Adriana Tami

Risk Factors for the Transmission of Methicillin-Resistant Staphylococcus aureus in an Adult Intensive Care Unit: Fitting a Model to the Data

Little is known about the amount of cross-transmission, the risk factors for infection, and the relative effectiveness of infection control procedures when methicillin-resistant Staphylococcus aureus (MRSA) infection occurs at highly endemic levels in intensive care units. A cohort study was done to identify exposures associated with cases that likely were the result of cross-transmission (i.e., occurring in clusters and with indistinguishable MRSA macrorestriction profiles). Fitting a simple stochastic model to the ascertained data allowed prediction of the effectiveness of infection control measures. Exposure to relative staff deficit (adjusted rate ratio, 1.05 independent; 95% confidence interval, 1.02-1.09) was the only factor significantly associated with potential transmission (P =.001). It was predicted that a 12% improvement in adherence to hand-hygiene policies might have compensated for staff shortage and prevented transmission during periods of overcrowding, shared care, and high workload but that this would be hard to achieve.

How many infections are caused by patient-to-patient transmission in intensive care units?*

Objective:The proportion of intensive care unit (ICU)-acquired infections that are a consequence of nosocomial cross-transmission between patients in tertiary ICUs is unknown. Such information would be useful for the implementation of appropriate infection control measures. Design:A prospective cohort study during 18 months. Setting:Five ICUs from two university hospitals. Patients:All patients admitted for ≥48 hrs. Measurement:ICU-acquired infections were ascertained during daily bedside patient and chart reviews. Episodes of potential cross-transmission were identified by highly discriminating genetic typing of all clinical and surveillance isolates of the ten bacterial species most frequently associated with nosocomial infections in ICUs. Isolation of indistinguishable isolates in two or more patients defined potential transmission episodes. Main Results:During 28,498 patient days, 431 ICU-acquired infections and 141 episodes of nosocomial transmissions were identified. A total of 278 infections were caused by the ten species that were genotyped, and 41 of these (14.5%) could be associated with transmissions between patients. Conclusion:Infections acquired during treatment in modern tertiary ICUs are common, but a causative role of direct patient-to-patient transmission can only be ascertained for a minority of these infections on the basis of routine microbiological investigations.

Determining the Genetic Structure of the Natural Population of Staphylococcus aureus: a Comparison of Multilocus Sequence Typing with Pulsed-Field Gel Electrophoresis, Randomly Amplified Polymorphic DNA Analysis, and Phage Typing

ABSTRACT We used a sample of Staphylococcus aureus strains that are carried by humans and that are representative of the natural population of S. aureus strains in order to assess the value of multilocus sequence typing (MLST), pulsed-field gel electrophoresis, randomly amplified polymorphic DNA analysis, and phage typing as epidemiological tools. Only MLST was able to define clonal complexes unambiguously. All DNA-based typing approaches achieved a high degree of agreement, implying phylogenetic concordance, but predicted epidemiological associations with variable accuracy.

Evaluation of Olyset insecticide-treated nets distributed seven years previously in Tanzania.

BackgroundInsecticide-treated nets represent currently a key malaria control strategy, but low insecticide re-treatment rates remain problematic. Olyset™ nets are currently one of two long-lasting insecticidal nets recommended by WHO. An assessment was carried out of the effect of Olyset™ nets after seven years of use in rural Tanzania.MethodsA survey of Olyset™ nets was conducted in two Tanzanian villages to examine their insecticide dosage, bioassay efficacy and desirability compared with ordinary polyester nets.ResultsOf 103 randomly selected nets distributed in 1994 to 1995, 100 could be traced. Most nets were in a condition likely to offer protection against mosquito biting. Villagers appreciated mainly the durability of Olyset™ nets and insecticide persistence. People disliked the small size of these nets and the light blue colour and preferred a smaller mesh size, features that can easily be modified. At equal price, 51% said they would prefer to buy an Olyset™ net and 49% opted for an ordinary polyester net. The average permethrin content was 33%-41% of the initial insecticide dose of 20,000 mg/Kg. Bioassay results indicated high knock-down rates at 60 minutes, but the mosquito mortality after 24 hours was rather low (mean: 34%). No significant correlation was found between bioassay results and insecticide concentration in and on the net.ConclusionsOlyset™ nets are popular, durable and with a much longer insecticide persistence than ordinary polyester nets. Hence, Olyset™ nets are one of the best choices for ITN programmes in rural malaria-endemic areas.

Field issues related to effectiveness of insecticide-treated nets in Tanzania

Abstract.  Insecticide‐treated nets (ITNs) impregnated with pyrethroid insecticides have become one of the most promising interventions to prevent malaria in highly endemic areas. Despite the large body of experience documenting their health impact and the best way to distribute them, some key practical issues remain unresolved. For example, the duration of effective life of a net under field conditions is unknown. The most important factor affecting net effectiveness is the issue of regular re‐treatment with insecticide. Washing is also an important determinant of insecticide longevity in the field. Trials were undertaken to provide some essential field information on ITNs within the site of an extended ITN programme in the Morogoro region of Tanzania. It was found that 45% of all nets were in bad condition (defined as more than seven large holes). It is concluded that an effective ‘life’ for polyester nets is 2–3 years. Further, two‐thirds of the 20% of nets that were reported as having been re‐treated within the last 12 months had less than 5 mg/m2 of insecticide. According to the World Health Organization this is insufficient to be effective. People reported that they washed their nets four to seven times per year, usually with soap. Observations showed that such washing does not harm the nets and that the wash‐water was unlikely to have an impact on the environment. Finally, bioassays were carried out with Anopheles gambiae on polyester netting with 0.5, 2, 5, 10 and 30 mg/m2 of deltamethrin, alphacypermethrin and lambdacyhalothrin to assess the effectiveness of pyrethroids. The results confirmed that even with low insecticide concentrations, nets can still provide partial protection.

Nottingham Staphylococcus aureus population study: prevalence of MRSA among elderly people in the community

The spread of methicillin resistant Staphylococcus aureus (MRSA) has caused problems in most hospitals in the United Kingdom in the past decade.1 The extent to which the community serves as a reservoir for MRSA is unknown despite the growing recognition of MRSA as a community pathogen in various countries.2 We investigated the prevalence of nasal carriage of MRSA in a sample of people aged 65 and over who live in their own homes and represent the elderly population in the Greater Nottingham Health District, where MRSA is endemic in hospitals.3 We used electoral ward level statistics from 1991 to combine the catchment areas of seven large general practices and provide a study population of which the demographic composition (age, sex, social class, ethnicity, and proportion of elderly people living alone) was representative of the Nottingham Health District, which in most respects is …

The dynamic changes of dominant clones of Staphylococcus aureus causing bloodstream infections in the European region: Results of a second structured survey

Staphylococcus aureus is one of the most important human pathogens and meticillin-resistant S. aureus (MRSA) presents a major cause of healthcare- and community-acquired infections. This study investigated the spatial and temporal changes of S. aureus causing bacteraemia in Europe over a five-year interval and explored the possibility of integrating pathogen-based typing data with epidemiological and clinical information at a European level. Between January 2011 and July 2011, 350 laboratories serving 453 hospitals in 25 countries collected 3,753 isolates (meticillin-sensitive S. aureus (MSSA) and MRSA) from patients with S. aureus bloodstream infections. All isolates were sent to the national staphylococcal reference laboratories and characterised by quality-controlled spa typing. Data were uploaded to an interactive web-based mapping tool. A wide geographical distribution of spa types was found, with some prevalent in all European countries. MSSA was more diverse than MRSA. MRSA differed considerably between countries with major international clones expanding or receding when compared to a 2006 survey. We provide evidence that a network approach of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of S. aureus populations such as early signalling of emerging strains, cross-border spread and importation by travel.

ama1 Genes of Sympatric Plasmodium vivax and P. falciparum from Venezuela Differ Significantly in Genetic Diversity and Recombination Frequency

Background We present the first population genetic analysis of homologous loci from two sympatric human malaria parasite populations sharing the same human hosts, using full-length sequences of ama1 genes from Plasmodium vivax and P. falciparum collected in the Venezuelan Amazon. Methodology/Principal Findings Significant differences between the two species were found in genetic diversity at the ama1 locus, with 18 distinct haplotypes identified among the 73 Pvama1 sequences obtained, compared to 6 unique haplotypes from 30 Pfama1 sequences, giving overall diversity estimates of h = 0.9091, and h = 0.538 respectively. Levels of recombination were also found to differ between the species, with P. falciparum exhibiting very little recombination across the 1.77kb sequence. In contrast, analysis of patterns of nucleotide substitutions provided evidence that polymorphisms in the ama1 gene of both species are maintained by balancing selection, particularly in domain I. The two distinct population structures observed are unlikely to result from different selective forces acting upon the two species, which share both human and mosquito hosts in this setting. Rather, the highly structured P. falciparum population appears to be the result of a population bottleneck, while the much less structured P. vivax population is likely to be derived from an ancient pool of diversity, as reflected in a larger estimate of effective population size for this species. Greatly reduced mosquito transmission in 1997, due to low rainfall prior to the second survey, was associated with far fewer P. falciparum infections, but an increase in P. vivax infections, probably due to hypnozoite activation. Conclusions/Significance The relevance of these findings to putative competitive interactions between these two important human pathogen species is discussed. These results highlight the need for future control interventions to employ strategies targeting each of the parasite species present in endemic areas.

Spatial effects of mosquito bednets on child mortality

BackgroundInsecticide treated nets (ITN) have been proven to be an effective tool in reducing the burden of malaria. Few randomized clinical trials examined the spatial effect of ITNs on child mortality at a high coverage level, hence it is essential to better understand these effects in real-life situation with varying levels of coverage. We analyzed for the first time data from a large follow-up study in an area of high perennial malaria transmission in southern Tanzania to describe the spatial effects of bednets on all-cause child mortality.MethodsThe study was carried out between October 2001 and September 2003 in 25 villages in Kilombero Valley, southern Tanzania. Bayesian geostatistical models were fitted to assess the effect of different bednet density measures on child mortality adjusting for possible confounders.ResultsIn the multivariate model addressing potential confounding, the only measure significantly associated with child mortality was the bed net density at household level; we failed to observe additional community effect benefit from bed net coverage in the community.ConclusionIn this multiyear, 25 village assessment, despite substantial known inadequate insecticide-treatment for bed nets, the density of household bed net ownership was significantly associated with all cause child mortality reduction. The absence of community effect of bednets in our study area might be explained by (1) the small proportion of nets which are treated with insecticide, and (2) the relative homogeneity of coverage with nets in the area. To reduce malaria transmission for both users and non-users it is important to increase the ITNs and long-lasting nets coverage to at least the present untreated nets coverage.

Sympatric Plasmodium falciparum isolates from Venezuela have structured var gene repertoires

BackgroundThe human malaria parasite Plasmodium falciparum expresses adhesins belonging to the erythrocyte membrane protein 1 (PfEMP1) family on the surface of the infected host erythrocyte. These antigens elicit a strain-specific antibody response that is associated with protection from disease. During clonal expansion of blood-stage parasites, the surface phenotype of the infected erythrocyte changes because of transcriptional switching among the 40 to 50 members of the highly polymorphic var multi-gene family which encode PfEMP1 variants. Studies to date have compared var repertoires of natural isolates from various geographical locations but have not addressed any within-population structure that may exist among repertoires.MethodsDistinct parasite genotypes from a single population co-circulating among a defined group of hosts were selected. PCR products encoding the DBL-α domain of PfEMP-1 were cloned and sequenced from each of three isolates. Repertoire similarity was statistically evaluated using combinatorial analysis. The chromosomal location of shared sequences was inferred from similarity to dbl-α of known location in the 3D7 genome.ResultsSympatric parasites were found to share few var gene sequences, even when alleles at other polymorphic loci were shared. A number of the sequences shared by at least two of the isolates studied were found to be related to 3D7 genomic sequences with non-telomeric chromosomal locations, or atypical domain structures, which may represent globally conserved loci.ConclusionThe parasite population studied is structured, with minimal overlap in PfEMP1 repertoires. The var gene family accumulates diversity more rapidly than other antigen genes examined. This may be facilitated by ectopic recombination among the sub-telomeric regions of P. falciparum chromosomes.