Origin of Two Most Virulent Agents of Human Malaria:<i>Plasmodium falciparum</i>and<i>Plasmodium vivax</i>

Boundenga, Larson

doi:10.5772/intechopen.84481

Cited by 10 publications

(12 citation statements)

References 64 publications

(102 reference statements)

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“…Hence, the training set prediction was affirmed by the leave-one-out (LOO) cross-validation method. The large Q 2 LOO value, 0.8317 calculated is a good indication of an excellent internal validation. The results of the external validation, R 2 ext = 0.7019, show the predictive strength of the model and hence its robustness.…”

Section: Model Validationmentioning

confidence: 80%

“…where R 2 ij represents the multiple regression's correlation coefficients between the descriptor i and the remaining j model descriptors.…”

Section: Multi-co-linearity Analysismentioning

confidence: 99%

“…where Y obs (test) and Y (test) indicates the test set predicted and observed activity values respectively, Ŷ training , indicates training set means activity. R 2 pred is the predicted coefficient of correlation estimated from the predicted test set activity.…”

Section: External Validationmentioning

confidence: 99%

“…Despite decades of efforts to curb and eradicate the malaria pandemic, it still retains its status as one of the most dangerous and fatal infections in the tropical and subtropical endemic countries, having over 500 million reported cases with approximately one million deaths yearly [1]. The disease is caused by Plasmodium falciparum (P. falciparum), the most lethal of all the five Plasmodium species, others are; Plasmodium malariae (P. malariae), Plasmodium knowlesi (P. knowlesi), Plasmodium falciparum (P. falciparum), Plasmodium vivax (P. vivax), and Plasmodium ovale (P. ovale) [2][3][4]. The protozoan parasite Plasmodium falciparum produced in the red blood cell (RBCs) requires various hosts for its growth and survival.…”

Section: Introductionmentioning

confidence: 99%

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In-silico Design of Aryl and Aralkyl Amine-Based Triazolopyrimidine Derivatives with Enhanced Activity Against Resistant Plasmodium falciparum

et al. 2020

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A blend of genetic algorithm with multiple linear regression (GA-MLR) method was utilized in generating a quantitative structure–activity relationship (QSAR) model on the antimalarial activity of aryl and aralkyl amine-based triazolopyrimidine derivatives. The structures of derivatives were optimized using density functional theory (DFT) DFT/B3LYP/6–31 + G* basis set to generate their molecular descriptors, where two (2) predictive models were developed with the aid of these descriptors. The model with an excellent statistical parameters; high coefficient of determination (R2) = 0.8884, cross-validated R2 (Q2cv) = 0.8317 and highest external validated R2 (R2pred) = 0.7019 was selected as the best model. The model generated was validated through internal (leave-one-out (LOO) cross-validation), external test set, and Y-randomization test. These parameters are indicators of robustness, excellent prediction, and validity of the selected model. The most relevant descriptor to the antimalarial activity in the model was found to be GATS6p (Geary autocorrelation—lag 6/weighted by polarizabilities), in the model due to its highest mean effect. The descriptor (GATS6p) was significant in the in-silico design of sixteen (16) derivatives of aryl and aralkyl amine-based triazolopyrimidine adopting compound DSM191 with the highest activity (pEC50 = 7.1805) as the design template. The design compound D8 was found to be the most active compound due to its superior hypothetical activity (pEC50 = 8.9545).

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Section: Model Validationmentioning

confidence: 80%

“…where R 2 ij represents the multiple regression's correlation coefficients between the descriptor i and the remaining j model descriptors.…”

Section: Multi-co-linearity Analysismentioning

confidence: 99%

Section: External Validationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In-silico Design of Aryl and Aralkyl Amine-Based Triazolopyrimidine Derivatives with Enhanced Activity Against Resistant Plasmodium falciparum

et al. 2020

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“…Animal trypanosomosis responds to many treatment drugs, among which is diminazene aceturate or DA (Berenil ® , Hoechst, Germany) as a conventional trypanocide so far although relapses have been reported [ 6 , 10 ]. Plasmodium falciparum , including Plasmodium vivax , Plasmodium knowlesi , Plasmodium ovale , and Plasmodium malariae , is a protozoan parasite that causes malaria in humans [ 11 ]. Therefore, protozoan parasites cause both trypanosomosis and plasmodosis of animals and human beings [ 12 ], among others.…”

Section: Introductionmentioning

confidence: 99%

Individual and combined anti-trypanosomal effects of arteether and diminazene aceturate in the treatment of experimental Trypanosoma brucei brucei infection in rats

et al. 2020

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Aim: Trypanosomosis is a vital protozoan disease of man and animals with devastating consequences in the tropical parts of the world, necessitating the investigation of the effects of diminazene aceturate (DA) and arteether (AR) on Trypanosoma brucei brucei experimental infection in rats. Materials and Methods: We used a total of 98 rats, which were divided into 14 groups (A-N) of seven rats each over 36 days after acclimatizing them. We administered 1×106 trypanosomes to the infected groups (B-N) with Group A as the unexposed control rats. Groups C-F became the infected and treated rats with 3.5 mg/kg, 7.0 mg/kg, 10.5 mg/kg, and 14.0 mg/kg of DA while Groups G-J became the infected and treated rats with 0.01 ml/kg, 0.02 ml/kg, 0.03 ml/kg, and 0.04 ml/kg of AR. Groups K-N became infected and treated rats with DA and AR combinations at similar doses. Results: Parasitemia suppression occurred in Groups G-J only but became cleared in Groups C-F and K-N. Survival time varied significantly (p<0.05) between Group B and the other infected groups. We recorded anemia in all the infected rats while significant (p<0.05) splenomegaly and hepatomegaly occurred in Groups G-J only compared to the other groups. Conclusion: AR did not inhibit or potentiate the anti-trypanosomal efficacy of DA, and therefore, it is comparatively less effective in combating T. brucei infection at the present doses and treatment regimen.

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Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women in Southeast Nigeria

et al. 2018

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Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent preventive treatment of malaria in pregnancy in most of sub-Saharan Africa. Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium falciparum. This study determined the prevalence of Pfdhfr and Pfdhps polymorphisms found in asymptomatic pregnant women attending antenatal care in Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women attending antenatal care clinics were enrolled after obtaining informed consent. Malaria diagnosis testing was done using thick and thin smears. Dried blood spot filter papers were collected. Parasite DNA was extracted from the filter papers using a chelex extraction. Extraction was followed by nested PCR and restriction enzyme digestion. P. falciparum infection was detected by microscopy in 7% (32/459) participants. Twenty-eight P. falciparum isolates were successfully genotyped. In the Pfdhfr gene, the triple mutation was almost fixed; S108N mutation was (100%), N51I (93%) and C59R mutations (93%), whereas the I164L mutation was absent. The prevalence of Pfdhps S436A, A437G, A581G and A613S mutations was 82.1% (23/28), 96.4% (27/28), 71.4% (20/28) and 71.4% (20/28) respectively. The K540E mutation was absent. The prevalence of the Pfdhfr triple mutation IRNI was 92.9% (26/28). The efficacy of SP as IPTp in Southeast Nigeria may be severely threatened. The continuous monitoring of SP molecular markers of resistance is required to assess thresholds. The evaluation of alternative preventive treatment strategies and drug options for preventing malaria in pregnancy may be necessary.

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Origin of Two Most Virulent Agents of Human Malaria:Plasmodium falciparumandPlasmodium vivax

Cited by 10 publications

References 64 publications

In-silico Design of Aryl and Aralkyl Amine-Based Triazolopyrimidine Derivatives with Enhanced Activity Against Resistant Plasmodium falciparum

In-silico Design of Aryl and Aralkyl Amine-Based Triazolopyrimidine Derivatives with Enhanced Activity Against Resistant Plasmodium falciparum

Individual and combined anti-trypanosomal effects of arteether and diminazene aceturate in the treatment of experimental Trypanosoma brucei brucei infection in rats

Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women in Southeast Nigeria

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