The effects of radiofrequency electromagnetic fields exposure on human self-reported symptoms: A systematic review of human experimental studies.

BACKGROUND: The technological applications of radiofrequency electromagnetic fields (RF-EMF) have been steadily increasing since the 1950s exposing large proportions of the population. The World Health Organization (WHO) is assessing the potential health effects of exposure to RF-EMF. OBJECTIVES: To systematically assess the effects of exposure to RF-EMF on self-reported non-specific symptoms in human subjects and to assess the accuracy of perceptions of presence or absence of RF-EMF exposure. METHODS: Eligibility criteria: experimental studies carried out in the general population and in individuals with idiopathic environmental intolerance attributed to EMF (IEI-EMF), in any language. INFORMATION SOURCES: Medline, Web of Science, PsycInfo, Cochrane Library, Epistemonikos, Embase and EMF portal, searched till April 2022. Risk of Bias (ROB): we used the RoB tool developed by OHAT adapted to the topic of this review. SYNTHESIS OF RESULTS: we synthesized studies using random effects meta-analysis and sensitivity analyses, where appropriate. RESULTS: Included studies: 41 studies were included, mostly cross over trials and from Europe, with a total of 2,874 participants. SYNTHESIS OF RESULTS: considering the primary outcomes, we carried out meta-analyses of 10 exposure-outcomes pairs. All evidence suggested no or small non-significant effects of exposure on symptoms with high (three comparisons), moderate (four comparisons), low (one comparison) and very low (two comparisons) certainty of evidence. The effects (standard mean difference, where positive values indicate presence of symptom being exposed) in the general population for head exposure were (95% confidence intervals) 0.08 (-0.07 to 0.22) for headache, -0.01 (-0.22 to 0.20) for sleeping disturbances and 0.13 (-0.51 to 0.76) for composite symptoms; and for whole-body exposure: 0.09 (-0.35 to 0.54), 0.00 (-0.15 to 0.15) for sleeping disturbances and -0.05 (-0.17 to 0.07) for composite symptoms. For IEI-EMF individuals SMD ranged from -0.19 to 0.11, all of them with confidence intervals crossing the value of zero. Further, the available evidence suggested that study volunteers could not perceive the EMF exposure status better than what is expected by chance and that IEI-EMF individuals could not determine EMF conditions better than the general population. DISCUSSION: Limitations of evidence: experimental conditions are substantially different from real-life situations in the duration, frequency, distance and position of the exposure. Most studies were conducted in young, healthy volunteers, who might be more resilient to RF-EMF than the general population. The outcomes of interest in this systematic review were symptoms, which are self-reported. The available information did not allow to assess the potential effects of exposures beyond acute exposure and in elderly or in chronically ill people. It cannot be ruled out that a real EMF effect in IEI-EMF groups is masked by a mix with insensitive subjects. However, studies on symptoms reporting and/or field perceptions did not find any evidence that there were particularly vulnerable individuals in the IEI-EMF group, although in open provocation studies, when volunteers were informed about the presence or absence of EMF exposure, such differences were consistently observed. INTERPRETATION: available evidence suggests that acute RF-EMF below regulatory limits does not cause symptoms and corresponding claims in the everyday life are related to perceived and not to real EMF exposure status.

The effects of radiofrequency electromagnetic fields exposure on tinnitus, migraine and non-specific symptoms in the general and working population: A systematic review and meta-analysis on human observational studies.

BACKGROUND: Applications emitting radiofrequency electromagnetic fields (RF-EMF; 100 kHz to 300 GHz) are widely used for communication (e.g. mobile phones), in medicine (diathermy) and in industry (RF heaters). OBJECTIVES: The objective is to systematically review the effects of longer-term or repeated local and whole human body radiofrequency electromagnetic field (RF-EMF) exposure on the occurrence of symptoms. Primary hypotheses were tinnitus, migraine and headaches in relation to RF-EMF exposure of the brain, sleep disturbances and composite symptom scores in relation to whole-body RF-EMF exposure. METHODS: Eligibility criteria: We included case-control and prospective cohort studies in the general population or workers estimating local or whole-body RF-EMF exposure for at least one week. INFORMATION SOURCES: We conducted a systematic literature search in various databases including Web of Science and Medline. Risk of bias: We used the Risk of Bias (RoB) tool developed by OHAT adapted to the topic of this review. SYNTHESIS OF RESULTS: We synthesized studies using random effects meta-analysis. RESULTS: Included studies: We included 13 papers from eight distinct cohort and one case-control studies with a total of 486,558 participants conducted exclusively in Europe. Tinnitus is addressed in three papers, migraine in one, headaches in six, sleep disturbances in five, and composite symptom scores in five papers. Only one study addressed occupational exposure. SYNTHESIS OF RESULTS: For all five priority hypotheses, available research suggests that RF-EMF exposure below guideline values does not cause symptoms, but the evidence is very uncertain. The very low certainty evidence is due the low number of studies, possible risk of bias in some studies, inconsistencies, indirectness, and imprecision. In terms of non-priority hypotheses numerous exposure-outcome combinations were addressed in the 13 eligible papers without indication for an association related to a specific symptom or exposure source. DISCUSSION: Limitations of evidence: This review topic includes various challenges related to confounding control and exposure assessment. Many of these aspects are inherently present and not easy to be solved in future research. Since near-field exposure from wireless communication devices is related to lifestyle, a particular challenge is to differentiate between potential biophysical effects and other potential effects from extensive use of wireless communication devices that may compete with healthy behaviour such as sleeping or physical activity. Future research needs novel and innovative methods to differentiate between these two hypothetical mechanisms. INTERPRETATION: This is currently the best available evidence to underpin safety of RF-EMF. There is no indication that RF-EMF below guideline values causes symptoms. However, inherent limitations of the research results in substantial uncertainty. OTHER: Funding: This review was partially funded by the WHO radioprotection programme. REGISTRATION: The protocol for this review has been registered in Prospero (reg no CRD42021239432) and published in Environment International (Röösli et al., 2021).

The effects of radiofrequency electromagnetic fields exposure on human self-reported symptoms: A protocol for a systematic review of human experimental studies.

BACKGROUND: The technological applications of radiofrequency electromagnetic fields (RF-EMF) have been steadily increasing since the 1950s across multiple sectors exposing large proportions of the population. This fact has raised concerns related to the potential consequences to people's health. The World Health Organization (WHO) is assessing the potential health effects of exposure to RF-EMF and has carried out an international survey amongst experts, who have identified six priority topics to be further addressed through systematic reviews, whereof the effects on symptoms is one of them. We report here the systematic review protocol of experimental studies in humans assessing the effects of RF-EMF on symptoms. OBJECTIVE: Our objectives are to assess the effects of exposure to electromagnetic fields (compared to no or lower exposure levels) on symptoms in human subjects. We will also assess the accuracy of perception of presence of exposure in volunteers with and without idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF). ELIGIBILITY CRITERIA: We will search relevant literature sources (e.g. the Web of Science, Medline, Embase, Epistemonikos) for randomized trials (comparing at least two arms) and randomised crossover trials of RF-EMF exposure that have assessed the effects on symptoms. We will also include studies that have measured the accuracy of the perception of the presence or absence of exposure. We will include studies in any language. STUDY APPRAISAL AND SYNTHESIS: Studies will be assessed against inclusion criteria by two independent reviewers. Data on study characteristics, participants, exposure, comparators and effects will be extracted using a specific template for this review, by two independent reviewers. Discrepancies will be solved by consensus. Risk of bias (ROB) will be assessed using the ROB Rating Tool for Human and Animal Studies and the level of confidence in the evidence of the exposure-outcome relations will be assessed using the GRADE approach. For the perception studies, we will use adapted versions of the ROB tool and GRADE assessment. Where appropriate, data will be combined using meta-analytical techniques.

The effects of radiofrequency electromagnetic fields exposure on tinnitus, migraine and non-specific symptoms in the general and working population: A protocol for a systematic review on human observational studies.

BACKGROUND: Applications emitting radiofrequency electromagnetic fields (RF-EMF; 100 kHz to 300 GHz) are widely used for communication (e.g. mobile phones), in medicine (diathermy) and in industry (RF heaters). Concern has been raised that RF-EMF exposure affects health related quality of life, because a part of the population reports to experience a variety of symptoms related to low exposure levels below regulatory limits. OBJECTIVES: To systematically review the effects of longer-term or repeated local and whole human body RF-EMF exposure on the occurrence of symptoms evaluating migraine, tinnitus, headaches, sleep disturbances and composite symptom scores as primary outcomes. METHODS: We will follow the WHO handbook for guideline development. For the development of the systematic review protocol we considered handbook for conducting systematic reviews for health effects evaluations from the National Toxicology Program-Office of Health Assessment and Translation (NTP-OHAT) and COSTER (Recommendations for the conduct of systematic reviews in toxicology and environmental health research). ELIGIBILITY CRITERIA: Peer-reviewed epidemiological studies in the general population or workers aiming to investigate the association between local or whole-body RF-EMF exposure for at least one week and symptoms are eligible for inclusion. Only cohort, case-control and panel studies will be included. INFORMATION SOURCES: We will search the scientific literature databases Medline, Web of Science, PsycInfo, Cochrane Library, Epistemonikos and Embase, using a predefined search strategy. This search will be supplemented by a search in the EMF-Portal and checks of reference lists of relevant papers and reviews. STUDY APPRAISAL AND SYNTHESIS METHOD: Data from included papers will be extracted according to predefined forms. Findings will be summarized in tables, graphical displays and in a narrative synthesis of the available evidence, complemented with meta-analyses. We will separately review effects of local, far field and occupational exposure. RISK OF BIAS: The internal validity of included studies will be assessed using the NTP-OHAT Risk of Bias Rating Tool for Human and Animal Studies, elaborated to observational RF-EMF studies. EVIDENCE APPRAISAL: To rate certainty of the evidence, we will use the OHAT GRADE-based approach for epidemiological studies. FRAMEWORK AND FUNDING: This protocol concerns one of the ten different systematic reviews considered in a larger systematic review of the World Health Organization to assess potential health effects of exposure to RF-EMF in the general and working population. REGISTRATION: PROSPERO CRD42021239432.

Exposure to radiofrequency electromagnetic fields: Comparison of exposimeters with a novel body-worn distributed meter.

BACKGROUND: Exposure to radiofrequency electromagnetic fields (RF-EMF) is often measured with personal exposimeters, but the accuracy of measurements can be hampered as carrying the devices on-body may result in body shielding. Further, the compact design may compromise the frequency selectivity of the sensor. The aim of this study was to compare measurements obtained using a multi-band body-worn distributed-exposimeter (BWDM) with two commercially available personal exposimeters (ExpoM-RF and EmeSpy 200) under real-life conditions. METHODS: The BWDM measured power density in 10 frequency bands (800, 900, 1800, 2100, 2600 MHz, DECT 1900 MHz, WiFi 2.4 GHz; with separate uplink/downlink bands for 900, 1800 and 2100 MHz); using 20 separate antennas integrated in a vest and placed on diametrically opposite locations on the body, to minimize body-shielding. RF-EMF exposure data were collected from several microenvironments (e.g. shopping areas, train stations, outdoor rural/ urban residential environments, etc.) by walking around pre-defined areas/routes in Belgium, Spain, France, the Netherlands and Switzerland. Measurements were taken every 1-4 s with the BWDM in parallel with an ExpoM-RF and an EmeSpy 200 exposimeter. We calculated medians and interquartile ranges (IQRs) and compared difference, ratios and correlations of geometric mean RF-EMF exposure levels per microenvironment as measured with the exposimeters and the BWDM. RESULTS: Across 267 microenvironments, medians and IQR of total BWDM measured RF-EMF exposure was 0.13 (0.05-0.33) mW/m2. Difference: IQR of exposimeters minus BWDM exposure levels was -0.011 (-0.049 to 0.0095) mW/m2 for the ExpoM-RF and -0.056 (-0.14 to -0.017) for the EmeSpy 200; ratios (exposimeter/BWDM) of total exposure had an IQR of 0.79 (0.55-1.1) for the ExpoM-RF and 0.29 (0.22-0.38) for the EmeSpy 200. Spearman correlations were 0.93 for the ExpoM-RF vs the BWDM and 0.96 for the EmeSpy 200 vs the BWDM. DISCUSSION AND CONCLUSIONS: Results indicate that exposimeters worn on-body provide somewhat lower total RF-EMF exposure as compared to measurements conducted with the BWDM, in line with effects from body shielding. Ranking of exposure levels of microenvironments showed high correspondence between the different device types. Our results are informative for the interpretation of existing epidemiological research results.

A real-world quality assessment study in six ExpoM-RF measurement devices.

Exposimeters measuring radiofrequency electromagnetic fields (RF-EMF) are commonly used to assess personal exposure to RF-EMF in real-life environments. They are usually calibrated in an anechoic chamber using single, well-defined signals such as the center frequency of each band, and standardized orientations, but it is not clear how different devices compare in the real environment where complex mixtures of signals from all directions are present. We thus tested the comparability of six ExpoM-RF exposimeters before and after calibration in an anechoic chamber by varying their position and orientation while repeatedly measuring 15 microenvironments (9 walking routes, 4 tram routes and 2 bus routes) on 6 different days. We modelled the geometric mean levels of RF-EMF as a function of orientation, position, device ID, whether the device was recently calibrated, correcting for the microenvironment in which each measurement took place. We found that systematic differences introduced by device ID, calibration, day of the week, orientation and position are relatively small compared to exposure differences between microenvironments. Any corrections (if desired) should include both device ID and calibration session, but would have a small impact considering the negligible differences between devices. This supports the validity of previous exposure measurement studies relying on ExpoM-RF devices, which did not correct for device ID. We further found that summarizing the exposure per microenvironment as geometric means results in better models than arithmetic means and medians, and recommend that further exposure assessment studies report observed levels as geometric means.

Topographic mapping of the interfaces between human and aquatic mosquito habitats to enable barrier targeting of interventions against malaria vectors.

Geophysical topographic metrics of local water accumulation potential are freely available and have long been known as high-resolution predictors of where aquatic habitats for immature Anopheles mosquitoes are most abundant, resulting in elevated densities of adult malaria vectors and human infection burden. Using existing entomological and epidemiological survey data, here we illustrate how topography can also be used to map out the interfaces between wet, unoccupied valleys and dry, densely populated uplands, where malaria vector densities and infection risk are focally exacerbated. These topographically identifiable geophysical boundaries experience disproportionately high vector densities and malaria transmission risk, because this is where Anopheles mosquitoes first encounter humans when they search for blood after emerging or ovipositing in the valleys. Geophysical topographic indicators accounted for 67% of variance for vector density but for only 43% for infection prevalence, so they could enable very selective targeting of interventions against the former but not the latter (targeting ratios of 5.7 versus 1.5 to 1, respectively). So, in addition to being useful for targeting larval source management to wet valleys, geophysical topographic indicators may also be used to selectively target adult Anopheles mosquitoes with insecticidal residual sprays, fencing, vapour emanators or space sprays to barrier areas along their fringes.

A Multi-Band Body-Worn Distributed Radio-Frequency Exposure Meter: Design, On-Body Calibration and Study of Body Morphology.

A multi-band Body-Worn Distributed exposure Meter (BWDM) calibrated for simultaneous measurement of the incident power density in 11 telecommunication frequency bands, is proposed. The BDWM consists of 22 textile antennas integrated in a garment and is calibrated on six human subjects in an anechoic chamber to assess its measurement uncertainty in terms of 68% confidence interval of the on-body antenna aperture. It is shown that by using multiple antennas in each frequency band, the uncertainty of the BWDM is 22 dB improved with respect to single nodes on the front and back of the torso and variations are decreased to maximum 8.8 dB. Moreover, deploying single antennas for different body morphologies results in a variation up to 9.3 dB, which is reduced to 3.6 dB using multiple antennas for six subjects with various body mass index values. The designed BWDM, has an improved uncertainty of up to 9.6 dB in comparison to commercially available personal exposure meters calibrated on body. As an application, an average incident power density in the range of 26.7-90.8 µW·m - 2 is measured in Ghent, Belgium. The measurements show that commercial personal exposure meters underestimate the actual exposure by a factor of up to 20.6.

Radiofrequency electromagnetic field exposure in everyday microenvironments in Europe: A systematic literature review.

The impact of the introduction and advancement in communication technology in recent years on exposure level of the population is largely unknown. The main aim of this study is to systematically review literature on the distribution of radiofrequency electromagnetic field (RF-EMF) exposure in the everyday environment in Europe and summarize key characteristics of various types of RF-EMF studies conducted in the European countries. We systematically searched the ISI Web of Science for relevant literature published between 1 January 2000 and 30 April 2015, which assessed RF-EMF exposure levels by any of the methods: spot measurements, personal measurement with trained researchers and personal measurement with volunteers. Twenty-one published studies met our eligibility criteria of which 10 were spot measurements studies, 5 were personal measurement studies with trained researchers (microenvironmental), 5 were personal measurement studies with volunteers and 1 was a mixed methods study combining data collected by volunteers and trained researchers. RF-EMF data included in the studies were collected between 2005 and 2013. The mean total RF-EMF exposure for spot measurements in European "Homes" and "Outdoor" microenvironments was 0.29 and 0.54 V/m, respectively. In the personal measurements studies with trained researchers, the mean total RF-EMF exposure was 0.24 V/m in "Home" and 0.76 V/m in "Outdoor". In the personal measurement studies with volunteers, the population weighted mean total RF-EMF exposure was 0.16 V/m in "Homes" and 0.20 V/m in "Outdoor". Among all European microenvironments in "Transportation", the highest mean total RF-EMF 1.96 V/m was found in trains of Belgium during 2007 where more than 95% of exposure was contributed by uplink. Typical RF-EMF exposure levels are substantially below regulatory limits. We found considerable differences between studies according to the type of measurements procedures, which precludes cross-country comparison or evaluating temporal trends. A comparable RF-EMF monitoring concept is needed to accurately identify typical RF-EMF exposure levels in the everyday environment.

The underlying reasons for very high levels of bed net use, and higher malaria infection prevalence among bed net users than non-users in the Tanzanian city of Dar es Salaam: a qualitative study.

BACKGROUND: Bed nets reduce malaria-related illness and deaths, by forming a protective barrier around people sleeping under them. When impregnated with long-lasting insecticide formulations they also repel or kill mosquitoes attempting to feed upon sleeping humans, and can even suppress entire populations of malaria vectors that feed predominantly upon humans. Nevertheless, an epidemiological study in 2012 demonstrated higher malaria prevalence among bed net users than non-users in urban Dar es Salaam, Tanzania. METHODS: Focus group discussions were conducted with women from four selected wards of Dar es Salaam city, focusing on four major themes relating to bed net use behaviours: (1) reasons for bed net use, (2) reasons for not using bed nets, (3) stimuli or reminders for people to use a bed net (4) perceived reasons for catching malaria while using a bed net. An analytical method by framework grouping of relevant themes was used address key issues of relevance to the study objectives. Codes were reviewed and grouped into categories and themes. RESULTS: All groups said the main reason for bed net use was protection against malaria. Houses with well-screened windows, with doors that shut properly, and that use insecticidal sprays against mosquitoes, were said not to use bed nets, while frequent attacks from malaria was the main stimulus for people to use bed nets. Various reasons were mentioned as potential reasons that compromise bed net efficacy, the most common of which were: (1) bed net sharing by two or more people, especially if one occupant tends to come to bed late at night, and does not tuck in the net 71%; (2) one person shares the bed but does not use the net, moving it away from the side on which s/he sleeps 68%; (3) ineffective usage habits, called ulalavi, in which a sprawling sleeper either touches the net while sleeping up against it or leaves a limb hanging outside of it 68%. Less common reasons mentioned included: (1) Small bed nets which become un-tucked at night (31%); (2) Bed nets with holes large enough to allow mosquitoes to pass (28%); and (3) Going to bed late after already being bitten outdoors (24%). CONCLUSIONS: Behaviours associated with bed net use like; bed sharing, bed net non compliant-bedfellow, sleeping pattern like ulalavi and some physical bed net attributes compromise its effectiveness and supposedly increase of malaria infection to bed net users. While some well-screened houses looked to instigate low malaria prevalence to non-bed net users.

Informing new or improved vector control tools for reducing the malaria burden in Tanzania: a qualitative exploration of perceptions of mosquitoes and methods for their control among the residents of Dar es Salaam.

BACKGROUND: The effectiveness of malaria prevention with long-lasting insecticidal nets and indoor residual spraying is limited by emerging insecticide resistance, evasive mosquito behaviours that include outdoor biting, sub-optimal implementation and inappropriate use. New vector control interventions are required and their potential effectiveness will be enhanced if existing household perceptions and practices are integrated into intervention design. METHODS: This qualitative descriptive study used focus groups discussions, in-depth interviews and photovoice methods to explore mosquito control perceptions and practices among residents in four study sites in Dar es Salaam, Tanzania. RESULTS: Mosquitoes were perceived as a growing problem, directly attributed to widespread environmental deterioration and lack of effective mosquito control interventions. Malaria and nuisance biting were perceived as the main problem caused by mosquitoes. Breeding sites were clearly distinguished from resting sites but residents did not differentiate between habitats producing malaria vector mosquitoes and others producing mostly nuisance mosquitoes. The most frequently mentioned protection methods in the wealthiest locations were bed nets, aerosol insecticide sprays, window screens, and fumigation, while bed nets were most frequently mentioned and described as 'part of the culture' in the least wealthy locations. Mosquito-proofed housing was consistently viewed as desirable, but considered unaffordable outside wealthiest locations. Slapping and covering up with clothing were most commonly used to prevent biting outdoors. Despite their utility outdoors, topical repellents applied to the skin were considered expensive, and viewed with suspicion due to perceived side effects. Improving the local environment was the preferred method for preventing outdoor biting. Affordability, effectiveness, availability, practicality, as well as social influences, such as government recommendations, socialization and internalization (familiarization and habit) were described as key factors influencing uptake. CONCLUSIONS: Outdoor transmission is widely accepted as an obstacle to malaria elimination. Larval source management, targeting both malaria vectors and nuisance-biting mosquitoes, is the preferred method for mosquito control among the residents of Dar es Salaam and should be prioritized for development alongside new methods for outdoor personal protection. Even if made available, effective and affordable, these additional interventions may require time and user experience to achieve positive reputations and trustworthiness.

Fine scale mapping of malaria infection clusters by using routinely collected health facility data in urban Dar es Salaam, Tanzania.

This study investigated whether passively collected routine health facility data can be used for mapping spatial heterogeneities in malaria transmission at the level of local government housing cluster administrative units in Dar es Salaam, Tanzania. From June 2012 to January 2013, residential locations of patients tested for malaria at a public health facility were traced based on their local leaders' names and geo-referencing the point locations of these leaders' houses. Geographic information systems (GIS) were used to visualise the spatial distribution of malaria infection rates. Spatial scan statistics was deployed to detect spatial clustering of high infection rates. Among 2407 patients tested for malaria, 46.6% (1121) could be traced to their 411 different residential housing clusters. One small spatially aggregated cluster of neighbourhoods with high prevalence was identified. While the home residence housing cluster leader was unambiguously identified for 73.8% (240/325) of malaria-positive patients, only 42.3% (881/2082) of those with negative test results were successfully traced. It was concluded that recording simple points of reference during routine health facility visits can be used for mapping malaria infection burden on very fine geographic scales, potentially offering a feasible approach to rational geographic targeting of malaria control interventions. However, in order to tap the full potential of this approach, it would be necessary to optimise patient tracing success and eliminate biases by blinding personnel to test results.

The epidemiology of residual Plasmodium falciparum malaria transmission and infection burden in an African city with high coverage of multiple vector control measures.

BACKGROUND: In the Tanzanian city of Dar es Salaam, high coverage of long-lasting insecticidal nets (LLINs), larvicide application (LA) and mosquito-proofed housing, was complemented with improved access to artemisinin-based combination therapy and rapid diagnostic tests by the end of 2012. METHODS: Three rounds of city-wide, cluster-sampled cross-sectional surveys of malaria parasite infection status, spanning 2010 to 2012, were complemented by two series of high-resolution, longitudinal surveys of vector density. RESULTS: Larvicide application using a granule formulation of Bacillus thuringiensis var. israelensis (Bti) had no effect upon either vector density (P = 0.820) or infection prevalence (P = 0.325) when managed by a private-sector contractor. Infection prevalence rebounded back to 13.8 % in 2010, compared with <2 % at the end of a previous Bti LA evaluation in 2008. Following transition to management by the Ministry of Health and Social Welfare (MoHSW), LA consistently reduced vector densities, first using the same Bti granule in early 2011 [odds ratio (OR) (95 % confidence interval (CI)) = 0.31 (0.14, 0.71), P = 0.0053] and then a pre-diluted aqueous suspension formulation from mid 2011 onwards [OR (95 % CI) = 0.15 (0.07, 0.30), P â‰ª 0.000001]. While LA by MoHSW with the granule formulation was associated with reduced infection prevalence [OR (95 % CI) = 0.26 (0.12, 0.56), P = 0.00040], subsequent liquid suspension use, following a mass distribution to achieve universal coverage of LLINs that reduced vector density [OR (95 % CI) = 0.72 (0.51, 1.01), P = 0.057] and prevalence [OR (95 % CI) = 0.80 (0.69, 0.91), P = 0.0013], was not associated with further prevalence reduction (P = 0.836). Sleeping inside houses with complete window screens only reduced infection risk [OR (95 % CI) = 0.71 (0.62, 0.82), P = 0.0000036] if the evenings and mornings were also spent indoors. Furthermore, infection risk was only associated with local vector density [OR (95 % CI) = 6.99 (1.12, 43.7) at one vector mosquito per trap per night, P = 0.037] among the minority (14 %) of households lacking screening. Despite attenuation of malaria transmission and immunity, 88 % of infected residents experienced no recent fever, only 0.4 % of these afebrile cases had been treated for malaria, and prevalence remained high (9.9 %) at the end of the study. CONCLUSIONS: While existing vector control interventions have dramatically attenuated malaria transmission in Dar es Salaam, further scale-up and additional measures to protect against mosquito bites outdoors are desirable. Accelerated elimination of chronic human infections persisting at high prevalence will require active, population-wide campaigns with curative drugs.

Spatially aggregated clusters and scattered smaller loci of elevated malaria vector density and human infection prevalence in urban Dar es Salaam, Tanzania.

BACKGROUND: Malaria transmission, primarily mediated by Anopheles gambiae, persists in Dar es Salaam (DSM) despite high coverage with bed nets, mosquito-proofed housing and larviciding. New or improved vector control strategies are required to eliminate malaria from DSM, but these will only succeed if they are delivered to the minority of locations where residual transmission actually persists. Hotspots of spatially clustered locations with elevated malaria infection prevalence or vector densities were, therefore, mapped across the city in an attempt to provide a basis for targeting supplementary interventions. METHODS: Two phases of a city-wide population-weighted random sample of cross-sectional household surveys of malaria infections were complemented by two matching phases of geographically overlapping, high-resolution, longitudinal vector density surveys; spanning 2010-2013. Spatial autocorrelations were explored using Moran's I and hotspots were detected using flexible spatial scan statistics. RESULTS: Seven hotspots of spatially clustered elevated vector density and eight of malaria infection prevalence were detected over both phases. Only a third of vectors were collected in hotspots in phase 1 (30 %) and phase 2 (33 %). Malaria prevalence hotspots accounted for only half of malaria infections detected in phase 1 (55 %) and phase 2 (47 %). Three quarters (76 % in phase 1 and 74 % in phase 2) of survey locations with detectable vector populations were outside of hotspots. Similarly, more than half of locations with higher infection prevalence (>10 %) occurred outside of hotspots (51 % in phase 1 and 54 % in phase 2). Vector proliferation hazard (exposure to An. gambiae) and malaria infection risk were only very loosely associated with each other (Odds ratio (OR) [95 % Confidence Interval (CI)] = 1.56 [0.89, 1.78], P = 0.52)). CONCLUSION: Many small, scattered loci of local malaria transmission were haphazardly scattered across the city, so interventions targeting only currently identifiable spatially aggregated hotspots will have limited impact. Routine, spatially comprehensive, longitudinal entomological and parasitological surveillance systems, with sufficient sensitivity and spatial resolution to detect these scattered loci, are required to eliminate transmission from this typical African city. Intervention packages targeted to both loci and hotspots of transmission will need to suppress local vector proliferation, treat infected residents and provide vulnerable residents with supplementary protective measures against exposure.

Malaria vectors and their blood-meal sources in an area of high bed net ownership in the western Kenya highlands.

BACKGROUND: Blood-meal sources of malaria vectors affect their capacity to transmit the disease. Most efficient malaria vectors prefer human hosts. However, with increasing personal protection measures it becomes more difficult for them to find human hosts. Here recent malaria vector blood-meal sources in western Kenya highlands were investigated. METHODS: Adult mosquitoes resting indoors, outdoors and exiting through windows were collected in three study areas within the western Kenya highlands from June 2011 to June 2013. A census of people, livestock and of insecticide-treated nets was done per house. Mosquito blood-meal sources were determined as human, goat, bovine or chicken using enzyme-linked-immunosorbent assays. RESULTS: Most (86.3 %) households possessed at least one bed net, 57.2 % had domesticated animals and 83.6 % had people sharing houses with livestock at night. Most (94.9 %) unfed malaria vectors were caught exiting through windows. Overall, 53.1 % of Anopheles gambiae sensu stricto obtained blood-meals from humans, 26.5 % from goats and 18.4 % from bovines. Single blood-meal sources by An. gambiae s.s. from humans were 26.5 %, 8.2 % from bovines and 2.0 % from goats. Mixed blood-meal sources by An. gambiae s.s. identified included: 24.5 % human/goat, 10.2 % human/bovine, 8.2 % human/bovine/goat and also 8.2 % bovine/goat. One An. arabiensis mosquito obtained blood-meal only from humans. CONCLUSION: An unusually high frequency of animal and mixed human-animal blood meals in the major malaria vector An. gambiae s.s. was revealed in the western Kenya highlands where bed net coverage is above the WHO target. The shift in blood-meal sources from humans to livestock is most likely the vectors' response to increased bed net coverage and the close location of livestock frequently in the same house as people at night. Livestock-targeted interventions should be considered under these circumstances to address residual malaria transmission.

Mapping hotspots of malaria transmission from pre-existing hydrology, geology and geomorphology data in the pre-elimination context of Zanzibar, United Republic of Tanzania.

BACKGROUND: Larval source management strategies can play an important role in malaria elimination programmes, especially for tackling outdoor biting species and for eliminating parasite and vector populations when they are most vulnerable during the dry season. Effective larval source management requires tools for identifying geographic foci of vector proliferation and malaria transmission where these efforts may be concentrated. Previous studies have relied on surface topographic wetness to indicate hydrological potential for vector breeding sites, but this is unsuitable for karst (limestone) landscapes such as Zanzibar where water flow, especially in the dry season, is subterranean and not controlled by surface topography. METHODS: We examine the relationship between dry and wet season spatial patterns of diagnostic positivity rates of malaria infection amongst patients reporting to health facilities on Unguja, Zanzibar, with the physical geography of the island, including land cover, elevation, slope angle, hydrology, geology and geomorphology in order to identify transmission hot spots using Boosted Regression Trees (BRT) analysis. RESULTS: The distribution of both wet and dry season malaria infection rates can be predicted using freely available static data, such as elevation and geology. Specifically, high infection rates in the central and southeast regions of the island coincide with outcrops of hard dense limestone which cause locally elevated water tables and the location of dolines (shallow depressions plugged with fine-grained material promoting the persistence of shallow water bodies). CONCLUSIONS: This analysis provides a tractable tool for the identification of malaria hotspots which incorporates subterranean hydrology, which can be used to target larval source management strategies.

Long-term trends in Anopheles gambiae insecticide resistance in Côte d'Ivoire.

BACKGROUND: Malaria control is heavily dependent on the use of insecticides that target adult mosquito vectors via insecticide treated nets (ITNs) or indoor residual spraying (IRS). Four classes of insecticide are approved for IRS but only pyrethroids are available for ITNs. The rapid rise in insecticide resistance in African malaria vectors has raised alarms about the sustainability of existing malaria control activities. This problem might be particularly acute in Côte d'Ivoire where resistance to all four insecticide classes has recently been recorded. Here we investigate temporal trends in insecticide resistance across the ecological zones of Côte d'Ivoire to determine whether apparent pan-African patterns of increasing resistance are detectable and consistent across insecticides and areas. METHODS: We combined data on insecticide resistance from a literature review, and bioassays conducted on field-caught Anopheles gambiae mosquitoes for the four WHO-approved insecticide classes for ITN/IRS. The data were then mapped using Geographical Information Systems (GIS) and the IR mapper tool to provide spatial and temporal distribution data on insecticide resistance in An. gambiae sensu lato from Côte d'Ivoire between 1993 and 2014. RESULTS: Bioassay mortality decreased over time for all insecticide classes, though with significant spatiotemporal variation, such that stronger declines were observed in the southern ecological zone for DDT and pyrethroids than in the central zone, but with an apparently opposite effect for the carbamate and organophosphate. Variation in relative abundance of the molecular forms, coupled with dramatic increase in kdr 1014F frequency in M forms (An. coluzzii) seems likely to be a contributory factor to these patterns. Although records of resistance across insecticide classes have become more common, the number of classes tested in studies has also increased, precluding a conclusion that multiple resistance has also increased. CONCLUSION: Our analyses attempted synthesis of 22 years of bioassay data from Côte d'Ivoire, and despite a number of caveats and potentially confounding variables, suggest significant but spatially-variable temporal trends in insecticide resistance. In the light of such spatio-temporal dynamics, regular, systematic and spatially-expanded monitoring is warranted to provide accurate information on insecticide resistance for control programme management.

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.

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.