Transmission Season Research Articles

Impact of nighttime human behavior on exposure to malaria vectors and effectiveness of using long-lasting insecticidal nets in the Ethiopian lowlands and highlands

BackgroundEthiopia continues to grapple with a persistent malaria burden, characterized by ongoing transmission and recurrent outbreaks. Human behavior influences both malaria exposure and the effectiveness of vector interventions, complicating malaria control efforts. Implementing tailored strategies that account for the complex interplay between human activities and vector behavior remains a challenge in both high- and low-transmission areas in Ethiopia, particularly for vulnerable highland populations and temporary labor migrants, due to lack of data. The aim of this study was to examine the spatiotemporal patterns of human—mosquito interactions and evaluate the effectiveness and suitability of long-lasting insecticidal nets (LLINs) in settings involving lowland resident populations, seasonal migrant workers and highland communities.MethodsConcurrent human and vector behavior data were collected from high-transmission lowlands (residents and temporary migrant workers) and vulnerable highlands populations. Hourly human behavior observations (HBOs), which examined LLIN use, indoor versus outdoor human presence and sleeping patterns, were paired in a crossover design with mosquito sampling using US Centers for Disease Control light traps (CDC LT) as a proxy for mosquito biting behavior. The study was conducted during the peak (October–December 2022) and minor (March–May 2023) malaria transmission seasons (‘peak’ and ‘minor’) for a total of 368 nights. In the highlands, four villages consisting of eight households per village were selected for surveillance; in the lowlands, four villages consisting of two resident villages and two farm sites with migrant workers, with eight households/structures per village or farm, were used for data collection. CDC LT and HBO data were integrated to evaluate HBO-adjusted human biting rates (HBO-adjusted HBR) of Anopheles mosquitoes.ResultsIn the highland villages, residents predominantly engaged in indoor activities, with their peak activity overlapping with the peak biting hours (1800-2200 hours). A substantial proportion of inhabitants slept indoors without LLINs in the peak and minor seasons (42.8% and 39.2%, respectively). Highland residents were significantly more exposed to malaria vectors indoors (88.4% peak, 88.6% minor) than outdoors during both transmission seasons. In lowland villages, both resident and seasonal migrant worker populations exhibited predominantly outdoor activity, particularly during peak biting hours (1800-2300 hours). Both residents and temporary migrants were significantly more exposed to Anopheles mosquitoes outdoors (resident: 65.0% peak, 67.1% minor; migrant: 70.5% peak, 80.0% minor) than indoors during both transmission seasons. LLIN usage was minimal and offered limited protection, with < 16.63% of person-time spent under nets by resident populations and 10.7% by migrant workers.ConclusionsMalaria control in Ethiopia requires context-specific strategies tailored to diverse ecological settings that consider the impact of human behavior on exposure to Anopheles mosquitoes. Limited LLIN effectiveness, human activities coinciding with peak biting times and minimal LLIN usage create significant protection gaps. Comprehensive control necessitates supplemental tools addressing exposure in all locations and times. In the Ethiopian highlands, where indoor activities predominate, increased LLIN usage combined with targeted indoor residual spraying could reduce transmission. In lowland areas, both residents and seasonal migrant workers face relatively higher outdoor exposure risks, requiring additional measures, such as topical and spatial repellents. We recommend implementing data-driven, hyperlocal approaches based on specific human—vector interactions to enhance malaria control effectiveness across the Ethiopian highlands and lowlands.Graphical

Effect of seasonal malaria chemoprevention on incidence of malaria among children under five years in Kotido and Moroto Districts, Uganda, 2021: time series analysis

BackgroundSeasonal malaria chemoprevention (SMC) refers to monthly administration of full treatment courses of anti-malarial medicine to children <5 years during high malaria transmission seasons. SMC has demonstrated effectiveness in Sahel and sub-Sahel countries in Africa. However, it was not implemented in Uganda until April 2021, when the country began SMC in the highly malaria-endemic Kotido and Moroto Districts. This study assessed the effect of SMC on malaria incidence among children <5 years of age in Kotido and Moroto Districts.MethodsAn interrupted time-series analysis was conducted using monthly national health data from the Uganda Ministry of Health District Health Information System 2. The monthly data for outpatient (uncomplicated) malaria among children <5 years was extracted for the 52 months before SMC implementation (Jan 2017–Apr 2021) and 8 months during SMC implementation (May–Dec 2021). The monthly incidence of uncomplicated malaria per 1000 children <5 years was computed before and during SMC implementation.ResultsIn Kotido District, malaria incidence was 693/1000 during SMC implementation period, compared to an expected 1216/1000 if SMC had not been implemented. The mean monthly malaria incidence was 87/1000, compared to an expected mean of 152/1000 if SMC had not been implemented. This represents a statistically significant mean monthly change of −65.4 (95% CI = −104.6, −26.2) malaria cases/1000 during SMC implementation, or a 43.0% decline. In Moroto District, malaria incidence was 713/1000 during SMC implementation period, compared to an expected 905/1000 if SMC had not been implemented. The mean monthly malaria incidence was 89/1000, compared to an expected 113/1000 if SMC had not been deployed. This represents a statistically significant mean monthly change of −24.0 (95% CI = −41.1, −6.8) malaria cases/1000 during SMC implementation, or a 21.2% decline.ConclusionImplementation of SMC substantially reduced the incidence of uncomplicated malaria among children <5 years in Moroto and Kotido Districts. Scaling up SMC in other districts with high malaria transmission could reduce malaria on a large scale across Uganda.

Microscopic prevalence and risk factors of asymptomatic malaria in Gorgora, western Dembia, Northwest Ethiopia: exploring hidden threats during minor transmission season

BackgroundMalaria poses a significant public health threat globally, particularly in African regions, where asymptomatic malaria is a considerable logistic problem. Individuals with asymptomatic malaria do not seek treatment, and thus they are invisible to health facilities and represent a substantial hidden reservoir of Plasmodium species. This study aimed to determine the prevalence of asymptomatic malaria and its associated factors in Gorgora, western Dembia district, Northwest Ethiopia.MethodsA community-based cross-sectional study was conducted from May to June 2023 in the Gorgora area, Western Dembia district, Northwest Ethiopia. Data were collected using a semi-structured questionnaire. Giemsa-stained blood smear microscopy was employed for the diagnosis of Plasmodium species. The data were entered into Epi Data version 4.6 and exported to SPSS version 25 for analysis. Bivariate and multivariable binary logistic regression analyses were conducted to identify associated factors.ResultsAmong the 357 individuals who participated in this study, 9.2% (33/357) [95% CI 6.40–12.70: p = 0.000] were confirmed to be infected with Plasmodium species. Plasmodium falciparum and Plasmodium vivax accounted for 66.7% and 33.3%, respectively. Not using bed nets [AOR = 7.3, 95% CI 2.08–23.46, p = 0.006)], previous malaria history [AOR = 2.6, 95% CI 1.01–6.45, p = 0.041], outdoor activities at night [AOR = 8.3, 95% CI 3.21–21.30, p = 0.000], and family size [AOR = 3.3, 95% CI 1.18–9.22, p = 0.023] were significantly associated with asymptomatic malaria (p < 0.05).ConclusionsA considerable proportion of asymptomatic Plasmodium infections was found which likely act as a reservoir of transmission. This has implications for ongoing malaria control programmes that are based on the treatment of symptomatic patients and highlight the need for intervention strategies targeting asymptomatic carriers. Not using bed nets, engaging in outdoor activities at night, and having a family size of more than five increased the odds of developing asymptomatic malaria. The district health office and health extension workers should collaborate to promote the regular use of mosquito bed nets among community residents.

Role of surveillance data in detecting malaria outbreaks in an epidemic-prone region in Kenya: findings from an investigation of a suspected outbreak in Nandi County

BackgroundApproximately 70% of the Kenyan population is at risk for malaria, including 19 million people in highland epidemic-prone and seasonal transmission areas. Surveillance data showed a 288% increase in malaria cases and an incidence rate of 10.5 per 1000 population between January and May 2021 in Nandi County. We investigated the increased incidence of malaria in Nandi County.MethodsWe abstracted demographic and clinical data from the laboratory register in health facilities with high malaria burden. Key informant interviews using a structured questionnaire collected healthcare worker perceptions on malaria interventions and personnel capacity. We calculated means and medians for continuous variables and frequency and proportions for categorical variables. Data quality assessment (DQA) was conducted to evaluate timeliness and completeness, data accuracy, and overall system assessment.ResultsWe reviewed 19,526 records from 12 health facilities. Females contributed 61% cases (11,862). A majority of cases, 21% (4111), were between the age group 15–24 years. Of the 19,498 tested, 2662 tested positive (test positivity rate, TPR = 13.7%). Microscopy accounted for 39% (1041) and RDT for 61% (1620) of tests conducted, with some patients being double tested using both tests. Kapsabet County Referral contributed 26% (5051) suspected cases, TPR 3.2%, and Chemase Health Centre TPR was 33.2%. Facilities experienced major RDTs stock-outs in the preceding 3 months while three (30%) of the 10 facilities assessed conducted laboratory Internal Quality Control (IQC) programmes. Of the 12 facilities assessed, four (33%) facilities had an over-reporting of suspected cases in the monthly summary, while three (25%) facilities were over-reported in the online tool. On reporting confirmed malaria cases, over-reporting was noted in three (25%) facilities in both the monthly summaries and the online tool. Data completeness was 77% and timeliness 93%.ConclusionThe increase in malaria cases in Nandi County displayed a seasonal pattern that coincided with either the long or short rainy seasons, the investigation did not reveal an active outbreak at the time of the inquiry. Sub-county hospitals in Tinderet and Aldai sub-counties had malaria cases exceeding both the alert and action thresholds at specific times during the year under review, suggesting a potential occurrence of unidentified outbreaks, while several other facilities had an increase of cases reaching alert thresholds, indicating upsurges. In healthcare settings, we noted there were problems with data quality. We advised routine data review, analysis, and feedback; mentorships for data analysis and on the job and support supervision; mentorships for malaria diagnosis; and installation of laboratory quality assurance.

In vitro and in vivo characterization of a novel West Nile virus lineage 2 strain

Over recent decades, West Nile virus (WNV) has continued to expand its geographical range, emerging in previously non-endemic areas, including northern Europe. In Europe, WNV lineage 2 strains are most prevalent and cause sporadic outbreaks of WNV disease in humans each transmission season. Here, we assessed the virulence of a newly emerged WNV lineage 2 strain that was isolated in the Netherlands in 2020 (WNV-NL20) and caused several cases of West Nile disease in humans and used a WNV lineage 2 strain related to major outbreaks of neuroinvasive disease in humans in central and south-eastern Europe in 2010 (WNV-578/10) as a reference. Infection of primary human cells of the blood-brain barrier in vitro did not show major differences in replication kinetics between WNV-578/10 and WNV-NL20. Experimental infection of mice showed that both WNV strains induced significant weight loss, neurological signs, and lethal disease. Neurological involvement was confirmed for both WNV strains by the presence of infectious virus and viral antigen in the brain. In conclusion, we show that the recent WNV-NL20 strain that emerged in the Netherlands is neurovirulent in mice. The use of in vitro and in vivo models to characterize the pathogenesis of emerging WNV strains may aid in predicting the neurovirulence of WNV infections in humans during potential future outbreaks.

Closing the gap in race-based inequities for seasonal influenza hospitalizations: a modeling study.

BIPOC (Black, Indigenous, and other People of Color) communities bear a disproportional burden of seasonal influenza hospitalizations in the United States. We developed a race-stratified (5 racial-ethnic groups) agent-based model of seasonal influenza transmission and quantify the effects of 5 idealized interventions aimed at reducing inequities in symptomatic infections and hospitalizations. The interventions assumed (i) equalized vaccination rates, (ii) equalized comorbidities, (iii) work-risk distribution proportional to the distribution of the population, (iv) reduced work contacts for all, or (v) a combination of equalizing vaccination rates and comorbidities and reducing work contacts. Our analysis suggests that symptomatic infections could be greatly reduced (by up to 17% in BIPOC adults aged 18-49) by strategies reducing work contacts or equalizing vaccination rates. All tested interventions reduced the inequity in influenza hospitalizations in all racial-ethnic groups, but interventions equalizing comorbidities were the most effective, with over 40% less hospitalizations in BIPOC groups. Inequities in hospitalizations in different racial-ethnic groups responded differently to interventions, pointing to the need of tailored interventions for different populations. Notably, these interventions resulted in better outcomes across all racial-ethnic groups, not only those prioritized by the interventions. In this simulation modeling study, equalizing vaccination rates and reducing number of work contacts (e.g., improving air filtration systems, tailored vaccination campaigns) reduced both inequity and the total number of symptomatic infections and hospitalizations in all age and racial-ethnic groups. Reducing inequity in influenza hospitalizations requires different interventions for different groups.

Severe Malaria in Angola: The Clinical Profile and Disease Outcome Among Adults from a Low-Endemic Area.

Severe malaria poses a significant public health concern in Angola, particularly among adults. This study assessed the clinical manifestations and outcomes of severe Plasmodium falciparum malaria in adult patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango (HCL), Angola. The study retrospectively reviewed medical records of patients over 14 years old admitted with severe malaria during the first quarter of 2021 and 2022, coinciding with the peak transmission season. The World Health Organization (WHO) criteria were used to clarify the disease severity. The cohort included 640 patients-167 in 2021 and 473 in 2022-distributed across the following departments: the Intensive Care Unit (ICU; n = 81), Medicine (MED; n = 458) and Infectiology (INF; n = 101). The median age was 26 years and 59.4% were males. Renal impairment was the most frequent severe manifestation, affecting 37.4% of cases. The mortality rate across the study period was 7%, showing a notable decrease from 10.2% in 2021 to 5.9% in 2022. The higher mortality rate in 2021 may reflect the impact of the COVID-19 pandemic, which limited hospital access and delayed care, resulting in more critical cases being admitted at a later stage. In 2022, with reduced COVID-19 pressures, earlier access to treatment may have improved outcomes, contributing to the lower mortality rate. This study emphasizes the need to assess the clinical burden of severe malaria in low-endemic regions, where shifting patterns may signal emerging threats such as antimalarial drug resistance. Further research is essential to optimize control strategies and strengthen surveillance systems, reducing morbidity and mortality.

Efficacy of attractive targeted sugar bait stations against malaria in Western Province Zambia: epidemiological findings from a two-arm cluster randomized phase III trial

BackgroundAttractive targeted sugar bait (ATSB) stations containing bait (to attract) and ingestion toxicant (to kill) sugar-foraging mosquitoes are hypothesized to reduce malaria transmission by shortening the lifespan of Anopheles vectors.MethodsA two-arm cluster-randomized controlled trial (cRCT) was conducted in Western Province Zambia. Seventy clusters of 250–350 households were assigned (1:1) by restricted randomization to an intervention arm (ATSB) or control arm (no ATSB) in the context of standard of care vector control (insecticide-treated nets and/or indoor residual spraying). Two ATSB stations (Westham Sarabi, 0.11% dinotefuran w/w) were maintained on exterior walls of eligible household structures for a 7-month deployment period (December-June) during the high malaria transmission season. The primary outcome was clinical malaria incidence among two consecutive seasonal cohorts of children aged 1–14 years, followed-up monthly from January-June in 2022 and 2023. Secondary outcome was Plasmodium falciparum prevalence among individuals aged over six months. Analysis compared clinical malaria incidence and prevalence between arms among the intention-to-treat population.ResultsATSB coverage, assessed by cross-sectional survey, was 98.3% in March–April 2022 and 89.5% in March–April 2023. 4494 children contributed any follow-up time to the cohort, with 2313 incident malaria cases in the intervention arm (1.28 per child per six-month transmission season), and 2449 in the control arm (1.38 per child-season). The incidence rate ratio between the two arms was 0.91 (95% CI 0.72–1.15, p = 0.42). 2536 individuals participated in cross-sectional surveys, with prevalence of P. falciparum 50.7% in the intervention arm and 53.5% in the control arm. The odds ratio between the two arms was 0.89 (95% CI 0.66–1.18, p = 0.42). Secondary covariable-adjusted and subgroup analyses did not substantially alter the findings. No serious adverse events associated with the intervention were reported.ConclusionsTwo ATSB stations deployed per eligible structure for two consecutive transmission seasons did not result in a statistically significant reduction in clinical malaria incidence among children aged 1–14 years or in P. falciparum prevalence in rural western Zambia. Further studies are needed to assess the efficacy of ATSB stations in different settings and with different deployment strategies.Trial registrationThe trial is registered with Clinicaltrials.gov (NCT04800055).

Current and Future Probability of Occurrence of the Floodwater Mosquito Aedes vexans (Meigen, 1830) in the Netherlands

ABSTRACTAedes vexans (Meigen, 1830) is a floodwater mosquito species that may cause significant nuisance and can serve as a vector for multiple arboviruses. Its distribution is expected to shift in the future as a result of changes in climate and land use. Understanding these shifts is important for estimating future disease risk. This study aims to identify habitat suitability and probability of occurrence of A. vexans. Using the Netherlands as a case study, we utilised an occurrence dataset generated by the Netherlands Centre for Monitoring of Vectors. We employed an auto machine learning approach to model generation, using a variety of modelling methodologies, determining the optimal ratio of presence: Absence datapoints in the training data and ultimately creating a 10‐model ensemble. We selected predictor variables relating to weather, land use, soil properties, flood risk and salinity. The probability of A. vexans presence was predicted on a 1 km grid for both the current Dutch situation and for four scenarios for 2050. Our analysis identified temperature, soil type and land cover as the primary determinants influencing the probability of A. vexans occurrence. Future projections reveal an increase in the likelihood of A. vexans occurrence in the study area, particularly along major river corridors and in regions with increasing amounts of artificial and natural areas. Additionally, the mosquito season is predicted to become longer under all future scenarios. Insights provided in our study can also be applied to other similar areas, such as other north‐western European countries or other urban deltas. This study shows for the first time detailed future occurrence predictions and also future seasonal predictions for this mosquito species. Seasonal predictions allow researchers to study how disease risk changes throughout the year, something which is particularly valuable given the predicted lengthening of the mosquito (and thus disease transmission) season.

Temporal genomics in Southern Zambia shows rising prevalence of Plasmodium falciparum mutations linked to delayed clearance after artemisinin-lumefantrine treatment

The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013 and 2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample from 2016 carrying K13 622I, no other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations were observed. However, in the more recent years (2016–2017) five novel K13-propeller-domain mutations, C532S, A578S, Q613E, D680N and G718S were identified at low prevalence. Moreover, 13% (CI, 9.6–17.2) of isolates had the AP2MU 160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015 and 2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.

Elucidating the influence of wild boar density on African swine fever spread in wild boar populations, Italy, 2022–2023

Abstract Wild boar density has been suggested to play a role in shaping African swine fever (ASF) transmission patterns. To provide quantitative estimates of the influence of wild boar density on ASF spread, a spatially‐explicit detection‐delay SIR mechanistic model of ASF transmission among density‐explicit wild boar habitat was developed and parameterised to observed epidemic data in northern Italy from January 2022 through September 2023. Wild boar density estimates were generated by the ENETWILD consortium. Infectious periods, local prevalence at time of first detection, detection rates, and seasonal recovery rates were estimated directly from surveillance data. Eight models were constructed utilizing static and seasonal transmission rates along with linear relationships between habitat susceptibility/infectivity and wild boar density. Transmission rate, relative susceptibility, and relative infectivity were estimated by fitting each model to the observed epidemic using sequential Monte Carlo approximate Bayesian computation. The model that most closely fit the full data used a seasonal transmission rate but did not support a wild boar density effect on ASF spread across the entire study period. However, further analyses of the model outputs suggest that wild boar density likely played a role in shaping ASF transmission patterns during the second wave only (October 2022 – September 2023). This observation could be due to a lack of power in the first wave, lower surveillance rates in that period, or be from density estimates no longer reflecting the true wild boar density distributions upon the start of the second wave. These results demonstrate that wild boar density impacted ASF propagation in northern Italy. Further investigation by estimating parameters for individual epidemic waves could be beneficial to better characterise the wave‐specific impact of wild boar density. The model developed here could be used in other contexts to evaluate if the influence of wild boar density is present across epidemic scenarios.

The Re-Emergence of Neuroinvasive Flaviviruses in Croatia During the 2022 Transmission Season.

(Re-)emerging arboviruses, such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV), and Usutu virus (USUV), are continuously increasing in incidence. We analyzed the epidemiological characteristics of flavivirus infections in humans, sentinel animals, and mosquitoes detected in the 2022 transmission season in Croatia. From April to November 2022, 110 hospitalized patients with neuroinvasive diseases (NID) were tested for the presence of arboviruses. RT-qPCR was used to detect TBEV, WNV, and USUV RNA. An ELISA and virus neutralization tests were used for the detection of flavivirus antibodies. TBEV infection was confirmed in 22 patients with NID. WNV NID was detected in six patients. TBE showed male predominance (81.8%; male-to-female ratio of 4.5:1). All but one WNV patients were males. TBE occurred from April to August, with the majority of patients (83.3%) being detected during the May-June-July period. WNV infections were recorded in August and September. In addition to human cases, asymptomatic WNV infections (IgM positive) were reported in 10 horses. For the first time in Croatia, WNV NID was observed in one horse that presented with neurological symptoms. Furthermore, USUV was confirmed in one dead blackbird that presented with neurological symptoms. A total of 1984 mosquitoes were collected in the City of Zagreb. Two Ae. albopictus pools tested positive for flavivirus RNA: one collected in July (USUV) and the other collected in August (WNV). A phylogenetic analysis of detected human and avian strains confirmed WNV lineage 2 and the USUV Europe 2 lineage. The presented results confirm the endemic presence of neuroinvasive flaviviruses in continental Croatia. The continuous monitoring of virus circulation in humans, sentinel animals, and mosquitoes is needed to reduce the disease burden.

Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites.

Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins like SG6 have been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with P. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO. We tested population-level human immune responses in longitudinal and cross-sectional plasma from individuals with known P. falciparum infection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay. AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinical P. falciparum infection and declined 3 months after infection. Reactivity to AgSAP and AgTRIO peaked after infection, with no differences between transmission seasons within region or between low and moderate transmission regions. This suggests that reactivity reflects exposure to infectious mosquitoes or recent bites rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes in P. falciparum-infected mosquito exposure.

Prolonged dry seasons lengthen coccidioidomycosis transmission seasons: implications for a changing California.

Coccidioidomycosis, a fungal disease caused by soil-borne Coccidioides spp., exhibits pronounced seasonal transmission, with incidence in California typically peaking in the fall. However, the influence of climate on the timing and duration of transmission seasons remains poorly understood. Using weekly data on reported coccidioidomycosis cases in California from 2000-2023, we developed a distributed-lag Markov state-transition model to estimate the effects of temperature and precipitation on the timing of transmission season onset and end. We found that transitions from cooler, wetter conditions to hotter, drier conditions accelerate season onset. Dry conditions (10 th percentile of precipitation) in the spring shifted season onset an average of 2.8 weeks (95% CI: 0.43-3.58) earlier compared to wet conditions (90 th percentile of precipitation). Conversely, transitions back to cooler, wetter conditions hastened season end, with dry fall conditions extending the season by an average of 0.69 weeks (95% CI: 0.37-1.41) compared to wet conditions. When dry conditions occurred in the spring and fall, the transmission season extended by 3.70 weeks (95% CI: 1.23-4.22). As California is expected to experience prolonged dry seasons with climate change, our findings suggest this shift may lengthen the time at which populations are at elevated coccidioidomycosis risk.

An observational analysis of the impact of deltamethrin + piperonyl butoxide insecticide-treated nets on malaria case incidence and entomological indicators in Ebonyi State, Nigeria, 2017–2021

BackgroundIntense pyrethroid resistance threatens the effectiveness of the primary vector control intervention, insecticide-treated nets (ITNs), in Nigeria, the country with the largest malaria burden globally. In this study, the epidemiological and entomological impact of a new type of ITN (piperonyl-butoxide [PBO] ITNs) distributed in Ebonyi State were evaluated. The epidemiological impact was also compared to the impact of standard pyrethroid-only ITNs in Cross River State.MethodsA controlled interrupted time series analysis was conducted on monthly malaria incidence data collected at the health facility level, using a multilevel mixed-effects negative binomial model. Data were analysed two years before and after the PBO ITN campaign in Ebonyi State (December 2017 to November 2021). A pre-post analysis, with no comparison group, was used to assess the impact of PBO ITNs on human biting rates and indoor resting density in Ebonyi during the high transmission season immediately before and after the PBO ITN campaign.ResultsIn Ebonyi, PBO ITNs were associated with a 46.7% decrease (95%CI: -51.5, -40.8%; p < 0.001) in malaria case incidence in the 2 years after the PBO ITN distribution compared to a modelled scenario of no ITNs distributed, with a significant decrease from 269.6 predicted cases per 1000 population to 143.6. In Cross River, there was a significant 28.6% increase (95%CI: -10.4, 49.1%; p < 0.001) in malaria case incidence following the standard ITN distribution, with an increase from 71.2 predicted cases per 1000 population to 91.6. In Ebonyi, the human biting rate was 72% lower (IRR: 0.28; 95%CI 0.21, 0.39; p < 0.001) and indoor resting density was 73% lower (IRR: 0.27; 95%CI 0.21, 0.35; p < 0.001) after the PBO ITNs were distributed.ConclusionsThe epidemiological and entomological impact of the PBO ITNs underscore the impact of these ITNs in areas with confirmed pyrethroid resistance. These findings contribute to ongoing research on the impact of new types of ITNs in Nigeria, providing critical evidence for the Nigeria National Malaria Elimination Programme and other countries for future ITN procurement decisions as part of mass ITN campaign planning and malaria programming.

Evolution of Pfdhps and Pfdhfr mutations before and after adopting seasonal malaria chemoprevention in Nanoro, Burkina Faso

Seasonal Malaria Chemoprevention consisting of monthly administration of amodiaquine/sulfadoxine-pyrimethamine to children aged 3–59 months during the transmission season could promote SP-resistance. Mutations in dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes were assessed before and after SMC adoption in Burkina Faso. A total of 769 dried blood spots were selected from studies conducted in Nanoro, Burkina Faso, between 2010 and 2020. Of those, 299 were pre-SMC (2010–2012) and 470 were post-SMC-samples. Pfdhps and Pfdhfr genes were PCR-amplified and sequenced. A systematic review/meta-analysis of published studies conducted in Burkina Faso (2009–2023) was additionally performed. In Nanoro, the prevalence of Pfdhfr triple mutations (CIRNI) rose from 43.6% pre-SMC to 89.4% post-SMC (p < 0.0001). There was no mutation in Pfdhfr 164 and Pfdhps 540; Pfdhps A437G mutation increased from 63.9% (2010–2012) to 84.7% (2020) (p < 0.0001). The VAGKGS haplotype was 2.8% (2020). Pfdhfr/Pfdhps quintuple mutant IRN-436A437G rose from 18.6% (2010–2012) to 58.3% (2020) (p < 0.0001). Meta-analysis results from Burkina Faso showed an increase in mutations at Pfdhfr N51I, C59R, S108N, and Pfdhps A437G after SMC adoption. Post-SMC, the pyrimethamine-resistance marker prevalence increased, while the sulfadoxine-resistance marker prevalence remained stable. Detection of emerging PfdhpsVAGKGS haplotypes in 2020 underscores the importance of continuous SP-resistance monitoring.

Why does malaria transmission continue at high levels despite universal vector control? Quantifying persistent malaria transmission by Anopheles funestus in Western Province, Zambia

BackgroundSome settings continue to experience a high malaria burden despite scale-up of malaria vector control to high levels of coverage. Characterisation of persistent malaria transmission in the presence of standard control measures, also termed residual malaria transmission, to understand where and when individuals are exposed to vector biting is critical to inform refinement of prevention and control strategies.MethodsSecondary analysis was performed using data collected during a phase III cluster randomized trial of attractive targeted sugar bait stations in Western Province, Zambia. Two seasonal cohorts of children aged 1–14 years were recruited and monitored monthly during the malaria transmission season, concurrent with entomological surveillance using a combination of human landing catch (HLC) and Centres for Disease Control (CDC) light traps at randomly selected households in study clusters. Behavioural data from cohort participants were combined with measured Anopheles funestus landing rates and sporozoite positivity to estimate the human behaviour-adjusted entomological inoculation rate (EIR).ResultsBehavioural data from 1237 children over 5456 child-visits in 20 entomology surveillance clusters were linked with hourly landing rates from 8131 female An. funestus trapped by HLC. Among all An. funestus tested by enzyme-linked immunosorbent assay (ELISA), 3.3% were sporozoite-positive. Mean EIR directly measured from HLC was 0.07 infectious bites per person per night (ib/p/n). When accounting for child locations over the evening and night, the mean behaviour-adjusted EIR was 0.02 ib/p/n. Children not sleeping under insecticide-treated nets (ITNs) experienced 13.6 infectious bites per person per 6 month season, 8% of which occurred outdoors, while ITN users received 1.3 infectious bites per person per 6 month season, 86% of which were received outdoors. Sleeping under an ITN can prevent approximately 90% of potential An. funestus bites among children.ConclusionsIn this setting ITNs have a high personal protective efficacy owing to peak An. funestus biting occurring indoors while most individuals are asleep. However, despite high household possession of ITNs (>90%) and high individual use (>70%), children in this setting experience more than one infectious bite per person per 6 month transmission season, sufficient to maintain high malaria transmission and burden. New tools and strategies are required to reduce the malaria burden in such settings.Graphical

Genetic diversity in the Plasmodium falciparum next-generation blood stage vaccine candidate antigen PfCyRPA in Senegal.

The Plasmodium falciparum cysteine-rich protective antigen (PfCyRPA) is a promising target as a next-generation blood-stage malaria vaccine and together with PCRCR complex members, the reticulocyte binding-like homologous protein 5 (PfRh5) and the Rh5-interacting protein (PfRipr), are currently being evaluated in clinical trials. PfCyRPA is essential for merozoite invasion and appears to be highly conserved within the P. falciparum parasite populations. Here, we used a targeted deep amplicon next-generation sequencing approach to assess the breadth of PfCyRPA genetic diversity in 95 P. falciparum clinical isolates from Kédougou, an area with a high seasonal malaria transmission in Senegal. Our data show the dominant prevalence of PfCyRPA wild type reference allele, while we also identify a total of 15 single nucleotide polymorphisms (SNPs). Of these, only five have previously been reported, while the majority of the SNPs were present as singletons within our sampled population. Moreover, the variant read frequency of the identified SNPs varied from 2.6 to 100%, while the majority of the SNPs were present at frequencies greater than 25% in polygenomic samples. We also applied a structure-based modelling approach to thread these SNPs onto PfCyRPA crystal structures and showed that these polymorphisms have different predicted functional impacts on the interactions with binding partner PfRH5 or neutralizing antibodies. Our prediction revealed that the majority of these SNPs have minor effects on PfCyRPA antibodies, while others alter its structure, stability, or interaction with PfRH5. Altogether, our present findings reveal conserved PfCyRPA epitopes which will inform downstream investigations on next-generation structure-guided malaria vaccine design.

Cycles of susceptibility: Immunity debt explains altered infectious disease dynamics post -pandemic.

The concept of immunity debt is a phenomenon resulting from the suppression of endemic pathogens during the COVID-19 pandemic due to non-pharmaceutical interventions (NPIs). The reduced circulation of various pathogens during the pandemic, particularly respiratory syncytial virus (RSV), altered typical infectious disease dynamics by reducing levels of population immunity usually acquired through exposure to infection. This concept is demonstrated through post-pandemic resurgence of diseases such as RSV and Group A Streptococcus, and highlights the interplay between reduced pathogen exposure and increased susceptibility in populations. The complexities and non-linear dynamics of seasonal transmission are observed in differences in pathogen resurgence across regions. These issues highlight the importance of comprehensive disease surveillance and public health strategies in mitigating these long-term epidemiological impacts.

Prevalence of Aedes Mosquitoes During the Dengue Transmission Season in Haridwar City of Uttarakhand State, India

Prevalence of Aedes Mosquitoes During the Dengue Transmission Season in Haridwar City of Uttarakhand State, India