Increase In Malaria Incidence Research Articles

Plasmodium falciparum population dynamics in East Africa and genomic surveillance along the Kenya-Uganda border

East African countries accounted for ~ 10% of all malaria prevalence worldwide in 2022, with an estimated 23.8 million cases and > 53,000 deaths. Despite recent increases in malaria incidence, high-resolution genome-wide analyses of Plasmodium parasite populations are sparse in Kenya, Tanzania, and Uganda. The Kenyan-Ugandan border region is a particular concern, with Uganda confirming the emergence and spread of artemisinin resistant P. falciparum parasites. To establish genomic surveillance along the Kenyan-Ugandan border and analyse P. falciparum population dynamics within East Africa, we generated whole-genome sequencing (WGS) data for 38 parasites from Bungoma, Western Kenya. These sequences were integrated into a genomic analysis of available East African isolate data (n = 599) and revealed parasite subpopulations with distinct genetic structure and diverse ancestral origins. Ancestral admixture analysis of these subpopulations alongside isolates from across Africa (n = 365) suggested potential independent ancestral populations from other major African populations. Within isolates from Western Kenya, the prevalence of biomarkers associated with chloroquine resistance (e.g. Pfcrt K76T) were significantly reduced compared to wider East African populations and a single isolate contained the PfK13 V568I variant, potentially linked to reduced susceptibility to artemisinin. Overall, our work provides baseline WGS data and analysis for future malaria genomic surveillance in the region.

The Relationship Between Climate Change and Indonesia's Malaria Burden

ABSTRACTMalaria has been with humans for thousands of years. It is caused by parasites of the genus Plasmodium that are transmitted by female Anopheles mosquitoes. The variation of global malaria distribution has recently been associated with changing climatic conditions, such as temperature, precipitation, windspeed, and humidity. One country where malaria transmission remains high in select subnational areas is Indonesia. Founded upon previous findings on the relationship between climate change and malaria, this research delves into the same equation for the case of Indonesia through a structural model which overcomes the variable co‐interaction between temperature, precipitation, windspeed, and humidity. This study follows an ecological study design with yearly longitudinal data (t = 20, n = 432). The method of analysis employed is a structural equation modelling approach for panel datasets with an output of factor loading values to determine association levels. The independent variable is a climate change construct of maximum, minimum, and average values from temperature, windspeed, relative humidity and precipitation as observables taken from the NASA Langley Research Center (LaRC) POWER Project. Meanwhile, the dependent variable is yearly malaria incidence rates at the city and regency level extracted from the Malaria Atlas Project dataset. All variables are standardized to account for unit differences. The SEM results indicate a standardized relationship between a latent climate variable with malaria incidence in a statistically significant manner. However, differences in coefficient directions between the three models indicate that the relationship remains elusive. In the maximum value model, a standard deviation increase in the climate change construct from its mean is associated with a 0.04 standard deviation increase in malaria incidence from its own mean (p < 0.001). On the other hand, in the minimum and average value models, a standard deviation increase in limate change construct from its mean is associated with a 0.12 and 0.09 standard deviation decrease of malaria incidence from its own mean respectively (p < 0.001). Although statistical significance was established across all models which indicated relatively good fit across select indices, the standardized coefficient values presented in this study suggest that any associations between long term climatic variations (measured by yearly data) and malarial incidences are modest at best. The results of the structural equation models also indicate that other factors are at play when it comes to malaria case variations—as explained by the residual terms across all models.

Malaria epidemics associated with low net use in preadolescent and young adult population in Dielmo (Senegal), a malaria pre-elimination area

BackgroundThe epidemic rebounds observed in 2010 and 2013 in Dielmo, a Senegalese village, during a decade (2008–2019) of universal coverage using a long-lasting insecticidal net (LLIN) strategy could have contributed to the resurgence of malaria. Thus, this study was undertaken to understand the implications of net ownership and use on malaria rebound events.MethodsA longitudinal study was carried out in Dielmo with 11 years of LLIN implementation from July 2008 to June 2019 with successive net renewals in 2011, 2014, 2016 and 2019. Quarterly cross-sectional surveys were performed to assess LLIN ownership and use by different age groups in the population. In addition, malaria incidence and transmission were assessed during the study period.ResultsOwnership of LLINs decreased significantly from 88% in the 1st year of net implementation to 70% during the first malaria upsurge and 72% during the second upsurge while net use decreased significantly from 66% during the 1st year to 58% during the first malaria upsurge and 53% during the second upsurge.Among young adults aged 15–29 years, net use decreased significantly from the 2nd year (51%) of net use to reach 43% during the first malaria upsurge and only 32% use during the second malaria upsurge. During the second malaria upsurge, net use was significantly lower among older children aged 10–14 years old than during the 1st year of net use (p < 0.001). During the first and the second malaria upsurges, the malaria incidence was significantly higher among children aged 10–14 years old (0.4 attacks per person-year) and young adults aged 15–29 years old (0.3 and 0.4 attacks per person, respectively) than during that the 1st year of net implementation (only 0.02 attacks per person-year for 10–14 year olds and 0.04 for 15–29 year olds; p < 0.001).ConclusionsThe first malaria upsurge occurred following a progressive decrease in net use after the 2nd year of their implementation with an important increase in malaria incidence among older children while the second malaria upsurge was significantly associated with the decrease of net use among older children and young adults. The regular use of nets in all age groups prevented the occurrence of a third malaria upsurge in Dielmo.Graphical

Towards an intelligent malaria outbreak warning model based intelligent malaria outbreak warning in the northern part of Benin, West Africa

BackgroundMalaria is one of the major vector-borne diseases most sensitive to climatic change in West Africa. The prevention and reduction of malaria are very difficult in Benin due to poverty, economic insatiability and the non control of environmental determinants. This study aims to develop an intelligent outbreak malaria early warning model driven by monthly time series climatic variables in the northern part of Benin.MethodsClimate data from nine rain gauge stations and malaria incidence data from 2009 to 2021 were extracted from the National Meteorological Agency (METEO) and the Ministry of Health of Benin, respectively. Projected relative humidity and temperature were obtained from the coordinated regional downscaling experiment (CORDEX) simulations of the Rossby Centre Regional Atmospheric regional climate model (RCA4).A structural equation model was employed to determine the effects of climatic variables on malaria incidence. We developed an intelligent malaria early warning model to predict the prevalence of malaria using machine learning by applying three machine learning algorithms, including linear regression (LiR), support vector machine (SVM), and negative binomial regression (NBiR).ResultsTwo ecological factors such as factor 1 (related to average mean relative humidity, average maximum relative humidity, and average maximal temperature) and factor 2 (related to average minimal temperature) affect the incidence of malaria. Support vector machine regression is the best-performing algorithm, predicting 82% of malaria incidence in the northern part of Benin.The projection reveals an increase in malaria incidence under RCP4.5 and RCP8.5 over the studied period.ConclusionThese results reveal that the northern part of Benin is at high risk of malaria, and specific malaria control programs are urged to reduce the risk of malaria.

Spatial spillovers and the relationship between deforestation and malaria: evidence from the Peruvian Amazon

Of all forest species that transmit disease to humans, mosquitoes are considered the most responsive to ecosystem changes caused by deforestation. This study examines the relationship between deforestation and malaria cases in the Peruvian Amazon region while addressing spatial interdependence among districts by using a Spatial Durbin Model. Our primary results suggest that the total effect of a decline of 1,000 hectares of forest cover is associated with an additional 69 malaria cases. The spatial model allows us to further determine that both direct and spillover effects are positive. Following the Avoided Cost approach in Barbier et al., we estimate that the cost of the additional malaria cases could approach USD 24.8 million, an amount similar to the recent health program funded by the Peruvian government to combat malaria. Our findings suggest that policy makers should consider the trade-offs between the economic benefits of deforestation and the cost associated with increased malaria incidence.

Impact of Iron Supplementation in Anemic Voluntary First-Time Blood Donors-Results of a Pilot Trial in Ghana

Introduction : Blood transfusion is a major developmental challenge in sub-Saharan Africa due to chronic inadequacy and shortage of major blood products. In Ghana, deferral of potential blood donors has been identified as a significant challenge. Anemia, accounts for nearly half of ineligible blood donors. The estimated prevalence of anemia is 42.4% in women of reproductive age and 18.8% among peri-urban men ( Spring and Ghana Health service 2016). Thus, a high prevalence of anemia accounting for nearly half of voluntary blood donor deferrals, may contribute to the country's poor availability of safe blood for transfusion. No prior investigation had been carried out in Ghana on whether potential blood donors, deferred due to anemia, would consider donating blood after receiving counselling and appropriate treatment. This study tested the hypothesis that low-dose iron supplementation will increase hemoglobin levels sufficiently among anemic individuals to make them eligible to donate blood. Data from this trial informed the design of a larger randomized control type 1 pragmatic effectiveness implementation hybrid trial. Methods:This was a longitudinal two-arm parallel-group trial (participants aged 18 - 60 years). We compared the hemoglobin levels among those with anemia, iron deficiency (ID) or iron deficiency anemia (IDA) who received iron supplementation to donors without ID or IDA (Control group) in a non-inferiority design(NCT04949165). Anemia, IDA and ID were defined and determined using World Health Organization cut-off values (WHO, 2011). Potential blood donors with hemoglobin values less than 10 g/dl were excluded from the study. Participants in the iron supplementation arm were given low-dose iron (65 mg elemental iron) three times weekly for four months while the control arm received the standard nutritional counselling practice. In-person visits occurred at two, four and six months and included blood draws for full blood count, peripheral blood film smear, malaria rapid test and serum ferritin. The primary outcome was hemoglobin level after four months. A structured questionnaire assessed adherence, nutritional counselling and adverse events every two weeks via phone. Results: Two hundred and twenty-three first-time voluntary blood donors consented and passed pre-screening donation requirements (105 in iron supplementation arm vs. 118 in the control arm). The mean ages were similar between the iron supplementation and control groups (19.7±2.5 vs. 20.1±3.1 years). In both groups, there were more females than males (iron: 75.2%; control: 51.7%). At screening, 43.9% (98/223) had anemia while 3.1% (7/223) had ID. Of those who had anemia, 84.7% (83/98) had ferritin at least 15 g/l while 15.3% (15/98) had IDA. Among controls who donated blood at screening with an interim 1 visit, 42.6% (20/47) of females and 20.9% (9/43) of males were anemic. Only 23.4% (11/47) of females but no male was ID after one blood donation. Among participants assigned to iron supplementation who were anemic at screening, 31.7% (20/63) of females and 28.6% (6/21) of males were no longer anemic at interim visit 1. Among iron participants who were ID at screening 53.3% (8/15) of females and no male (0/2) were iron replete at interim visit 1. Only half of the participants receiving iron supplementation self-reported perfect adherence at the first and second interim visits (end of iron supplementation). A small proportion of participants reported side effects of dark stools and abdominal pain. We did not observe bacterial infections or increased malaria incidence. The mean hemoglobin values decreased over time from baseline to month four in the control group (screening: N=118, 13.4±1.3 g/dl; interim visit 2: N=74, 12.3±1.5 g/dl) and increased in the iron supplementation group (screening: N=105, 11.3±0.9 g/dl; interim visit 2: N=56, 11.4±1.3 g/dl). However, the primary comparison, mean hemoglobin difference between the iron supplementation and control arm at four months, did not meet the threshold to reject the inferiority hypothesis. Conclusion: The prevalence of ID and IDA among voluntary first-time blood donors was lower than previously published estimates. Adherence to low-dose iron supplementation three times a week was poor. Hemoglobin levels in the iron supplementation arm were not close enough to those in the control group after four months of iron supplementation to declare non-inferiority.

Revisiting the Impact of Dams on Malaria and Agriculture

We estimate the effect of large dams on malaria incidence in India between 1975 and 1995. We combine instrumental variables approach with a panel model with unobserved common factors allowing us to fully capture the endogeneity of dam location and unobserved time-varying heterogeneity. Dams result in increased malaria incidence in districts where dams are located and in downstream areas. We find that the construction of a large dam increases a district’s annual malaria incidence by about 0.9 to 1.4 percent, and by about 1 to 1.5 percent in downstream districts. We also find that this malaria-increasing effect of dams persists over time. Our results imply that the construction of dams in malaria-sensitive areas should be coupled with direct interventions, such as the wide deployment of insecticide-treated nets or the roll-out of future vaccines. Furthermore, we examine the contribution of agricultural development to this malaria-increasing effect of dams. We find that dam construction benefits agriculture in the vicinity of dams, as well as in downstream areas. These positive effects are driven by increased irrigation and cultivation in the vicinity of dams, while they are driven by changes in cropping patterns in downstream areas, where the cultivation of high-yielding variety crops increases. Finally, a back-of-the-envelope calculation suggests that the agricultural production gains from dam construction dominate the economic losses resulting from increased malaria.

Application of mathematical modelling to inform national malaria intervention planning in Nigeria

BackgroundFor their 2021–2025 National Malaria Strategic Plan (NMSP), Nigeria’s National Malaria Elimination Programme (NMEP), in partnership with the World Health Organization (WHO), developed a targeted approach to intervention deployment at the local government area (LGA) level as part of the High Burden to High Impact response. Mathematical models of malaria transmission were used to predict the impact of proposed intervention strategies on malaria burden.MethodsAn agent-based model of Plasmodium falciparum transmission was used to simulate malaria morbidity and mortality in Nigeria’s 774 LGAs under four possible intervention strategies from 2020 to 2030. The scenarios represented the previously implemented plan (business-as-usual), the NMSP at an 80% or higher coverage level and two prioritized plans according to the resources available to Nigeria. LGAs were clustered into 22 epidemiological archetypes using monthly rainfall, temperature suitability index, vector abundance, pre-2010 parasite prevalence, and pre-2010 vector control coverage. Routine incidence data were used to parameterize seasonality in each archetype. Each LGA’s baseline malaria transmission intensity was calibrated to parasite prevalence in children under the age of five years measured in the 2010 Malaria Indicator Survey (MIS). Intervention coverage in the 2010–2019 period was obtained from the Demographic and Health Survey, MIS, the NMEP, and post-campaign surveys.ResultsPursuing a business-as-usual strategy was projected to result in a 5% and 9% increase in malaria incidence in 2025 and 2030 compared with 2020, while deaths were projected to remain unchanged by 2030. The greatest intervention impact was associated with the NMSP scenario with 80% or greater coverage of standard interventions coupled with intermittent preventive treatment in infants and extension of seasonal malaria chemoprevention (SMC) to 404 LGAs, compared to 80 LGAs in 2019. The budget-prioritized scenario with SMC expansion to 310 LGAs, high bed net coverage with new formulations, and increase in effective case management rate at the same pace as historical levels was adopted as an adequate alternative for the resources available.ConclusionsDynamical models can be applied for relative assessment of the impact of intervention scenarios but improved subnational data collection systems are required to allow increased confidence in predictions at sub-national level.

Increased malaria incidence following irrigation practices in the Endorheic Rift Valley Basin of Sidama Region, Ethiopia.

Water resource development practice such as irrigation is key to ensuring economic growth and food security in developing countries. However, unintended public health problems such as malaria linked to such development projects have been a concern. This study aimed to determine the impact of irrigation on malaria incidence and vector mosquito abundance in southern Ethiopia. Eight years' malaria morbidity data were extracted from the medical registers of health facilities in both irrigated and non-irrigated settings. Additionally, adult and larval malaria vector surveys were carried out in both irrigated and non-irrigated villages. The trend of malaria incidence, case distribution across age and sex, seasonality, parasite species proportion, and mosquito density were analyzed and compared between irrigated and non-irrigated villages. The result showed that annual mean malaria incidence was 6.3 higher in the irrigated (95% CI: 0.7-33.6) than in the non-irrigated villages (95% CI: 1.2-20.6). Although a remarkable declining trend in malaria incidence was observed for four successive years (2013-2017), a significant resurgence between 2018 and 2020 was noted following the introduction of irrigation schemes. The densities of adult Anopheles mosquitoes were 15-fold higher in the irrigated compared to non-irrigated villages. Of the total potential mosquito-breeding habitats surveyed, the majority (93%) were from irrigated villages. Higher malaria incidence, adult Anopheles density, and mosquito-breeding habitat were recorded in the irrigated villages compared to non-irrigated villages. These observations have important implications for the effectiveness of existing malaria interventions. Environmental management could help reduce the breeding of malaria vector mosquitoes around irrigation schemes.

Effects of Contrasting Areas of Land Occupation and Housing Types on Malaria Incidence and Severity in Children under Five Years in Bolifamba, Buea

Purpose: Studies relating vector breeding sites, biting cycle and vector competence to malaria incidence in the most vulnerable population of endemic areas of the Mount Cameroon region are lacking. The purpose of this study was to compare the incidence and severity of malaria in children under 5 years in contrasting areas of land occupation in Bolifamba.&#x0D; Methodology: A cohort study design was used. In phase 1, Bolifamba South West Region was stratified in to three zones namely; zone I (Non-swampy/moderately populated), zone II (permanently swampy/highly populated) and zone III (temporally swampy/sparsely populated). Parents filled informed consent forms. A structured questionnaire was used to enroll 752 children under five years. In phase 2, entomological survey, DNA extraction and PCR for molecular form of parasite and infection were employed. Data was analyzed using the SPSS version 20. Malaria incidence was determined using Poisson regression. Kruskal-wallis test was used to compare malaria incidence and EIR. A Stratified sampling technique was used. A sample size of 752 was determine using a confidence level of 95%, ± 3% margin of error, 50% degree of variability, 95% response rate.&#x0D; Findings: The incidence of malaria in children under five years in Bolifamba was 11.2%. Malaria incidence per zone was: zone I (13.7%), zone II (14.7%) and zone III (5.2%). One thousand and seventy mosquitoes were collected. Anopheles gambiae complex (588) was the only malaria vector found in all Zones. P. falciparum and P. malariae were found in the three zones. The EIR; zone I (2.4), zone II (4.8) and zone III (3.6).&#x0D; Conclusion: Malaria incidence in children under five in contrasting areas differs and plank houses increase malaria incidence. The peak biting period was 1- 2am. Contrasting areas of the same town or village have different parous, infective and entomological inoculation rates.&#x0D; Recommendations: Mass distribution of insecticide treated bed nets to children under five years in Bolifamba by the government. Encourage the population to build block houses with ceilings. Monthly community clean up campaigns organized by each quarter head to drain stagnant water around houses in Bolifamba. Provision of better malaria control measures in order to eradicate malaria in Bolifamba.

Amphibian collapses increased malaria incidence in Central America *

Biodiversity in ecosystems plays an important role in supporting human welfare, including regulating the transmission of infectious diseases. Many of these services are not fully-appreciated due to complex environmental dynamics and lack of baseline data. Multicontinental amphibian decline due to the fungal pathogen Batrachochytrium dendrobatidis (Bd) provides a stark example. Even though amphibians are known to affect natural food webs—including mosquitoes that transmit human diseases—the human health impacts connected to their massive decline have received little attention. Here we leverage a unique ensemble of ecological surveys, satellite data, and newly digitized public health records to show an empirical link between a wave of Bd-driven collapse of amphibians in Costa Rica and Panama and increased human malaria incidence. Subsequent to the estimated date of Bd-driven amphibian decline in each ‘county’ (canton or distrito), we find that malaria cases are significantly elevated for several years. For the six year peak of the estimated effect, the annual expected county-level increase in malaria ranges from 0.76 to 1.1 additional cases per 1000 population. This is a substantial increase given that cases country-wide per 1000 population peaked during the timeframe of our study at approximately 1.5 for Costa Rica and 1.1 for Panama. This previously unidentified impact of biodiversity loss illustrates the often hidden human welfare costs of conservation failures. These findings also show the importance of mitigating international trade-driven spread of similar emergent pathogens like Batrachochytrium salamandrivorans.

Elucidating the status of malaria in Andaman and Nicobar Islands post-millennium 2000.

Malaria is a major vector-borne disease in the Indian sub-continent and has been pestering Andaman and Nicobar islands (ANI's) as well since British colonial times. A retrospective data mining technique has been adhered to assess the status of malaria for nineteen years from 2000 to 2019 in ANI's. The altered environment due to 2004 tsunami had increased malaria incidence significantly during (2005-2010). The Nicobar district recorded high incidence of malaria while the least in the north and middle Andaman district. Comparative high incidence of malaria was documented due to Plasmodium falciparum than Plasmodium vivax in the Nicobar district between 2005 and 2009. The declining trend of malaria-positive cases in ANI's was observed post 2010, articulating various initiatives taken by the local Andaman and Nicobar administration to curb this vector-borne disease. The initiatives were like (1) large-scale release of larvivorous fish, Gambusia affinis in the transient water pools, (2) outdoor application of DDT, (3) indoor application of Pyrethrum, (4) malaria awareness drive that led to the curbing of the proliferation not only the malaria vector but also other potential mosquito vector species as well, and (5) implementation of revised drug policy.

Moderate Rainfall and High Humidity During the Monsoon Season, Negligence in Using Malaria Protection Methods and High Proportion of Mild Symptomatic Patients Were the Driving Forces for Upsurge of Malaria Cases in 2018 Among Tea Tribe Populations in Endemic Dolonibasti Health Sub-center, Udalguri District, Assam State, North-East India.

Malaria elimination is a global priority, which India has also adopted as a target. Despite the malaria control efforts like long-lasting insecticidal nets distribution, rounds of indoor residual spray, the introduction of bi-valent rapid diagnostic tests and artemisinin combination therapy, malaria remained consistent in Dolonibasti sub-center of Orang block primary health center (BPHC) under the district Udalguri, Assam state followed by abrupt rise in cases in 2018. Therefore, we aimed to investigate the factors driving the malaria transmission in the outbreak area of Dolonibasti sub-center. Malaria epidemiological data (2008–2018) of Udalguri district and Orang BPHC was collected. The annual (2011-2018) and monthly (2013–2018) malaria and meteorological data of Dolonibasti sub-center was collected. An entomological survey, Knowledge, Attitude and Practices study among malaria cases (n = 120) from Dolonibasti was conducted. In 2018, 26.1 % (2136/ 8188) of the population of Dolonibasti were found to be malaria positive, of which 55% were adults (n = 1176). Majority of cases were from tea tribe populations (90%), either asymptomatic or with fever only, 67.5 % (81/120) had experienced malaria infection during past years. The outbreak was characterized by a strong increase in cases in June 2018, high proportion of slide falciparum rate of 26.1% (other years average, 15.8%) and high proportion of P. falciparum of 81.2 % (other years average, 84.3%). Anopheles minimus s.l. was the major vector with 28.6% positivity and high larval density in paddy fields/ drainage area. Annual relative humidity was associated with rise in malaria cases, annual parasite incidence (rs = 0.69, 90%CI; p = 0.06) and slide positivity rate (rs = 0.83, 95%CI; p = 0.01). Older people were less educated (rs = −0.66; p < 0.001), had lesser knowledge about malaria cause (rs = −0.42; χ2=21.80; p < 0.001) and prevention (rs = −0.18; p = 0.04). Malaria control practices were followed by those having knowledge about cause of malaria (rs = 0.36; χ2 = 13.50; p < 0.001) and prevention (rs = 0.40; χ2 = 17.71; p < 0.001). Altogether, 84.6% (44/52) of the respondents did not use protective measures. We described a sudden increase in malaria incidence in a rural, predominantly tea tribe population group with high illiteracy rate and ignorance on protective measures against malaria. More efforts that are concerted needed to educate the community about malaria control practices.

A Cautionary Tale Regarding the Use of Causal Inference to Study How Environmental Change Influences Tropical Diseases.

There has been substantial interest on the effect of large-scale environmental change, such as deforestation, on human health. An important and relatively recent development has been the use of causal-inference approaches (e.g., instrumental variables [IVs]) to more properly analyze this type of observational data. Here, we discuss an important study that attempted to disentangle the effect of malaria on deforestation from the effect of deforestation on malaria using an IV approach. The authors found that deforestation increases malaria (e.g., they estimate that a 10% increase in deforestation leads to a 3.3% increase in malaria incidence) through ecological mechanisms, whereas malaria reduces deforestation through socioeconomic mechanisms. An important characteristic of causal-inference approaches is that they are critically dependent on the plausibility of the underlying assumptions and that, differently from standard statistical models, many of these assumptions are not testable. In particular, we show how important assumptions of the IV approach adopted in the study described earlier were not met and that, as a result, it is possible that the correct conclusion could have been the opposite of that reported by the authors (e.g., deforestation decreases, rather than increasing, malaria through ecological mechanisms). Causal-inference approaches may be critical to characterize the relationship between environmental change and disease risk, but conclusions based on these methods can be even more unreliable than those from traditional methods if careful attention is not given to the plausibility of the underlying assumptions.

The impact of stopping and starting indoor residual spraying on malaria burden in Uganda

The scale-up of malaria control efforts has led to marked reductions in malaria burden over the past twenty years, but progress has slowed. Implementation of indoor residual spraying (IRS) of insecticide, a proven vector control intervention, has been limited and difficult to sustain partly because questions remain on its added impact over widely accepted interventions such as bed nets. Using data from 14 enhanced surveillance health facilities in Uganda, a country with high bed net coverage yet high malaria burden, we estimate the impact of starting and stopping IRS on changes in malaria incidence. We show that stopping IRS was associated with a 5-fold increase in malaria incidence within 10 months, but reinstating IRS was associated with an over 5-fold decrease within 8 months. In areas where IRS was initiated and sustained, malaria incidence dropped by 85% after year 4. IRS could play a critical role in achieving global malaria targets, particularly in areas where progress has stalled.

Role of Anopheles stephensi Mosquitoes in Malaria Outbreak, Djibouti, 2019.

Anopheles stephensi mosquitoes share urban breeding sites with Aedes aegypti and Culex quinquefasciatus mosquitoes in the Republic of Djibouti. We present evidence that A. stephensi mosquitoes might be responsible for an increase in malaria incidence in this country. We also document resistance of Plasmodium falciparum to dihydroartemisinin/piperaquine.

Prevalence and Risk Factors of Asymptomatic Plasmodium Infection in Gondar Zuria District, Northwest Ethiopia.

BackgroundMalaria is one of the major public health problems worldwide. In Ethiopia, an increase in malaria incidence may be attributed to the presence of community-wide asymptomatic Plasmodium infection. This study aims to assess asymptomatic Plasmodium infection and associated factors in Gondar Zuria district, Northwest Ethiopia.MethodsA community-based cross-sectional study was conducted in Gondar Zuria district from May to June 2019. Angacha and Hamsafeg villages were randomly selected from Tachtseda and Hamsafeg kebeles, respectively. Fifty-three (53) households were selected using systematic random sampling to recruit a total of 251 study participants. Sociodemographic data were collected using structured questionnaires. Thin and thick blood films were prepared and examined for evidence of parasites. Data were entered and analyzed using SPSS version 23. The association between dependent (asymptomatic Plasmodium infection) and independent (sex, age group, family size and previous history of malaria) variables was explored using bivariate and multivariate logistic regression. Statistically significant association was declared at a P-value of <0.05.ResultsA total of 251 individuals were tested, of whom 53.4% were females and 33.5% were above the age of 30 years. The prevalence of asymptomatic Plasmodium infection was 12%. The highest prevalence of malaria was observed in females (6.4%) and among the age group 15–29 years (4.4%). The majority (70%) of study participants had <500 parasites/μL of blood. A high parasitemia level (ie ≥1000 parasites/μL of blood) was observed in the age group 15–29 years. Age group, bed net usage and previous history of malaria were significantly associated with asymptomatic Plasmodium infection (P<0.05).ConclusionAsymptomatic Plasmodium infection remains an important public health problem in the study area. Further studies using more sensitive diagnostic methods are required to scale up the eradication and control program of malaria.

Lack of Consistent Malaria Incidence Hotspots in a Highland Kenyan Area During a 10-Year Period of Very Low and Unstable Transmission.

The use of spatial data in malaria elimination strategies is important to understand whether targeted interventions against malaria can be used, particularly in areas with limited resources. We previously documented consistent areas of increased malaria incidence in the epidemic-prone area of Kipsamoite in highland Kenya from 2001 to 2004. In this area and a neighboring subcounty (Kapsisiywa), malaria incidence decreased substantially in 2005, going from peak incidence of 31.7 per 1,000 persons in June 2004 to peak incidence of 7.4 per 1,000 persons in May 2005. Subsequently, the use of indoor residual spraying and artemisinin combination therapy malaria treatment led to a possible interruption of malaria transmission for a 13-month period from 2007 to 2008, after which the incidence returned to very low levels until an epidemic in April-July 2013. In the present study, we used novel kernel density estimation methods to determine whether areas of increased malaria incidence were consistent in six periods of peak incidence from 2003 to 2013, and to assess patterns of incidence in the period before versus. after the period of possible interruption. Areas of highest incidence differed during peak malaria transmission periods over the years 2003-2013, and differed before and after the potential malaria interruption. In this epidemic-prone region with very low malaria transmission, consistent malaria "hotspots" identified in a time of higher transmission are no longer present. Ongoing assessment of spatial malaria epidemiology to identify and target current areas of elevated malaria risk may be important in campaigns to control or eliminate malaria in epidemic-prone areas.

Discovery of FNDR-20123, a histone deacetylase inhibitor for the treatment of Plasmodium falciparum malaria

BackgroundEmergence of anti-malarial drug resistance and perpetual increase in malaria incidence necessitates the development of novel anti-malarials. Histone deacetylases (HDAC) has been shown to be a promising target for malaria, despite this, there are no HDAC inhibitors in clinical trials for malaria treatment. This can be attributed to the poor pharmacokinetics, bioavailability and selectivity of the HDAC inhibitors.MethodsA collection of HDAC inhibitors were screened for anti-malarial activity, and the best candidate was profiled in parasite-killing kinetics, growth inhibition of sensitive and multi-drug resistant (MDR) strains and against gametocytes. Absorption, distribution, metabolism and excretion pharmacokinetics (ADME-PK) parameters of FNDR-20123 were determined, and in vivo efficacy was studied in a mouse model for Plasmodium falciparum infection.ResultsA compound library of HDAC inhibitors (180 in number) was screened for anti-malarial activity, of which FNDR-20123 was the most potent candidate. The compound had been shown to inhibit Plasmodium HDAC with IC50 of 31 nM and human HDAC with IC50 of 3 nM. The IC50 obtained for P. falciparum in asexual blood-stage assay was 42 nM. When compared to atovaquone and pyrimethamine, the killing profiles of FNDR-20123 were better than atovaquone and comparable to pyrimethamine. The IC50 values for the growth inhibition of sensitive and MDR strains were similar, indicating that there is no cross-resistance and a low risk of resistance development. The selected compound was also active against gametocytes, indicating a potential for transmission control: IC50 values being 190 nM for male and > 5 µM for female gametocytes. FNDR-20123 is a stable candidate in human/mouse/rat liver microsomes (> 75% remaining post 2-h incubation), exhibits low plasma protein binding (57% in humans) with no human Ether-à-go–go-Related Gene (hERG) liability (> 100 µM), and does not inhibit any of the cytochrome P450 (CYP) isoforms tested (IC50 > 25 µM). It also shows negligible cytotoxicity to HepG-2 and THP-1 cell lines. The oral pharmacokinetics in rats at 100 mg/kg body weight shows good exposures (Cmax = 1.1 µM) and half-life (T1/2 = 5.5 h). Furthermore, a 14-day toxicokinetic study at 100 mg/kg daily dose did not show any abnormality in body weight or gross organ pathology. FNDR-20123 is also able to reduce parasitaemia significantly in a mouse model for P. falciparum infection when dosed orally and subcutaneously.ConclusionFNDR-20123 may be a suitable candidate for the treatment of malaria, which can be further developed.

Risk factors associated with high malaria incidence among communities in selected wards in Binga district, Zimbabwe: a case-control study

Background: Malaria remains a global problem with 216 million cases reported in 2016 and 90% of these cases were recorded in African countries. In 2018 Binga district in Zimbabwe experienced epidemics which resulted in an increase in malaria incidence from 14/1000 in 2015 to 34/1000 in 2018. This occurrence reversed the progress of wards that were moving towards malaria elimination. This study, therefore, was conducted to investigate risk factors that were associated with high malaria incidence in selected wards in Binga District. Methods: A case-control study was conducted on sixty-one systematically randomly selected malaria cases that were matched with one hundred and eighty-three controls to identify risk factors associated with malaria infection in selected wards. The sample size was determined using EPI INFO sample size calculator and matching is done using geographic location and sex of respondents. Information on previous exposure to a risk factor(s) was obtained through a researcher administered questionnaire. Multiple Logistic Regression was conducted to determine the relationship between risk factors and malaria incidence in cases and controls on STATA Version 12 SE. Results: On comparison, cases were more likely to have been sleeping in poorly constructed shelters with one or more house openings [OR= 5.47; CI=2.39-12.51], their household located near an active/potential mosquito breeding site or water body [OR= 5.86; CI= 2.61- 13.17] and did not own a treated bed net [OR= 9.14; CI=4.08-20.45]. Early Treatment seeking behaviour had a significant protective effect [OR= 0.51; CI= 0.39-0.86] and delay to seek treatment was influenced by distance to a health facility [OR=5.91; CI=3.02-11.55] just to mention a fewAU: Please confirm that the provided email ''18851726962@163.com" is the correct address for official communication, else provide an alternate e-mail address to replace the existing one. Conclusions: Findings of this study highlight important risk factors that are influential in the transmission of malaria. There is a need for the district to invest in source reduction by use of larvicides and reduction of possible breeding sites so as to minimise breeding. There is need to also embark on awareness campaigns to educate the community members on how they could eliminate some of the risk factors that are related to attitudes and practices. These strategies if adopted could improve the community's outcomes in as far as malaria is concerned.