Search

Abstract 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.

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.

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.

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.

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.

Abstract 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.

Background: Resistance of malaria parasites to existing drugs complicates treatment, but an antimalarial vaccine that could protect against this disease is not yet available. It is therefore necessary to find new effective and affordable medicines. Medicinal plants could be a potential source of antimalarial agents. Some medicinal plants from Burkina Faso were evaluated for their antiplasmodial and cytotoxic properties in vitro. Methods: Crude dichloromethane, methanol, water-methanol, aqueous and alkaloids extracts were prepared for 12 parts of 10 plants. Chloroquine-resistant malaria strain K1 was used for the in vitro sensibility assay. The Plasmodium lactacte dehydrogenase technique was used to determine the 50% inhibitory concentration of parasites activity (IC50). The cytotoxic effects were determined with HepG2 cells, using the tetrazolium-based colorimetric technique, and the selectivity index (SI) was calculated. Results: Sixty crude extracts were prepared. Seven extracts from Terminalia avicenoides showed IC50 1. The other plants have mostly moderate or no antimalarial effects. Some extracts from Cordia myxa, Ficus capraefolia and Opilia celtidifolia showed cytotoxicity, with an SI ranging between 0.4 and 0.9. Conclusion: Our study showed a good antiplasmodial in vitro activity of Terminalia avicenoides, Combretum collinum and Ficus capraefolia. These three plants may contain antiplasmodial molecules that could be isolated by bio-guided phytochemical studies.

Background. Anopheles arabiensis is increasingly dominating malaria transmission in Africa. The exophagy in mosquitoes threatens the effectiveness of indoor vector control strategies. This study aimed to evaluate the effectiveness of fungus against An. arabiensis when applied on cattle and their environments. Methods. Experiments were conducted under semi-field and small-scale field conditions within Kilombero valley. The semi-field reared females of 5–7 days old An. arabiensis were exposed to fungus-treated and untreated calf. Further, wild An. arabiensis were exposed to fungus-treated calves, mud-huts, and their controls. Mosquitoes were recaptured the next morning and proportion fed, infected, and survived were evaluated. Experiments were replicated three times using different individuals of calves. Results. A high proportion of An. arabiensis was fed on calves (>0.90) and become infected (0.94) while resting on fungus-treated mud walls than on other surfaces. However, fungus treatments reduced fecundity and survival of mosquitoes. Conclusion. This study demonstrates for the first time the potential of cattle and their milieu for controlling An. arabiensis. Most of An. arabiensis were fed and infected while resting on fungus-treated mud walls than on other surfaces. Fungus treatments reduced fecundity and survival of mosquitoes. These results suggest deployment of bioinsecticide zooprophylaxis against exophilic An. arabiensis.

Intermittent preventive treatment of malaria in children (IPTc) is a promising new approach to the control of malaria in areas of seasonal malaria transmission but it is not known if IPTc adds to the protection provided by an insecticide-treated net (ITN).An individually randomised, double-blind, placebo-controlled trial of seasonal IPTc was conducted in Burkina Faso in children aged 3 to 59 months who were provided with a long-lasting insecticide-treated bednet (LLIN). Three rounds of treatment with sulphadoxine pyrimethamine plus amodiaquine or placebos were given at monthly intervals during the malaria transmission season. Passive surveillance for malaria episodes was established, a cross-sectional survey was conducted at the end of the malaria transmission season, and use of ITNs was monitored during the intervention period. Incidence rates of malaria were compared using a Cox regression model and generalized linear models were fitted to examine the effect of IPTc on the prevalence of malaria infection, anaemia, and on anthropometric indicators. 3,052 children were screened and 3,014 were enrolled in the trial; 1,505 in the control arm and 1,509 in the intervention arm. Similar proportions of children in the two treatment arms were reported to sleep under an LLIN during the intervention period (93%). The incidence of malaria, defined as fever or history of fever with parasitaemia ≥ 5,000/µl, was 2.88 (95% confidence interval [CI] 2.70-3.06) per child during the intervention period in the control arm versus 0.87 (95% CI 0.78-0.97) in the intervention arm, a protective efficacy (PE) of 70% (95% CI 66%-74%) (p

Interventions that reduce exposure to malaria infection may lead to delayed malaria morbidity and mortality. We investigated whether intermittent preventive treatment of malaria in children (IPTc) was associated with an increase in the incidence of malaria after cessation of the intervention.An individually randomised, trial of IPTc, comparing three courses of sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) with placebos was implemented in children aged 3-59 months during the 2008 malaria transmission season in Burkina Faso. All children in the trial were given a long lasting insecticide treated net; 1509 children received SP+AQ and 1505 received placebos. Passive surveillance for malaria was maintained until the end of the subsequent malaria transmission season in 2009, and active surveillance for malaria infection, anaemia and malnutrition was conducted.On thousand, four hundred and sixteen children (93.8%) and 1399 children (93.0%) initially enrolled in the intervention and control arms of the trial respectively were followed during the 2009 malaria transmission season. During the period July 2009 to November 2009, incidence rates of clinical malaria were 3.84 (95%CI; 3.67-4.02) and 3.45 (95%CI; 3.29-3.62) episodes per child during the follow up period in children who had previously received IPT or placebos, indicating a small increase in risk for children in the former intervention arm (IRR = 1.12; 95%CI 1.04-1.20) (P = 0.003). Children who had received SP+AQ had a lower prevalence of malaria infection (adjusted PR: 0.88 95%CI: 0.79-0.98) (P = 0.04) but they had a higher parasite density (P = 0.001) if they were infected. There was no evidence that the risks of moderately severe anaemia (Hb

BACKGROUND. Malaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another. METHODS. The 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 [micro]g or 100 [micro]g R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 [micro]g or 50 [micro]g, respectively). The allocation was random and double-blind for this phase I trial. RESULTS. The 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 [micro]g 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. CONCLUSION. All 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 REGISTRATION. Pan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189. FUNDING. The study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311)., Introduction Plasmodium falciparum malaria is transmitted by mosquitoes of the genus Anopheles. During a blood meal from an infected person, the female mosquito ingests sexual-stage parasites, which fertilize in the [...]