Outcomes of TB contact tracing and predictors of success: a 10-year retrospective cohort analysis in Birmingham, UK.

BACKGROUND: Contacts of TB cases in Birmingham and Solihull, UK, are offered screening for TB infection. Between 1990 and 2010, only 59.1% of contacts completed screening. The service has since increased screening staff numbers, changed screening locations and increased screening follow-up. Our primary aim was to identify whether screening completion rates have improved. Our secondary aim was to identify predictors of screening completion.METHODS: This was a retrospective analysis of all contacts of TB patients in Birmingham and Solihull between 1 January 2011 and 31 December 2020, stratified by pulmonary and extrapulmonary TB (PTB or EPTB) index infection. Multiple logistic regression analysis for predictors of screening completion was performed.RESULTS: A total of 3,255 index cases and 27,820 contacts were identified. TB incidence has declined, in keeping with national trends. Screening completion has improved from 59.1% of contacts to 74.9% overall since service improvements were made, with improvement in screening completion for contacts of both PTB and EPTB index cases (OR 1.087, 95% CI 1.074-1.101; P < 0.001) and (OR 1.048, 95% CI 1.019-1.078; P = 0.001), respectively.CONCLUSIONS: Changes made to the TB service have improved screening outcomes over the last decade. Significant predictors of screening completion have been identified, highlighting areas for targeted resource allocation.

Validation of dried blood spot sampling for detecting SARS-CoV-2 antibodies and total immunoglobulins in a large cohort of asymptomatic young adults.

BACKGROUND: Detecting antibody responses following infection with SARS-CoV-2 is necessary for sero-epidemiological studies and assessing the role of specific antibodies in disease, but serum or plasma sampling is not always viable due to logistical challenges. Dried blood spot sampling (DBS) is a cheaper, simpler alternative and samples can be self-collected and returned by post, reducing risk for SARS-CoV-2 exposure from direct patient contact. The value of large-scale DBS sampling for the assessment of serological responses to SARS-CoV-2 has not been assessed in depth and provides a model for examining the logistics of using this approach to other infectious diseases. The ability to measure specific antigens is attractive for remote outbreak situations where testing may be limited or for patients who require sampling after remote consultation. METHODS: We compared the performance of SARS-CoV-2 anti-spike and anti-nucleocapsid antibody detection from DBS samples with matched serum collected by venepuncture in a large population of asymptomatic young adults (N = 1070) living and working in congregate settings (military recruits, N = 625); university students, N = 445). We also compared the effect of self-sampling (ssDBS) with investigator-collected samples (labDBS) on assay performance, and the quantitative measurement of total IgA, IgG and IgM between DBS eluates and serum. RESULTS: Baseline seropositivity for anti-spike IgGAM antibody was significantly higher among university students than military recruits. Strong correlations were observed between matched DBS and serum samples in both university students and recruits for the anti-spike IgGAM assay. Minimal differences were found in results by ssDBS and labDBS and serum by Bland Altman and Cohen kappa analyses. LabDBS achieved 82.0% sensitivity and 98.2% specificity and ssDBS samples 86.1% sensitivity and 96.7% specificity for detecting anti-spike IgGAM antibodies relative to serum samples. For anti-SARS-CoV-2 nucleocapsid IgG there was qualitatively 100% agreement between serum and DBS samples and weak correlation in ratio measurements. Strong correlations were observed between serum and DBS-derived total IgG, IgA, and IgM. CONCLUSIONS: This is the largest validation of DBS against paired serum for SARS-CoV-2 specific antibody measurement and we have shown that DBS retains performance from prior smaller studies. There were no significant differences regarding DBS collection methods, suggesting that self-collected samples are a viable sampling collection method. These data offer confidence that DBS can be employed more widely as an alternative to classical serology.

Deployment of whole genome next-generation sequencing of SARS-CoV-2 in a military maritime setting.

BACKGROUND: SARS-CoV-2 can spread rapidly on maritime platforms. Several outbreaks of SARS-CoV-2 have been reported on warships at sea, where transmission is facilitated by living and working in close quarters. Core components of infection control measures such as social distancing, patient isolation and quarantine of exposed persons are extremely difficult to implement. Whole genome sequencing (WGS) of SARS-CoV-2 has facilitated epidemiological investigations of outbreaks, impacting on outbreak management in real time by identifying transmission patterns, clusters of infection and guiding control measures. We suggest such a capability could mitigate against the impact of SARS-CoV-2 in maritime settings. METHODS: We set out to establish SARS-CoV-2 WGS using miniaturised nanopore sequencing technology aboard the Royal Fleet Auxiliary ARGUS while at sea. Objectives included designing a simplified protocol requiring minimal reagents and processing steps, the use of miniaturised equipment compatible for use in limited space, and a streamlined and standalone data analysis capability to allow rapid in situ data acquisition and interpretation. RESULTS: Eleven clinical samples with blinded SARS-CoV-2 status were tested at sea. Following viral RNA extraction and ARTIC sequencing library preparation, reverse transcription and ARTIC PCR-tiling were performed. Samples were subsequently barcoded and sequenced using the Oxford Nanopore MinION Mk1B. An offline version of the MinKNOW software was used followed by CLC Genomics Workbench for downstream analysis for variant identification and phylogenetic tree construction. All samples were correctly classified, and relatedness identified. CONCLUSIONS: It is feasible to establish a small footprint sequencing capability to conduct SARS-CoV-2 WGS in a military maritime environment at sea with limited access to reach-back support. This proof-of-concept study has highlighted the potential of deploying such technology in the future to military environments, both maritime and land-based, to provide meaningful clinical data to aid outbreak investigations.

The 2022 monkeypox outbreak: A UK military perspective.

With the emergence of SARS-CoV-2 and now monkeypox, the UK Defence Medical Services have been required to provide rapid advice in the management of patients with airborne high consequence infectious diseases (A-HCID). The Defence Public Health Network (DPHN) cadre, consisting of closely aligned uniformed and civilian public health specialists have worked at pace to provide evidence-based recommendations on the clinical management, public health response and policy for monkeypox, with military medicine and pathology clinicians (primarily infectious disease physicians and medical microbiologists). Military environments can be complicated and nuanced requiring specialist input and advice to non-specialists as well as unit commanders both in the UK and overseas. DPHN and military infection clinicians have close links with the UK National Health Service (NHS) and the UK Health Security Agency (UKHSA), allowing for a dynamic two-way relationship that encompasses patient management, public health response, research and development of both UK military and national guidelines. This is further demonstrated with the Royal Air Force (RAF) Air Transport Isolator (ATI) capability, provided by Defence to support the UK Government and UKHSA. Military infectious disease clinicians are also embedded within NHS A-HCID units. In this manuscript we provide examples of the close interdisciplinary working of the DPHN and Defence clinicians in managing military monkeypox patients, co-ordinating the public health response, advising the Command and developing monkeypox policy for Defence through cross-government partnership. We also highlight the co-operation between civilian and military medical authorities in managing the current outbreak.

Does vitamin D supplementation prevent SARS-CoV-2 infection in military personnel? Review of the evidence.

For most individuals residing in Northwestern Europe, maintaining replete vitamin D status throughout the year is unlikely without vitamin D supplementation and deficiency remains common. Military studies have investigated the association with vitamin D status, and subsequent supplementation, with the risk of stress fractures particularly during recruit training. The expression of nuclear vitamin D receptors and vitamin D metabolic enzymes in immune cells additionally provides a rationale for the potential role of vitamin D in maintaining immune homeostasis. One particular area of interest has been in the prevention of acute respiratory tract infections (ARTIs). The aims of this review were to consider the evidence of vitamin D supplementation in military populations in the prevention of ARTIs, including SARS-CoV-2 infection and consequent COVID-19 illness. The occupational/organisational importance of reducing transmission of SARS-CoV-2, especially where infected young adults may be asymptomatic, presymptomatic or paucisymptomatic, is also discussed.

Staphylococcus aureus colonization and acquisition of skin and soft tissue infection among Royal Marines recruits: a prospective cohort study.

OBJECTIVES: Skin and soft tissue infections (SSTIs) are a serious health issue for military personnel. Of particular importance are those caused by methicillin-resistant Staphylococcus aureus and Panton-Valentine leucocidin (PVL)-positive S. aureus (PVL-SA), as they have been associated with outbreaks of SSTIs. A prospective observational study was conducted in Royal Marine (RM) recruits to investigate the prevalence of PVL-SA carriage and any association with SSTIs. METHODS: A total of 1012 RM recruits were followed through a 32-week training programme, with nose and throat swabs obtained at weeks 1, 6, 15 and 32. S. aureus isolates were characterized by antibiotic susceptibility testing, spa typing, presence of mecA/C and PVL genes. Retrospective review of the clinical notes for SSTI acquisition was conducted. RESULTS: S. aureus colonization decreased from Week 1 to Week 32 (41% to 26%, p < 0.0001). Of 1168 S. aureus isolates, three out of 1168 (0.3%) were MRSA and ten out of 1168 (0.9%) PVL-positive (all MSSA) and 169 out of 1168 (14.5%) were resistant to clindamycin. Isolates showed genetic diversity with 238 different spa types associated with 25 multi-locus sequence type (MLST) clonal complexes. SSTIs were seen in 35% (351/989) of recruits with 3 training days lost per recruit. SSTI acquisition rate was reduced amongst persistent carriers (p < 0.0283). CONCLUSIONS: Nose and throat carriage of MRSA and PVL-SA was low among recruits, despite a high incidence of SSTIs being reported, particularly cellulitis. Carriage strains were predominantly MSSA with a marked diversity of genotypes. Persistent nose and/or throat carriage was not associated with SSTI acquisition. Putative person-to-person transmission within troops was identified based on spa typing requiring further research to confirm and explore potential transmission routes.

Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone.

BACKGROUND: Limited data exist describing supportive care management, laboratory abnormalities and outcomes in patients with Ebola virus disease (EVD) in West Africa. We report data which constitute the first description of the provision of enhanced EVD case management protocols in a West African setting. METHODS: Demographic, clinical and laboratory data were collected by retrospective review of clinical and laboratory records of patients with confirmed EVD admitted between 5 November 2014 and 30 June 2015. RESULTS: A total of 44 EVD patients were admitted (median age 37 years (range 17-63), 32/44 healthcare workers), and excluding those evacuated, the case fatality rate was 49% (95% CI 33%-65%). No pregnant women were admitted. At admission 9/44 had stage 1 disease (fever and constitutional symptoms only), 12/44 had stage 2 disease (presence of diarrhoea and/or vomiting) and 23/44 had stage 3 disease (presence of diarrhoea and/or vomiting with organ failure), with case fatality rates of 11% (95% CI 1%-58%), 27% (95% CI 6%-61%), and 70% (95% CI 47%-87%) respectively (p = 0.009). Haemorrhage occurred in 17/41 (41%) patients. The majority (21/40) of patients had hypokalaemia with hyperkalaemia occurring in 12/40 patients. Acute kidney injury (AKI) occurred in 20/40 patients, with 14/20 (70%, 95% CI 46%-88%) dying, compared to 5/20 (25%, 95% CI 9%-49%) dying who did not have AKI (p = 0.01). Ebola virus (EBOV) PCR cycle threshold value at baseline was mean 20.3 (SD 4.3) in fatal cases and 24.8 (SD 5.5) in survivors (p = 0.007). Mean national early warning score (NEWS) at admission was 5.5 (SD 4.4) in fatal cases and 3.0 (SD 1.9) in survivors (p = 0.02). Central venous catheters were placed in 37/41 patients and intravenous fluid administered to 40/41 patients (median duration of 5 days). Faecal management systems were inserted in 21/41 patients, urinary catheters placed in 27/41 and blood component therapy administered to 20/41 patients. CONCLUSIONS: EVD is commonly associated life-threatening electrolyte imbalance and organ dysfunction. We believe that the enhanced levels of protocolized care, scale and range of medical interventions we report, offer a blueprint for the future management of EVD in resource-limited settings.

Use of an ultraviolet tracer in simulation training for the clinical management of Ebola virus disease.

In October 2014 the UK military deployed to Sierra Leone to provide care for healthcare workers affected by Ebola virus disease. A training package designed by the Army Medical Services Training Centre prepared the deploying personnel in the required infection prevention and control measures. The training used ultraviolet tracer to provide validation of the skills required when treating patients with Ebola and to confirm subsequent decontamination. This training construct provided useful feedback to clinicians on their infection control measures and would be useful in the context of any infection spread by droplets and fomites.

An unusual case of anaemia and lymphadenopathy in a soldier on deployment.

We describe the case of a British soldier, originally from southeast Africa, who presented to the British military hospital in Helmand Province, southern Afghanistan, with a history of constitutional upset, profound anaemia and diffuse lymphadenopathy with hepatosplenomegaly. Following evacuation to the UK investigations revealed a rare (and a not so rare) diagnosis. This case raises a number of questions regarding the population at risk, the prevalence of endemic diseases in this population and laboratory capabilities in the deployed setting.

Panton-Valentine Leukocidin Staphylococcus aureus (PVL-SA) - an uninvited stowaway aboard a Royal Navy submarine.

The toxin Panton-Valentine Leukocidin (PVL) is a virulence factor produced by some strains of Staphylococcus aureus (S. aureus, SA) that destroys leucocytes. PVL-SA predominantly results in skin and soft tissue infections (SSTIs) but may also cause invasive disease, including necrotising pneumonia, which may affect healthy young individuals and has a high mortality. We describe a case of PVL-SA in a submariner who presented at sea and which resulted in a requirement to both alter the submarine's programme and undertake population screening. The case highlights many important issues pertinent to military populations including clinical and public health considerations.

Acinetobacter in modern warfare.

Increasing appreciation of the role of Acinetobacter baumannii in the aetiology of severe nosocomial infections, together with its ability to employ several mechanisms to rapidly develop resistance to multiple classes of antimicrobial agents, has led to growing interest in this organism over recent years. Recognition and subsequent investigation of the significance of pathogenic Acinetobacter infections in military personnel sustaining injuries during the conflicts in Afghanistan and Iraq has provided an important contribution to the epidemiology of infections with Acinetobacter spp. The following review examines this recent military experience.

Morbidity rates on Vanguard Class submarines during nuclear deterrent patrol: a retrospective review over 13 years.

The submarines responsible for the United Kingdom's nuclear deterrent have carried a junior doctor as their medical officer since the program's inception. The Vanguard Class of submarine carries approximately 150 men and deploys for about 3 months at a time. One of the central tenets of submarine operations is to remain undetected and as such the submarine will only surface in an emergency, which may include the evacuation of casualties. The prime reason for carriage of a medical officer is to mitigate against the need to evacuate personnel for medical reasons. We examined the medical section of the patrol reports submitted upon completion of each patrol over a 13 year period to determine both the rates of medical and dental attendance onboard and also the occurrence of potential medical threats to patrol integrity. The most common reasons for attendance were dermatological and musculoskeletal, consistent with previous studies of this population and working environment. There were few dental cases due to the high rates of dental fitness in the pre-sailing crews. Patrol threatening cases occurred at a rate of approximately 1 per 3 patrols, with acute appendicitis being the most common presentation. This progressed to evacuation at a rate of 1 per 15 patrols, with the successful onboard management in 79% of cases. The junior doctor onboard has limited monitoring equipment and formulary, no diagnostic equipment, basic surgical equipment and no opportunity to seek senior advice, and is therefore reliant on clinical judgement. Despite the limitations placed on the doctor on board these submarines they have proven to be effective in reducing the rate of medical evacuation.

Racial and ethnic disparities in survival in lung transplant candidates with idiopathic pulmonary fibrosis.

Minority patients have worse outcomes than nonminority patients in a variety of pulmonary diseases. We aimed to compare the survival of Black and Hispanic patients to that of others with idiopathic pulmonary fibrosis (IPF). We performed a retrospective cohort study of patients with IPF who were evaluated for lung transplantation at our center. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare survival between groups. Black and Hispanic patients had spirometry, lung volumes and diffusion capacity that were similar to others, but had worse exercise capacity. Minority patients had a significantly increased risk of death compared to others independent of transplantation status (hazard ratio = 3.3, 95% CI 1.2-8.9, p = 0.02). Differences in exercise capacity, pulmonary hemodynamics and socioeconomic factors appeared to account for some of the differences in survival. Black and Hispanic patients with IPF had an increased risk of death following referral for lung transplantation. This finding may be due to differences in disease progression and/or differences in access to medical care among minority patients. Future studies should confirm our findings in a larger cohort. The elimination of racial and ethnic disparities in outcome should be a priority for clinicians and researchers in this field.

Laboratory considerations in the surgical treatment of acute hematogenous osteomyelitis of the calcaneus.

Surgical treatment of acute hematogenous osteomyelitis of the calcaneus is uncommon in the literature. Laboratory considerations to aid diagnosis as well as methods of diagnosis, surgical intervention, and management with a review of the literature are presented. A case of a 10-year-old female with acute hematogenous osteomyelitis of the calcaneus treated by surgical drainage, bone biopsy, and management with 12-month follow-up is discussed.

Ankle-joint salvage following a tibial pilon fracture. A case report.

This article presents a case of a tibial pilon fracture following a motor-vehicle accident. It discusses the main classification system and mechanism of injury for such fractures and emphasizes an alternative form of treatment of the usually suggested ankle fusion: an arthrectomy, which allows motion, thereby salvaging the ankle joint.

Clinical perspective of the treatment of fifth metatarsal fractures.

The authors present a retrospective study of fifth metatarsal fractures. These fractures include Jones fractures, avulsion fractures, spiral and oblique midshaft fractures, and the author-termed "tulip" fracture (impaction fracture of the fifth metatarsal head). These fractures were fixated with the cannulated screw, Kirschner wires, and cerclage loop wires combined with Kirschner wires. A one-way analysis of variance (ANOVA) was performed on the data to test for any significant difference in the fixation type used and the overall healing time. The ANOVA was found to be nonsignificant, F(2,10) = 0.379, p < 0.05. Therefore, it can be concluded that all three types of fixation work equally well. Other analyses were performed on each of the three specific types of fractures to see if there was any difference in fixating the fracture versus no fixation and immobilization. This information was significant for only the Jones fracture, F(1,5)2.23, p < 0.05, meaning that Jones fractures heal in a significantly shorter amount of time when some type of open reduction internal fixation is used. Since there was no difference in healing time between the different types of fixation, the authors advise that the cannulated screw be strongly considered because of its efficiency of insertion. In addition, because of the vascularity, muscle insertions, and motion related to the fifth metatarsal, the authors recommend that most Jones fractures be fixated for a more rapid return to function.

Brain myosin-V is a two-headed unconventional myosin with motor activity.

Chicken myosin-V is a member of a recently recognized class of myosins distinct from both the myosins-I and the myosins-II. We report here the purification, electron microscopic visualization, and motor properties of a protein of this class. Myosin-V molecules consist of two heads attached to an approximately 30 nm stalk that ends in a globular region of unknown function. Myosin-V binds to and decorates F-actin, has actin-activated magnesium-ATPase activity, and is a barbed-end-directed motor capable of moving actin filaments at rates of up to 400 nm/s. Myosin-V does not form filaments. Each myosin-V heavy chain is associated with approximately four calmodulin light chains as well as two less abundant proteins of 23 and 17 kd.

Influences on specialty choice of family physician graduates of a tertiary care medical school.

A survey of 392 University of Michigan Medical School family physician alumni who graduated from medical school between 1950 and 1984 explored factors influencing respondent specialty choice and satisfaction with specialty choice. The strongest influences on specialty choice were the opportunity to treat a variety of illnesses, know patients personally, and work with people as opposed to things. The traditional medical school setting offered an environment of high-quality education, opportunities to see a variety of illnesses, and a model of tertiary, uncoordinated, discontinuous care that the respondents were determined not to replicate in their own medical careers. Fifty-nine percent of the respondents had no reservations about their decision to become family physicians, 74% said they would return to the University of Michigan if they were to enter medical school again, and 91% were greatly or moderately satisfied with their choice, indicating their satisfaction with their career choice and medical school.