Effective autodissemination of pyriproxyfen to breeding sites by the exophilic malaria vector Anopheles arabiensis in semi-field settings in Tanzania.

BACKGROUND: Malaria vector control strategies that target adult female mosquitoes are challenged by the emergence of insecticide resistance and behavioural resilience. Conventional larviciding is restricted by high operational costs and inadequate knowledge of mosquito-breeding habitats in rural settings that might be overcome by the juvenile hormone analogue, Pyriproxyfen (PPF). This study assessed the potential for Anopheles arabiensis to pick up and transfer lethal doses of PPF from contamination sites to their breeding habitats (i.e. autodissemination of PPF). METHODS: A semi-field system (SFS) with four identical separate chambers was used to evaluate PPF-treated clay pots for delivering PPF to resting adult female mosquitoes for subsequent autodissemination to artificial breeding habitats within the chambers. In each chamber, a tethered cow provided blood meals to laboratory-reared, unfed female An. arabiensis released in the SFS. In PPF-treated chambers, clay pot linings were dusted with 0.2 - 0.3 g AI PPF per pot. Pupae were removed from the artificial habitats daily, and emergence rates calculated. Impact of PPF on emergence was determined by comparing treatment with an appropriate control group. RESULTS: Mean (95% CI) adult emergence rates were (0.21 ± 0.299) and (0.95 ± 0.39) from PPF-treated and controls respectively (p < 0.0001). Laboratory bioassay of water samples from artificial habitats in these experiments resulted in significantly lower emergence rates in treated chambers (0.16 ± 0.23) compared to controls 0.97 ± 0.05) (p < 0.0001). In experiments where no mosquitoes introduced, there were no significant differences between control and treatment, indicating that transfer of PPF to breeding sites only occurred when mosquitoes were present; i.e. that autodissemination had occurred. Treatment of a single clay pot reduced adult emergence in six habitats to (0.34 ± 0.13) compared to (0.98 ± 0.02) in the controls (p < 0.0001), showing a high level of habitats coverage amplification of the autodissemination event. CONCLUSION: The study provides proof of principle for the autodissemination of PPF to breeding habitats by malaria vectors. These findings highlight the potential for this technique for outdoor control of malaria vectors and call for the testing of this technique in field trials.

Increasing role of Anopheles funestus and Anopheles arabiensis in malaria transmission in the Kilombero Valley, Tanzania.

BACKGROUND: In order to sustain the gains achieved by current malaria control strategies, robust surveillance systems that monitor dynamics of vectors and their roles in malaria transmission over time are essential. This longitudinal study demonstrates the trends in malaria vector dynamics and their relative contribution to malaria transmission in hyperendemic transmission settings in Tanzania. METHODS: The study was conducted in two villages within the Kilombero Valley, in rural Tanzania for five consecutive years (2008-2012). Seventy-two houses were selected per village and each house was sampled for mosquitoes monthly using a CDC light trap. Collected mosquitoes were assessed for species identity and sporozoite infection status using PCR and ELISA, respectively. Anopheles funestus and Anopheles arabiensis susceptibility to insecticides was assessed using WHO guidelines. RESULTS: A total of 100,810 malaria vectors were collected, of which 76% were Anopheles gambiae s. l. and 24% were An. funestus. Of all An. funestus samples that amplified with PCR (n = 2,737), 97% were An. funestus s.s., 2% were Anopheles rivorulum and 1% Anopheles leesoni. Whereas for An. gambiae s.l. (n = 8,117), 93% were An. arabiensis and 7% were Anopheles gambiae s.s. The proportion of An. gambiae s.s. identified by PCR (2,924) declined from 0.2% in the year 2008 to undetectable levels in 2012. Malaria transmission intensity significantly decreased from an EIR of 78.14 infectious bites/person/year in 2008 to 35 ib/p/yr in 2011 but rebounded to 226 ib/p/yr in 2012 coinciding with an increased role of An. funestus in malaria transmission. Insecticide susceptibility tests indicated high levels of resistance in An. funestus against deltamethrin (87%), permethrin (65%), lambda cyhalothrin (74%), bendiocarb (65%), and DDT (66%). Similarly, An. arabiensis showed insecticide resistance to deltamethrin (64%), permethrin (77%) and lambda cyhalothrin (42%) in 2014. CONCLUSION: The results indicate the continuing role of An. arabiensis and the increasing importance of An. funestus in malaria transmission, and pyrethroid resistance development in both species. Complementary vector control and surveillance tools are needed that target the ecology, behaviour and insecticide resistance management of these vector species, in order to preserve the efficacy of LLINs.

A pilot intervention to improve uptake and equality of childhood influenza vaccination in an area of Wales, through the introduction of a mixed delivery model including nursery school immunisation sessions.

The schools-based influenza vaccination programme has seen consistently high uptake in Wales, however coverage in pre-school two and three-year olds is lower. One health board area (Cwm Taf University Health Board (UHB)) developed an intervention to offer live attenuated influenza vaccine (LAIV) for three-year olds attending nursery schools alongside the existing general practice (GP) programme. During the pilot, sessions were delivered by health visitors, working with school nurses. The mixed delivery model led to vaccination data being recorded in two separate data systems. To evaluate the impact of the pilot on overall vaccine uptake, data linkage was carried out within the Secure Anonymised Information Linkage (SAIL) Databank. Overall influenza vaccine uptake was calculated for each health board in Wales for two and three-year olds for the 2015-16, 2016-17, and 2017-18 influenza programmes. Uptake in two-year olds in Cwm Taf UHB and also uptake in three-year olds in other health boards in Wales were the comparison groups. Uptake of influenza vaccine in the 2015-16 (pre-intervention) period was 41.0% for three-year olds in Cwm Taf UHB. Following the intervention, coverage increased to 70.7% and 71.5% for 2016-17 and 2017-18 respectively. The same increases in uptake were not seen in two-year olds in Cwm Taf UHB or in three-year olds in non-intervention health boards. In Cwm Taf UHB resident three-year olds in 2015-16 there was an inequality gap in the uptake of 17.4 percentage points between the most and least deprived areas. Uptake increased across all deprivation quintiles in 2016-17 and 2017-18; and the inequality gap decreased to 10.3 and 13.4 percentage points respectively. Influenza vaccination uptake and equality of uptake in three-year olds can be improved by adopting a mixed delivery model across nursery school based immunisation sessions with the additional option of influenza vaccination at GPs.

Dimensions of equality in uptake of COVID-19 vaccination in Wales, UK: A multivariable linked data population analysis.

Vaccination has proven to be effective at preventing severe outcomes of COVID-19 infection, and uptake in the population has been high in Wales. However, there is a risk that high-level vaccination coverage statistics may mask hidden inequalities in under-served populations, many of whom may be at increased risk of severe outcomes of COVID-19 infection. The study population included 1,436,229 individuals aged 18 years and over, alive and residence in Wales as at 31st July 2022, and excluded immunosuppressed or care home residents. We compared people who had received one or more vaccinations to those with no vaccination using linked data from nine datasets within the Secure Anonymised Information Linkage (SAIL) databank. Multivariable analysis was undertaken to determine the impact of a range of sociodemographic characteristics on vaccination uptake, including ethnicity, country of birth, severe mental illness, homelessness and substance use. We found that overall uptake of first dose of COVID-19 vaccination was high in Wales (92.1 %), with the highest among those aged 80 years and over and females. Those aged under 40 years, household composition (aOR 0.38 95 %CI 0.35-0.41 for 10+ size household compared to two adult household) and being born outside the UK (aOR 0.44 95 %CI 0.43-0.46) had the strongest negative associations with vaccination uptake. This was followed by a history of substance misuse (aOR 0.45 95 %CI 0.44-0.46). Despite high-level population coverage in Wales, significant inequalities remain across several underserved groups. Factors associated with vaccination uptake should not be considered in isolation, to avoid drawing incorrect conclusions. Ensuring equitable access to vaccination is essential to protecting under-served groups from COVID-19 and further work needs to be done to address these gaps in coverage, with focus on tailored vaccination pathways and advocacy, using trusted partners and communities.

Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes. METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups. FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (ß 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity. INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation. FUNDING: None.

Polymorphisms in Anopheles gambiae immune genes associated with natural resistance to Plasmodium falciparum.

Many genes involved in the immune response of Anopheles gambiae, the main malaria vector in Africa, have been identified, but whether naturally occurring polymorphisms in these genes underlie variation in resistance to the human malaria parasite, Plasmodium falciparum, is currently unknown. Here we carried out a candidate gene association study to identify single nucleotide polymorphisms (SNPs) associated with natural resistance to P. falciparum. A. gambiae M form mosquitoes from Cameroon were experimentally challenged with three local wild P. falciparum isolates. Statistical associations were assessed between 157 SNPs selected from a set of 67 A. gambiae immune-related genes and the level of infection. Isolate-specific associations were accounted for by including the effect of the isolate in the analysis. Five SNPs were significantly associated to the infection phenotype, located within or upstream of AgMDL1, CEC1, Sp PPO activate, Sp SNAKElike, and TOLL6. Low overall and local linkage disequilibrium indicated high specificity in the loci found. Association between infection phenotype and two SNPs was isolate-specific, providing the first evidence of vector genotype by parasite isolate interactions at the molecular level. Four SNPs were associated to either oocyst presence or load, indicating that the genetic basis of infection prevalence and intensity may differ. The validity of the approach was verified by confirming the functional role of Sp SNAKElike in gene silencing assays. These results strongly support the role of genetic variation within or near these five A. gambiae immune genes, in concert with other genes, in natural resistance to P. falciparum. They emphasize the need to distinguish between infection prevalence and intensity and to account for the genetic specificity of vector-parasite interactions in dissecting the genetic basis of Anopheles resistance to human malaria.

Fall-Risk-Increasing Drugs in People With Dementia Who Live in a Residential Aged Care Facility: A Pilot Study.

Background  Psychotropic medications feature in prescribing guidelines for the treatment of depression in dementia as well as the management of behavioural and psychological symptoms of dementia (BPSD). They include antidepressants, antipsychotics, and benzodiazepines, and are among an established collective of pharmacotherapies known as fall-risk-increasing drugs (FRIDs). These psychoactive medications are known to increase fall risk in elderly adults, including those with a dementia diagnosis. Medication reviews are an integral part of falls prevention programs in residential aged care and provide an opportunity to modify medications to reduce fall risk related to pharmacotherapy. Objectives  This pilot study explores the characteristics of a group of elderly people with dementia living in residential care with a focus on patterns of falls and usage of psychotropic medications. Methods  This is a retrospective study conducted using data collected from health records. The Neuroscience-based Nomenclature (NbN) classification of psychotropic medicines is employed to highlight relevant pharmacological domains targeted by the medications rather than traditional drug classes. Results  Four pharmacological neurotransmitter domains emerged as key players in the pharmacotherapy of study participants. These were serotonin, dopamine, noradrenaline, and gamma-aminobutyric acid A (GABA-A). Serotonin was the most frequently implicated domain as related to observed usage of psychotropic treatments for depression and BPSD. Over the retrospective study period, 75% of participants were taking prescribed psychotropics known to target these four domains, and most (69.4%) were elderly women over the age of 80. Many participants experienced multiple falls, mostly among women, and most falls were rated as harmful to some degree. Conclusion  This study observes recurrent falls and frequent usage of psychoactive drugs in elderly people with dementia. We conclude that further investigations are both warranted to support prescribing guidelines for dementia and feasible according to the methodology of this pilot study.

Protocol for CLASSIC PBB: comparison of lower airway sampling strategies in children with protracted bacterial bronchitis.

BACKGROUND: Protracted bacterial bronchitis (PBB) is an endobronchial infection and a the most common cause of chronic wet cough in young children. It is treated with antibiotics, which can only be targeted if the causative organism is known. As most affected children do not expectorate sputum, lower airway samples can only be obtained by bronchoalveolar lavage (BAL) samples taken during flexible bronchoscopy (FB-BAL). This is invasive and is therefore reserved for children with severe or relapsing cases. Most children with PBB are treated empirically with broad spectrum antibiotics. CLASSIC PBB will compare the pathogen yield from two less invasive strategies with that from FB-BAL to see if they are comparable. METHODS: 131 children with PBB from four UK centres referred FB-BAL will be recruited. When attending for FB-BAL, they will have a cough swab and an induced sputum sample obtained. The primary outcome will be the discordance of the pathogen yield from the cough swab and the induced sputum when compared with FB-BAL. Secondary outcomes will be the sensitivity of each sampling strategy, the success rate of the induced sputum in producing a usable sample and the tolerability of each of the three sampling strategies. DISCUSSION: If either or both of the two less invasive airway sampling strategies are shown to be a useful alternative to FB-BAL, this will lead to more children with PBB having lower airway samples enabling targeted antibiotic prescribing. It would also reduce the need for FB, which is known to be burdensome for children and their families. TRIAL REGISTRATION NUMBER: ISRCTN79883982.

Cervical cancer screening among ethnically diverse black women: knowledge, attitudes, beliefs, and practices.

This is a descriptive study of cervical cancer screening knowledge, attitudes, beliefs, and practices among ethnically diverse black women. We conducted 6 focus groups with Haitian, African, English-speaking Caribbean, and African American women recruited from a federally qualified health center. Overall, there was limited knowledge and confusion across ethnic groups about cervical cancer and its risk factors, the Pap test, and the human papilloma virus (HPV) and its association with cervical cancer. At the same time, there were distinct differences between ethnic groups in knowledge, practices, and cultural beliefs about cervical cancer. African women knew the least among all the groups, while African American participants had the greatest knowledge of HPV. However, their knowledge was still limited. Patient-doctor relationship was the single most important facilitator for cervical cancer screening. Barriers to cervical cancer screening included cost, busy work schedule, fear of the unknown, lack of insurance or being unemployed, and fear of disclosing immigration status. Interventions with ethnically diverse black women would benefit from recognizing cultural barriers and misconceptions that vary by ethnic group. Culturally based strategies suggested by the focus groups include the use of existing social networks, the use of indigenous community-based health workers, and the inclusion of women of all ages in cervical cancer education because of the roles they have in extended families.

Agrochemical spray drift; assessment and mitigation--a review.

During application of agrochemicals spray droplets can drift beyond the intended target to non-target receptors, including water, plants and animals. Factors affecting this spray drift include mode of application, droplet size, which can be modified by the nozzle types, formulation adjuvants, wind direction, wind speed, air stability, relative humidity, temperature and height of released spray relative to the crop canopy. The rate of fall of spray droplets depends upon the size of the droplets but is modified by entrainment in a mobile air mass and is also influenced by the rate of evaporation of the liquid constituting the aerosol. The longer the aerosol remains in the air before falling to the ground (or alternatively striking an object above ground) the greater the opportunity for it to be carried away from its intended target. In general, all size classes of droplets are capable of movement off target, but the smallest are likely to move the farthest before depositing on the ground or a non-target receptor. It is not possible to avoid spray drift completely but it can be minimized by using best-management practices. These include using appropriate nozzle types, shields, spray pressure, volumes per area sprayed, tractor speed and only spraying when climatic conditions are suitable. Field layout can also influence spray drift, whilst crop-free and spray-free buffer zones and windbreak crops can also have a mitigating effect. Various models are available to estimate the environmental exposure from spray drift at the time of application.

Successful biodegradable stent insertion in an infant with severe bronchomalacia and cystic fibrosis.

We report the first case of biodegradable airway stent insertion for a patient with bronchomalacia and cystic fibrosis (CF). This female infant with antenatally diagnosed cystic fibrosis developed respiratory distress by three weeks of age. On lower airway examination she was found to have severe left main stem bronchomalacia causing left upper lobe hyperinflation and subsequent right upper lobe collapse. By eight weeks of age she developed life-threatening respiratory failure requiring high pressure invasive ventilation. A biodegradable bronchial stent was inserted to the left main bronchus at thirteen weeks of age with successful extubation from invasive respiratory support four days later. A second biodegradable stent was inserted nine weeks later, due to persistent bronchomalacia following stent degradation and redevelopment of oxygen requirement. She was discharged home off all respiratory support eight weeks later and has remained well, requiring no further surgical intervention for bronchomalacia to date, now age three years.

Low linkage disequilibrium in wild Anopheles gambiae s.l. populations.

BACKGROUND: In the malaria vector Anopheles gambiae, understanding diversity in natural populations and genetic components of important phenotypes such as resistance to malaria infection is crucial for developing new malaria transmission blocking strategies. The design and interpretation of many studies here depends critically on Linkage disequilibrium (LD). For example in association studies, LD determines the density of Single Nucleotide Polymorphisms (SNPs) to be genotyped to represent the majority of the genomic information. Here, we aim to determine LD in wild An. gambiae s.l. populations in 4 genes potentially involved in mosquito immune responses against pathogens (Gambicin, NOS, REL2 and FBN9) using previously published and newly generated sequences. RESULTS: The level of LD between SNP pairs in cloned sequences of each gene was determined for 7 species (or incipient species) of the An. gambiae complex. In all tested genes and species, LD between SNPs was low: even at short distances (< 200 bp), most SNP pairs gave an r2 < 0.3. Mean r2 ranged from 0.073 to 0.766. In most genes and species LD decayed very rapidly with increasing inter-marker distance. CONCLUSIONS: These results are of great interest for the development of large scale polymorphism studies, as LD generally falls below any useful limit. It indicates that very fine scale SNP detection will be required to give an overall view of genome-wide polymorphism. Perhaps a more feasible approach to genome wide association studies is to use targeted approaches using candidate gene selection to detect association to phenotypes of interest.

Bioavailability of xenobiotics in the soil environment.

It is often presumed that all chemicals in soil are available to microorganisms, plant roots, and soil fauna via dermal exposure. Subsequent bioaccumulation through the food chain may then result in exposure to higher organisms. Using the presumption of total availability, national governments reduce environmental threshold levels of regulated chemicals by increasing guideline safety margins. However, evidence shows that chemical residues in the soil environment are not always bioavailable. Hence, actual chemical exposure levels of biota are much less than concentrations present in soil would suggest. Because "bioavailability" conveys meaning that combines implications of chemical sol persistency, efficacy, and toxicity, insights on the magnitude of a chemicals soil bioavailability is valuable. however, soil bioavailability of chemicals is a complex topic, and is affected by chemical properties, soil properties, species exposed, climate, and interaction processes. In this review, the state-of-art scientific basis for bioavailability is addressed. Key points covered include: definition, factors affecting bioavailability, equations governing key transport and distributive kinetics, and primary methods for estimating bioavailability. Primary transport mechanisms in living organisms, critical to an understanding of bioavailability, also presage the review. Transport of lipophilic chemicals occurs mainly by passive diffusion for all microorganisms, plants, and soil fauna. Therefore, the distribution of a chemical between organisms and soil (bioavailable proportion) follows partition equilibrium theory. However, a chemical's bioavailability does not always follow partition equilibrium theory because of other interactions with soil, such as soil sorption, hysteretic desorption, effects of surfactants in pore water, formation of "bound residue", etc. Bioassays for estimating chemical bioavailability have been introduced with several targeted endpoints: microbial degradation, uptake by higher plants and soil fauna, and toxicity to organisms. However, there bioassays are often time consuming and laborious. Thus, mild extraction methods have been employed to estimate bioavailability of chemicals. Mild methods include sequential extraction using alcohols, hexane/water, supercritical fluids (carbon dioxide), aqueous hydroxypropyl-beta-cyclodextrin extraction, polymeric TENAX beads extraction, and poly(dimethylsiloxane)-coated solid-phase microextraction. It should be noted that mild extraction methods may predict bioavailability at the moment when measurements are carried out, but not the changes in bioavailability that may occur over time. Simulation models are needed to estimate better bioavailability as a function of exposure time. In the past, models have progressed significantly by addressing each group of organisms separately: microbial degradation, plant uptake via evapotranspiration processes, and uptake of soil fauna in their habitat. This approach has been used primarily because of wide differences in the physiology and behaviors of such disparate organisms. However, improvement of models is badly needed, Particularly to describe uptake processes by plant and animals that impinge on bioavailability. Although models are required to describe all important factors that may affect chemical bioavailability to individual organisms over time (e.g., sorption/desorption to soil/sediment, volatilization, dissolution, aging, "bound residue" formation, biodegradation, etc.), these models should be simplified, when possible, to limit the number of parameters to the practical minimum. Although significant scientific progress has been made in understanding the complexities in specific methodologies dedicated to determining bioavailability, no method has yet emerged to characterized bioavailability across a wide range of chemicals, organisms, and soils/sediments. The primary aim in studying bioavailability is to define options for addressing bioremediation or environmental toxicity (risk assessment), and that is unlikely to change. Because of its importance in estimating research is needed to more comprehensively address the key environmental issue of "bioavailability of chemicals in soil/sediment."

Interdisciplinary Healthcare Students' Experiences of Intimidation, Harassment, and Discrimination During Training.

Healthcare professionals are trained on cultural competence and the treatment of patients with respect. Little research exists to examine intimidation, harassment, and discrimination (IHD) of interdisciplinary health professions trainees in the clinical training experience or policies around such actions. We surveyed a group of interdisciplinary students in the advanced years of their programs about IHD while in clinical training. Descriptive data and open-ended questions were analyzed. Of 87 respondents, the most frequently observed and experienced IHD were inappropriate verbal comments, 26.4% and 41.4%, respectively; the most frequent basis of observed IHD was race/ethnicity (17.2%) and the most frequently experienced was gender (26.4%). Physicians were noted most often to be the primary source of IHD (16.1%), followed by nurses (12.6%) and fellow trainees (12.6%). Of respondents experiencing IHD, 12 reported harassment, 11 reported intimidation, 6 reported discrimination, and 4 reported bias. When asked if anyone intervened at the time of the incident, 21 replied yes, most often supervisors or colleagues who were told (n=12). The incidence of IHD in clinical training warrants development of interdisciplinary training initiatives to address these issues.

Paediatric deaths in a tertiary government hospital setting, Malawi.

Background: Malawisuccessfully achieved Millennium Development Goal (MDG) four by decreasing the under-5 mortality rate by two-thirds in 2012. Despite this progress child mortality is still high and in 2013, the leading causes of death in under-5s were malaria, acute respiratory infections and HIV/AIDS. Aims: To determine the causes of inpatient child death including microbiological aetiologies in Malawi. Methods: A prospective, descriptive study was undertaken in Queen Elizabeth Central Hospital over 12 months in 2015/2016. Data was collected for every paediatric covering HIV and nutritional status, cause of death, and microbiology. Deaths of inborn neonates were excluded. Results: Of 13,827 admissions, there were 488 deaths, giving a mortality rate of 3.5%. One-third of deaths (168) occurred in the first 24 h of admission and 255 after 48 h Sixty-eight per cent of those who died (332) were under 5 years of age. The five leading causes of death were sepsis (102), lower respiratory tract infection (67), acute gastroenteritis with severe dehydration (51), malaria (37) and meningitis (34). The leading non-communicable cause of death was solid tumour (12). Of the 362 children with a known HIV status 134 (37.0%) were HIV-infected or HIV-exposed. Of the 429 children with a known nutrional status, 93 had evidence of severe acute malnutrition (SAM). Blood cultures were obtained from 252 children 51 (20.2%) grew pathogenic bacteria with Klebsiella pneumoniae, Escherichia coli and Staphylococcus aureus being the most common. Conclusion: Despite a significant reduction in paediatric inpatient mortality in Malawi, infectious diseases remain the predominant cause. Abbreviations: ART: anti-retroviral therapy; Child PIP: Child Healthcare Problem Identification Programme; CCF: congestive cardiac failure; CNS: central nervous system; CoNS: coagulase-negative staphylococci; CSF: cerebrospinal fluid; DNA pcr: deoxyribonucleic acid polymerase chain reaction; ETAT: emergency triage assessment and treatment; LMIC: low- and middle-income countries; MDG: Millennium Development Goals; MRI: magnetic resonance imaging; MRSA: methicillin-resistant Staphylococcus aureus; NAI: non-accidental injury; NTS: non-typhi salmonella; PJP: Pneumocystis jiroveci pneumonia; PSHD: presumed severe HIV disease; QECH: Queen Elizabeth Central Hospital; RHD: rheumatic heart disease; RTA: road traffic accident; TB: tuberculosis; TBM: tuberculous meningitis; WHO: World Health Organization; SAM: severe acute malnutrition.

Comparison of herbicide regimes and the associated potential environmental effects of glyphosate-resistant crops versus what they replace in Europe.

While cultivation of transgenic crops takes place in seven of the EU member states, this constitutes a relatively limited part of the total acreage planted to these crops worldwide. The only glyphosate-resistant (GR) crop grown commercially until recently has been soybean in Romania. In addition, large-scale experimental European data exist for GR sugar and fodder beets, and, to a lesser extent, GR oilseed rape. These GR crops are likely to have an impact both on the use of herbicides and on the environmental impact of the latter. From the data on these GR crops, it appears that quantities of herbicides applied to GR beets are decreased while those on GR soybean are slightly increased compared with their conventional counterparts. Depending on the parameters used for prediction or measurement of environmental impacts of GR crops, generally similar or less negative impacts were observed compared with conventional crops. Favourable environmental effects of the glyphosate-containing herbicide regimes on GR crops appear feasible, provided appropriate measures for maintaining biodiversity and prevention of volunteers and gene flow are applied.

Altered pesticide use on transgenic crops and the associated general impact from an environmental perspective.

The large-scale commercial cultivation of transgenic crops has undergone a steady increase since their introduction 10 years ago. Most of these crops bear introduced traits that are of agronomic importance, such as herbicide or insect resistance. These traits are likely to impact upon the use of pesticides on these crops, as well as the pesticide market as a whole. Organizations like USDA-ERS and NCFAP monitor the changes in crop pest management associated with the adoption of transgenic crops. As part of an IUPAC project on this topic, recent data are reviewed regarding the alterations in pesticide use that have been observed in practice. Most results indicate a decrease in the amounts of active ingredients applied to transgenic crops compared with conventional crops. In addition, a generic environmental indicator -- the environmental impact quotient (EIQ) -- has been applied by these authors and others to estimate the environmental consequences of the altered pesticide use on transgenic crops. The results show that the predicted environmental impact decreases in transgenic crops. With the advent of new types of agronomic trait and crops that have been genetically modified, it is useful to take also their potential environmental impacts into account.

Pesticide residues in food--acute dietary exposure.

Consumer risk assessment is a crucial step in the regulatory approval of pesticide use on food crops. Recently, an additional hurdle has been added to the formal consumer risk assessment process with the introduction of short-term intake or exposure assessment and a comparable short-term toxicity reference, the acute reference dose. Exposure to residues during one meal or over one day is important for short-term or acute intake. Exposure in the short term can be substantially higher than average because the consumption of a food on a single occasion can be very large compared with typical long-term or mean consumption and the food may have a much larger residue than average. Furthermore, the residue level in a single unit of a fruit or vegetable may be higher by a factor (defined as the variability factor, which we have shown to be typically x3 for the 97.5th percentile unit) than the average residue in the lot. Available marketplace data and supervised residue trial data are examined in an investigation of the variability of residues in units of fruit and vegetables. A method is described for estimating the 97.5th percentile value from sets of unit residue data. Variability appears to be generally independent of the pesticide, the crop, crop unit size and the residue level. The deposition of pesticide on the individual unit during application is probably the most significant factor. The diets used in the calculations ideally come from individual and household surveys with enough consumers of each specific food to determine large portion sizes. The diets should distinguish the different forms of a food consumed, eg canned, frozen or fresh, because the residue levels associated with the different forms may be quite different. Dietary intakes may be calculated by a deterministic method or a probabilistic method. In the deterministic method the intake is estimated with the assumptions of large portion consumption of a 'high residue' food (high residue in the sense that the pesticide was used at the highest recommended label rate, the crop was harvested at the smallest interval after treatment and the residue in the edible portion was the highest found in any of the supervised trials in line with these use conditions). The deterministic calculation also includes a variability factor for those foods consumed as units (eg apples, carrots) to allow for the elevated residue in some single units which may not be seen in composited samples. In the probabilistic method the distribution of dietary consumption and the distribution of possible residues are combined in repeated probabilistic calculations to yield a distribution of possible residue intakes. Additional information such as percentage commodity treated and combination of residues from multiple commodities may be incorporated into probabilistic calculations. The IUPAC Advisory Committee on Crop Protection Chemistry has made 11 recommendations relating to acute dietary exposure.

Comprehensive sterilization of malaria vectors using pyriproxyfen: a step closer to malaria elimination.

One of the main challenges to malaria elimination is the resilience of vectors, such as Anopheles arabiensis, that evade lethal exposure to insecticidal control measures or express resistance to their active ingredients. This study investigated a novel technology for population control that sterilizes mosquitoes using pyriproxyfen, a juvenile hormone analogue. Females of An. arabiensis were released in a semifield system divided into four equal sections, and each section had a mud hut sheltering a tethered cow providing a blood source for mosquitoes. In all sections, the inner mud hut walls and roofs were lined with black cotton cloth. In one-half of the sections, the cloth was dusted with pyriproxyfen. An overwhelming 96% reduction in adult production was achieved in pyriproxyfen-treated sections compared with control sections. This unprecedented level of control can be exploited to design new vector control strategies that particularly target existing behaviorally resilient and insecticide-resistant populations.