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Scientific Articles

NOT Open Access | The cytochrome P450 CYP325A is a major driver of pyrethroid resistance in the major malaria vector Anopheles funestus in Central Africa

September 23, 2021 - 07:55 -- NOT Open Access
Author(s): 
Wamba ANR, Ibrahim SS, Kusimo MO, Muhammad A, Mugenzi LMJ, Irving H, Wondji MJ, Hearn J, Bigoga JD, Wondji CS
Reference: 
Insect Biochem Mol Biol. 2021 Sep 14;138:103647

The overexpression and overactivity of key cytochrome P450s (CYP450) genes are major drivers of metabolic resistance to insecticides in African malaria vectors such as Anopheles funestus s.s. Previous RNAseq-based transcription analyses revealed elevated expression of CYP325A specific to Central African populations but its role in conferring resistance has not previously been demonstrated. In this study, RT-qPCR consistently confirmed that CYP325A is highly over-expressed in pyrethroid-resistant An. funestus from Cameroon, compared with a control strain and insecticide-unexposed mosquitoes.

Not Open Access | Knockdown times in a simple assay determination of insecticide resistance in malaria vectors

September 23, 2021 - 07:53 -- NOT Open Access
Author(s): 
Charlwood JD, Kampango A
Reference: 
Trans R Soc Trop Med Hyg. 2021 Sep 16:trab140

Determining the insecticide resistance status of malaria vectors, particularly to insecticides used on mosquito nets, is important but is limited to a relatively small number of locations. We describe a simple assay that enables this information to be obtained over a much wider area.

Immunoprofiles associated with controlled human malaria infection and naturally acquired immunity identify a shared IgA pre-erythrocytic immunoproteome

September 18, 2021 - 04:19 -- Open Access
Author(s): 
Berry AA, Obiero JM, Lyke KE, et al.
Reference: 
NPJ Vaccines. 2021 Sep 13;6(1):115

Knowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses. We assessed IgG and IgA antibody responses in adult sera collected during two controlled human malaria infection (CHMI) studies in malaria-naïve volunteers and in 1- to 6-year-old malaria-exposed Malian children on a 251 P. falciparum antigen protein microarray. IgG profiles in the two CHMI groups were equivalent and differed from Malian children.

Health-seeking behaviour and cost of fever treatment to households in a malaria-endemic setting of northern Ghana: a cross-sectional study

September 18, 2021 - 04:17 -- Open Access
Author(s): 
Dalaba MA, Welaga P, Akweongo P, et al.
Reference: 
BMJ Open. 2021 Sep 13;11(9):e05222

To examine the health-seeking behaviour and cost of fever treatment to households in Ghana.

NOT Open Access | Preclinical evidence of synergism between atovaquone and chemotherapy by AMPK-dependent mitochondrial dysfunction

September 18, 2021 - 04:15 -- NOT Open Access
Author(s): 
Xie F, Gong J, Tan H, Zhang H, Ma J
Reference: 
Eur J Pharmacol. 2021 Sep 15;907:174256

Chemoresistance has been associated with increased reliance on mitochondrial functions in many cancers, including lung cancer. Atovaquone is an anti-malaria drug and mitochondrial inhibitor. In this work, we attempted to explore whether atovaquone can be repurposed for lung cancer treatment to overcome chemoresistance. We showed that atovaquone inhibited proliferation, colony formation and survival in non-small cell lung cancer cell (NSCLC) cells. Of note, the effective dose of atovaquone was clinically achievable.

NOT Open Access | The Role of Ultrasensitive Molecular Methods for Detecting Malaria-The Broader Perspective

September 18, 2021 - 04:14 -- NOT Open Access
Author(s): 
Kamaliddin C, Sutherland CJ, Houze S, Cottrell G, Briand V, Castaneda Mogollon D, Pillai DR
Reference: 
Clin Infect Dis. 2021 Sep 15;73(6):e1387-e1390

Ultrasensitive molecular diagnostics are lowering the limit of detection for malaria parasites in the blood and providing insights not captured by conventional tools such as microscopy and rapid antigen tests. Low-level malaria infections identified by molecular tools may influence clinical outcomes, transmission events, and elimination efforts.

Prioritization of Molecular Targets for Antimalarial Drug Discovery

September 18, 2021 - 04:12 -- Open Access
Author(s): 
Forte B, Ottilie S, Gilbert IH, et al.
Reference: 
ACS Infect Dis. 2021 Sep 15

There is a shift in antimalarial drug discovery from phenotypic screening toward target-based approaches, as more potential drug targets are being validated in Plasmodium species. Given the high attrition rate and high cost of drug discovery, it is important to select the targets most likely to deliver progressible drug candidates. In this paper, we describe the criteria that we consider important for selecting targets for antimalarial drug discovery.

Comparison of the impact of allelic polymorphisms in PfAMA1 on the induction of T Cell responses in high and low malaria endemic communities in Ghana

September 18, 2021 - 04:10 -- Open Access
Author(s): 
Ebenezer A. Ofori, John K. A. Tetteh, Augustina Frimpong, Harini Ganeshan, Maria Belmonte, Bjoern Peters, Eileen Villasante, Martha Sedegah, Michael F. Ofori and Kwadwo A. Kusi
Reference: 
Malaria Journal 2021 20:367, 10 September 2021

Malaria eradication requires a combined effort involving all available control tools, and these efforts would be complemented by an effective vaccine. The antigen targets of immune responses may show polymorphisms that can undermine their recognition by immune effectors and hence render vaccines based on antigens from a single parasite variant ineffective against other variants. This study compared the influence of allelic polymorphisms in Plasmodium falciparum apical membrane antigen 1 (PfAMA1) peptide sequences from three strains of P. falciparum (3D7, 7G8 and FVO) on their function as immunodominant targets of T cell responses in high and low malaria transmission communities in Ghana.

New Insights into the Spread of Resistance to Artemisinin and its Analogues

September 15, 2021 - 12:04 -- Open Access
Author(s): 
Noreen N, Ullah A, Salman SM, Mabkhot Y, Alsayari A, Badshah SL
Reference: 
J Glob Antimicrob Resist. 2021 Sep 10:S2213-7165(21)00208-3

The causative agent of malaria, Plasmodium falciparum, has been developing resistance to several drugs worldwide since more than five decades. Initially, resistance was toward drugs such as chloroquine, pyrimethamine, sulfadoxine, mefloquine, and quinine. Research studies are now reporting the resistance of parasites to the most effective and novel drug used against malaria infection worldwide, that is, artemisinin; for this reason, the first-line treatment strategy, including artemisinin combination therapy, is becoming unsuccessful in areas where drug resistance is highly prevalent.

Epidemiological and clinical implications of asymptomatic malaria and schistosomiasis co-infections in a rural community in western Kenya

September 15, 2021 - 12:01 -- Open Access
Author(s): 
Kamau E, Yates A, Polyak CS, et al.
Reference: 
BMC Infect Dis. 2021 Sep 9;21(1):937

Malaria and schistosomiasis present considerable disease burden in tropical and sub-tropical areas and severity is worsened by co-infections in areas where both diseases are endemic. Although pathogenesis of these infections separately is well studied, there is limited information on the pathogenic disease mechanisms and clinical disease outcomes in co-infections. In this study, we investigated the prevalence of malaria and schistosomiasis co-infections, and the hematologic and blood chemistry abnormalities in asymptomatic adults in a rural fishing community in western Kenya.

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