Protective effects of Olyset® Net on Plasmodium falciparum infection after three years of distribution in western Kenya.

BACKGROUND: Several types of insecticides, treating technologies and materials are available for long-lasting insecticide-treated nets (LLINs). The variations may result in different efficacies against mosquitoes and correspondingly infection risks for the Plasmodium falciparum malaria parasite. This cross-sectional study investigated whether infection risk varied among children who slept under different LLIN brands in rural villages of western Kenya. METHODS: Children sleeping under various types of LLINs were tested for P. falciparum infection using a diagnostic polymerase chain reaction (PCR) assay. Data were collected for other potential factors associated with infection risk: sleeping location (with bed/without bed), number of persons sharing the same net, dwelling wall material, gap of eaves (open/close), proportional hole index, socio-economic status, and density of indoor resting anophelines. Bed-net efficacy against the Anopheles gambiae susceptible strain was estimated using the WHO cone test and the tunnel test. The residual insecticide content on nets was measured. RESULTS: Seven LLIN brands were identified, and deltamethrin-based DawaPlus® 2.0 was the most popular (48%) followed by permethrin-based Olyset® Net (28%). The former LLIN was distributed in the area about six months before the present study was conducted, and the latter net was distributed at least three years before. Of 254 children analysed, P. falciparum PCR-positive prevalence was 58% for DawaPlus® 2.0 users and 38% for Olyset® users. The multiple regression analysis revealed that the difference was statistically significant (adjusted OR: 0.67, 95% credible interval: 0.45-0.97), whereas the confounders were not statistically important. Among randomly selected net samples, all DawaPlus® 2.0 (n = 20) and 95% of Olyset® (n = 19) passed either the cone test or the tunnel test. CONCLUSIONS: Olyset® was more effective in reducing infection risk compared with DawaPlus® 2.0. Although the data from the present study were too limited to explain the mechanism clearly, the results suggest that the characteristics of the former brand are more suitable for the conditions, such as vector species composition, of the study area.

Spatial assessment of heavy metals contamination in household garden soils in rural Limpopo Province, South Africa.

Heavy metal pollution in soil poses a serious health threat to humans living in close proximity and in contact with contaminated soil. Exposure to heavy metals can result in a range of adverse health effects, including skin lesions, cardiovascular effects, lowering of IQ scores and cancers. The main objectives of this study were to (1) use a portable XRF spectrophotometer to measure concentrations of lead (Pb), arsenic (As), mercury (Hg) and cadmium (Cd) in residential soils in rural Giyani in the Limpopo province of South Africa; (2) to assess the spatial distribution of soil metal concentrations; and (3) to assess pollution levels in residential soils. There were elevated levels of As at one of the sites where 54% of soil samples exceeded the Canadian reference levels for As of 20 mg/kg. Using the geoaccumulation index (Igeo) to determine contamination levels of As, 57% of soil samples from the most polluted site were found to be moderately to heavily and extremely contaminated with As (Igeo class 2-5). The site is located near the Giyani Greenstone Belt, which is characterized by abandoned mines and artisanal mining activities. Gold ores are closely associated with sulphide minerals such as arsenopyrite, and these have been found to contain high amounts of As. This study highlighted the potential for soil contamination and the importance of site-specific risk assessment in the context of environment and health impact assessments prior to major developments, including human settlement developments.

Antimalarial bednet protection of children disappears when shared by three or more people in a high transmission setting of western Kenya.

A sizeable proportion of households is forced to share single long-lasting insecticide treated net (LLIN). However, the relationship between increasing numbers of people sharing a net and the risk for Plasmodium infection is unclear. This study revealed whether risk for Plasmodium falciparum infection is associated with the number of people sharing a LLIN in a holoendemic area of Kenya. Children ⩽5 years of age were tested for P. falciparum infection using polymerase chain reaction. Of 558 children surveyed, 293 (52.5%) tested positive for parasitaemia. Four hundred and fifty-eight (82.1%) reported sleeping under a LLIN. Of those, the number of people sharing a net with the sampled child ranged from 1 to 5 (median = 2). Children using a net alone or with one other person were at lower risk than non-users (OR = 0.29, 95% CI 0.10-0.82 and OR = 0.47, 95% CI 0.22-0.97, respectively). On the other hand, there was no significant difference between non-users and children sharing a net with two (OR = 0.88, 95% CI 0.44-1.77) or more other persons (OR = 0.75, 95% CI 0.32-1.72). LLINs are effective in protecting against Plasmodium infection in children when used alone or with one other person compared with not using them. Public health professionals should inform caretakers of the risks of too many people sharing a net.

First detection of a Vssc allele V1016G conferring a high level of insecticide resistance in Aedes albopictus collected from Europe (Italy) and Asia (Vietnam), 2016: a new emerging threat to controlling arboviral diseases.

IntroductionAedes albopictus (Skuse) is an important vector of arboviral diseases, including dengue, chikungunya and Zika virus disease. Monitoring insecticide resistance and mechanisms by which the mosquito develops resistance is crucial to minimise disease transmission.AimTo determine insecticide resistance status and mechanisms in Ae. albopictus from different geographical regions.MethodsWe sampled 33 populations of Ae. albopictus from Asia, Europe and South America, and tested these for susceptibility to permethrin, a pyrethroid insecticide. In resistant populations, the target site for pyrethroids, a voltage-sensitive sodium channel (Vssc) was genotyped. Three resistant sub-strains, each harbouring a resistance allele homozygously, were established and susceptibilities to three different pyrethroids (with and without a cytochrome P450 inhibitor) were assayed.ResultsMost populations of Ae. albopictus tested were highly susceptible to permethrin but a few from Italy and Vietnam (4/33), exhibited high-level resistance. Genotyping studies detected a knockdown resistance (kdr) allele V1016G in Vssc for the first time in Ae. albopictus. Two previously reported kdr alleles, F1534C and F1534S, were also detected. The bioassays indicated that the strain homozygous for the V1016G allele showed much greater levels of pyrethroid resistance than other strains harbouring F1534C or F1534S.ConclusionThe V1016G allele was detected in bothAsian and Italian Ae. albopictus populations, thus a spread of this allele beyond Italy in Europe cannot be ruled out. This study emphasises the necessity to frequently and regularly monitor the V1016G allele in Ae. albopictus, particularly where this mosquito species is the main vector of arboviruses.

Biology of Anopheles saperoi, an Endemic Species in Okinawajima, the Ryukyu Archipelago, Japan.

Biological studies of Anopheles saperoi were conducted using larval and adult mosquito collections in the northern part of Okinawajima of the Ryukyu Archipelago from June 2009 to July 2010. Anopheles saperoi was the most collected species in the northern Okinawajima, except Motobu Peninsula, where it was not collected. The southern distribution of An. saperoi was Sugita Stream, Nago City. Anopheles saperoi was collected throughout the year with reproduction (gonotrophic cycle) observed year-round. Immature densities varied for Hinna and Yona streams, and were negatively affected by precipitation patterns. Human attraction activity of females varied for by study area and collection time and was positively affected by temperature, but negatively by heavy rainfall. The greatest female human attraction activity was observed during 3:00-5:00 p.m., with peak at twilight. Parity rates varied from 23.1% to 83.3% throughout the year.

Sleeping on the floor decreases insecticide treated bed net use and increases risk of malaria in children under 5 years of age in Mbita District, Kenya.

Children who sleep on the floor are less likely to use long-lasting insecticidal nets (LLINs); however, the relationship between sleeping location and Plasmodium falciparum infection has not been investigated sufficiently. This study revealed whether sleeping location (bed vs floor) is associated with P. falciparum infection among children 7-59 months old. More than 60% of children slept on the floor. Younger children were significantly more likely to sleep in beds [odds ratio, OR 2.31 (95% confidence interval (CI) 2.02-2.67)]. Nearly 70% of children slept under LLINs the previous night. LLIN use among children who slept on the floor was significantly less than ones sleeping in beds [OR 0.49 (95% CI 0.35-0.68)]. The polymerase chain reaction (PCR) based P. falciparum infection rate and slide based infection rate were 65.2 and 29.7%, respectively. Both infections were significantly higher among children slept on the floor [OR1.51 (95% CI 1.08-2.10) for PCR base, OR 1.62 (95% CI 1.14-2.30) for slide base] while net availability was not significant. Sleeping location was also significant for slide based infection with fever (⩾ 37.5 °C) [2.03 (95% CI 1.14-3.84)] and high parasitemia cases (parasite ⩾ 2500 µL(-1)) [2.07 (95% CI 1.03-4.50)]. The results suggest that sleeping location has a direct bearing on the effectiveness of LLINs.

Insecticide-treated net use before and after mass distribution in a fishing community along Lake Victoria, Kenya: successes and unavoidable pitfalls.

BACKGROUND: Insecticide-treated nets (ITNs) have proven instrumental in the successful reduction of malaria incidence in holoendemic regions during the past decade. As distribution of ITNs throughout sub-Saharan Africa (SSA) is being scaled up, maintaining maximal levels of coverage will be necessary to sustain current gains. The effectiveness of mass distribution of ITNs, requires careful analysis of successes and failures if impacts are to be sustained over the long term. METHODS: Mass distribution of ITNs to a rural Kenyan community along Lake Victoria was performed in early 2011. Surveyors collected data on ITN use both before and one year following this distribution. At both times, household representatives were asked to provide a complete accounting of ITNs within the dwelling, the location of each net, and the ages and genders of each person who slept under that net the previous night. Other data on household material possessions, education levels and occupations were recorded. Information on malaria preventative factors such as ceiling nets and indoor residual spraying was noted. Basic information on malaria knowledge and health-seeking behaviours was also collected. Patterns of ITN use before and one year following net distribution were compared using spatial and multi-variable statistical methods. Associations of ITN use with various individual, household, demographic and malaria related factors were tested using logistic regression. RESULTS: After infancy (<1 year), ITN use sharply declined until the late teenage years then began to rise again, plateauing at 30 years of age. Males were less likely to use ITNs than females. Prior to distribution, socio-economic factors such as parental education and occupation were associated with ITN use. Following distribution, ITN use was similar across social groups. Household factors such as availability of nets and sleeping arrangements still reduced consistent net use, however. CONCLUSIONS: Comprehensive, direct-to-household, mass distribution of ITNs was effective in rapidly scaling up coverage, with use being maintained at a high level at least one year following the intervention. Free distribution of ITNs through direct-to-household distribution method can eliminate important constraints in determining consistent ITN use, thus enhancing the sustainability of effective intervention campaigns.

Geographic expansion of the introduced Aedes albopictus and other native Aedes species in the Democratic Republic of the Congo.

BACKGROUND: Aedes albopictus has been reported in several Central African countries, including the Democratic Republic of the Congo (DRC). The establishment of this mosquito species poses a serious threat as a vector of various infectious diseases. Although Ae. albopictus has been reported in the western region of the DRC, information about its distribution is still scarce in the country. The aim of this study was to investigate the current nationwide distribution of the invasive Ae. albopictus, as well as other native Aedes mosquitoes, in the DRC and to identify suitable areas for its future expansion. METHODS: Two entomological surveys were conducted in 2017-2019 and 2022. Based on the occurrence sites of Ae. albopictus, important environmental variables were identified. Then, geographical areas suitable for Ae. albopictus establishment were determined using the maximum entropy model. The distribution and abundance of Ae. albopictus were also compared with those of the major native Aedes species. RESULTS: Aedes albopictus was found in the western, northern, central, and eastern regions of the DRC, but it was not found in the southeastern region. The maximum entropy model predicted that most parts of the DRC are suitable for the establishment of this mosquito. The unsuitable areas encompassed the eastern highlands, known for their low temperatures, and the southeastern highlands, which experience both low temperatures and a long dry season. The native Aedes species found were Aedes aegypti, Aedes simpsoni, Aedes africanus, and Aedes vittatus. Aedes albopictus dominated in the western and northern regions, while Ae. aegypti was more prevalent in other regions. CONCLUSIONS: Aedes albopictus has been well established in the western and northern regions of the DRC. This mosquito is expanding its distribution while replacing the native Aedes species. Most of the country is suitable for the establishment of this mosquito species, except the highlands of the eastern and the southeastern regions.

When they don't bite, we smell money: understanding malaria bednet misuse.

Insecticide-treated nets (ITNs) are a major tool to control malaria. Over recent years increased ITN coverage has been associated with decreased malaria transmission. However, ITN 'misuse' has been increasingly reported and whether this emergent behaviour poses a threat to successful malaria control and elimination is an open question. Here, we use a game theory mathematical model to understand the possible roles of poverty and malaria infection protection by individual and emerging 'community effects' on the 'misuse' of malaria bednets. We compare model predictions with data from our studies in Lake Victoria Islands (LVI), Kenya and Aneityum, Vanuatu. Our model shows that alternative ITN use is likely to emerge in impoverished populations and could be exacerbated if ITNs become ineffective or when large 'community effects' emerge. Our model predicted patterns of ITN use similar to the observed in LVI, where 'misuse' is common and the high ITN use in Aneityum, more than 20 years after malaria elimination in 1990. We think that observed differences in ITN use may be shaped by different degrees of economic and social development, and educational components of the Aneityum elimination, where traditional cooperative attitudes were strengthened with the malaria elimination intervention and post-elimination surveillance.

Effect of housing factors on infestation by Aedes aegypti (L.) and Aedes albopictus Skuse in urban Hanoi City, Vietnam.

To determine the effect of housing factors on infestation with Aedes aegypti (L.) and Aedes albopictus Skuse we conducted an entomological survey and inspection of 267 urban houses in Hanoi City, Vietnam. Two hundred ten pupae and 194 adult Ae. aegypti were collected from 19 and 88 houses, respectively. One hundred eighty-one pupae and 24 adult Ae. albopictus were collected from 21 and 14 houses, respectively. The presence of a private well was associated with increasing infestation with Ae. aegypti adults (p = 0.01) and increased the risk of Ae. aegypti and Ae. albopictus pupal presence (p = 0.04 for Ae. aegypti, p = 0.03 for Ae. albopictus). The presence of an outdoor space in the household premises was associated with a higher risk of Ae. albopictus pupal presence (p = 0.004) and a higher risk of high levels of Ae. albopictus adults (p = 0.01); however, it had no association with infestation with Ae. aegypti. The presence of an air-conditioning unit (p = 0.03) and four or more rooms in the residence (p = 0.02) were negatively and positively associated with the risk for Ae. albopictus presence, respectively.

Indian Ocean dipole and rainfall drive a Moran effect in East Africa malaria transmission.

BACKGROUND: Patterns of concerted fluctuation in populations-synchrony-can reveal impacts of climatic variability on disease dynamics. We examined whether malaria transmission has been synchronous in an area with a common rainfall regime and sensitive to the Indian Ocean Dipole (IOD), a global climatic phenomenon affecting weather patterns in East Africa. METHODS: We studied malaria synchrony in 5 15-year long (1984-1999) monthly time series that encompass an altitudinal gradient, approximately 1000 m to 2000 m, along Lake Victoria basin. We quantified the association patterns between rainfall and malaria time series at different altitudes and across the altitudinal gradient encompassed by the study locations. RESULTS: We found a positive seasonal association of rainfall with malaria, which decreased with altitude. By contrast, IOD and interannual rainfall impacts on interannual disease cycles increased with altitude. Our analysis revealed a nondecaying synchrony of similar magnitude in both malaria and rainfall, as expected under a Moran effect, supporting a role for climatic variability on malaria epidemic frequency, which might reflect rainfall-mediated changes in mosquito abundance. CONCLUSIONS: Synchronous malaria epidemics call for the integration of knowledge on the forcing of malaria transmission by environmental variability to develop robust malaria control and elimination programs.

Exploring the Association between Ambient Temperature and Daily Hospital Admissions for Diarrhea in Mopani District, Limpopo Province, South Africa.

Diarrhea contributes significantly to global morbidity and mortality. There is evidence that diarrhea prevalence is associated with ambient temperature. This study aimed to determine if there was an association between ambient temperature and diarrhea at a rural site in South Africa. Daily diarrheal hospital admissions (2007 to 2016) at two large district hospitals in Mopani district, Limpopo province were compared to average daily temperature and apparent temperature (Tapp, 'real-feel' temperature that combined temperature, relative humidity, and wind speed). Linear regression and threshold regression, age-stratified to participants ≤5 years and >5 years old, considered changes in daily admissions by unit °C increase in Tapp. Daily ranges in ambient temperature and Tapp were 2-42 °C and -5-34 °C, respectively. For every 1 °C increase in average daily temperature, there was a 6% increase in hospital admissions for diarrhea for individuals of all ages (95% CI: 0.04-0.08; p < 0.001) and a 4% increase in admissions for individuals older than 5 years (95% CI: 0.02-0.05; p < 0.001). A positive linear relationship between average daily Tapp and all daily diarrheal admissions for children ≤5 years old was not statistically significant (95% CI: -0.00-0.03; p = 0.107). Diarrhea is common in children ≤5 years old, however, is more likely triggered by factors other than temperature/Tapp, while it is likely associated with increased temperature in individuals >5 years old. We are limited by lack of data on confounders and effect modifiers, thus, our findings are exploratory. To fully quantify how temperature affects hospital admission counts for diarrhea, future studies should include socio-economic-demographic factors as well as WASH-related data such as personal hygiene practices and access to clean water.

Utilizing a novel high-resolution malaria dataset for climate-informed predictions with a deep learning transformer model.

Climatic factors influence malaria transmission via the effect on the Anopheles vector and Plasmodium parasite. Modelling and understanding the complex effects that climate has on malaria incidence can enable important early warning capabilities. Deep learning applications across fields are proving valuable, however the field of epidemiological forecasting is still in its infancy with a lack of applied deep learning studies for malaria in southern Africa which leverage quality datasets. Using a novel high resolution malaria incidence dataset containing 23 years of daily data from 1998 to 2021, a statistical model and XGBOOST machine learning model were compared to a deep learning Transformer model by assessing the accuracy of their numerical predictions. A novel loss function, used to account for the variable nature of the data yielded performance around + 20% compared to the standard MSE loss. When numerical predictions were converted to alert thresholds to mimic use in a real-world setting, the Transformer's performance of 80% according to AUROC was 20-40% higher than the statistical and XGBOOST models and it had the highest overall accuracy of 98%. The Transformer performed consistently with increased accuracy as more climate variables were used, indicating further potential for this prediction framework to predict malaria incidence at a daily level using climate data for southern Africa.

Evaluation of the protective efficacy of Olyset®Plus ceiling net on reducing malaria prevalence in children in Lake Victoria Basin, Kenya: study protocol for a cluster-randomized controlled trial.

BACKGROUND: In the Lake Victoria Basin of western Kenya, malaria remains highly endemic despite high coverage of interventions such as insecticide-impregnated long-lasting insecticidal nets (LLIN). The malaria-protective effect of LLINs is hampered by insecticide resistance in Anopheles vectors and its repurposing by the community. Ceiling nets and LLIN with synergist piperonyl butoxide (PBO-LLIN) are novel tools that can overcome the problems of behavioral variation of net use and metabolic resistance to insecticide, respectively. The two have been shown to reduce malaria prevalence when used independently. Integration of these two tools (i.e., ceiling nets made with PBO-LLIN or Olyset®Plus ceiling nets) appears promising in further reducing the malaria burden. METHODS: A cluster-randomized controlled trial is designed to assess the effect of Olyset®Plus ceiling nets on reducing malaria prevalence in children on Mfangano Island in Homa Bay County, where malaria transmission is moderate. Olyset®Plus ceiling nets will be installed in 1315 residential structures. Malaria parasitological, entomological, and serological indicators will be measured for 12 months to compare the effectiveness of this new intervention against conventional LLIN in the control arm. DISCUSSION: Wider adoption of Olyset®Plus ceiling nets to complement existing interventions may benefit other malaria-endemic counties and be incorporated as part of Kenya's national malaria elimination strategy. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000045079. Registered on 4 August 2021.

Regime shifts and heterogeneous trends in malaria time series from Western Kenya Highlands.

Large malaria epidemics in the East African highlands during the mid and late 1990s kindled a stream of research on the role that global warming might have on malaria transmission. Most of the inferences using temporal information have been derived from a malaria incidence time series from Kericho. Here, we report a detailed analysis of 5 monthly time series, between 15 and 41 years long, from West Kenya encompassing an altitudinal gradient along Lake Victoria basin. We found decreasing, but heterogeneous, malaria trends since the late 1980s at low altitudes (<1600 m), and the early 2000s at high altitudes (>1600 m). Regime shifts were present in 3 of the series and were synchronous in the 2 time series from high altitudes. At low altitude, regime shifts were associated with a shift from increasing to decreasing malaria transmission, as well as a decrease in variability. At higher altitudes, regime shifts reflected an increase in malaria transmission variability. The heterogeneity in malaria trends probably reflects the multitude of factors that can drive malaria transmission and highlights the need for both spatially and temporally fine-grained data to make sound inferences about the impacts of climate change and control/elimination interventions on malaria transmission.

The Indian Ocean Dipole and malaria risk in the highlands of western Kenya.

Epidemics of malaria in the East African highlands in the last 2 decades have often been associated with climate variability, particularly the El Niño-Southern Oscillation (ENSO). However, there are other factors associated with malaria risk and there is increased interest in the influences of the Indian Ocean Dipole (IOD), a climate mode of coupled ocean-atmosphere variability, on East African rainfall. This study explores the relationship between IOD and the number of malaria patients in 7 hospitals from 2 districts in the western Kenyan highlands, controlling for the effects of ENSO. We examined temporal patterns (1982-2001) in the number of malaria cases in relation to the dipole mode index (DMI), defined as the difference in sea surface temperature anomaly between the western (10 degrees S-10 degrees N, 50 degrees-70 degrees E) and eastern (10 degrees S-0 degrees, 90 degrees-110 degrees E) tropical Indian Ocean. We used Poisson regression models, adjusted for ENSO index Niño 3 region (NINO3), seasonal and interannual variations. The number of malaria patients per month increased by 3.4%-17.9% for each 0.1 increase above a DMI threshold (3-4 months lag). Malaria cases increased by 1.4%-10.7% per month, for each 10 mm increase in monthly rainfall (2-3 months lag). In 6 of 7 places, there was no evidence of an association between NINO3 and the number of malaria cases after adjusting for the effect of DMI. This study suggests that the number of malaria cases in the western Kenyan highlands increases with high DMI in the months preceding hospital visits.

A comparative study of dengue virus vectors in major parks and adjacent residential areas in Ho Chi Minh City, Vietnam.

The primary dengue virus vectors, Aedes aegypti and Aedes albopictus, are primarily daytime biting mosquitoes. The risk of infection is suspected to be considerable in urban parks due to visitor traffic. Despite the importance of vector control for reducing dengue transmission, little information is available on vector populations in urban parks. The present study characterized mosquito habitats and estimated vector densities in the major urban parks in Ho Chi Minh City, Vietnam and compared them with those in adjacent residential areas. The prevalences of habitats where Aedes larvae were found were 43% and 9% for the parks and residential areas, respectively. The difference was statistically significant (prevalence ratio [PR]: 5.00, 95% CI: 3.85-6.49). The prevalences of positive larval habitats were significantly greater in the parks for both species than the residential areas (PR: 1.52, 95% CI: 1.04-2.22 for A. aegypti, PR: 10.10, 95% CI: 7.23-14.12 for A. albopictus). Larvae of both species were positively associated with discarded containers and planters. Aedes albopictus larvae were negatively associated with indoor habitats, but positively associated with vegetation shade. The adult density of A. aegypti was significantly less in the parks compared with the residential areas (rate ratio [RR]; 0.09, 95% CI: 0.05-0.16), while the density of A. albopictus was significantly higher in the parks (RR: 9.99, 95% CI: 6.85-14.59). When the species were combined, the density was significantly higher in the parks (RR: 2.50, 95% CI: 1.92-3.25). The urban parks provide suitable environment for Aedes mosquitoes, and A. albopictus in particular. Virus vectors are abundant in the urban parks, and the current vector control programs need to have greater consideration of urban parks.

Novel Antiviral Efficacy of Hedyotis diffusa and Artemisia capillaris Extracts against Dengue Virus, Japanese Encephalitis Virus, and Zika Virus Infection and Immunoregulatory Cytokine Signatures.

Currently, there are no specific therapeutics for flavivirus infections, including dengue virus (DENV) and Zika virus (ZIKV). In this study, we evaluated extracts from the plants Hedyotis diffusa (HD) and Artemisia capillaris (AC) to determine the antiviral activity against DENV, ZIKV, and Japanese encephalitis virus (JEV). HD and AC demonstrated inhibitory activity against JEV, ZIKV, and DENV replication and reduced viral RNA levels in a dose-responsive manner, with non-cytotoxic concentration ranging from 0.1 to 10 mg/mL. HD and AC had low cytotoxicity to Vero cells, with CC50 values of 33.7 ± 1.6 and 30.3 ± 1.7 mg/mL (mean ± SD), respectively. The anti-flavivirus activity of HD and AC was also consistent in human cell lines, including human glioblastoma (T98G), human chronic myeloid leukemia (K562), and human embryonic kidney (HEK-293T) cells. Viral-infected, HD-treated cells demonstrated downregulation of cytokines including CCR1, CCL26, CCL15, CCL5, IL21, and IL17C. In contrast, CCR1, CCL26, and AIMP1 were elevated following AC treatment in viral-infected cells. Overall, HD and AC plant extracts demonstrated flavivirus replication inhibitory activity, and together with immunoregulatory cytokine signatures, these results suggest that HD and AC possess bioactive compounds that may further be refined as promising candidates for clinical applications.

Predicting malaria outbreaks from sea surface temperature variability up to 9 months ahead in Limpopo, South Africa, using machine learning.

Malaria is the cause of nearly half a million deaths worldwide each year, posing a great socioeconomic burden. Despite recent progress in understanding the influence of climate on malaria infection rates, climatic sources of predictability remain poorly understood and underexploited. Local weather variability alone provides predictive power at short lead times of 1-2 months, too short to adequately plan intervention measures. Here, we show that tropical climatic variability and associated sea surface temperature over the Pacific and Indian Oceans are valuable for predicting malaria in Limpopo, South Africa, up to three seasons ahead. Climatic precursors of malaria outbreaks are first identified via lag-regression analysis of climate data obtained from reanalysis and observational datasets with respect to the monthly malaria case count data provided from 1998-2020 by the Malaria Institute in Tzaneen, South Africa. Out of 11 sea surface temperature sectors analyzed, two regions, the Indian Ocean and western Pacific Ocean regions, emerge as the most robust precursors. The predictive value of these precursors is demonstrated by training a suite of machine-learning classification models to predict whether malaria case counts are above or below the median historical levels and assessing their skills in providing early warning predictions of malaria incidence with lead times ranging from 1 month to a year. Through the development of this prediction system, we find that past information about SST over the western Pacific Ocean offers impressive prediction skills (~80% accuracy) for up to three seasons (9 months) ahead. SST variability over the tropical Indian Ocean is also found to provide good skills up to two seasons (6 months) ahead. This outcome represents an extension of the effective prediction lead time by about one to two seasons compared to previous prediction systems that were more computationally costly compared to the machine learning techniques used in the current study. It also demonstrates the value of climatic information and the prediction framework developed herein for the early planning of interventions against malaria outbreaks.