Post-traumatic osteomyelitis in Middle East war-wounded civilians: resistance to first-line antibiotics in selected bacteria over the decade 2006-2016.

BACKGROUND: War-wounded civilians in Middle East countries are at risk of post-traumatic osteomyelitis (PTO). We aimed to describe and compare the bacterial etiology and proportion of first-line antibiotics resistant bacteria (FLAR) among PTO cases in civilians from Syria, Iraq and Yemen admitted to the reconstructive surgical program of Médecins Sans Frontières (MSF) in Amman, Jordan, and to identify risk factors for developing PTO with FLAR bacteria. METHODS: We retrospectively analyzed the laboratory database of the MSF program. Inclusion criteria were: patients from Iraq, Yemen or Syria, admitted to the Amman MSF program between October 2006 and December 2016, with at least one bone biopsy sample culture result. Only bone samples taken during first orthopedic surgery were included in the analysis. To assess factors associated with FLAR infection, logistic regression was used to estimate odds ratio (ORs) and 95% confidence intervals (CI). RESULTS: 558 (76.7%) among 727 patients included had ≥1 positive culture results. 318 were from Iraq, 140 from Syria and 100 from Yemen. Median time since injury was 19 months [IQR 8-40]. Among the 732 different bacterial isolates, we identified 228 Enterobacteriaceae (31.5%), 193 Staphylococcus aureus (26.3%), 99 Pseudomonas aeruginosa (13.5%), and 21 Acinetobacter baumanii (2.8%). Three hundred and sixty four isolates were FLAR: 86.2% of Enterobacteriaceae, 53.4% of Pseudomonas aeruginosa, 60.5% of S. aureus and 45% of Acinetobacter baumannii. There was no difference in bacterial etiology or proportion of FLAR according to the country of origin. In multivariate analysis, a FLAR infection was associated with an infection of the lower extremity, with a time since the injury ≤12 months compared with time > 30 months and with more than 3 previous surgeries. CONCLUSIONS: Enterobacteriaceae were frequently involved in PTO in war wounded civilians from Iraq, Yemen and Syria between 2006 and 2016. Proportion of FLAR was high, particularly among Enterobacteriaceae, regardless of country of origin.

Publisher Correction: Genomic insights into the 2016-2017 cholera epidemic in Yemen.

In the HTML version of this Letter, the affiliations for authors Andrew S. Azman, Dhirendra Kumar and Thandavarayan Ramamurthy were inverted (the PDF and print versions of the Letter were correct); the affiliations have been corrected online.

Genomic insights into the 2016-2017 cholera epidemic in Yemen.

Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.

Cholera epidemic in Yemen, 2016-18: an analysis of surveillance data.

BACKGROUND: In war-torn Yemen, reports of confirmed cholera started in late September, 2016. The disease continues to plague Yemen today in what has become the largest documented cholera epidemic of modern times. We aimed to describe the key epidemiological features of this epidemic, including the drivers of cholera transmission during the outbreak. METHODS: The Yemen Health Authorities set up a national cholera surveillance system to collect information on suspected cholera cases presenting at health facilities. Individual variables included symptom onset date, age, severity of dehydration, and rapid diagnostic test result. Suspected cholera cases were confirmed by culture, and a subset of samples had additional phenotypic and genotypic analysis. We first conducted descriptive analyses at national and governorate levels. We divided the epidemic into three time periods: the first wave (Sept 28, 2016, to April 23, 2017), the increasing phase of the second wave (April 24, 2017, to July 2, 2017), and the decreasing phase of the second wave (July 3, 2017, to March 12, 2018). We reconstructed the changes in cholera transmission over time by estimating the instantaneous reproduction number, Rt. Finally, we estimated the association between rainfall and the daily cholera incidence during the increasing phase of the second epidemic wave by fitting a spatiotemporal regression model. FINDINGS: From Sept 28, 2016, to March 12, 2018, 1 103 683 suspected cholera cases (attack rate 3·69%) and 2385 deaths (case fatality risk 0·22%) were reported countrywide. The epidemic consisted of two distinct waves with a surge in transmission in May, 2017, corresponding to a median Rt of more than 2 in 13 of 23 governorates. Microbiological analyses suggested that the same Vibrio cholerae O1 Ogawa strain circulated in both waves. We found a positive, non-linear, association between weekly rainfall and suspected cholera incidence in the following 10 days; the relative risk of cholera after a weekly rainfall of 25 mm was 1·42 (95% CI 1·31-1·55) compared with a week without rain. INTERPRETATION: Our analysis suggests that the small first cholera epidemic wave seeded cholera across Yemen during the dry season. When the rains returned in April, 2017, they triggered widespread cholera transmission that led to the large second wave. These results suggest that cholera could resurge during the ongoing 2018 rainy season if transmission remains active. Therefore, health authorities and partners should immediately enhance current control efforts to mitigate the risk of a new cholera epidemic wave in Yemen. FUNDING: Health Authorities of Yemen, WHO, and Médecins Sans Frontières.

SANS studies of the effects of surfactant head group on aggregation properties in water/glycol and pure glycol systems.

Aggregation in mixed water-glycol and pure glycol solvents has been investigated with four related surfactants, bearing common C12 tails: anionic, sodium dodecylsulfate (SDS); cationic, dodecyltrimethylammonium bromide (C12TAB); zwitterionic C12-amidopropyldimethylamine betaine (betaine) and nonionic, octaethyleneglycol monododecyl ether (C12E8). The solvent media were water, water/ethylene glycol, and water/propylene glycol mixtures, as well as pure ethylene glycol (EG) and propylene glycol (PG), spanning relative dielectrics epsilon(r) from 79 to 30. Results from small-angle neutron scattering (SANS) experiments, employing deuterated solvents, were consistent with the presence of ellipsoidal, or cylindrical micelles, depending on solvent and surfactant type. In pure EG and PG solvents the ionic and zwitterionic surfactants exhibit only weak aggregation, with much smaller micelles than normally found in water. However, interestingly, pure EG is identified as a solvent in which nonionic C12E8 aggregates strongly, mirroring the behavior in water. In contrast when the solvent is changed to PG (epsilonr=30) aggregation of C12E8 is only minimal. Hence, aggregation is shown to be strongly dependent on surfactant type and identity of the glycol solvent.

Controlling aggregation of nonionic surfactants using mixed glycol media.

The extent of aggregation of nonionic surfactants can be controlled by the composition of mixed solvents with two miscible glycols, ethylene glycol (EG)/propylene glycol (PG). Three nonionic surfactants bearing a common E8 ethoxylated headgroup, but with variations in the hydrocarbon chain, have been investigated: octaethylene monododecyl ether (C12E8), octaethylene monotetradecyl ether (C14E8), and octaethylene monohexadecyl ether (C16E8). The hydrogen-bonding solvents were EG/PG mixtures at different PG levels, defined in terms of the concentration (mol %) of PG. Aggregation was investigated using small-angle neutron scattering (SANS) with h-CiE8 surfactants, at 10 and 5 wt %, in deuterated glycol solvents to improve contrast. Increasing PG concentration (mol %) in the background EG/PG solvent leads to a consistent decrease in the SANS intensity, until in pure d-PG only very weak scattering is observed. These SANS data were analyzed using cylinder or ellipsoidal form factors for the EG-rich and PG-rich systems, respectively, hence demonstrating an aggregate shape change as a function of solvent composition. The results show that aggregation of nonionic surfactants occurs in glycol solvents and that the EG:PG ratio may be used as an effective means to switch aggregation "on" or "off", as required.

Unexpected adsorption behavior of nonionic surfactants from glycol solvents.

Adsorption and interfacial properties of model methyl-capped nonionic surfactants C8E4OMe [C8H17O(C2H4O)4CH3] and C10E4OMe [C10H21O(C2H4O)4CH3] were studied in water and water/ethylene glycol mixtures as well as pure ethylene glycol. Critical micellar concentrations (cmc's), surface tensions, and surface excess were determined using surface tension (ST) and neutron reflection (NR) as a function of solvent type and surfactant tail length. The ST results show a strong dependence on solvent type in terms of cmc. The NR data were analyzed using a single-layer model for the adsorbed surfactant films. Surprisingly, the adsorption parameters obtained in both water and pure ethylene glycol were very similar, and variations in film thickness or area per molecule are negligible in respect of the uncertainties. Similarly, for C10E4OMe, estimates for the free energies of adsorption and micellization show only a weak solvent dependence. These results suggest that for such model nonionic surfactants dilute solution properties are dictated by solvophobicity, which is quite similar for this class of water, glycol, and water-glycol mixtures. More specifically, the nature of the adsorption layer appears to be hardly affected by the type of solvent subphase. The findings highlight the significance of solvophobicity and show that model nonionic surfactants can behave very similarly in hydrogen-bonding glycol solvents and water.