The Mycoplasma conjunctivae genome sequencing, annotation and analysis

Infectious keratoconjunctivitis (IKC) is a contagious eye disease primarily caused by Mycoplasma conjunctivae in domestic and wild Caprinae. Chlamydophila species have also been detected in ruminants with IKC. The objectives...

BackgroundInfectious keratoconjunctivitis (IKC) is one of the most common ocular diseases in ruminants worldwide. In addition to keratitis and conjunctivitis, animals with IKC can develop uveitis, corneal ulcer, and in severe cases, blindness. The bacteria Moraxella spp. has been described as the primary causative agent of infectious bovine keratoconjunctivitis (IBK) in cattle (Bos taurus), while Chlamydia spp. and Mycoplasma conjunctivae are considered the main causative agents of IKC in sheep (Ovis aries). Previous studies indicated cervid herpesvirus 2 (CvHV2) as the primary causative agent of IKC in semi-domesticated reindeer (Rangifer tarandus tarandus). The aim of the study was to investigate the presence and prevalence of potential pathogens for IKC in reindeer, and compare the ocular microbiota of animals with IKC, with apparently healthy animals.ResultsSemi-domesticated reindeer (n = 341), with (n = 108) or without (n = 113) ocular clinical signs, or with no information on clinical status (n = 120), were sampled in Norway, Sweden and Finland in 2010–2014. Seroprevalence was 37.4% for alphaherpesvirus (95/254), 3.8% for gammaherpesvirus (8/211) and 7.1% for pestivirus (15/211) (ELISA). PCR analyses of conjunctival swab samples revealed a prevalence of 28.5% for CvHV2 (57/200), 11.9% for Chlamydiaceae (16/135) and 1.0% for M. conjunctivae (2/197). Bacteriological cultivation of 202 conjunctival swab samples revealed bacterial growth from 75.2% of the samples, with Moraxella spp. being isolated from 21.6% (11/51) of the animals with and 5.6% (5/84) without ocular clinical signs. A significant association (p < 0.001) existed between the presence of clinical signs of IKC and CvHV2 DNA in the affected eyes, an association that was not present for other microorganisms.ConclusionsThese results support the hypothesis that CvHV2 is the primary agent of IKC in semi-domesticated reindeer in Fennoscandia, with Moraxella bovoculi being a secondary candidate, since it was isolated in two different outbreaks of IKC. Further studies should be carried out to better understand the infection biology and the pathogenesis of IKC in reindeer.

The humoral immune response of three alpine chamois (Rupicapra rupicapra rupicapra), two alpine ibex (Capra ibex ibex) and three domestic sheep naturally affected with infectious keratoconjunctivitis (IKC), and four ibex and two sheep experimentally infected with Mycoplasma conjunctivae was analysed. In addition, the local immune response to M. conjunctivae was analysed using conjunctival washes from chamois and sheep. Immunoblot analysis of sera using whole cell antigens of M. conjunctivae revealed the major immunogenic proteins which had molecular masses of 175, 83, 68, 60, 50, 42, 36, and 33 kDa. Major antigens were found at 83, 68, 60, and 42 kDa in both sera and conjunctival washes from naturally infected animals of all three Caprinae species. In experimentally infected animals, antibodies to the 68 and 60 kDa antigens were dominant. Naturally infected animals showed much stronger immune reactions than those experimentally infected, and specific antibodies appeared 2 to 4 wk after experimental infection. To evaluate possible cross-reactions, whole cell antigen of M. conjunctivae was analysed by immunoblot against hyperimmune sera of closely related Mycoplasma spp. Antibodies to the 175, 73, 68, 60, and 33 kDa antigens appeared to be specific to M. conjunctivae. Cross-reactions mainly with 83, 50, and 42 kDa antigens were detected, in particular with M. ovipneumoniae and M. bovoculi hyperimmune sera, but also with antisera against M. capricolum capricolum and M. putrefaciens.

A serine-rich membrane protein named LppS from Mycoplasma conjunctivae, the aetiological agent of infectious keratoconjunctivitis (IKC) of domestic and wild Caprinae, was characterized. Gene cloning and sequence analysis of the lppS gene revealed that it encoded a membrane protein precursor. The protein had a typical signal sequence and a signal peptidase II cleavage site followed by a cysteine residue representing a potential acylation site. The mature LppS protein had an apparent molecular mass of 150 kDa and was found in the detergent-associated fraction of Tween 20 extracted M. conjunctivae proteins. It possessed a serine-rich domain of 41 aa with 37 (90.2 %) serine residues. Twenty-seven of these serine residues were contiguous. The protein adhered to lamb joint synovial cells. Using an in vitro adhesion model, Fab fragments from IgG directed against recombinant purified LppS were shown to specifically inhibit adhesion of M. conjunctivae to lamb cells. Thus, LppS is likely to be an adhesin of M. conjunctivae that may play an important role in the pathogenesis of IKC.

The management of infectious diseases in wildlife reservoirs is challenging and faces several limitations. However, detailed knowledge of host–pathogen systems often reveal heterogeneity among the hosts’ contribution to transmission. Management strategies targeting specific classes of individuals and/or areas, having a particular role in transmission, could be more effective and more acceptable than population-wide interventions. In the wild population of Alpine ibex (Capra ibex—a protected species) of the Bargy massif (French Alps), females transmit brucellosis (Brucella melitensis) infection in ~90% of cases, and most transmissions occur in the central spatial units (“core area”). Therefore, we expanded an individual-based model, developed in a previous study, to test whether strategies targeting females or the core area, or both, would be more effective. We simulated the relative efficacy of realistic strategies for the studied population, combining test-and-remove (euthanasia of captured animals with seropositive test results) and partial culling of unmarked animals. Targeting females or the core area was more effective than untargeted management options, and strategies targeting both were even more effective. Interestingly, the number of ibex euthanized and culled in targeted strategies were lower than in untargeted ones, thus decreasing the conservation costs while increasing the sanitary benefits. Although there was no silver bullet for the management of brucellosis in the studied population, targeted strategies offered a wide range of promising refinements to classical sanitary measures. We therefore encourage to look for heterogeneity in other wildlife diseases and to evaluate potential strategies for improving management in terms of efficacy but also acceptability.

SummaryBackgroundPreterm birth remains the major cause of neonatal death worldwide. South Asia contributes disproportionately to deaths among preterm births worldwide, yet few population-based studies have assessed the underlying causes of deaths. Novel evaluations, including histological and bacteriological assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of preterm deaths. We sought to assess underlying and contributing causes of preterm neonatal deaths in India and Pakistan.MethodsThe project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe) was a prospective cohort study done in three hospitals in Davangere, India, and two hospitals in Karachi, Pakistan. All pregnant females older than 14 years were screened at the time of presentation for delivery, and those with an expected or known preterm birth, defined as less than 37 weeks of gestation, were enrolled. Liveborn neonates with a weight of 1000 g or more who died by 28 days after birth were included in analyses. Placentas were collected and histologically evaluated. In addition, among all neonatal deaths, with consent, minimally invasive tissue sampling was performed for histological analyses. PCR testing was performed to assess microbial pathogens in the placental, blood, and fetal tissues collected. An independent panel reviewed available data, including clinical description of the case and all clinical maternal, fetal, and placental findings, and results of PCR bacteriological investigation and minimally invasive tissue sampling histology, from all eligible preterm neonates to determine the primary and contributing maternal, placental, and neonatal causes of death.FindingsBetween July 1, 2018, and March 26, 2020, of the 3470 preterm neonates enrolled, 804 (23%) died by 28 days after birth, and, of those, 615 were eligible and had their cases reviewed by the panel. Primary maternal causes of neonatal death were hypertensive disease (204 [33%] of 615 cases), followed by maternal complication of pregnancy (76 [12%]) and preterm labour (76 [11%]), whereas the primary placental causes were maternal and fetal vascular malperfusion (172 [28%] of 615) and chorioamnionitis, funisitis, or both (149 [26%]). The primary neonatal cause of death was intrauterine hypoxia (212 [34%] of 615) followed by congenital infections (126 [20%]), neonatal infections (122 [20%]), and respiratory distress syndrome (126 [20%]).InterpretationIn south Asia, intrauterine hypoxia and congenital infections were the major causes of neonatal death among preterm babies. Maternal hypertensive disorders and placental disorders, especially maternal and fetal vascular malperfusion and placental abruption, substantially contributed to these deaths.FundingBill & Melinda Gates Foundation.

Severe keratinous hoof afflictions have been recorded in ibex (Capra ibex ibex) since 1995 and more recently in mouflon (Ovis aries musimon) in Switzerland. Based on clinical observations and comparison with diseases known to affect domestic ungulates, it was hypothesized these wild ungulates were affected by foot rot associated with infection with Dichelobacter nodosus. Dichelobacter nodosus has been shown to be the essential pathogen for initiation and establishment of foot rot, a highly contagious foot disease of sheep and goats. Because these bacteria could not be cultivated from affected ibex, we developed a nested polymerase chain reaction that allowed detection of D. nodosus without culture. Using this assay, we were able to diagnose D. nodosus infections of ibex, mouflon, and domestic sheep in natural outbreaks. From these results we conclude that D. nodosus plays an etiological role in foot rot not only in domestic but also in wild Caprinae.

Infections by Chlamydiae are associated with ocular disease in humans and animals. In this study, the presence and diversity of Chlamydia spp. was assessed in diseased and healthy eyes of domestic sheep and wild ruminants that share mountain habitats in northern Spain. The presence of Chlamydia spp. was tested by real-time PCR in 1786 conjunctival swabs collected from both eyes of 893 animals from mountain habitats in northern Spain, and chlamydial species were identified in the positive samples by ArrayTube microarray methods. Chlamydial DNA was detected in 0.6% (CI95% 0.2–1.3) of the Pyrenean chamois (Rupicapra pyrenaica) and 1.4% (CI95% <0.01–8.1) of the sheep (Ovis aries) sampled, with Chlamydia pecorum the only chlamydial species identified. No association of C. pecorum with ocular disease or co-infection with Mycoplasma conjunctivae was found. Further studies on the pathogenesis of infectious keratoconjunctivitis are needed to better understand the ecology of C. pecorum and its possible role as a ruminant pathogen at the wildlife–livestock interface.

Decline in Forced Expiratory Volume in 1 Second in Older Adults with Sickle Cell Disease Is Similar to Adults with Cystic Fibrosis

To better characterize the cause and location of death after radical prostatectomy (RP), as early mortality is relatively uncommon after RP, with little known about the cause of death among men who die within 30 days of RP, and the trend toward earlier discharge after surgery means that a greater proportion of early mortality after RP may occur out of hospital. Using the Ontario Cancer Registry, we identified 11,010 men (mean age 68 years) who had a RP in the province of Ontario between 1990 and 1999. We identified the occurrence and location of all deaths within 30 days of RP. The cause of death was obtained from death certificate information. Logistic regression was used to examine factors (age, comorbidity, year of surgery) associated with the location of death. Of the 11,010 men, 53 died within 30 days of RP (0.5%); of these 53 men, 28 (53%) died in hospital. Neither age, comorbidity nor year of surgery were significantly associated with location of death (P > 0.05). Major causes of death included cardiovascular disease (38%) and pulmonary embolism (13%). More than half of the patients who died out of hospital had an unknown cause of death. Almost half of all deaths within 30 days of RP occur out of hospital; the two most common causes of death are potentially preventable. More detailed cause-of-death information may help to identify opportunities for prevention.

background Verbal autopsy (VA) is used to ascertain causes of death using information obtained from bereaved relatives. Causes of death can be ascertained from VA questionnaires by a panel of physicians or from predefined algorithms. In a previous study, we developed data-derived algorithms using VA data from 796 adult deaths in hospitals in Tanzania, Ethiopia, and Ghana (primary sites). These computerized algorithms accurately estimated the cause-specific mortality fractions (CSMFs) for deaths due to injuries, meningitis, TB/AIDS and diarrhoeal diseases in the primary sites. Since the same data were used to generate and to validate the algorithms, the accuracy of our algorithms may have been overestimated. We report here on the validity of the algorithms when they were applied to VA data from two secondary sites in Ghana and Tanzania. Here, 'validity' is taken to mean the degree to which the algorithms replicated the physician-generated CSMF for major causes of death, when applied to the same VA data. methods VA interviews were conducted in two secondary sites: in Navrongo, Ghana, on 406 adult deaths, where three local physicians independently reviewed the questionnaires and assigned a cause of death. In Morogoro, Tanzania, VA interviews were conducted on 209 adult deaths, and a panel of physicians independently reviewed the VA questionnaires together with the hospital death certificates or hospital records to determine the cause of death. The CSMF obtained using each algorithm was compared with the CSMF obtained using physician review. results For injuries and meningitis, the algorithms and physician review estimated a similar CSMF in the Morogoro and Navrongo data. For TB/AIDS, the algorithm estimated a similar CSMF as the physicians in Morogoro. The algorithm for diarrhoeal diseases did not agree closely with the physicians in Morogoro or Navrongo. conclusions In general, our data-derived algorithms for assigning causes of death due to injuries, meningitis, and TB/AIDS estimated a similar CSMF as the physicians in the secondary sites. Recommendations for further validation and refinement are discussed. Computerized algorithms offer a potentially quick, affordable, and feasible method for assigning causes of death in mortality surveillance or studies using VA.

The genetic basis of sudden death in young people - Cardiac and non-cardiac.

The majority of travelers from the UK and Scotland visit Europe, particularly Spain and France, as well as North America, yet surveillance that aids in travel medicine guidance continues to focus on infectious diseases relating to developing countries. Here, we report on causes of death among all bodies returned to Scotland for cremation. Data collected by the Scottish Government on bodies being returned from abroad for cremation was collated for the period 2000 to 2004, and analyzed to identify the cause and location of death among travelers as well as to test the hypothesis that for death due to failure of the circulatory system among Scots there was a significant association between age at death and whether death occurred in Scotland or abroad. Of the 572 deaths reported between 2000 and 2004, 73% occurred in the European region and 10% in the Americas. With respect to the cause, trauma accounted for 20.4%, infectious diseases 1.5%, and other non-infectious causes accounted for 75.5% of deaths. Among the latter, the major cause of death was due to failure of the circulatory system (77.0%). A significant association was observed between death abroad due to failure of the circulatory system and younger age at death for all (χ(2) = 26.9, df = 3, p < 0.001) and for males (χ(2) = 20.7, df = 3, p < 0.001) but not for females (χ(2) = 2.7, df = 1, p = 0.099). The data indicates a low rate of death among Scots traveling abroad, with trauma and other non-infectious causes being the most common cause of death; failure of the circulatory system was the most common cause of death in the latter group. Europe and the Americas were the most common locations of death. Although travel health services should continue to advise travelers to developing countries on infectious disease risks, it is also important that travel health acts as venue for providing key advice and preventative means to all travelers, including those to developed countries. Those agencies, organizations, and companies who deal with travelers along their journey should also engage with travel health experts and practitioners to reduce the risk of adverse outcomes, including death, to travelers.

Using rigorous and transparent methods, Lawn et al. 3 have provided, for 193 countries in the year 2000, systematic estimates, with associated uncertainty, of the distribution of neonatal deaths for programme-relevant causes. Only 2.5% of neonatal deaths had reliable cause-of-death information available through vital registration systems, primarily in well-developed countries. The distribution of reported causes of deaths varied substantially between countries and across studies. The major direct causes of neonatal deaths globally were estimated to be infections (sepsis, pneumonia, tetanus, and diarrhoea; 35%), preterm birth (28%), and birth asphyxia (23%). There was substantial uncertainty around these estimates owing to the limited quantity and quality of data from settings in which the great majority (97.5%) of neonatal deaths had occurred. It is obvious that complex statistical models are not a panacea, and collecting reliable information on the causes of deaths should receive due attention. Simultaneously, it would be pertinent to highlight other important limitations and practical implications of this review. Several studies included in this review, primarily from low-income and middle-income countries, used verbal autopsy (lay reporting) tools to determine the causes of deaths. The neonate, especially in the first week of life, offers a limited symptomatic response to different insults resulting in substantial overlap of clinical manifestations of several diseases. The sensitivity and specificity of verbal autopsy technique in correctly identifying various causes of deaths is, therefore, sub-optimal. Validation studies suggest that although major congenital malformations and neonatal tetanus have high levels of sensitivity (0.79–0.98 for tetanus) and specificity (>0.9), the performance for other important conditions like septicaemia is poor. 4,5 The instrument using both open-ended

Rise in Youth Suicide Rates Confounds Experts