Typhoid and paratyphoid fever

Typhoid fever is estimated to have caused 21·6 million illnesses and 216 500 deaths globally in 2000, affecting all ages. There is also one case of paratyphoid fever for every four of typhoid. The global emergence of multidrug-resistant strains and of strains with reduced susceptibility to fluoroquinolones is of great concern. We discuss the occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Developments are being made in our understanding of the molecular pathogenesis, and genomic and proteomic studies reveal the possibility of new targets for diagnosis and treatment. Further, we review guidelines for use of diagnostic tests and for selection of antimicrobials in varying clinical situations. The importance of safe water, sanitation, and immunisation in the presence of increasing antibiotic resistance is paramount. Routine immunisation of school-age children with Vi or Ty21a vaccine is recommended for countries endemic for typhoid. Vi vaccine should be used for 2-5 year-old children in highly endemic settings

Principal investigator in a box: Version 1.2 documentation

Principal Investigator (PI) in a box is a computer system designed to help optimize the scientific results of experiments that are performed in space. The system will assist the astronaut experimenters in the collection and analysis of experimental data, recognition and pursuit of 'interesting' results, optimal use of the time allocated to the experiment, and troubleshooting of the experiment apparatus. This document discusses the problems that motivate development of 'PI-in-a-box', and presents a high- level system overview and a detailed description of each of the modules that comprise the current version of the system

Rotavirus nonstructural protein NSP4 induces heterotypic antibody responses during natural infection in children

Seroconversion of immunoglobulin A (IgA) and immunoglobulin G (IgG) (≥4-fold rise) to rotavirus nonstructural protein 4 (NSP4) was determined, by use of enzyme-linked immunosorbent assay with fusion proteins glutathione S-transferase (GST)-NSP4 from strains SA11 (A), 116E (B), and RRV (C), in 40 children with acute rotavirus gastroenteritis and in 30 with the same disease due to other pathogens. The IgG seroconversion rates in the rotavirus group were 67.5%, 70%, and 60% when recombinant (r) NSP4A, -B, and -C, respectively, were used as antigen in the assay, and, for rotavirus-uninfected children, rates were 10%, 13%, and 7%. IgA seroconversion occurred in 57%, 70%, and 50%, respectively, of children with rotavirus gastroenteritis; in rotavirus-uninfected children, 1 child each seroconverted to the different rNSP4s. Among 9 children infected with strain NSP4A, 7, 6, and 5 children showed IgG seroconversion, and, among 18 infected with NSP4A, -B, and -C, 16, 17, and 15, respectively, showed IgG seroconversion. Between NSP4A-infected and NSP4B-infected children, IgA responses were similar to IgG responses. In conclusion, significant NSP4-specific antibody response occurs in natural rotavirus infection, and the antibody response appears to be broad and heterotypic in nature

Setting research priorities to improve global newborn health and prevent stillbirths by 2025.

BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. METHODS: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. RESULTS: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. CONCLUSION: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Setting research priorities to improve global newborn health and prevent stillbirths by 2025

Background In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. Methods We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed

Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis

Background Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). Objectives This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. Methods Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. Results The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. Conclusions Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB