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Bioorganic Chemistry Jul 2024Patents tend to define a huge chemical space described by the combinatorial nature of Markush structures. However, the optimization of new principal active ingredient is...
Patents tend to define a huge chemical space described by the combinatorial nature of Markush structures. However, the optimization of new principal active ingredient is frequently driven by a simple Free Wilson approach. This procedure leads to a highly focused study on the chemical space near a hit compound leaving many unexplored regions that may present highly biological active reservoirs. This study aims to demonstrate that this unveiled chemical space can hide compounds with interesting potential biological activity that would be worth pursuing. This underlines the value and necessity of broadening an approach beyond conventional strategies. Hence, we advocate for an alternative methodology that may be more efficient in the early drug discovery stages. We have selected the case of Tafenoquine, a single-dose treatment for the radical cure of P. vivax malaria approved by the FDA in 2018, as an example to illustrate the process. Through the deep exploration of the Tafenoquine chemical space, seven compounds with potential antimalarial activity have been rationally identified and synthesized. This small set is representative of the chemical diversity unexplored by the 58 analogs reported to date. After biological assessment, results evidence that our approach for rational design has proven to be a very efficient exploratory methodology suitable for the early drug discovery stages.
Topics: Antimalarials; Aminoquinolines; Structure-Activity Relationship; Molecular Structure; Dose-Response Relationship, Drug; Humans; Parasitic Sensitivity Tests; Plasmodium vivax; Plasmodium falciparum
PubMed: 38788364
DOI: 10.1016/j.bioorg.2024.107472 -
Tropical Medicine and Infectious Disease May 2024Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused...
Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus and is transmitted by female mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by followed by . Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city.
PubMed: 38787045
DOI: 10.3390/tropicalmed9050112 -
Tropical Medicine and Infectious Disease May 2024Greece has been malaria-free since 1974, after an intense malaria control program. However, as Greece hosts migrant populations from malaria-endemic countries, there is...
Greece has been malaria-free since 1974, after an intense malaria control program. However, as Greece hosts migrant populations from malaria-endemic countries, there is a risk of introducing the disease to specific vulnerable and receptive areas of the country. Knowledge of the genetic diversity of populations is essential for understanding the dynamics of malaria disease transmission in a given region. We used nine highly polymorphic markers to genotype 124 -infected archived DNA samples from human blood specimens referred to the NMRL from all over Greece throughout 2015-2019. The genotypic variability of the samples studied was noted, as they comprised several unique haplotypes, indicative of the importation of a large number of different strains in the country. However, only a few events of local transmission were recorded. Genotyping revealed and confirmed the same clusters as those identified through epidemiological investigation. In only one introduction event was the index case found. No sustained/ongoing malaria transmissions in/between the studied regions or during consecutive years or additional foci of local transmission were observed. Genotyping is an important component in assisting malaria surveillance, as it provides information concerning the patterns of introduction and the effectiveness of implemented malaria control and elimination measures.
PubMed: 38787035
DOI: 10.3390/tropicalmed9050102 -
Tropical Medicine and Infectious Disease Apr 2024The genetic diversity within the circumsporozoite surface protein (PvCSP) of , the predominant malaria species in Thailand, is primarily observed in the northwestern...
The genetic diversity within the circumsporozoite surface protein (PvCSP) of , the predominant malaria species in Thailand, is primarily observed in the northwestern region along the Thailand-Myanmar border. However, as cases shift to southern provinces, particularly Yala Province near the Thailand-Malaysia border, PvCSP diversity remains understudied. Between 2018 and 2020, 89 isolates were collected in Yala Province, a significant malaria hotspot. Employing polymerase chain reaction amplification, restriction fragment length polymorphism (PCR-RFLP), and DNA sequencing, the gene encoding PvCSP () was analyzed. All Yala isolates belonged to the VK210 type, distinct from strains in the western region near the Myanmar border. The central repeat region of revealed two common peptide repeat motifs-GDRADGQPA and GDRAAGQPA-across all southern isolates. Sequence analysis identified two subtypes, with S1 more prevalent (92%) than S2 (8%). This study underscores the limited diversity of VK210 variants of populations in southern Thailand. These baseline findings facilitate monitoring for potential new parasite variants, aiding in the future control and management of in the region.
PubMed: 38787027
DOI: 10.3390/tropicalmed9050094 -
Health Science Reports May 2024Malaria is one of the biggest public health challenges in Ethiopia that has hampered the country's economic growth and development, and the government is on track to...
BACKGROUND
Malaria is one of the biggest public health challenges in Ethiopia that has hampered the country's economic growth and development, and the government is on track to reduce malaria prevalence by 80% by 2025.
OBJECTIVE
As a result, the purpose of this study was to examine the trends in malaria prevalence in Wayu Tuqa District, Gute Health Center, over the last 10 years (2013-2022).
MATERIAL AND METHODS
A retrospective analysis was undertaken to identify the patterns of malaria cases in Wayu Tuqa District, Gute Health Center, from 2013 to 2022 by evaluating the malaria registration laboratory logbook. All socio-demographic data, as well as the year, month, and malaria prevalence, were obtained using a predesigned data collection form from previous years.
RESULTS
In this study, 3402 (22.50%) of the total 15,040 probable patients had malaria. was the most common species, accounting for 82.84% (2818) of the total, followed by (16.00%) (547). Males and people over the age of 15 were the most affected demographics.
CONCLUSION
In this study, the highest number of malaria cases were observed in 2021 and 2022, respectively. Furthermore, the autumn season had the highest incidence of malaria cases, 40% (1339), while the spring season had the lowest prevalence, 16% (546). The general trend of plasmodium species at Gute Health Center over the previous 10 years (2013-2022) has not shown inconsistent trends. As a result, proper malaria prevention and control planning, implementation, and monitoring should be strengthened at all levels.
PubMed: 38784252
DOI: 10.1002/hsr2.2156 -
Infectious Diseases of Poverty May 2024Lao PDR has made significant progress in malaria control. The National Strategic Plans outline ambitious targets, aiming for the elimination of Plasmodium falciparum and... (Review)
Review
BACKGROUND
Lao PDR has made significant progress in malaria control. The National Strategic Plans outline ambitious targets, aiming for the elimination of Plasmodium falciparum and P. vivax malaria from all northern provinces by 2025 and national elimination by 2030. This article presents an overview of malaria epidemiology, surveillance, and response systems in Lao PDR, emphasizing experiences and achievements in transmission reduction.
METHODS
Data on surveillance, monitoring and evaluation systems, human resources, infrastructure, and community malaria knowledge during 2010-2020 were systematically gathered from the national program and relevant documents. The collected information was synthesized, and discussions on challenges and future prospects were provided.
RESULTS
Malaria control and elimination activities in Lao PDR were implemented at various levels, with a focus on health facility catchment areas. There has been significant progress in reducing malaria transmission throughout the country. Targeted interventions, such as case management, vector control, and community engagement, using stratification of control interventions by catchment areas have contributed to the decline in malaria cases. In elimination areas, active surveillance strategies, including case and foci investigation, are implemented to identify and stop transmission. The surveillance system has facilitated timely detection and response to malaria cases, enabling these targeted interventions in higher-risk areas.
CONCLUSIONS
The malaria surveillance and response system in Lao PDR has played a crucial role in reducing transmission and advancing the country towards elimination. Challenges such as importation, drug resistance, and sustaining support require ongoing efforts. Further strengthening surveillance, improving access to services, and addressing transmission determinants are key areas of focus to achieve malaria elimination and enhance population health in Lao PDR.
Topics: Laos; Humans; Disease Eradication; Malaria; Epidemiological Monitoring; Malaria, Vivax; Population Surveillance; Malaria, Falciparum
PubMed: 38783374
DOI: 10.1186/s40249-024-01202-7 -
Malaria Journal May 2024Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the...
Evaluation of naturally acquired immune responses against novel pre-erythrocytic Plasmodium vivax proteins in a low endemic malaria population located in the Peruvian Amazon Basin.
BACKGROUND
Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity.
METHODS
Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used.
RESULTS
In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58-99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9-35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses.
CONCLUSIONS
These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.
Topics: Plasmodium vivax; Peru; Humans; Malaria, Vivax; Adult; Male; Young Adult; Adolescent; Female; Middle Aged; Protozoan Proteins; Antigens, Protozoan; Immunoglobulin G; Antibodies, Protozoan; Enzyme-Linked Immunosorbent Assay; Child; Aged; Enzyme-Linked Immunospot Assay
PubMed: 38783317
DOI: 10.1186/s12936-024-04978-z -
Journal of Parasitology Research 2024Malaria is one of the major public health problems in sub-Saharan Africa, including Ethiopia. Children under the age of five are immunologically naive to plasmodium...
Malaria is one of the major public health problems in sub-Saharan Africa, including Ethiopia. Children under the age of five are immunologically naive to plasmodium parasites, making them the most vulnerable group to clinical manifestations of malaria infection. Despite the severity of the disease in children under five years of age, most studies on malaria focus on the adult population. In the present study, a cross-sectional study design based on health facilities was used during the minor malaria season from February 18 to May 28, 2023, at Mohammed Akile Memorial General Hospital, in Afar Regional State, district of Amibara located in the town of Berta. The finding revealed that 19.8% prevalence among symptomatic children with 61.04% and 38.96% of and , respectively. In the present study area, malaria infection in children under five years of age is significantly associated with the presence of stagnant water in the residential area, inappropriate or no use of insecticide-treated net, and indoor residual spraying (IRS). The prevalence of malaria among symptomatic children under five years of age is higher compared to the national prevalence of malaria among the general population. Therefore, community mobilization through health promotion, aiming to interrupt the transmission of malaria at the community level, is paramount.
PubMed: 38774540
DOI: 10.1155/2024/6365077 -
Journal of Parasitology Research 2024Despite extensive efforts and achievements made in prevention and control, malaria is still a public health problem in Ethiopia. Currently, the case number has been...
BACKGROUND
Despite extensive efforts and achievements made in prevention and control, malaria is still a public health problem in Ethiopia. Currently, the case number has been climbing, even changing the epidemiology to the previously low-burden reporting locations. Therefore, our study is aimed at assessing malaria prevalence and associated risk factors in outpatients, Northwest Ethiopia.
METHODS
A facility-based cross-sectional study was conducted among 318 malaria-suspected outpatients from October 22 to December 15, 2022, at Teda Health Center, Northwest Ethiopia. Sociodemographic characteristics and malaria risk factors were assessed by a face-to-face interview using a pretested questionnaire. parasites were detected by using microscopy on a blood film stained with 10% and 3% Giemsa stain. The data were analyzed using Statistical Package for Social Sciences software version 25, and statistical significance was reported at a value < 0.05.
RESULTS
Of the 318 study participants, 124 (39.0%; 95%CI = 33.6% - 44.6%) tested positive for infection. , , and mixed infections were identified in 71 (57.3%), 47 (37.9%), and 6 (4.8%), respectively, among positive study participants. Individuals above the age of 15 (AOR = 2.704, 95% CI 1.370-5.336) were more likely to be infected with than under-five-year-old individuals. Rural residents (AOR = 2.56, 95% CI 1.281-5.098), those who sleep or work outside at night (AOR = 1.99, 95% CI 1.020-3.875), and individuals who did not use long-lasting insecticide-treated net (AOR = 3.26, 95% CI 1.633-6.499) and had a family member with a history of malaria (AOR = 2.902, 95%CI = 1.671 - 5.041) had higher odds of acquiring infection than their counterparts.
CONCLUSION
In our study area, malaria was a major health problem, with being the dominant species. Multiple environmental and behavioural factors were associated with the infection acquisition. Therefore, urgent holistic intervention is required.
PubMed: 38774539
DOI: 10.1155/2024/8919098 -
Journal of Mathematical Biology May 2024Malaria is a vector-borne disease that exacts a grave toll in the Global South. The epidemiology of Plasmodium vivax, the most geographically expansive agent of human...
Malaria is a vector-borne disease that exacts a grave toll in the Global South. The epidemiology of Plasmodium vivax, the most geographically expansive agent of human malaria, is characterised by the accrual of a reservoir of dormant parasites known as hypnozoites. Relapses, arising from hypnozoite activation events, comprise the majority of the blood-stage infection burden, with implications for the acquisition of immunity and the distribution of superinfection. Here, we construct a novel model for the transmission of P. vivax that concurrently accounts for the accrual of the hypnozoite reservoir, (blood-stage) superinfection and the acquisition of immunity. We begin by using an infinite-server queueing network model to characterise the within-host dynamics as a function of mosquito-to-human transmission intensity, extending our previous model to capture a discretised immunity level. To model transmission-blocking and antidisease immunity, we allow for geometric decay in the respective probabilities of successful human-to-mosquito transmission and symptomatic blood-stage infection as a function of this immunity level. Under a hybrid approximation-whereby probabilistic within-host distributions are cast as expected population-level proportions-we couple host and vector dynamics to recover a deterministic compartmental model in line with Ross-Macdonald theory. We then perform a steady-state analysis for this compartmental model, informed by the (analytic) distributions derived at the within-host level. To characterise transient dynamics, we derive a reduced system of integrodifferential equations, likewise informed by our within-host queueing network, allowing us to recover population-level distributions for various quantities of epidemiological interest. In capturing the interplay between hypnozoite accrual, superinfection and acquired immunity-and providing, to the best of our knowledge, the most complete population-level distributions for a range of epidemiological values-our model provides insights into important, but poorly understood, epidemiological features of P. vivax.
Topics: Humans; Plasmodium vivax; Superinfection; Malaria, Vivax; Animals; Mathematical Concepts; Mosquito Vectors; Disease Reservoirs; Models, Biological; Computer Simulation; Anopheles
PubMed: 38772937
DOI: 10.1007/s00285-024-02088-7