Biology subjects

Yakob, L.

Publications and source records attributed to Yakob, L..

8 recordsLinked to original sources

bioRxiv2020

Temperature alters gene expression in mosquitoes during arbovirus infection

Arthropod-borne viruses (arboviruses) such as dengue, Zika and chikungunya constitute a significant proportion of the global disease burden. The principal vector of these pathogens is the mosquito Aedes (Ae.) aegypti, and its ability to transmit virus to a human host is influenced by environmental factors such as temperature. However, exactly how ambient temperature influences virus replication within mosquitoes remains poorly elucidated, particularly at the molecular level. Here, we use chikungunya virus (CHIKV) as a model to understand how the host mosquito transcriptome responds to arbovirus infection under different ambient temperatures. We exposed CHIKV-infected mosquitoes to 18 {degrees}C, 28 {degrees}C and 32 {degrees}C, and found higher temperature correlated with higher virus replication levels, particularly at early time points post-infection. Lower ambient temperatures resulted in reduced virus replication levels. Using RNAseq, we found that temperature significantly altered gene expression levels in mosquitoes, particularly components of the immune response. The highest number of significantly differentially expressed genes in response to CHIKV was observed at 28 {degrees}C, with a markedly more muted effect observed at either lower (18 {degrees}C) or higher (32 {degrees}C) temperatures. At the higher temperature, the expression of many classical immune genes, including Dicer-2 in the RNAi pathway, was not substantially altered in response to CHIKV. Upregulation of Toll, IMD and JAK-STAT pathways was only observed at 28 {degrees}C. Time post infection also led to substantially different gene expression profiles, and this effect varied depending upon the which temperature mosquitoes were exposed to. Taken together, our data indicate temperature significantly modulates mosquito gene expression in response to infection, potentially leading to impairment of immune defences at higher ambient temperatures.

microbiology↗

bioRxiv2020

Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis

Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce insect pollinator species. Here we present a promising, environment-friendly alternative that targets insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded. RNAi silencing of either the first two enzymes in the tyrosine degradation pathway (TAT and HPPD) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, it did not affect bumblebee survival. A mathematical model shows that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current elimination programmes.

biochemistry↗

bioRxiv2019

Optimizing systemic insecticide use to improve malaria control

Long 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 strategys 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.\n\nSignificanceThe 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 hosts 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.

epidemiology↗

bioRxiv2018

Detection of a novel insect specific flavivirus across ecologically diverse populations of Aedes aegypti on the Caribbean Island of Saint Lucia

Outbreaks of mosquito-borne arboviral diseases including dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV) and chikungunya virus (CHIKV) have recently occurred in the Caribbean. The geographical range of the principle vectors responsible for transmission, Aedes (Ae.) aegypti and Ae. albopictus is increasing and greater mosquito surveillance is needed in the Caribbean given international tourism is so prominent. The island of Saint Lucia has seen outbreaks of DENV and CHIKV in the past five years but vector surveillance has been limited with the last studies dating back to the late 1970s. Natural disasters have changed the landscape of Saint Lucia and the island has gone through significant urbanisation. In this study, we conducted an entomological survey of Ae. aegypti and Ae. albopictus distribution across the island and analysed environmental parameters associated with the presence of these species. Although we collected Ae. aegypti across a range of sites across the island, no Ae. albopictus were collected despite traps being placed in diverse ecological settings. The number of Ae. aegypti collected was significantly associated with higher elevation and semi-urban settings yielded female mosquito counts per trap-day that were 5-fold lower than urban settings. Screening for arboviruses revealed a high prevalence of a novel insect-specific flavivirus closely related to cell fusing agent virus (CFAV). We discuss the implications that natural disasters, water storage and lack of mosquito surveillance have on arboviral outbreaks in Saint Lucia and implications for insect only flaviviruses on surveillance and detection of pathogenic flaviviruses.

ecology↗

bioRxiv2018

Malaria control dynamics may explain inconsistent outcomes from bednet trials: a modeling study

BACKGROUNDLong-lasting insecticidal bednets have unparalleled efficacy in reducing malaria burden. However, insecticidal resistance and bednet avoidance behaviors among the mosquito vectors are now widespread.\n\nMETHODSReviewing the relevant field and semi-field studies highlights the ubiquity of zoophagic and spatiotemporal (biting outdoors or at different times of day) plasticity among vectors in response to bednet deployment. Transmission models coupled with the population genetics of vectors are developed to assess the impact on malaria control caused by insecticide resistance and the avoidance behaviors of mosquitoes.\n\nRESULTSInteractions between physiological resistance and behavioral resilience among mosquito vectors can significantly impact malaria control efforts both in the short- and long-term. The possibility of misleading observations from injudiciously timed assessments of malaria control programs is demonstrated through simulation.\n\nCONCLUSIONSCurrently, there are no guidelines to inform when during a bednet trial its effectiveness should be measured. The importance of this oversight is described in the context of recent randomized controlled bednet trials.

epidemiology↗

bioRxiv2018

Assessing the blood-host plasticity and dispersal rate of the malaria vector Anopheles coluzzii

Difficulties with observing the dispersal of insect vectors in the field have hampered understanding of several aspects of their behaviour linked to disease transmission. Here, a novel method based on detection of blood-meal sources is introduced to inform two critical and understudied mosquito behaviours: plasticity in the malaria vectors blood-host choice and vector dispersal. Strategically located collections of Anopheles coluzzii from a malaria-endemic village of southern Ghana showed statistically significant variation in host species composition of mosquito blood-meals. Trialling a new sampling approach gave the first estimates for the remarkably local spatial scale across which host choice is plastic. Using quantitative PCR, the blood-meal digestion was then quantified for field-caught mosquitoes and calibrated according to timed blood digestion in colony mosquitoes. We demonstrate how this new molecular Sella score approach can be used to estimate the dispersal rate of blood-feeding vectors caught in the field.

ecology↗

bioRxiv2018

A systematic review and meta-analysis of the human blood index of the major African malaria vectors

BACKGROUNDThe proportion of mosquito blood-meals that are of human origin, referred to as the human blood index or HBI, is a key determinant of malaria transmission. We conducted a systematic review of the HBI for the major African malaria vectors.\n\nRESULTSEvidence is presented for higher HBI among Anopheles gambiae (M/S forms and An. coluzzii/An. gambiae s.s. are not distinguished for most studies and therefore combined) as well as An. funestus when compared with An. arabiensis (prevalence odds ratio adjusted for collection location [i.e. indoor or outdoor]: 1.62; 95%CI 1.09-2.42; 1.84; 95%CI 1.35-2.52, respectively). This finding is keeping with the entomological literature which describes An. arabiensis to be more zoophagic than the other major African vectors. However, analysis also revealed that HBI was more associated with location of mosquito captures (R2=0.29) than with mosquito (sibling) species (R2=0.11).\n\nCONCLUSIONSOur findings call into question the appropriateness of current methods of assessing host preferences among disease vectors and have important implications for strategizing vector control.

ecology↗

bioRxiv2018

Projecting the end of the Zika virus epidemic in Latin America: a modelling analysis

Background Zika virus (ZIKV) emerged in Latin America & the Caribbean (LAC) region in 2013, and has had serious implications for population health in the region. In 2016, the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. In 2017, Zika cases declined, but future incidence in LAC remains uncertain due to gaps in our understanding, considerable variation in surveillance and a lack of a comprehensive collation of data from affected countries.\n\nMethods Our analysis combines information on confirmed and suspected Zika cases across LAC countries and a spatio-temporal dynamic transmission model for ZIKV infection to determine key transmission parameters and projected incidence in 91 major cities within 35 countries. Seasonality was determined by spatio-temporal estimates of Aedes aegypti vector capacity. We used country and state-level data from 2015 to mid-2017 to infer key model parameters, country-specific disease reporting rates, and the 2018 projected incidence. A 10-fold cross-validation approach was used to validate parameter estimates to out-of-sample epidemic trajectories.\n\nResults There was limited transmission in 2015, but in 2016 and 2017 there was sufficient opportunity for wide-spread ZIKV transmission in most cities, resulting in the depletion of susceptible individuals. We predict that the highest number of cases in 2018 within some Brazilian States (Sao Paulo and Rio de Janeiro), Colombia and French Guiana, but the estimated number of cases were no more than a few hundred. Model estimates of the timing of the peak in incidence were correlated (p<0.05) with the reported peak in incidence. The reporting rate varied across countries, with lower reporting rates for those with only confirmed cases compared to those who reported both confirmed and suspected cases.\n\nConclusions The findings suggest that the ZIKV epidemic is by and large over, with incidence projected to be low in most cities in LAC in 2018. Local low levels of transmission are probable but the estimated rate of infection suggests that most cities have a population with high levels of herd immunity.

epidemiology↗