scholarly journals Synergism in Antiplasmodial Activities of Artemether and Lumefantrine in Combination with Securidaca longipedunculata Fresen (Polygalaceae)

Plants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 47
Author(s):  
Douglas O. Ochora ◽  
Esezah K. Kakudidi ◽  
Jane Namukobe ◽  
Perpetua Ipulet ◽  
Dancan M. Wakoli ◽  
...  
Keyword(s):  
Drug Combination ◽  
Ex Vivo ◽  
Malaria Prevalence ◽  
Sub Saharan Africa ◽  
Cross Resistance ◽  
Field Isolates ◽  
Malaria Burden ◽  
Inhibition Concentration ◽  
Sub Saharan ◽  
Emergence Of Resistance

Malaria is the most lethal parasitic disease in the world. The frequent emergence of resistance by malaria parasites to any drug is the hallmark of sustained malaria burden. Since the deployment of artemisinin-based combination therapies (ACTs) it is clear that for a sustained fight against malaria, drug combination is one of the strategies toward malaria elimination. In Sub-Saharan Africa where malaria prevalence is the highest, the identification of plants with a novel mechanism of action that is devoid of cross-resistance is a feasible strategy in drug combination therapy. Thus, artemether and lumefantrine were separately combined and tested with extracts of Securidaca longipedunculata, a plant widely used to treat malaria, at fixed extract–drug ratios of 4:1, 3:1, 1:1, 1:2, 1:3, and 1:4. These combinations were tested for antiplasmodial activity against three strains of Plasmodium falciparum (W2, D6, and DD2), and seven field isolates that were characterized for molecular and ex vivo drug resistance profiles. The mean sum of fifty-percent fractional inhibition concentration (FIC50) of each combination and singly was determined. Synergism was observed across all fixed doses when roots extracts were combined with artemether against D6 strain (FIC50 0.403 ± 0.068) and stems extract combined with lumefantrine against DD2 strain (FIC50 0.376 ± 0.096) as well as field isolates (FIC50 0.656 ± 0.067). Similarly, synergism was observed in all ratios when leaves extract were combined with lumefantrine against W2 strain (FIC50 0.456 ± 0.165). Synergism was observed in most combinations indicating the potential use of S. longipedunculata in combination with artemether and lumefantrine in combating resistance.

scholarly journals BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-Saharan Africa

2019 ◽  
Vol 4 (6) ◽  
pp. e001862 ◽  
Author(s):  
Mike LT Berendsen ◽  
Sjors WL van Gijzel ◽  
Jeroen Smits ◽  
Quirijn de Mast ◽  
Peter Aaby ◽  
...  
Keyword(s):  
Malaria Prevalence ◽  
Sub Saharan Africa ◽  
Cluster Sampling ◽  
Bcg Vaccination ◽  
Malaria Burden ◽  
Specific Effects ◽  
Effective Interventions ◽  
Sub Saharan ◽  
Ssa Countries ◽  
Transmission Reservoir

IntroductionMalaria continues to be a major cause of morbidity and mortality in sub-Saharan Africa (SSA) without effective interventions. Bacillus Calmette-Guérin (BCG) vaccine possesses protective non-specific effects, which extend beyond protection against tuberculosis. This study explores whether BCG is associated with protection against malaria in children under the age of 5 years in SSA.MethodsWe used data from the Demographic Health Survey programme, including 34 206 children from 13 SSA countries. BCG status was taken from vaccination cards when present; if not, mother’s recall was used. Presence of malaria was defined as a positive rapid diagnostic test. Maternally reported presence or absence of fever in the previous 2 weeks defined symptomatic status. Multilevel logistic regression was used to account for the two-stage cluster sampling method.ResultsOf the 34 206 children, 12 325 (36.0%) children were malaria positive and 29 766 (87.0%) were BCG vaccinated. After correction for relevant child, maternal and household factors, BCG vaccination was associated with a lower malaria prevalence (adjusted OR (aOR)=0.94, 95% CI 0.90 to 0.98), especially among children of whom BCG information was retrieved from a vaccination card (aORcard=0.88, 95% CI 0.82 to 0.94). Restricting the analysis to children from regions with suboptimal BCG coverage increased the association (aORcard=0.81, 95% CI 0.73 to 0.89). We observed an increasingly beneficial association with each month of age of the child (aORcard=0.996, 95% CI 0.993 to 0.999). BCG associations were similar for asymptomatic (aORcard=0.86, 95% CI 0.81 to 0.92) and symptomatic (aORcard=0.89, 95% CI 0.78 to 1.01) malaria.ConclusionsBCG vaccination is associated with protection against malaria. This protection is highest in regions with suboptimal BCG coverage. These results indicate a possible role for timely BCG vaccination in the protection of malaria and its elimination by reducing the transmission reservoir. If confirmed in further research, our findings have substantial implications for global efforts to reduce malaria burden.

scholarly journals Relationship between changing malaria burden and low birth weight in sub-Saharan Africa: A difference-in-differences study via a pair-of-pairs approach

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Siyu Heng ◽  
Wendy P O'Meara ◽  
Ryan A Simmons ◽  
Dylan S Small
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Confidence Interval ◽  
Malaria Prevalence ◽  
Sub Saharan Africa ◽  
World Health ◽  
Difference In Differences ◽  
Malaria Burden ◽  
Percentage Points ◽  
Sub Saharan

Background:According to the World Health Organization (WHO), in 2018, an estimated 228 million malaria cases occurred worldwide with most cases occurring in sub-Saharan Africa. Scale-up of vector control tools coupled with increased access to diagnosis and effective treatment has resulted in a large decline in malaria prevalence in some areas, but other areas have seen little change. Although interventional studies demonstrate that preventing malaria during pregnancy can reduce the rate of low birth weight (i.e. child’s birth weight <2500 g), it remains unknown whether natural changes in parasite transmission and malaria burden can improve birth outcomes.Methods:We conducted an observational study of the effect of changing malaria burden on low birth weight using data from 18,112 births in 19 countries in sub-Saharan African countries during the years 2000–2015. Specifically, we conducted a difference-in-differences study via a pair-of-pairs matching approach using the fact that some sub-Saharan areas experienced sharp drops in malaria prevalence and some experienced little change.Results:A malaria prevalence decline from a high rate (Plasmodium falciparum parasite rate in children aged 2-up-to-10 (i.e. PfPR2-10) > 0.4) to a low rate (PfPR2-10 < 0.2) is estimated to reduce the rate of low birth weight by 1.48 percentage points (95% confidence interval: 3.70 percentage points reduction, 0.74 percentage points increase), which is a 17% reduction in the low birth weight rate compared to the average (8.6%) in our study population with observed birth weight records (1.48/8.6 ≈ 17%). When focusing on first pregnancies, a decline in malaria prevalence from high to low is estimated to have a greater impact on the low birth weight rate than for all births: 3.73 percentage points (95% confidence interval: 9.11 percentage points reduction, 1.64 percentage points increase).Conclusions:Although the confidence intervals cannot rule out the possibility of no effect at the 95% confidence level, the concurrence between our primary analysis, secondary analyses, and sensitivity analyses, and the magnitude of the effect size, contribute to the weight of the evidence suggesting that declining malaria burden can potentially substantially reduce the low birth weight rate at the community level in sub-Saharan Africa, particularly among firstborns. The novel statistical methodology developed in this article–a pair-of-pairs approach to a difference-in-differences study–could be useful for many settings in which different units are observed at different times.Funding:Ryan A. Simmons is supported by National Center for Advancing Translational Sciences (UL1TR002553). The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

scholarly journals Is the current decline in malaria burden in sub-Saharan Africa due to a decrease in vector population?

2011 ◽  
Vol 10 (1) ◽  
Author(s):  
Dan W Meyrowitsch ◽  
Erling M Pedersen ◽  
Michael Alifrangis ◽  
Thomas H Scheike ◽  
Mwelecele N Malecela ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Malaria Burden ◽  
Vector Population ◽  
Sub Saharan

scholarly journals Characterizing Permethrin and Etofenprox Resistance in Two Common Laboratory Strains of Anopheles gambiae (Diptera: Culicidae)

Insects ◽  
2018 ◽  
Vol 9 (4) ◽  
pp. 146 ◽  
Author(s):  
Aaron Gross ◽  
Jeffrey Bloomquist
Keyword(s):  
Anopheles Gambiae ◽  
Pyrethroid Resistance ◽  
Laboratory Strain ◽  
Pyrethroid Insecticide ◽  
Sub Saharan Africa ◽  
Cross Resistance ◽  
Type I ◽  
Mosquito Vector ◽  
Sub Saharan ◽  
Anopheles Gambiae Giles

Anopheles gambiae Giles (Diptera: Culicidae) is the most prolific malaria vector in sub-Saharan Africa, where widespread insecticide resistance has been reported. An. gambiae laboratory strains are commonly used to study the basic biology of this important mosquito vector, and also in new insecticide discovery programs, where insecticide-susceptible and -resistant strains are often used to screen new molecules for potency and cross-resistance, respectively. This study investigated the toxicity of permethrin, a Type-I pyrethroid insecticide, and etofenprox, a non-ester containing pyrethroid insecticide, against An. gambiae at three life stages. This characterization was performed with susceptible (G3; MRA-112) and resistant (Akdr; MRA-1280) An. gambiae strains; the Akdr strain is known to contain the L1014F mutation in the voltage-sensitive sodium channel. Surprisingly, etofenprox displays a lower level of resistance than permethrin against all stages of mosquitoes, except in a headless larval paralysis assay designed to minimize penetration factors. In first-instar An. gambiae larvae, permethrin had significant resistance, determined by the resistance ratio (RR50 = 5), but etofenprox was not significantly different (RR50 = 3.4) from the wild-type strain. Fourth-instar larvae displayed the highest level of resistance for permethrin (RR50 = 108) and etofenprox (RR50 = 35). Permethrin (PC50 = 2 ppb) and etofenprox (PC50 = 9 ppb) resulted in headless larval paralysis (5-h), but resistance, albeit lower, was still present for permethrin (RR50 = 5) and etofenprox (RR50 = 6.9). In adult female mosquitoes, permethrin displayed higher resistance (RR50 = 14) compared to etofenprox (RR50 = 4.3). The level of etofenprox resistance was different from that previously reported for a similar Akron An. gambiae laboratory strain (MRA-913). The chemical synergists piperonyl butoxide (PBO) and diethyl maleate (DEM) were able to synergize permethrin, but not etofenprox in the resistant strain (Akdr). In conclusion, multiple mechanisms are likely involved in pyrethroid resistance, but resistance profiles are dependent upon selection. Etofenprox is an effective insecticide against An. gambiae in the lab but will likely suffer from resistance in the field.

scholarly journals Recrudescence ofPlasmodium malariaeafter Quinine

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Irfanali R. Kugasia ◽  
Farhana K. Polara ◽  
Hussein Assallum
Keyword(s):  
Case Reports ◽  
Plasmodium Malariae ◽  
Sub Saharan Africa ◽  
Case Patient ◽  
Liver Stage ◽  
Literature Research ◽  
Development Of Resistance ◽  
Sub Saharan ◽  
Emergence Of Resistance

Plasmodium malariaecauses uncommon benign malaria found in the malaria endemic regions mostly of Sub-Saharan Africa. AsPlasmodium malariaedoes not have a continued liver stage in humans the only way to have reinfection without reexposure is through recrudescence. However, reports of its recrudescence after antimalarials are rare with only a handful of case reports in the literature. Research in this field to date has not been able to establish definitively an emergence of resistance inPlasmodium malariaeto commonly used antimalarials. In the presented case, patient had a recrudescence ofP. malariaeafter full treatment with quinine and clindamycin. This recrudescence was treated with full course of chloroquine with clearance of parasite from blood immediately after treatment and at two months’ follow up. The recrudescence in this case cannot be explained by mechanisms explained in prior articles. We propose that the indolence of some of thePlasmodium malariaetrophozoites in the blood can shield them from the effect of the toxic effects of antimalarials and enable them to produce recrudescence later. However, when recrudescence happens, this should not be considered a case of development of resistance and a course of chloroquine should be considered.

EVALUATING PYRETHROID ALTERNATIVES FOR THE MANAGEMENT OF COTTON BOLLWORMS AND RESISTANCE IN CAMEROON

2009 ◽  
Vol 45 (1) ◽  
pp. 35-46 ◽  
Author(s):  
J. ACHALEKE ◽  
M. VAISSAYRE ◽  
T. BREVAULT
Keyword(s):  
Pyrethroid Resistance ◽  
Resistance Management ◽  
Sub Saharan Africa ◽  
Cross Resistance ◽  
Cotton Production ◽  
Suitable Alternative ◽  
Early Peak ◽  
Sub Saharan ◽  
On Farm ◽  
Cotton Pest

SUMMARYIn sub-Saharan Africa, the bollworm complex, including Helicoverpa armigera, Diparopsis watersi and Earias spp., threatens the continued success of cotton production. Pyrethroid resistance in H. armigera led to serious crop losses while endosulfan, a suitable alternative to pyrethroids, was banned for cotton pest management. Five candidates with no cross-resistance to pyrethroids were evaluated in both on-station and on-farm trials from 2002 to 2006. Two applications were made at the early peak of H. armigera infestation in September, the period when pyrethroid use should be restricted for resistance management purposes. Results showed that, as expected, bollworm infestation consistently peaked from mid-September to mid-October. Spinosad, thiodicarb and emamectin-benzoate were the most suitable alternatives to reduce damage, regardless of the cotton bollworm species. Indoxacarb and lufenuron were less effective in controlling D. watersi. On-farm experiments confirmed the suitability of spinosad for control of pyrethroid-resistant H. armigera, particularly on late sown fields. These new chemistries offer control of bollworms which justify their relevance for pyrethroid resistance management in Cameroon and sub-Saharan Africa.

scholarly journals CLIPB10 is a Terminal Protease in the Regulatory Network That Controls Melanization in the African Malaria Mosquito Anopheles gambiae

2021 ◽  
Vol 10 ◽  
Author(s):  
Xin Zhang ◽  
Miao Li ◽  
Layla El Moussawi ◽  
Sally Saab ◽  
Shasha Zhang ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Serine Proteases ◽  
Ex Vivo ◽  
Protein A ◽  
Tumor Formation ◽  
Sub Saharan Africa ◽  
Humoral Immune ◽  
Wide Range ◽  
Sub Saharan

Humoral immune responses in animals are often tightly controlled by regulated proteolysis. This proteolysis is exerted by extracellular protease cascades, whose activation culminates in the proteolytic cleavage of key immune proteins and enzymes. A model for such immune system regulation is the melanization reaction in insects, where the activation of prophenoxidase (proPO) leads to the rapid formation of eumelanin on the surface of foreign entities such as parasites, bacteria and fungi. ProPO activation is tightly regulated by a network of so-called clip domain serine proteases, their proteolytically inactive homologs, and their serpin inhibitors. In Anopheles gambiae, the major malaria vector in sub-Saharan Africa, manipulation of this protease network affects resistance to a wide range of microorganisms, as well as host survival. However, thus far, our understanding of the molecular make-up and regulation of the protease network in mosquitoes is limited. Here, we report the function of the clip domain serine protease CLIPB10 in this network, using a combination of genetic and biochemical assays. CLIPB10 knockdown partially reversed melanotic tumor formation induced by Serpin 2 silencing in the absence of infection. CLIPB10 was also partially required for the melanization of ookinete stages of the rodent malaria parasite Plasmodium berghei in a refractory mosquito genetic background. Recombinant serpin 2 protein, a key inhibitor of the proPO activation cascade in An. gambiae, formed a SDS-stable protein complex with activated recombinant CLIPB10, and efficiently inhibited CLIPB10 activity in vitro at a stoichiometry of 1.89:1. Recombinant activated CLIPB10 increased PO activity in Manduca sexta hemolymph ex vivo, and directly activated purified M. sexta proPO in vitro. Taken together, these data identify CLIPB10 as the second protease with prophenoloxidase-activating function in An. gambiae, in addition to the previously described CLIPB9, suggesting functional redundancy in the protease network that controls melanization. In addition, our data suggest that tissue melanization and humoral melanization of parasites are at least partially mediated by the same proteases.

scholarly journals Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa

2018 ◽  
Author(s):  
Claire L Jeffries ◽  
Gena G Lawrence ◽  
George Golovko ◽  
Mojca Kristan ◽  
James Orsborne ◽  
...  
Keyword(s):  
16S Rrna ◽  
Disease Control ◽  
Molecular Analysis ◽  
Malaria Prevalence ◽  
Sub Saharan Africa ◽  
16S Rrna Sequencing ◽  
Malaria Vectors ◽  
Rrna Sequencing ◽  
Dominant Member ◽  
Sub Saharan

AbstractAnopheles (An.) mosquitoes contain bacteria that can influence Plasmodium parasites. Wolbachia, a common insect endosymbiont, has historically been considered absent from Anopheles but has recently been found in An. gambiae populations. Here, we assessed a range of Anopheles species from five malaria-endemic countries for Wolbachia and Plasmodium infection. Strikingly, we found Wolbachia infections in An. coluzzii, An. gambiae s.s, An. arabiensis, An. moucheti and An. species ‘A’ increasing the number of Anopheles species known to be naturally infected by this endosymbiont. Molecular analysis suggests the presence of phylogenetically diverse novel strains, while qPCR and 16S rRNA sequencing indicates that Wolbachia is the dominant member of the microbiota in An. moucheti and An. species ‘A’. We found no evidence of Wolbachia/Asaia co-infections, and presence of these endosymbionts did not have significant effects on malaria prevalence. We discuss the importance of novel Wolbachia strains in Anopheles and potential implications for disease control.

scholarly journals All Nets are Equal, But Some Nets are More Equal Than Others

2020 ◽  
Vol 31 (1) ◽  
pp. 2-4
Author(s):  
Mark Rowland
Keyword(s):  
Sub Saharan Africa ◽  
World Health ◽  
Insecticide Treated Nets ◽  
Comparative Performance ◽  
Malaria Burden ◽  
Test Product ◽  
Dramatic Decline ◽  
The World ◽  
Sub Saharan ◽  
Health Organization

Much of the dramatic decline in malaria in sub-Saharan Africa since 2000 is due to the massive investment in long-lasting insecticide treated nets (LLIN). According to the latest figures from the World Health Organization (WHO), over half of Africa's population now has access to LLIN, increasing from 33% in 2010 to 57% in 2019 (WHO 2019). In 2018 alone, 197 million LLINs were delivered to Africa by manufacturers. Despite this, LLIN coverage has improved only marginally since 2015. The malaria burden worldwide has fallen only slightly from an estimated 231 million cases of malaria in 2017 to 228 million in 2018, and is at a standstill in Africa. WHO policy is to assess candidate 2nd-in-class products for entomological efficacy only. Due to the significant variation in the specifications of the candidates, to generate the required assurance of comparative performance to 1st in class, WHO has designed a non-inferiority trial design to demonstrate whether each candidate 2nd-in-class test product is no worse in experimental hut trials.

scholarly journals Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Oliver J Watson ◽  
Hannah C Slater ◽  
Robert Verity ◽  
Jonathan B Parr ◽  
Melchior K Mwandagalirwa ◽  
...  
Keyword(s):  
Democratic Republic Of Congo ◽  
False Negative ◽  
Malaria Diagnosis ◽  
Parasite Prevalence ◽  
Malaria Prevalence ◽  
Sub Saharan Africa ◽  
Gene Deletions ◽  
High Frequencies ◽  
Sub Saharan ◽  
Selection Of

Rapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent P. falciparum RDTs detect histidine-rich protein 2 (PfHRP2). However, pfhrp2 gene deletions yielding false-negative RDTs, first reported in South America in 2010, have been confirmed in Africa and Asia. We developed a mathematical model to explore the potential for RDT-led diagnosis to drive selection of pfhrp2-deleted parasites. Low malaria prevalence and high frequencies of people seeking treatment resulted in the greatest selection pressure. Calibrating our model against confirmed pfhrp2-deletions in the Democratic Republic of Congo, we estimate a starting frequency of 6% pfhrp2-deletion prior to RDT introduction. Furthermore, the patterns observed necessitate a degree of selection driven by the introduction of PfHRP2-based RDT-guided treatment. Combining this with parasite prevalence and treatment coverage estimates, we map the model-predicted spread of pfhrp2-deletion, and identify the geographic regions in which surveillance for pfhrp2-deletion should be prioritised.

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