Christopher M. Stone

Sugar Deprivation Reduces Insemination of Anopheles gambiae (Diptera: Culicidae), Despite Daily Recruitment of Adults, and Predicts Decline in Model Populations

ABSTRACT Our research tests the hypothesis that the inability to sugar-feed reduces the insemination rate in mosquito populations. To test this, we measured the effects of sugar availability on cumulative insemination performance of male Anopheles gambiae Giles s. s. (Diptera: Culicidae) during 10-d periods of continual emergence of equal numbers of both sexes, and we evaluated the implications at the population level with a matrix population model. On each day of each of four replicates, 20 newly emerged mosquitoes of each sex were recruited into the populations within two mesocosms, large walk-in enclosures with simulated natural conditions. Each mesocosm contained a cage to replicate the experiment on a small scale. Scented sucrose was absent or present (control). A human host was available nightly as a bloodmeal source in both mesocosms. Sugar availability and enclosure size significantly influenced female insemination. In the mesocosms, with sugar 49.7% of the females were inseminated, compared with 10.9% of the females without sugar. In the small cages, the insemination rates were 76.0 and 23.5%, respectively. In the mesocosms, cumulative survival of females after 10 d was 51.6% with sugar and 25.6% without sugar. In the cages, female survival was 95 and 73%, respectively. Sensitivity analysis of the population projection matrix shows that both reduced male survival and reduced mating capability due to a lack of sugar contributed to lower insemination rates in females, and in the absence of sugar the insemination rate was lowered to an extent that led to population decline.

Effects of Plant-Community Composition on the Vectorial Capacity and Fitness of the Malaria Mosquito Anopheles gambiae

Dynamics of Anopheles gambiae abundance and malaria transmission potential rely strongly on environmental conditions. Female and male An. gambiae use sugar and are affected by its absence, but how the presence or absence of nectariferous plants affects An. gambiae abundance and vectorial capacity has not been studied. We report on four replicates of a cohort study performed in mesocosms with sugar-poor and sugar-rich plants, in which we measured mosquito survival, biting rates, and fecundity. Survivorship was greater with access to sugar-rich plant species, and mortality patterns were age-dependent. Sugar-poor populations experienced Weibull mortality patterns, and of four populations in the sugar-rich environment, two female and three male subpopulations were better fitted by Gompertz functions. A tendency toward higher biting rates in sugar-poor mesocosms, particularly for young females, was found. Therefore, vectorial capacity was pulled in opposing directions by nectar availability, resulting in highly variable vectorial capacity values.

Contemporary and emerging strategies for eliminating human African trypanosomiasis due to Trypanosoma brucei gambiense: review

To review current and emerging tools for Gambiense HAT control and elimination, and propose strategies that integrate these tools with epidemiological evidence.

A survival and reproduction trade-off is resolved in accordance with resource availability by virgin female mosquitoes

The first 2-4 days after an Anopheles gambiae female mosquito emerges are critical to her survival and reproductive success. Yet, the order of behavioural events (mating, sugar feeding, blood feeding) during this time has received little attention. We discovered that among female cohorts sampled from emergence, sugar feeding had a higher probability than blood feeding of occurring first, and mating rarely occurred before a meal was taken. The night after emergence, 48% of females fed on sugar in mesocosms, and 25% fed on human blood; in the absence of sugar, 49% of females fed on human blood. After 5 days, 39% of the sugar-supplied females had blood fed and mated, and were fructose negative, whereas only 8% of the sugar-denied females had both blood fed and mated by this time. The model that best explained the transitions suggests that females made use of two distinct behavioural pathways, the most common one being to sugar-feed, then mate, and then seek blood. Other females sought blood first, then mated, and forwent a sugar meal. Lipid levels were higher in females with access to sugar than in females without access to sugar, particularly for those in later gonotrophic stages, while glycogen levels in the sugar-supplied group were higher throughout. In single-night experiments with females having had access to sucrose since emergence, those given a blood meal 1 day before spending a night with males had higher insemination rates than those not receiving the blood meal. These results indicate that the trade-off between survival and immediate reproduction is resolved by young adult females in accordance with availability of resources and gonotrophic state.

Plant-sugar feeding and vectorial capacity

Sugar feeding is a common behaviour of male and female mosquitoes, sand flies, and other Dipteran vectors. In some species it is essential to one or both sexes; in others it is facultative. Even among females of anthropophilic species that are predisposed to a diet of frequent blood meals sugar is often taken, depending on internal state and opportunity. This opportunism is expressed as an increased likelihood of feeding on nectar when access to blood and oviposition sites is limited. Newly emerged Anopheles gambiae females sometimes show a preference for sugar before mating even when blood hosts are available, likely depending both on the strength of plant and animal kairomones and on the attractive qualities of each. Incorporation of sugar in the diet by mosquitoes affects certain components of their vectorial capacity. Environmental conditions, such as bed net coverage and abundance of nectar sources, will affect the extent to which mosquitoes feed on sugar. If the effect of sugar on vectorial capacity is significant, these conditions will impact transmission rates of vector-borne diseases and should be included in epidemiological models. Vectorial capacity is pulled in opposing directions by sugar feeding, through its effect on the two most important components, survival and biting rate. Survival of females feeding on sugar and blood is greater than that of females restricted to a blood-only diet, according to the vast majority of studies, whereas biting rates usually are depressed when sugar is available, but field evidence is scarce. Vector density results from survival and fecundity. Most studies on vectors suggest that although fecundity per gonotrophic cycle is enhanced by sugar feeding, long-term reproductive fitness in anthropophilic species is slightly depressed. Vector competence appears to be negatively affected by sugar feeding. In certain cases plant nectar contains factors that inhibit development of the parasite in the vector. More common may be positive effects on the vector’s immune response, but this appears to depend heavily on the host-parasite system, condition of the vector, and possibly genotype-by-environment interactions. Estimating the combined effect of these factors at different levels of sugar intake remains difficult at this point, but an overall impression is that vectorial capacity is somewhat decreased in environments where sugar is readily accessed. Sugar feeding behaviour can be exploited for control, the most promising methods employing sugar solutions combined with attractants and oral insecticides for direct control and attractive phytochemicals for surveillance. Main questions facing both approaches are their suitability in verdant areas where attractants will compete with a diverse flora. For females of anthropophilic species in settings with abundant blood hosts, the question may be whether populations can be effectively suppressed by targeting male mosquitoes.

What Is Needed to Eradicate Lymphatic Filariasis? A Model-Based Assessment on the Impact of Scaling Up Mass Drug Administration Programs

Background Lymphatic filariasis (LF) is a neglected tropical disease for which more than a billion people in 73 countries are thought to be at-risk. At a global level, the efforts against LF are designed as an elimination program. However, current efforts appear to aim for elimination in some but not all endemic areas. With the 2020 goal of elimination looming, we set out to develop plausible scale-up scenarios to reach global elimination and eradication. We predict the duration of mass drug administration (MDA) necessary to reach local elimination for a variety of transmission archetypes using an existing model of LF transmission, estimate the number of treatments required for each scenario, and consider implications of rapid scale-up. Methodology We have defined four scenarios that differ in their geographic coverage and rate of scale-up. For each scenario, country-specific simulations and calculations were performed that took into account the pre-intervention transmission intensity, the different vector genera, drug regimen, achieved level of population coverage, previous progress toward elimination, and potential programmatic delays due to mapping, operations, and administration. Principal Findings Our results indicate that eliminating LF by 2020 is unlikely. If MDA programs are drastically scaled up and expanded, the final round of MDA for LF eradication could be delivered in 2028 after 4,159 million treatments. However, if the current rate of scale-up is maintained, the final round of MDA to eradicate LF may not occur until 2050. Conclusions/Significance Rapid scale-up of MDA will decrease the amount of time and treatments required to reach LF eradication. It may also propel the program towards success, as the risk of failure is likely to increase with extended program duration.

Mathematical models of human african trypanosomiasis epidemiology.

Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is usually fatal if untreated and transmission occurs in foci across sub-Saharan Africa. Mathematical modelling of HAT began in the 1980s with extensions of the Ross-Macdonald malaria model and has since consisted, with a few exceptions, of similar deterministic compartmental models. These models have captured the main features of HAT epidemiology and provided insight on the effectiveness of the two main control interventions (treatment of humans and tsetse fly control) in eliminating transmission. However, most existing models have overestimated prevalence of infection and ignored transient dynamics. There is a need for properly validated models, evolving with improved data collection, that can provide quantitative predictions to help guide control and elimination strategies for HAT.

Seeing beyond 2020: an economic evaluation of contemporary and emerging strategies for elimination of Trypanosoma brucei gambiense.

BACKGROUND Trypanosoma brucei (T b) gambiense is targeted to reach elimination as a public health problem by 2020 and full elimination by 2030. To achieve these goals, stakeholders need to consider strategies to accelerate elimination. Hence, we aimed to model several options related to current and emerging methods for case detection, treatment, and vector control across settings to assess cost-effectiveness and the probability of elimination. METHODS Five intervention strategies were modelled over 30 years for low, moderate, and high transmission settings. Model parameters related to costs, efficacy, and transmission were based on available evidence and parameter estimation. Outcomes included disability-adjusted life-years (DALYs), costs, and long-term prevalence. Sensitivity analyses were done to calculate the uncertainty of the results. FINDINGS To reach elimination targets for 2020 across all settings, approaches combining case detection, treatment, and vector control would be most effective. Elimination in high and moderate transmission areas was probable and cost-effective when strategies included vector control and novel methods, with incremental cost-effectiveness ratios (ICERs) ranging from US

Implications of Heterogeneous Biting Exposure and Animal Hosts on Trypanosomiasis brucei gambiense Transmission and Control

400 to

An Effective Indoor Mesocosm for Studying Populations of Anopheles gambiae in Temperate Climates

1500 per DALY averted. In low transmission areas, approaches including the newest interventions alone or in combination with tiny targets (vector control) were cost-effective, with ICERs of