scholarly journals Optimizing systemic insecticide use to improve malaria control

2019 ◽  
Author(s):  
Hannah R. Meredith ◽  
Luis Furuya-Kanamori ◽  
Laith Yakob

AbstractLong lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood-hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that over-dependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability. Here, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through a mathematical model simulation. The review identified drugs from four classes commonly used in livestock and companion animals: avermectics, milbemycins, isoxazolines, and spinosyns. Simulations predicted that isoxazoline and spinosyn drugs were promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations. These findings will provide a guide for investigating and applying different systemic insecticides to achieve better mosquito control strategies.SignificanceThe widespread use of long lasting insecticidal nets (LLINs) and indoor residual spray has selected for mosquitoes that are resistant to pyrethroids or avoid exposure by feeding outdoors or on livestock. Systemic insecticides, drugs that render a host’s blood toxic to feeding mosquitoes, could be an effective control strategy for mosquitoes with pyrethroid resistance and/or outdoor feeding tendencies. Here, a number of existing systemic insecticide candidates are identified and their pharmacokinetic properties in different drug-host-route scenarios consolidated. These data were used to parameterise a mathematical model that illustrated the projected gains achievable in malaria control programmes already employing LLINs. The findings provide a guide for investigating and applying different systemic insecticides to improve mosquito control strategies and reduce malaria transmission.

2019 ◽  
Vol 4 (6) ◽  
pp. e001776 ◽  
Author(s):  
Hannah R Meredith ◽  
Luis Furuya-Kanamori ◽  
Laith Yakob

BackgroundLong-lasting insecticidal nets and indoor residual sprays have significantly reduced the burden of malaria. However, several hurdles remain before elimination can be achieved: mosquito vectors have developed resistance to public health insecticides, including pyrethroids, and have altered their biting behaviour to avoid these indoor control tools. Systemic insecticides, drugs applied directly to blood hosts to kill mosquitoes that take a blood meal, offer a promising vector control option. To date, most studies focus on repurposing ivermectin, a drug used extensively to treat river blindness. There is concern that overdependence on a single drug will inevitably repeat past experiences with the rapid spread of pyrethroid resistance in malaria vectors. Diversifying the arsenal of systemic insecticides used for mass drug administration would improve this strategy’s sustainability.MethodsHere, a review was conducted to identify systemic insecticide candidates and consolidate their pharmacokinetic/pharmacodynamic properties. The impact of alternative integrated vector control options and different dosing regimens on malaria transmission reduction are illustrated through mathematical model simulation.ResultsThe review identified drugs from four classes commonly used in livestock and companion animals: avermectins, milbemycins, isoxazolines and spinosyns. Simulations predicted that isoxazolines and spinosyns are promising candidates for mass drug administration, as they were predicted to need less frequent application than avermectins and milbemycins to maintain mosquitocidal blood concentrations.ConclusionsThese findings will provide a guide for investigating and applying different systemic insecticides to achieve more effective and sustainable control of malaria transmission.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Fereshteh Ghahvechi Khaligh ◽  
Abbas Jafari ◽  
Elena Silivanova ◽  
Mikhail Levchenko ◽  
Bahlol Rahimi ◽  
...  

Abstract Background Malaria is the most common vector-borne disease transmitted to humans by Anopheles mosquitoes. Endectocides and especially ivermectin will be available as a vector control tool soon. The current review could be valuable for trial design and clinical studies to control malaria transmission. Methods PubMed/MEDLINE, Scopus, Web of Science, and Science Direct were searched for original English published papers on (“Malaria chemical control” OR “Malaria elimination” OR “Anopheles vector control” OR “Malaria zooprophylaxis”) AND (“Systemic insecticides” OR “Endectocides” OR “Ivermectin”). The last search was from 19 June 2019 to 31 December 2019. It was updated on 17 November 2020. Two reviewers (SG and FGK) independently reviewed abstracts and full-text articles. Data were extracted by one person and checked by another. As meta-analyses were not possible, a qualitative summary of results was performed. Results Thirty-six published papers have used systemic insecticides/endectocides for mosquito control. Most of the studies (56.75%) were done on Anopheles gambiae complex species on doses from 150 μg/kg to 400 μg/kg in several studies. Target hosts for employing systemic insecticides/drugs were animals (44.2%, including rabbit, cattle, pig, and livestock) and humans (32.35%). Conclusions Laboratory and field studies have highlighted the potential of endectocides in malaria control. Ivermectin and other endectocides could soon serve as novel malaria transmission control tools by reducing the longevity of Anopheles mosquitoes that feed on treated hosts, potentially decreasing Plasmodium parasite transmission when used as mass drug administration (MDA).


2020 ◽  
Vol 376 (1818) ◽  
pp. 20190817 ◽  
Author(s):  
Joel Hellewell ◽  
Ellie Sherrard-Smith ◽  
Sheila Ogoma ◽  
Thomas S. Churcher

Malaria control in sub-Saharan Africa relies on the widespread use of long-lasting insecticidal nets (LLINs) or the indoor residual spraying of insecticide. Disease transmission may be maintained even when these indoor interventions are universally used as some mosquitoes will bite in the early morning and evening when people are outside. As countries seek to eliminate malaria, they can target outdoor biting using new vector control tools such as spatial repellent emanators, which emit airborne insecticide to form a protective area around the user. Field data are used to incorporate a low-technology emanator into a mathematical model of malaria transmission to predict its public health impact across a range of scenarios. Targeting outdoor biting by repeatedly distributing emanators alongside LLINs increases the chance of elimination, but the additional benefit depends on the level of anthropophagy in the local mosquito population, emanator effectiveness and the pre-intervention proportion of mosquitoes biting outdoors. High proportions of pyrethroid-resistant mosquitoes diminish LLIN impact because of reduced mosquito mortality. When mosquitoes are highly anthropophagic, this reduced mortality leads to more outdoor biting and a reduced additional benefit of emanators, even if emanators are assumed to retain their effectiveness in the presence of pyrethroid resistance. Different target product profiles are examined, which show the extra epidemiological benefits of spatial repellents that induce mosquito mortality. This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases’.


10.2196/20904 ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. e20904
Author(s):  
Edgard Diniba Dabira ◽  
Harouna M Soumare ◽  
Steven W Lindsay ◽  
Bakary Conteh ◽  
Fatima Ceesay ◽  
...  

Background With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission. Objective The study objective is to evaluate the impact of MDA with IVM plus dihydroartemisinin-piperaquine (DP) on malaria transmission in an area with high coverage of malaria control interventions. Methods The study is a cluster randomized trial in the Upper River Region of The Gambia and included 32 villages (16 control and 16 intervention). A buffer zone of ~2 km was created around all intervention clusters. MDA with IVM plus DP was implemented in all intervention villages and the buffer zones; control villages received standard malaria interventions according to the Gambian National Malaria Control Program plans. Results The MDA campaigns were carried out from August to October 2018 for the first year and from July to September 2019 for the second year. Statistical analysis will commence once the database is completed, cleaned, and locked. Conclusions This is the first cluster randomized clinical trial of MDA with IVM plus DP. The results will provide evidence on the impact of MDA with IVM plus DP on malaria transmission. Trial Registration ClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313 International Registered Report Identifier (IRRID) DERR1-10.2196/20904


2020 ◽  
Author(s):  
Edgard Diniba Dabira ◽  
Harouna M Soumare ◽  
Steven W Lindsay ◽  
Bakary Conteh ◽  
Fatima Ceesay ◽  
...  

BACKGROUND With a decline in malaria burden, innovative interventions and tools are required to reduce malaria transmission further. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) has been identified as a potential tool to further reduce malaria transmission, where coverage of vector control interventions is already high. However, the impact is limited in time. Combining an ACT with an endectocide treatment that is able to reduce vector survival, such as ivermectin (IVM), could increase the impact of MDA and offer a new tool to reduce malaria transmission. OBJECTIVE The study objective is to evaluate the impact of MDA with IVM plus dihydroartemisinin-piperaquine (DP) on malaria transmission in an area with high coverage of malaria control interventions. METHODS The study is a cluster randomized trial in the Upper River Region of The Gambia and included 32 villages (16 control and 16 intervention). A buffer zone of ~2 km was created around all intervention clusters. MDA with IVM plus DP was implemented in all intervention villages and the buffer zones; control villages received standard malaria interventions according to the Gambian National Malaria Control Program plans. RESULTS The MDA campaigns were carried out from August to October 2018 for the first year and from July to September 2019 for the second year. Statistical analysis will commence once the database is completed, cleaned, and locked. CONCLUSIONS This is the first cluster randomized clinical trial of MDA with IVM plus DP. The results will provide evidence on the impact of MDA with IVM plus DP on malaria transmission. CLINICALTRIAL ClinicalTrials.gov NCT03576313; https://clinicaltrials.gov/ct2/show/NCT03576313 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/20904


Author(s):  
Emmanuel Hakizimana ◽  
Jean Marie Ntaganda

This research paper investigated the dynamics of malaria transmission in Rwanda using the nonlinear forces of infections which are included in SEIR-SEI mathematical model for human and mosquito populations. The mathematical modeling of malaria studies the interaction among the human and mosquito populations in controlling malaria transmission and eventually eliminating malaria infection. This work investigates the optimal control strategies for minimizing the rate of malaria transmission by applying three control variables through Caputo fractional derivative. The optimal control problems for malaria model found the control parameters which minimize infection. The numerical simulation showed that the number of exposed and infected people and mosquito population are decreased due to the control strategies. Finally, this work found out that the transmission of malaria in Rwanda can be minimized by using the combination of controls like Insecticide Treated bed Nets (ITNs), Indoor Residual Spray (IRS) and Artemisinin based Combination Therapies (ACTs).


2020 ◽  
Author(s):  
Moussa KEITA ◽  
Nafomon SOGOBA ◽  
Boïssé Traoré ◽  
Fousseyni Kané ◽  
Boubacar Coulibaly ◽  
...  

Abstract Background:Vector control relies heavily on Long-lasting insecticidal nets ( (LLINs) and Indoor Residual Spraying (IRS) in selected districts in Mali including Koulikoro district. As part of strengthening vector control strategies in the district, IRS was initiated by the National Malaria Control Program (NMCP) with the support of the US President's Malaria Initiative (PMI) since 2008. LLINs coverage was 93.3% and 98.2% for IRS in Koulikoro, the only district of the region where IRS was supported by PMI. Following mosquito vector resistance to both pyrethroid and carbamates, organophosphate (pirimiphos-methyl) was used for the IRS campaigns of 2015 and 2016 in the district of Koulikoro. In this study, we assessed the effect of IRS on malaria transmission by comparing entomological indices in of the district of Koulikoro, where IRS was implemented and its neighbored district of Banamba, where IRS had never been implemented. Methods:The study was conducted in two villages of each district (Koulikoro and Banamba). Pyrethrum spray catches and entry window trapping were used to collect mosquitoes on a monthly basis. WHO tube tests were carried out to assess mosquito susceptibility to insecticides. Mosquitoes were identified to species level by PCR and their infection to P. falciparum was detected by ELISA.Results:Of the 527 specimens identified, An. coluzzii was the most frequent species (95%) followed by An. gambiae (4%) and An. arabiensis (1%). Its density was rainfall dependent in the no-IRS area, and almost independent in the IRS area. The infection rate (IR) in the no-IRS area was 0.96%, while it was null in the IRS area. In the no-IRS area, the entomological inoculation rates (EIR) was 0.21 infective bites /person month with a peak in September. High resistance to pyrethroids and carbamates and susceptibility to organophosphates was observed at all sites.Conclusion:The introduction of pirimiphos-methyl based IRS in the area resulted in a significant decrease in malaria transmission. An.gambiae s.l., the main malaria vector of the area, was resistant to pyrethroids and carbamates, and remained susceptible to the organophosphates.


2020 ◽  
Author(s):  
Mouhamad Sy ◽  
Awa Deme ◽  
Joshua L. Warren ◽  
Rachel F. Daniels ◽  
Baba Dieye ◽  
...  

ABSTRACTMolecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal—a region of exceptionally low malaria transmission (entomological inoculation rate (EIR) less than 1). Genetic identity (identity by state) was established using a 24 single nucleotide polymorphism molecular barcode and a multivariable linear regression model was used to establish genetic and spatial relationships. Our results show clustering of genetically similar parasites within households and a decline in genetic similarity of parasites with increasing distance. One household showed extremely high diversity and warrants further investigation as to the source of these diverse genetic types. This study illustrates the utility of genomic data with traditional epidemiological approaches for surveillance and detection of trends and patterns in malaria transmission not only by neighborhood but also by household. This approach can be implemented regionally and countrywide to strengthen and support malaria control and elimination efforts.


PEDIATRICS ◽  
1995 ◽  
Vol 96 (1) ◽  
pp. 117-117
Author(s):  
R. Rueben

The factors that make pregnant women particularly vulnerable to morbidity and mortality with falciparum malaria and their relationship to current control strategies are reviewed. Pregnant women, particularly during their first pregnancy, are at greatest risk of severe falciparum malaria in areas of high and continuous malaria transmission and under conditions of unstable malaria in which they do not develop protective immunity. The author recommends chemoprophylaxis with chloroquine for pregnant women living in holoendemic and hyperendemic areas of Africa and Papua, New Guinea. Chloroquine is safe, but drug resistance has increasingly limited its utility, distribution is a formidable problem. In rural areas where poorly developed health care system are better developed and malaria transmission is less intense, the emphasis should be on early diagnosis and treatment. Women are potentially the key to the implementation of malaria control programs, yet recent studies indicate that underprivileged women frequently do not attend malaria clinics and are often missed in projects with passive surveillance. Additional research and community interventions are needed to enable women with malaria to obtain treatment and to involve them in malaria control measures at the village level.


2015 ◽  
Vol 112 (10) ◽  
pp. 3014-3019 ◽  
Author(s):  
Yael Artzy-Randrup ◽  
Andrew P. Dobson ◽  
Mercedes Pascual

It is extremely likely that the malaria vaccines currently in development will be used in conjunction with treated bednets and other forms of malaria control. The interaction of different intervention methods is at present poorly understood in a disease such as malaria where immunity is more complex than for other pathogens that have been successfully controlled by vaccination. Here we develop a general mathematical model of malaria transmission to examine the interaction between vaccination and bednets. Counterintuitively, we find that the frailty of malaria immunity will potentially cause both synergistic and antagonistic interactions between vaccination and the use of bednets. We explore the conditions that create these tensions, and outline strategies that minimize their detrimental impact. Our analysis specifically considers the three leading vaccine classes currently in development: preerythrocytic (PEV), blood stage (BSV), and transmission blocking (TBV). We find that the combination of BSV with treated bednets can lead to increased morbidity with no added value in terms of elimination; the interaction is clearly antagonistic. In contrast, there is strong synergy between PEV and treated bednets that may facilitate elimination, although transient stages are likely to increase morbidity. The combination of TBV with treated bednets is synergistic, lowering both morbidity and elimination thresholds. Our results suggest that vaccines will not provide a straightforward solution to malaria control, and that future programs need to consider the synergistic and antagonistic interactions between vaccines and treated bednets.


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