MicrobiologyBytes

Bacterial associates are ubiquitous among insects, including mosquitoes. Wolbachia are obligate endosymbiotic bacteria that infect numerous insects, many of which are vectors of pathogenic microorganisms. Interest has centered around Wolbachia as a means of reducing arthropod-borne disease due to the capacity of the bacteria to manipulate the reproduction of the insect host, which in turn favors their own transmission.

Recent studies show that Wolbachia can directly cause pathogen interference (PI) in their invertebrate hosts, whereby infected insects are less susceptible to pathogens. Infection with Wolbachia bacteria has been shown to reduce pathogen levels in multiple mosquito species. Anopheles mosquitoes (the obligate vectors of human malaria) are naturally uninfected with Wolbachia, and stable artificial infections have not yet succeeded in this genus; however somatic infections can be established that can be used to assess the effect of Wolbachia infection in Anopheles. Here, we show that infection with two different Wolbachia strains can significantly reduce levels of the human malaria parasite Plasmodium falciparum in Anopheles gambiae. After infection, Wolbachia disseminate throughout the mosquito but are notably absent from the gut and ovaries. The mosquito immune system is first induced in response to Wolbachia infection, but is then suppressed as the infection progresses. The Wolbachia strain wMelPop is highly virulent to Anopheles only after blood feeding. If stable infections can be established in Anopheles, and they act in a similar manner to somatic infections, Wolbachia could potentially be used as part of a strategy to control malaria.

Wolbachia Infections Are Virulent and Inhibit the Human Malaria Parasite Plasmodium Falciparum in Anopheles Gambiae. 2011 PLoS Pathog 7(5): e1002043. doi:10.1371/journal.ppat.1002043
Endosymbiotic Wolbachia bacteria are potent modulators of pathogen infection and transmission in multiple naturally and artificially infected insect species, including important vectors of human pathogens. Anopheles mosquitoes are naturally uninfected with Wolbachia, and stable artificial infections have not yet succeeded in this genus. Recent techniques have enabled establishment of somatic Wolbachia infections in Anopheles. Here, we characterize somatic infections of two diverse Wolbachia strains (wMelPop and wAlbB) in Anopheles gambiae, the major vector of human malaria. After infection, wMelPop disseminates widely in the mosquito, infecting the fat body, head, sensory organs and other tissues but is notably absent from the midgut and ovaries. Wolbachia initially induces the mosquito immune system, coincident with initial clearing of the infection, but then suppresses expression of immune genes, coincident with Wolbachia replication in the mosquito. Both wMelPop and wAlbB significantly inhibit Plasmodium falciparum oocyst levels in the mosquito midgut. Although not virulent in non-bloodfed mosquitoes, wMelPop exhibits a novel phenotype and is extremely virulent for approximately 12–24 hours post-bloodmeal, after which surviving mosquitoes exhibit similar mortality trajectories to control mosquitoes. The data suggest that if stable transinfections act in a similar manner to somatic infections, Wolbachia could potentially be used as part of a strategy to control the Anopheles mosquitoes that transmit malaria.

To control mosquito-borne diseases like dengue fever, researchers need to look at the behavior of people, not just the insect that transmits the disease. Vector-borne diseases constitute a largely neglected and enormous burden on public health in many resource-challenged environments, demanding efficient control strategies that could be developed through improved understanding of pathogen transmission. Human movement – which determines exposure to vectors – is a key behavioral component of vector-borne disease epidemiology that is poorly understood.

A new paper attempts to develop a conceptual framework to organize past studies by the scale of movement and then examine movements at fine-scale – i.e. people going through their regular, daily routine – that determine exposure to insect vectors for their role in the dynamics of pathogen transmission. The authors develop a model to quantify risk of vector contact across locations people visit, with emphasis on mosquito-borne dengue virus in the Amazonian city of Iquitos, Peru.

An example scenario illustrates how movement generates variation in exposure risk across individuals, how transmission rates within sites can be increased, and that risk within sites is not solely determined by vector density, as is commonly assumed. This analysis illustrates the importance of human movement for pathogen transmission, yet little is known – especially for populations most at risk to vector-borne diseases (e.g. dengue, leishmaniasis, etc.). The authors outline several important considerations for designing epidemiological studies to encourage investigation of individual human movement, based on this experience studying dengue.

The incidence of dengue fever in Iquitos has varied from around five percent to over 30 percent after new virus serotype introductions. There is no vaccine and no cure for dengue, which is transmitted by the tiger-striped, day-biting mosquito, Aedes aegypti. To track individual human movement, the research team used satellite-based global positioning system (GPS) and culturally-sensitive interviews that were developed by the team. The researchers developed a conceptual model showing that the relevance of human movement at a particular scale depends on vector behavior. Focusing on Aedes aegypti, they illustrated how vector-biting behavior combined with fine-scale movements of individual humans engaged in daily routines can influence transmission. They also outlined several considerations for designing epidemiological studies to encourage studies of individual human movement. They hope to arrive at a better notion of the spatial scale on which dengue transmission occurs and from an operational standpoint, at what scale to focus interventions. Another aim is to encourage researchers of other mosquito-borne diseases, such as malaria, to perform more incisive examination of individual movements.

The Role of Human Movement in the Transmission of Vector-Borne Pathogens. PLoS Negl Trop Dis 3(7): e481 doi:10.1371/journal.pntd.0000481
Human movement is a key behavioral factor in many vector-borne disease systems because it influences exposure to vectors and thus the transmission of pathogens. Human movement transcends spatial and temporal scales with different influences on disease dynamics. Here we develop a conceptual model to evaluate the importance of variation in exposure due to individual human movements for pathogen transmission, focusing on mosquito-borne dengue virus. We develop a model showing that the relevance of human movement at a particular scale depends on vector behavior. Focusing on the day-biting Aedes aegypti, we illustrate how vector biting behavior combined with fine-scale movements of individual humans engaged in their regular daily routine can influence transmission. Using a simple example, we estimate a transmission rate (R0) of 1.3 when exposure is assumed to occur only in the home versus 3.75 when exposure at multiple locations – e.g. market, friends – due to movement is considered. Movement also influences for which sites and individuals risk is greatest. For the example considered, intriguingly, our model predicts little correspondence between vector abundance in a site and estimated R0 for that site when movement is considered. This illustrates the importance of human movement for understanding and predicting the dynamics of a disease like dengue. To encourage investigation of human movement and disease, we review methods currently available to study human movement and, based on our experience studying dengue in Peru, discuss several important questions to address when designing a study. Human movement is a critical, understudied behavioral component underlying the transmission dynamics of many vector-borne pathogens. Understanding movement will facilitate identification of key individuals and sites in the transmission of pathogens such as dengue, which then may provide targets for surveillance, intervention, and improved disease prevention.

Related:

• Dengue Virus
• Pathogenic Flaviviruses
• Changing patterns of chikungunya virus

Bluetongue is a disease of ruminants caused by Bluetongue virus (BTV) and it is transmitted by biting midges. In sheep, clinical signs of BTV infection can include fever, vasodilation, swelling and, in severe cases, death, although the severity of symptoms varies with the breed of sheep, the individual animal and the strain of virus involved. Cattle are a major reservoir host for BTV infection, primarily because of the less obvious clinical signs in these animals. After an exhaustive search for a natural agent of transmission, Culicoides midges were shown to be the vectors for Bluetongue virus (Culicoides and the emergence of bluetongue virus in northern Europe. Trends Microbiol 2009 17(4): 172-178).

Although BTV infection was initially centred in Africa, the virus was first detected in Greece in 1989, from where it has spread steadily north. Since the disease is spread exclusively by insects, and because the virus is quite specific about which midge species can be used as vectors, predictions about the spread of the disease were based on known ranges of different midge species, which in turn depends on climate. However, midges can sometimes be carried over very long distances by weather systems, or by ships or aircraft.

Despite widespread speculation regarding the exact origin of BTV-8 as the strain of the virus found in northern Europe, no single convincing hypothesis has been proposed. Although future full-genome sequencing might assist this task (as was the case in the incursion of West Nile virus into North America), the small number of reference strains of BTV-8 from areas of potential origin collected before the incursion into northern Europe makes it unlikely that this approach will provide unambiguous evidence. As long as our understanding of the potential routes of virus introduction remains poor, we will be unable to accurately estimate the potential for future introductions of BTV, as has been illustrated by the more recent detection of BTV-6 in Europe, or of other midge-borne arboviruses, such as African horse sickness virus (AHSV).

Subscribe to podcasts (free):
[iTunes] Enhanced podcasts & videos
[RSS] mp3 podcasts (audio only)
Play this episode: Enhanced version | Audio only

Although the technology to produce safe, effective, inactivated vaccines existed, no coordinated action was taken by any Member State of the European Union (EU) to begin production of a BTV-8 vaccine until late 2007, when the full damage began to become evident. This was in part due to the assumption that the virus would not overwinter under northern European conditions (despite the fact that BTV had been documented overwintering successfully in other areas with far cooler winter temperatures). In the absence of an available vaccine, knowledge concerning the entomology of the insects involved in BTV transmission became paramount.

The spread of BTV has provided a severe test of the way in which the movement of vector-borne pathogens is predicted, identified and controlled in Europe. There are many arobovirus diseases (spread by arthropod vectors such as midges, mosquitos and ticks), affecting human as well as animal health. Whether BTV represents a herald for future incursions by other arboviruses into Europe remains difficult to know. It is clear that there exists a similar potential for emergence of other insect-borne pathogens on grounds of climate alone, but where different vectors are used – for example, in the case of AHSV – the dynamics of the current BTV outbreak cannot easily be used to estimate risk. What has been shown by this outbreak is that arbovirus–vector relationships are highly dynamic and extremely difficult to combat. Unless regions that are potentially at risk of transmission are prepared to invest the resources required to provide adequate information regarding vectors and suitable control methods, this will remain the case.

Related:

• Bluetongue virus
• How does bluetongue virus survive the winter?
• Bluetongue virus polymerase

Dengue fever and Dengue hemorrhagic fever have emerged as some of the most important mosquito-borne virus diseases in the tropics. No effective vaccine or antiviral drug therapy is currently available against Dengue viruses and the mechanisms of pathogenesis in Dengue infections remain elusive. Recently, virus-induced apoptosis mediated by the Unfolded Protein Response (UPR, or ER stress response) has been hypothesised to represent a crucial pathogenic event in virus infection. In Dengue virus infection, cells elicit an UPR which is observed at the level of translation attenuation (seen by phosphorylation of eIF2alpha) and activation of other specific pathways. Interestingly, specific serotypes of Dengue virus modulate the UPR with different selectivity. Perturbation of the UPR by preventing the dephosphorylation of the translation initiation factor eIF2alpha considerably alters virus infectivity. This report provides evidence that Dengue infection induces and regulates the three branches of the UPR signaling cascades. This is a basis for understanding of Dengue virus regulation and conditions beneficial to virus infection. Furthermore, modulators of UPR such as Salubrinal that inhibit Dengue replication may open up avenues for anti-viral therapy.

Dengue virus serotype infection specifies the activation of the unfolded protein response
Virology Journal 2007 4: 91