ObjectiveThe objective of this study was to characterise the incidence rates of herpes zoster (HZ), also known as shingles, and risk of complications across the world.DesignWe systematically reviewed studies examining the incidence rates of HZ, temporal trends of HZ, the risk of complications including postherpetic neuralgia (PHN) and HZ-associated hospitalisation and mortality rates in the general population. The literature search was conducted using PubMed, EMBASE and the WHO library up to December 2013.ResultsWe included 130 studies conducted in 26 countries. The incidence rate of HZ ranged between 3 and 5/1000 person-years in North America, Europe and Asia-Pacific, based on studies using prospective surveillance, electronic medical record data or administrative data with medical record review. A temporal increase in the incidence of HZ was reported in the past several decades across seven countries, often occurring before the introduction of varicella vaccination programmes. The risk of developing PHN varied from 5% to more than 30%, depending on the type of study design, age distribution of study populations and definition. More than 30% of patients with PHN experienced persistent pain for more than 1 year. The risk of recurrence of HZ ranged from 1% to 6%, with long-term follow-up studies showing higher risk (5–6%). Hospitalisation rates ranged from 2 to 25/100 000 person-years, with higher rates among elderly populations.ConclusionsHZ is a significant global health burden that is expected to increase as the population ages. Future research with rigorous methods is important.

For microbial pathogens, phylogeographic differentiation seems to be relatively common. However, the neutral population structure of Salmonella enterica serovar Typhi reflects the continued existence of ubiquitous haplotypes over millennia. In contrast, clinical use of fluoroquinolones has yielded at least 15 independent gyrA mutations within a decade and stimulated clonal expansion of haplotype H58 in Asia and Africa. Yet, antibiotic-sensitive strains and haplotypes other than H58 still persist despite selection for antibiotic resistance. Neutral evolution in Typhi appears to reflect the asymptomatic carrier state, and adaptive evolution depends on the rapid transmission of phenotypic changes through acute infections.Many bacterial taxa can be subdivided into multiple, discrete clonal groupings (clonal complexes, or ecotypes) that have diverged and differentiated as a result of clonal replacement, selective sweeps, periodic selection, and/or population bottlenecks (1). Geographic isolation and clonal replacement can also result in phylogeographic differences between bacterial pathogens from different parts of the world (2), even within young, genetically monomorphic pathogens (3) (supporting online material text) such as Mycobacterium tuberculosis (4) and Yersinia pestis (5). Typhi is a genetically monomorphic (6), human-restricted bacterial pathogen that causes 21 million cases of typhoid fever and 200,000 deaths per year, predominantly in southern Asia, Africa, and South America (7). Typhi also enters a carrier state in rare individuals [such as Mortimer's example of "Mr. N the milker" (8)], who can shed high levels of these bacteria for decades in the absence of clinical symptoms. Genome sequences are available from strains CT18 (9) and Ty2 (10), but † To whom correspondence should be addressed. E-mail: achtman@mpiib-berlin. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts the global diversity, population genetic structure, and evolutionary history of Typhi were poorly understood. It has been speculated that Typhi evolved in Indonesia, which is the exclusive source of isolates with the z66 flagellar antigen (11).We investigated the evolutionary history and population genetic structure of Typhi by mutation discovery (12) We anticipated that housekeeping genes would exhibit diminished levels of nucleotide diversity, π, as a result of purifying selection, and that pathogenicity genes would exhibit elevated levels as a result of diversifying selection. However, π did not differ significantly with gene category (P > 0.05, analysis of variance) (table S1). Purifying selection should result in Ka/Ks (the ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site) values that are less than 1.0 and diversifying selection should result in ratios higher than 1.0. A trend in this direction was observed (table S1), but it was not particularly strong. We therefore concluded that these 88 BiPs largely reflect the lack of strong selection a...

No abstract

No abstract

The Vi vaccine was effective in young children and protected unvaccinated neighbors of Vi vaccinees. The potential for combined direct and indirect protection by Vi vaccine should be considered in future deliberations about introducing this vaccine in areas where typhoid fever is endemic. (ClinicalTrials.gov number, NCT00125008.)

Abstract. Malaria remains the most important parasitic cause of mortality in humans. Its presentation is thought to vary according to the intensity of Plasmodium falciparum transmission. However, detailed descriptions of presenting features and risk factors for death are only available from moderate transmission settings. Such descriptions help to improve case management and identify priority research areas. Standardized systematic procedures were used to collect clinical and laboratory data on 6,624 children admitted to hospital over a 1-year period in an intensely malarious part of Tanzania. Frequencies of signs and symptoms were calculated and their association with a fatal outcome was assessed using multivariate logistic regression. There were 72 deaths among 2,432 malaria cases (case fatality rate [CFR] ϭ 3.0%); 44% of the cases and 54% of the deaths were in individuals less than 1 year of age. There was no association between level of parasitemia and CFR. Increased risk of dying was independently found in all children with hypoglycemia (odds ratio [OR] ϭ 6.7, 95% confidence interval [CI] ϭ 3.9-11.7), in children 1-7 months of age with tachypnea (OR ϭ 8.8, 95% CI ϭ 2.6-30.5) and dehydration (OR ϭ 5.0, 95% CI ϭ 1.9-14.2), and in children 8 months to 4 years of age with chest indrawing (OR ϭ 4.7, 95% CI ϭ 2.0-11.2) and inability to localize a painful stimulus (OR ϭ 6.9, 95% CI ϭ 2.9-16.5). Children in the bottom quartile of weight-for-age were more likely to die (OR ϭ 2.1, 95% CI ϭ 1.3-3.5). Eight percent of the malaria cases had severe anemia (packed cell volume Ͻ 15%) but 24% received a blood transfusion. The epidemiology of malaria disease may be more complex than previously thought. Improved case management in a wide variety of health facilities may result from adequate identification and treatment of dehydration and hypoglycemia. Transfusion-requiring anemia is a major problem and sustainable, effective preventive measures are urgently needed.More than half of the world's population lives in areas endemic for Plasmodium falciparum malaria, resulting in more than 400 million clinical cases and between one and three million deaths every year. 1 Young children living in sub-Saharan Africa carry the largest part of this burden. 2 Although the epidemiology of P. falciparum infection has been well described in a variety of settings, the description of malaria as a life-threatening disease is less complete. Such descriptions can improve case management by identifying children at highest risk of dying; focusing scarce resources on such patients may reduce case fatality rates. Furthermore, these studies provide valuable insights into underlying pathophysiologic processes.Common manifestations of severe malaria in children include cerebral malaria and severe anemia. The relative importance of each presentation is thought to vary according to the intensity of transmission, with severe anemia being increasingly important as transmission intensity increases and cerebral malaria more common at lower transmission inten...

Little is known about the causes of enteric fever in Asia. Most cases are believed to be caused by Salmonella enterica serovar Typhi and the remainder by S. Paratyphi A. We compared their incidences by using standardized methods from population-based studies in China, Indonesia, India, and Pakistan.

Methicillin-resistant Staphylococcus aureus (MRSA)and vancomycin-resistant enterococcus (VRE) infections cause significant morbidity and mortality among liver transplant candidates and recipients. To assess rates of MRSA and VRE colonization, we obtained active surveillance cultures from 706 liver transplant candidates and recipients within 24 h of admission to an 11-bed liver transplant ICU from October 2000 to December 2005. Patients were followed prospectively to determine the cumulative risk of MRSA or VRE infection or death by colonization status. Outcomes were assessed by Kaplan-Meier survival analysis and Cox regression and multivariate logistic regression adjusting for covariates. The prevalence of newly detected MRSA nasal and VRE rectal colonization was 6.7% and 14.6%, respectively. Liver transplant candidates and recipients with MRSA colonization had an increased risk of MRSA infection (adjusted OR = 15.64, 95% CI 6.63-36.89) but not of death (adjusted OR = 1.00, 95% CI 0.43-2.30), whereas those with VRE colonization had an increased risk both of VRE infection (adjusted OR = 3.61, 95% CI 2.01-6.47) and of death (adjusted OR = 2.12, 95% CI 1.27-3.54) compared with noncolonized patients. Prevention and control strategies, including use of active surveillance cultures, should be implemented to reduce the rates of both MRSA and VRE colonization in this high-risk patient population.