Characterizing the epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico

Background

Mexico''s local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April–December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission.

Methods and Findings

We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April–December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April–May (Mexico City area), a second wave in June–July (southeastern states), and a geographically widespread third wave in August–December. The median age of laboratory confirmed ILI cases was ∼18 years overall and increased to ∼31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8–2.1, 1.6–1.9, and 1.2–1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%–37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific fall pandemic waves began 2–5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases.

Conclusions

We documented three spatially heterogeneous waves of the 2009 A/H1N1 pandemic virus in Mexico, which were characterized by a relatively young age distribution of cases. Our study highlights the importance of school cycles on the transmission dynamics of this pandemic influenza strain and suggests that school closure and other mitigation measures could be useful to mitigate future influenza pandemics. Please see later in the article for the Editors'' Summary     

The effect of interpersonal psychotherapy and other psychodynamic therapies versus 'treatment as usual' in patients with major depressive disorder

Background

Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Interpersonal psychotherapy and other psychodynamic therapies may be effective interventions for major depressive disorder, but the effects have only had limited assessment in systematic reviews.

Methods/Principal Findings

Cochrane systematic review methodology with meta-analysis and trial sequential analysis of randomized trials comparing the effect of psychodynamic therapies versus ‘treatment as usual’ for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included six trials randomizing a total of 648 participants. Five trials assessed ‘interpersonal psychotherapy’ and only one trial assessed ‘psychodynamic psychotherapy’. All six trials had high risk of bias. Meta-analysis on all six trials showed that the psychodynamic interventions significantly reduced depressive symptoms on the 17-item Hamilton Rating Scale for Depression (mean difference −3.12 (95% confidence interval −4.39 to −1.86;P<0.00001), no heterogeneity) compared with ‘treatment as usual’. Trial sequential analysis confirmed this result.

Discussion

We did not find convincing evidence supporting or refuting the effect of interpersonal psychotherapy or psychodynamic therapy compared with ‘treatment as usual’ for patients with major depressive disorder. The potential beneficial effect seems small and effects on major outcomes are unknown. Randomized trials with low risk of systematic errors and low risk of random errors are needed.     

Sudden loading during a dynamic lifting task: a simulation study

It is believed that nurses risk the development of back pain as a consequence of sudden loadings during tasks in which they are handling patients. Forward dynamics simulations of sudden loads (applied to the arms) during dynamic lifting tasks were performed on a two-dimensional whole-body model. Loads were in the range of -80 kg to 80 kg, with the initial load being 20 kg. Loading the arm downwards with less than that which equals a mass of 20 kg did not change the compressive forces on the spine when compared to a normal lifting motion with a 20 kg mass in the hands. However when larger loads (40 kg to 80 kg extra in the hands) were simulated, the compressive forces exceeded 13,000 N (above 3400 N is generally considered a risk factor). Loading upwards led to a decrease in the compressive forces but to a larger backwards velocity at the end of the movement. In the present study, it was possible to simulate a fast lifting motion. The results showed that when loading the arms downwards with a force that equals 40 kg or more, the spine was severely compressed. When loading in the opposite direction (unloading), the spine was not compressed more than during a normal lifting motion. In practical terms, this indicates that if a nursing aide tries to catch a patient who is falling, large compressive forces are applied to the spine.     

Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces

The biosynthetic pathway of the red-pigmented antibiotic, prodigiosin, produced by Serratia sp. is known to involve separate pathways for the production of the monopyrrole, 2-methyl-3-n-amyl-pyrrole (MAP) and the bipyrrole, 4-methoxy-2,2'-bipyrrole-5-carbaldehyde (MBC) which are then coupled in the final condensation step. We have previously reported the cloning, sequencing and heterologous expression of the pig cluster responsible for prodigiosin biosynthesis in two Serratia sp. In this article we report the creation of in-frame deletions or insertions in every biosynthetic gene in the cluster from Serratia sp. ATCC 39006. The biosynthetic intermediates accumulating in each mutant have been analysed by LC-MS, cross-feeding and genetic complementation studies. Based on these results we assign specific roles in the biosynthesis of MBC to the following Pig proteins: PigI, PigG, PigA, PigJ, PigH, PigM, PigF and PigN. We report a novel pathway for the biosynthesis of MAP, involving PigD, PigE and PigB. We also report a new chemical synthesis of MAP and one of its precursors, 3-acetyloctanal. Finally, we identify the condensing enzyme as PigC. We reassess the existing literature and discuss the significance of the results for the biosynthesis of undecylprodigiosin by the Red cluster in Streptomyces coelicolor A3(2).     

Cyanogenic glycosides: a case study for evolution and application of cytochromes P450

Cyanogenic glycosides are ancient biomolecules found in more than 2,650 higher plant species as well as in a few arthropod species. Cyanogenic glycosides are amino acid-derived β-glycosides of α-hydroxynitriles. In analogy to cyanogenic plants, cyanogenic arthropods may use cyanogenic glycosides as defence compounds. Many of these arthropod species have been shown to de novo synthesize cyanogenic glycosides by biochemical pathways that involve identical intermediates to those known from plants, while the ability to sequester cyanogenic glycosides appears to be restricted to Lepidopteran species. In plants, two atypical multifunctional cytochromes P450 and a soluble family 1 glycosyltransferase form a metabolon to facilitate channelling of the otherwise toxic and reactive intermediates to the end product in the pathway, the cyanogenic glycoside. The glucosinolate pathway present in Brassicales and the pathway for cyanoalk(en)yl glucoside synthesis such as rhodiocyanosides A and D in Lotus japonicus exemplify how cytochromes P450 in the course of evolution may be recruited for novel pathways. The use of metabolic engineering using cytochromes P450 involved in biosynthesis of cyanogenic glycosides allows for the generation of acyanogenic cassava plants or cyanogenic Arabidopsis thaliana plants as well as L. japonicus and A. thaliana plants with altered cyanogenic, cyanoalkenyl or glucosinolate profiles.     

Cardiovascular effects of epinephrine during rewarming from hypothermia in an intact animal model.

Rewarming from accidental hypothermia is often complicated by "rewarming shock," characterized by low cardiac output (CO) and a sudden fall in peripheral arterial pressure. In this study, we tested whether epinephrine (Epi) is able to prevent rewarming shock when given intravenously during rewarming from experimental hypothermia in doses tested to elevate CO and induce vasodilation, or lack of vasodilation, during normothermia. A rat model designed for circulatory studies during experimental hypothermia and rewarming was used. A total of six groups of animals were used: normothermic groups 1, 2, and 3 for dose-finding studies, and hypothermic groups 4, 5, and 6. At 20 and 24 degrees C during rewarming, group 4 (low-dose Epi) and group 5 (high-dose Epi) received bolus injections of 0.1 and 1.0 microg Epi, respectively. At 28 degrees C, Epi infusion was started in groups 4 and 5 with 0.125 and 1.25 microg/min, respectively. Group 6 served as saline control. After rewarming, both CO and stroke volume were restored in group 4, in contrast to groups 5 and 6, in which both CO and stroke volume remained significantly reduced (30%). Total peripheral resistance was significantly higher in group 5 during rewarming from 24 to 34 degrees C, compared with groups 4 and 6. This study shows that, in contrast to normothermic conditions, Epi infused during hypothermia induces vasoconstriction rather than vasodilation combined with lack of CO elevation. The apparent dissociation between myocardial and vascular responses to Epi at low temperatures may be related to hypothermia-induced myocardial failure and changes in temperature-dependent adrenoreceptor affinity.     

Identification of amyloidogenic proteins in the microbiomes of a rat Parkinson's disease model and wild‐type rats

Cross seeding between amyloidogenic proteins in the gut is receiving increasing attention as a possible mechanism for initiation or acceleration of amyloid formation by aggregation‐prone proteins such as αSN, which is central in the development of Parkinson''s disease (PD). This is particularly pertinent in view of the growing number of functional (i.e., benign and useful) amyloid proteins discovered in bacteria. Here we identify two amyloidogenic proteins, Pr12 and Pr17, in fecal matter from PD transgenic rats and their wild type counterparts, based on their stability against dissolution by formic acid (FA). Both proteins show robust aggregation into ThT‐positive aggregates that contain higher‐order β‐sheets and have a fibrillar morphology, indicative of amyloid proteins. In addition, Pr17 aggregates formed in vitro showed significant resistance against FA, suggesting an ability to form highly stable amyloid. Treatment with proteinase K revealed a protected core of approx. 9 kDa. Neither Pr12 nor Pr17, however, affected αSN aggregation in vitro. Thus, amyloidogenicity does not per se lead to an ability to cross‐seed fibrillation of αSN. Our results support the use of proteomics and FA to identify amyloidogenic protein in complex mixtures and suggests that there may be numerous functional amyloid proteins in microbiomes.     

Genetic variation of Zoarces viviparus: six populations revisited after about 35 years

Totally, 417 eelpouts from six localities were collected in November-December 2007. Among these, 314 were females and from 246 of these females, one offspring was collected. The selected populations were also studied 36-38 years ago with the same technique, horizontal starch gel electrophoresis. The same enzymes were analysed at that time and now, but additional enzymes were analysed in the samples collected now, totally five enzymes representing 10 loci. A strong congruence in the genetic composition was found between the samples collected 36-38 years ago and those collected in 2007. No effect of pollutants in the environment was seen on the genetic variation by means of isozymes, but deformed offspring was observed and furthermore at one locality a high frequency of not pregnant females in the sample was observed.