Serological Titers Research Articles

Application of different laboratory techniques to monitor the behaviour of a Mycoplasma synoviae vaccine (MS-H) in broiler breeders

BackgroundMycoplasma synoviae (MS) is a major poultry pathogen which causes severe economic losses in all the productive sectors. The prevalence of MS in European countries has increased in the last few years, leading to greater attention to the available methods to prevent its spread. The main strategy currently applied for its containment is the development and maintenance of MS-free breeder flocks. A live MS vaccine (MS-H) obtained by mutagenizing an Australian field strain has recently been introduced in Italy. The aim of the present study was to evaluate the vaccine behaviour in broiler breeder groups at different production stages and the effectiveness of the available laboratory tests in discriminating the MS-H from a field strain.ResultsThe vaccine diffused extensively through the population, shown by the wide serological response (over 80% of positive samples in RSA and 85% in ELISA), the high serological titres, the positivity of all the tracheal samples collected during the production phase by MS PCR and the positivity by cultivation from tracheal swabs at the end-point (55 weeks after vaccination). In contrast, only one swab from a sternal bursa was positive in MS PCR, while all the joint and oviduct samples were negative. There was no evidence of vertical transmission. Different genotyping techniques were used to achieve a clear classification of the MS positive samples. The vlhA and the obg gene analysis showed that most of the strains were homologous with the vaccine, but some ambiguous samples were further investigated with the multi locus sequence typing (MLST) scheme which confirmed the homology.ConclusionsThe development of a multi-technique approach to monitor vaccinated avian flocks, based both on serological and biomolecular methods, is advised as well as the use of effective genotyping techniques to analyse the MS strains circulating in high densely populated poultry areas.

Trends in Q fever serologic testing by immunofluorescence from four large reference laboratories in the United States, 2012\u20132016

Laboratory testing for Q fever (Coxiella burnetii) is essential for a differential diagnosis, yet little is known about Q fever diagnostic testing practices in the United States. We retrospectively analyzed Q fever immunoglobulin G (IgG) indirect immunofluorescence assay (IFA) testing data between 1/1/2012–10/31/2016 from ARUP, LabCorp, Mayo Medical Laboratories, and Quest Diagnostics. Data included IgG phase I and phase II titers, patient age and sex, and state and date of specimen collection. On average, 12,821 specimens were tested for Q fever annually by the participating laboratories. Of 64,106 total specimens, 84.1% tested negative for C. burnetii-specific antibodies. Positive titers ranged from 16 to 262,144 against both phase I and phase II antigens. Submission of specimens peaked during the summer months, and more specimens were submitted from the West North Central division. Testing occurred more frequently in males (53%) and increased with age. In conclusion, few U.S. Q fever cases are reported, despite large volumes of diagnostic specimens tested. Review of commercial laboratory data revealed a lack of paired serology samples and patterns of serology titers that differ from case reporting diagnostic criteria.

MAT cross-reactions or vaccine cross-protection: retrospective study of 863 leptospirosis canine cases

Dogs are naturally exposed to numerous pathogenic serogroups. Leptospirosis vaccines are claimed to afford a clinical protection restricted to the serogroups of which they are composed. ObjectivesDogs exhibiting liver and kidney injury were suspected of having leptospirosis. The purpose of this study was to compare the microscopic agglutination test (MAT) results in naive and vaccinated dogs experiencing leptospirosis outcomes. Only MAT-positive animals were included in the study. MethodsOver five years, 3 512 dogs were suspected of having leptospirosis. For each case, biochemical parameter results were recorded. Leptospirosis involvement was investigated by MAT performed against 6 major serogroups (Icterohaemorrhagiae, Canicola, Australis, Autumnalis, Grippotyphosa and Sejroë). MAT-positive results confirmed leptospirosis cases in 147 naïve dogs and in 580 fully vaccinated dogs. Serological titres of agglutinating antibodies were related to the severity of liver and kidney failure. ResultsThe most prevalent outcome of leptospirosis in unvaccinated dogs was liver failure (57.8%) compared to 51.7% for kidney disease, but the most severe onset (90.8%) was found among the cases of acute kidney injury compared to the severe (42.3%) hepatitis cases. In dogs vaccinated by bivalent Icterohaemorrhagiae and Canicola bacterins, hepatitis decreased from 57.8 to 46.5% and acute kidney injury from 51.7 to 21.6%. The decrease was shown in leptospirosis cases induced by field strains belonging to the six most prevalent serogroups, including the 4 serogroups heterologous to the vaccine. ConclusionCommon vaccination was efficient in decreasing hepatitis and kidney failure induced by field Leptospira spp infection regardless of the MAT-prominent serogroup and limited the disease severity in the remaining cases.

Brucellosis Relapse: A Retrospective Study of Risk Factors among Saudi Patients

Background and study aim: Brucellosis is one of the most common zoonotic infections worldwide. Brucella organisms are able to survive and even multiply within mononuclear cells explaining the tendency of the disease to have a prolonged clinical course and relapse. The incidence of relapse in Brucellosis remains high; ranging from 5-30% of patients. The aim of this study is to evaluate possible risk factors of Brucellosis relapse. Patients and Methods: A retrospective study of 127 patients was conducted to evaluate risk factors of Brucellosis relapse. The diagnosis of relapse was based on recurrence of clinical picture within 3-6 months from treatment, increase agglutinating antibody titers and PCR. Different demographic, clinical, laboratory and serological parameters were studied based on the data gathered from the patients` electronic files. Results: Out of 127 patients, 21 (16.5%) patients were diagnosed as relapsers. No significant differences were found between relapsed and non-relapsed patients regarding age, sex, residence, clinical features, complications, lymphocytic count and serological titers. As regard treatment, regimens included Streptomycin and Doxycycline had a significant decrease in relapse occurrence. Conclusion: Anti-microbial regimen included Streptomycin and Doxycycline is the only preventive factor for Brucellosis relapse.

Abstract 3051: Prognostic value of 18F-FDG PET/CT parameters in patients with primary pulmonary lymphoepithelioma-like carcinoma

Abstract Introduction Pretreatment tumor metabolic burden, which measured by fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) have been shown to predict outcomes in various malignancies. Epstein-Barr virus (EBV) serology titer in pulmonary LELC is correlated to stage. However, the prognostic value of 18F-FDG PET/CT in patients with pulmonary lymphoepithelioma-like carcinoma (LELC) and the relationship between EBV viral load remained unknown. The current study aims to investigate the prognostic value and association between functional parameters of 18F-FDG PET/CT and serum EBV DNA in patients with pulmonary LELC. Methods This retrospective study comprised 32 patients with pulmonary LELC who underwent pretreatment 18F-FDG PET/CT between January 2008 and December 2016. The EBV viral load and the functional parameters of 18F-FDG PET/CT were used for survival analysis. Results The value of pre-treatment serum EBV DNA had significantly positive correlation with whole MTV (r = 0.63, P = 0.0337) and whole TLG (r = 0.77, P = 0.0093). Advanced tumor stage (≥III) and high whole MTV (≥72.58) significantly predicted poor PFS. Multivariate survival analysis for PFS showed that there was a trend toward a lower risk of recurrence in patients with early tumor stage (≤II) (HR = 0.112, 95% CI =0.011-1.117, P = 0.062, Table 3), albeit not significantly so. Advanced tumor stage (≥III), high whole MTV (≥72.58) and high whole TLG (≥278.4) were predictors of poor OS. However, in multivariate survival analysis, none of them were independent predictors for OS. EBV viral load was not prognostic factor for both PFS and OS. Conclusion Greater whole MTV and whole TLG predicted poorer OS in patients with primary pulmonary LELC. Functional parameter of 18F-FDG PET/CT may provide useful prognostic information. Serum EBV DNA was closely related to whole MTV and TLG, but not a prognostic factor. Citation Format: Yueh-Fu Fang, Chun-Yu Lin. Prognostic value of 18F-FDG PET/CT parameters in patients with primary pulmonary lymphoepithelioma-like carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3051.

Abstract 4942: Serologic markers of infectious agents and ovarian cancer: Markers of prior Chlamydia trachomatis infection associated with increased ovarian cancer risk in two independent populations

Abstract Background: Pelvic inflammatory disease (PID) has been associated with ovarian cancer and Chlamydia trachomatis (chlamydia) is the leading cause of PID in the developed world. Primary infection with chlamydia is often asymptomatic and may persist for several months/years, thus ascertainment of PID in epidemiologic studies is challenging due to pervasive misclassification and under-reporting. To improve our understanding of the role of chlamydia and other infectious agents in developing ovarian cancer, we evaluated serologic markers of infection with incident ovarian cancer using a staged approach in two independent populations. Methods: Studies included: 1) a case-control study conducted in Poland of 278 ovarian cancer cases diagnosed from 2000 to 2003 and age- and study site-matched controls (n=556) and 2) a nested case-control study from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial including 160 women who eventually developed ovarian cancer and 159 matched controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the association between serologic marker titers and ovarian cancer risk using logistic regression adjusted for matching factors and potential confounders. We evaluated laboratory cutpoints indicative of prior chlamydia infection and tested more stringent marker thresholds, identified in Poland and applied in PLCO, that could be relevant for a PID-like infection. Results: In the Polish study, positivity for the chlamydia plasmid-encoded Pgp3 protein was associated with increased ovarian cancer risk [OR (95% CI): 1.63 (1.20-2.22)]; when a positive result was redefined at a higher titer, ovarian cancer risk increased [cutpoint 2: 2.00 (1.38-2.89); cutpoint 3 (max OR): 2.19 (1.29-3.73)]. All other chlamydia markers measured were associated with increased risk at the more stringent positivity threshold in Poland. In the prospective PLCO study, Pgp3 was associated with elevated risk at the laboratory cutpoint [1.43 (0.78-2.63)]; using higher thresholds, Pgp3 was associated with increased ovarian cancer risk [cutpoint 2: 2.25 (1.07-4.71); cutpoint 3: 2.53 (0.63-10.08)]. In both studies, markers of other infections (i.e., Mycoplasma genitalium, herpes simplex virus-2, human papillomavirus, herpes simplex virus-1, polyomavirus, hepatitis B, hepatitis C, Epstein Barr virus, cytomegalovirus) measured were not associated with risk. Conclusions: In two independent populations, the gold standard serologic marker of prior/current chlamydia infection (Pgp3) was associated with a doubling in ovarian cancer risk, whereas markers of other infectious agents were unrelated. Although these findings need to be replicated, they suggest potential ovarian cancer risk reduction through targeted treatment of chlamydia infections. Citation Format: Britton Trabert, Tim Waterboer, Sally B. Coburn, Louise A. Brinton, Mark E. Sherman, Jolanta Lissowska, Beata Peplonska, Patricia Hartge, Michael Pawlita, Nicolas Wentzensen. Serologic markers of infectious agents and ovarian cancer: Markers of prior Chlamydia trachomatis infection associated with increased ovarian cancer risk in two independent populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4942.

Is Italian population protected from Poliovirus? Results of a seroprevalence survey in Florence, Italy

ABSTRACTObjectives: Periodical assessments of population susceptibility to polioviruses (PV) is essential for evaluating population protection and planning appropriate vaccination strategies. The aim of the current work was to assess serological protective titers against all three polioviruses in the general population of Florence. Methods: A convenience sample of 328 sera, collected in 2009 in Florence (Central Italy) was analyzed. Samples were considered protective if neutralizing antibodies were detected at dilutions ≥1:8, according to the WHO protocols. Results: The immune coverage was 75.3%, 69.2% and 46% for PV1, PV2 and PV3, respectively. The protective titers of neutralizing antibodies were generally higher in children up to 14 years of age, with 74.4% (PV1), 75.6% (PV2) and 56.7% (PV3) of seroprevalence. From the age of 11 years, most of the study subjects were seronegative for PV3. Conclusions: In a polio-free country with strong migration pressures, such as Italy, our results bring clear support to the recent recommendation of Italian health authorities to introduce a fifth dose of IPV vaccine in adolescence all over the country.

High incidence of leptospirosis in an observational study of hospital outpatients in Vanuatu highlights the need for improved awareness and diagnostic capacities.

BackgroundEstimates of leptospirosis morbidity identified Oceania as the region with highest burden. Besides Australia and New Zealand, Oceania is home of Pacific Island Countries and Territories, most of which are developing countries facing a number of challenges. Their archipelago geography notably affects health infrastructure and access to healthcare. Although human leptospirosis was formerly identified in Vanuatu, there is a lack of knowledge of this disease in the country. We aimed to identify leptospirosis in outpatients visiting the hospital.Methodology/Principal findingsWe conducted a clinical study to investigate leptospirosis as a cause of non-malarial acute febrile illness in Vanuatu. A total 161 outpatients visiting the outpatient clinics at Port Vila Central Hospital for internal medicine were recruited over 20 month. We showed that leptospirosis significantly affects humans in Vanuatu: 12 cases were confirmed by real-time PCR on acute blood samples (n = 5) or by high serology titers evidencing a recent infection (MAT titer ≥800 or ELISA≥18 Units, n = 7). A high rate of positive serology was also evidenced, by MAT (100<titer<800, 9 patients) or ELISA IgM (ELISA≥12 Units, 20 patients, including 6 also positive in MAT), showing frequent exposure to pathogenic leptospires, notably from serogroup Australis.Conclusions/SignificanceThe high numbers of both seropositive patients and acute leptospirosis cases observed in outpatients visiting Port Vila Central Hospital suggest a high exposure to pathogenic Leptospira in the population studied. The MAT serology pointing to serogroup Australis as well as exposure history suggest that livestock animals largely contribute to the burden of human leptospirosis in Vanuatu. The analysis of residential and travel data suggests that the risk might even be higher in other islands of the Vanuatu archipelago. Altogether, our study emphasizes the need to increase awareness and build laboratory capacity to improve the medical care of leptospirosis in Vanuatu.

Development of Dengue Virus Serotype-Specific NS1 Capture Assays for the Rapid and Highly Sensitive Identification of the Infecting Serotype in Human Sera.

Dengue fever can be caused by one of four distinct dengue virus (DENV) serotypes that cocirculate in many parts of the world. Point of care serotype-specific nonstructural protein-1 (NS1) capture assays for the rapid serotyping of DENV in human sera would greatly support epidemiological surveillance and potentially also prognosis in individual patients. To ensure both serotype specificity and broad coverage of variants within serotypes, we have applied an innovative approach for the generation and selection of serotype-specific anti-NS1 mAbs. To elicit mAbs against conformational epitopes, NMRI mice were immunized with living HEK 293 transfectants expressing the native target Ags in multiple display on the cell surface. For each serotype, three different NS1 sequence variants were sequentially used for immunization of mice, hybridoma selection, and capture assay development, respectively. Selection of optimal combinations of capturing and detecting mAbs yielded highly sensitive and specific NS1 serotyping ELISAs (st-ELISAs) for the four serotypes. st-ELISA testing of 41 dengue patient sera showed a 100% concordance with the serotype determined by serotype-specific reverse transcriptase real-time quantitative PCR. The respective NS1 variants could be detected for ∼10 d after the onset of illness. Ab-dependent enhancement of DENV infections may be associated with a specific range of pre-existing anti-DENV serological Ab titers. Testing of patient sera with the developed st-ELISAs will not only be useful for epidemiological studies and surveillance, but it may also help to develop and validate assays that can distinguish protective versus enhancing Ab responses for risk assessment for the development of severe dengue disease in individual patients.

Diagnosis of ocular toxocariasis by detecting antibodies in the vitreous humor

Abstract Objectives To demonstrate the production of the local toxocara antibodies in the vitreous of patients with negative serology. Material and methods Retrospective review of the medical records of patients seen in a Tertiary Referral Hospital, and at an Eye Institute, with an ocular diagnosis of toxocariasis who had a negative serology and positive titers in the vitreous. Results After reviewing the medical records of 40 patients with a diagnosis of ocular toxocariasis, a total of six cases (15%) were found with a negative serology and a positive vitreous titer for toxocara antibody, both of them performed using an ELISA procedure. The mean age was 18 years, there were no differences observed between males and females. A peripheral granuloma was the most common clinic finding, and all patients underwent vitrectomy either to remove epiretinal membranes or to repair retinal detachments. Conclusion A negative serology does not rule out a diagnosis of ocular toxocariasis. Vitreous samples may be necessary to confirm a clinical diagnosis.

Diagnóstico de toxocariasis ocular mediante la demostración de anticuerpos en el humor vítreo

ObjectivesTo demonstrate the production of the local toxocara antibodies in the vitreous of patients with negative serology. Material and methodsRetrospective review of the medical records of patients seen in a Tertiary Referral Hospital, and at an Eye Institute, with an ocular diagnosis of toxocariasis who had a negative serology and positive titres in the vitreous. ResultsAfter reviewing the medical records of 40 patients with a diagnosis of ocular toxocariasis, a total of six cases (15%) were found with a negative serology and a positive vitreous titre for toxocara antibody, both of them performed using an ELISA procedure. The mean age was 18 years, there were no differences observed between males and females. A peripheral granuloma was the most common clinic finding, and all patients underwent vitrectomy either to remove epiretinal membranes or to repair retinal detachments. ConclusionA negative serology does not rule out a diagnosis of ocular toxocariasis. Vitreous samples may be necessary to confirm a clinical diagnosis.

Efficacy of a high-potency multivalent foot-and-mouth disease virus vaccine in cattle against heterologous challenge with a field virus from the emerging A/ASIA/G-VII lineage

In 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East were discovered to be caused by a viral lineage (A/ASIA/G-VII), which has recently emerged from the Indian sub-continent. In vitro vaccine matching data generated by the World Reference Laboratory (WRLFMD) indicated that A/ASIA/G-VII field viruses were poorly matched with vaccines (A-SAU-95, A22 IRQ and A-IRN-05) that are already used in the region. In order to assess the likely performance of one of these commercially available FMD vaccines, sixteen cattle were vaccinated with a polyvalent vaccine which contained two serotype A components (A-SAU-95 and A-IRN-05) with a homologous potency of at least 6PD50, and two cattle were left unvaccinated as controls. Twenty-one days later, all 18 cattle were challenged by tongue inoculation with an FMDV field isolate A/IRN/22/2015 from the A/ASIA/G-VII lineage, in line with the European Pharmacopeia PPG test conditions. The two control animals developed generalised FMD, and 7/16 vaccinated animals developed at least one foot lesion, thus only 56.3% were defined as protected. For the vaccine components, there was a significant increase in the probability of protection with increasing serological titres for A-SAU-95 (p = 0.03), but not for A-IRN-05 (p = 0.42). Analysis of FMDV in blood and nasal swabs suggested that vaccination reduced shedding and potential onward spread of FMD virus even if the animal developed foot lesions. In summary, the results from this study suggest that whilst this vaccine would not be appropriate for use in an emergency situation (in previously FMD-free countries), it may be partially effective in the field in endemic countries where repeat prophylactic vaccination is practiced. For emergency reactive vaccination, the findings from this study support the idea that a new vaccine strain should be developed that is tailored to the A/ASIA/G-VII lineage.

A Web Application to Facilitate Syphilis Reactor Grid Evaluations.

Many health departments use a "reactor grid" to determine which laboratory-reported syphilis serologic test results require investigation. We developed a Web-based tool, the Syphilis Reactor Grid Evaluator (SRGE), to facilitate health department reactor grid evaluations and test the tool using data from Seattle & King County, Washington. We developed SRGE using the R Shiny Web application framework. When populated with a data set including titer results and final disposition codes, SRGE displays the percent of verified early syphilis cases by serologic titer result and patient age in each cell of the grid. The results can be optionally stratified by sex, test type, and previous rapid plasma reagin titer. The impact of closing laboratory results without investigation in cells selected by the user is dynamically computed. The SRGE calculates the percent of all laboratory reports closed ("efficiency gained"), the proportion of all early syphilis cases closed without investigation ("case finding loss"), and the ratio of percent of cases identified for investigation to percent of all laboratory reports investigated ("efficiency ratio"). After defining algorithms, users can compare them side-by-side, combine subgroup-specific algorithms, and export results. We used SRGE to compare the current Public Health-Seattle & King County (PHSKC) reactor grid to 5 alternate algorithms. Of 13,504 rapid plasma reagin results reported to PHSKC from January 1, 2006, to December 31, 2015, 1565 were linked to verified early syphilis cases. Updating PHSKC's current reactor grid could result in an efficiency gain of 4.8% to 25.2% (653-3403 laboratory reports) and case finding loss of 1% to 8.4% (10-99 fewer cases investigated). The Syphilis Reactor Grid Evaluator can be used to rapidly evaluate alternative approaches to optimizing the reactor grid. Changing the reactor grid in King County to close more laboratory results without investigation could improve efficiency with minimal impact on syphilis case finding.

Pacemaker lead endocarditis: A rare cause of relapsing brucellosis.

Implantable cardioverter-defibrillator endocarditis is a rare and potentially life threatening complication of brucellosis of difficult management for clinicians. We report an unusual case of pacemaker-related endocarditis due to Brucella melitensis in a patient with previous history of neurobrucellosis. Our patient was admitted to a hospital with severe swelling of his pacemaker pocket implanted 8 years earlier for sick sinus syndrome. Although pocket site cultures were positive for Brucella but blood cultures were not and serologic titer by the Rose Bengal test was positive. Transesophageal echocardiography showed two vegetations on the pacemaker leads. The patient was treated with doxycycline, rifampin and gentamicin with full recovery and the entire pacemaker apparatus was surgically explanted. Interestingly, two year prior this admission, the patient presented with meningoencephalitis diagnosed with neurobrucellosis proven by positive growth of Brucella mellitensis from the CSF. The patient was treated with doxycycline, rifampin and gentamicin with full recovery and the pacemaker had been removed. Reports of Brucella infection of prosthetic implants and devices have increased over the past decade. Consequently, potential relapsing of the disease and occupational exposure to Brucella should be considered in the differential diagnosis and management of cardiac device infection.

Evidence of interspecies transmission of pathogenic Leptospira between livestock and a domestic cat dwelling in a dairy cattle farm.

A domestic cat dwelling in a dairy cattle farm with haematuria was referred for a physical examination. The examination showed no abnormalities therefore complementary exams were performed. Leukocytosis with neutrophilia, monocytosis and hyperproteinaemia were detected. The urine analysis showed a bacterial infection without ultrasound findings. Serological titers to Leptospira interrogans serovar Pomona and Autumnalis were detected. Molecular analysis demonstrated the presence of Leptospira spp. in urine. The findings were consistent with subclinical leptospirosis. The cattle herd had evidence of Leptospira infection. The microbiological exams confirmed the presence of the Leptospira spp. in urine and serum. According to the evidence presented in this study, cats that dwell within a dairy farm could play a role in the Leptospira infection epidemiologically. The importance of feline leptospirosis must be evaluated with leptospirosis control in livestock.

Clinical Characteristics of Patients Diagnosed with Strongyloidiasis in a United States Urban Outpatient Dermatology Department: A Case Series

Background: Although considered a tropical disease, strongyloidiasis may be encountered in non-endemic regions, primarily amongst immigrants and travelers from endemic areas. Chronic strongyloides infection may be under-detected owing to its non-specific cutaneous presentation and the low sensitivity of commonly used screening tools. Methods: 18 consecutive patients with serologic evidence of strongyloides infestation who presented to a single urban, academic dermatology clinic between September 2013 and October 2016 were retrospectively included. Patient age, sex, country of origin, strongyloides serology titer, absolute eosinophil count, presenting cutaneous manifestations, and patient reported subjective outcome of pruritus after treatment were obtained via chart review. Results: Of the 18 patients, all had non-specific pruritic dermatoses, 36% had documented eosinophila and none were originally from the United States. A majority reported subjective improvement in their symptoms after treatment. Conclusion: Strongyloides infection and serologic testing should be considered in patients living in non-endemic regions presenting with pruritic dermatoses and with a history of exposure to an endemic area.Key Points:Chronic strongyloidiasis can be encountered in non-endemic areas and clinical manifestations are variableEosinophilia was not a reliable indicator of chronic infection in this case series Dermatologists should consider serologic testing for strongyloidiasis in patients with a history of exposure and unexplained pruritus

Heartworm-associated respiratory disease (HARD) induced by immature adult Dirofilaria immitis in cats

BackgroundA controlled, blind research study was conducted to define the initial inflammatory response and lung damage associated with the death of immature adult Dirofilaria immitis in cats as compared with cats developing adult heartworm infections and cats on preventive medication.MethodsThree groups of cats were utilized, 10 per group. All cats were infected with 100 third-stage (L3) larvae by subcutaneous injection. Group A cats were treated topically with selamectin (Revolution®; Zoetis) per label directions at 28 days post infection (PI) and once monthly for 8 months. Group B cats were treated orally with ivermectin (Ivomec®; Merial) at 150 μg/kg at 70 days PI, then every 2 weeks for 5 months. Group C cats were untreated PI. At baseline (Day 0) and on Days 70, 110, 168, and 240 PI, peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected on all cats. Upon completion of the study (Day 245), cats were euthanized and necropsies were conducted.ResultsResults were analyzed statistically between groups by ANOVA and by paired sample T testing for changes within the group over time. The selamectin-treated cats (Group A) did not develop radiographically evident changes throughout the study and were free of adult heartworms or worm fragments at necropsy. The heartworm life cycle was abbreviated with oral doses of ivermectin (Group B), shown by the absence of adult heartworms or worm fragments at necropsy. The early stage of immature adult worm in Group B cats, however, did induce severe pulmonary airway, interstitial, and arterial lung lesions, revealing that the abbreviated infection is a significant cause of respiratory pathology in cats. Cats in Groups B and C could not be differentiated based on radiographic changes, serologic antibody titers, complete blood count, or bronchoalveolar lavage cytology at any time point throughout the study. Eighty percent of cats in Group A and 100% of cats in Groups B and C became heartworm antibody positive at some time point post infection.ConclusionsThe clinical implications of this study are that cats that become infected with immature adult heartworms may not develop fully mature heartworms and are only transiently heartworm antibody positive, but do develop Heartworm-Associated Respiratory Disease (HARD).

Effectiveness of single-dose azithromycin to treat latent yaws: a longitudinal comparative cohort study.

Treatment of latent yaws is a crucial component of the WHO yaws eradication strategy to prevent relapse and the resulting transmission to uninfected children. We assessed the effectiveness of single-dose azithromycin to treat patients with latent yaws. This population-based cohort study included children (age <20 years) living on Lihir Island, Papua New Guinea, with high-titre (rapid plasma reagin titre ≥1:8) latent or active yaws, between April, 2013, and May, 2015. Latent yaws was defined as lack of suspicious skin lesions or presence of ulcers negative for Treponema pallidum subsp pertenue on PCR, and active yaws was defined as ulcers positive for T pertenue on PCR. All children received one oral dose of 30 mg/kg azithromycin. The primary endpoint was serological cure, defined as a two-dilution decrease in rapid plasma reagin titre by 24 months after treatment. Treatment of latent yaws was taken to be non-inferior to that of active yaws if the lower limit of the two-sided 95% CI for the difference in rates was higher than or equal to -10%. This study is registered with ClinicalTrials.gov, number NCT01955252. Of 311 participants enrolled, 273 (88%; 165 with latent yaws and 108 with active yaws) completed follow-up. The primary endpoint was achieved in 151 (92%) participants with latent yaws and 101 (94%) with active yaws (risk difference -2·0%, 95% CI -8·3 to 4·3), meeting the prespecified criteria for non-inferiority. On the basis of decline in serological titre, oral single-dose azithromycin was effective in participants with latent yaws. This finding supports the WHO strategy for the eradication of yaws based on mass administration of the entire endemic community irrespective of clinical status. Newcrest Mining Limited and ISDIN laboratories.

Toxocariasis: critical analysis of serology in patients attending a public referral center for ophthalmology in Brazil.

To analyze the contribution of IgG anti-Toxocara antibodies in the diagnosis of ocular toxocariasis (OT) in serum samples of patients attending a public referral center for ophthalmology in Brazil and to determine the most frequent ocular signs and symptoms. This was a retrospective descriptive study of a cohort of outpatients followed from December 1989 to May 2006. IgG anti-Toxocara antibody titers were determined by enzyme-linked immunosorbent assay. The results were correlated with the clinical and funduscopic findings. Of the diagnoses for the 126 patients, 42 were considered as probable OT, 48 as negative, and 36 as inconclusive. The median IgG anti-Toxocara antibody titers of the patients with probable OT were significantly higher than those of the patients in the negative or inconclusive groups (P=0.0001). Higher titers were observed more frequently in patients in the probable OT group (P=0.01) than in the negative group, in which titers were absent or lower in most patients (P<0.0001). The right eye was affected more in the OT group than in the negative group (P=0.01), and inflammation was located mostly in the intermediate and posterior poles. The mean age of the patients diagnosed with probable OT was significantly lower (mean, 8years) than that of the negative patients (mean, 14.5years) (P=0.006). Higher levels of antibodies could help with the diagnosis of OT in patients with symptoms and clinical signs; however, negative results cannot exclude possible OT. Conversely, patients with negative serology or low titers make the diagnosis of OT less likely.

Anti-Rickettsia rickettsii antibodies in capybaras (Hydrochoerus hydrochaeris Linnaeus, 1766) from an agricultural landscape in Araras, São Paulo, Brazil

Spotted fever is a typically endemic infectious disease caused by rickettsiae from the spotted fever group, of which Rickettsia rickettsii is the main etiologic agent. It presents high mortality rates in Brazil, with transmission to humans or animals through the bite of infected ticks. The capybara (Hydrochoerus hydrochaeris) is an important reservoir for Rickettsia spp.; these bacteria can circulate in an infected animal presenting only fever as a clinical sign of the disease, as demonstrated by experimental infection. Considering the high zoonotic potential and the damage caused to human, animal, and environmental health, this study searched for anti-Rickettsia rickettsii antibodies in capybaras from an agricultural landscape in the city of Araras, State of São Paulo, Brazil. The indirect immunofluorescence (IFA) technique was used to detect anti-R. rickettsii antibodies. From the 28 serum samples tested using IFA, 18 (64.28%) were considered reactive, with antibody titers ranging from 256 to 2048. Seven (38.88%) samples presented titers of 256, three (16.67%) with titers of 512, five (27.78%) with titers of 1024, and three (16.67%) with titers of 2048. However, it was not possible to significantly associate gender to these serologic results. These results demonstrate that at some point during their lives, the studied capybaras were exposed to the etiologic agent, but it is impossible to know when this occurred. Further studies need to be performed to clarify which serological titers ensure an infection in capybaras, based on clinical and laboratory assessment of rickettsemia, and to establish the relationship between titers and the chronicity of disease. This is necessary owing to the possibility of cross-reactions with other rickettsiae species of the same subgroup, leading to the need for molecular tests to confirm diagnosis.