Rationale: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal, dominantly inherited genodermatosis that predisposes to fibrofolliculomas, kidney neoplasms, lung cysts, and spontaneous pneumothorax. Objectives: We evaluated 198 patients from 89 families with BHDS to characterize the risk factors for pneumothorax and genotypepulmonary associations. Methods: Helical computed tomography scans of the chest were used to screen for pulmonary abnormalities. BHD mutation data were used for genotype-pulmonary associations. We examined the relationship of pneumothorax with categorical parameters (sex, smoking history, and lung cysts) and continuous parameters (number of cysts, lung cyst volume, and largest cyst diameter and volume). Logistic regression analyses were used to identify the risk factors associated with pneumothorax. Measurements and Main Results: Twenty-four percent (48/198) of patients with BHDS had a history of pneumothorax. The presence of lung cysts was significantly associated with pneumothorax (p ϭ 0.006). Total lung cyst volume, largest cyst diameter and volume, and every parameter related to the number of lung cysts were significantly associated (p Ͻ 0.0001) with pneumothorax. A logistic regression analysis showed that only the total number of cysts in the right parenchymal lower lobe and the total number of cysts located on the pleural surface in the right middle lobe were needed to classify a patient as to whether or not he or she was likely to have a pneumothorax. Exon location of the BHD mutation was associated with the numbers of cysts (p ϭ 0.0002). Conclusions: This study indicates that patients with BHDS have a significant association between lung cysts and spontaneous pneumothorax.

BackgroundMalaria transmission intensity is a crucial determinant of malarial disease burden and its measurement can help to define health priorities. Rapid, local estimates of transmission are required to focus resources better but current entomological and parasitological methods for estimating transmission intensity are limited in this respect. An alternative is determination of antimalarial antibody age-specific sero-prevalence to estimate sero-conversion rates (SCR), which have been shown to correlate with transmission intensity. This study evaluated SCR generated from samples collected from health facility attendees as a tool for a rapid assessment of malaria transmission intensity.Methodology and Principal FindingsThe study was conducted in north east Tanzania. Antibodies to Plasmodium falciparum merozoite antigens MSP-119 and AMA-1 were measured by indirect ELISA. Age-specific antibody prevalence was analysed using a catalytic conversion model based on maximum likelihood to generate SCR. A pilot study, conducted near Moshi, found SCRs for AMA-1 were highly comparable between samples collected from individuals in a conventional cross-sectional survey and those collected from attendees at a local health facility. For the main study, 3885 individuals attending village health facilities in Korogwe and Same districts were recruited. Both malaria parasite prevalence and sero-positivity were higher in Korogwe than in Same. MSP-119 and AMA-1 SCR rates for Korogwe villages ranged from 0.03 to 0.06 and 0.07 to 0.21 respectively. In Same district there was evidence of a recent reduction in transmission, with SCR among those born since 1998 [MSP-119 0.002 to 0.008 and AMA-1 0.005 to 0.014 ] being 5 to 10 fold lower than among individuals born prior to 1998 [MSP-119 0.02 to 0.04 and AMA-1 0.04 to 0.13]. Current health facility specific estimates of SCR showed good correlations with malaria incidence rates in infants in a contemporaneous clinical trial (MSP-119 r2 = 0.78, p<0.01 & AMA-1 r2 = 0.91, p<0.001).ConclusionsSCRs generated from age-specific anti-malarial antibody prevalence data collected via health facility surveys were robust and credible. Analysis of SCR allowed detection of a recent drop in malaria transmission in line with recent data from other areas in the region. This health facility-based approach represents a potential tool for rapid assessment of recent trends in malaria transmission intensity, generating valuable data for local and national malaria control programs to target, monitor and evaluate their control strategies.

Summary Background Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions. We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal, where influenza viruses circulate throughout the year. Methods In this phase 4, randomised, placebo-controlled trial, we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal. We randomised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight, stratified by gestational age at enrolment (17–25 weeks vs 26–34 weeks). Women were eligible if they were married, 15–40 years of age, 17–34 weeks’ gestation at enrolment, and had not previously received any influenza vaccine that season. We collected serum samples before and after immunisation, and cord blood from a subset of women and infants. Staff masked to allocation made home visits every week from enrolment to 6 months after delivery. Midnasal swabs for respiratory virus PCR testing were collected during maternal acute febrile respiratory infections, and from infants with any respiratory symptom. We assessed vaccine immunogenicity, safety, and three primary outcomes: the incidence of maternal influenza-like illness in pregnancy and 0–180 days postpartum, the incidence of low birthweight (<2500 g), and the incidence of laboratory-confirmed infant influenza disease from 0 to 180 days. This trial is registered with ClinicalTrials.gov, number NCT01034254. Findings From April 25, 2011, to Sept 9, 2013, we enrolled 3693 women in two cohorts of 2090 (1041 assigned to placebo and 1049 to vaccine) and 1603 (805 assigned to placebo and 798 to vaccine), with 3646 liveborn infants (cohort 1, 999 in placebo group and 1010 in vaccine group; cohort 2, 805 in placebo group and 798 in vaccine group). Immunisation reduced maternal febrile influenza-like illness with an overall efficacy of 19% (95% CI 1 to 34) in the combined cohorts; 9% efficacy (−16 to 29) in the first cohort, and 36% efficacy (9 to 55) in the second cohort. For laboratory-confirmed influenza infections in infants aged 0–6 months, immunisation had an overall efficacy for the combined cohorts of 30% (95% CI 5 to 48); in the first cohort, the efficacy was 16% (−19 to 41), and in the second cohort it was 60% (26 to 88). Maternal immunisation reduced the rates of low birthweight by 15% (95% CI 3–25) in both cohorts combined. The rate of small for gestational age infants was not modified by immunisation. The number of adverse events was similar regardless of immunisation status. Miscarriage occurred in three (0·2%) participants in the placebo group versus five (0·3%) in the vaccine group, stillbirth occurred in 31 (1·7%) versus 33 (1·8%), and congenital defects occurred in 18 (1·0%) versus 20 (1·1%). Five women died in the placebo group and three died in the vaccine group. The number of infant deaths at age 0–6 months was similar in each group (50 in...

Bone and joint infection contributes significantly to clinical activity within outpatient parenteral antimicrobial therapy (OPAT) services. The OVIVA (oral versus intravenous antibiotics for bone and joint infection) randomized study has challenged the practice of prolonged intravenous therapy, because non-inferiority of oral antibiotic therapy was demonstrated, thereby implying that early transition to oral therapy is an appropriate alternative to prolonged intravenous therapy. We examine the caveats to the study and discuss the implications for OPAT practice, highlighting the importance of careful oral antibiotic selection with attention to bioavailability, bone penetration, drug interactions, compliance and toxicity monitoring. We emphasize that ambulatory antibiotic therapy (whether intravenous or oral) in this patient group requires expert multidisciplinary management, monitoring and follow-up, and ideally should be undertaken within existing OPAT or, more accurately, complex outpatient antibiotic therapy (COpAT) services.

We present extremity wound microbiology data from 250 combat casualties (2009)(2010)(2011)(2012). Confirmed extremity wound infections (EWIs) were based on clinical and laboratory findings. Suspected EWIs had isolation of organisms from wound cultures with associated signs/symptoms not meeting clinical diagnostic criteria. Colonized wounds had organisms isolated without any infection suspicion. A total of 335 confirmed EWIs (131 monomicrobial and 204 polymicrobial) were assessed. Gram-negative bacteria were predominant (57% and 86% of monomicrobial and polymicrobial infections, respectively). In polymicrobial infections, 61% grew only bacteria, while 30% isolated bacteria and mold. Multidrug resistance was observed in 32% of isolates from first monomicrobial EWIs ±3 days of diagnosis, while it was 44% of isolates from polymicrobial EWIs. Approximately 96% and 52% of the suspected and colonized wounds, respectively, shared ≥1 organism in common with the confirmed EWI on the same patient. Understanding of combatrelated EWIs can lead to improvements in combat casualty care.

We examined risk factors for combat-related extremity wound infections (CEWI) among U.S. military patients injured in Iraq and Afghanistan (2009–2012). Patients with ≥1 combat-related, open extremity wound admitted to a participating U.S. hospital (≤7 days postinjury) were retrospectively assessed. The population was classified based upon most severe injury (amputation, open fracture without amputation, or open soft-tissue injury defined as non-fracture/non-amputation wounds). Among 1271 eligible patients, 395 (31%) patients had ≥1 amputation, 457 (36%) had open fractures, and 419 (33%) had open soft-tissue wounds as their most severe injury, respectively. Among patients with traumatic amputations, 100 (47%) developed a CEWI compared to 66 (14%) and 12 (3%) patients with open fractures and open soft-tissue wounds, respectively. In a Cox proportional hazard analysis restricted to CEWIs ≤30 days postinjury among the traumatic amputation and open fracture groups, sustaining an amputation (hazard ratio: 1.79; 95% confidence interval: 1.25–2.56), blood transfusion ≤24 hours postinjury, improvised explosive device blast, first documented shock index ≥0.80, and &gt;4 injury sites were independently associated with CEWI risk. The presence of a non-extremity infection at least 4 days prior to a CEWI diagnosis was associated with lower CEWI risk, suggesting impact of recent exposure to directed antimicrobial therapy. Further assessment of early clinical management will help to elucidate risk factor contribution. The wound classification system provides a comprehensive approach in assessment of injury and clinical factors for the risk and outcomes of an extremity wound infection.

Background: Sero-epidemiological methods are being developed as a tool for rapid assessment of malaria transmission intensity. Simple blood collection methods for use in field settings will make this more feasible. This paper describes validation of such a method, by analysing immunoglobulins from blood retained within immunophoretic rapid diagnostic tests (RDTs) for Plasmodium falciparum. RDTs are now widely used for the diagnosis of malaria and estimation of parasite rates, and this method represents a further use for these devices in malaria control.

Background Tranexamic acid (TXA) has been shown to reduce mortality from severe hemorrhage. Although recent data suggest that TXA has anti-inflammatory properties, few analyses have investigated the impact of TXA on infectious complications in trauma patients. We examined the association between TXA administration and infection risk among injured military personnel. Methods Patients administered TXA were matched by injury severity score to patients who did not receive TXA. Conditional logistic regression was used to examine risk factors associated with infections within 30 days. A Cox proportional analysis evaluated risk factors in a time-to-first infection model. Results A total of 335 TXA recipients were matched to 626 patients not administered TXA. A greater proportion of TXA recipients had an infection compared to the comparative group (P <0.001). The univariate analysis estimated an unadjusted odds ratio (OR) of 2.5 (95 per cent confidence interval [CI]: 1.8–3.4) for the association of TXA with infection risk; however, upon multivariable analysis, TXA administration was not significant (OR: 1.3; CI: 0.8–1.9). Blast injuries, intensive care unit (ICU) admission, and receipt of ≥10 units of blood within 24 hours post-injury were independently associated with infection risk. The Cox proportional model confirmed association with ICU admission and blood transfusions. Moreover, traumatic amputations were also significantly associated with a reduced time-to-first infection. Conclusion In life-threatening military injuries matched for injury severity, TXA recipients did not have a higher risk for infections nor was time to developed infections shorter than in non-recipients. Extent of blood loss, blast injuries, extremity amputations, and intensive care stay were associated with infections.