Update on the global epidemiology of intussusception: a systematic review of incidence rates, age distributions and case-fatality ratios among children aged <5 years, before the introduction of rotavirus vaccination.

BACKGROUND: In some countries that have introduced oral rotavirus vaccines, a small but elevated risk of intussusception-a rare bowel disorder-has been reported. Updated estimates on the global epidemiology of intussusception are needed to help predict the potential number of intussusception cases that could be caused by the vaccine in different settings. METHODS: We estimated incidence rates, age distributions and case-fatality ratios (CFRs) for intussusception hospital admissions among children aged <5 years, before the introduction of rotavirus vaccines. We included all articles identified in a systematic review between January 2002 and January 2018, and contacted authors for more granular unpublished data on age distributions. RESULTS: We identified 128 articles containing 227 country datasets (61 age distributions, 71 incidence rates and 95 CFRs). The median age of intussusception ranged from 29 weeks in Africa (83% of cases in the first year of life) to 70 weeks in the Western Pacific region (35% of cases in the first year of life). The median (range) annual incidence of intussusception hospital admissions per 100 000 aged <1 year ranged from 34 (13-56) in Africa to 90 (9-380) in the Western Pacific region. We found extreme differences between the CFRs in Africa (1 death in every 10 hospital admissions) and the rest of the world (fewer than 1 death in every 100-2000 hospital admissions). CONCLUSION: Intussusception epidemiology varies by country and region. Understanding and recognizing these differences will be important when assessing the potential number of intussusception cases associated with rotavirus vaccines

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase

Broadening the age restriction for initiating rotavirus vaccination in regions with high rotavirus mortality: benefits of mortality reduction versus risk of fatal intussusception.

INTRODUCTION: Recently developed rotavirus vaccines have the potential to reduce diarrhea mortality in children in developing countries. Available data to date do not indicate risk of intussusception with these new vaccines. To avoid a potential unanticipated risk post-licensure, it is recommended that rotavirus immunization be initiated before 12 weeks of age when background intussusception rates are low. This policy could exclude a substantial number of children from vaccination, especially in developing countries where delays in vaccination are common. METHODS: We conducted a scenario analysis to assess the potential benefits of mortality reduction from rotavirus versus the risk of fatal intussusception when the first dose of the vaccine is strictly administered by 12 weeks of age compared with a free strategy with vaccine administered before 1 year of age using data on rotavirus disease, vaccine safety and efficacy, and current diphtheria-tetanus-pertussis vaccination rates, and by incorporating hypothetical risks of intussusception. RESULTS: In developing countries, assuming vaccine efficacy of 50% and 75% for doses 1 and 2, respectively, and a hypothetical sixfold and threefold increased relative risk of intussusception within 7 days of doses 1 and 2, respectively, initiating rotavirus immunization before 12 weeks of age would prevent 194,564 of the 517,959 annual rotavirus-associated deaths among children <5 years, while potentially resulting in 1106 fatal intussusception events. Administration of the first dose to infants up to 1 year of age would prevent an additional 54,087 rotavirus-associated deaths (total=248,651) while potentially resulting in an additional 1226 intussusception deaths (total=2332). CONCLUSION: In developing countries, the additional lives saved by broadening the age restrictions for initiation of rotavirus vaccination would far outnumber the hypothetical excess intussusception deaths that would accompany such an approach

Potential intussusception risk versus health benefits from rotavirus vaccination in Latin America.

BACKGROUND: With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine, the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination. To inform policy considerations, we estimated excess intussusception cases and mortality potentially caused by rotavirus vaccine for each of the 14 countries and compared these estimates to hospitalizations and deaths expected to be averted through vaccination. METHODS: We used regional rotavirus disease burden and rotavirus vaccine efficacy data, global natural intussusception and regional rotavirus vaccine-related risk estimates, and country-specific diphtheria, tetanus, and pertussus vaccination coverage rates to estimate rotavirus vaccine coverage rates. We performed a probabilistic sensitivity analysis to account for uncertainty in these parameters. RESULTS: For an aggregate hypothetical birth cohort of 9.5 million infants in these 14 countries, rotavirus vaccine would annually prevent 144 746 (90% confidence interval [CI], 128 821-156 707) hospitalizations and 4124 deaths (90% CI, 3740-4239) due to rotavirus in their first 5 years of life but could cause an additional 172 hospitalizations (90% CI, 126-293) and 10 deaths (90% CI, 6-17) due to intussusception, yielding benefit-risk ratios for hospitalization and death of 841:1 (90% CI, 479:1 to 1142:1) and 395:1 (90% CI, 207:1 to 526:1), respectively. In an uncertainty analysis using 10 000 simulations of our probabilistic parameters, in comparing rotavirus disease averted to intussusception events caused, the hospitalization ratio was never below 100:1, and our death ratio fell below 100:1 only once. CONCLUSIONS: The health benefits of vaccination far outweigh the short-term risks and support continued rotavirus vaccination in Latin America

The Manchester Color Wheel: validation in secondary school pupils

<p>Abstract</p> <p>Background</p> <p>As part of our research programme into facilitating improved ways of communicating with patients, especially about more sensitive clinical issues, we have been investigating whether there are any non-verbal methods that might aid this process. One such approach is to ask patients to choose a color in response to a particular question, for instance about health or psychological status, and for this purpose we developed the Manchester Color Wheel (MCW). This instrument consists of positive, neutral and negative colors and its validation in normal adults and those with anxiety or depression showed that it is responsive to change and reproducible. It also has the capacity to identify a positive frame of mind. We concluded that it might be a particularly useful instrument in adolescents and therefore this study aimed to validate it in a secondary school.</p> <p>Methods</p> <p>620 pupils (aged 11–17 years, mean age 14.0 years, 298 (48.1%) males, 322 (51.9%) females) at Sale Grammar School in Greater Manchester were asked to relate their mood to a MCW color and also complete the Hospital Anxiety Depression (HAD) questionnaire. To give these pupils an experience in science, 197 were divided into four subgroups for an ‘experiment’ to ascertain whether, compared to controls, a change in mood color choice could be induced by participation in sport, music or art activities.</p> <p>Results</p> <p>Although mood color and HAD depression score are unlikely to be measuring exactly the same psychological state, a negative mood color was chosen by 62.5% of HAD depressed compared to only 14.5% of HAD normal pupils (p < 0.001). In contrast, a positive mood color was chosen by 48.9% of normal and only 18.8% of depressed pupils (p < 0.001). In the ‘experiment’, compared to controls, all activities resulted in an increased choice of positive mood colors which reached significance for sport and music.</p> <p>Conclusion</p> <p>This study confirms the potential utility of the MCW to rapidly and easily assess a variety of health issues in large populations, including adolescents. Some of our results should also be of interest to educationalists.</p