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1.
Analyst ; 147(12): 2662-2670, 2022 Jun 13.
Article in English | MEDLINE | ID: covidwho-1864777

ABSTRACT

Malaria was regarded as the most devastating infectious disease of the 21st century until the COVID-19 pandemic. Asexual blood staged parasites (ABS) play a unique role in ensuring the parasite's survival and pathogenesis. Hitherto, there have been no spectroscopic reports discriminating the life cycle stages of the ABS parasite under physiological conditions. The identification and quantification of the stages in the erythrocytic life cycle is important in monitoring the progression and recovery from the disease. In this study, we explored visible microspectrophotometry coupled to machine learning to discriminate functional ABS parasites at the single cell level. Principal Component Analysis (PCA) showed an excellent discrimination between the different stages of the ABS parasites. Support Vector Machine Analysis provided a 100% prediction for both schizonts and trophozoites, while a 92% and 98% accuracy was achieved for predicting control and ring staged infected RBCs, respectively. This work shows proof of principle for discriminating the life cycle stages of parasites in functional erythrocytes using visible microscopy and thus eliminating the drying and fixative steps that are associated with other optical-based spectroscopic techniques.


Subject(s)
COVID-19 , Malaria, Falciparum , Malaria , Parasites , Animals , Erythrocytes/parasitology , Humans , Life Cycle Stages , Machine Learning , Microspectrophotometry , Pandemics , Plasmodium falciparum/physiology
2.
Lancet Infect Dis ; 22(3): 377-389, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1839424

ABSTRACT

BACKGROUND: WHO recently approved a partially effective vaccine that reduces clinical malaria in children, but increased vaccine activity is required to pursue malaria elimination. A phase 1 clinical trial was done in Mali, west Africa, to assess the safety, immunogenicity, and protective efficacy of a three-dose regimen of Plasmodium falciparum sporozoite (PfSPZ) Vaccine (a metabolically active, non-replicating, whole malaria sporozoite vaccine) against homologous controlled human malaria infection (CHMI) and natural P falciparum infection. METHODS: We recruited healthy non-pregnant adults aged 18-50 years in Donéguébougou, Mali, and surrounding villages (Banambani, Toubana, Torodo, Sirababougou, Zorokoro) for an open-label, dose-escalation pilot study and, thereafter, a randomised, double-blind, placebo-controlled main trial. Pilot study participants were enrolled on an as-available basis to one group of CHMI infectivity controls and three staggered vaccine groups receiving: one dose of 4·5 × 105, one dose of 9 × 105, or three doses of 1·8 × 106 PfSPZ via direct venous inoculation at approximately 8 week intervals, followed by homologous CHMI 5 weeks later with infectious PfSPZ by direct venous inoculation (PfSPZ Challenge). Main cohort participants were stratified by village and randomly assigned (1:1) to receive three doses of 1·8 × 106 PfSPZ or normal saline at 1, 13, and 19 week intervals using permuted block design by the study statistician. The primary outcome was safety and tolerability of at least one vaccine dose; the secondary outcome was vaccine efficacy against homologous PfSPZ CHMI (pilot study) or against naturally transmitted P falciparum infection (main study) measured by thick blood smear. Combined artesunate and amodiaquine was administered to eliminate pre-existing parasitaemia. Outcomes were analysed by modified intention to treat (mITT; including all participants who received at least one dose of investigational product; safety and vaccine efficacy) and per protocol (vaccine efficacy). This trial is registered with ClinicalTrials.gov, number NCT02627456. FINDINGS: Between Dec 20, 2015, and April 30, 2016, we enrolled 56 participants into the pilot study (five received the 4·5 × 105 dose, five received 9 × 105, 30 received 1·8 × 106, 15 were CHMI controls, and one withdrew before vaccination) and 120 participants into the main study cohort with 60 participants assigned PfSPZ Vaccine and 60 placebo in the main study. Adverse events and laboratory abnormalities post-vaccination in all dosing groups were few, mainly mild, and did not differ significantly between vaccine groups (all p>0·05). Unexpected severe transaminitis occured in four participants: one participant in pilot phase that received 1·8 × 106 PfSPZ Vaccine, one participant in main phase that received 1·8 × 106 PfSPZ Vaccine, and two participants in the main phase placebo group. During PfSPZ CHMI, approximately 5 weeks after the third dose of 1·8 × 106 PfSPZ, none of 29 vaccinees and one of 15 controls became positive on thick blood smear; subsequent post-hoc PCR analysis for submicroscopic blood stage infections detected P falciparum parasites in none of the 29 vaccine recipients and eight of 15 controls during CHMI. In the main trial, 32 (58%) of 55 vaccine recipients and 42 (78%) of 54 controls became positive on thick blood smear during 24-week surveillance after vaccination. Vaccine efficacy (1-hazard ratio) was 0·51 per protocol (95% CI 0·20-0·70; log-rank p=0·0042) and 0·39 by mITT (0·04-0·62; p=0·033); vaccine efficacy (1-risk ratio) was 0·24 per-protocol (0·02-0·41; p=0·031) and 0·22 mITT (0·01-0·39; p=0·041). INTERPRETATION: A three-dose regimen of PfSPZ Vaccine was safe, well tolerated, and conferred 51% vaccine efficacy against intense natural P falciparum transmission, similar to 52% vaccine efficacy reported for a five-dose regimen in a previous trial. FUNDING: US National Institute of Allergy and Infectious Diseases, National Institutes of Health, Sanaria. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.


Subject(s)
Malaria Vaccines , Malaria, Falciparum , Malaria , Adolescent , Adult , Animals , Child , Double-Blind Method , Humans , Malaria/drug therapy , Malaria, Falciparum/drug therapy , Mali , Middle Aged , Pilot Projects , Plasmodium falciparum , Seasons , Sporozoites , Young Adult
3.
Lancet ; 399(10337): 1777, 2022 05 07.
Article in English | MEDLINE | ID: covidwho-1829704
4.
BMC Genomics ; 23(1): 237, 2022 Mar 26.
Article in English | MEDLINE | ID: covidwho-1793988

ABSTRACT

BACKGROUND: Novel antimalarials should be effective across all species of malaria parasites that infect humans, especially the two species that bear the most impact, Plasmodium falciparum and Plasmodium vivax. Protein kinases encoded by pathogens, as well as host kinases required for survival of intracellular pathogens, carry considerable potential as targets for antimalarial intervention (Adderley et al. Trends Parasitol 37:508-524, 2021;  Wei et al. Cell Rep Med 2:100423, 2021). To date, no comprehensive P. vivax kinome assembly has been conducted; and the P. falciparum kinome, first assembled in 2004, requires an update. The present study, aimed to fill these gaps, utilises a recently published structurally-validated multiple sequence alignment (MSA) of the human kinome (Modi et al. Sci Rep 9:19790, 2019). This MSA is used as a scaffold to assist the alignment of all protein kinase sequences from P. falciparum and P. vivax, and (where possible) their assignment to specific kinase groups/families. RESULTS: We were able to assign six P. falciparum previously classified as OPK or 'orphans' (i.e. with no clear phylogenetic relation to any of the established ePK groups) to one of the aforementioned ePK groups. Direct phylogenetic comparison established that despite an overall high level of similarity between the P. falciparum and P. vivax kinomes, which will help in selecting targets for intervention, there are differences that may underlie the biological specificities of these species. Furthermore, we highlight a number of Plasmodium kinases that have a surprisingly high level of similarity with their human counterparts and therefore not well suited as targets for drug discovery. CONCLUSIONS: Direct comparison of the kinomes of Homo sapiens, P. falciparum and P. vivax sheds additional light on the previously documented divergence of many P. falciparum and P. vivax kinases from those of their human host. We provide the first direct kinome comparison between the phylogenetically distinct species of P. falciparum and P. vivax, illustrating the key similarities and differences which must be considered in the context of kinase-directed antimalarial drug discovery, and discuss the divergences and similarities between the human and Plasmodium kinomes to inform future searches for selective antimalarial intervention.


Subject(s)
Malaria, Falciparum , Malaria, Vivax , Humans , Malaria, Falciparum/parasitology , Malaria, Vivax/parasitology , Phylogeny , Plasmodium falciparum/genetics , Plasmodium vivax/genetics
5.
BMJ Open ; 12(3): e053922, 2022 03 31.
Article in English | MEDLINE | ID: covidwho-1774956

ABSTRACT

OBJECTIVES: Malaria is a vector-borne disease that remains a serious public health problem due to its climatic sensitivity. Accurate prediction of malaria re-emergence is very important in taking corresponding effective measures. This study aims to investigate the impact of climatic factors on the re-emergence of malaria in mainland China. DESIGN: A modelling study. SETTING AND PARTICIPANTS: Monthly malaria cases for four Plasmodium species (P. falciparum, P. malariae, P. vivax and other Plasmodium) and monthly climate data were collected for 31 provinces; malaria cases from 2004 to 2016 were obtained from the Chinese centre for disease control and prevention and climate parameters from China meteorological data service centre. We conducted analyses at the aggregate level, and there was no involvement of confidential information. PRIMARY AND SECONDARY OUTCOME MEASURES: The long short-term memory sequence-to-sequence (LSTMSeq2Seq) deep neural network model was used to predict the re-emergence of malaria cases from 2004 to 2016, based on the influence of climatic factors. We trained and tested the extreme gradient boosting (XGBoost), gated recurrent unit, LSTM, LSTMSeq2Seq models using monthly malaria cases and corresponding meteorological data in 31 provinces of China. Then we compared the predictive performance of models using root mean squared error (RMSE) and mean absolute error evaluation measures. RESULTS: The proposed LSTMSeq2Seq model reduced the mean RMSE of the predictions by 19.05% to 33.93%, 18.4% to 33.59%, 17.6% to 26.67% and 13.28% to 21.34%, for P. falciparum, P. vivax, P. malariae, and other plasmodia, respectively, as compared with other candidate models. The LSTMSeq2Seq model achieved an average prediction accuracy of 87.3%. CONCLUSIONS: The LSTMSeq2Seq model significantly improved the prediction of malaria re-emergence based on the influence of climatic factors. Therefore, the LSTMSeq2Seq model can be effectively applied in the malaria re-emergence prediction.


Subject(s)
Deep Learning , Malaria, Falciparum , Malaria , China/epidemiology , Climate Change , Humans , Malaria/epidemiology
6.
PLoS Pathog ; 18(2): e1010282, 2022 02.
Article in English | MEDLINE | ID: covidwho-1753213

ABSTRACT

Immunization with radiation-attenuated sporozoites (RAS) can confer sterilizing protection against malaria, although the mechanisms behind this protection are incompletely understood. We performed a systems biology analysis of samples from the Immunization by Mosquito with Radiation Attenuated Sporozoites (IMRAS) trial, which comprised P. falciparum RAS-immunized (PfRAS), malaria-naive participants whose protection from malaria infection was subsequently assessed by controlled human malaria infection (CHMI). Blood samples collected after initial PfRAS immunization were analyzed to compare immune responses between protected and non-protected volunteers leveraging integrative analysis of whole blood RNA-seq, high parameter flow cytometry, and single cell CITEseq of PBMCs. This analysis revealed differences in early innate immune responses indicating divergent paths associated with protection. In particular, elevated levels of inflammatory responses early after the initial immunization were detrimental for the development of protective adaptive immunity. Specifically, non-classical monocytes and early type I interferon responses induced within 1 day of PfRAS vaccination correlated with impaired immunity. Non-protected individuals also showed an increase in Th2 polarized T cell responses whereas we observed a trend towards increased Th1 and T-bet+ CD8 T cell responses in protected individuals. Temporal differences in genes associated with natural killer cells suggest an important role in immune regulation by these cells. These findings give insight into the immune responses that confer protection against malaria and may guide further malaria vaccine development. Trial registration: ClinicalTrials.gov NCT01994525.


Subject(s)
Immunity , Inflammation , Malaria Vaccines/immunology , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Sporozoites/immunology , Adult , Animals , Anopheles/parasitology , Female , Humans , Immunization/methods , Insect Bites and Stings/immunology , Malaria, Falciparum/parasitology , Male , Mosquito Vectors/parasitology , T-Lymphocytes/immunology , Vaccination/methods , Vaccines, Attenuated/immunology
8.
Int J Environ Res Public Health ; 19(5)2022 02 23.
Article in English | MEDLINE | ID: covidwho-1736891

ABSTRACT

The conventional paper-based system for malaria surveillance is time-consuming, difficult to track and resource-intensive. Few digital platforms are in use but wide-scale deployment and acceptability remain to be seen. To address this issue, we created a malaria surveillance mobile app that offers real-time data to stakeholders and establishes a centralised data repository. The MoSQuIT app was designed to collect data from the field and was integrated with a web-based platform for data integration and analysis. The MoSQuIT app was deployed on mobile phones of accredited social health activists (ASHA) working in international border villages in the northeast (NE) Indian states of Assam, Tripura and Arunachal Pradesh for 20 months in a phased manner. This paper shares the challenges and opportunities associated with the use of MoSQuIT for malaria surveillance. MoSQuIT employs the same data entry formats as the NVBDCP's malaria surveillance programme. Using this app, a total of 8221 fever cases were recorded, which included 1192 (14.5%) cases of P. falciparum malaria, 280 (3.4%) cases of P. vivax malaria and 52 (0.6%) mixed infection cases. Depending on network availability, GPS coordinates of the fever cases were acquired by the app. The present study demonstrated that mobile-phone-based malaria surveillance facilitates the quick transmission of data from the field to decision makers. Geospatial tagging of cases helped with easy visualisation of the case distribution for the identification of malaria-prone areas and potential outbreaks, especially in hilly and remote regions of Northeast India. However, to achieve the full operational potential of the system, operational challenges have to be overcome.


Subject(s)
Malaria, Falciparum , Malaria, Vivax , Malaria , Mobile Applications , Telemedicine , Fever , Humans , India/epidemiology , Malaria/epidemiology , Malaria, Falciparum/epidemiology , Malaria, Vivax/epidemiology
9.
Travel Med Infect Dis ; 47: 102307, 2022.
Article in English | MEDLINE | ID: covidwho-1730130

ABSTRACT

BACKGROUND: Eliminating malaria along the China-Vietnam border remains one of the greatest challenges in China, especially during the coronavirus disease 2019 (COVID-19) pandemic, which has disrupted the continuity of malaria control and elimination programs. Understanding the factors associated with asymptomatic malaria infection will inform control interventions aimed at elimination of the disease among migrants from Vietnam working in China, who constitute an at-risk population. METHODS: From March 2018 to September 2019, 108 migrants from Vietnam working in Ningming County, Guangxi, were enrolled in this study. Each person was interviewed using a structured questionnaire. Blood samples were collected and sent for PCR detection and sequencing. The obtained sequences were analyzed using the BLAST program and DNAMAN software. RESULTS: The proportion of participants with malaria knowledge was low, with 19.4% (21/108) reporting knowledge about transmission, 23.2% (25/108) reporting knowledge about clinical symptoms, 7.4% (8/108) reporting awareness of the risk of death and 14.8% (16/108) reporting awareness of prevention methods. No significant difference in the malaria knowledge rate was found among occupational groups, except in the migrant worker group, whose knowledge rate was higher than those in the other occupational groups (χ2 = 32.452, p < 0.001). Although most of the participants (80.6%, 87/108) owned mosquito nets, only approximately half of the participants (49.1%, 53/108) reported using bed nets. The parasitological analysis revealed that 5.6% (6/108) of all the participants were positive for malaria, including 5 participants with Plasmodium falciparum and 1 participant with Plasmodium vivax malaria. There were no statistically significant differences in the positivity rates among the different age, sex, family-size, nationality, occupational, and behavior groups. The positivity rates in individuals who did not use mosquito nets, did not use mosquito coils, and did not install mosquito nets were 4.8% (1/21), 6.8% (3/44), and 3.6% (2/55), respectively. CONCLUSION: Health education focused on high-risk populations, such as migrant workers and forest goers, should be strengthened. Verbal communication and information transmission via the internet, radio, and mobile phone platforms may be required during the COVID-19 pandemic. Further risk assessments and proactive case detection should also be performed in Ningming County and other border counties in Guangxi to detect active and asymptomatic infections in a timely manner and prevent re-establishment of the disease in these communities.


Subject(s)
COVID-19 , Malaria, Falciparum , Malaria, Vivax , Malaria , Transients and Migrants , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , China/epidemiology , Humans , Malaria/drug therapy , Malaria/epidemiology , Malaria/prevention & control , Malaria, Falciparum/epidemiology , Malaria, Vivax/epidemiology , Pandemics , Plasmodium vivax , Vietnam/epidemiology
12.
Malar J ; 20(1): 470, 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1639119

ABSTRACT

BACKGROUND: Malaria-associated anaemia, arising from symptomatic, asymptomatic and submicroscopic infections, is a significant cause of morbidity worldwide. Induced blood stage malaria volunteer infection studies (IBSM-VIS) provide a unique opportunity to evaluate the haematological response to early Plasmodium falciparum and Plasmodium vivax infection. METHODS: This study was an analysis of the haemoglobin, red cell counts, and parasitaemia data from 315 participants enrolled in IBSM-VIS between 2012 and 2019, including 269 participants inoculated with the 3D7 strain of P. falciparum (Pf3D7), 15 with an artemisinin-resistant P. falciparum strain (PfK13) and 46 with P. vivax. Factors associated with the fractional fall in haemoglobin (Hb-FF) were evaluated, and the malaria-attributable erythrocyte loss after accounting for phlebotomy-related losses was estimated. The relative contribution of parasitized erythrocytes to the malaria-attributable erythrocyte loss was also estimated. RESULTS: The median peak parasitaemia prior to treatment was 10,277 parasites/ml (IQR 3566-27,815), 71,427 parasites/ml [IQR 33,236-180,213], and 34,840 parasites/ml (IQR 13,302-77,064) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. The median Hb-FF was 10.3% (IQR 7.8-13.3), 14.8% (IQR 11.8-15.9) and 11.7% (IQR 8.9-14.5) in those inoculated with Pf3D7, PfK13 and P. vivax, respectively, with the haemoglobin nadir occurring a median 12 (IQR 5-21), 15 (IQR 7-22), and 8 (IQR 7-15) days following inoculation. In participants inoculated with P. falciparum, recrudescence was associated with a greater Hb-FF, while in those with P. vivax, the Hb-FF was associated with a higher pre-treatment parasitaemia and later day of anti-malarial treatment. After accounting for phlebotomy-related blood losses, the estimated Hb-FF was 4.1% (IQR 3.1-5.3), 7.2% (IQR 5.8-7.8), and 4.9% (IQR 3.7-6.1) in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. Parasitized erythrocytes were estimated to account for 0.015% (IQR 0.006-0.06), 0.128% (IQR 0.068-0.616) and 0.022% (IQR 0.008-0.082) of the malaria-attributable erythrocyte loss in participants inoculated with Pf3D7, PfK13, and P. vivax, respectively. CONCLUSION: Early experimental P. falciparum and P. vivax infection resulted in a small but significant fall in haemoglobin despite parasitaemia only just at the level of microscopic detection. Loss of parasitized erythrocytes accounted for < 0.2% of the total malaria-attributable haemoglobin loss.


Subject(s)
Anemia/drug therapy , Antimalarials/therapeutic use , Erythrocytes/parasitology , Malaria, Falciparum/drug therapy , Malaria, Vivax/drug therapy , Parasitemia/drug therapy , Adult , Anemia/parasitology , Female , Humans , Malaria, Falciparum/complications , Malaria, Falciparum/parasitology , Malaria, Vivax/complications , Malaria, Vivax/parasitology , Male , Middle Aged , Parasitemia/parasitology , Plasmodium falciparum/drug effects , Plasmodium vivax/drug effects , Young Adult
13.
J Travel Med ; 28(8)2021 Dec 29.
Article in English | MEDLINE | ID: covidwho-1597866

ABSTRACT

We report the case of a 29-year-old male in whom COVID-19 concerns led to a delayed diagnosis of falciparum malaria. The patient developed symptoms of cerebral malaria with cytotoxic lesions of the corpus callosum in magnetic resonance imaging.


Subject(s)
Antimalarials , COVID-19 , Malaria, Cerebral , Malaria, Falciparum , Adult , Antimalarials/therapeutic use , Humans , Malaria, Cerebral/diagnosis , Malaria, Cerebral/drug therapy , Malaria, Falciparum/diagnosis , Malaria, Falciparum/drug therapy , Male , Pandemics , Plasmodium falciparum , SARS-CoV-2
14.
Int J Mol Sci ; 22(24)2021 Dec 17.
Article in English | MEDLINE | ID: covidwho-1594431

ABSTRACT

Malaria is still one of the most dangerous infectious diseases and the emergence of drug resistant parasites only worsens the situation. A series of new tetrahydro-ß-carbolines were designed, synthesized by the Pictet-Spengler reaction, and characterized. Further, the compounds were screened for their in vitro antiplasmodial activity against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Moreover, molecular modeling studies were performed to assess the potential action of the designed molecules and toxicity assays were conducted on the human microvascular endothelial (HMEC-1) cell line and human red blood cells. Our studies identified N-(3,3-dimethylbutyl)-1-octyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b] indole-3-carboxamide (7) (a mixture of diastereomers) as the most promising compound endowed with the highest antiplasmodial activity, highest selectivity, and lack of cytotoxicity. In silico simulations carried out for (1S,3R)-7 provided useful insights into its possible interactions with enzymes essential for parasite metabolism. Further studies are underway to develop the optimal nanosized lipid-based delivery system for this compound and to determine its precise mechanism of action.


Subject(s)
Antimalarials/chemistry , Antimalarials/pharmacology , Carbolines/chemistry , Carbolines/pharmacology , Plasmodium falciparum/drug effects , Antimalarials/chemical synthesis , Carbolines/chemical synthesis , Cell Line , Drug Design , Humans , Malaria, Falciparum/drug therapy , Molecular Docking Simulation , Plasmodium falciparum/enzymology , Plasmodium falciparum/metabolism
15.
BMJ Open ; 11(11): e048073, 2021 11 17.
Article in English | MEDLINE | ID: covidwho-1583118

ABSTRACT

PURPOSE: This population-based open cohort study aims to investigate biological and sociodemographic drivers of malaria transmission in the main urban hotspot of Amazonian Brazil. PARTICIPANTS: Nearly 20% of the households in the northwestern town of Mâncio Lima were randomly selected and 2690 participants were enrolled since April 2018. Sociodemographic, housing quality, occupational, behavioural and morbidity information and travel histories were collected during consecutive study visits. Blood samples from participants>3 months old were used for malaria diagnosis and human genetic studies; samples from participants with laboratory-confirmed malaria have been cryopreserved for genetic and phenotypic characterisation of parasites. Serology was introduced in 2020 to measure the prevalence and longevity of SARS-CoV-2 IgG antibodies. FINDINGS TO DATE: Malaria prevalence rates were low (up to 1.0% for Plasmodium vivax and 0.6% for P. falciparum) during five consecutive cross-sectional surveys between April-May 2018 and October-November 2020; 63% of infections diagnosed by microscopy were asymptomatic. Malaria risk is heterogeneously distributed, with 20% study participants contributing 86% of the overall burden of P. vivax infection. Adult males are at greatest risk of infection and human mobility across the urban-rural interface may contribute to sustained malaria transmission. Local P. vivax parasites are genetically diverse and fragmented into discrete inbred lineages that remain stable across space and time. FUTURE PLANS: Two follow-up visits, with similar study protocols, are planned in 2021. We aim to identify high-risk individuals that fuel onwards malaria transmission and represent a priority target for more intensive and effective control interventions. TRIAL REGISTRATION NUMBER: NCT03689036.


Subject(s)
COVID-19 , Malaria, Falciparum , Malaria, Vivax , Malaria , Adult , Brazil/epidemiology , Cohort Studies , Cross-Sectional Studies , Humans , Infant , Malaria/epidemiology , Malaria, Vivax/epidemiology , Male , Prevalence , SARS-CoV-2
16.
Front Cell Infect Microbiol ; 11: 805482, 2021.
Article in English | MEDLINE | ID: covidwho-1581379

ABSTRACT

Control measures have significantly reduced malaria morbidity and mortality in the last two decades; however, the downward trends have stalled and have become complicated by the emergence of COVID-19. Significant efforts have been made to develop malaria vaccines, but currently only the RTS,S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO, for widespread use among children in sub-Saharan Africa. The efficacy of RTS,S/AS01 is modest, and therefore the development of more efficacious vaccines is still needed. In addition, the development of transmission-blocking vaccines (TBVs) to reduce the parasite transmission from humans to mosquitoes is required toward the goal of malaria elimination. Few TBVs have reached clinical development, and challenges include low immunogenicity or high reactogenicity in humans. Therefore, novel approaches to accelerate TBV research and development are urgently needed, especially novel TBV candidate discovery. In this mini review we summarize the progress in TBV research and development, novel TBV candidate discovery, and discuss how to accelerate novel TBV candidate discovery.


Subject(s)
COVID-19 , Malaria Vaccines , Malaria, Falciparum , Malaria , Animals , Child , Humans , Malaria/prevention & control , Malaria, Falciparum/prevention & control , Plasmodium falciparum , SARS-CoV-2
17.
Front Immunol ; 12: 565625, 2021.
Article in English | MEDLINE | ID: covidwho-1574690

ABSTRACT

Sub-Saharan Africa has generally experienced few cases and deaths of coronavirus disease 2019 (COVID-19). In addition to other potential explanations for the few cases and deaths of COVID-19 such as the population socio-demographics, early lockdown measures and the possibility of under reporting, we hypothesize in this mini review that individuals with a recent history of malaria infection may be protected against infection or severe form of COVID-19. Given that both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium falciparum (P. falciparum) merozoites bind to the cluster of differentiation 147 (CD147) immunoglobulin, we hypothesize that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis, hence protecting individuals with a recent P. falciparum infection against COVID-19 infection or severity. This mini review therefore discusses the potential biological link between P. falciparum infection and COVID-19 infection or severity and further highlights the importance of CD147 immunoglobulin as an entry point for both SARS-CoV-2 and P. falciparum into host cells.


Subject(s)
Basigin/immunology , COVID-19 , Immunologic Memory , Malaria, Falciparum , Plasmodium falciparum/immunology , SARS-CoV-2/immunology , Africa South of the Sahara/epidemiology , COVID-19/epidemiology , COVID-19/immunology , Humans , Malaria, Falciparum/epidemiology , Malaria, Falciparum/immunology , Merozoites/immunology , Severity of Illness Index
18.
J Antimicrob Chemother ; 76(11): 2854-2862, 2021 10 11.
Article in English | MEDLINE | ID: covidwho-1537567

ABSTRACT

BACKGROUND: The first potential focus for artemisinin resistance in South America was recently confirmed with the presence of the C580Y mutation in the Plasmodium falciparum kelch 13 gene (pfk13) in Guyana. OBJECTIVES: This study aimed to strengthen pfk13 monitoring in the Amazon basin countries, to compile the available data and to evaluate the risk of spreading of mutations. METHODS: Sanger sequencing was done on 862 samples collected between 1998 and 2019, and a global map of pfk13 genotypes available for this region was constructed. Then, the risk of spreading of mutations based on P. falciparum case importation between 2015 and 2018 within countries of the Amazon basin was evaluated. RESULTS: No additional pfk13 C580Y foci were identified. Few mutations (0.5%, 95% CI = 0.3%-0.8%) in the propeller domain were observed in the general parasite population of this region despite a high proportion of K189T mutations (49.1%, 95% CI = 46.2%-52.0%) in the non-propeller domain. Case information revealed two patterns of intense human migration: Venezuela, Guyana and the Roraima State in Brazil; and French Guiana, Suriname and the Amapá State in Brazil. CONCLUSIONS: There are few pfk13 mutant foci, but a high risk of dispersion in the Amazon basin, mainly from the Guiana Shield, proportionate to mining activities. Therefore, access to prompt diagnosis and treatment, and continuous molecular monitoring is essential in these geographical areas.


Subject(s)
Malaria, Falciparum , Mutation , Plasmodium falciparum , Antimalarials/pharmacology , Antimalarials/therapeutic use , Brazil , Drug Resistance , Humans , Kelch Repeat , Plasmodium falciparum/genetics , Protozoan Proteins/genetics
19.
Acta Parasitol ; 67(1): 55-60, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1525614

ABSTRACT

Plasmodium resistance to antimalarial drugs is an obstacle to the elimination of malaria in endemic areas. This situation is particularly dramatic for Africa, which accounts for nearly 92% of malaria cases worldwide. Drug pressure has been identified as a key factor in the emergence of antimalarial drug resistance. Indeed, this pressure is favoured by several factors, including the use of counterfeit forms of antimalarials, inadequate prescription controls, poor adherence to treatment regimens, dosing errors, and the increasing use of other forms of unapproved antimalarials. This resistance has led to the replacement of chloroquine (CQ) by artemisinin-based combination therapies (ACTs) which are likely to become ineffective in the coming years due to the uncontrolled use of Artemisia annua in the sub-Saharan African region for malaria prevention and COVID-19. The use of Artemisia annua for the prevention of malaria and COVID-19 could be an important factor in the emergence of resistance to Artemisinin-based combination therapies.


Subject(s)
Antimalarials , Artemisia annua , Artemisinins , COVID-19 , Malaria, Falciparum , Malaria , Plasmodium , Antimalarials/pharmacology , Antimalarials/therapeutic use , Artemisinins/pharmacology , Artemisinins/therapeutic use , COVID-19/prevention & control , Humans , Malaria/drug therapy , Malaria/epidemiology , Malaria/prevention & control , Malaria, Falciparum/drug therapy , Plasmodium falciparum
20.
Elife ; 102021 07 19.
Article in English | MEDLINE | ID: covidwho-1513059

ABSTRACT

The emergence of mutant K13-mediated artemisinin (ART) resistance in Plasmodium falciparum malaria parasites has led to widespread treatment failures across Southeast Asia. In Africa, K13-propeller genotyping confirms the emergence of the R561H mutation in Rwanda and highlights the continuing dominance of wild-type K13 elsewhere. Using gene editing, we show that R561H, along with C580Y and M579I, confer elevated in vitro ART resistance in some African strains, contrasting with minimal changes in ART susceptibility in others. C580Y and M579I cause substantial fitness costs, which may slow their dissemination in high-transmission settings, in contrast with R561H that in African 3D7 parasites is fitness neutral. In Cambodia, K13 genotyping highlights the increasing spatio-temporal dominance of C580Y. Editing multiple K13 mutations into a panel of Southeast Asian strains reveals that only the R561H variant yields ART resistance comparable to C580Y. In Asian Dd2 parasites C580Y shows no fitness cost, in contrast with most other K13 mutations tested, including R561H. Editing of point mutations in ferredoxin or mdr2, earlier associated with resistance, has no impact on ART susceptibility or parasite fitness. These data underline the complex interplay between K13 mutations, parasite survival, growth and genetic background in contributing to the spread of ART resistance.


Subject(s)
Artemisinins/pharmacology , Drug Resistance/drug effects , Drug Resistance/genetics , Mutation , Plasmodium falciparum/drug effects , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , Africa , Antimalarials/pharmacology , Asia , Cambodia , Humans , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Molecular Epidemiology
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