Biology subjects

Crellen, T.

Publications and source records attributed to Crellen, T..

3 recordsLinked to original sources

bioRxiv2018

Transmission dynamics and between-species interactions of multidrug-resistant Enterobacteriaceae

Widespread resistance to antibiotics is among the gravest threats to modern medicine, and controlling the spread of multi-drug resistant Enterobacteriaceae has been given priority status by the World Health Organization. Interventions to reduce transmission within hospital wards may be informed by modifiable patient-level risk factors for becoming colonised, however understanding of factors that influence a patients risk of acquisition is limited. We analyse data from a one year prospective carriage study in a neonatal intensive care unit in Cambodia using Bayesian hierarchical models to estimate the daily probability of acquiring multi-drug resistant organisms, while accounting for patient-level time-varying covariates, including interactions between species, and interval-censoring of transmission events. We estimate the baseline daily probability for becoming colonised with third generation cephalosporin resistant (3GC-R) Klebsiella pneumoniae as 0.142 (95% credible interval [CrI] 0.066, 0.27), nearly ten times higher than the daily probability of acquiring 3GC-R Escherichia coli (0.016 [95% CrI 0.0038, 0.049]). Prior colonization with 3GC-R K. pneumoniae was associated with a greatly increased risk of a patient acquiring 3GC-R E. coli (odds ratio [OR] 6.4 [95% CrI 2.8, 20.9]). Breast feeding was associated with a reduced risk of colonization with both 3GC-R K. pneumoniae (OR 0.73 [95% CrI 0.38, 1.5]) and E. coli (OR 0.62 [95% CrI 0.28, 1.6]). The use of an oral probiotic (Lactobacillus acidophilus) did not show clear evidence of protection against colonization with either 3GC-R K. pneumoniae (OR 0.83 [95% CrI 0.51, 1.3]) or 3GC-R E. coli (OR 1.3 [95% CrI 0.77, 2.1]). Antibiotic consumption within the past 48 hours did not strongly influence the risk of acquiring 3GC-R K. pneumoniae. For 3GC-R E. coli, ceftriaxone showed the strongest effect for increasing the risk of acquisition (OR 2.2 [95% CrI 0.66, 6.2]) and imipenem was associated with a decreased risk (OR 0.31 [95% CrI 0.099, 0.76). Using 317 whole-genome assemblies of K. pneumoniae, we determined putatively related clusters and used a range of models to infer transmission rates. Model comparison strongly favored models with a time-varying force of infection term that increased in proportion with the number of colonized patients, providing evidence of patient-to-patient transmission, including among a cluster of Klebsiella quasipneumoniae. Our findings provide support for the hypothesis that K. pneumoniae can be spread person-to-person within ward settings. Subsequent horizontal gene transfer within patients from K. pneumoniae provides the most parsimonious explanation for the strong association between colonization with 3GC-R K. pneumoniae and acquisition of 3GC-R E. coli.

epidemiology↗

bioRxiv2018

What drives mortality among HIV patients in a conflict setting? A prospective cohort study in the Central African Republic

BackgroundProvision of antiretroviral therapy (ART) during conflict settings is rarely attempted and little is known about the expected patterns of mortality. The Central African Republic (CAR) continues to have a low coverage of ART despite an estimated 120,000 people living with HIV and 11,000 AIDS-related deaths in 2013. We present results from a cohort in Zemio, Haut-Mboumou prefecture. This region had the highest prevalence of HIV nationally (14.8% in 2010) and was subject to repeated attacks by armed groups on civilians during the observed period.\n\nMethodsConflict from armed groups can impact cohort mortality rates i) directly if HIV patients are victims of armed conflict, or ii) indirectly if population displacement or fear of movement reduces access to ART. Using monthly counts of civilian deaths, injuries and abductions, we estimated the impact of the conflict on patient mortality. We also determine patient-level risk factors for mortality and how this varies with time spent in the cohort. Model-fitting was performed in a Bayesian framework, using generalised-linear models with terms accounting for temporal autocorrelation.\n\nResultsPatients were recruited and observed from October 2011 to May 2017. Overall 1631 patients were enrolled, giving 4107 person-years and 148 deaths. Our first model shows that patient mortality did not increase during periods of heightened conflict. The monthly risk (probability) of mortality was markedly higher at the beginning of the program (0.047 in November 2011 [95% credible interval; CrI 0.0078, 0.21]) and had declined greater than ten-fold by the end of the observed period (0.0016 in June 2017 [95% CrI 0.00042, 0.0036]). Our second model shows the risk of mortality for individual patients was highest in the first five months spent in the cohort. Male sex was associated with a higher mortality (odds ratio; OR 1.7 [95% CrI 1.2, 2.8]) along with the severity of opportunistic infections at baseline.\n\nConclusionsOur results show that chronic conflict did not appear to adversely affect rates of mortality in this cohort, and that mortality was driven predominantly by patient specific risk factors. In areas initiating ART for the first time, particular attention should be focussed on stabilising patients with advanced symptoms.\n\nFundingMedecins Sans Frontieres

epidemiology↗

bioRxiv2016

Genomes of an entire Plasmodium subgenus reveal paths to virulent human malaria

Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite P. praefalciparum. Little is known about the other gorilla and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers as well as convergent evolution were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor shows a host specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate confidently for the first time the timing of the beginning of speciation to be 40,000-60,000 years ago followed by a population bottleneck around 4,000-6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans.

evolutionary biology↗