the climate of northern Iran and easy transportation of contaminated particles, appropriate measures should be taken to control and prevent this disease.</p>

Sample size determination for fold-increase endpoints defined by paired interval-censored data

ABSTRACTMedical studies often define binary end-points by comparing the ratio of a pair of measurements at baseline and end-of-study to a clinically meaningful cut-off. For example, vaccine trials may define a response as at least a four-fold increase in antibody titers from baseline to end-of-study. Accordingly, sample size is determined based on comparisons of proportions. Since the pair of measurements is quantitative, modeling the bivariate cumulative distribution function to estimate the proportion gives more precise results than using dichotomization of data. This is known as the distributional approach to the analysis of proportions. However, this can be complicated by interval-censoring. For example, due to the nature of some laboratory measurement methods, antibody titers are interval-censored. We derive a sample size formula based on the distributional approach for paired interval-censored data. We compare the sample size requirement in detecting an intervention effect using the distributional approach to a conventional approach of dichotomization. Some practical guidance on applying the sample size formula is given.

Treatment of Tropical and Travel Related Rickettsioses

Infections with organisms of the genera Rickettsia and Orientia are undifferentiated in regard to their manifesting signs and symptoms. Hence, a high degree of suspicion is required when a patient has a compatible illness coupled with exposure to potential vectors. Confirmatory diagnosis is usually retrospective, as it is obtained through serologic methods to determine seroconversion or a fourfold increase in antibody titers from acute to convalescent phase sera. Since many of these infections are associated with considerable morbidity and mortality, empiric treatment is imperative when illness is suspected. Antibiotics in the tetracycline class are highly active in vitro and have an excellent track record in the treatment of these diseases. Of the antibiotics in this class, doxycycline is the drug of choice, as it has excellent bioavailability, ease of twice daily dosing, and more favorable gastrointestinal tolerability. The usual duration of treatment is 7 days. In the most severe rickettsiosis, Rocky Mountain spotted fever, use of the usual alternative, chloramphenicol, is associated with a higher case fatality rate. Therefore, doxycycline is recommended in children <8 years of age—short courses do not cause appreciable staining of developing permanent teeth. Chloramphenicol is not available in its oral form in the USA, and the parenteral formulation is becoming difficult to acquire. In countries where available, it should be used with careful consideration of the risk-benefit ratio when weighed against the pathogenicity of the suspected agent. For infection with less pathogenic spotted fever group and typhus group rickettsiae (e.g., R. conorii and R. typhi), fluoroquinolones are an alternative. The agent that causes scrub typhus, Orientia tsutsugamushi, is intrinsically resistant to fluoroquinolones. Azithromycin can be used for scrub typhus in areas where there is reported failure of doxycycline or when a safer agent is required (i.e., pregnancy).

Human infection with a novel tick-borne Anaplasma species in China: a surveillance study

Anaplasma phagocytophilum and Anaplasma ovis cause human infections. We investigated the potential for human pathogenicity of a newly discovered Anaplasma species infecting goats in China. We collected blood samples from patients with a history of tick bite in the preceding 2 months at Mudanjiang Forestry Central Hospital of Heilongjiang Province from May 1, to June 10, 2014, to detect the novel Anaplasma species by PCR. We inoculated positive samples into cell cultures. We characterised the isolated pathogen by morphological and phylogenetic analyses. We tested serum antibodies by indirect immunofluorescence assay. 28 (6%) of 477 patients assessed were infected with the novel Anaplasma species according to PCR and sequencing. We isolated the pathogen in vitro from three patients. Phylogenetic analyses of rrs, gltA, groEL, msp2, and msp4 showed that the pathogen was distinct from all known Anaplasma species. We provisionally nominate it "Anaplasma capra". 22 (92%) of 24 patients with data available had seroconversion or a four-fold increase in antibody titres. All 28 patients developed non-specific febrile manifestations, including fever in 23 (82%), headache in 14 (50%), malaise in 13 (46%), dizziness in nine (32%), myalgia in four (14%), and chills in four (14%). Additionally, ten (36%) of 28 patients had rash or eschar, eight (29%) had lymphadenopathy, eight (29%) had gastrointestinal symptoms, and three (11%) had stiff neck. Five patients were admitted to hospital because of severe disease. Six (35%) of 17 patients with data available had high hepatic aminotransferase concentrations. The emergence of "A capra" as a cause of human disease suggests that individuals living in or travelling to endemic regions in northern China should take precautions to reduce their risk of exposure to this novel tick-borne pathogen. Natural Science Foundation of China and the US National Institutes of Health.

Scrub typhus: Clinical spectrum and outcome.

Sir, We read with great interest the article “Scrub typhus: Clinical spectrum and outcome” in the April 2015 issue of Indian Journal of Critical Care Medicine.[1] The article definitely enlightens about the clinical presentations, complications, and management of scrub typhus patients in Southern India. We agree with the authors that high cost, nonavailability, and the requirement of technical expertise for conducting confirmatory investigations such as indirect immunofluorescence assay (gold standard), indirect immunoperoxidase test or polymerase chain reaction-based tests are the major hurdles in making an accurate diagnosis of scrub typhus in India. Weil-Felix test serves as a useful and affordable tool for laboratory diagnosis of rickettsial diseases in resource-poor countries. Recently, immunochromatographic tests (ICT) to detect antibodies against Orientia tsutsugamushi are commercially available and is used by many hospitals. However, there is no large-scale evaluation of these assays in our country so far. As the scrub typhus cases in the present study were diagnosed by ICT as well as Weil-Felix test, there are certain aspects of these tests, which need to be discussed in a little depth. First, it will be informative if the authors can shed more light on the results of Weil-Felix test according to OX-2, OX-19, and OX-K titers. Second, it would be helpful if the manufacturers’ details of the ICT can be provided such as sensitivity, specificity, positive and negative predictive values, and the types of antibodies (IgM/total) detected. Diagnosis by Weil-Felix test based on a single acute serum sample requires using a cut-off antibody titer.[2] Cut-offs ranging from 1:10 to 1:400 are quoted, often with little corroborating evidence and without establishing titers in the healthy local population (necessary to distinguish background immunity from acute infection); that cut off is then used for all patients, irrespective of whether or not they come from a scrub-typhus-endemic environment.[2] There is variation in the single Weil-Felix test cut-off titers used for the diagnosis of scrub typhus in different published studies across India.[3,4] With a single serum sample available, the test is suggestive of infection only at a high cut-off titer (>1:320) at which the positive predictive value and the specificity is reliable,[3] majority of Indian studies have used a cut-off titer >1:80.[4] Although agreement exists that a ≥ four-fold increase in antibody titer between two consecutive samples is diagnostic, such a diagnosis is retrospective and cannot guide initial treatment.[2] In the current study, the authors have mentioned about 70.5% (24/34) scrub typhus patients without acute respiratory distress syndrome (ARDS) belonged to endemic areas. Of these 34 patients, only four patients had high Weil-Felix titer of 1:320, three patients had 1:160 and 20 patients had 1:80. Low titer (1:80) in these 20 patients can probably be explained by the fact that, about 50% of scrub typhus patients have a positive test result only during the 2nd week of illness,[5] while in the current study, tests were performed in the 1st week of illness, (5.264 ± 0.431 days). Testing of paired sera sample might have yielded more relevant information in this group. Similarly in the other group, (scrub typhus patients with ARDS), 83.3% were from endemic areas. Of these 24 patients, 10 patients had Weil-Felix titer 1:320, six patients had 1:160 and eight patients had 1:80. Thus, higher percentage of patients having high titer in the ARDS group could either be due to more number of patients from endemic areas in this group or due to the tests performed in the 2nd week of illness (11.333 ± 0.570 days). However, positive ICT in all these cases raises a very important issue. Should all positive ICT cases be considered as diagnostic of scrub typhus? Should single Weil-Felix titers as low as 1:20 or 1:40 raise an alarm to the clinicians in suspected cases of typhus? The present study in a tertiary care hospital has addressed one of the important neglected zoonoses of public health importance. A prospective evaluation of several commercial antibody-based rapid tests in Thailand had yielded the following sensitivities and specificities (the Panbio IgM ICT), 46% and 95%, respectively; the Standard Diagnostics IgM ICT, 68% and 73%, respectively; the AccessBio IgM ICT, 56% and 90%, respectively; and the AccessBio total antibody ABt ICT, 61% and 68%, respectively, during the acute phase of scrub typhus infection.[6] More studies in India should evaluate the rapid, point of care diagnostic assays as well as enzyme-linked immunosorbent assays (which includes Indian O. tsutsugamushi genotypes of scrub typhus) for optimal patient benefit.

HIV virological suppression influences response to the AS03‐adjuvanted monovalent pandemic influenza A H1N1 vaccine in HIV‐infected children

DesignChildren with HIV are especially susceptible to complications from influenza infection, and effective vaccines are central to reducing disease burden in this population. We undertook a prospective, observational study to investigate the safety and immunogenicity of the inactivated split-virion AS03-adjuvanted pandemic H1N1(2009) vaccine in children with HIV.SettingNational referral centre for Paediatric HIV in Ireland.SampleTwenty four children with HIV were recruited consecutively and received two doses of the vaccine. The serological response was measured before each vaccine dose (Day 0 and Day 28) and 2 months after the booster dose. Antibody titres were measured using a haemagglutination inhibition (HAI) assay. Seroprotection was defined as a HAI titre ≥ 1:40; seroconversion was defined as a ≥ fourfold increase in antibody titre and a postvaccination titre ≥ 1:40.Main outcome measuresThe seroconversion rates after prime and booster doses were 75% and 71%, respectively. HIV virological suppression at the time of immunization was associated with a significantly increased seroconversion rate (P = 0·009), magnitude of serological response (P = 0·02) and presence of seroprotective HAI titres (P = 0·017) two months after the booster dose. No other factor was significantly associated with the seroconversion/seroprotection rate. No serious adverse effects were reported. Vaccination had no impact on HIV disease progression. The AS03-adjuvanted pandemic H1N1 vaccine appears to be safe and immunogenic among HIV-infected children. A robust serological response appears to be optimized by adherence to a HAART regimen delivering virological suppression.

Does vaccine dose predict response to the monovalent pandemic H1N1 influenza a vaccine in children with acute lymphoblastic leukemia? A single‐centre study

Vaccination against influenza is an important strategy in preventing severe infection among children with acute lymphoblastic leukemia (ALL). Successful vaccination depends on both vaccine and host-related factors. We conducted a study on factors predicting the immunogenicity of the monovalent pandemic H1N1 (pH1N1) influenza A vaccine in children with ALL. Children with ALL in our hospital were recruited and received two doses of the inactivated split-virion AS03-adjuvanted vaccine. The serological response was measured before each vaccine dose (Day 0 and 28) and 3 months after the second dose. Antibody titres were measured using a hemagglutination-inhibition assay. Seroconversion was defined as a ≥fourfold increase in antibody titre and a post-vaccination titre ≥1:40. Pre and post-vaccination titres were available from 45 children with ALL after one dose of the vaccine and 39 children after two doses. The seroconversion rate was 11.1% after one dose and 25.6% after the second dose. Univariate analysis demonstrated a significantly higher (P = 0.01) seroconversion rate among children who received the adult dose (0.5 ml) of the vaccine and a trend towards increased seroconversion (P = 0.07) by multivariate analysis. Factors including age, gender, lymphocyte count, treatment phase and regimen did not significantly affect the seroconversion rate. Children who received the adult dose demonstrated a significantly greater magnitude of serological response after both one dose (P = 0.04) and two doses (P = 0.001). These data suggest that the immunogenicity of the pH1N1 vaccine among children with ALL is improved by repeated and adult doses of the vaccine.

Influenza A H1N1 2009 Vaccine in Patients with Hematological Diseases: Good Safety and Immunogenicity Even in Heavily Chemotherapy-Treated Patients

AbstractAbstract 1054 Background:Patients with hematological malignancies are more susceptible for viral infections including influenza, which may be associated with prolonged illness, increased morbidity and mortality. In 2009, the World Health Organization classified the novel influenza A(H1N1) virus as pandemic. The impact of this viral infection in patients (pts) with hematological disorders was unknown, and there were concerns about the risk of serious complications. In Sweden, institutional guidelines recommended two doses of the AS03-adjuvanted inactivated H1N1 split vaccine Pandemrix™ from GlaxoSmithKline in these pts. Aims:Prospectively determine the safety, immunogenicity, and clinical efficacy of influenza A (H1N1) 2009 vaccination in patients with hematological diseases. Compare the immunological response to that obtained by the trivalent seasonal influenza vaccine (TIV). Patients and methods:31 pts were included (myeloma 9, CLL 5, AML 6, ALL 2, CML 2, others 5), out of which 13 had undergone hematopoietic stem cell transplantation (HSCT). All received influenza A(H1N1) 2009 vaccine at day 0, and 28, and the majority (n=25) seasonal influenza vaccine at day 56. Serum for antibody analyses by validated HI-assays was taken at day 0, 28, 56 and 86 and at 1 year. The response to vaccination (seroconversion) was defined as at least a four-fold increase in antibody titer after vaccination or, in case prevaccination HI-titer was < 10, a post-vaccination titer of HI > 40 or greater. Considering that the HI-assay for influenza B differed from the A strains only the seroconversion rate was considered for the influenza B. Results:The A (H1N1) vaccine was well tolerated and no severe adverse events were reported. At day 28, a total of 16(52%) patients had protective levels of antibodies to A (H1N1) 2009 and 15(48%) had a seroconversion response. After the second dose of the vaccine, 25(81%) reached both protective levels of antibodies and seroconversion. At 1 year, protective levels of antibodies against A (H1N1) 2009 remained in 56% of responding patients. Seroconversion response was observed in 9/13 patients who had undergone HSCT, including 5/9 pts who had been transplanted within1–5 months, as well as in all (n=9) pts with myeloma having advanced disease and/or ongoing intense treatment.Following vaccination with TIV and evaluated at day 86, protective antibody levels and seroconversion response against A/Brisbane/59/2007 H1N1-like virus were detected in 10(40%) respective 7(28%), and against A/Uruguay/10/2007/H3N2-like virus in 14(56%) respective 10(40%). As for B/Brisbane/60/2008-like virus, seroconversion response was found in 5(20%) of all pts. Response to the pandemic influenza A (H1N1) 2009 vaccine was better than that to the three TIV strains (p<0.001, p<0.009 and p<0.001 respectively). Conclusion:A substantial proportion of patients with hematological malignancies including even heavily treated Myeloma and HSCT patients mounted a good response to the adjuvanted influenza A (H1N1) 2009 vaccine. This vaccine was well tolerated and had a significantly better immunogenicity than that of the non-adjuvanted seasonal influenza vaccine. Disclosures:Cherif:GSK: Research Funding. Pauksens:GSK: Research Funding.

Efficacy and safety of the H1N1 monovalent vaccine in renal-transplant recipients and dialysis patients

Background: The (H1N)1v influenza virus infection emerged in 2009 as a serious disease in targeted populations. Herein, we report on the tolerability and efficacy of (anti-H1N1)v vaccination in dialysis and transplant patients.Methods: 18 renal-transplant recipients (RTR) and 19 dialysis patients (DP) [12 patients treated with peritoneal dialysis (PDP), 7 patients treated with haemodialysis (HDP)] were enrolled. DPs received one monovalent H1N1 adjuvanted-vaccine injection, and RTRs received two unadjuvanted vaccine injections within a 21-day period. Serologic response was defined as a haemagglutination inhibition titre of >40 (seroprotection) and/or at least a four-fold increase in antibody titre from baseline (seroconversion).Results: Seroprotection rate after vaccination was greater in DPs than RTRs (p = 0.007), as was seroconversion (p = 0.001). Serologic response was similar in PDPs and HDPs.Conclusions:. Serologic response was satisfactory in DPs, whichever dialysis mode (DPD or HDP). It was low in RTRs as compared to DPs. word count 149

The pandemic H1N1 influenza vaccine results in low rates of seroconversion for patients with hematological malignancies

Patients with hematological malignancies are at increased risk of influenza and its complications, but evidence for the efficacy of influenza vaccination in this population is limited. We sought to determine whether patients being treated for hematological malignancies were able to mount protective antibodies to the H1N1 influenza vaccine. Pre- and post-vaccination plasma samples were collected from patients with hematological malignancies during the 2009–2010 influenza season. Seroconversion was defined as a four-fold increase in antibody titer, as measured by the hemagglutinin inhibition test. Sixty-two patients received the H1N1 vaccine and 41 patients were unvaccinated controls. The rate of seroconversion among vaccinated patients was 21%, which was significantly higher than that in unvaccinated patients (0%), but significantly lower than that previously reported for healthy adults. Physicians should be aware that influenza vaccination may not generate an immune response in patients with hematological malignancies. Larger studies are required to confirm these results.

The Pandemic H1N1 Influenza Vaccine Results In Low Rates of Seroconversion In Patients with Hematological Malignancies

AbstractAbstract 3110 Background:Patients with hematological malignancies are at increased risk of influenza and its complications. However, evidence for the efficacy of influenza vaccination in this population is limited and contradictory [Pollyea et al., J Clin Oncol. 2010]. The adjuvanted pandemic H1N1 vaccine has been shown to be highly effective in healthy adults, with reported rates of seroprotection and seroconversion of over 90% [Plennevaux et al., Lancet 2010]. We sought to determine whether patients being treated for hematological malignancies were able to mount a protective antibody response to the H1N1 pandemic influenza vaccine. Methods:Patients being treated for hematological malignancies at the London Regional Cancer Program during the 2009–2010 influenza season were invited to participate. Patients who had received the vaccine prior to the commencement of the study in November 2009 were excluded. Pre-vaccination plasma samples were collected in November 2009, and post-vaccination samples were collected from January through March 2010. At the time of second sample collection, patients were asked to complete a questionnaire asking if and when they had received the H1N1 influenza vaccine. Plasma samples from patients who elected not to be vaccinated formed a control group. Antibody titration was performed by the hemagglutinin inhibition test. Our primary outcome was the rate of seroconversion, as defined by a fourfold increase in antibody titres. We also measured geometric mean titres (GMT), geometric mean titre ratios, (GMTR, defined as the ratio of the post-vaccination titre to the pre-vaccination titre), and rates of seroprotection (titre ≥ 1:80). Statistical analysis was done using Mann-Whitney U, chi-squared, or Fisher's Exact Tests, as appropriate. Results:Sixty-two patients received the H1N1 vaccine and 41 patients chose not to be vaccinated. The rate of seroconversion among vaccinated patients was 21%, which was significantly higher than that in unvaccinated patients (0%) and significantly lower than that in healthy individuals. The GMTR was significantly higher in the vaccinated group than the unvaccinated group (2.2 ± 2.5 vs. 1.2 ± 0.6, p = 0.041). There were no significant differences in the geometric mean titres or the rates of seroprotection between the vaccinated and unvaccinated groups. Of the 46 patients on active chemotherapy who received the vaccine, 10 (22%) seroconverted and 16 (35%) mounted seroprotective titres. Of the 12 patients on active Rituximab who received the vaccine, 2 (17%) seroconverted and 4 (33%) mounted seroprotective titres. There were no significant differences in the rates of seroconversion and seroprotection between patients on or off chemotherapy or between patients on or off Rituximab. Conclusions:Only 21% of patients with hematological malignancies were able to produce a fourfold increase in antibody titres in response to the H1N1 influenza vaccine, a rate significantly lower than that previously reported for healthy patients. We were unable to identify any clinical factors predictive of a response to the vaccine. Physicians should be aware that patients with hematological malignancies are less likely to receive protection from the influenza vaccine, and should consider alternate strategies to minimize the morbidity and mortality from influenza in this population. Larger studies are indicated to confirm these results.Table 1Vaccinated (N=62)Unvaccinated (N=41)P valueMean age64.6 ± 13.761.5 ± 18.00.620Female gender [N(%)]29 (47)16 (39)0.566Diagnosis [N(%)]Acute leukemia4 (6)7 (17)0.250CLL6 (10)2 (5)CML3 (5)0Lymphoma24 (39)21 (51)Multiple myeloma16 (26)7 (17)Myelodysplasia2 (3)0Myeloproliferative disorder6 (10)4 (10)Other1 (2)0Chemotherapy [N(%)]Past or active chemotherapy56 (90)40 (98)0.304Active chemotherapy46 (74)31 (76)0.871Past or active Rituximab16 (26)20 (49)0.029Active Rituximab12 (19)15 (37)0.086ResultsSeroconversion [N (%)[95% CI]]13 (21 [13–33])0 (0 [0–8])0.001Seroprotection [N (%)[95% CI]]25 (40 [29–53])9 (22 [12–37])0.058Pre-vaccination GMT40 ± 2265 ± 1130.957Pre-vaccination median titre4040Post-vaccination GMT73 ± 7369 ± 1130.134Post-vaccination median titre4040GMTR2.2 ± 2.51.2 ± 0.60.041 Disclosures:No relevant conflicts of interest to declare.

Low rate of seroconversion after vaccination with a split virion, adjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected patients

To determine rates of seroconversion after single vaccination with a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HIV-1-infected patients (ClinicalTrials.gov Identifier: NCT01017172). Single center diagnostic study. Institutional HIV outpatient department of an urban university clinic. Adult HIV-1-infected individuals. Serum samples were taken before and 21 days after vaccination. Antibody titers determined by hemagglutination inhibition assay. Seroconversion to vaccination was defined by either an antibody titer of 1: 10 or less before and of at least 1: 40 after or at least 1: 10 before and at least four-fold increase in antibody titer 21 days after single vaccination. One hundred and sixty patients (125 men/35 women) were analyzed. Before vaccination, 23 patients (14.4%) had a hemagglutination inhibition assay titer of at least 1: 40. A median of 22 +/- 3 days after vaccination, 110 (69%) patients seroconverted. Seroconverters were younger (45.1 +/- 10.0 vs. 48.8 +/- 11.3 years; P = 0.04), had a higher CD4 cell count (532 +/- 227 vs. 475 +/- 281 cells/microl; P = 0.03) and were more likely to have received a previous H5N1 vaccination in 2009 (25 vs. 8%; P = 0.02) when compared to nonresponders. No other significant differences were found comparing the two groups (prevaccination hemagglutination inhibition assay titer of > or =1: 40, AIDS, HAART, HIV RNA PCR <50 copies/ml or CD4 nadir, CD4 and CD8 percentage, sex, BMI, chronic hepatitis B or C). Seroconversion after one dose of a split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine of HIV-infected patients was 69%. Studies to investigate whether a second dose of the vaccine will increase seroconversion rate are needed.

Cardiovascular activity and the antibody response to vaccination

Objective To examine the relationship between cardiovascular activity in response to acute psychological stress and the antibody response to vaccination. Methods Fifty-seven healthy participants were vaccinated with the trivalent influenza vaccine and meningococcal A+C polysaccharides. Antibody levels were measured at baseline and 5-weeks post-vaccination. Cardiovascular activity was measured at rest, during, and following a mental arithmetic stress task in 54 participants. Results Participants demonstrating a fourfold increase in antibody titre to the A/Panama and B/Shangdong influenza strains and to meningococcal A showed greater blood pressure reactions toward the end of the acute stress task. In addition, there was some evidence of delayed diastolic blood pressure recovery in those who were responders to A/Panama and B/Shangdong influenza strains. Conclusion The present results suggest that heightened cardiovascular reactivity to stress and delayed recovery may not necessarily be detrimental to all aspects of health and may be associated with an enhanced immune response to antigen challenge.

Serological and molecular survey of Anaplasma species infection in dogs with suspected tickborne disease in Portugal

Fifty-five dogs with suspected tickborne disease were tested by immunofluorescence assay and PCR for Anaplasma phagocytophilum infection. Thirty (54·5 per cent) of the dogs were seropositive and five of them...