Should outbreak response immunization be recommended for measles outbreaks in middle- and low-income countries? An update.

Measles caused mortality in >164,000 children in 2008, with most deaths occurring during outbreaks. Nonetheless, the impact and desirability of conducting measles outbreak response immunization (ORI) in middle- and low-income countries has been controversial. World Health Organization guidelines published in 1999 recommended against ORI in such settings, although recently these guidelines have been reversed for countries with measles mortality reduction goals

Too little but not too late: Results of a literature review to improve routine immunization programs in developing countries

<p>Abstract</p> <p>Background</p> <p>Globally, immunization services have been the center of renewed interest with increased funding to improve services, acceleration of the introduction of new vaccines, and the development of a health systems approach to improve vaccine delivery. Much of the credit for the increased attention is due to the work of the GAVI Alliance and to new funding streams. If routine immunization programs are to take full advantage of the newly available resources, managers need to understand the range of proven strategies and approaches to deliver vaccines to reduce the incidence of diseases. In this paper, we present strategies that may be used at the sub-national level to improve routine immunization programs.</p> <p>Methods</p> <p>We conducted a systematic review of studies and projects reported in the published and gray literature. Each paper that met our inclusion criteria was rated based on methodological rigor and data were systematically abstracted. Routine-immunization – specific papers with a methodological rigor rating of greater than 60% and with conclusive results were reported.</p> <p>Results</p> <p>Greater than 11,000 papers were identified, of which 60 met our inclusion criteria and 25 papers were reported. Papers were grouped into four strategy approaches: bringing immunizations closer to communities (n = 11), using information dissemination to increase demand for vaccination (n = 3), changing practices in fixed sites (n = 4), and using innovative management practices (n = 7).</p> <p>Conclusion</p> <p>Immunization programs are at a historical crossroads in terms of developing new funding streams, introducing new vaccines, and responding to the global interest in the health systems approach to improving immunization delivery. However, to complement this, actual service delivery needs to be strengthened and program managers must be aware of proven strategies. Much was learned from the 25 papers, such as the use of non-health workers to provide numerous services at the community level. However it was startling to see how few papers were identified and in particular how few were of strong scientific quality. Further well-designed and well-conducted scientific research is warranted. Proposed areas of additional research include integration of additional services with immunization delivery, collaboration of immunization programs with new partners, best approaches to new vaccine introduction, and how to improve service delivery.</p

Development of aggression subtypes from childhood to adolescence:a group-based multi-trajectory modelling perspective

The persistence of elevated subtypes of aggression beginning in childhood have been associated with long-term maladaptive outcomes. Yet it remains unclear to what extent there are clusters of individuals following similar developmental trajectories across forms (i.e., physical and indirect) and functions (i.e., proactive and reactive) of aggression. We aimed to identify groups of children with distinct profiles of the joint development of forms and functions of aggression and to identify risk factors for group membership. A sample of 787 children was followed from birth to adolescence. Parent and teacher reports, and standardised assessments were used to measure two forms and two functions of aggressive behaviour, between six and 13 years of age along with preceding child, maternal, and family-level risk-factors. Analyses were conducted using a group-based multi-trajectory modelling approach. Five trajectory groups emerged: non-aggressors, low-stable, moderate-engagers, high-desisting, and high-chronic. Coercive parenting increased membership risk in the moderate-engagers and high-chronic groups. Lower maternal IQ increased membership risk in both high-desisting and high-chronic groups, whereas maternal depression increased membership risk in the high-desisting group only. Never being breastfed increased membership risk in the moderate-engagers group. Boys were at greater risk for belonging to groups displaying elevated aggression. Individuals with chronic aggression problems use all subtypes of aggression. Risk factors suggest that prevention programs should start early in life and target mothers with lower IQ. Strategies to deal with maternal depression and enhance positive parenting while replacing coercive parenting tactics should be highlighted in programming efforts

Challenges in measuring measles case fatality ratios in settings without vital registration

Measles, a highly infectious vaccine-preventable viral disease, is potentially fatal. Historically, measles case-fatality ratios (CFRs) have been reported to vary from 0.1% in the developed world to as high as 30% in emergency settings. Estimates of the global burden of mortality from measles, critical to prioritizing measles vaccination among other health interventions, are highly sensitive to the CFR estimates used in modeling; however, due to the lack of reliable, up-to-date data, considerable debate exists as to what CFR estimates are appropriate to use. To determine current measles CFRs in high-burden settings without vital registration we have conducted six retrospective measles mortality studies in such settings. This paper examines the methodological challenges of this work and our solutions to these challenges, including the integration of lessons from retrospective all-cause mortality studies into CFR studies, approaches to laboratory confirmation of outbreaks, and means of obtaining a representative sample of case-patients. Our experiences are relevant to those conducting retrospective CFR studies for measles or other diseases, and to those interested in all-cause mortality studies

The Murchison Widefield Array: The Square Kilometre Array Precursor at Low Radio Frequencies

The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80–300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07