Increased glycemic variability in pregnant women with Roux-en-Y gastric bypass compared with sleeve gastrectomy.

INTRODUCTION: Bariatric surgery is associated with adverse pregnancy outcomes such as reduced birth weight and premature birth. One possible mechanism for this is increased glycemic variability (GV) which occurs after bariatric surgery. The objective of this study was to compare the effect of Roux-en-Y gastric bypass (RYGB) versus vertical sleeve gastrectomy (SG) on GV during pregnancy and to investigate the relationships of GV, type of bariatric surgery and maternal and neonatal outcomes. RESEARCH DESIGN AND METHODS: Fourteen pregnant women after RYGB and 14 after SG were investigated with continuous glucose monitoring in their second or third trimester in this observational study carried out as part of routine clinical care. RESULTS: Pregnant women with RYGB had similar mean interstitial glucose values but significantly increased indices of GV and a lower %time in range 3.9-7.8 mmol/L (70-140 mg/dL), compared with SG. CONCLUSIONS: Pregnant women who have undergone RYGB have greater GV during pregnancy compared with those who have undergone SG. Further research is needed to establish the relationship between GV and pregnancy outcomes to determine the preferred bariatric operation in women of reproductive age, and whether interventions to reduce GV might improve outcomes.

An Integrated Ecological Niche Modelling Framework for Risk Mapping of Peste des Petits Ruminants Virus Exposure in African Buffalo (Syncerus caffer) in the Greater Serengeti-Mara Ecosystem.

Peste des petits ruminants (PPR) is a highly contagious viral disease of small ruminants that threatens livelihoods and food security in developing countries and, in some cases, wild ungulate species conservation. The Greater Serengeti-Mara Ecosystem (GSME) encompasses one of the major wildlife populations of PPR virus (PPRV)-susceptible species left on earth, although no clinical disease has been reported so far. This study aimed to gain further knowledge about PPRV circulation in the GSME by identifying which factors predict PPRV seropositivity in African buffalo (Syncerus caffer). Following an ecological niche modeling framework to map host-pathogen distribution, two models of PPRV exposure and buffalo habitat suitability were performed using serological data and buffalo censuses. Western Maasai Mara National Reserve and Western Serengeti National Park were identified as high-risk areas for PPRV exposure in buffalo. Variables related to wildlife-livestock interaction contributed to the higher risk of PPRV seropositivity in buffalo, providing supportive evidence that buffalo acquire the virus through contact with infected livestock. These findings can guide the design of cost-effective PPRV surveillance using buffalo as a sentinel species at the identified high-risk locations. As more intensive studies have been carried out in Eastern GSME, this study highlights the need for investigating PPRV dynamics in Western GSME.

Modelling flock heterogeneity in the transmission of peste des petits ruminants virus and its impact on the effectiveness of vaccination for eradication.

Peste des petits ruminants (PPR) is an acute infectious disease of small ruminants targeted for global eradication by 2030. The Global Strategy for Control and Eradication (GSCE) recommends mass vaccination targeting 70% coverage of small ruminant populations in PPR-endemic regions. These small ruminant populations are diverse with heterogeneous mixing patterns that may influence PPR virus (PPRV) transmission dynamics. This paper evaluates the impact of heterogeneous mixing on (i) PPRV transmission and (ii) the likelihood of different vaccination strategies achieving PPRV elimination, including the GSCE recommended strategy. We develop models simulating heterogeneous transmission between hosts, including a metapopulation model of PPRV transmission between villages in lowland Ethiopia fitted to serological data. Our results demonstrate that although heterogeneous mixing of small ruminant populations increases the instability of PPRV transmission-increasing the chance of fadeout in the absence of intervention-a vaccination coverage of 70% may be insufficient to achieve elimination if high-risk populations are not targeted. Transmission may persist despite very high vaccination coverage (>90% small ruminants) if vaccination is biased towards more accessible but lower-risk populations such as sedentary small ruminant flocks. These results highlight the importance of characterizing small ruminant mobility patterns and identifying high-risk populations for vaccination and support a move towards targeted, risk-based vaccination programmes in the next phase of the PPRV eradication programme. Our modelling approach also illustrates a general framework for incorporating heterogeneous mixing patterns into models of directly transmitted infectious diseases where detailed contact data are limited. This study improves understanding of PPRV transmission and elimination in heterogeneous small ruminant populations and should be used to inform and optimize the design of PPRV vaccination programmes.

Dual biologic therapy for the treatment of rheumatic diseases and asthma: a case series.

Objective: Combination biological therapies are being considered increasingly for patients with multiple co-morbidities requiring biologics. There are limited data available on this approach, and concerns remain about the possible risk of adverse events, particularly infection. Methods: We present three patients on dual biologics for rheumatic disease and asthma. The biologic combinations used were etanercept and mepolizumab, infliximab and omalizumab, and etanercept and omalizumab. The time on combination biologic therapies ranged from 24 to 36 months. Patients were monitored for any serious adverse events. Results: All three patients were able to tolerate combined biologic therapies, with no serious adverse events. All three patients gained improvement in their rheumatic and asthma disease control, with reduction in disease activity scores and reduction in steroid usage. Conclusion: The decision to start dual biologic therapy should be considered carefully, on a case-by-case basis. The number of patients who are on combination biological therapy is small, and data are sparse. Real-world data are needed to examine the long-term benefits and risks of different forms of combination biologic therapies.

Sequestration and Destruction of Rinderpest Virus-Containing Material 10 Years after Eradication.

In 2021, the world marked 10 years free from rinderpest. The United Nations Food and Agriculture Organization and World Organisation for Animal Health have since made great strides in consolidating, sequencing, and destroying stocks of rinderpest virus-containing material, currently kept by only 14 known institutions. This progress must continue.

Managing liver fluke on hill farms.

This focus article has been prepared by Amanda Carson and Bryony Jones of the APHA Small Ruminant Expert Group and Dai Grove-White of the University of Liverpool.

Review of Peste des Petits Ruminants Occurrence and Spread in Tanzania.

Peste des petits ruminants (PPR) is an important transboundary animal disease of domestic small ruminants, camels, and wild artiodactyls. The disease has significant socio-economic impact on communities that depend on livestock for their livelihood and is a threat to endangered susceptible wild species. The aim of this review was to describe the introduction of PPR to Tanzania and its subsequent spread to different parts of the country. On-line databases were searched for peer-reviewed and grey literature, formal and informal reports were obtained from Tanzanian Zonal Veterinary Investigation Centres and Laboratories, and Veterinary Officers involved with PPR surveillance were contacted. PPR virus (PPRV) was confirmed in northern Tanzania in 2008, although serological data from samples collected in the region in 1998 and 2004, and evidence that the virus was already circulating in Uganda in 2003, suggests that PPRV might have been present earlier than this. It is likely that the virus which became established in Tanzania was introduced from Kenya between 2006-7 through the cross-border movement of small ruminants for trade or grazing resources, and then spread to eastern, central, and southern Tanzania from 2008 to 2010 through movement of small ruminants by pastoralists and traders. There was no evidence of PPRV sero-conversion in wildlife based on sera collected up to 2012, suggesting that they did not play a vectoring or bridging role in the establishment of PPRV in Tanzania. PPRV lineages II, III and IV have been detected, indicating that there have been several virus introductions. PPRV is now considered to be endemic in sheep and goats in Tanzania, but there has been no evidence of PPR clinical disease in wildlife species in Tanzania, although serum samples collected in 2014 from several wild ruminant species were PPRV sero-positive. Similarly, no PPR disease has been observed in cattle and camels. In these atypical hosts, serological evidence indicates exposure to PPRV infection, most likely through spillover from infected sheep and goats. Some of the challenges for PPRV eradication in Tanzania include movements of small ruminants, including transboundary movements, and the capacity of veterinary services for disease surveillance and vaccination. Using wildlife and atypical domestic hosts for PPR surveillance is a useful indicator of endemism and the ongoing circulation of PPRV in livestock, especially during the implementation of vaccination to control or eliminate the disease in sheep and goats. PPR disease has a major socio-economic impact in Tanzania, which justifies the investment in a comprehensive PPRV eradication programme.

Peste des Petits Ruminants Virus Infection at the Wildlife-Livestock Interface in the Greater Serengeti Ecosystem, 2015-2019.

Peste des petits ruminants (PPR) is a viral disease of goats and sheep that occurs in Africa, the Middle East and Asia with a severe impact on livelihoods and livestock trade. Many wild artiodactyls are susceptible to PPR virus (PPRV) infection, and some outbreaks have threatened endangered wild populations. The role of wild species in PPRV epidemiology is unclear, which is a knowledge gap for the Global Strategy for the Control and Eradication of PPR. These studies aimed to investigate PPRV infection in wild artiodactyls in the Greater Serengeti and Amboseli ecosystems of Kenya and Tanzania. Out of 132 animals purposively sampled in 2015-2016, 19.7% were PPRV seropositive by ID Screen PPR competition enzyme-linked immunosorbent assay (cELISA; IDvet, France) from the following species: African buffalo, wildebeest, topi, kongoni, Grant's gazelle, impala, Thomson's gazelle, warthog and gerenuk, while waterbuck and lesser kudu were seronegative. In 2018-2019, a cross-sectional survey of randomly selected African buffalo and Grant's gazelle herds was conducted. The weighted estimate of PPRV seroprevalence was 12.0% out of 191 African buffalo and 1.1% out of 139 Grant's gazelles. All ocular and nasal swabs and faeces were negative by PPRV real-time reverse transcription-polymerase chain reaction (RT-qPCR). Investigations of a PPR-like disease in sheep and goats confirmed PPRV circulation in the area by rapid detection test and/or RT-qPCR. These results demonstrated serological evidence of PPRV infection in wild artiodactyl species at the wildlife-livestock interface in this ecosystem where PPRV is endemic in domestic small ruminants. Exposure to PPRV could be via spillover from infected small ruminants or from transmission between wild animals, while the relatively low seroprevalence suggests that sustained transmission is unlikely. Further studies of other major wild artiodactyls in this ecosystem are required, such as impala, Thomson's gazelle and wildebeest.

Uterine Transplantation: Review of Livebirths and Reproductive Implications.

Uterine transplantation (UTx) is a fertility restoring treatment for women with absolute uterine factor infertility. At a time when there is no question of the procedure's feasibility, and as the number of livebirths begins to increase exponentially, various important reproductive, fetal, and maternal medicine implications have emerged. Detailed outcomes from 17 livebirths following UTx are now available, which are reviewed herein, along with contextualized extrapolation from pregnancy outcomes in other solid organ transplants. Differences in recipient demographics and reproductive aspirations between UTx and other transplant recipients make extrapolating management strategies and outcomes in other solid organ transplants inappropriate. Whereas preterm delivery remains prominent, small for gestational age or hypertensive disorders do not appear to be as prevalent following UTx when compared to other solid organ transplants. Given the primary objective of undertaking UTx is to achieve a livebirth, publication of reproductive outcomes is essential at this early stage, to reflect on and optimize the management of future cases.

European Reference Network for Rare Vascular Diseases (VASCERN) position statement on cerebral screening in adults and children with hereditary haemorrhagic telangiectasia (HHT).

Hereditary haemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia inherited as an autosomal dominant trait. Approximately 10 % of patients have cerebral vascular malformations, a proportion being cerebral arteriovenous malformations (AVMs) and fistulae that may lead to potentially devastating consequences in case of rupture. On the other hand, detection and treatment related-risks are not negligible, and immediate. While successful treatment can be undertaken in individual cases, current data do not support the treatment of unruptured AVMs, which also present a low risk of bleeding in HHT patients. Screening for these AVMs is therefore controversial.Structured discussions, distinctions of different cerebrovascular abnormalities commonly grouped into an "AVM" bracket, and clear guidance by neurosurgical and neurointerventional radiology colleagues enabled the European Reference Network for Rare Vascular Disorders (VASCERN-HHT) to develop the following agreed Position Statement on cerebral screening:1) First, we emphasise that neurological symptoms suggestive of cerebral AVMs in HHT patients should be investigated as in general neurological and emergency care practice. Similarly, if an AVM is found accidentally, management approaches should rely on expert discussions on a case-by-case basis and individual risk-benefit evaluation of all therapeutic possibilities for a specific lesion.2) The current evidence base does not favour the treatment of unruptured cerebral AVMs, and therefore cannot be used to support widespread screening of asymptomatic HHT patients.3) Individual situations encompass a wide range of personal, cultural and clinical states. In order to enable informed patient choice, and avoid conflicting advice, particularly arising from non-neurovascular interpretations of the evidence base, we suggest that all HHT patients should have the opportunity to discuss knowingly brain screening issues with their healthcare provider.4) Any screening discussions in asymptomatic individuals should be preceded by informed pre-test review of the latest evidence regarding preventative and therapeutic efficacies of any interventions. The possibility of harm due to detection of, or intervention on, a vascular malformation that would not have necessarily caused any consequence in later life should be stated explicitly.We consider this nuanced Position Statement provides a helpful, evidence-based framework for informed discussions between healthcare providers and patients in an emotionally charged area.

Characterisation of Peste Des Petits Ruminants Disease in Pastoralist Flocks in Ngorongoro District of Northern Tanzania and Bluetongue Virus Co-Infection.

Peste des petits ruminants (PPR) disease was first confirmed in Tanzania in 2008 in sheep and goats in Ngorongoro District, northern Tanzania, and is now endemic in this area. This study aimed to characterise PPR disease in pastoralist small ruminant flocks in Ngorongoro District. During June 2015, 33 PPR-like disease reports were investigated in different parts of the district, using semi-structured interviews, clinical examinations, PPR virus rapid detection test (PPRV-RDT), and laboratory analysis. Ten flocks were confirmed as PPRV infected by PPRV-RDT and/or real-time reverse transcription-polymerase chain reaction (RT-qPCR), and two flocks were co-infected with bluetongue virus (BTV), confirmed by RT-qPCR. Phylogenetic analysis of six partial N gene sequences showed that the PPR viruses clustered with recent lineage III Tanzanian viruses, and grouped with Ugandan, Kenyan and Democratic Republic of Congo isolates. No PPR-like disease was reported in wildlife. There was considerable variation in clinical syndromes between flocks: some showed a full range of PPR signs, while others were predominantly respiratory, diarrhoea, or oro-nasal syndromes, which were associated with different local disease names (olodua-a term for rinderpest, olkipiei-lung disease, oloirobi-fever, enkorotik-diarrhoea). BTV co-infection was associated with severe oro-nasal lesions. This clinical variability makes the field diagnosis of PPR challenging, highlighting the importance of access to pen-side antigen tests and multiplex assays to support improved surveillance and targeting of control activities for PPR eradication.

Pastoralist knowledge of sheep and goat disease and implications for peste des petits ruminants virus control in the Afar Region of Ethiopia.

Pastoralist areas of Ethiopia are vulnerable to drought, causing livelihood loss and famine. One approach to increasing pastoralist resilience is the control of livestock disease, but there is limited information from pastoralist areas to inform control strategies. This study aimed to explore pastoralist concepts of small ruminant disease and implications for infectious disease surveillance and control in the pastoralist Afar Region. During 2013-14, qualitative and quantitative methods were applied in two villages of one district in the mid-west of the region. Semi-structured group interviews, incorporating participatory tools, explored pastoralist knowledge of small ruminant diseases and their impact. These were followed by multiple visits in different seasons to 70 households for semi-structured and informal interviews, observation of management practices, clinical examinations, and weekly questionnaires of mortality and morbidity. Thematic analysis was applied to interview transcripts and field notes, and descriptive statistical analysis to quantitative data. Afar concepts of disease causation, terminology and treatment were predominantly naturalistic, related to observable signs and physical causes, rather than personalistic factors (misfortune due to magical or spiritual agents). Disease occurrence was associated with malnutrition and adverse weather, and disease spread with contact between animals during grazing, watering and migration. Disease occurrence varied by season with most syndromes increasing in frequency during the dry season. Names for disease syndromes were related to the main clinical sign or body part affected; 70 terms were recorded for respiratory syndromes, diarrhoea, sheep and goat pox, lameness, skin diseases, ectoparasites, urinary and neurological syndromes and abortion. Some syndromes with pathognomonic signs could be linked to biomedical diagnoses but most were non-specific with several possible diagnoses. The syndromes causing greatest impact were diarrhoea and respiratory disease, due to mortality, reduced milk production, weight loss, abortion, weak offspring and reduced market value. Afar applied a range of traditional methods and modern medicines to prevent or treat disease, based on livestock keeper knowledge, advice of local specialists and occasionally advice from district veterinarians or animal health workers. In relation to surveillance for peste des petits ruminants (PPR), several terms were used for PPR-like syndromes, depending on the predominance of respiratory or diarrhoea signs. Therefore, whenever these terms are encountered during surveillance, the associated disease events should be fully investigated and samples collected for laboratory confirmation. The Afar naturalistic concepts of disease parallel biomedical concepts and provide a good foundation for communication between veterinarians and pastoralists in relation to PPR surveillance and control measures.

Optimization and evaluation of a non-invasive tool for peste des petits ruminants surveillance and control.

Peste des petits ruminants (PPR) is a highly contagious and devastating viral disease affecting mainly sheep and goats, but also a large number of wild species within the order Artiodactyla. A better understanding of PPR transmission dynamics in multi-host systems is necessary to efficiently control the disease, in particular where wildlife and livestock co-occur. Notably, the role of wildlife in PPR epidemiology is still not clearly understood. Non-invasive strategies to detect PPR infection without the need for animal handling could greatly facilitate research on PPR epidemiology and management of the disease in atypical hosts and in complex field situations. Here, we describe optimized methods for the direct detection of PPR virus genetic material and antigen in fecal samples. We use these methods to determine the detection window of PPR in fecal samples, and compare the sensitivity of these methods to standard invasive sampling and PPR diagnostic methods using field samples collected at a wildlife-livestock interface in Africa. Our results show that quantitative reverse transcription PCR (RT-QPCR) amplification of PPRV from fecal swabs has good sensitivity in comparison to ocular swabs. Animals infected by PPRV could be identified relatively early on and during the whole course of infection based on fecal samples using RT-QPCR. Partial gene sequences could also be retrieved in some cases, from both fecal and ocular samples, providing important information about virus origin and relatedness to other PPRV strains. Non-invasive strategies for PPRV surveillance could provide important data to fill major gaps in our knowledge of the multi-host PPR epidemiology.

World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection.

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [-13910*T (rs4988235), -13907*G (rs41525747), -13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.

Herd-level animal management factors associated with the occurrence of bovine neonatal pancytopenia in calves in a multi-country study.

Since 2007, mortality associated with a previously unreported haemorrhagic disease has been observed in young calves in several European countries. The syndrome, which has been named 'bovine neonatal pancytopenia' (BNP), is characterised by thrombocytopenia, leukocytopenia and a panmyelophthisis. A herd-level case-control study was conducted in four BNP affected countries (Belgium, France, Germany and the Netherlands) to identify herd management risk factors for BNP occurrence. Data were collected using structured face-to-face and telephone interviews of farm managers and their local veterinarians. In total, 363 case farms and 887 control farms were included in a matched multivariable conditional logistic regression analysis. Case-control status was strongly associated with the odds of herd level use of the vaccine PregSure® BVD (PregSure, Pfizer Animal Health) (matched adjusted odds ratio (OR) 107.2; 95% CI: 41.0-280.1). This was also the case for the practices of feeding calves colostrum from the calf's own dam (OR 2.0; 95% CI: 1.1-3.4) or feeding pooled colostrum (OR 4.1; 95% CI: 1.9-8.8). Given that the study had relatively high statistical power and represented a variety of cattle production and husbandry systems, it can be concluded with some confidence that no other herd level management factors are competent causes for a sufficient cause of BNP occurrence on herd level. It is suggested that genetic characteristics of the dams and BNP calves should be the focus of further investigations aimed at identifying the currently missing component causes that together with PregSure vaccination and colostrum feeding represent a sufficient cause for occurrence of BNP in calves.

Eco-social processes influencing infectious disease emergence and spread.

The complexity and connectedness of eco-social processes have major influence on the emergence and spread of infectious diseases amongst humans and animals. The disciplinary nature of most research activity has made it difficult to improve our understanding of interactions and feedback loops within the relevant systems. Influenced by the One Health approach, increasing efforts have recently been made to address this knowledge gap. Disease emergence and spread is strongly influenced by host density and contact structures, pathogen characteristics and pathogen population and molecular evolutionary dynamics in different host species, and host response to infection. All these mechanisms are strongly influenced by eco-social processes, such as globalization and urbanization, which lead to changes in global ecosystem dynamics, including patterns of mobility, human population density and contact structures, and food production and consumption. An improved understanding of epidemiological and eco-social processes, including their interdependence, will be essential to be able to manage diseases in these circumstances. The interfaces between wild animals, domestic animals and humans need to be examined to identify the main risk pathways and put in place appropriate mitigation. Some recent examples of emerging infectious disease are described to illustrate eco-social processes that are influencing disease emergence and spread.

In Vitro Functional Analyses of Infrequent Nucleotide Variants in the Lactase Enhancer Reveal Different Molecular Routes to Increased Lactase Promoter Activity and Lactase Persistence.

The genetic trait that allows intestinal lactase to persist into adulthood in some 35% of humans worldwide operates at the level of transcription, the effect being caused by cis-acting nucleotide changes upstream of the lactase gene (LCT). A single nucleotide substitution, -13910 C>T, the first causal variant to be identified, accounts for lactase persistence over most of Europe. Located in a region shown to have enhancer function in vitro, it causes increased activity of the LCT promoter in Caco-2 cells, and altered transcription factor binding. Three other variants in close proximity, -13907 C>G, -13915 T>C and -14010 G>C, were later shown to behave in a similar manner. Here, we study four further candidate functional variants. Two, -14009 T>G and -14011 C>T, adjacent to the well-studied -14010 G>C variant, also have a clear effect on promoter activity upregulation as assessed by transfection assays, but notably are involved in different molecular interactions. The results for the two other variants (-14028 T>C, -13779 G>C) were suggestive of function, -14028*C showing a clear change in transcription factor binding, but no obvious effect in transfections, while -13779*G showed greater effect in transfections but less on transcription factor binding. Each of the four variants arose on independent haplotypic backgrounds with different geographic distribution.

Pregnancy and ketoacidosis: Is pancreatitis a missing link?

Non-diabetic ketoacidosis is increasingly recognised in pregnancy, particularly during the third trimester, and is usually associated with vomiting. In many cases, the cause of the vomiting is not identified and resolves rapidly, alongside the metabolic abnormalities, following delivery. Here, we report three cases in which pancreatitis was identified as an underlying cause of the gastrointestinal symptoms. To our knowledge, these are the first reports of pancreatitis precipitating non-diabetic ketoacidosis in pregnancy. This case series highlights the importance of searching for a precipitant for non-diabetic ketoacidosis in pregnancy, rather than focusing solely on management of the resulting metabolic abnormalities.