Evaluation of Alternative Doxycycline Antibiotic Regimes in an Inhalational Murine Model of Q Fever.

The timing of the initiation of antibiotic treatment has been shown to impact the clinical outcome of many bacterial infections, including Q fever. Delayed, suboptimal or incorrect antibiotic treatment has been shown to result in poor prognosis, resulting in the progression of acute disease to long-term chronic sequalae. Therefore, there is a requirement to identify an optimal, effective therapeutic regimen to treat acute Q fever. In the study, the efficacies of different doxycycline monohydrate regimens (pre-exposure prophylaxis, post-exposure prophylaxis or treatment at symptom onset or resolution) were evaluated in an inhalational murine model of Q fever. Different treatment lengths (7 or 14 days) were also evaluated. Clinical signs and weight loss were monitored during infection and mice were euthanized at different time points to characterize bacterial colonization in the lungs and the dissemination of bacteria to other tissues including the spleen, brain, testes, bone marrow and adipose. Post-exposure prophylaxis or doxycycline treatment starting at symptoms onset reduced clinical signs, and also delayed the systemic clearance of viable bacteria from key tissues. Effective clearance was dependent on the development of an adaptive immune response, but also driven by sufficient bacterial activity to maintain an active immune response. Pre-exposure prophylaxis or post-exposure treatment at the resolution of clinical signs did not improve outcomes. These are the first studies to experimentally evaluate different doxycycline treatment regimens for Q fever and illustrate the need to explore the efficacy of other novel antibiotics.

Clinical activity at the UK military level 2 hospital in Bentiu, South Sudan during Op TRENTON from June to September 2017.

INTRODUCTION: Diseases and non-battle injuries (DNBIs) are common on UK military deployments, but the collection and analysis of clinically useful data on these remain a challenge. Standard medical returns do not provide adequate clinical information, and clinician-led approaches have been laudable, but not integrated nor standardised nor used long-term. Op TRENTON is a novel UK military humanitarian operation in support of the United Nations Mission in South Sudan, which included the deployment of UK military level 1 and level 2 medical treatment facilities at Bentiu to provide healthcare for UK and United Nations (UN) personnel. METHODS: A service evaluation of patient consultations and admissions at the UK military level 2 hospital was performed using two data sets collected by the emergency department (ED) and medicine (MED) teams. RESULTS: Over a three-month (13-week) period, 286 cases were seen, of which 51% were UK troops, 29% were UN civilians and 20% were UN troops. The ED team saw 175 cases (61%) and provided definitive care for 113 (40%), whereas the MED team saw and provided definitive care for 128 cases (45%). Overall, there were 75% with diseases and 25% with non-battle injuries. The most common diagnoses seen by the ED team were musculoskeletal injuries (17%), unidentified non-malarial undifferentiated febrile illness (UNMUFI) (17%), malaria (13%), chemical pneumonitis (13%) and wounds (8%). The most common diagnoses seen by the MED team were acute gastroenteritis (AGE) (56%), UNMUFI (12%) and malaria (9%). AGE was due to viruses (31%), diarrhoeagenic Escherichia coli (32%), other bacteria (6%) and protozoa (12%). CONCLUSION: Data collection on DNBIs during the initial phase of this deployment was clinically useful and integrated between different departments. However, a standardised, long-term solution that is embedded into deployed healthcare is required. The clinical activity recorded here should be used for planning, training, service development and targeted research.

Bending the curve: force health protection during the insertion phase of the Ebola outbreak response.

After >10 years of enduring operations in Iraq and Afghanistan, Defence Strategic Direction is returning to a contingency posture. As the first post-Afghanistan operation, in September 2014, a UK Joint Inter-Agency Task Force deployed to Sierra Leone in response to the Ebola virus disease (EVD) epidemic in West Africa. The aims were expanding treatment capacity, assisting with training and supporting host nation resilience. The insertion phase of this deployment created a unique set of challenges for force health protection. In addition to the considerable risk of tropical disease and trauma, deployed personnel faced the risks of working in an EVD epidemic. This report explores how deployed medical assets overcame the difficulties of mounting a short-notice contingent operation in a region of the world with inherent major climatic and health challenges.

Diagnosis of Febrile Illnesses Other Than Ebola Virus Disease at an Ebola Treatment Unit in Sierra Leone.

Patients with febrile illnesses presenting to an Ebola treatment unit in Sierra Leone had a wide range of diagnoses other than Ebola virus disease. Rapid diagnostic tests were useful in confirming these diagnoses, reducing the length of patient stay with valuable consequences. These alternative diagnoses should assist in future planning.

Seroconversion for infectious pathogens among UK military personnel deployed to Afghanistan, 2008-2011.

Military personnel are at high risk of contracting vector-borne and zoonotic infections, particularly during overseas deployments, when they may be exposed to endemic or emerging infections not prevalent in their native countries. We conducted seroprevalence testing of 467 UK military personnel deployed to Helmand Province, Afghanistan, during 2008-2011 and found that up to 3.1% showed seroconversion for infection with Rickettsia spp., Coxiella burnetii, sandfly fever virus, or hantavirus; none showed seroconversion for infection with Crimean-Congo hemorrhagic fever virus. Most seroconversions occurred in personnel who did not report illness, except for those with hantavirus (70% symptomatic). These results indicate that many exposures to infectious pathogens, and potentially infections resulting from those exposures, may go unreported. Our findings reinforce the need for continued surveillance of military personnel and for education of health care providers to help recognize and prevent illnesses and transmission of pathogens during and after overseas deployments.

"Zone of vulnerability" for radial nerve injury: anatomic study.

The authors of this study sought improved understanding of the radial nerve course through the brachium and hypothesized that the most proximal aspect of the triceps tendon (PATT) serves as a useful superficial landmark for localizing the nerve. It was also hypothesized that a poorly appreciated area of vulnerability for nerve injury exists where the radial nerve runs along the lateral cortex of the humerus proximal to its transit through the lateral intermuscular septum (LIMS). The authors assessed 33 fresh-frozen cadaveric specimens. A 6.7-cm span of the nerve lies directly on the periosteum of the humerus before piercing the LIMS. The proximal 4.6~cm abuts the posterior cortex. The final 2.1~cm just proximal to the LIMS runs along the lateral cortex. The nerve at the posterior midline of the humerus is 2.3~cm proximal to the level of the PATT. The radial nerve lies directly on the lateral humeral cortex for 2~cm proximal to its transit through the LIMS. The PATT appears to be a consistent and practical superficial landmark to determine the location of the radial nerve from a posterior approach.

LeishMan recommendations for treatment of cutaneous and mucosal leishmaniasis in travelers, 2014.

BACKGROUND: Treatment of cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) in travelers is still controversial. Over the last decade, national and international consortia have published recommendations for treating CL in travelers. These guidelines harmonize many issues, but there are some discrepancies. METHODS: Leishmania parasites causing CL can now be genotyped by polymerase chain reaction techniques for detecting Leishmania DNA. Therefore, treatment recommendations can now be species based rather than based on geographical exposure. To review the evidence on which the recommendations were based, "LeishMan" (Leishmaniasis Management), a group of experts from 13 institutions in eight European countries, performed a PubMed MEDLINE) literature search and considered unpublished evidence and the experts' own personal experiences. The Oxford evidence grading system was used to evaluate the information. RESULTS AND CONCLUSION: In this article, the authors provide practical treatment recommendations for imported CL and ML in Europe, drawn up from the review by the European experts.

Misdiagnosis of cutaneous leishmaniasis and recurrence after surgical excision.

Cutaneous Leishmaniasis (CL) occurs in British troops deployed to Belize, Afghanistan, Iraq and elsewhere. From 1998 to 2009, 156 (45%) of 343 confirmed cases seen in the UK were in military personnel. CL is a rare disease and requires specialist clinical management because numerous pitfalls exist during diagnosis and treatment. A 19-year-old soldier developed CL on his neck 6 weeks after taking part in jungle warfare training in Belize. However, this was not suspected and the diagnosis was not made from either a skin biopsy or following surgical excision. The travel history and the patient's own photograph prompted retrospective investigations that confirmed this was CL due to Leishmania mexicana. Three months after surgery, the disease recurred locally and was treated appropriately with a good outcome. British military personnel with suspected CL should be referred to the UK Role 4 Military Infectious Diseases & Tropical Medicine Service.

A brief history of British military experiences with infectious and tropical diseases.

Infectious and tropical diseases have been a problem for British expeditionary forces ever since the Crusades. Outbreaks were especially common on Navy ships from the 16th to 18th centuries due to poor living conditions and travel to the tropics. However, since these occurred in small, isolated and controlled environments it meant that naval medical practitioners were able to keep detailed records and develop empirical approaches for their prevention. The first Royal Naval Hospitals were established in response to these diseases and Royal Navy doctors made valuable early contributions towards understanding them. Even larger outbreaks of infectious and tropical diseases occurred in the Army during the Napoleonic, Crimean and Boer Wars and throughout the colonial era, which strongly influenced the formation of the Army Medical Services including provision for teaching and research. The establishment of germ theory led to a golden era of discovery regarding these diseases and British Army doctors made numerous important contributions. Subsequent improvements in prevention, diagnosis and treatment reduced the mortality from infectious and tropical diseases during the World Wars, but they remained a significant problem in the non-European campaigns and also the numerous 'small wars' that followed. Even in the 21st century some of these diseases still cause outbreaks with significant morbidity and impact on deployments, but the military clinical and academic resources to deal with them are now much reduced. Preventive measures such as hygiene, sanitation, infection control, vaccination and chemoprophylaxis are invaluable, but history shows that these can become neglected over time and disrupted or overwhelmed during the early or most intense stages of military operations. This is why military specialists in infectious diseases, tropical medicine, sexual health, medical microbiology and communicable diseases control are still required.

Undifferentiated febrile illnesses in military personnel.

Undifferentiated febrile illnesses (UFIs) present with acute symptoms, objective fever and no specific organ focus on clinical assessment. The term is mostly used in developing and tropical countries where a wide range of infections may be responsible. Laboratory diagnosis often requires specialist microbiology investigations that are not widely available, and serology tests that only become positive during convalescence. Optimal clinical management requires a good travel history, awareness of local endemic diseases, an understanding of the features that may help distinguish different causes and appropriate use of empirical antibiotics. This review describes the most common examples of UFI in military personnel on overseas deployments, and provides a practical approach to their initial management.

Tropical skin diseases in British military personnel.

Skin complaints are common in travellers to foreign countries and are responsible for up to 25% of medical consultations by military personnel during deployments in the tropics. They also have relatively high rates of field hospital admission, medical evacuation and referral to UK Role 4 healthcare facilities. Non-infectious tropical skin diseases include sunburn, heat rash, arthropod bites, venomous bites, contact dermatitis and phytophotodermatitis. During tropical deployments skin infections that commonly occur in military personnel may become more frequent, severe and difficult to treat. Several systemic tropical infections have cutaneous features that can be useful in making early diagnoses. Tropical skin infections such as cutaneous larva migrans, cutaneous myiasis, cutaneous leishmaniasis and leprosy do occur in British troops and require specialist clinical management. This illustrated review focuses on the most significant tropical skin diseases that have occurred in British military personnel in recent years. Clinical management of these conditions on deployments would be improved and medical evacuations could be reduced if a military dermatology 'reach-back' service (including a telemedicine facility) was available.

Routine deworming of children at deployed military healthcare facilities.

The World Health Organization advocates mass antihelminthic treatment of school-age children in areas of high prevalence of soil-transmitted helminths. Soil-transmitted helminths prevalence in Afghanistan is 20-50%, but a high proportion of children do not attend school, so may be missed by deworming programs. The primary function of military medical assets in a theater of war is to provide life, limb and eyesight saving treatment. Additional humanitarian aid in the form of nonemergency treatment has also been provided in Afghanistan for thousands of civilian children. Children represent 3-15% of the patients treated at deployed military medical facilities. We report on recent experience of deployed surgical teams in southern Afghanistan who have noticed high levels of soil-transmitted helminths in war-injured patients. Military medical assets may provide an opportunity to integrate a policy of deworming of children into existing programs of humanitarian support. This would not be a substitute for mass deworming programs, but a supplementation.

A single multilocus sequence typing (MLST) scheme for seven pathogenic Leptospira species.

BACKGROUND: The available Leptospira multilocus sequence typing (MLST) scheme supported by a MLST website is limited to L. interrogans and L. kirschneri. Our aim was to broaden the utility of this scheme to incorporate a total of seven pathogenic species. METHODOLOGY AND FINDINGS: We modified the existing scheme by replacing one of the seven MLST loci (fadD was changed to caiB), as the former gene did not appear to be present in some pathogenic species. Comparison of the original and modified schemes using data for L. interrogans and L. kirschneri demonstrated that the discriminatory power of the two schemes was not significantly different. The modified scheme was used to further characterize 325 isolates (L. alexanderi [n = 5], L. borgpetersenii [n = 34], L. interrogans [n = 222], L. kirschneri [n = 29], L. noguchii [n = 9], L. santarosai [n = 10], and L. weilii [n = 16]). Phylogenetic analysis using concatenated sequences of the 7 loci demonstrated that each species corresponded to a discrete clade, and that no strains were misclassified at the species level. Comparison between genotype and serovar was possible for 254 isolates. Of the 31 sequence types (STs) represented by at least two isolates, 18 STs included isolates assigned to two or three different serovars. Conversely, 14 serovars were identified that contained between 2 to 10 different STs. New observations were made on the global phylogeography of Leptospira spp., and the utility of MLST in making associations between human disease and specific maintenance hosts was demonstrated. CONCLUSION: The new MLST scheme, supported by an updated MLST website, allows the characterization and species assignment of isolates of the seven major pathogenic species associated with leptospirosis.

Estimating the true accuracy of diagnostic tests for dengue infection using bayesian latent class models.

BACKGROUND: Accuracy of rapid diagnostic tests for dengue infection has been repeatedly estimated by comparing those tests with reference assays. We hypothesized that those estimates might be inaccurate if the accuracy of the reference assays is not perfect. Here, we investigated this using statistical modeling. METHODS/PRINCIPAL FINDINGS: Data from a cohort study of 549 patients suspected of dengue infection presenting at Colombo North Teaching Hospital, Ragama, Sri Lanka, that described the application of our reference assay (a combination of Dengue IgM antibody capture ELISA and IgG antibody capture ELISA) and of three rapid diagnostic tests (Panbio NS1 antigen, IgM antibody and IgG antibody rapid immunochromatographic cassette tests) were re-evaluated using bayesian latent class models (LCMs). The estimated sensitivity and specificity of the reference assay were 62.0% and 99.6%, respectively. Prevalence of dengue infection (24.3%), and sensitivities and specificities of the Panbio NS1 (45.9% and 97.9%), IgM (54.5% and 95.5%) and IgG (62.1% and 84.5%) estimated by bayesian LCMs were significantly different from those estimated by assuming that the reference assay was perfect. Sensitivity, specificity, PPV and NPV for a combination of NS1, IgM and IgG cassette tests on admission samples were 87.0%, 82.8%, 62.0% and 95.2%, respectively. CONCLUSIONS: Our reference assay is an imperfect gold standard. In our setting, the combination of NS1, IgM and IgG rapid diagnostic tests could be used on admission to rule out dengue infection with a high level of accuracy (NPV 95.2%). Further evaluation of rapid diagnostic tests for dengue infection should include the use of appropriate statistical models.

Hydrogen storage materials discovery via high throughput ball milling and gas sorption.

The lack of a high capacity hydrogen storage material is a major barrier to the implementation of the hydrogen economy. To accelerate discovery of such materials, we have developed a high-throughput workflow for screening of hydrogen storage materials in which candidate materials are synthesized and characterized via highly parallel ball mills and volumetric gas sorption instruments, respectively. The workflow was used to identify mixed imides with significantly enhanced absorption rates relative to Li2Mg(NH)2. The most promising material, 2LiNH2:MgH2 + 5 atom % LiBH4 + 0.5 atom % La, exhibits the best balance of absorption rate, capacity, and cycle-life, absorbing >4 wt % H2 in 1 h at 120 °C after 11 absorption-desorption cycles.