Associated patterns of insecticide resistance in field populations of malaria vectors across Africa.

The development of insecticide resistance in African malaria vectors threatens the continued efficacy of important vector control methods that rely on a limited set of insecticides. To understand the operational significance of resistance we require quantitative information about levels of resistance in field populations to the suite of vector control insecticides. Estimation of resistance is complicated by the sparsity of observations in field populations, variation in resistance over time and space at local and regional scales, and cross-resistance between different insecticide types. Using observations of the prevalence of resistance in mosquito species from the Anopheles gambiae complex sampled from 1,183 locations throughout Africa, we applied Bayesian geostatistical models to quantify patterns of covariation in resistance phenotypes across different insecticides. For resistance to the three pyrethroids tested, deltamethrin, permethrin, and λ-cyhalothrin, we found consistent forms of covariation across sub-Saharan Africa and covariation between resistance to these pyrethroids and resistance to DDT. We found no evidence of resistance interactions between carbamate and organophosphate insecticides or between these insecticides and those from other classes. For pyrethroids and DDT we found significant associations between predicted mean resistance and the observed frequency of kdr mutations in the Vgsc gene in field mosquito samples, with DDT showing the strongest association. These results improve our capacity to understand and predict resistance patterns throughout Africa and can guide the development of monitoring strategies.

Indoor residual spraying for malaria control in sub-Saharan Africa 1997 to 2017: an adjusted retrospective analysis.

BACKGROUND: Indoor residual spraying (IRS) is a key tool for controlling and eliminating malaria by targeting vectors. To support the development of effective intervention strategies it is important to understand the impact of vector control tools on malaria incidence and on the spread of insecticide resistance. In 2006, the World Health Organization (WHO) stated that countries should report on coverage and impact of IRS, yet IRS coverage data are still sparse and unspecific. Here, the subnational coverage of IRS across sub-Saharan Africa for the four main insecticide classes from 1997 to 2017 were estimated. METHODS: Data on IRS deployment were collated from a variety of sources, including the President's Malaria Initiative spray reports and National Malaria Control Programme reports, for all 46 malaria-endemic countries in sub-Saharan Africa from 1997 to 2017. The data were mapped to the applicable administrative divisions and the proportion of households sprayed for each of the four main insecticide classes; carbamates, organochlorines, organophosphates and pyrethroids was calculated. RESULTS: The number of countries implementing IRS increased considerably over time, although the focal nature of deployment means the number of people protected remains low. From 1997 to 2010, DDT and pyrethroids were commonly used, then partly replaced by carbamates from 2011 and by organophosphates from 2013. IRS deployment since the publication of resistance management guidelines has typically avoided overlap between pyrethroid IRS and ITN use. However, annual rotations of insecticide classes with differing modes of action are not routinely used. CONCLUSION: This study highlights the gaps between policy and practice, emphasizing the continuing potential of IRS to drive resistance. The data presented here can improve studies on the impact of IRS on malaria incidence and help to guide future malaria control efforts.

Is Antimicrobial Resistance a Bigger Problem in Tertiary Care Hospitals Than in Small Community Hospitals in the United States?

Large tertiary care hospitals (TCHs) are thought to have higher antimicrobial resistance (AMR) rates when compared to small community hospitals (SCHs) as they provide care to patients with higher disease severity. However, we found no systematic differences in AMR rates between TCHs and SCHs in the United States.

Implementation of the global plan for insecticide resistance management in malaria vectors: progress, challenges and the way forward.

In recent years, there has been an increase in resistance of malaria vectors to insecticides, particularly to pyrethroids which are widely used in insecticide-treated nets. The Global Plan for Insecticide Resistance Management in malaria vectors (GPIRM), released in May 2012, is a collective strategy for the malaria community to tackle this challenge. This review outlines progress made to date and the challenges experienced in the implementation of GPIRM, and outlines focus areas requiring urgent attention. Whilst there has been some advancement, uptake of GPIRM at the national level has generally been poor for various reasons, including limited availability of vector control tools with new mechanisms of action as well as critical financial, human and infrastructural resource deficiencies. There is an urgent need for a global response plan to address these deficits and ensure the correct and efficient use of available tools in order to maintain the effectiveness of current vector control efforts whilst novel vector control tools are under development. Emphasis must be placed on enhancing national capacities (such as human and infrastructural resources) to enable efficient monitoring and management of insecticide resistance, and to support availability and accessibility of appropriate new vector control products. Lack of action by the global community to address the threat of insecticide resistance is unacceptable and deprives affected communities of their basic right of universal access to effective malaria prevention. Aligning efforts and assigning the needed resources will ensure the optimal implementation of GPIRM with the ultimate goal of maintaining effective malaria vector control.

Impact of IRS: Four-years of entomological surveillance of the Indian Visceral Leishmaniases elimination programme.

BACKGROUND: In 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016. METHODS: Eight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS. RESULTS: Complete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019. CONCLUSION: Through effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets.

Acinetobacter baumannii Resistance Trends in Children in the United States, 1999-2012.

BACKGROUND: Acinetobacter baumannii is a common cause of healthcare-associated infections. Carbapenem-resistant (CR) A baumannii is a significant threat globally. We used a large reference laboratory database to study the epidemiology of A baumannii in children in the United States. METHODS: Antimicrobial susceptibility data from The Surveillance Network were used to phenotypically identify antibiotic resistance in A baumannii isolates in children 1-17 years of age between January 1999 and July 2012. Logistic regression analysis was used to calculate trends in the prevalence of antibiotic resistance in A baumannii. Isolates from infants (<1 year old) were excluded. RESULTS: The crude proportion of cephalosporin-resistant (CephR) A baumannii increased from 13.2% in 1999 to 23.4% in 2012 with a peak of 32.5% in 2008, and the proportion of CR A baumannii increased from 0.6% in 1999 to 6.1% in 2012 with a peak of 12.7% in 2008. From 1999 to 2012, the proportion of CephR and CR A baumannii increased each year by 3% and 8%, respectively (CephR odds ratio [OR] = 1.03, 95% confidence interval [CI], 1.01-1.04; CR OR = 1.08, 95% CI, 1.05-1.12); however, after 2008, a significant decrease in trend was observed (CephR OR = 0.78, 95% CI, 0.71-0.87; CR OR = 0.73, 95% CI, 0.62-0.86), but resistance remained higher than baseline (1999). CONCLUSIONS: Overall, between 1999 and 2012, CephR and CR A baumannii isolates increased in children; however, a decreasing trend was observed after 2008.There is a need for ongoing surveillance of A baumannii infections and continued assessment of effective prevention strategies in vulnerable populations.

How Should the Value Attributes of Novel Antibiotics Be Considered in Reimbursement Decision Making?

Antibiotics have revolutionized the treatment of bacterial infections. However, it is widely held that there is underinvestment in antibiotics research and development relative to the socially optimal level for a number of reasons. In this article, we discuss whether existing health technology assessment procedures recognize the full economic and societal value of new antibiotics to patients and society when making reimbursement decisions. We present three recommendations for modelling the unique attributes of value that are specific to novel antibiotics. We find, based on a review of the literature, that some of the value elements proposed by our framework have previously been discussed qualitatively by health technology assessment bodies when evaluating antibiotics, but are not yet formally captured via modelling. We present a worked example to show how it may be possible to capture these dimensions of value in a more quantitative manner. We conclude by answering the question of the title as follows: the unique attributes of novel antibiotics should be considered in reimbursement decision making, in a way that captures the full range of benefits these important technologies bring to patients, health care systems, and society.

Is the efficacy of antibiotic prophylaxis for surgical procedures decreasing? Systematic review and meta-analysis of randomized control trials.

OBJECTIVE: Rising antibiotic resistance could reduce the effectiveness of antibiotics in preventing postoperative infections. We investigated trends in the efficacy of antibiotic prophylaxis regimens for 3 commonly performed surgical procedures-appendectomy, cesarean section, and colorectal surgery-and 1 invasive diagnostic procedure, transrectal prostate biopsy (TRPB). DESIGN: Systematic review and meta-analysis. METHODS: We searched PubMed and Cochrane databases (through October 31, 2017) for randomized control trials (RCTs) that measured the efficacy of antibiotic prophylaxis for 4 index procedures in preventing postoperative infections (surgical site infections [SSIs] following the 3 surgical procedures and a combination of urinary tract infections [UTIs] and sepsis following TRPB). RESULTS: Of 399 RCTs, 74 studies (9 appendectomy, 11 cesarean section, 39 colorectal surgery, and 15 TRPB) were included. Multilevel logistic regression models with random intercepts for each study showed no statistically significant increase in SSIs over time for appendectomy (adjusted odds ratio [aOR] per year, 1.03; 95% confidence interval [CI], 0.92-1.16; P=.57), cesarean section (aOR per year, 1.01; 95% CI, 0.96-1.05; P=.80), and TRPB (aOR per year, 0.95; 95% CI, 0.77-1.18; P=.67). However, there was a significant increase in SSIs proportion following colorectal surgery (aOR per year, 1.049; 95% CI, 1.03-1.07; P<.001). CONCLUSION: The efficacy of antibiotic prophylaxis agents in preventing SSIs following colorectal surgery has declined. Small number of RCTs and low infections rates limited our ability to assess true effect for simple appendectomy, cesarean section, or TRPB.

Mapping Geospatial Processes Affecting the Environmental Fate of Agricultural Pesticides in Africa.

The application of agricultural pesticides in Africa can have negative effects on human health and the environment. The aim of this study was to identify African environments that are vulnerable to the accumulation of pesticides by mapping geospatial processes affecting pesticide fate. The study modelled processes associated with the environmental fate of agricultural pesticides using publicly available geospatial datasets. Key geospatial processes affecting the environmental fate of agricultural pesticides were selected after a review of pesticide fate models and maps for leaching, surface runoff, sedimentation, soil storage and filtering capacity, and volatilization were created. The potential and limitations of these maps are discussed. We then compiled a database of studies that measured pesticide residues in Africa. The database contains 10,076 observations, but only a limited number of observations remained when a standard dataset for one compound was extracted for validation. Despite the need for more in-situ data on pesticide residues and application, this study provides a first spatial overview of key processes affecting pesticide fate that can be used to identify areas potentially vulnerable to pesticide accumulation.

Analysis-ready datasets for insecticide resistance phenotype and genotype frequency in African malaria vectors.

The impact of insecticide resistance in malaria vectors is poorly understood and quantified. Here a series of geospatial datasets for insecticide resistance in malaria vectors are provided, so that trends in resistance in time and space can be quantified, and the impact of resistance found in wild populations on malaria transmission in Africa can be assessed. Specifically, data have been collated and geopositioned for the prevalence of insecticide resistance, as measured by standard bioassays, in representative samples of individual species or species complexes. Data are provided for the Anopheles gambiae species complex, the Anopheles funestus subgroup, and for nine individual vector species. Data are also given for common genetic markers of resistance to support analyses of whether these markers can improve the ability to monitor resistance in low resource settings. Allele frequencies for known resistance-associated markers in the Voltage-gated sodium channel (Vgsc) are provided. In total, eight analysis-ready, standardised, geopositioned datasets encompassing over 20,000 African mosquito collections between 1957 and 2017 are released.