Changes in Inflammatory Cytokine Levels in Rectal Mucosa Associated With Neisseria gonorrheae and/or Chlamydia trachomatis Infection and Treatment Among Men Who Have Sex With Men in Lima, Peru.

BACKGROUND: Neisseria gonorrheae and Chlamydia trachomatis are associated with mucosal inflammation and human immunodeficiency virus 1 (HIV-1) transmission. We assessed levels of inflammatory cytokines in men who have sex with men (MSM) with and without rectal gonorrhea and/or chlamydia in Lima, Peru. METHODS: We screened 605 MSM reporting condomless receptive anal intercourse for rectal N. gonorrheae/C. trachomatis using nucleic acid testing. We identified 101 cases of gonorrhea and/or chlamydia and randomly selected 50 N. gonorrheae/C. trachomatis positive cases and matched 52 negative controls. We measured levels of IL-1ß, IL-6, IL-8, and TNF-α in rectal secretions. Tests for HIV-1, rectal N. gonorrheae/C. trachomatis, and mucosal cytokines were repeated after 3 and 6 months. Cytokine levels in cases and uninfected controls were compared using Wilcoxon rank-sum tests and linear regression. RESULTS: MSM with gonorrhea/chlamydia had elevated levels of all cytokines in rectal mucosa compared with matched controls (all P values <.001). Following antibiotic treatment there were no significant differences in cytokine levels at 3- or 6-month follow-up evaluations (all P values >.05). DISCUSSION: Rectal gonorrhea/chlamydia infection is associated with transient mucosal inflammation and cytokine recruitment. Our data provide proof of concept for rectal sexually transmitted infection screening as an HIV prevention strategy for MSM. Clinical Trials Registration. NCT03010020.

A genomic test of subspecies in the Eunota togata species group (Coleoptera: Cicindelidae): Morphology masks evolutionary relationships and taxonomy.

Most of the world's biodiversity is described primarily or exclusively using morphological traits that may not always reflect the true evolutionary units. Accurate taxonomy is critical for conservation efforts and re-evaluation of traditional taxonomy may often be warranted since species and subspecies are frequently the focus of conservation and faunistic studies. Here, we test comprehensive taxonomic hypotheses of morphologically defined subspecies in the tiger beetle, Eunota togata (LaFerté-Sénectère, 1841). The four recognized subspecies were delineated based mainly on the dorsal coloration and extent of white markings termed maculations. We combine inferences from mtDNA genealogies and genome-wide multilocus data to elucidate the evolutionary relationships within the group and assess the taxonomic implications. Three of the four subspecific taxa delineated by morphology were not supported by the genomic or mtDNA data. In fact, the species-level diversity in this group was underestimated, as E. togata was found to represent three well-supported distinct species in all genetic analyses. Emerging from these analyses, we also document an intriguing example of convergent evolution in lighter colored E. togata adapting to similar white saline backgrounds. Our collective work underscores the importance of using molecular methods to reevaluate morphological based taxonomy for species and subspecies delimitation and conservation.

Estimating the cause-specific relative risks of non-optimal temperature on daily mortality: a two-part modelling approach applied to the Global Burden of Disease Study.

BACKGROUND: Associations between high and low temperatures and increases in mortality and morbidity have been previously reported, yet no comprehensive assessment of disease burden has been done. Therefore, we aimed to estimate the global and regional burden due to non-optimal temperature exposure. METHODS: In part 1 of this study, we linked deaths to daily temperature estimates from the ERA5 reanalysis dataset. We modelled the cause-specific relative risks for 176 individual causes of death along daily temperature and 23 mean temperature zones using a two-dimensional spline within a Bayesian meta-regression framework. We then calculated the cause-specific and total temperature-attributable burden for the countries for which daily mortality data were available. In part 2, we applied cause-specific relative risks from part 1 to all locations globally. We combined exposure-response curves with daily gridded temperature and calculated the cause-specific burden based on the underlying burden of disease from the Global Burden of Diseases, Injuries, and Risk Factors Study, for the years 1990-2019. Uncertainty from all components of the modelling chain, including risks, temperature exposure, and theoretical minimum risk exposure levels, defined as the temperature of minimum mortality across all included causes, was propagated using posterior simulation of 1000 draws. FINDINGS: We included 64·9 million individual International Classification of Diseases-coded deaths from nine different countries, occurring between Jan 1, 1980, and Dec 31, 2016. 17 causes of death met the inclusion criteria. Ischaemic heart disease, stroke, cardiomyopathy and myocarditis, hypertensive heart disease, diabetes, chronic kidney disease, lower respiratory infection, and chronic obstructive pulmonary disease showed J-shaped relationships with daily temperature, whereas the risk of external causes (eg, homicide, suicide, drowning, and related to disasters, mechanical, transport, and other unintentional injuries) increased monotonically with temperature. The theoretical minimum risk exposure levels varied by location and year as a function of the underlying cause of death composition. Estimates for non-optimal temperature ranged from 7·98 deaths (95% uncertainty interval 7·10-8·85) per 100 000 and a population attributable fraction (PAF) of 1·2% (1·1-1·4) in Brazil to 35·1 deaths (29·9-40·3) per 100 000 and a PAF of 4·7% (4·3-5·1) in China. In 2019, the average cold-attributable mortality exceeded heat-attributable mortality in all countries for which data were available. Cold effects were most pronounced in China with PAFs of 4·3% (3·9-4·7) and attributable rates of 32·0 deaths (27·2-36·8) per 100 000 and in New Zealand with 3·4% (2·9-3·9) and 26·4 deaths (22·1-30·2). Heat effects were most pronounced in China with PAFs of 0·4% (0·3-0·6) and attributable rates of 3·25 deaths (2·39-4·24) per 100 000 and in Brazil with 0·4% (0·3-0·5) and 2·71 deaths (2·15-3·37). When applying our framework to all countries globally, we estimated that 1·69 million (1·52-1·83) deaths were attributable to non-optimal temperature globally in 2019. The highest heat-attributable burdens were observed in south and southeast Asia, sub-Saharan Africa, and North Africa and the Middle East, and the highest cold-attributable burdens in eastern and central Europe, and central Asia. INTERPRETATION: Acute heat and cold exposure can increase or decrease the risk of mortality for a diverse set of causes of death. Although in most regions cold effects dominate, locations with high prevailing temperatures can exhibit substantial heat effects far exceeding cold-attributable burden. Particularly, a high burden of external causes of death contributed to strong heat impacts, but cardiorespiratory diseases and metabolic diseases could also be substantial contributors. Changes in both exposures and the composition of causes of death drove changes in risk over time. Steady increases in exposure to the risk of high temperature are of increasing concern for health. FUNDING: Bill & Melinda Gates Foundation.

Forecasting Trachoma Control and Identifying Transmission-Hotspots.

BACKGROUND: Tremendous progress towards elimination of trachoma as a public health problem has been made. However, there are areas where the clinical indicator of disease, trachomatous inflammation-follicular (TF), remains prevalent. We quantify the progress that has been made, and forecast how TF prevalence will evolve with current interventions. We also determine the probability that a district is a transmission-hotspot based on its TF prevalence (ie, reproduction number greater than one). METHODS: Data on trachoma prevalence come from the GET2020 global repository organized by the World Health Organization and the International Trachoma Initiative. Forecasts of TF prevalence and the percent of districts with local control is achieved by regressing the coefficients of a fitted exponential distribution for the year-by-year distribution of TF prevalence. The probability of a district being a transmission-hotspot is extrapolated from the residuals of the regression. RESULTS: Forecasts suggest that with current interventions, 96.5% of surveyed districts will have TF prevalence among children aged 1-9 years <5% by 2030 (95% CI: 86.6%-100.0%). Districts with TF prevalence < 20% appear unlikely to be transmission-hotspots. However, a district having TF prevalence of over 28% in 2016-2019 corresponds to at least 50% probability of being a transmission-hotspot. CONCLUSIONS: Sustainable control of trachoma appears achievable. However there are transmission-hotspots that are not responding to annual mass drug administration of azithromycin and require enhanced treatment in order to reach local control.

Single-dose azithromycin for child growth in Burkina Faso: a randomized controlled trial.

BACKGROUND: In lower resource settings, previous randomized controlled trials have demonstrated evidence of increased weight gain following antibiotic administration in children with acute illness. We conducted an individually randomized trial to assess whether single dose azithromycin treatment causes weight gain in a general population sample of children in Burkina Faso. METHODS: Children aged 8 days to 59 months were enrolled in November 2019 and followed through June 2020 in Nouna Town, Burkina Faso. Participants were randomly assigned to a single oral dose of azithromycin (20 mg/kg) or matching placebo. Anthropometric measurements were collected at baseline and 14 days and 6 months after enrollment. The primary anthropometric outcome was weight gain velocity in g/kg/day from baseline to 14 days and 6 months in separate linear regression models. RESULTS: Of 450 enrolled children, 230 were randomly assigned to azithromycin and 220 to placebo. Median age was 26 months (IQR 16 to 38 months) and 51% were female. At 14 days, children in the azithromycin arm gained a mean difference of 0.9 g/kg/day (95% CI 0.2 to 1.6 g/kg/day, P = 0.01) more than children in the placebo arm. There was no difference in weight gain velocity in children receiving azithromycin compared to placebo at 6 months (mean difference 0.04 g/kg/day, 95% CI - 0.05 to 0.13 g/kg/day, P = 0.46). There were no significant differences in other anthropometric outcomes. CONCLUSIONS: Transient increases in weight gain were observed after oral azithromycin treatment, which may provide short-term benefits. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT03676751 . Registered 19/09/2018.

When, Who, and How to Sample: Designing Practical Surveillance for 7 Neglected Tropical Diseases as We Approach Elimination.

As neglected tropical disease programs look to consolidate the successes of moving towards elimination, we need to understand the dynamics of transmission at low prevalence to inform surveillance strategies for detecting elimination and resurgence. In this special collection, modelling insights are used to highlight drivers of local elimination, evaluate strategies for detecting resurgence, and show the importance of rational spatial sampling schemes for several neglected tropical diseases (specifically schistosomiasis, soil-transmitted helminths, lymphatic filariasis, trachoma, onchocerciasis, visceral leishmaniasis, and gambiense sleeping sickness).

Trachoma Prevalence After Discontinuation of Mass Azithromycin Distribution.

BACKGROUND: As the World Health Organization seeks to eliminate trachoma by 2020, countries are beginning to control the transmission of trachomatous inflammation-follicular (TF) and discontinue mass drug administration (MDA) with oral azithromycin. We evaluated the effect of MDA discontinuation on TF1-9 prevalence at the district level. METHODS: We extracted from the available data districts with an impact survey at the end of their program cycle that initiated discontinuation of MDA (TF1-9 prevalence <5%), followed by a surveillance survey conducted to determine whether TF1-9 prevalence remained below the 5% threshold, warranting discontinuation of MDA. Two independent analyses were performed, 1 regression based and 1 simulation based, that assessed the change in TF1-9 from the impact survey to the surveillance survey. RESULTS: Of the 220 districts included, TF1-9 prevalence increased to >5% from impact to surveillance survey in 9% of districts. Regression analysis indicated that impact survey TF1-9 prevalence was a significant predictor of surveillance survey TF1-9 prevalence. The proportion of simulations with >5% TF1-9 prevalence in the surveillance survey was 2%, assuming the survey was conducted 4 years after MDA. CONCLUSION: An increase in TF1-9 prevalence may represent disease resurgence but could also be due to measurement error. Improved diagnostic tests are crucial to elimination of TF1-9 as a public health problem.

Species delimitation, discovery and conservation in a tiger beetle species complex despite discordant genetic data.

In an age of species declines, delineating and discovering biodiversity is critical for both taxonomic accuracy and conservation. In recent years, there has been a movement away from using exclusively morphological characters to delineate and describe taxa and an increase in the use of molecular markers to describe diversity or through integrative taxonomy, which employs traditional morphological characters, as well as genetic or other data. Tiger beetles are charismatic, of conservation concern, and much work has been done on the morphological delineation of species and subspecies, but few of these taxa have been tested with genetic analyses. In this study, we tested morphologically based taxonomic hypotheses of polymorphic tiger beetles in the Eunota circumpicta (LaFerté-Sénectère, 1841) species complex using multilocus genomic and mtDNA analyses. We find multiple cryptic species within the previous taxonomic concept of Eunota circumpicta, some of which were historically recognized as subspecies. We found that the mtDNA and genomic datasets did not identify the same taxonomic units and that the mtDNA was most at odds with all other genetic and morphological patterns. Overall, we describe new cryptic diversity, which raises important conservation concerns, and provide a working example for testing species and subspecies validity despite discordant data.

Comparing Azithromycin to Amoxicillin in the Management of Uncomplicated Severe Acute Malnutrition in Burkina Faso: A Pilot Randomized Trial.

Azithromycin is a promising alternative to amoxicillin in the management of uncomplicated severe acute malnutrition (SAM) as it can be administered as a single dose and has efficacy against several pathogens causing infectious disease and mortality in children under 5. In this pilot trial, we aimed to establish the feasibility of a larger randomized controlled trial and provide preliminary evidence comparing the effect of azithromycin to amoxicillin on weight gain in children with uncomplicated SAM. We enrolled children 6-59 months old with uncomplicated SAM at six healthcare centers in Burkina Faso. Participants were randomized to a single dose of azithromycin or a 7-day course of amoxicillin and followed weekly until nutritional recovery and again at 8 weeks. Apart from antibiotics, participants received standard of care, which includes ready-to-use therapeutic food. Primary feasibility outcomes included enrollment potential, refusals, and loss to follow-up. The primary clinical outcome was weight gain (g/kg/day) over 8 weeks. Outcome assessors were masked. Between June and October 2020, 312 children were screened, 301 were enrolled with zero refusals, and 282 (93.6%) completed the 8-week visit. Average weight gain was 2.5 g/kg/day (standard deviation [SD] 2.0) in the azithromycin group and 2.6 (SD 1.7) in the amoxicillin group (mean difference -0.1, 95% CI -0.5 to 0.3, P = 0.63). Fewer adverse events were reported in the azithromycin group (risk ratio 0.50, 95% CI 0.31-0.82, P = 0.006). With strong enrollment and follow-up, a fully powered trial in this setting is feasible.

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal electron sources.

In both the International Commission on Radiological Protection (ICRP) and Medical Internal Radiation Dose (MIRD) schemata of internal dosimetry, the S-value is defined as the absorbed dose to a target organ per nuclear decay of the radionuclide in a source organ. Its computation requires data on the energies and yields of all radiation emissions from radionuclide decay, the mass of the target organ, and the value of the absorbed fraction-the fraction of particle energy emitted in the source organ that is deposited in the target organ. The specific absorbed fraction (SAF) is given as the ratio of the absorbed fraction and the target mass. Historically, in the early development of both schemata, computational simplifications were made to the absorbed fraction in considering both organ self-dose ([Formula: see text]) and organ cross-dose ([Formula: see text]). In particular, the value of the absorbed fraction was set to unity for all 'non-penetrating' particle emissions (electrons and alpha particles) such that they contributed only to organ self-dose. As radiation transport codes for charged particles became more widely available, it became increasingly possible to abandon this distinction and to explicitly consider the transport of internally emitted electrons in a manner analogous to that for photons. In this present study, we report on an extensive series of electron SAFs computed in a revised series of the UF/NCI pediatric phantoms. A total of 28 electron energies-0-10 MeV-along a logarithmic energy grid are provided in electronic annexes, where 0 keV is associated with limiting values of the SAF. Electron SAFs were computed independently for collisional energy losses (SAFCEL) and radiation energy losses (SAFREL) to the target organ. A methodology was employed in which values of SAFREL were compiled by first assembling organ-specific and electron energy-specific bremsstrahlung x-ray spectra, and then using these x-ray spectra to re-weight a previously established monoenergetic database of photon SAFs for all phantoms and source-target combinations. Age-dependent trends in the electron SAF were demonstrated for the majority of the source-target organ pairs, and were consistent to values given for the ICRP adult phantoms. In selected cases, however, anticipated age-dependent trends were not seen, and were attributed to anatomical differences in relative organ positioning at specific phantom ages. Both the electron SAFs of this study, and the photon SAFs from our companion study, are presently being used by ICRP Committee 2 in its upcoming pediatric extension to ICRP Publication 133.

Specific absorbed fractions for a revised series of the UF/NCI pediatric reference phantoms: internal photon sources.

Assessment of radiation absorbed dose to internal organs of the body from the intake of radionuclides, or in the medical setting through the injection of radiopharmaceuticals, is generally performed based upon reference biokinetic models or patient imaging data, respectively. Biokinetic models estimate the time course of activity localized to source organs. The time-integration of these organ activity profiles are then scaled by the radionuclide S-value, which defines the absorbed dose to a target tissue per nuclear transformation in various source tissues. S-values are computed using established nuclear decay information (particle energies and yields), and a parameter termed the specific absorbed fraction (SAF). The SAF is the ratio of the absorbed fraction-fraction of particle energy emitted in the source tissue that is deposited in the target tissue-and the target organ mass. While values of the SAF may be computed using patient-specific or individual-specific anatomic models, they have been more widely available through the use of computational reference phantoms. In this study, we report on an extensive series of photon SAFs computed in a revised series of the University of Florida and the National Cancer Institute pediatric reference phantoms which have been modified to conform to the specifications embodied in the ICRP reference adult phantoms of Publication 110 (e.g. organs modeled, organ ID numbers, blood contribution to elemental compositions). Following phantom anatomical revisions, photon radiation transport simulations were performed using MCNPX v2.7 in each of the ten phantoms of the series-male and female newborn, 1 year old, 5 year old, 10 year old, and 15 year old-for 60 different tissues serving as source and/or target regions. A total of 25 photon energies were considered from 10 keV to 10 MeV along a logarithm energy grid. Detailed analyses were conducted of the relative statistical errors in the Monte Carlo target tissue energy deposition tallies at low photon energies and over all energies for source-target combinations at large intra-organ separation distances. Based on these analyses, various data smoothing algorithms were employed, including multi-point weighted data smoothing, and log-log interpolation at low energies (1 keV and 5 keV) using limiting SAF values based upon target organ mass to bound the interpolation interval. The final dataset is provided in a series of ten electronic supplemental files in MS Excel format. The results of this study were further used as the basis for assessing the radiative component of internal electron source SAFs as described in our companion paper (Schwarz et al 2021) for this same pediatric phantom series.

Azithromycin for uncomplicated severe acute malnutrition: study protocol for a pilot randomized controlled trial.

BACKGROUND: Given the high risk of infectious mortality among children with severe acute malnutrition (SAM), the World Health Organization recommends routine administration of a broad-spectrum antibiotic like amoxicillin as part of the management of uncomplicated SAM. However, evidence for the efficacy of amoxicillin to improve nutritional recovery or reduce mortality has been mixed. With a long half-life and evidence of efficacy to reduce mortality in high-risk populations, azithromycin is a potential alternative to amoxicillin in the management of SAM. In this pilot study, we aim to compare the efficacy of azithromycin to amoxicillin to improve nutritional outcomes in children with uncomplicated SAM. METHODS: This pilot randomized controlled trial will enroll 300 children with uncomplicated SAM from 6 Centre de Santé et de Promotion Sociale in the Boromo health district in Burkina Faso. Eligible children are randomized to receive a single directly observed dose of oral azithromycin or a 7-day course of oral amoxicillin in addition to the standard package of care for uncomplicated SAM. Enrolled children are followed weekly until nutritional recovery, and all children return for a final study visit at 8 weeks after enrollment. Anthropometric indicators, vital status, and clinical outcomes are monitored at each visit and compared by arm. Primary feasibility outcomes include enrollment potential, refusals, loss to follow-up, and completeness of data collection. The primary clinical outcome is weight gain (g/kg/day) over the 8-week study period. DISCUSSION: This pilot trial will establish the feasibility of conducting a full-scale randomized controlled trial to evaluate alternative antibiotics in this setting and provide preliminary evidence for the efficacy of azithromycin compared to amoxicillin to improve outcomes for children with SAM. TRIAL REGISTRATION: This trial was first registered on clinicaltrials.gov on 26 June 2018 ( NCT03568643 ).

Stopping azithromycin mass drug administration for trachoma: A systematic review.

The World Health Organization (WHO) recommends continuing azithromycin mass drug administration (MDA) for trachoma until endemic regions drop below 5% prevalence of active trachoma in children aged 1-9 years. Azithromycin targets the ocular strains of Chlamydia trachomatis that cause trachoma. Regions with low prevalence of active trachoma may have little if any ocular chlamydia, and, thus, may not benefit from azithromycin treatment. Understanding what happens to active trachoma and ocular chlamydia prevalence after stopping azithromycin MDA may improve future treatment decisions. We systematically reviewed published evidence for community prevalence of both active trachoma and ocular chlamydia after cessation of azithromycin distribution. We searched electronic databases for all peer-reviewed studies published before May 2020 that included at least 2 post-MDA surveillance surveys of ocular chlamydia and/or the active trachoma marker, trachomatous inflammation-follicular (TF) prevalence. We assessed trends in the prevalence of both indicators over time after stopping azithromycin MDA. Of 140 identified studies, 21 met inclusion criteria and were used for qualitative synthesis. Post-MDA, we found a gradual increase in ocular chlamydia infection prevalence over time, while TF prevalence generally gradually declined. Ocular chlamydia infection may be a better measurement tool compared to TF for detecting trachoma recrudescence in communities after stopping azithromycin MDA. These findings may guide future trachoma treatment and surveillance efforts.

Epidemiology of Underweight among Infants in Rural Burkina Faso.

Infant undernutrition is thought to contribute to growth failure and mortality. We evaluated the patterns in underweight in a population-based sample of children aged 1-11 months in rural northwestern Burkina Faso. Data were collected during the baseline assessment of a community-randomized trial evaluating mass azithromycin distribution in Nouna District, Burkina Faso. A door-to-door census was undertaken for all households in all communities. Infants aged 1-11 months were weighed for weight-based dosing in the trial and their weights were used to calculate weight-for-age Z-scores (WAZ). Underweight was defined as WAZ ≤ 2. We evaluated the age patterns in WAZ and underweight by demographic, seasonal, and geographic characteristics. Of 7,109 infants, 6,077 had accurate weight and global positioning system (GPS) coordinate data (85.5%). Infants were a median of 6 months old (interquartile range [IQR] 3-8) and 48.4% were female. Mean WAZ was -0.68 (SD 1.6) and 19.0% were underweight. The WAZ decreased with increasing age, and the prevalence of underweight increased from 2.5% among 1-month-olds to 27.6% among 11-month-olds. Underweight was more common among boys than girls (22.1% among boys versus 15.6% among girls). Improved latrine use by the household was associated with increased WAZ, and this effect was stronger in male compared with female infants. Given the large burden of underweight among infants, interventions addressing undernutrition should specifically include infants.

Access to Improved Sanitation and Nutritional Status among Preschool Children in Nouna District, Burkina Faso.

Access to improved sanitation and hygiene may improve child nutritional status by reducing exposure to enteric pathogens. We evaluated this relationship as part of the Community Health with Azithromycin Trial, a community-randomized trial of azithromycin versus placebo for the prevention of child mortality in rural Burkina Faso. Before the baseline study visit, a door-to-door household survey was conducted for all households in the study area. During the baseline study census, which occurred approximately 9 months after the household survey, a mid-upper arm circumference (MUAC) measurement was obtained from each child. We evaluated the relationship between household improved latrine use compared with unimproved latrines or open defecation and MUAC in children aged 6-59 months. Among 32,172 children with household survey data and MUAC measurements, 931 (2.9%) had an MUAC less than 12.5 cm and were classified as having moderate acute malnutrition (MAM). The odds of MAM were higher in children living in households with an unimproved latrine than those with an improved latrine (adjusted odds ratio: 1.60; 95% CI: 1.11-2.31). Children in households with unimproved latrines and households that practiced open defection had approximate 0.15 cm reduced MUAC compared with those in households with an improved latrine. There was a small, but statistically significant, association between improved latrine and nutritional status in preschool children as measured by MUAC.

Insecticide-treated bed net access and use among preschool children in Nouna District, Burkina Faso.

BACKGROUND: We evaluated universal insecticide-treated bed net access and use in children <5 y of age in a rural area of Burkina Faso. METHODS: A door-to-door enumerative census was conducted in Nouna District, Burkina Faso in December 2018 through April 2019. The most recent mass bed net distribution campaign occurred in June 2016. Heads of households were interviewed about household bed net ownership and use by children <5 y of age. We evaluated the relationship between demographic and socio-economic factors and household universal bed net access and use by children. RESULTS: In 23 610 households with at least one child <5 y of age, 71 329 bed nets were reported (94.5% insecticide-treated). One-third (35.2%) of households had universal access and two-thirds (67.0%) of children slept under an insecticide-treated net the previous night. Children in households with universal access more often slept under a net the previous night (adjusted odds ratio 4.81 [95% confidence interval 4.39-5.26]). CONCLUSIONS: Bed net coverage was substantially less than the 80% World Health Organization target for universal coverage in Nouna District. Insecticide-treated nets were used preferentially for children, but important gaps remain in consistent bed net use in this population. Structural and behavioural interventions are needed to close these gaps.

Adverse Events and Clinic Visits following a Single Dose of Oral Azithromycin among Preschool Children: A Randomized Placebo-Controlled Trial.

Biannual mass azithromycin distribution reduces all-cause child mortality in some settings in sub-Saharan Africa; however, adverse events and short-term infectious outcomes following treatment have not been well characterized. Children aged 0-59 months were recruited in Nouna Town, Burkina Faso, and randomized 1:1 to a single directly observed oral 20 mg/kg dose of azithromycin or placebo. At 14 days after treatment, caregivers were interviewed about adverse event symptoms their child experienced since treatment and if they had sought health care for their child. All children had tympanic temperature measured at the 14-day visit. We compared adverse events and clinic visits using logistic regression models between azithromycin- and placebo-controlled children. Of 450 children enrolled, 230 were randomized to azithromycin and 220 to placebo. On average, children were aged 28 months, and 50.9% were female. Caregivers of 20% of children reported that their child experienced at least one adverse event, with no significant difference between study arms (19.9% azithromycin; 20.0% placebo, logistic regression P = 0.96). Vomiting was more often reported by caregivers of azithromycin-treated children than by those of placebo-treated children (7.2% azithromycin, 1.9% placebo, logistic regression P = 0.01). There were no significant differences in other adverse events or clinic visits. Adverse events following a single oral dose of azithromycin in preschool children were rare and mild. Azithromycin administration appears safe in this population.

The effect of air pollution on deaths, disease burden, and life expectancy across China and its provinces, 1990-2017: an analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Air pollution is an important public health concern in China, with high levels of exposure to both ambient and household air pollution. To inform action at provincial levels in China, we estimated the exposure to air pollution and its effect on deaths, disease burden, and loss of life expectancy across all provinces in China from 1990 to 2017. METHODS: In all 33 provinces, autonomous regions, municipalities, and special administrative regions in China, we estimated exposure to air pollution, including ambient particulate matter pollution (defined as the annual gridded concentration of PM2·5), household air pollution (defined as the percentage of households using solid cooking fuels and the corresponding exposure to PM2·5), and ozone pollution (defined as average gridded ozone concentrations). We used the methods of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 to estimate deaths and disability-adjusted life-years (DALYs) attributable to air pollution, and what the life expectancy would have been if air pollution levels had been less than the minimum level causing health loss. FINDINGS: The average annual population-weighted PM2·5 exposure in China was 52·7 µg/m3 (95% uncertainty interval [UI] 41·0-62·8) in 2017, which is 9% lower than in 1990 (57·8 µg/m3, 45·0-67·0). We estimated that 1·24 million (95% UI 1·08-1·40) deaths in China were attributable to air pollution in 2017, including 851 660 (712 002-990 271) from ambient PM2·5 pollution, 271 089 (209 882-346 561) from household air pollution from solid fuels, and 178 187 (67 650-286 229) from ambient ozone pollution. The age-standardised DALY rate attributable to air pollution was 1513·1 per 100 000 in China in 2017, and was higher in males (1839·8 per 100 000) than in females (1198·3 per 100 000). The age-standardised death rate attributable to air pollution decreased by 60·6% (55·7-63·7) for China overall between 1990 and 2017, driven by an 85·4% (83·2-87·3) decline in household air pollution and a 12·0% (1·4-22·1) decline in ambient PM2·5 pollution. 40·0% of DALYs for COPD were attributable to air pollution, as were 35·6% of DALYs for lower respiratory infections, 26·1% for diabetes, 25·8% for lung cancer, 19·5% for ischaemic heart disease, and 12·8% for stroke. We estimated that if the air pollution level in China was below the minimum causing health loss, the average life expectancy would have been 1·25 years greater. The DALY rate per 100 000 attributable to air pollution varied across provinces, ranging from 482·3 (371·1-604·1) in Hong Kong to 1725·6 (720·4-2653·1) in Xinjiang for ambient pollution, and from 18·7 (9·1-34·0) in Shanghai to 1804·5 (1339·5-2270·1) in Tibet for household pollution. Although the overall mortality attributable to air pollution decreased in China between 1990 and 2017, 12 provinces showed an increasing trend during the past 27 years. INTERPRETATION: Pollution from ambient PM2·5 and household burning of solid fuels decreased markedly in recent years in China, after extensive efforts to control emissions. However, PM2·5 concentrations still exceed the WHO Air Quality Guideline for the entire population of China, with 81% living in regions exceeding the WHO Interim Target 1, and air pollution remains an important risk factor. Sustainable development policies should be implemented and enforced to reduce the impact of air pollution on long-term economic development and population health. FUNDING: Bill & Melinda Gates Foundation; and China National Key Research and Development Program.