ARTICLE | doi:10.20944/preprints202303.0492.v1
Subject: Medicine And Pharmacology, Tropical Medicine Keywords: Malaria parasitaemia; Risk factors; Malaria Diagnosis; infectious mode in children
Online: 28 March 2023 (14:58:24 CEST)
Background: Malaria remains a serious public health concern worldwide, particularly in tropical and subtropical regions, and the leading causes of mortality and morbidity in children especially among those aged under five in developing countries. Malaria can be fatal if not promptly and accurately diagnosed, especially in children.This study was carried out to determine the level of malaria infection and its associated risk factors among febrile children.Methods: Blood samples were collected and analyzed from two- hundred (200) systematically selected febrile children aged 1-10 years old. assay of samples collected were carried out using standard methods.data were collected using a pretested structured questionnaire. Results: Results obtained from study subjects shows that, of the eighty-seven (87) infected subjects, 34 (39.1%) were aged 1-5 years, while 52 (59.8%) were within the range of 6 years and above.severity of infection showed 48 (55.2%) with scanty parasitic infection while 25 (28.7%) showed moderate infection, and 13 (14.9%) showed heavy infection.The association of age and level of parasitemia showed that 34 (58.8% ) subjects below 5 years, recorded scanty malaria compared to 14.7% with severe malaria within the age range.Considering gender, of the 33 infected female subjects, 45.5% had scanty malaria, 36.4% showed moderate malaria, while 18.2% had severe malaria, compared to the males subjects.Conclusion: This study reveals the prevalence of malaria infection with some level of severity among children at our study location.The need for prompt diagnosis and improved access to all malaria interventions becomes relevant,with a special focus on the high risk group.
ARTICLE | doi:10.20944/preprints202202.0086.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Malaria transmission; Sub-microscopic; low-density; parasitaemia; rapid diagnostic test
Online: 7 February 2022 (12:55:46 CET)
Global malaria epidemiology has changed in the last decade with a substantial increase in cases and death being recorded. Over 90% of global cases and deaths occur in Sub-Saharan Africa (SSA). Tanzania accounts for about 4% of all cases and deaths reported in recent years. It is believed that several factors contribute to the resurgence of malaria, parasite resistance to antimalarials and mosquito resistance to insecticides being at the top of the list. The presence of sub-microscopic infections poses a significant challenge to malaria rapid diagnostic tests (mRDT), particularly in low-endemic areas. Our cross-sectional surveys in Handeni and Moshi, Tanzania assessed the effect of low parasite density on mRDT. A significant difference (P˂0.001) in malaria prevalence by mRDT, light microscopy (LM) and nested polymerase chain reaction (PCR) was found among age groups. In comparison to all other groups, school-age children (5-15 years) had the highest prevalence of malaria. Based on the results of this study, mRDT may miss up to 6% of cases of malaria mainly due to low-density parasitaemia. Routinely used mRDT will likely miss the sub-microscopic parasitemia which will ultimately contribute to the continued spread of malaria and hinder efforts to control and eliminate it.
ARTICLE | doi:10.20944/preprints202208.0275.v2
Subject: Environmental And Earth Sciences, Environmental Science Keywords: projections; CMIP6; climate; impacts; health; malaria; Malaria; Senegal
Online: 16 August 2022 (05:46:38 CEST)
Malaria is a constant reminder of the climate change impacts on health. Many studies have investigated the influence of climatic parameters on the of malaria transmission. Climate conditions can modulate malaria transmission through increased temperature, which reduces the duration of the parasite's reproductive cycle inside the mosquito. The intensity and frequency of the rainfall modulate the development of the mosquito population. In this study, the Liverpool Malaria Model (LMM) is used to simulate the spatio-temporal variation of the malaria incidence in Senegal. The simulations are based on the WATCH Forcing Data applied to ERA-Interim data (WFDEI) used as a point of reference, and biased-corrected CMIP6 models, separating historical and projections for 3 Shared Socio-economic Pathways scenarios (SSP126, SSP245 and SSP585). Our results highlight a strong increase in temperatures, especially towards eastern Senegal under the SSP245 but mainly the SSP585 scenarios. The ability of the LMM model to simulate the seasonality of malaria incidence is assessed. The model reveals a period of high malaria transmission between September and November with a maximum reached in October. Results indicate a decrease in malaria incidence in certain regions of the country for the far future and for the extreme scenario. This study is importance for the planning, prioritization, and implementation of control activities in Senegal.
ARTICLE | doi:10.20944/preprints202010.0522.v1
Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: malaria model; transition matrix; Markov chain; malaria statistics
Online: 26 October 2020 (12:22:20 CET)
The purpose of this study is to estimate the mean transitioning probabilities from a Healthy state to malaria positive uncomplicated state or to malaria positive severe state. It also classifies the various transitioning probabilities of moving through the various states based on some baseline characteristics. Malaria test results for 2019 over a 12-month period were collected from the University of Ghana school clinic. An H-U model for the study was developed and the transition rates from the cross-sectional data are indicated. With two states Healthy (H) and Uncomplicated (U) forming a state space, there were four possible transitions. The results show that the probability of transitioning from a Healthy state to a malaria positive state is 0.03% while the probability that an individual will remain at Healthy state (H) after the test is 99.73%. It was found that if an individual is already positive and has taken medication the probability that its second test came out negative is 6.45% while the chances that it will remain positive but uncomplicated is 93.55%. The study also showed that in the long run, about 95.98% of persons who visited the student clinic with malaria symptoms recorded negative tests for malaria parasite while about 4% recorded positive for malaria. In terms of disaggregation by gender, it was realized that the number of reported negative test results were higher for females (97.08%) than for males (96.13%). However, the infection rate is higher for males (3.87%) than females (2.92%). It is recommended that in as much as the University of Ghana has two health centers (a clinic and hospital), there should be a centralized system to track students’ health so research done would not be biased.
ARTICLE | doi:10.20944/preprints201809.0186.v1
Subject: Computer Science And Mathematics, Applied Mathematics Keywords: malaria; mass action; malaria-pneumonia; optimal control; pneumonia
Online: 11 September 2018 (08:01:51 CEST)
Malaria and Pneumonia are leading causes of serious illness in children and adults worldwide with their death rate and prevalence on the rise. Such alarming statistics may retard the milestones so far achieved in meeting the Millennium Development Goals 4 and 6 whose targets are to improve child survival and reverse the high prevalence of diseases such as pneumonia and malaria respectively. Two sub-models of malaria-pneumonia co-infection namely malaria model and pneumonia model were considered first and then followed by the full malaria-pneumonia co-infection model. The malaria model, pneumonia model and co-infection model basic reproduction numbers denoted by Rm, Rp and Rmp respectively was obtained using the Next Generation Matrix method. The model disease free equilibrium’s local and global stability was analysed using Descartes’ Rule of signs and Comparison method. The bifurcation analysis for the malaria, pneumonia and co-infection models was studied using the Centre Manifold Theory. The sensitivity indices of the model basic reproduction numbers Rm, Rp and Rmp to the parameters in the models were calculated. Optimal control theory was applied using the Pontryagins’ Maximum Principle to investigate optimal strategies for controlling the spread of malaria, pneumonia and co-infection models using insecticide treated bed nets (u1(t)) spraying of mosquitoes insecticides (u2(t)), sanitation (u3(t)), vaccination (u4(t)), anti-malaria drugs (u5(t)), anti-pneumonia drugs (u6(t)), both anti-malaria drugs and anti-pneumonia drugs (u7(t)) as the system time control variables. Numerical simulations using a set of parameter values were provided to validate the analytical results.
REVIEW | doi:10.20944/preprints202202.0067.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Antimalarial Drug; Malaria Vaccine; Drug Discovery; Artimisnine; K13; Malaria
Online: 4 February 2022 (10:22:34 CET)
Mosquitoes conveying Plasmodium store parasites into the skin of the mammalian host. Parasites make a trip through the circulation system to the liver, where they cross a few hepatocytes prior to building up a disease. Inside the last hepatocyte the parasite goes through morphogenesis and afterward abiogenetically partitions to become more than 20,000 blood-infective parasites, called merozoites. On account of P. vivax, P. ovale, and P. cynomolgi, the parasites can stay lethargic in the liver in structures called hypnozoites. The merozoites are delivered once again into the circulation system, where they start the repetitive blood stage. Inside erythrocytes, a little division of parasites separate into male or female gametocytes. These gametocytes are ingested by the mosquito during blood taking care of, where they will duplicate explicitly, in the long run prompting the arrangement of sporozoites
ARTICLE | doi:10.20944/preprints201811.0429.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: drug repurposing; drug repositioning; computational biology; drug discovery; computational pharmacology; malaria; multitargeting; malaria treatment
Online: 19 November 2018 (07:31:08 CET)
Drug repurposing is a valuable tool for combating the slowing rates of novel therapeutic discovery. The Computational Analysis of Novel Drug Opportunities (CANDO) platform performs shotgun repurposing of 2030 indications/diseases using 3733 drugs/compounds to predict interactions with 46,784 proteins and relating them via proteomic interaction signatures. An accuracy is calculated by comparing interaction similarities of drugs approved for the same indications. We performed a unique subset analysis by breaking down the full protein library into smaller subsets and then recombining the best performing subsets into larger supersets. Up to 14% improvement in accuracy is seen upon benchmarking the supersets, representing a 100–1000 fold reduction in the number of proteins considered relative to the full library. Further analysis revealed that libraries comprised of proteins with more equitably diverse ligand interactions are important for describing compound behavior. Using one of these libraries to generate putative drug candidates against malaria results in more drugs that could be validated in the biomedical literature than the list suggested by the full protein library. Our work elucidates the role of particular protein subsets and corresponding ligand interactions that play a role in drug repurposing, with implications for drug design and machine learning approaches to improve the CANDO platform.
ARTICLE | doi:10.20944/preprints202108.0160.v1
Subject: Biology And Life Sciences, Insect Science Keywords: Pyrethroid; pyrethroid resistance; insecticide resistance; insecticide resistance management; vector control; malaria; malaria control; mosquito; Anopheles
Online: 6 August 2021 (11:19:25 CEST)
Pyrethroid resistance is widespread in malaria vectors. However, differential mortality in discriminating dose assays to different pyrethroids is often observed in wild populations. When this occurs, it is unclear if this differential mortality should be interpreted as an indication of differential levels of susceptibility within the pyrethroid class, and if so, if countries should consider selecting one specific pyrethroid for programmatic use over another. A review of evidence from molecular studies, resistance testing with laboratory colonies and wild populations, and mosquito behavioural assays was conducted to answer these questions. Evidence suggests that in areas where pyrethroid resistance exists, different results in insecticide susceptibility assays with specific pyrethroids currently in common use (deltamethrin, permethrin, α-cypermethrin and λ-cyhalothrin) are not necessarily indicative of an operationally relevant difference in potential performance. Consequently, it is not advisable to use rotation between these pyrethroids as an insecticide resistance management strategy. Less commonly used pyrethroids (bifenthrin and etofenprox) may have sufficiently different modes of action, though further work would be needed to examine how this may apply to insecticide resistance management.
ARTICLE | doi:10.20944/preprints201907.0341.v1
Subject: Computer Science And Mathematics, Probability And Statistics Keywords: malaria; indwelling malaria control; insecticide treated net (ITN); pregnancy; socio-economic; logistic regression; odds ratio
Online: 30 July 2019 (14:40:53 CEST)
Malaria is endemic in Nigeria and remains a major public health problem, taking its greatest toll on children under age 5 and pregnant women, although it is preventable, treatable, and curable. This study investigates the Impact of socio-economic factors and indoor mosquito control on malaria prevalent among pregnant women in Nigeria using logistic regression. To achieve this, secondary data obtained from 2015 Nigeria Malaria Indicator survey, executed by the National Malaria Elimination Programme (NMEP) and the National Population Commission (NPopC), with a nationally representative sample of more than 8,000 consisting of 7,745 households. The results from the logistic regression with odds ratio revealed that pregnant women are more like to be affected by malaria fever (though not significant) compared to women that are not pregnant. The income levels of the household does not significant reduce the incidence of malaria fever among pregnant women in Niger. Concerning the malaria presenting measure, only dwelling sprayed by private company significantly reduce the incidence of malaria fever among pregnant women (P-value=0.020<0.05) compared to dwelling sprayed by government and NGOs and also to Insecticide Treated Net. Also pregnant women in the urban centers are less likely to have malaria fever compared to pregnant women in rural communities in Nigeria. Also, pregnant women with atleast a secondary school level of education are less likely to be affected by malaria fever compared to pregnant women with no formal education. The fitted logistic model passed the goodness-of-test fit; the classification test for the logistic model was correctly classified at about 67.02%. Therefore, this study recommends that government and NGOs should intensify their efforts in the area of dwelling spraying, awareness campaign of the danger of malaria fever among pregnant women and infants, engaged in effective distribution of insecticide treated net in order to reduce the incidence of malaria fever among pregnant women living in rural communities in Nigeria.
ARTICLE | doi:10.20944/preprints202207.0461.v1
Subject: Computer Science And Mathematics, Information Systems Keywords: Malaria; digital; epidemic; mixed infections; reinforcement
Online: 29 July 2022 (11:25:46 CEST)
Malaria is a long-standing disease and one of the top life-threatening diseases, yet its treatment has not changed, while the world has already embraced the Fourth Industrial Revolution (4IR). A wave of research on digitizing monitoring mechanisms of such a deadly disease has surfaced. Automated malaria screening is one of the detection processes which are gaining popularity in the research domain. However, the process needs to be coupled with other processes aiming a nationally or regionally contextualised malaria monitoring system. This paper proposes a digital malaria monitoring system in the context of an African country or region. One advantage of such a digital system is that is enables a novel disease spread forecasting model based on the dynamics of different malaria types. The architecture of the diagnosis system is described, and the disease spread model is mathematically modelled in terms of a SPITR (Susceptible- Protected- Infected-Treated- Recovered) epidemic model which is further analysed. The forecasting model is expressed and analysed whereas experiments are conducted using a Monte Carlo simulation method. The design of the monitoring system has inspired how predictions can be made in the complex cases such as mixed infections. Results show that reinforcing the model parameter makes a significant improvement on the disease prediction.
ARTICLE | doi:10.20944/preprints202111.0243.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Feature Selection; Malaria Diagnosis; Supervised learning
Online: 15 November 2021 (10:36:16 CET)
Malaria remains an important cause of death, especially in sub-Saharan Africa with about 228 million malaria cases worldwide and an estimated 405,000 deaths in 2019. Currently, malaria is diagnosed in the health facility using a microscope (BS) or rapid malaria diagnostic test (MRDT) and with area where these tools are inadequate the presumptive treatment is performed. Apart from that self-diagnosis and treatment is also practiced in some of the households. With the high-rate self-medication on malaria drugs, this study aimed at computing the most significant features using feature selection methods for best prediction of malaria in Tanzania that can be used in developing a machine learning model for malaria diagnosis. A malaria symptoms and clinical diagnosis dataset were extracted from patients’ files from four (4) identified health facilities in the regions of Kilimanjaro and Morogoro. These regions were selected to represent the high endemic areas (Morogoro) and low endemic areas (Kilimanjaro) in the country. The dataset contained 2556 instances and 36 variables. The random forest classifier a tree based was used to select the most important features for malaria prediction. Regional based features were obtained to facilitate accurate prediction. The feature ranking as indicated that fever is universally the most influential feature for predicting malaria followed by general body malaise, vomiting and headache. However, these features are ranked differently across the regional datasets. Subsequently, six predictive models, using important features selected by feature selection method, were used to evaluate the features performance. The features identified complies with malaria diagnosis and treatment guideline provided with WHO and Tanzania Mainland. The compliance is observed so as to produce a prediction model that will fit in the current health care provision system in Tanzania.
ARTICLE | doi:10.20944/preprints202107.0491.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Households; antimalarial; Health seeking behaviour; malaria
Online: 21 July 2021 (11:51:26 CEST)
(1) Background: The Democratic Republic of the Congo (DRC) is heavily affected by malaria despite availability of effective treatments. Ignorance and unrecommended behaviour toward a suspected malaria case in households may contribute to this problem. (2) Method: In communities of one rural and one urban Health Centers in each of the 11 previous provinces of DRC, all households with a case of malaria in the 15 days prior to the survey were selected. The patient or caregiver (responder) were interviewed. Logistic regression was used to assess predictors of knowledge of recommended antimalarials and good behaviour in case of suspected malaria. (3) Results: 1,732 households participated; about 62% (1060/1721) of the responders were informed about antimalarials, 70.1% (742/1059) knew the recommended antimalarial and 58.6% (995/1699) resorted on self-medication. Predictors of knowledge of antimalarials were education to secondary school or university, information from media and smaller households. Predictors of good behaviour were catholic religion and smaller households. Receiving information from CHW failed to be determinants of knowledge or adequate attitude. (4) Conclusion: malaria control in DRC is hampered by ignorance and non-adherence to national recommendations. These aspects are influenced by unsuccessful communication, size of households and level of education.
ARTICLE | doi:10.20944/preprints202305.1096.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Malaria; Plasmodium enolase; Band 3; antibodies; hRBCghosts
Online: 16 May 2023 (05:17:02 CEST)
The antibodies targeting invasive proteins of Plasmodium falciparum (Pf) merozoites is a clever strategy against malaria parasite. The recent finding that Plasmodium merozoites surface enolase is a target for growth neutralizing antibodies has generated interest in identifying its re-ceptor (s) on erythrocytes. In the present study, several biochemical experiments were undertaken involving recombinant Pf enolase and antibody against it to search for its cognate receptor. The binding of rPfeno to erythrocytes was selectively sensitive to trypsin but resistant to neuramini-dase. Failure of yeast enolase binding to human red blood cells under similar conditions indicat-ed high specificity of parasite Pfeno. The mass spectrometric and immunological analyses of pro-teins obtained in pull downs and co-immunoprecipitation samples led to identification of band 3 as an interactor/receptor for Plasmodium enolase. Structural characterization of sequences of band 3 - rPfeno interacting regions revealed C-terminal exocytic regions of band 3 to be binding to Pfeno. Similarly, band 3 binding regions of rPfeno were also identified. Identification of receptor-ligand (band 3: Pfeno) pair paves the way for antimalarial anti-Pf enolase-based vaccine, anti-Pf enolase antibodies as drug and also for developing novel small molecule-based invasion inhibi-tory therapeutics including peptidomimetics that could disrupt the band 3: Pfeno protein-protein interactions.
ARTICLE | doi:10.20944/preprints202304.1240.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: IL17A; malaria; Plasmodium falciparum; serum level; polymorphism.
Online: 30 April 2023 (02:35:08 CEST)
Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria, whether IL-17A gene polymorphisms are involved in severe malaria susceptibility and the polymorphism’s influence on the IL-17A serum levels. 125 malaria patients and 48 free malaria controls were enrolled in this research. Malaria patients were classified into severe malaria (SM) and uncomplicated malaria (UM). IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum level and malaria outcome. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P<0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (GG). According to our results, it can be concluded that IL-17A may play a role in protection against fatal malaria outcomes.
ARTICLE | doi:10.20944/preprints202108.0108.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: malaria; Plasmodium knowlesi; trends; retrospective; incidence; Malaysia
Online: 4 August 2021 (12:02:44 CEST)
While there has been a tremendous decline in malaria disease burden in the remote parts of the Malaysia, little is known about malaria incidence in its urban localities. This study aimed to analyse trends of malaria cases in urban Kuala Lumpur, Malaysia. All suspected cases presented to a university hospital in Kuala Lumpur from January 2005 to December 2020 were examined by microscopy. Infection status was analysed using descriptive statistics and curve estimation analysis. Of 3105 blood films examined, 92 (3%) were microscopically confirmed malaria cases. Plasmodium vivax infections accounted for the majority (36.9%) of all malaria cases. Nearly half (47.8%) of cases were found among foreign cases (P<0.001). The majority of foreign cases were males (86.4%) and came from Southeast Asian countries (65.9%). Curve estimation analysis showed significant decreases of malaria cases due to P. vivax (R2 = 0.598; P<0.001) and Plasmodium falciparum (R2 = 0.0259, P = 0.029), but increase for Plasmodium knowlesi (R2 = 0.325, P = 0.021) during the 16 years. This study revealed that malaria incidence in urban Kuala Lumpur is low and has remained stable since 2005. However, P. knowlesi played a significant role in the increase of overall malaria in the area, highlighting the importance of continued vigilance and improved surveillance.
ARTICLE | doi:10.20944/preprints202011.0277.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Malaria; Anopheles funestus; Insecticide resistance; Mount Cameroon
Online: 9 November 2020 (11:07:47 CET)
Increased levels of insecticide resistance in major malaria vectors such as Anopheles funestus threaten the effectiveness of insecticide-based control programmes. Understanding the landscape features impacting the spread of resistance makers is necessary to design suitable resistance management strategies. Here we examined the influence of the highest mountain in West Africa (Mount Cameroon; 4,100 meters elevation) on the spread of metabolic and target-site resistance alleles in An. funestus populations. Vector composition varied across the four localities surveyed along the altitudinal cline with major vectors exhibiting high parity rate (80.5%). Plasmodium infection rates ranged from 0.79% (An. melas) to 4.67% (An. funestus). High frequencies of GSTe2R (67% - 81%) and RdlR (49% - 90%) resistance alleles were observed in An. funestus throughout the study area, with GSTe2R frequency increasing with altitude whereas the opposite is observed for RdlR. Patterns of genetic diversity and population structure analyses revealed high levels of polymorphisms with 12 and 16 haplotypes respectively for GSTe2 and Rdl. However, the reduced diversity patterns of resistance allele carriers revealed signatures of positive selection on the two genes across the study area irrespective of the altitude. Despite slight variations associated with the altitude, the spread of resistance alleles suggest that control strategies could be implemented against malaria vectors across mountainous landscapes.
ARTICLE | doi:10.20944/preprints202007.0004.v1
Subject: Biology And Life Sciences, Insect Science Keywords: Blood Meal Source; Malaria; Honduras; Plasmodium spp
Online: 2 July 2020 (12:52:53 CEST)
Malaria remains a life-threatening disease in many tropical countries. Honduras has successfully reduced malaria transmission as different control methods have been applied focusing mainly on indoor mosquitoes. The selective pressure exerted by the use of insecticides inside the households could modify the feeding behavior of the mosquitoes forcing them to search for available animal hosts outside the houses. These animal hosts in the peridomicile could consequently become an important factor in maintaining vector populations in endemic areas. Herein, we investigated the blood meal sources and Plasmodium spp. infection on anophelines collected outdoors in endemic areas of Honduras. Individual PCR reactions with species-specific primers were used to detect five feeding sources on 181 visibly engorged mosquitoes. In addition, a subset of these mosquitoes where chosen for pathogen analysis by a nested PCR approach. Most mosquitoes fed on multiple hosts (2 to 4), and 24.9% of mosquitoes were fed on a single host, animal or human. Chicken and bovine were the most frequent blood meal sources (29.5% and 27.5% respectively). The average human blood index (HBI) was 22.1%. None of the mosquitoes was found to be infected with Plasmodium spp. Our results show the opportunistic and zoophilic behavior of Anopheles mosquitoes in Honduras.
ARTICLE | doi:10.20944/preprints202209.0461.v1
Subject: Social Sciences, Psychology Keywords: Persuasive Technology; Malaria Prevention and Control Support System (MPCSS); active inter-vention tool; Mosquitoes; Malaria Related Deaths (MRDs)
Online: 29 September 2022 (08:49:42 CEST)
Malaria is one of the leading causes of illnesses and deaths in Africa at large and Nigeria in particular, especially amongst pregnant women and children under the age of five years. Our research revealed that though the government has deployed so many intervention systems to contend with this death-causing vector—the mosquitoes, malaria related deaths (MRDs) have continued to increase. This is because people have not sufficiently adopted those intervention systems to protect themselves. Further enquiries into the ineffective compliance of the people to the intervention systems revealed that the interventions are passive in nature. Based on these, we set up three measurable research outcomes to enable us to determine the appropriateness of persuasive technology in solving the malaria problem. We technically avoided a one-size-fits-all design approach and adopted Participatory System Design (PSD) and User-Centered Design (UCD) approaches in our system design methodologies. Well-structured questionnaires were used to extract information from the participants. The data obtained from the research survey was used in modeling the intervention system. The research was conducted in three phases: baseline, development and deployment of an intervention system—the Malaria Prevention and Control Support System (MPCSS), and an evaluation study to determine the performance of the intervention system. The research led to the following achievements: (1) encouraged an increase in the number of people who participated in malaria prevention and control activities by lowering the rate of malaria cases from 96.9% to 68.5% and increasing ownership of mosquito nets from 54% to 85.5%; (2) demonstrated that persuasive technology could be used to increase public awareness and knowledge of a given subject as noted in our evaluation result; and (3) demonstrated that persuasive technology is a veritable active intervention to combat malaria.
ARTICLE | doi:10.20944/preprints202201.0023.v1
Subject: Biology And Life Sciences, Insect Science Keywords: Malaria; Anopheles gambiae; vector control; neonicotinoids; cross-resistance
Online: 4 January 2022 (20:40:51 CET)
Background: New insecticides with novel modes of action such as neonicotinoids have recently been recommended for public health use by WHO. Resistance monitoring of such novel insecticides requires a robust protocol to monitor the development of resistance in natural populations. In this study, we comparatively used three different solvents to assess the susceptibility of malaria vectors to neonicotinoids across Africa.Methods: Mosquitoes were collected from May to July 2021 from three agricultural settings in Cameroon (Njombe-Penja, Nkolondom, and Mangoum), the Democratic Republic of Congo (Ndjili-Brasserie), Ghana (Atatam), and Uganda (Mayuge). Using the CDC bottle test, we compared the effect of three different solvents (ethanol, acetone, acetone+MERO) on the efficacy of neonicotinoids against Anopheles gambiae s.l. In addition, TaqMan assays were used to genotype key pyrethroid-resistant markers in An. gambiae and to evaluate potential cross-resistance between pyrethroids and clothianidin.Results: Lower mortalities were observed for all populations when using absolute ethanol or acetone alone as solvent (11.4- 51.9% mortality for Nkolondom, 31.7- 48.2% for Mangoum, 34.6- 56.1% for Mayuge, 39.4- 45.6% for Atatam, 83.7- 89.3% for Congo and 71.05- 95.9% for Njombe pendja) compared to acetone + MERO for which 100% mortality was observed for all the populations. Synergist assays (PBO, DEM and DEF) revealed a significant increase of mortality suggesting that metabolic resistance mechanisms are contributing to the reduced susceptibility. A negative association was observed between the L1014F-kdr mutation and clothianidin resistance with a greater frequency of homozygote resistant mosquitoes among the dead than among survivors (OR=0.5; P=0.02). However, the I114T-GSTe2 was in contrast significantly associated with a greater ability to survive clothianidin with a higher frequency of homozygote resistant among survivors than other genotypes (OR=2.10; P=0.013). Conclusions: This study revealed a contrasted susceptibility pattern depending on the solvents with ethanol/acetone resulting in lower mortality, thus possibly overestimating resistance, whereas the addition of MERO consistently increased the efficacy of neonicotinoids in terms of percentage mortalities and time to final mortality. The addition of MERO could however prevent the early detection of resistance development. We therefore recommend monitoring susceptibility using both acetone alone and acetone+MERO (8-10µg/ml for clothianidin) to capture the accurate resistance profile of the mosquito populations.
ARTICLE | doi:10.20944/preprints202009.0716.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Malaria elimination; Mathematical model; Human mobility; Intervention chemotherapy
Online: 29 September 2020 (14:42:16 CEST)
In central Senegal malaria incidences have declined from 2000 to 2010 in response to scaling-up of control measures and then remained stable, making elimination improbable. Additional control measures are needed to reduce transmission. We simulated chemoprophylaxis interventions targeting malaria hotspots, using a meta-population mathematical model based on differential equation framework and incorporating human mobility. The model was fitted to weekly malaria incidences from 45 villages. Three approaches for selecting intervention targets were compared: a) villages with malaria cases during the low transmission season of the previous year; b) villages with highest incidences during the high transmission season of the previous year; c) villages with highest connectivity with adjacent populations. Our modeling, considering human mobility, showed that the intervention strategies targeting hotspots would be effective in reducing malaria incidence in both targeted and untargeted areas. But whatever the intervention, pre-elimination stage (1-5 cases per 1,000 per year) would not be reached without simultaneously increasing vector control by more than 10%. Targeted interventions allow increasing overall malaria control and elimination potential.
ARTICLE | doi:10.20944/preprints202009.0641.v1
Subject: Business, Economics And Management, Accounting And Taxation Keywords: Malaria; Risk Maps; Remote Sensing; Ethiopia; Hydroelectric Dams
Online: 26 September 2020 (14:41:53 CEST)
Malaria is a disease spread by female mosquitos of the Anopheles genus. It is acutely prevalent in Sub-Saharan Africa, where 90% of malaria deaths occur annually. One Sub-Saharan African country historically impacted by malaria is Ethiopia. In the past twenty years, malaria prevalence has decreased throughout Sub-Saharan Africa; yet, anthropogenic environmental changes are changing the landscape of malaria. Scholarly literature has cited a positive relationship between hydroelectric dams and malaria in Sub-Saharan Africa. Ethiopia is currently expanding their hydroelectric infrastructure. The Gilgel Gibe III Dam is located on the Omo River in Southwestern Ethiopia. It began generating electricity in 2015 and its reservoir has a capacity of 14,700 million m3 of water. This research utilized Geographic Information Systems and Remote Sensing to identify populations at an increased risk of malaria due to Gilgel Gibe III Dam. Two different techniques were employed: the proximity approach and the remote sensing approach. The proximity approach was based on distance from the reservoir. It identified all populations living within three kilometers of the reservoir as being at an increased risk. The remote sensing approach evaluated the slope, elevation, water content, and land surface temperature of the study area to create a mosquito breeding habitat risk map. Then, populations living within three kilometers of the two main High-Risk areas were identified. This study suggests that mosquito breeding habitat risk is not equally distributed throughout the Gilgel Gibe III Reservoir. This causes certain populations to be at a heightened risk of malaria.
SHORT NOTE | doi:10.20944/preprints202004.0208.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: malaria; COVID-19; SARS-COV-2; chloroquine; hydroxychloroquine
Online: 13 April 2020 (07:47:36 CEST)
World is currently experiencing a new pandemic for which no curative treatment is available. At this time, coronavirus disease 2019 (Covid-19) has reached 183 countries and has caused several deaths. Many reports presented chloroquine (CQ) and hydrochloroquine (HCQ), former drugs used against malaria, as the best current choice to fight this terrible disease. As these molecules had been withdrawn in malaria treatment policy due to chemoresistance, their reintroduction could have some consequences. Though local malaria prevalence could decrease for a while, molecular changes are likely to happen on some plasmodium falciparum genes involved in conferring drug resistance. This could threaten efforts in malaria control, if these molecules are widely administered.
REVIEW | doi:10.20944/preprints201811.0107.v1
Subject: Engineering, Architecture, Building And Construction Keywords: Built Environment, Design Decisions, Vector Borne Diseases, Malaria
Online: 5 November 2018 (11:01:08 CET)
Although significant efforts have been made to combat the spread of vector-borne diseases (VBDs), they still account for more than 17% of all infectious diseases. According to the World Health Organization (WHO), there were 216 million estimated cases in 2016, which is a 9.3% decrease from the estimated cases reported one decade earlier. It is known that the built environment, through features such as openings, can propagate the spread of malaria. There have been some significant efforts directed at addressing this risk. This notwithstanding, there are some knowledge gaps that have resulted in a missed opportunity for synergistically tackling the problem of vectors through leveraging design decisions made by built environment professionals. This work assesses the extent to which design decisions in the built environment can have a positive impact on the efforts directed at mitigating the risk of malaria based on selected cases from East Africa. Secondary data derived from relevant urban health journals as well as repositories curated by leading health agencies such as WHO were synthesized and analyzed using a web of causation approach. The outcome of the analysis is a schema of primary and secondary source (risk) factors. The use of the web of causation approach revealed the existing factor-to-factor interactions that could have a reinforcing effect. This information was used to identify the critical linkages and interdependencies across different factors. The outcome of the analysis was mapped against risk factors that can be linked to decisions made during the six primary phases of the construction life cycle: preliminary phase, conceptual design, detailed design, construction, facilities management, and end of life/disuse. The findings of the research have established that 1) there is, in fact, a built environment–related opportunity that can be leveraged to advance the impact of malaria mitigation effort; 2) cross-disciplinary synergies are critical to managing the interdependencies and complexity of malaria risk factors that have a reinforcing effect; and 3) a knowledge-management framework that serves as a decision support tool would be valuable for sharing data under a push-and-pull mechanism, in which data shared in real time can address the timeliness of mitigating the spread of malaria at the earliest stages for the greatest impact. Based on the findings, a conceptual architecture for a decision support framework has been proposed. This will be developed into a knowledge-management platform in subsequent efforts.
ARTICLE | doi:10.20944/preprints202305.0722.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Anomaly detection; Malaria data; Machine learning; big data; epidemic
Online: 10 May 2023 (09:34:36 CEST)
Disease surveillance is critical to monitor ongoing control activities, detect early outbreaks and to inform intervention priorities and policies. Unfortunately, most data from disease surveillance remain under-utilised to support decision-making in real-time. Using the Brazilian Amazon malaria surveillance data as a case study, we explore unsupervised anomaly detection machine learning techniques to analyse and discover potential anomalies. We found that our models are able to detect early outbreaks, peak of outbreaks as well as change points in the proportion of positive malaria cases. Specifically, the sustained rise in malaria in the Brazilian Amazon in 2016 was flagged by several models. We also found that no single model detects all the anomalies across all health regions. The approaches using Clustering-based local outlier algorithm ranked first before Principal component analysis and Stochastic outlier selection in maximising the number of anomalies detected in local health regions. Because of this, we also provide the minimum number of machine learning models (top-k models) to maximise the number of anomalies detected across different health regions. We discovered that the top-3 models that maximise the coverage of the number and types of anomalies detected across the 13 health regions are: Principal component analysis, Stochastic outlier selection and Multi-covariance determinant. Anomaly detection approaches provide interesting solutions to discover patterns of epidemiological importance when confronted with a large volume of data across space and time. Our exploratory approach can be replicated for other diseases and locations to inform timely interventions and actions toward endemic disease control.
REVIEW | doi:10.20944/preprints202301.0192.v1
Subject: Biology And Life Sciences, Parasitology Keywords: malaria vaccine, patents, stage of development.; transmission-blocking vaccines
Online: 11 January 2023 (03:08:51 CET)
Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite's complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite's replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite’s life cycle.
ARTICLE | doi:10.20944/preprints202301.0050.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Plasmodium falciparum chloroquine resistance; mutations; CVINT; malaria; allele frequency
Online: 4 January 2023 (03:04:50 CET)
The replacement of chloroquine with artemisinin-based combination therapies (ACTs) for over a decade has had varying impacts on the ability of malaria parasite to sustain its chloroquine resistance prowess in different malaria-endemic regions. We evaluated the frequency of Plasmodium falciparum chloroquine resistance transporter (PfCRT) mutations in an endemic area of southwest Nigeria 17 years after replacement of chloroquine with ACTs for malaria treatment. Genomic DNA was isolated from dried blood spot samples obtained from 129 patients (aged 1-35 years) with microscopically confirmed P. falciparum infection. PfCRT fragments covering codons 72-76, CVMNK (wildtype) and A220 were amplified and sequenced. Two mutant PfCRT haplotypes on residues 72-76 (CVIET and CVINT) were identified with a prevalence of 18.6% and 2.3%, respectively. Interestingly, the CVINT haplotype was identified for the first time in this region. A220S changes were found in 16.3% of samples occurring concurrently with the CVIET haplotype, while a Q271E mutation occurred in a wildtype isolate. The reduced prevalence of the PfCRT mutant alleles in this study may suggest a gradual disappearance of chloroquine-resistant malaria parasites following reduced drug pressure. It may also be an indicator of the ability of malaria parasites to develop resistance gradually against the current first-line regimen.
ARTICLE | doi:10.20944/preprints202208.0001.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Seasonal malaria chemoprevention; Plasmodium falciparum; Burkina Faso; Mali; Niger
Online: 1 August 2022 (03:27:50 CEST)
This study aims to evaluate the factors influencing the adherence to the 2nd and 3rd doses during each cycle of seasonal malaria chemoprevention (SMC) in Burkina Faso, Mali, and Niger. Overall, 3,132 people were interviewed during surveys between 2019 and 2020 in 15 health districts. The median age was 30 years. In Burkina , Mali, and Niger, the proportions of non-adherence were 4.15% , 5.60%, and 13.30%, respectively (95% CI (-3.27% -0.37 %, p = 0.114 ) for the 2nd dose and 3.98%, 5.60% and 14.39% for the 3rd dose. The main cause of non-adherence to the 2nd and 3rd doses was other illnesses in 28.5% and 29.78% respectively in Burkina, 5.35% and 5.35% in Mali and 1.6% and 0.75% in Niger. It was followed by vomiting in 12.24% and 10.63% for Burkina and 2.45% and 3.78% in Niger. The last causes were refusal in 6.12% and 4.25% in Burkina , 33.9% and 15.25% in Mali and 0.8% and 1.51% in Niger. Non-adherence of doses related to parents was primary due to their absence in 28.5% and 27.65% in Burkina , 16.07% and 16.07% in Mali and 7.37 % and 6.06% in Niger. Travelling was the second cause in 12.24 % and 12.76% in Burkina , 19.64% and 19.64% in Mali and 0.81% and 0.75% in Niger. Non-adherence related to community distributors was mainly due to missing of the doses in 4.08% and 4.25% in Burkina , 23.21% and 23.21% in Mali, 77.04% and 76.51% in Niger. Our study reported very small proportions of non-adherence to 2nd and 3rd doses of SMC and identified the main causes of non-adherence.
ARTICLE | doi:10.20944/preprints202205.0021.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Anopheles gambiae; Cameroon; Malaria; Pyrethroids; Resistance Escalation; Cytochrome P450s
Online: 5 May 2022 (05:07:43 CEST)
(1) Background: Malaria remains a global public health problem. Unfortunately, the resistance of malaria vectors to insecticides commonly used threatens disease control and elimination efforts. Molecular mechanisms helping some malaria vectors to now survive to greater doses of insecticides remains poorly understood. Here, we elucidated the pattern of resistance escalation in the main malaria vector Anopheles gambiae in a pesticide-driven agricultural hotspot in Cameroon and its impact on vector control tools; (2) Methods: Larval stages and indoor blood-fed females (F0) were collected in Mangoum in May and November and forced to lay eggs; the emerging mosquitoes were used for WHO tube, synergist and cone tests. Molecular identification was done using SINE PCR whereas TaqMan-based PCR was used for genotyping of L1014F/S and N1575Y kdr and the G119S-ACE1 resistance markers. Transcription profile of candidate resistance genes was performed using qRT-PCR methods. Characterization of the breeding water and soil from Mangoum was also performed using HPLC technique; (3) Results: An. gambiae s.s. was the only species in Mangoum with 4.10 % infection with Plasmodium. These mosquitoes were resistant to all the four classes of insecticides with mortality rates <7% for pyrethroids and DDT and <54% for carbamates and organophophates. This population also exhibited high resistance intensity to pyrethroids (permethrin, alpha-cypermethrin and deltamethrin) after exposure to 5X and 10X discriminating doses and Synergist assays with PBO revealed only a partial recovery of susceptibility to permethrin, alpha-cypermethrin and deltamethrin. Only PBO-based nets (Olyset plus and permaNet 3.0) and Royal Guard showed an optimal efficacy. A high amount of alpha-cypermethrin was detected in breeding sites (5.16 fold LOD) suggesting ongoing selection from agricultural pesticides. The 1014F-kdr allele was fixed (100%) whereas the 1575Y-kdr (37.5%) and the 119S Ace-1R (51.1%) are moderately present. Elevated expression of P450s respectively in permethrin and deltamethrin resistant mosquitoes [CYP6M2 (10 and 34-fold), CYP6Z1(17 and 29-fold), CYP6Z2 (13 and 65-fold), CYP9K1 (13 and 87-fold)] supports their role in the observed resistance besides other mechanisms including chemosensory genes as SAP1 (28 and 13-fold), SAP2 (5 and 5-fold),SAP3 (24 and 8-fold) and cuticular genes as CYP4G16 (6 and 8-fold) and CYP4G17 (5 and 27-fold). However, these candidate genes were not associated with resistance escalation as expression level did not differ significantly between 1x, 5x and 10x surviving mosquitoes. (4) Conclusions: Intensive and multiple resistance is being selected in malaria vectors from pesticide-based agricultural hotspot of Cameroon leading to loss of efficacy of pyrethroid-only nets. Further studies are needed to decipher the molecular basis underlying such resistance escalation to better assess its impact on control interventions.
ARTICLE | doi:10.20944/preprints202112.0387.v1
Subject: Social Sciences, Cognitive Science Keywords: Early diagnosis; behavior; illness; malaria; Mwanza; treatment-seeking; Tanzania
Online: 23 December 2021 (11:50:15 CET)
Early diagnosis of malaria and treatment seeking behavior play key role in controlling and preventing further complication related to malaria disease. Aim of this study was to determine the responses on early malaria diagnosis and treatment seeking behavior among outpatient clients attending at Sekou toure regional referral hospital in Mwanza, Tanzania. Methods: A cross-sectional study was conducted among outpatient client at Sekou-Touré regional referral hospital, convenient simple random sampling used and self-administered questionnaire were used to collect data and data was entered into Microsoft excel and then exported to SPSS version 25.0 for further analysis and presented on the percentages and table. The analysis of strength of relationships between categorical variables was conducted using the Chi-square test. A p-value of ≤ 0.05 was considered to be statistically significant. Results: A total of 192 respondents completed the study with a response rate of 97.6%. The study revealed that Most of the respondents about 90.6% stated they would seek treatment from health facility when symptoms appear. However, only 6.3% seek treatment within 24 hours of onset of illness (p= 0.017). Half of respondents (50.5%) experienced malaria symptoms in the past six months and only 30% seek for treatment at health facility. Preference of health facility, (51%) respondents were going direct to pharmacy to buy medicine for self-treatment. Overall, cost of service, time consumed and distance of health facility especially health center shows significant with such delay. Conclusion: A low proportion of malaria-suspected patients sought treatment within 24 h of fever onset compared to the national target. Distance from the health facility, cost of service and time consumed were found to be predictors of early treatment-seeking behavior for malaria. Strengthening strategies tailored to increasing awareness for communities about malaria, importance of going hospital and early treatment-seeking behavior is essential.
ARTICLE | doi:10.20944/preprints202012.0186.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: asymptomatic malaria; Plasmodium falciparum; Dzanga Sangha; Central African Republic
Online: 8 December 2020 (09:40:22 CET)
According to the World Health Organization 94% of global malaria cases and 94% of global malaria deaths have been reported from Africa. Unfortunately, it is difficult to determine the exact prevalence of disease in some African countries due to a large number of asymptomatic cases. The aim of this study was to assess the prevalence of malaria infections in seemingly healthy children living in the Central African Republic (CAR). CareStartTM Malaria HRP2 Pf Ag RDT targeting Plasmodium falciparum was used to test a group of 500 asymptomatic children aged 1-15 years old (330 settled Bantu and 170 semi-nomadic BaAka Pygmies) inhabiting the villages in the Dzanga Sangha region (south-west CAR) in March 2020. 32.4% of asymptomatic Bantu and 40.6% of asymptomatic Pygmy children had a positive result of malaria RDT. The mean age of the study participants with RDT (+) was 8.7 in Bantu and 7.0 years in Pygmies; the mean body temperature was 36.8oC in both groups; the mean haemoglobin level was 10.6 g/dL and 10.1 g/dL, respectively. Our findings allowed us to demonstrate the high prevalence of asymptomatic malaria infections in south-west CAR. RDTs seem to be a useful tool for the detection of Plasmodium falciparum in areas with limited possibilities of using other diagnostic methods, such as light microscopy and molecular biology.
ARTICLE | doi:10.20944/preprints202004.0261.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Malaria; Electrolytes; Plasmodium falciparum; Plasmodium vivax; Pearson's Correlation Coefficient
Online: 16 April 2020 (07:43:20 CEST)
Background: Malaria is one of the most common diseased conditions across most developing countries caused by one of four species of Plasmodium. P. falciparum and P.vivax are the main agents responsible for malaria in Nigeria. Malarial infection has been shown to be associated with abnormalities in fluids, electrolytes and acid base balances. Electrolyte imbalance and mineral disturbances are majorly identified clinical symptoms in various infectious diseases including malaria. Electrolyte imbalance in malarial infection is capable of enhancing disease severity. The aim of this study was to investigate the effects of malarial infection on electrolytes parameters. Methods: Finger prick blood samples, Thick and Thin Giemsa-stained blood smears, were collected from 100 malaria-suspected individuals representing all age groups. The Giemsa-stained blood smears were examined microscopically. Demographic information was obtained using structured questionnaires. The electrolytes levels (Na, K, Cl- and HCO3-) in malarial patients were analyzed using standard procedures, Pearson's Correlation Coefficient correlation technique was used to investigate the relationship, and the strength of association between the variables. Results: The mean bound of patients’ sodium level was observed to fall within the specified normal limits of 125mmol/L – 145mmol/L; except for positive malaria patients belonging to the MP-(++) which will fall below the 125mmol/L (i.e. 126.25mmol/L – 1.77mmol/L = 124.48mmol/L). The spread of the sodium data taken from the patients were observed to fall within the normal limits leaving only the boxplot’s lower whisker out, that is, observations falling within the first quartile, except for MP-(++) patients with observations in the first to second quartile spreading outside the normal lower limit, in contrast for the negative tested patients, the box and its whiskers were almost engulfed within the normal limits. Conclusion: In our study we found that Plasmodium falciparum altered more in electrolytes parameters than Plasmodium vivax. The biochemical markers can be used as biomarkers to confirmation of malaria. This study discovered a significant linear relationship based on the Pearson product-moment correlation between creatinine and urea, potassium and chloride, potassium and creatinine, potassium and urea. The mean sodium and chloride level of positive malaria [MP-(++)] patients were observed to fall outside the normal limit.
ARTICLE | doi:10.20944/preprints201907.0355.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: blood lead; plasmodium malaria parasites; anemia; free erythrocytes protoporphyrin
Online: 31 July 2019 (11:52:32 CEST)
Lead pollutants mainly from urban agricultural practices, Leaded paints, Leaded fuels spillages, Lead-contaminated air, soils, and water sources pause a health threat to urban children in Uganda. Prolonged Lead exposure affects iron metabolism, by competitively blocking iron absorption leading to anemia. Blood Lead (BL) inhibits key enzymes ferrochelatase and aminolevulinic acid dehydrogenase (ALAD) involved in hemoglobin (Hb) biosynthesis even at very low levels. Lead poisoning and malaria infection geographically overlap, and both produce similar hematological outcome especially in children. Malaria parasites cause anemia by destroying parasitized red blood cells, therefore, co-existence of BL and malaria parasites infection worsens the anemia status of the host. This study aimed at expounding the extent of heme synthesis inhibition by BL levels among a study group of malaria positive children by measuring levels of free erythrocyte protoporphyrin (FEP) in blood samples. Briefly venous blood samples from 198 children were analyzed for malaria parasite densities by the thick smear method, hemoglobin (Hb) concentrations determined by the standard cyan methemoglobin method, BLL were analyzed on an atomic absorption spectrophotometer and FEP levels were fluorometrically measured. The results showed means of BLL (9.3 µg/dL), Hb (7.5 g/dL), FEP/Hb (8.3 µg/g) and parasite density (PD) (3.21×103 parasites / µL) among the study group. A majority of 151/198 (76.3%) of the children were moderately anemic while 8/198 (4%) were severely anemic. There was weak correlation between PD and Hb (R²= -0.15, P-value < 0.001), as compared to one between FEP/Hb and Hb (R²= -0.6, P-value=0.001). The study concludes that BL is a significant contributor to malaria anemia and should be considered in the management of anemia in malaria-endemic areas.
COMMUNICATION | doi:10.20944/preprints201809.0589.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: squaraine dye; near infrared; fluorescence; chloroquine; malaria; Plasmodium falciparium
Online: 29 September 2018 (10:15:33 CEST)
Chloroquine was among the first of several effective drug treatments against malaria until the onset of chloroquine resistance. In light of diminished clinical efficacy of chloroquine as an antimalarial therapeutic, there is potential in efforts to adapt chloroquine for other clinical applications, such as in combination therapies and in diagnostics. In this context, we designed and synthesized a novel asymmetrical squaraine dye coupled with chloroquine (SQR1-CQ). In this study, SQR1-CQ was used to label live Plasmodium falciparum (P. falciparum) parasite cultures of varying sensitivities towards chloroquine. SQR1-CQ positively stained ring, mature trophozoite and schizont stages of both chloroquine–sensitive and chloroquine–resistant P. falciparum strains. In addition, SQR1-CQ exhibited significantly higher fluorescence, when compared to a chloroquine-BODIPY (borondipyrromethene) conjugate. We also achieved successful SQR1-CQ labelling of P. falciparum directly on thin blood smear preparations. Drug efficacy experiments measuring half-maximal inhibitory concentration (IC50) showed lower concentration of effective inhibition against resistant strain K1 by SQR1-CQ compared to conventional chloroquine. Taken together, the versatile and highly fluorescent labelling capability of SQR1-CQ and promising preliminary IC50 findings potentiates it to be further developed as a promising diagnostic bioimaging tool with drug efficacy against chloroquine-resistant P. falciparum.
REVIEW | doi:10.20944/preprints201804.0189.v1
Subject: Chemistry And Materials Science, Organic Chemistry Keywords: anti-malaria activity; plants; natural products; ethnopharmacology; Plasmodium parasites
Online: 16 April 2018 (05:55:07 CEST)
Malaria, as a major global health problem, continues to affect a large number of people each year, especially those in the developing countries. Effective drug discovery is still one of the main efforts to control malaria. As natural products are still considered as a key source for discovery and development of therapeutic agents, we have evaluated more than 2000 plant extracts against Plasmodium falciparum. As a result, we discovered dozens of plant leads that displayed antimalarial activity. Our phytochemical study of some of these plant extracts led to identification of several potent antimalarial compounds. The prior comprehensive review article entitled “Antimalarial activity of plant metabolites” by Schwikkard and Van Heerden (2002) reported structures of plant-derived compounds with antiplasmodial activity and covered literature up to the year 2000. As a continuation of this effort, the present review covers the antimalarial compounds isolated from plants, including marine plants, reported in the literatures from 2001 to the end of 2017. During the span of the last 17 years, 175 antiplasmodial compounds were discovered from plants. These active compounds are organized in our review article according to their plant families. In addition, we also include ethnobotanical information of the antimalarial plants discussed.
ARTICLE | doi:10.20944/preprints202303.0494.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: malaria vector; deep learning; image classification; drone images; epidemiological control
Online: 28 March 2023 (15:57:27 CEST)
Disease control programs need to identify breeding sites of mosquitoes which transmit malaria and other diseases to target interventions and identify environmental risk factors. Increasing availability of very high resolution drone data provides new opportunities to find and characterize these vector breeding sites. Within this study, we identified land cover types associated with malaria vector breeding sites in West Africa. Drone images from two malaria endemic regions in Burkina Faso and Côte d’Ivoire were assembled and labeled using open-source tools. We developed and applied a workflow using region of interest-based and deep learning methods to classify these habitat types from very high resolution natural color imagery. Analysis methods achieved a dice coefficient ranging between 0.68 and 0.88 for different vector habitat types; however, this classifier consistently identified the presence of specific habitat types of interest. This establishes a framework for developing deep learning approaches to identify vector breeding sites and highlights the need to evaluate how results will be used by control programs.
ARTICLE | doi:10.20944/preprints202301.0493.v1
Subject: Medicine And Pharmacology, Obstetrics And Gynaecology Keywords: Plasmodium; malaria; Intermittent Preventive Treatment; Prevalence and Public health facilities
Online: 27 January 2023 (06:40:54 CET)
Introduction: Uganda has got the highest prevalence rate of malaria among the risk groups compared to other parts of the world. In addition, Uganda bears a particularly large burden from the disease which is limited by a lack of reliable data, but it is clear that the prevalence of malaria infection, incidence of disease, and mortality among pregnant women all remain very high. According to the Iganga DHIS2 Jan-May report, a higher number of pregnant women received Intermittent Preventive Treatment one (IPT1) and the numbers dropped for IPT2 and IPT3. The district is also referral point of the greater Busoga region and has got several challenges towards malaria control. The study aimed at assessing the uptake of Intermittent Preventive Treatment and the prevalence of malaria among pregnant women in Iganga district so as to generate evidence for scaling up appropriate interventions for IPT uptake among pregnant women. Methods: The research was a retrospective study using secondary data to assess the uptake of IPT and prevalence of malaria for financial year 2019/2020 in nine Public Health Centre IIIs and one Public Health Centre IV. In this study IPT was defined as the administration of a curative dose of an effective antimalarial drug to all pregnant women without testing for presence of malaria parasite and at least three doses as recommended. Secondary data from HMIS was obtained and analyzed to assess the uptake of IPT services and the prevalence of malaria among pregnant women was determined using proportions. Results: The study found that of 6,672 women who received the first dose of IPT-SP, 1671 (25%) of the women received less than 2 doses of IPT and 46% of pregnant women received more than 2 doses of IPT. The study showed that a total of 3,435 pregnant women tested positive for malaria which brings the prevalence to 50%, and being highest among pregnant women aged 20-24 years at 50%. Conclusions: The study showed that the uptake of IPT was relatively low among lower age groups with a relatively high prevalence of malaria among the same age group. This calls for all stakeholders (DHO, MOH, Iganga District, NGOs e.t.c) urgent attention thus to ensure mass sensitization about malaria and IPT importance with IEC and ITN distribution, early diagnosis and treatment, giving incentives to ANC attending mothers, control of the vector.
ARTICLE | doi:10.20944/preprints202202.0107.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Malaria; Resistance; Mutation; Virtual screening; Phytochemicals; Dihydrofolate Reductase –Tymidylate Synthase
Online: 8 February 2022 (12:06:36 CET)
Resistance to Pyrimethamine, an antimalarial medicine has been reported to be due to mutations in Dihydrofolate reductase-thymidylate synthase (DHFR-TS). Phytochemicals, particularly from plants that been used in ethnomedicine, have been reported to have privileged structures that might bind strongly to the mutants of DHFR-TS. The aim of this study is to identify phytochemicals of Acalypha wilkesiana, Cymbopogon citratus, Azadirachta indica, and Morinda lucida with high binding affinities for the Plasmodium falciparum DHFR-TS. The three-dimensional structures of the phytochemicals, wide type and mutant forms of DHTR-TS were obtained from PubChem and Protein Databank (PDB) respectively. They were appropriately prepared and molecular docking simulations was implemented to predict binding affinities of the phytochemicals to the wildtype and mutant forms of DHTR-TS. Druglikeness assessment was implemented to triage the top binding phytochemicals and molecular dynamics simulations was done to establish the stability of the interaction of the top-ranked phytochemical with one of the mutants of DHFR-TS. Nineteen phytochemicals showed higher binding affinities to both the wild type and mutant forms DHFR-TS than Pyrimethamine. Molecular dynamics revealed that the receptor-ligand binding of luteolin, the top-ranked, drug like phytochemicals, to the quadruple mutant was stable.
ARTICLE | doi:10.20944/preprints202107.0270.v1
Subject: Chemistry And Materials Science, Analytical Chemistry Keywords: drug design; falcipain; malaria; peptidomimetics; Plasmodium falciparum; virtual screening; pharmacophore.
Online: 12 July 2021 (14:48:13 CEST)
In this work antiparasitic peptidomimetics inhibitors (PEP) of falcipain-3 (FP3) of Plasmodium falciparum (Pf) have been proposed using structure-based and computer-aided molecular design. Beginning with the crystal structure of PfFP3-K11017 complex (PDB ID: 3BWK), three-dimensional (3D) models of FP3-PEPx complexes with known activities (IC50exp) were prepared by in situ modification, based on molecular mechanics and implicit solvation to compute Gibbs free energies (GFE) of inhibitor-FP3 complex formation. This resulted in a quantitative structure-activity relationships (QSAR) model based on a linear correlation between computed GFE (ΔΔGcomp) and the experimentally measured IC50exp: (pIC50exp=-(IC50exp/109) =-0.4517×∆∆Gcomp+4.0865 ; R2 = 0.89). Apart from the structure-based relationship, a ligand-based quantitative pharmacophore model (PH4) of novel PEP analogs where substitutions were directed by comparative analysis of the active site interactions was derived using the proposed bound conformations of the PEPx. This provided structural information useful for the design of virtual combinatorial libraries (VL), which was virtually screened based on the 3D-QSAR PH4. The end results were predictory inhibitory activities falling within the low nanomolar concentration range.
ARTICLE | doi:10.20944/preprints202103.0693.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: malaria; Anopheles; coluzzii; gambiae; 2La; chromosomal; inversion; thermotolerance; permethrin; resistance
Online: 29 March 2021 (13:05:04 CEST)
Climate change is impacting the spread/intensity of vector-borne diseases, including malaria, and accelerating evolutionary/adaptive changes in vector species. These changes including chromoso-mal inversions and overexpression and/or changes in allele frequencies of thermotoler-ance-associated genes, may facilitate insecticide resistance through pleiotropy. This study investi-gated the impact of thermotolerance on pyrethroid resistance in four populations of malaria vector An. gambiae, from savanna/sub-Sahel of northern Nigeria. Anopheles coluzzii and An. gambiae were the only malaria vectors found, sympatric in all the sites, with the former species predominant. High thermotolerance was observed, with no mortality at 38°C, and LT50 of ~44°C. Significantly high permethrin resistance was observed (mortality <50%) in heat-hardened (44°C) larvae from two sites, BUK and Pantami, compared with control, and heat-hardened adult females from Auyo (mortality = 3.00%±1.20, χ2 = 5.83, p<0.01) compared with control (12.00%±4.65). The 2La chromosomal inver-sion was detected at ~50% in larvae and 58% in adult females. Significant association was observed (OR = 7.2, p<0.03) between permethrin resistance and 2La/+a rearrangement compared with 2L+a/+a, in BUK larvae. For all sites permethrin resistance correlated with 2La/a homozygosity in adult fe-males [OR = 5.02, p=0.01). qRT-PCR identified 6 genes commonly induced/overexpressed, including heat shock protein 70 (AGAP004581) which was 2468x and 5x overexpressed in heat-hardened and permethrin-resistant females, respectively, trehalose-6-phosphate synthase (AGAP008227), and ionotropic glutamate receptor genes, IR25a (AGAP010272) and IR21a (AGAP008511). This study highlights challenges associated with insecticide-based malaria vector control, and the epidemiological significance of taking climate variables into account for design/choice of control measures.
ARTICLE | doi:10.20944/preprints201909.0012.v2
Subject: Biology And Life Sciences, Insect Science Keywords: Ace-1 G119S mutation; insecticide resistance; Anopheles gambiae; Cameroon; malaria
Online: 8 October 2019 (11:49:05 CEST)
Growing resistance is reported to carbamate insecticides in malaria vectors in Cameroon. However, the contribution of acetylcholinesterase (Ace-1) to this resistance remains uncharacterised. Here, we established that the G119S mutation is driving resistance to carbamates in Anopheles gambiae populations from Cameroon. Insecticide bioassay on field collected mosquitoes from Bankeng, a locality in southern Cameroon, showed high resistance to the carbamates bendiocarb (64.8 ± 3.5 % mortality) and propoxur (55.71 ± 2.9 %) but a full susceptibility to the organophosphate fenithrothion. The TaqMan genotyping of the G119S mutation in field-collected adults revealed the presence of this resistance allele (39%). A significant correlation was observed between the Ace-1R and carbamate resistance at allelic [(bendiocarb; OR = 75.9; P<0.0001) and (propoxur; OR= 1514; P<0.0001)] and genotypic [RR vs SS (bendiocarb; OR = 120.8; P<0.0001) and (propoxur; OR= 3277; P<0.0001) levels. Furthermore, the presence of the mutation was confirmed by sequencing an Ace-1 portion flanking codon 119. The cloning of this fragment revealed a likely duplication of Ace-1 in Cameroon as mosquitoes exhibited at least three distinct haplotypes. Phylogenetic analyses showed that the predominant Ace-1R allele is identical to that from West Africa suggesting a recent introduction of this allele in Central Africa from the West. The spread of this Ace-1R represents a serious challenge to future implementation of IRS-based interventions using carbamates or organophosphates in Cameroon
ARTICLE | doi:10.20944/preprints201809.0214.v2
Subject: Computer Science And Mathematics, Applied Mathematics Keywords: malaria; transfusion–transmitted; basic reproduction number; stability; equilibrium; optimal control
Online: 10 January 2019 (04:56:22 CET)
An SIRS (Susceptible–Infected–Removed-Susceptible) mathematical model for the transmission dynamics of the Transfusion–Transmitted Malaria (TTM) model with optimal control pair u1(t) and u2(t) was developed and studied in this research work. The model Transfusion–Transmitted Malaria disease–free equilibrium and endemic equilibriums points were determined. The model exhibited two equilibriums; disease-free and endemic equilibrium. It is shown that the disease–free equilibrium was locally asymptotically stable if the associated basic reproduction numbers R0 is less than unity while the disease persists if R0 is greater than unity. The global stability of the Transfusion–Transmitted Malaria model at the disease-free equilibrium was established using the comparison method. The optimality system was derived and an optimal control model of blood screening and drug treatment for the Transfusion–Transmitted Malaria model was investigated. Conditions for the optimal control were considered using Pontryagin’s Maximum Principle and solved numerically using the Forward and Backward Finite Difference Method (FBDM). Numerical results obtained are in perfect agreement with our analytical results.
REVIEW | doi:10.20944/preprints201712.0097.v1
Subject: Computer Science And Mathematics, Mathematics Keywords: malaria; red blood cells segmentation; mathematical morphology; medical image analysis
Online: 14 December 2017 (17:10:19 CET)
This paper investigates existing mathematical morphology based techniques applied for performing malaria parasites detection and identification in both Giemsa and Leishman stained blood smears images. Malaria is an epidemic health disease and a rapid, accurate diagnosis is necessary for proper intervention. Generally, pathologists visually examine blood stained slides for malaria diagnosis; this kind of visual inspection is subjective, errorprone and time consuming. In order to cope with such issues, computer-aided methods have been increasingly evolved for abnormal erythrocyte and/or parasites detection, segmentation and semi/fully automated classification. The aim of this paper is to present a review of recent mathematical morphology based methods for malaria parasite detection.
ARTICLE | doi:10.20944/preprints202108.0168.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: malaria; fever; Plasmodium falciparum; Falciparum vivax; under-five; determinants; risk factors
Online: 6 August 2021 (14:09:07 CEST)
Background/Purpose: Over the last two decades, malaria has remained a major worldwide public health concern, especially in the developing countries leading to high morbidity and mortality among children. Nigeria is the world most burdened malaria endemic nation, contributing more than a quarter of global malaria cases. This study determined the prevalence of malaria among children 6-59 months in Nigeria, and the effects of individual and contextual factors. Methods: The study utilized data from 2018 Nigeria Demographic and Health Survey (NDHS) involving a weighted sample size of 10,185 children who were tested for malaria using rapid diagnostic test (RDT). Given the hierarchical structure of the data set, such that children at level-1 are nested in community at level-2, and nested in states and Federal Capital Territory (FCT) at level-3, multilevel mixed effect logistic regression models were used for the analysis. Results: The proportion of children 6-59 months of age in Nigeria that had malaria fever positive as assessed by RDTs was 35.5% (3,418/10185), (CI: 33.9-37.1). Kebbi State had the highest proportion of children 6-59 months who were malaria positive, 77.6%, (CI: 70.2-83.5), followed by Katsina State, 55.5%, (CI: 47.7-63.1). The Federal Capital Territory (FCT), Abuja had the proportion of 29.6%, (CI: 21.6-39.0), malaria positive children of 6-59 months of age. Children between the age of 48 and 59 months were 2.68 times more likely to have malaria fever than children 6-11 months of age (AOR=2.68, 95% CI: 2.03-3.54). Also, children from the rural area (AOR= 2.12, 95% CI: 1.75-2.57), were more likely to suffer from malaria infection compare with children from urban area. Conclusion: The study identified some individual and contextual predictors of malaria among children in Nigeria. These factors are areas that need to be considered for policy designs and implementations toward control and total elimination of malaria-related morbidity and mortality among children in Nigeria.
ARTICLE | doi:10.20944/preprints202011.0610.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Artesunate; Drug resistance; Malaria; Quinine; Rapid diagnostic test; Plasmodium falciparum; Sahel
Online: 24 November 2020 (09:51:45 CET)
Severe malaria in adults is not well studied in Sahelian Africa. Clinical features and mortality associated with severe Plasmodium falciparum malaria in adult patients hospitalized in Kiffa, southern Mauritania, were analysed. Patients over 15 years old admitted for severe malaria between August 2016 and December 2019 were included in the present retrospective study. The World Health Organization (WHO) criteria were used to define severe malaria. The presenting clinical characteristics and outcome were compared. Of 4266 patients hospitalized during the study period, 573 (13.4%) had a positive rapid diagnostic test for malaria, and 99 (17.3%; mean age, 37.5 years; range 15–79 years; sex-ratio M/F, 2.1) satisfied the criteria for severe malaria. On admission, the following signs and symptoms were observed in more than one-fourth of the patients: fever (98%), impairment of consciousness (81.8%), multiple convulsions (70.7%), cardiovascular collapse (61.6%), respiratory distress (43.4%), severe anaemia ≤ 80 g/L (36.4%), haemoglobinuria (27.3%), and renal failure (25.3%). Patients were treated with parenteral quinine or artemether. Fourteen (14.1%) patients died. Multiple convulsions, respiratory distress, severe anaemia, haemoglobinuria, acute renal failure, jaundice, and abnormal bleeding occurred more frequently (P < 0.05) in deceased patients. Mortality due to severe falciparum malaria is high among adults in southern Mauritania. An adoption of the WHO-recommended first-line treatment for severe malaria, i.e. parenteral artesunate, is required to lower the mortality rate associated with severe malaria.
ARTICLE | doi:10.20944/preprints202207.0191.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: malaria diagnosis; Pfhrp2; amino acid repeats; sequence variation; genetic polymorphism; Plasmodium falciparum
Online: 13 July 2022 (07:49:05 CEST)
Malaria rapid diagnosis test (RDT) is crucial for managing the disease, and the effectiveness of detection depends on parameters such as sensitivity and specificity of the RDT. Several factors can affect the performance of RDT. In this study, we focus on pfhrp2 sequence variation and its impact on RDTs targeted by antigens encoded by pfhrp2. Field samples collected during cross-sectional surveys in Tanzania were sequenced to investigate pfhrp2 sequence diversity and evaluate the impact on HRP2-based RDT performance. We observed significant mean differences in amino acid repeats between current and previous studies. Several new amino acid repeats were found to occur at different frequencies, including types AAY, AHHAHHAAN and AHHAA. Based on the abundance of types 2 and 7 amino acid repeats, the binary predictive model was able to predict RDT insensitivity by about 69 % in the study area. About 85% of the major epitopes targeted by Monoclonal antibodies (MAbs) in RDT were identified. Our study suggests that the extensive sequence variation in the pfhrp2 could contribute to reduced RDT sensitivity. The correlation between the different combinations of amino acid repeats and the performance of RDT in different malaria transmission settings should be investigated further.
REVIEW | doi:10.20944/preprints202101.0447.v1
Subject: Medicine And Pharmacology, Tropical Medicine Keywords: Malaria, Fever, Plasmodium falciparum, falciparum vivax, under-five, determinants, risk factors, review
Online: 22 January 2021 (13:08:29 CET)
Background/Purpose: In recent times, Sub-Sahara Africa (SSA) had been rated by the World Health Organization, (WHO), as the most malaria endemic region in the world. Evidence synthesis of the risk factors associated with malaria among children aged under-five in SSA is urgently needed. This would help to inform decisions that policy makers and executors in the region need to make for the effective distribution of scare palliative resources to curb the spread of the illness. This scoping review is aimed to identify studies that have used multivariate classical regression analysis to determine risk factors associated with malaria among children under-five years old in SSA. Methods/Design: The search terms followed PICOTS, (Population, Intervention, Comparator, Outcome, Timing, Setting), and were used in searching through the following databases: PubMed, MEDLINE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, and MeasureDHS. The databases were searched for published articles from January 1990 to December 2020. Results: Among the 1154 studies identified, only thirteen (13) studies met the study’s inclusion/exclusion criteria. Narrative syntheses were performed on the selected papers to synchronise the various risk factors identified. Factors ranging from child-related, (age, birth order and use of bed net), parental/household-related, (maternal age and education status, household wealth index) and community-related variables, (community wealth status, free bed net distribution), were some of the identified significant risk factors. Conclusion: It is timely to have a synthesis of risk factors that influence the malaria status of children under-five in SSA. The outcome of the review will increase the knowledge of the epidemiology of morbidity that will form the basis for designing efficient and cost-effective distribution of palliatives and controls of malaria in SSA.
ARTICLE | doi:10.20944/preprints201809.0534.v1
Subject: Social Sciences, Geography, Planning And Development Keywords: syndemic; El Niño; infectious disease; diarrhea; malaria; respiratory; cholera; spatial cluster; GIS
Online: 27 September 2018 (06:04:08 CEST)
El Niño is a quasi-periodic pattern of climate variability and extremes often associated with hazards and disease. While El Niño links to individual diseases have been examined, less is known about the cluster of multi-disease risk referred to as an ecosyndemic, which emerges during extreme events. The objective of this study was to explore a mapping approach to represent the spatial distribution of ecosyndemics in Piura, Peru at the district-level during the first few months of 1998. Using geographic information systems and multivariate analysis, two methodologies were employed to map disease overlap of 7 climate-sensitive diseases and construct an ecosyndemic index, which was then mapped and applied to another El Niño period as proof of concept. The main findings showed that many districts across Piura faced multi-disease risk over several weeks in the austral summer of 1998. The distribution of ecosyndemics were spatially clustered in western Piura among 11 districts. Furthermore, the ecosydemic index in 1998 when compared to 1983 showed a strong positive correlation, demonstrating the utility of the index. The study supports PAHO efforts to develop multi-disease based and interprogrammatic approaches to control and prevention, particularly for climate and poverty-related infections in Latin America and the Caribbean.
REVIEW | doi:10.20944/preprints202009.0552.v1
Subject: Biology And Life Sciences, Insect Science Keywords: Malaria; Amazon; Brazil; Anopheles darlingi; Plasmodium; Control; Challenges; Strategies; Conventional; Novel; Vector; Mosquito
Online: 23 September 2020 (15:26:43 CEST)
In Brazil, malaria transmission is mostly confined to the Amazon, where substantial progress has been achieved towards disease control in the past decade. Vector control has been historically considered a fundamental part of the main malaria control programs implemented in Brazil. However, the conventional vector-control tools have been insufficient to eliminate local vector populations due to the complexity of the Amazonian rainforest environment and ecological features of malaria vector species in the Amazon, especially Anopheles darlingi. Malaria elimination in Brazil and worldwide eradication will require a combination of conventional and new approaches that takes into account the regional specificities of vector populations and malaria transmission dynamics. Here we present an overview on both conventional and novel promising vector-focused tools to curb malaria transmission in the Brazilian Amazon. If well designed and employed, these new vector-based approaches may improve the implementation of malaria-control programs, particularly in remote or difficult-to-access areas and in regions where existing interventions have been unable to eliminate disease transmission. However, much effort still has to be put on research expanding the knowledge of neotropical malaria vectors to set the steppingstones for the development of such innovative tools.
ARTICLE | doi:10.20944/preprints202007.0377.v1
Subject: Biology And Life Sciences, Insect Science Keywords: mosquito; Anopheles; microbiota; malaria; Plasmodium; metabolism; immunity; TCA cycle; nitrogen excretion; amino acids
Online: 17 July 2020 (11:00:53 CEST)
The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host fitness, it is therefore considered as a potential target to reduce malaria transmission. While immune induction, secretion of antimicrobials and metabolic competition are three typical mechanisms of microbiota-mediated protection against invasive pathogens in mammals, the involvement of metabolic competition or mutualism in mosquito-microbiota and microbiota-Plasmodium interactions has not been investigated. Here, we describe a metabolome analysis of the midgut of An. coluzzii provided with a sugar-meal or a blood-meal, under conventional or antibiotic-treated conditions. We observed that the antibiotic treatment affects the tricarboxylic acid cycle and nitrogen metabolism, notably resulting in decreased abundance of free amino acids. Linking our results with published data, we identified candidate pathways which may participate in microbiota/Plasmodium interactions via metabolic interactions or immune modulation.
ARTICLE | doi:10.20944/preprints202111.0108.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Plasmodium; malaria; type III beta phosphatidylinositol 4-kinase; virtual screening; homology modeling; molecular dynamics
Online: 5 November 2021 (08:44:31 CET)
Plasmodium species that cause malaria, a disease responsible for about half a million deaths per annum despite concerted efforts to combat it. The causative agent depends on type III beta phosphatidylinositol 4-kinase (PPI4K) during the development of merozoite. PPI4K is the only clinically validated Plasmodium kinase so far and its inhibitors are effective both in vitro and in vivo. In this work, a small library of ~22 000 fragments was virtually screened using PPI4K homology model to discover potential ligands of the enzyme. 16 virtual hits were selected based on ≤ -9.0 kcal/mol binding energy cut off and were subjected to similarity and substructure searching after they had passed PAINS screening. The derivatives obtained showed improved binding energies, which ranged from -10.00 to -13.80 kcal/mol. Moreover, the topmost ranking compound 31, with interesting drug-like quality was stable within the protein’s binding cavity during the 10 ns molecular dynamics simulation period. In addition, analysis of its binding pose revealed some unique binding interactions with PPI4K active site residues as the basis for the observed improved binding affinity. Overall, compound 31 appears to be a viable starting point for the development of PPI4K inhibitors with antimalarial activity.
ARTICLE | doi:10.20944/preprints202012.0249.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Neglected tropical diseases; Latin America and the Caribbean; Bibliometric analysis; HIV/AIDS; Malaria; Tuberculosis.
Online: 10 December 2020 (10:56:11 CET)
(1) Background: Neglected tropical diseases (NTDs) have been overlooked on the global health agenda and in the priorities of national systems in low- and middle-income countries (LMICs). In 2012, the Sustainable Development Goals (SDGs) were created to ensure healthy lives and promoting well-being for all. This roadmap set out to accelerate work to overcome the global impact of NTDs. Almost a decade has passed since NTDs were re-launched as a global priority. Investment in research and development, as well as the production of scientific literature on NTDs, is expected to have increased significantly. (2) Methods: A bibliometric analysis of the scientific production of Latin America and the Caribbean (LAC) was carried out in relation to 19 endemic NTDs. These data were compared with the scientific production in malaria, tuberculosis and HIV / AIDS. The database available from Thomson Reuters Web of Science (WoS) was used. In addition, the average annual growth percentage was calculated for each disease. (3) Results: In the last decade, the NTDs with the highest number of publications in the world were dengue and leishmaniasis. The United States was the most prolific country in the world in 15 out of 19 NTDs analyzed. In the LAC region, Brazil was the largest contributor for 16 of the 19 NTDs analyzed. Arboviral diseases showed the highest average annual growth. The number of publications for malaria, tuberculosis and HIV /AIDS was considerably higher than for NTDs. The contribution of most LAC countries, especially those considered as LMICs, is inadequate and does not reflect the relevance of NTDs for the public health of the population. (4) Conclusion: This is the first bibliometric analysis to assess the trend of scientific documents on endemic NTDs in LAC. Our results could be used by decision makers both to strengthen investment policies in research and development in NTDs.
ARTICLE | doi:10.20944/preprints202201.0063.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Malaria, Plasmodium berghei, Plasmodium falciparum, hepatic stages, blood stages, prophylaxis, tazopsine, dextromethorphan, N-alkylation, hit compounds.
Online: 6 January 2022 (10:11:44 CET)
The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).
REVIEW | doi:10.20944/preprints202111.0190.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Malaria; proteases; Plasmodium rhomboids; dipeptidyl aminopeptidases; apical membrane antigen; subtilisin-like proteins; glucose transporters; schizogony; plasmepsins
Online: 9 November 2021 (15:50:12 CET)
There is an overarching need to find alternative treatment options for malaria and this quest is more pressing in current times due to the morbidity and mortality data arising from most endemic countries and partially owing to the fact that the SARS-Cov-2 pandemic has diverted much public health attention. Additionally, the therapeutic options available for malaria has been severely threatened with the emergence of resistance to almost all existing drugs by the human malaria parasite. The Artemisinin Combination Therapies (ACTs) which hitherto have been the mainstay for malaria have encountered resistance in South East Asia, a notorious ground zero for the emergence of antimalarial drug resistance. This review analyses few key druggable targets of the parasite and the potential to leverage strategic inhibitors to mitigate the scourge of malaria by providing a concise assessment of the essential proteins of the malaria parasite that could serve as targets. Furthermore, this work provides a summary of the advances made in malaria parasite biology and the potential to leverage such findings for antimalarial drug production.
ARTICLE | doi:10.3390/sci2020045
Subject: Medicine And Pharmacology, Tropical Medicine Keywords: adverse drug reactions; antimalarial; Ghana; herbal remedies; malaria; questionnaire; street sale; orthodox; unnatural medicines; patient preference
Online: 12 June 2020 (00:00:00 CEST)
Malaria is a serious infection affecting millions of people in Africa. Our study investigated the personal preferences and applications of antimalarial medicines in Ghana. Based on over 1000 questionnaires distributed in Ghana from January to May 2019, we noticed that although Western medications to fight this disease are widely available, most patients in Ghana prefer treatment with locally produced herbal remedies. This preference appears to be due to a combination of traditional venues for obtaining medicines “on the street” rather than in licensed pharmacies, trust in local and “green” products, extensive advertisement of such local products, and an inherent distrust of imported and synthetic or unnatural medicines. Going local and natural is a trend also observed in other countries across the globe, and adds to the acceptance or rejection of drugs regardless of their activity or toxicity. In fact, adverse side effects associated with herbal remedies, such as general weakness and swollen, sore mouth, do not seem to deter the respondents of this study in Ghana. We propose a combination of (a) increasing public awareness of the benefits of modern medicine and (b) an improvement and control of the quality of herbal remedies to raise the standard of malaria treatment in countries such as Ghana.
ARTICLE | doi:10.20944/preprints202105.0710.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Gut microbiota; Mycobiota; Bacteria; Fungi; Malaria; Plasmodium falciparum; 16S metagenomics; ITS metagenomics; Children; Cohort; Mali; Dogon country
Online: 31 May 2021 (08:25:57 CEST)
The gut microbiota has recently been associated with susceptibility/resistance to malaria in animal models and humans, yet the impact of the gut microbiota on the risk of a malaria attack remains to be assessed. This study aims at assessing the influence of the gut microbiota on malaria attacks and Plasmodium parasitæmia in children living in a malaria-endemic area in Mali. Three hundred healthy children were included in a 16-months cohort study in Bandiagara. Their gut bacteria and fungi community structures were characterised via 16S and ITS metabarcoding from stool samples collected at inclusion. Clinician team monitored the occurrence of malaria attacks. Asymptomatic carriage of Plasmodium was assessed by qPCR. Over the 16-month period, 107 (36%) children experienced at least one occurrence of malaria attacks, and 82 (27%) at least one asymptomatic Plasmodium parasitæmia episode. A higher gut bacteria richness was independently associated with susceptibility to asymptomatic parasitæmia episodes and malaria attacks; while the Shannon H diversity and Chao-1 richness index of gut fungi community structure was relatively homogeneous in children who were and were not infected with P. falciparum. Using a linear discriminant effect size analysis of operational taxonomic units assigned to the species level, 17 bacteria, including Clostridiaceae, Eubacteriaceae, Senegalimassilia sp., Atopobiaceae and Lachnosipraceae, and seven fungi, including Dioszegia fristigensis, Ogataea polymorpha and Cutaneotrichosporon cyanovorans, were associated with susceptibility; whereas eight bacteria, including, Bifidobacterium spp., Weissela confusa and Peptostreptococcacea, and 3 fungi, Malassezia sp., Niesslia exosporoides, and Didymocrea leucaenae, were associated with resistance to malaria. Moreover, 15 bacteria, including Coproccus eutactus, Terrisporobacter petrolearius, Klebsiella pneumoniae and Ruminococcaceae, and 13 fungi, including Wallemia mellicola, were associated with susceptibility, whereas 19 bacteria, including Bifidobacterium spp., Bacteroides fragilis, Peptostreptococcacea, and Lactobacillus ruminis, and three fungi, including Cryptococcus neoformans, were associated with resistance to asymptomatic Plasmodium parasitæmia episodes. Further studies are needed to confirm these findings that point the way towards strategies aiming to reduce the risk of malaria by modulating gut microbiota components in at-risk populations.
REVIEW | doi:10.20944/preprints202004.0179.v2
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; SARS-CoV-2; human coronavirus; control; vitamin D; antibiotic resistance; antimicrobial agents; BCG; malaria; climate; latitude
Online: 15 April 2020 (08:25:18 CEST)
Mankind faces a coronavirus pandemic originating from a seafood market in Wuhan, China since December 2019. The pathogen was named novel coronavirus (n-CoV) and bats are the identified key reservoir. The coronavirus disease 2019 (COVID-19) quickly spread over China across the globe, turned into a pandemic with exponentially increasing numbers of cases and significant mortality rate. China reacted with lockdowns and strict control measurements to prevent spreading the virus. The treatment of severe cases was hampered by lack of specific vaccines. Vaccine-development and production is a painstaking process and can only be enforced by international cooperation. Different supportive treatment options surfaced due to combinations of antiviral agents with antibiotic drugs. Elderly, male, immune-suppressed patients with co-morbidities showed a high mortality rate. Health literacy, strong immune system, adequate serum 25-hydroxyvitamin D (25(OH)D) concentrations and healthy life style choices can support fast recovery. Antibiotic resistance needs to be addressed by development of new generation antimicrobials against nosocomial infections in preparation for future outbreaks. Plant-biosynthesis of nanomaterials and antiseptics may help in prevention and recovery rate. Prevalence of COVID-19 maybe inversely related to BCG vaccination, endemicity of malaria, humidy and temperature but directly with latitude. Recommendations to prevent the spread of COVID-19 should be followed strictly.
ARTICLE | doi:10.20944/preprints202304.1207.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: Malaria; Amazon biome; INLA; Land use/cover interactions; Bird and amphibian rich-ness-endemics; Landscape composition; Biological diversity; Spatio-temporal modeling
Online: 29 April 2023 (04:29:50 CEST)
Malaria is a prevalent disease in several tropical and subtropical regions, including Brazil, where remains a significant public health concern. Despite control efforts, reintroduction of endemics in areas without cases for decades poses a challenge. To assess factors influencing ma-laria risk, regional outbreak cluster analysis and a spatio-temporal models were developed for the Brazilian Amazon, incorporating climate, land use/cover interactions, endemic bird, and amphibian richness. Results showed that amphibian, bird richness and endemism correlated with a reduction in malaria risk. Presence of forest had a positive effect on risk, but it depended on its juxtaposition with anthropic land uses. Biodiversity and landscape composition, rather than forest formation presence alone, modulated malaria risk in the period. Areas with low en-demic species diversity and high human activity, predominantly anthropogenic landscapes posed high malaria risk. This study underscores the importance of considering the broader eco-logical context in malaria control efforts.
ARTICLE | doi:10.20944/preprints202211.0005.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: Epidemics; Twitter; Natural Language Processing; Topic Modelling; Sentiment Analysis; ARI; Cholera; Ebola; HIV/AIDS; Influenza; Malaria; Spanish influenza; Swine flu; Tuberculosis; Typhus; Yellow fever; and Zika
Online: 1 November 2022 (01:17:14 CET)
At the end of 2019, while the world was being hit by the COVID-19 virus and, consequently, was living a global health crisis, many other pandemics were putting humankind in danger. The role of social media is of paramount importance in these kinds of contexts since they help health systems to cope with emergencies by contributing to conducting some activities such as the identification of public concerns, the detection of infections’ symptoms, and the traceability of the virus diffusion. In this paper, we have analyzed comments on events related to cholera, ebola, HIV/AIDS, influenza, malaria, Spanish influenza, swine flu, tuberculosis, typhus, yellow fever, and zika, collecting 369,472 tweets from the 3rd of March to the 15th of September, 2022. Our analysis has started with the collection of comments composed of unstructured texts on which we have applied natural language processing solutions. Afterward, we have employed topic modelling and sentiment analysis techniques to obtain a collection of people’s concerns and attitudes toward these pandemics. According to our findings, people's discussions were mostly about malaria, influenza, and tuberculosis and the focus was on the diseases themselves. As regards emotions, the most popular were fear, trust, and disgust where trust is mainly regarding HIV/AIDS tweets.