A Multiplex PCR and DNA-Sequencing Workflow on Serum for the Diagnosis and Species Identification for Invasive Aspergillosis and Mucormycosis.

There has been significant increase in the use of molecular tools for the diagnosis of invasive aspergillosis (IA) and mucormycosis. However, their range of detection may be too limited as species diversity and coinfections are increasing. Here, we aimed to evaluate a molecular workflow based on a new multiplex PCR assay detecting the whole Aspergillus genus and the Mucorales order followed by a species-specific PCR or a DNA-sequencing approach for IA and/or mucormycosis diagnosis and species identification on serum. Performances of the MycoGENIE Aspergillus spp./Mucorales spp. duplex PCR kit were analyzed on a broad range of fungal strains and on sera from high-risk patients prospectively over a 12-month period. The kit allowed the detection of nine Aspergillus species and 10 Mucorales (eight genera) strains assessed. No cross-reactions between the two targets were observed. Sera from 744 patients were prospectively analyzed, including 35 IA, 16 mucormycosis, and four coinfections. Sensitivity varies from 85.7% (18/21) in probable/proven IA to 28.6% (4/14) in COVID-19-associated pulmonary aspergillosis. PCR-positive samples corresponded to 21 A. fumigatus, one A. flavus, and one A. nidulans infections. All the disseminated mucormycosis were positive in serum (14/14), including the four Aspergillus coinfections, but sensitivity fell to 33.3% (2/6) in localized forms. DNA sequencing allowed Mucorales identification in serum in 15 patients. Remarkably, the most frequent species identified was Rhizomucor pusillus (eight cases), whereas it is barely found in fungal culture. This molecular workflow is a promising approach to improve IA and mucormycosis diagnosis and epidemiology.

Semifield Evaluation of Improved Passive Outdoor Host Seeking Device (POHD) for Outdoor Control of Anopheles arabiensis Mosquitoes.

Despite the considerable progress made so far, the effectiveness and mass application of odour-baited outdoor mosquito control devices in pipelines is limited by several factors. These include the design and size of the devices, optimal placement of attractive blends, and nature of materials into which the blends are impregnated. The primary aim of this study was to manipulate these factors to improve the attractiveness of our recently developed passive outdoor host seeking device (POHD) to outdoor biting Anopheles arabiensis. Specifically, the study aimed to determine optimal placement of odour blends and killing bioactives in POHD for maximum attraction and killing of An. arabiensis and to assess the effects of blend types, formulation, and residual activity on attractiveness of the POHD to An. arabiensis. The POHDs baited with attractive blends, carbon dioxide (CO2), and bendiocarb-treated electrostatic netting were placed either towards the top or bottom openings, and other modifications were exposed to An. arabiensis under the semifield system at Ifakara Health Institute (IHI). Each night, a total of 100 starved female, 3-7-day-old, semifield reared An. arabiensis mosquitoes were released, collected the next morning (alive or dead), counted, and recorded. Live mosquitoes were maintained in the semifield insectary and monitored for 24 hours mortality. Each treatment combination of the POHD was tested in three replicates. Overall, the results indicated that the proportion of mosquitoes attracted to and killed in the POHD varied with position of attractants and killing agent (bendiocarb). The POHD with bottom placed attractants and bendiocarb attracted and killed higher proportion of mosquitoes compared to the POHD with top placed attractants and bendiocarb. The highest mortalities were observed when the POHD was baited with a combination of attractive blends and CO2. Moreover, the residual activity of attractive blends applied inside POHD varied with type and formulation of attractive blend. The POHD packed with Mbita and Ifakara blend in microencapsulated pellets (granules) attracted higher proportion of mosquitoes than that baited with soaked nylon-strip formulation of either blends. Interestingly, POHD baited with Mbita blend in microencapsulated pellets (granules) formulation attracted and killed higher proportion of mosquitoes (>90%) than that baited with Ifakara blend even 9 months after application. Conclusively, the POHD remained effective for a relatively longer period of time when baited with bottom placed synthetic blends and CO2 combination, thus warranting further trials under real life situations.

The Use of Granular Cyclopentanone as Alternative to Artificial Source of Carbon Dioxide in Improved Passive Outdoor Host Seeking Device (POHD).

Reliable sources of CO2 that are relatively cheap, obtainable, and easy to sustain are immediately required for scaling up of odor-baited mosquito surveillance and control devices. Several odor-baited devices are in the pipeline; however, their scale-up against residual malaria transmission, particularly in resource poor areas, is limited by the unavailability of reliable sources of CO2 and reliance on electrical power sources among other factors. We evaluated the use of granular cyclopentanone as an alternative to artificial or yeast fermentation-produced CO2 in passive outdoor host seeking device (POHD). Experiments were conducted against semifield reared An. arabiensis within the semifield system (SFS) at Ifakara Health Institute. Mosquitoes were tested against odor-baited POHDs augmented with yeast fermentation-produced CO2, granular cyclopentanone, attractive blends (Mbita or Ifakara), or their combinations. An insecticide, bendiocarb, was a killing agent used as a proxy for marking the mosquitoes visit the POHDs. Relative attractiveness of different treatment combinations was compared based on the proportion of dead mosquitoes that visited the POHD. The POHD augmented with granules of cyclopentanone alone was attractive to An. arabiensis as much as, or more than, POHDs augmented with yeast fermentation-produced CO2. The POHD baited with CO2 attracted more mosquitoes than those POHDs baited with synthetic blends alone; when these blends are combined with CO2, they attracted more mosquitoes than individual blends. More importantly, such POHDs baited with cyclopentanone attracted far greater proportion of mosquitoes than the POHD baited with either Mbita or Ifakara blend alone. The granular cyclopentanone strongly enhanced/potentiated the attractiveness of POHD baited with Mbita blends against mosquitoes compared to that of POHD baited with Ifakara blend. Moreover, the granular cyclopentanone retained its residual activity against An. arabiensis for up to 2 months after application particularly when used in combination with Mbita blend. In conclusion, this study demonstrates that cyclopentanone granules have the potential to substitute sources of CO2 in outdoor-based surveillance and control devices, thus warranting evaluation of such alternative under realistic field conditions.

Passive Outdoor Host Seeking Device (POHD): Designing and Evaluation against Outdoor Biting Malaria Vectors.

Odor-baited devices are increasingly needed to compliment long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) for control of residual malaria transmission. However, the odor-baited devices developed so far are bulky, dependent on the source of electricity and carbon dioxide (CO2), and they are logistically unsuitable for scaling up in surveillance and control of malaria vectors. We designed a passive and portable outdoor host seeking device (POHD) and preliminarily evaluated suitable components against Anopheles arabiensis that maintains residual malaria transmission. Experiments were conducted using semifield reared An. arabiensis within the semifield system at Ifakara Health Institute (IHI) in southeastern Tanzania. These mosquitoes were exposed to Suna traps® baited with BG lures or source of light and augmented with carbon dioxide (CO2) in view of identifying best attractants necessary to improve attractiveness of designed POHD. Two Suna traps® were hanged at the corner but outside the experimental hut in a diagonal line and rotated between four corners to control for the effect of position and wind direction on mosquito catches. Furthermore, mosquitoes were also exposed to either a bendiocarb-treated or bendiocarb-untreated POHD baited with Mbita blend, Ifakara blend, and worn socks and augmented with warmth (i.e., 1.5 liter bottle of warm water) inside an experimental hut or a screened rectangular box. This study demonstrated that mosquitoes were more strongly attracted to Suna trap® baited with BG lures and CO2 relative to those traps baited with a source of light and CO2. The POHD baited with synthetic blends attracted and killed greater proportion of An. arabiensis compared with POHD baited with worn socks. Efficacy of the POHD was unaffected by source of warmth, and it was reduced by about 50% when the device was tested inside a screened rectangular box relative to closed experimental hut. Overall, this study demonstrates that the POHD baited with synthetic blends (Mbita and Ifakara blends) and bendiocarb can effectively attract and kill outdoor biting malaria vector species. Such POHD baited with synthetic blends may require the source of CO2 to enhance attractiveness to mosquitoes. Further trials are, therefore, ongoing to evaluate attractiveness of improved design of POHD baited with slow-release formulation of synthetic blends and sustainable source of CO2 to malaria vectors under semifield and natural environments.

Sanitary quality improvement of fish produced in the northern Benin cotton basin water reservoirs by cage culture and fish transfer in agricultural contaminant-free water: human health implications.

Northern Benin water reservoirs may remain valuable resources for fish production if the ecotoxicological risks related to agricultural pesticides are eradicated. The present work was undertaken (i) to evaluate sanitary quality and human health implications of fish (Clarias gariepinus and Oreochromis niloticus) reared in cages compared with those produced in pens installed in a contaminated water reservoir (Batran) and a reference water reservoir (Songhaï) and (ii) to test the efficacy of fish transferring to water without agricultural contaminants on fish health status. Pathogenic bacteria and pesticide residues were analyzed by phenotypic and biochemical identification and gas chromatography coupled with mass spectrometry, respectively. For both species, Aeromonas species occur in fish reared in pens at Batran. In Batran, regardless of infrastructure and species, residues of 4,4'-DDE (Dichlorodiphenyldichloroethylene) (1.4-4.9 µg/kg) and Chlorpyriphos (ethyl) (2.8-12.1 µg/kg) were measured, while only the last molecule was found in C. gariepinus from Songhaï (8.9-8.10 µg/kg). Irrespective of the species in the Batran water reservoir, Chlorpyriphos (ethyl) concentration was higher in cages and lower in pens, while 4, 4'-DDE was more concentrated in fish farmed in pens. Levels of these pesticide residues were well below World Health Organization/Food and Agriculture Organization permissible limits and the risk analyzed indicates no potential adverse health implications in consumption of these fish. Also, fish bacteriological quality was in compliance with the international standards. The fish decontamination approach used herein results in a reduction of the splenic macrophage phagocytic activity in both studied fish species.

Efficacy of Olyset Duo, a bednet containing pyriproxyfen and permethrin, versus a permethrin-only net against clinical malaria in an area with highly pyrethroid-resistant vectors in rural Burkina Faso: a cluster-randomised controlled trial.

BACKGROUND: Substantial reductions in malaria incidence in sub-Saharan Africa have been achieved with massive deployment of long-lasting insecticidal nets (LLINs), but pyrethroid resistance threatens control. Burkina Faso is an area with intense malaria transmission and highly pyrethroid-resistant vectors. We assessed the effectiveness of bednets containing permethrin, a pyrethroid, and pyriproxyfen, an insect growth regulator, versus permethrin-only (standard) LLINs against clinical malaria in children younger than 5 years in Banfora, Burkina Faso. METHODS: In this two-group, step-wedge, cluster-randomised, controlled, superiority trial, standard LLINs were incrementally replaced with LLINs treated with permethrin plus pyriproxyfen (PPF) in 40 rural clusters in Burkina Faso. In each cluster, 50 children (aged 6 months to 5 years) were followed up by passive case detection for clinical malaria. Cross-sectional surveys were done at the start and the end of the transmission seasons in 2014 and 2015. We did monthly collections from indoor light traps to estimate vector densities. Primary endpoints were the incidence of clinical malaria, measured by passive case detection, and the entomological inoculation rate. Analyses were adjusted for clustering and for month and health centre. This trial is registered as ISRCTN21853394. FINDINGS: 1980 children were enrolled in the cohort in 2014 and 2157 in 2015. At the end of the study, more than 99% of children slept under a bednet. The incidence of clinical malaria was 2·0 episodes per child-year in the standard LLIN group and 1·5 episodes per child-year in the PPF-treated LLIN group (incidence rate ratio 0·88 [95% CI 0·77-0·99; p=0·04]). The entomological inoculation rate was 85 (95% CI 63-108) infective bites per transmission season in the standard LLIN group versus 42 (32-52) infective bites per transmission season in the PPF-treated LLIN group (rate ratio 0·49, 95% CI 0·32-0·66; p<0·0001). INTERPRETATION: PPF-treated LLINs provide greater protection against clinical malaria than do standard LLINs and could be used as an alternative to standard LLINs in areas with intense transmission of Plasmodium falciparum malaria and highly pyrethroid-resistant vectors. FUNDING: EU Seventh Framework Programme.

Electrostatic coating enhances bioavailability of insecticides and breaks pyrethroid resistance in mosquitoes.

Insecticide resistance poses a significant and increasing threat to the control of malaria and other mosquito-borne diseases. We present a novel method of insecticide application based on netting treated with an electrostatic coating that binds insecticidal particles through polarity. Electrostatic netting can hold small amounts of insecticides effectively and results in enhanced bioavailability upon contact by the insect. Six pyrethroid-resistant Anopheles mosquito strains from across Africa were exposed to similar concentrations of deltamethrin on electrostatic netting or a standard long-lasting deltamethrin-coated bednet (PermaNet 2.0). Standard WHO exposure bioassays showed that electrostatic netting induced significantly higher mortality rates than the PermaNet, thereby effectively breaking mosquito resistance. Electrostatic netting also induced high mortality in resistant mosquito strains when a 15-fold lower dose of deltamethrin was applied and when the exposure time was reduced to only 5 s. Because different types of particles adhere to electrostatic netting, it is also possible to apply nonpyrethroid insecticides. Three insecticide classes were effective against strains of Aedes and Culex mosquitoes, demonstrating that electrostatic netting can be used to deploy a wide range of active insecticides against all major groups of disease-transmitting mosquitoes. Promising applications include the use of electrostatic coating on walls or eave curtains and in trapping/contamination devices. We conclude that application of electrostatically adhered particles boosts the efficacy of WHO-recommended insecticides even against resistant mosquitoes. This innovative technique has potential to support the use of unconventional insecticide classes or combinations thereof, potentially offering a significant step forward in managing insecticide resistance in vector-control operations.

Ivermectin-treated cattle reduces blood digestion, egg production and survival of a free-living population of Anopheles arabiensis under semi-field condition in south-eastern Tanzania.

BACKGROUND: Anopheles arabiensis feed on cattle and contributes to residual transmission of malaria in areas with high coverage of long-lasting insecticide-treated nets and indoor residual spraying in East Africa. This study aimed to evaluate the effects of ivermectin-treated cattle as a complementary vector control tool against population of An. arabiensis under the semi-field conditions in south-eastern Tanzania. METHODS: The free-living population of An. arabiensis was allowed to forage on untreated or ivermectin-treated cattle in alternating nights within the semi-field system in south-eastern Tanzania. Fresh blood fed mosquitoes were collected in the morning using mouth aspirators and assessed for their blood meal digestion, egg production, and survivorship. The residual activity of ivermectin-treated cattle was also determined by exposing mosquitoes to the same treatments after every 2 days until day 21 post-treatments. These experiments were replicated 3 times using different individual cattle. RESULTS: Overall, the ivermectin-treated cattle reduced blood meal digestion in the stomach of An. arabiensis, and their subsequent egg production and survival over time. The ivermectin-treated cattle halved blood meal digestion in mosquitoes, but reduced their egg production for up to 15 days. The ivermectin-treated cattle reduced the survival, and median survival times (1-3 days) of An. arabiensis than control cattle. The daily mortality rates of mosquitoes fed on ivermectin-treated cattle increased by five-fold relative to controls in the first week, and it gradually declined up to 21 days after treatment. CONCLUSION: This study demonstrates that long-lasting effects of ivermectin-treated cattle on egg production and survival of An. arabiensis may sustainably suppress their vector density, and reduce residual transmission of malaria. This study suggests that ivermectin-treated non-lactating cattle (i.e. calves, heifers and bulls) could be suitable option for large-scale malaria vector control without limiting consumption of milk and meat by communities in rural settings. Furthermore, simulation models are underway to predict the impact of ivermectin-treated cattle alone, or in combination with LLIN/IRS, the frequency of treatment, and their coverage required to significantly suppress population of An. arabiensis and reduce residual transmission of malaria.

Is there an association between mesenteric panniculitis and lymphoma? A case control analysis.

AIM: To determine the prevalence and association of mesenteric panniculitis (MP) in a group of patients with non-Hodgkin's lymphoma (NHL) compared to control group. MATERIALS AND METHODS: We retrospectively evaluated computed tomography (CT) and combined positron-emission tomography (PET) with CT examinations of a total of 166 patients who were diagnosed with NHL over a period of 5 years (2008-2013). The control group consisted of 332 subjects who were matched for gender and age at the time period the examinations were performed on the study group. A combination of radiological signs and absence of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-uptake was used to establish the diagnosis of MP and distinguish it from the involvement of mesentery by lymphoma. RESULTS: MP was identified in three patients (prevalence 1.8%) from the study group as compared to seven subjects out of 332 (2.1%) in the control group (p=0.556). During the course of follow-up no changes in the imaging features of MP were seen in either group. Additionally, 27 (16.2%) patients from the study group were found to have changes in the mesentery, which were attributed to the involvement of the mesentery in the primary disease. CONCLUSION: The prevalence of MP among patients with NHL was found to be 1.8%, which corresponds to the range of its prevalence in the general population. This is contrary to the proposition that MP is associated with NHL.

Eave tubes for malaria control in Africa: initial development and semi-field evaluations in Tanzania.

BACKGROUND: Presented here are a series of preliminary experiments evaluating "eave tubes"-a technology that combines house screening with a novel method of delivering insecticides for control of malaria mosquitoes. METHODS: Eave tubes were first evaluated with overnight release and recapture of mosquitoes in a screened compartment containing a hut and human sleeper. Recapture numbers were used as a proxy for overnight survival. These trials tested physical characteristics of the eave tubes (height, diameter, angle), and different active ingredients (bendiocarb, LLIN material, fungus). Eave tubes in a hut with closed eaves were also compared to an LLIN protecting a sleeper in a hut with open eaves. Eave tubes were then evaluated in a larger compartment containing a self-replicating mosquito population, vegetation, and multiple houses and cattle sheds. In this "model village", LLINs were introduced first, followed by eave tubes and associated house modifications. RESULTS: Initial testing suggested that tubes placed horizontally and at eave height had the biggest impact on mosquito recapture relative to respective controls. Comparison of active ingredients suggested roughly equivalent effects from bendiocarb, LLIN material, and fungal spores (although speed of kill was slower for fungus). The impact of treated netting on recapture rates ranged from 50 to 70 % reduction relative to controls. In subsequent experiments comparing bendiocarb-treated netting in eave tubes against a standard LLIN, the effect size was smaller but the eave tubes with closed eaves performed at least as well as the LLIN with open eaves. In the model village, introducing LLINs led to an approximate 60 % reduction in larval densities and 85 % reduction in indoor catches of host-seeking mosquitoes relative to pre-intervention values. Installing eave tubes and screening further reduced larval density (93 % relative to pre intervention values) and virtually eliminated indoor host-seeking mosquitoes. When the eave tubes and screening were removed, larval and adult catches recovered to pre-eave tube levels. CONCLUSIONS: These trials suggest that the "eave tube" package can impact overnight survival of host-seeking mosquitoes and can suppress mosquito populations, even in a complex environment. Further testing is now required to evaluate the robustness of these findings and demonstrate impact under field conditions.

Eave tubes for malaria control in Africa: an introduction.

In spite of massive progress in the control of African malaria since the turn of the century, there is a clear and recognized need for additional tools beyond long-lasting insecticide-treated bed nets (LLINs) and indoor residual spraying (IRS) of insecticides, to progress towards elimination. Moreover, widespread and intensifying insecticide resistance requires alternative control agents and delivery systems to enable development of effective insecticide resistance management strategies. This series of articles presents a novel concept for malaria vector control, the 'eave tube', which may fulfil these important criteria. From its conceptualization to laboratory and semi-field testing, to demonstration of potential for implementation, the stepwise development of this new vector control approach is described. These studies suggest eave tubes (which comprise a novel way of delivering insecticides plus screening to make the house more 'mosquito proof') could be a viable, cost-effective, and acceptable control tool for endophilic and endophagic anophelines, and possibly other (nuisance) mosquitoes. The approach could be applicable in a wide variety of housing in sub-Saharan Africa, and possibly beyond, for vectors that use the eave as their primary house entry point. The results presented in these articles were generated during an EU-FP7 funded project, the mosquito contamination device (MCD) project, which ran between 2012 and 2015. This was a collaborative project undertaken by vector biologists, product developers, modellers, materials scientists, and entrepreneurs from five different countries.

Laparoscopy following peritoneal entry during transanal endoscopic microsurgery may increase the safety and maximize the benefits of the transanal excision.

BACKGROUND: Peritoneal entry (PE) during transanal endoscopic microsurgery (TEM) for tumors of the upper rectum is not an uncommon complication. The suture line of the rectal defect performed for PE is not devoid of leaks. Diagnostic laparoscopy after PE enables visualization and testing of the suture line. Here, we report the outcome of patients undergoing laparoscopy for PE following TEM. METHODS: Data pertaining to patients undergoing laparoscopy for PE following TEM between 2004 and 2013 were retrospectively collected. RESULTS: One hundred and forty-one TEM procedures were performed, and 19 (13 %) with PE were included. The mean age was 68.1 ± 10.6 years, mean distance from the anal verge 12.5 ± 2 cm, and mean tumor size 2 cm. Lesions were located in the lateral wall (n = 14), anteriorly (n = 4), and posteriorly (n = 1). Indications for TEM were: adenoma (n = 13), indeterminate margins after polypectomy (n = 4, a submucosal lesion (n = 1), and a T1N0 adenocarcinoma (n = 1). In all patients, the rectal wall defect was closed primarily. Twelve patients underwent additional laparoscopy and suture line leak testing. In one patient, a small leak was detected which was repaired laparoscopically. In another, a hematoma of the suture line was observed and a drain was left in place. The mean operative time was 109 min (range 80-135 min) for TEM and 33 min (range 22-45 min) for laparoscopy. A diverting ileostomy was fashioned in one patient on postoperative day 3 after TEM without laparoscopy. No other major complications were observed. CONCLUSIONS: Laparoscopy after PE during TEM permits visualization and testing of the suture line. It is not associated with increased morbidity, and it may increase the safety of TEM.

The impact of livestock on the abundance, resting behaviour and sporozoite rate of malaria vectors in southern Tanzania.

BACKGROUND: Increases in the coverage of long-lasting insecticidal nets (LLINs) have significantly reduced the abundance of Anopheles gambiae sensu stricto in several African settings, leaving its more zoophagic sibling species Anopheles arabiensis as the primary vector. This study investigated the impact of livestock ownership at the household level on the ecology and malaria infection rate of vectors in an area of Tanzania where An. arabiensis accounts for most malaria transmission. METHODS: Mosquito vectors were collected resting inside houses, animal sheds and in outdoor resting boxes at households with and without livestock over three years in ten villages of the Kilombero Valley, Tanzania. Additionally, the abundance and sporozoite rate of vectors attempting to bite indoors at these households was assessed as an index of malaria exposure. RESULTS: The mean abundance of An. gambiae s.l. biting indoors was similar at houses with and without livestock. In all years but one, the relative proportion of An. arabiensis within the An. gambiae s.l. species complex was higher at households with livestock. Livestock presence had a significant impact on malaria vector feeding and resting behaviour. Anopheles arabiensis were generally found resting in cattle sheds where livestock were present, and inside houses when absent. Correspondingly, the human blood index of An. arabiensis and An. funestus s.l. was significant reduced at households with livestock, whereas that of An. gambiae s.s. was unaffected. Whilst there was some evidence that sporozoite rates within the indoor-biting An. gambiae s.l population was significantly reduced at households with livestock, the significance of this effect varied depending on how background spatial variation was accounted for. CONCLUSIONS: These results confirm that the presence of cattle at the household level can significantly alter the local species composition, feeding and resting behaviour of malaria vectors. However, the net impact of this livestock-associated variation in mosquito ecology on malaria exposure risk was unclear. Further investigation is required to distinguish whether the apparently lower sporozoite rates observed in An. gambiae s.l. at households with livestock is really a direct effect of cattle presence, or an indirect consequence of reduced risk within areas where livestock keepers choose to live.

Genomic integrity of the Y chromosome sequence-tagged-sites in infertile and Down syndrome Jordanian males.

The long arm of the Y chromosome contains nonoverlapping regions termed azoospermia factor (AZF) with great influence on male fertility. Microdeletions at these regions minimise the males' ability to father offsprings. In this preliminary study, we attempted to screen the presence or absence of twenty Y chromosome's sequence-tagged sites (STS) associated with fertility in infertile and Down syndrome (DS) males. Genomic DNA from 35 fertile, 74 infertile and 22 karyotyped DS males was extracted and amplified in multiplex polymerase chain reaction (PCR) containing 20 primer pairs that amplify Y-specific STS that cover functional regions associated with AZF and spermatogenesis-related genes. Our results indicated the integrity of the Y chromosome at the 20 fertility markers for both the fertile and Down syndrome males. However, the results of the infertile males showed the presence of microdeletions at these Y-specific STS. Three samples showed Y chromosome microdeletion when blood and seminal fluid genomic DNA were assayed, while two samples showed microdeletion only when seminal fluid genomic DNA was assayed. The current study demonstrated that the molecular genetic aspect of infertility should be given proper attention when dealing with infertility cases. Furthermore, our results indicate the importance of genetic counselling in managing infertility cases.

Evaluation of the DN-Mini (miniaturized double net) trap for sampling host-seeking Anopheles mosquitoes in malaria-endemic villages of southern Tanzania.

BACKGROUND: Surveillance of malaria vectors is crucial for assessing the transmission risk and impact of control measures. Human landing catches (HLC) directly estimate the biting rates but raise ethical concerns due to the exposure of volunteers to mosquito-borne pathogens. A common alternative is the CDC-light trap, which is effective for catching host-seeking mosquitoes indoors but not outdoors. New, exposure-free methods are needed for sampling mosquitoes indoors and outdoors in ways that reflect their natural risk profiles. The aim of this study was therefore to evaluate the efficacy of the miniaturized double net trap (DN-Mini) for sampling host-seeking mosquitoes in south-eastern Tanzania, where malaria transmission is dominated by Anopheles funestus. METHODS: Adult mosquitoes were collected from 222 randomly selected houses across three villages (74 per village) in Ulanga district, south-eastern Tanzania, using the DN-Mini traps, CDC-Light traps, and Prokopack aspirators. First, we compared CDC-light and DN-Mini traps for collecting indoor host-seeking mosquitoes, while Prokopack aspirators were used for indoor-resting mosquitoes. Second, we deployed the DN-Mini and Prokopack aspirators to collect host-seeking and resting mosquitoes indoors and outdoors. Generalized linear mixed models (GLMM) with a negative binomial distribution were used to compare the effectiveness of the traps for catching different mosquito species. RESULTS: The DN-Mini was 1.53 times more efficient in collecting An. funestus indoors (RR = 1.53, 95% CI: 1.190-1.98) compared to the CDC-Light trap. However, for Anopheles arabiensis, the DN-Mini caught only 0.32 times as many mosquitoes indoors as the CDC-Light traps (RR = 0.32, 95% CI: 0.183-0.567). Both An. funestus and An. arabiensis were found to be more abundant indoors than outdoors when collected using the DN-Mini trap. Similarly, the Prokopack aspirator was greater indoors than outdoors for both An. funestus and An. arabiensis. CONCLUSION: The DN-Mini outperformed the CDC-light trap in sampling the dominant malaria vector, An. funestus species, but was less effective in capturing An. arabiensis, and for both vector species, the biting risk was greater indoors than outdoors when measured using the DN-Mini trap. These findings highlight the importance of selecting appropriate trapping methods based on mosquito species and behaviors.

Solicited Cough Sound Analysis for Tuberculosis Triage Testing: The CODA TB DREAM Challenge Dataset.

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial.

INTRODUCTION: Seasonal malaria chemoprevention (SMC) involves repeated administrations of sulfadoxine-pyrimethamine plus amodiaquine to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. While highly impactful in reducing Plasmodium falciparum malaria burden in controlled research settings, the impact of SMC on infection prevalence is moderate in real-life settings. It remains unclear what drives this efficacy decay. Recently, the WHO widened the scope for SMC to target all vulnerable populations. The Ministry of Health (MoH) in Burkina Faso is considering extending SMC to children below 10 years old. We aim to assess the impact of SMC on clinical incidence and parasite prevalence and quantify the human infectious reservoir for malaria in this population. METHODS AND ANALYSIS: We will perform a cluster randomised trial in Saponé Health District, Burkina Faso, with three study arms comprising 62 clusters of three compounds: arm 1 (control): SMC in under 5-year-old children, implemented by the MoH without directly observed treatment (DOT) for the full course of SMC; arm 2 (intervention): SMC in under 5-year-old children, with DOT for the full course of SMC; arm 3 (intervention): SMC in under 10-year-old children, with DOT for the full course of SMC. The primary endpoint is parasite prevalence at the end of the malaria transmission season. Secondary endpoints include the impact of SMC on clinical incidence. Factors affecting SMC uptake, treatment adherence, drug concentrations, parasite resistance markers and transmission of parasites will be determined. ETHICS AND DISSEMINATION: The London School of Hygiene & Tropical Medicine's Ethics Committee (29193) and the Burkina Faso National Medical Ethics Committee (Deliberation No 2023-05-104) approved this study. The findings will be presented to the community; disease occurrence data and study outcomes will also be shared with the Burkina Faso MoH. Findings will be published irrespective of their results. TRIAL REGISTRATION NUMBER: NCT05878366.

A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults.

BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36-amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 µg or 100 µg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 µg or 50 µg, respectively). The allocation was random and double-blind for this phase I trial.RESULTSThe vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 µg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).

Effect of weekly fever-screening and treatment and monthly RDT testing and treatment on the infectious reservoir of malaria parasites in Burkina Faso: a cluster-randomised trial.

BACKGROUND: The majority of Plasmodium spp infections in endemic countries are asymptomatic and a source of onward transmission to mosquitoes. We aimed to examine whether Plasmodium falciparum transmission and malaria burden could be reduced by improving early detection and treatment of infections with active screening approaches. METHODS: In this 18-month cluster randomised study in Sapone, Burkina Faso, households were enrolled and randomly assigned (1:1:1) to one of three groups: group 1 (control) received standard of care only, group 2 received active weekly, at home, fever screening by a community health worker regardless of symptoms, participants with a fever received a rapid diagnostic test (RDT) and treatment if RDT positive, and group 3 received active weekly fever screening (as in group 2) plus a monthly RDT regardless of symptoms, and treatment if RDT positive. Eligible households had a minimum of three eligible residents, one in each age group (<5 years, 5-15 years, and >15 years). The primary outcome was parasite prevalence by quantitative PCR (qPCR) in the end-of-study cross-sectional survey. Secondary outcomes included parasite and gametocyte prevalence and density in all three end-of-season cross-sectional surveys, incidence of infection, and the transmissibility of infections to mosquitoes. This trial was registered at ClinicalTrials.gov (NCT03705624) and is completed. FINDINGS: A total of 906 individuals from 181 households were enrolled during two phases, and participated in the study. 412 individuals were enrolled between Aug 9 and 17, 2018, and participated in phase 1 and 494 individuals were enrolled between Jan 10 and 31, 2019, in phase 2. In the end-of-study cross-sectional survey (conducted between Jan 13 and 21, 2020), Pfalciparum prevalence by qPCR was significantly lower in group 3 (29·26%; 79 of 270), but not in group 2 (45·66%; 121 of 265), when compared with group 1 (48·72%; 133 of 273; risk ratio 0·65 [95% CI 0·52-0·81]; p=0·0001). Total parasite and gametocyte prevalence and density were also significantly lower in group 3 in all surveys. The largest differences were seen at the end of the dry season, with gametocyte prevalence 78·4% and predicted transmission potential 98·2% lower in group 3 than in group 1. INTERPRETATION: Active monthly RDT testing and treatment can reduce parasite carriage and the infectious reservoir of P falciparum to less than 2% when used during the dry season. This insight might inform approaches for malaria control and elimination. FUNDING: Bill & Melinda Gates Foundation, European Research Council, and The Netherlands Organization for Scientific Research.