Fourfold Rise In Antibody Titer Research Articles

Prevalence and risk factors for human leptospirosis at a hospital serving a pastoralist community, Endulen, Tanzania.

Leptospirosis is suspected to be a major cause of illness in rural Tanzania associated with close contact with livestock. We sought to determine leptospirosis prevalence, identify infecting Leptospira serogroups, and investigate risk factors for leptospirosis in a rural area of Tanzania where pastoralist animal husbandry practices and sustained livestock contact are common. We enrolled participants at Endulen Hospital, Tanzania. Patients with a history of fever within 72 hours, or a tympanic temperature of ≥38.0°C were eligible. Serum samples were collected at presentation and 4-6 weeks later. Sera were tested using microscopic agglutination testing with 20 Leptospira serovars from 17 serogroups. Acute leptospirosis cases were defined by a ≥four-fold rise in antibody titre between acute and convalescent serum samples or a reciprocal titre ≥400 in either sample. Leptospira seropositivity was defined by a single reciprocal antibody titre ≥100 in either sample. We defined the predominant reactive serogroup as that with the highest titre. We explored risk factors for acute leptospirosis and Leptospira seropositivity using logistic regression modelling. Of 229 participants, 99 (43.2%) were male and the median (range) age was 27 (0, 78) years. Participation in at least one animal husbandry practice was reported by 160 (69.9%). We identified 18 (7.9%) cases of acute leptospirosis, with Djasiman 8 (44.4%) and Australis 7 (38.9%) the most common predominant reactive serogroups. Overall, 69 (30.1%) participants were Leptospira seropositive and the most common predominant reactive serogroups were Icterohaemorrhagiae (n = 20, 29.0%), Djasiman (n = 19, 27.5%), and Australis (n = 17, 24.6%). Milking cattle (OR 6.27, 95% CI 2.24-7.52) was a risk factor for acute leptospirosis, and milking goats (OR 2.35, 95% CI 1.07-5.16) was a risk factor for Leptospira seropositivity. We identified leptospirosis in approximately one in twelve patients attending hospital with fever from this rural community. Interventions that reduce risks associated with milking livestock may reduce human infections.

Assessing the immunogenicity of three different inactivated polio vaccine schedules for use after oral polio vaccine cessation, an open label, phase IV, randomized controlled trial

BackgroundAfter global oral poliovirus vaccine (OPV) cessation, the Strategic Advisory Group of Experts on Immunization (SAGE) currently recommends a two-dose schedule of inactivated poliovirus vaccine (IPV) beginning ≥14-weeks of age to achieve at least 90% immune response. We aimed to compare the immunogenicity of three different two-dose IPV schedules started before or at 14-weeks of age. MethodsWe conducted a randomized, controlled, open-label, inequality trial at two sites in Dhaka, Bangladesh. Healthy infants at 6-weeks of age were randomized into one of five arms to receive two-dose IPV schedules at different ages with and without OPV. The three IPV-only arms are presented: Arm C received IPV at 14-weeks and 9-months; Arm D received IPV at 6-weeks and 9-months; and Arm E received IPV at 6 and 14-weeks. The primary outcome was immune response defined as seroconversion from seronegative (<1:8) to seropositive (≥1:8) after vaccination, or a four-fold rise in antibody titers and median reciprocal antibody titers to all three poliovirus types measured at 10-months of age. FindingsOf the 987 children randomized to Arms C, D, and E, 936 were included in the intention-to-treat analysis. At 10-months, participants in Arm C (IPV at 14-weeks and 9-months) had ≥99% cumulative immune response to all three poliovirus types which was significantly higher than the 77–81% observed in Arm E (IPV at 6 and 14-weeks). Participants in Arm D (IPV at 6-weeks and 9-months) had cumulative immune responses of 98–99% which was significantly higher than that of Arm E (p value < 0.0001) but not different from Arm C. InterpretationResults support current SAGE recommendations for IPV following OPV cessation and provide evidence that the schedule of two full IPV doses could begin as early as 6-weeks.

Immunogenicity of trivalent seasonal influenza vaccine in patients with chronic obstructive pulmonary disease

ABSTRACT Objective: Current evidence on the immunogenicity of influenza vaccination in patients with chronic obstructive pulmonary disease (COPD) is limited. To address this need for additional knowledge, we conducted a study on the immunogenicity of trivalent seasonal influenza vaccine (TIV) in COPD patients. Methods: We recruited patients from respiratory outpatient clinics of three hospitals in Tangshan, Hebei province who had stable confirmed COPD, were less than 80 y old, and reported not having had influenza or receiving TIV during the study season prior to enrollment. Patients who had a history of allergy to any TIV component or were classified as having very severe COPD were excluded from the study. Eligible and consenting participants were given one dose of TIV after obtaining a baseline blood sample. A second blood sample was obtained 5 weeks later. We used hemagglutination inhibition (HI) assays to measure antibody responses. We considered seropositive to be an HI titer ≥1:10. We considered seroprotection to be an HI titer ≥1:40 and seroconversion to be either a change from seronegative to a post-vaccination titer of ≥1:40 or a fourfold rise in antibody titer among baseline seropositive subjects. Each subject was followed for 1 month to assess the frequency and type of adverse events. Results: Eighty-eight subjects completed our study; the median age was 64 y; most (62.5%) had moderately severe COPD; 48.9% of the subjects had comorbid conditions in addition to COPD. Post–vaccination seropositive rates for influenza H1N1, H3N2, and B were all 100%; corresponding seroprotection rates were 96.6%, 93.2%, and 98.9%; seroconversion rates were 81.8%, 87.5%, and 75.0%. There were no statistical differences in seroconversion (P = .10) and seroprotection (P = .30) among the three types of influenza virus. Geometric mean titers (1:) of HI antibodies to H1N1, H3N2, and B were 18.8 (95% CI: 14.0–25.1), 12.2 (95% CI: 9.6–15.4), and 31.8 (95% CI: 26.1–38.8) at baseline, and 267.0 (95% CI: 213.8–333.4), 190.3 (95% CI: 151.7–238.6), and 201.1 (95% CI: 166.5-242.8) after vaccination. Conclusion: The immunogenicity of one dose of influenza vaccine was excellent in COPD patients. Our study supports recommending influenza vaccination for COPD patients to provide protection from influenza and its complications.

Investigation and response to an outbreak of leptospirosis among raspberry workers in Australia, 2018

In 2018, an outbreak of leptospirosis was identified among raspberry workers from a mixed-berry farm in New South Wales, Australia. Initial testing had not revealed a cause, but eventually leptospirosis was detected via polymerase chain reaction (PCR). Further serological testing detected Leptospira borgpetersenii serovar Arborea, of which rodents are the predominant reservoir. Leptospirosis is rare in Australia, with outbreaks usually related to flooding. We conducted an investigation to identify risk factors for infection, to inform control measures. Cases were detected through laboratory notifications, hospital-based syndromic surveillance, awareness-raising among farm employees and clinician alerts. Confirmed cases had a four-fold rise in antibody titre or single titre ≥400 on microscopic agglutination test, and a positive IgM. Probable cases had a positive Leptospira PCR or IgM, and possible cases had a clinically compatible illness. We conducted a case-control study among raspberry workers on the farm and compared reported exposures between cases and seronegative controls. We assessed environmental risks on-site and tested rodents for leptospirosis. We identified 84 cases over a 5-month period (50 confirmed, 19 probable and 15 possible). Compared with controls, cases were less likely to wear gloves and more recently employed. Cases also more commonly reported always having scratched hands, likely from the thorns on raspberry plants. We observed evidence of rodent activity around raspberry plants and three of thirteen trapped mice tested positive for Leptospira Arborea. Control measures included enhanced glove use, doxycycline prophylaxis and rodent control. This is the largest known outbreak of leptospirosis in Australia. Workers were likely exposed through scratches inflicted during harvesting, which became contaminated with environmental leptospires from mice. Leptospirosis should be considered an occupational risk for raspberry workers, requiring protective measures. Chemoprophylaxis may assist in controlling outbreaks. PCR assists in the early diagnosis and detection of leptospirosis and should be included in surveillance case definitions.

Leptospirosis complicated with Guillain Barre syndrome, papillitis and thrombotic thrombocytopenic Purpura; a case report

BackgroundLeptospirosis is a zoonosis commonly prevalent in tropical countries. Clinical course of leptospirosis varies from mild to severe disease. Here we present a case of leptospirosis complicated with Guillain-Barre Syndrome (GBS), papillitis, and Thrombotic Thrombocytopenic Purpura(TTP).Case presentationA 21-year-old Asian male presented with fever, myalgia, oliguria and dyspnoea where he was managed as for leptospirosis complicated with pulmonary haemorrhages and acute renal failure. Leptospirosis was confirmed by Microscopic Agglutination Test(MAT) with a fourfold rise in antibody titre between acute and convalescent serum. The highest antibody titre was against Leptospira antigen serogroup Semaranga (strain Patoc) (1:1280) followed by serogroup Australis (strain Australis) (1:640) and serogroup Autumnalis (strain Bankgkinang) (1:320). Two weeks later he developed blindness, ascending weakness of lower limbs with global areflexia and an acute inflammatory demyelinating polyradiculopathy(AIDP) variant GBS was confirmed with nerve conduction studies. TTP complicated the picture several days later. He was initiated on plasmapheresis where clinical improvement was seen after 14 cycles. He had an incomplete neurological recovery with permanent vision loss but completely recovered from TTP. He also had permanent renal impairment.ConclusionLeptospirosis should be suspected and treated empirically in the relevant clinical settings where it can present with an atypical clinical picture as in our case with an acute febrile illness followed by GBS as well as TTP.

Risk factors for human acute leptospirosis in northern Tanzania.

IntroductionLeptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania.MethodsWe enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012–2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables.ResultsWe identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis.ConclusionsIn our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease.

An outbreak investigation of typhoid fever in Pondicherry, South India, 2013

Background: Preliminary investigation at Pediatric ward of Indira Gandhi Medical College revealed admission of a cluster of typhoid cases who were residents of one particular street in a nearby locality. Objectives: This study was undertaken to estimate the magnitude of the outbreak, identify the source of infection, and, thereby, institute control measures. Materials and Methods: An investigation team including 10 MBBS students carried out a sanitary survey, house-to-house survey, data collection using epidemiological case sheets, and spot mapping. Typhoid diagnosis was confirmed as per the IDSP guidelines, i.e., either a blood culture growth positive for Salmonella typhi or a fourfold rise in antibody titer. An age- and gender-matched case–control study was conducted to find the association of occurrence of typhoid with various possible sources of infection. Water samples were collected from the affected households and public taps for investigation. Results: Rapid survey of all the 6 streets of Thilaspet covered 1106 people living in 283 households. All nine confirmed cases were residents of one particular street. The attack rate calculated was 3.4% in this street. A significant association of occurrence of typhoid was found only with consumption of raw drinking water (OR = 12.6, P = 0.01). Water samples only from the affected street tested positive for the presence of coliforms. The sanitary survey documented water pipeline breakage at the junction of this street. Further spread of disease was stopped by advocating drinking of boiled water and repair of pipeline. Conclusion: Strengthening of disease surveillance for early identification of localized outbreaks and instituting control measures can effectively control disease spread.

Influenza vaccination in children being treated with chemotherapy for cancer

Influenza infection is a potential cause of severe morbidity in children with cancer; therefore vaccination against influenza is recommended. However, data are conflicting regarding the immune response to influenza vaccination in children with cancer, and the value of vaccination remains unclear. 1. To assess the efficacy of influenza vaccination in stimulating an immunological response in children with cancer during chemotherapy, compared with control groups.2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or in stimulating immunological response in children with cancer treated with chemotherapy, compared with placebo, no intervention or different dosage schedules.3. To identify the adverse effects associated with influenza vaccines in children with cancer treated with chemotherapy, compared with other control groups. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2012) and EMBASE (1980 to 2012) up to August 2012. We also searched reference lists of relevant articles and conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the Infectious Diseases Society of America (IDSA), the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Paediatric Oncology (SIOP). We considered randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in which the serological response to influenza vaccination of children with cancer was compared with that of control groups. We also considered RCTs and CCTs that compared the effects of influenza vaccination on clinical response and/or immunological response in children with cancer being treated with chemotherapy, compared with placebo, no intervention or different dosage schedules. Two independent review authors assessed the methodological quality of included studies and extracted the data. We included 1 RCT and 9 CCTs (total number of participants = 770). None of the included studies reported clinical outcomes. All included studies reported on influenza immunity and adverse reactions to vaccination. In five studies, immune responses to influenza vaccine were compared in 272 children receiving chemotherapy and 166 children not receiving chemotherapy. In four studies, responses to influenza vaccine were assessed in 236 children receiving chemotherapy compared with responses in 142 healthy children. Measures used to assess immune responses included a four-fold rise in antibody titre after vaccination, development of a haemagglutination inhibition (HI) titre > 32 and pre- and post-vaccination geometric mean titres (GMTs). Immune responses in children receiving chemotherapy were consistently weaker (four-fold rise of 38% to 65%) than those in children who had completed chemotherapy (50% to 86%) and in healthy children (53% to 89%). In terms of adverse effects, 391 paediatric oncology patients received influenza vaccine, and the adverse effects described included mild local reactions and low-grade fever. No life-threatening or persistent adverse effects were reported. Paediatric oncology patients receiving chemotherapy are able to generate an immune response to the influenza vaccine, but it remains unclear whether this immune response protects them from influenza infection or its complications. We are awaiting results from well-designed RCTs addressing the clinical benefit of influenza vaccination in these patients.

A Reappraisal of Clinical Characteristics of Typhoid Fever

Background: Recent reports from developing countries show that the clinical presentation, diagnosis and treatment of typhoid have significantly altered often leading to missed diagnosis. The incidence of complications is also reported to be variable. The consequence of missed diagnosis is immense in terms of burden on limited health resources and patients’ suffering. Therefore, its clinical spectrum requires constant reappraisal to update our physicians with current knowledge. This study was carried out to determine the changes in clinical pattern of typhoid fever. Patients &amp; Methods: A total of 106 children, aged up to 14 years, diagnosed primarily as typhoid fever, were included as study population. The diagnostic criteria were either positive blood culture for Salmonella typhi or Salmonella paratyphi or at least a four-fold rise in antibody titre on Widal test. The study included mode of clinical presentations, treatment received before admission, Widal test findings and culture and sensitivity to antibiotics. Results: The mean age of the patients was 5.2 years and males were a little than the females. The mean duration of illness was 11.2±3.3 days. Majority of the patients presented with classical signs and symptoms like step ladder pattern of fever (nearly 70%) coated tongue (69.8%), diarrhoea (49.1%), toxemia (68.9%), relative leucopenia (71.7%), hepatomegaly (55.7%), pain in the right hypochondrium (41.5%) and splennomegaly (18.9%). Very few cases had a typical manifestations. Over 85% of the patients had raised SGPT (&gt;40 IU/L) and 13.8% had detectable jaundice (serum billirubin &gt;3 mg/dl). Widal test demonstrated that about 45% of the patients’ ‘O’ antibody titer increased to 4-fold, 27.4% to 8-fold or more. In case of antibody ‘H’, 35.8% exhibited 4-fold and 39.7% 8-fold or more increase. Of the 103 cases, 68(66%) were positive for Salmonella typhi. Majority of the isolated organisms was sensitive to cefixime, ceftriaxone and gentamycin (83%, 84% and 82% respectively). The second line of sensitivity was obtained to amikacin (64.2%), meropenem (50%), ciprofloxacin (46.2%), imepenem (46.2%) and azithromycin (43.4%). The least sensitive drugs were amoxicillin (28.3%), cotrimoxazole (27.4%) and chloramphenicol (22.6%). Onethird (33.8%) of the patients had multidrug resistant (MDR) strains. However, No significant association was found between multi-drug resistant (MDR) strains and atypical clinical manifestations. Conclusion: Clinical presentation of most typhoid fever still conforms with the classic pattern. High fever, anorexia, coated tongue, diarrhoea, relative leucopenia and hepatosplenomegaly are still common manifestations of typhoid fever. So, majority of the patients could be treated blindly based on clinical diagnosis. However, treatment should be given with first line of drugs like cefexime or ceftriaxone. DOI: http://dx.doi.org/10.3357/bjch.v34i3.10357 BJCH 2010; 34(3): 80-85

Meningitis in children in Fiji: etiology, epidemiology, and neurological sequelae

To describe the etiology, epidemiology, neurological sequelae, and quality of life of children aged 1 month to less than 5 years admitted with meningitis to the Colonial War Memorial Hospital (CWMH), Suva, Fiji. Over a 3-year period, all eligible children with suspected meningitis admitted to CWMH had blood drawn for culture. Of these children, those for whom is was possible were tested for a four-fold rise in antibody titers to Haemophilus influenzae type b (Hib) and pneumococcal surface adhesin A (PsaA). Cerebrospinal fluid (CSF) was taken for bacteriological culture and antigen testing. CSF was also tested by PCR for Streptococcus species, Neisseria meningitidis, Hib, Mycobacterium tuberculosis, and enterovirus. Pneumococcal isolates were serotyped using multiplex-PCR reverse-line blot hybridization. Following discharge, cases underwent a neurological assessment, audiometry, and quality of life assessment (Pediatric Quality of Life Inventory (PedsQL) tool). There were 70 meningitis cases. Meningitis was more common in indigenous Fijian than Indo-Fijian children. Enterovirus was the most common etiological agent and appeared to be outbreak-associated. Streptococcus pneumoniae was the most common bacterial cause of meningitis with an annual incidence of 9.9 per 100000 under 5 years old (95% confidence interval 4.9-17.7) and a case fatality rate of 36%. With the exception of deafness, neurological sequelae were more frequent in cases of bacterial meningitis than in viral meningitis (18.5% vs. 0%, p=0.04). Quality of life at follow-up was significantly lower in patients with bacterial meningitis than in those with viral meningitis (p=0.003) or meningitis of unknown etiology (p=0.004). During the study period an outbreak of enterovirus occurred making it the most common etiological agent identified. However in the absence of this outbreak, S. pneumoniae was the most common cause of childhood meningitis in Fiji. Bacterial meningitis is associated with serious sequelae and a reduced quality of life.

Cumulative incidence of pandemic influenza A (H1N1) 2009 by a community-based serological cohort study in Selenghe Province, Mongolia

Large community outbreaks of pandemic A (H1N1) 2009 occurred between October and December 2009 in Mongolia. A serological study was conducted among the general population by testing paired sera collected before and after the first wave of pandemic in Selenghe province, Mongolia. None of the study participants had been vaccinated for pandemic A (H1N1) 2009 before the second samples were collected. The objective of this study was to estimate cumulative incidence of pandemic A (H1N1) 2009 in different age-groups of Selenghe province residents. After informed consent was obtained from apparently healthy volunteers, the paired sera and background information were collected. Antibody titers were measured using hemagglutinin inhibition (HI) and microneutralization (MN) assays for A/California/07/2009pdm. A fourfold rise in antibody titers was regarded as the evidence of infection. The overall cumulative incidences in the study group for all ages were 28.8% (76/264) by HI, 35.2% (93/264) by MN, and 25.0% (66/264) by both HI and MN. Cumulative incidences of infection varied among age-groups, with children aged 2-4 and 5-9 years having high cumulative incidence of infection. Overall cumulative incidences of infection in the whole population were estimated to be 23.0% (4946/21460) by HI, 30.2% (6473/21460) by MN, and 18.8% (4036/21460) by both HI and MN. This study indicates that about one-fourth of the total population in Selenghe province was infected with pandemic A (H1N1) 2009 virus during the first wave of the pandemic.

Incidence of Influenza in Healthy Adults and Healthcare Workers: A Systematic Review and Meta-Analysis

BackgroundWorking in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs).Methods and FindingsWe searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction.From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs.ConclusionsCompared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza.

Observational study to investigate vertically acquired passive immunity in babies of mothers vaccinated against H1N1v during pregnancy

The primary objective was to determine the proportion of babies who acquired passive immunity to A/H1N1v, born to mothers who accepted vaccination as part of the national vaccination programme while pregnant (during the second and/or third trimesters) against the novel A/H1N1v influenza virus (exposed group) compared with unvaccinated (unexposed) mothers. An observational study at three sites in the UK. The purpose was to determine if mothers immunised against A/H1N1v during the pandemic vaccination period transferred that immunity to their child in utero. Three sites in the UK [Queen's Medical Centre, Nottingham; City Hospital, Nottingham (both forming University Hospitals Nottingham), and Leicester Royal Infirmary (part of University Hospitals Leicester)]. All pregnant women in the second and third trimester presenting at the NHS hospitals above to deliver were eligible to participate in the study. Women were included regardless of age, social class, ethnicity, gravida and parity status, past and current medical history (including current medications), ethnicity, mode of delivery and pregnancy outcome (live/stillbirth). At enrolment, participants provided written consent and completed a questionnaire. At parturition, venous cord blood was obtained for serological antibody analysis. Serological analysis was undertaken by the Respiratory Virus Unit (RVU), Health Protection Agency (HPA) Centre for Infections, London. The primary end point in the study was the serological results of the cord blood samples for immunity to A/H1N1v. Regarding a suitable threshold for the determination of a serological response consistent with clinical protection, this issue is somewhat complex for pandemic influenza. The European Medicines Agency (EMEA) Committee for Human Medicinal Products (CHMP) judges that a haemagglutination inhibition (HI) titre of 1 : 40 is an acceptable threshold. However, this level was set in the context of licensing plain trivalent seasonal vaccine, where a titre of 1 : 40 is but one of several related immunogenicity criteria, and supported by paired sera capable of demonstrating a fourfold rise in antibody titre in response to vaccination. The current study mainly investigated the effects of an AS03-adjuvanted monovalent vaccine, and it was not possible to obtain paired sera where the initial sample was taken before vaccination (in vaccinated subjects). Of possibly greater relevance is the fact that it has been established from the study of early outbreaks of pandemic influenza in secondary schools in the UK (HPA, unpublished observations) that an HI antibody titre of 1 : 32 seems to be the threshold for a humoral response to 'wild-type' A/H1N1v infection. On that basis, a threshold of 1 : 32 is at least as appropriate as one of 1 : 40, especially in unvaccinated individuals. Given the difficulties that would accrue by applying thresholds of 1 : 32 in unvaccinated patients and 1 : 40 in vaccinated patients, we have therefore applied a threshold of 1 : 32 and 1 : 40, to increase the robustness of our findings. Differences arising are described. A microneutralisation (MN) titre of 1 : 40 may be also used, although it is not part of the CHMP criteria for vaccine licensure. Nonetheless, we utilised this analysis as a secondary end point, based on a conservative threshold of 1 : 60. Reverse cumulative distribution percentage curves for haemagglutinin dilution and MN titres demonstrate background immunity in babies of unvaccinated mothers of 25%-30%. Humoral immunity in babies of vaccinated mothers was present in 80% of the group. The difference in positive immunity between the babies of unvaccinated and vaccinated mothers was statistically significant (chi-squared test, p < 0.001). Our findings reveal a highly significant difference in HI titres between babies born to mothers vaccinated with pandemic-specific vaccine against A/H1N1v during the 2009-10 pandemic period. The subjects recruited were comparable from a baseline perspective and thus do not represent different groups that otherwise could have introduced bias into the study. Continued circulation of 2009 A/H1N1-like viruses is uncertain, but is possible as seasonal influenza in years to come. It is possible that future seasonal waves may display increased virulence. Given the adverse outcomes experienced for a small proportion of pregnant women during the influenza pandemic of 2009-10, this study provides useful evidence to support vaccination in pregnancy to protect both the mother and baby. The National Institute for Health Research Health Technology Assessment programme.

Investigation of Cytokine Gene Polymorphisms in Korean Patients with Scrub Typhus

Background: Scrub typhus is caused by Orientia tsutsugamushi and can become severe and potentially life-threatening. It is suggested that specific host factors can modify the host response during O. tsutsugamushi infection. It is known that susceptibility and outcome of infectious disease are associated with genetic polymorphisms of some cytokines. Materials and Methods: Peripheral blood of 144 patients who were diagnosed with scrub typhus and of 311 unrelated healthy subjects were collected. A diagnosis of scrub typhus was made upon demonstration of a fourfold rise in antibody titer to O. tsutsugamushi in paired serum specimens in an indirect immunofluorescent (IFA) test. Genomic DNAs were extracted from peripheral mononuclear cells and genotypings for IL-1 (-511C/T), IL-1β (+3953T/C), IL-2 (-330T/G), IL-4 (-590C/T), IL-4R(-1902G/A), IL-10 (-1082G/A), IL-10 (-819C/T), TNF-α (-238G/A) and TNF-α (-308G/A) were performed simultaneously using PCR-SSP (sequence specific polymorphisms) assay. Results: The frequency of IL-1 (-511T/T) (OR=0.53, P<0.01) and IL-2 (-330T/ T) (OR=0.56, P<0.01) were significantly decreased, but that of IL-2(-330G/G) (OR=4.49, P<0.01) was increased, in the scrub typhus patients compared to the healthy controls. And, there were no statistically significant differences in the genetic polymorphisms of IL-4 (-590C/T), IL-4Rα (-1902G/A), IL-10 (-1082G/A), IL-10 (-819C/T), TNF-α (-238G/A), TNF-α (-308G/A) genes, in the scrub typhus patients compared to the unrelated healthy controls. Conclusions: Cytokine polymorphisms in the IL-1 (-511T/T) and the IL-2 genes may influence the host response to O. tsutsugamushi.

Outcome of influenza vaccination in combat-related post-traumatic stress disorder (PTSD) patients

Post-traumatic stress disorder (PTSD) is an anxiety disorder that can occur after exposure to extreme traumatic experience such as war trauma, and is accompanied by fear, helplessness or horror. Exposure to trauma can result in immune dysregulation and influence susceptibility to infectious disease as well as vaccine efficacy. The aim of the study was to determine the relation of psychological stress and the immune response to influenza vaccination in combat-related PTSD patients (n = 28). Detection of anti-viral antibody titre was performed by inhibition of haemagglutination assay. Ex vivo tetramer staining of CD8(+) T lymphocytes was used to monitor T cells specific for human leucocyte antigen (HLA)-A*0201-restricted influenza A haemagglutinin antigens before and after vaccination. Twenty patients showed a fourfold antibody titre increase to one or both influenza A viral strains, and 18 of them showed the same response for both influenza B viral strains. Ten of 15 healthy controls showed a fourfold rise in antibody titre to both influenza A viral strains and eight of them showed the same response for both influenza B viral strains. HLA-A*0201(+) PTSD patients (n = 10) showed a significant increase of influenza-specific CD8 T cells after vaccination. Although those PTSD patients had a lower number of influenza-specific CD8(+) T cells before vaccination compared to HLA-A*0201(+) healthy controls (n = 6), there was no difference in influenza A antibody titre between PTSD patients and control subjects before vaccination. The generated humoral and cellular immune response in PTSD patients argues against the hypothesis that combat-related PTSD in war veterans might affect protection following influenza vaccination.

Assessment of the immune response to trivalent split influenza vaccine in children with solid tumors

To assess the immune response to influenza vaccine in children with solid tumors receiving chemotherapy or under the influence of chemotherapy. Forty-five children (aged 1-18) with solid tumors on chemotherapy or within 6 months of completion of chemotherapy were included in the study. The children received two doses of intramuscular trivalent split influenza vaccine with 1 month apart in November-December 2003 (children <4 age 0.25 ml; >4 age 0.5 ml). Antibody titer was detected in the pre-vaccination and 4-week post-vaccination sera by hemagglutination inhibition (HI) method. Immune responses were measured as protective, geometric mean titers (GMT), and fourfold rises in HI titers. We revealed that the post-vaccination GMT for each of the three antigens in patients with solid tumors has increased significantly (P < 0.05). A fourfold rise in the percentage of post-vaccination antibody titers has been detected as 84.4% for H(1)N(1), 77.8% for H(3)N(2), 60% for B. Stratification of patients as on active chemotherapy or being within 6 months of completion of chemotherapy in terms of fourfold rise in antibody titers exposed a statistically significant difference for only B (P = 0.34). Post-vaccination protective rates were between 86 and 97%. Due to the interruptions in treatment caused by influenza infections, and economic benefits of the vaccine, we suggest that inactivated influenza vaccine should be applied as two doses annually in patients with solid tumor.

Disseminated Bartonella infection following liver transplantation*

Bartonella henselae has not only been identified as the causative agent of cat scratch disease, but it is also associated with other significant infectious syndromes in the immunocompromised population. We describe two cases of B. henselae associated diseases in liver transplant recipients who both had contact with cats. The first recipient developed localized skin manifestation of bacillary angiomatosis in association with granulomatous hepatitis. He tested positive for Immunoglobulin G (IgG) antibodies against B. henselae. The second patient developed axillary lymphadenopathy, with biopsy showing necrotizing granulomatous inflammation and polymerase chain reaction studies were positive for B. henselae DNA. Her serology for bartonellosis showed a fourfold rise in antibody titers during her hospitalization. Both patients responded to treatment with Azithromycin in combination with Doxycycline. These were the only cases within a series of 467 consecutive liver transplants performed in 402 patients performed during a 4-year period. Although bartonellosis is a rare infection in liver transplantation recipients, it should always be included in the differential diagnosis of patients presenting with fever, central nervous system (CNS) symptoms, skin lesions, lymphadenopathy, and hepatitis especially if prior contact with cats is reported.

Legionnaire's disease: a nosocomial outbreak in Turkey

Six nosocomial cases of Legionella pneumophila occurred over a two-week period, with one further case being diagnosed retrospectively after 30 days. Strains isolated from the hospital water system were clonally related to a single sputum isolate. A sero-epidemiological investigation into legionella exposure amongst staff and inpatients was undertaken at the eight-year-old Inonu University Medical Centre in Turkey, which has 600 beds and central air conditioning. There is no disinfection programme for the hospital water system. A total of 500 serum samples (400 hospital staff and 100 inpatients) were screened for antibody to L. pneumophila by enzyme-linked immunosorbent assay (ELISA). Seroreactive cases were confirmed by a four-fold antibody rise in ELISA, a high indirect immunofluorescent assay (IFA) antibody titre or a positive urinary antigen test. ELISA showed that 24 (6%) of the 400 hospital staff and seven (7%) of the 100 inpatients had antibody titres higher than the cut-off value. ELISA-seroreactive cases were followed for two to four weeks. Of these subjects, seven (three patients and four staff) showed a four-fold rise in antibody titre by ELISA, six (three patients and three staff) had a high IFA titre, three patients with pneumonia had a positive urinary antigen test, and one of these patients also had a positive sputum culture. In addition, 22 water distribution systems were screened for the presence of L. pneumophila by culture. L. pneumophila was isolated from 15 sites. Pulsed-field gel electrophoresis typing indicated that all strains isolated from water systems were identical and clonally related to the strain isolated from sputum. Superheating and flushing of water systems were undertaken with legionella being re-isolated from four sites. Repeated superheating and flushing eliminated legionella completely. This study demonstrated that rapid detection of L. pneumophila and adequate superheating and flushing of water systems are effective for elimination and reduction of spread of this organism.

Leptospiral pneumonia

Severe leptospirosis rarely presents with primary pulmonary manifestations, without any associated jaundice or renal dysfunction. The authors report a nine-year-old boy who presented with complaints of abrupt onset of high fever; with myalgia, headache, and pain in right chest region, productive cough with hemoptysis and vomiting developing over the past 72 hours. Chest radiograph showed consolidation in the right upper lobe with air bronchogram. A history of contact with sewage water and presence of conjunctival suffusion in a child with pneumonia made us suspect leptospirosis. Following prompt initiation of parenteral penicillin therapy the child's complaints resolved over the next five days. Dri-Dot test to detect anti-Leptospira antibodies was positive. The diagnosis of leptospirosis was confirmed by a positive microagglutination test to Leptospira interrogans serovar Australis by a fourfold rise in antibody titer in paired sera collected during convalescence. Leptospirosis presenting with pulmonary hemorrhage has been associated with significant mortality but it can be successfully treated with early clinical suspicion of alveolar hemorrhage and prompt therapy.

Influenza among U.K. Pilgrims to Hajj, 2003

To the Editor: Each year, approximately 2 million Muslims travel from all over the world to participate in hajj. Approximately 22,000 pilgrims travel from the United Kingdom to Makkah, Saudi Arabia; of those, approximately 1,000 pilgrims reside in the east end of London. In the past, infectious diseases research conducted during these pilgrimages focused on meningococcal disease because of outbreaks associated with the hajj. Since 2000, the dates of the hajj have been moved back into the winter season; this time change could lead to a seasonal increase in outbreaks of respiratory infections caused by influenza and other viruses. From 1991 to 1992, influenza A was a common cause of respiratory infection in pilgrims tested in Makkah (1). However, the incidence rate of influenza among pilgrims from Europe is not well-known. A previous study of influenzalike illness among pilgrims from Pakistan reported rates of 36% in influenza-vaccinated pilgrims and 62% in influenza-nonvaccinated pilgrims; these results were based on clinical endpoints without microbiologic confirmation (2). We assessed the risk for influenza infection among a cohort of pilgrims from the east end of London who participated in the hajj in 2003. From December 2002 to January 2003, we enrolled 115 participants who planned to take part in hajj in 2003. The study was approved by the North London Multicentre Research Ethics Committee and the Trustees of East London Mosque. Informed consent was obtained through appropriate translators. All participants attended the East London Mosque, Whitechapel, London; 30 were vaccinated with influenza vaccine (A/New Caledonia/20/99 [H1N1]-like strain, A /Moscow/10/99 [H3N2]-like strain, B/Sichuan/379/99-like strain). Venous blood samples were collected, and questionnaires were completed before the participants departed for the hajj and within 2–3 weeks of their return in February to March 2003. Tests for influenza A and B were conducted by using hemagglutination inhibition against the following influenza antigens: A/NewCalidonia/20/99, A/Wuhan/371/91, A/Sydney/5/97, A/Panama/2007/99, B/Sichuan/379/99, and B/Harbin/7/94. A diagnosis of influenza was made based on seroconversion with at least a fourfold rise in antibody titer. Based on seroconversion, the influenza attack rate among all pilgrims was 38% (44/115). The attack rate was 30% among the vaccinated and 41% among the nonvaccinated participants (Table) (odds ratio for influenza in vaccinees = 0.61, p = 0.28). Of the 44 patients, 42 (37%) were infected with influenza A H3N2; 1 had influenza A H1N1, and 1 had influenza B infection. Six influenza A H3N2 patients were dually infected; two patients seroconverted to A H1N1, and four patients seroconverted to influenza B. Nearly half (21/44) of the patients with influenza received a course of antimicrobial drugs while on the hajj compared with 38% (27/71) of those who did not seroconvert. The attack rate in the vaccinated patients was lower than the rate in nonvaccinated patients, which is consistent with some protective effect of the influenza vaccine. Table Seroconversion and respiratory symptoms due to influenza infection and vaccination status among U.K. pilgrims Even though blood was collected from five convalescing patients within 3 weeks of their return from the hajj, some of the patients may have acquired influenza B infection immediately after their return to the United Kingdom, as it was the main strain circulating in the United Kingdom in late February to March 2003. Many pilgrims from throughout the world, some of whom may carry H3N2 drift variants, mingle closely during the hajj. This type of exposure increases the risk for worldwide spread of new drift variants and other contagious respiratory diseases (3). Given the potential for the high influenza attack rate documented in this study, all pilgrims, regardless of age, should be offered influenza vaccination before they travel on the hajj during winter months. On-site testing for influenza should be available to medical services in Makkah (and countries of origin), and treatment with a neuraminidase inhibitor should be offered to persons who test positive and have been symptomatic for <48 hours (4). This treatment should lessen the transmission risk to pilgrims during the crowded events during travel and on their return home (5). When pilgrims return from the hajj, physicians should be informed that pilgrims may bring back new drift variants of influenza; physicians should consider the diagnosis and treat persons at risk and their close contacts (4).