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Results for “PLoS Neglected Tropical Diseases”

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11 recordsLinked to original sources
USGS2017

Protection of bats (Eptesicus fuscus) against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine

Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN- luc , negative control) in mice and big brown bats ( Eptesicus fuscus ). Mice vaccinated and boosted intradermally with 1 x 10 7 plaque forming units (PFU) of each RCN-rabies vaccine construct developed neutralizing antibodies and survived at significantly higher rates than controls. No significant difference in antibody titers or survival was noted between rabies-vaccinated groups. Bats were vaccinated either oronasally (RCN-G, RCN-MoG) with 5x10 7 PFU or by topical application in glycerin jelly (RCN-MoG, dose 2x10 8 PFU), boosted (same dose and route) at 46 days post vaccination (dpv), and then challenged with wild-type big brown variant RABV at 65 dpv. Prior to challenge, 90% of RCN-G and 75% of RCN-MoG oronasally vaccinated bats had detectable levels of serum rabies neutralizing antibodies. Bats from the RCN- luc and topically vaccinated RCN-MoG groups did not have measurable antibody responses. The RCN-rabies constructs were highly protective and not significantly different from each other. RCN-MoG provided 100% protection (n = 9) when delivered oronasally and 83% protection (n = 6) when delivered topically; protection provided by the RCN-G construct was 70% (n = 10). All rabies-vaccinated bats survived at a significantly (P ≤ 0.02) higher rate than control bats (12%; n = 8). We have demonstrated the efficacy of a novel, in silico designed rabies MoG antigen that conferred protection from rabies challenge in mice and big brown bats in laboratory studies. With further development, topical or oronasal administration of the RCN-MoG vaccine could potentially mitigate rabies in wild bat populations, reducing spillover of this deadly disease into humans, domestic mammals, and other wildlife.

PLoS Neglected Tropical Diseases↗
USGS2015

Modelling the effects of seasonality and socioeconomic impact on the transmission of Rift Valley fever virus

Rift Valley fever (RVF) is an important mosquito-borne viral zoonosis in Africa and the Middle East that causes human deaths and significant economic losses due to huge incidences of death and abortion among infected livestock. Outbreaks of RVF are sporadic and associated with both seasonal and socioeconomic effects. Here we propose an almost periodic three-patch model to investigate the transmission dynamics of RVF virus (RVFV) among ruminants with spatial movements. Our findings indicate that, in Northeastern Africa, human activities, including those associated with the Eid al Adha feast, along with a combination of climatic factors such as rainfall level and hydrological variations, contribute to the transmission and dispersal of the disease pathogen. Moreover, sporadic outbreaks may occur when the two events occur together: 1) abundant livestock are recruited into areas at risk from RVF due to the demand for the religious festival and 2) abundant numbers of mosquitoes emerge. These two factors have been shown to have impacts on the severity of RVF outbreaks. Our numerical results present the transmission dynamics of the disease pathogen over both short and long periods of time, particularly during the festival time. Further, we investigate the impact on patterns of disease outbreaks in each patch brought by festival- and seasonal-driven factors, such as the number of livestock imported daily, the animal transportation speed from patch to patch, and the death rate induced by ceremonial sacrifices. In addition, our simulations show that when the time for festival preparation starts earlier than usual, the risk of massive disease outbreaks rises, particularly in patch 3 (the place where the religious ceremony will be held).

PLoS Neglected Tropical Diseases↗
USGS2024

Comparing microbiological and molecular diagnostic tools for the surveillance of anthrax

The diagnosis of anthrax, a zoonotic disease caused by Bacillus anthracis can be complicated by detection of closely related species. Conventional diagnosis of anthrax involves microscopy, culture identification of bacterial colonies and molecular detection. Genetic markers used are often virulence gene targets such as B. anthracis protective antigen ( pagA , also called BAPA, occurring on plasmid pXO1), lethal factor ( lef , on pXO1), capsule-encoding capB/C (located on pXO2) as well as chromosomal Ba-1. Combinations of genetic markers using real-time/quantitative polymerase chain reaction (qPCR) are used to confirm B . anthracis from culture but can also be used directly on diagnostic samples to avoid propagation and its associated biorisks and for faster identification. We investigated how the presence of closely related species could complicate anthrax diagnoses with and without culture to standardise the use of genetic markers using qPCR for accurate anthrax diagnosis. Using blood smears from 2012–2020 from wildlife mortalities (n = 1708) in Kruger National Park in South Africa where anthrax is endemic, we contrasted anthrax diagnostic results based on qPCR, microscopy, and culture. From smears, 113/1708 grew bacteria in culture, from which 506 isolates were obtained. Of these isolates, only 24.7% (125 isolates) were positive for B . anthracis based on genetic markers or microscopy. However, among these, merely 4/125 (3.2%) were confirmed B . anthracis isolates (based on morphology, microscopy, and sensitivity testing to penicillin and gamma-phage) from the blood smear, likely due to poor survival of spores on stored smears. This study identified B . cereus sensu lato , which included B . cereus and B . anthracis , Peribacillus spp., and Priestia spp. clusters using gyrB gene in selected bacterial isolates positive for pagA region using BAPA probe. Using qPCR on blood smears, 52.1% (890 samples) tested positive for B . anthracis based on one or a combination of genetic markers which included the 25 positive controls. Notably, the standard lef primer set displayed the lowest specificity and accuracy. The Ba-1+BAPA+ lef combination showed 100% specificity, sensitivity, and accuracy. Various marker combinations, such as Ba-1+ capB , BAPA+ capB , Ba-1+BAPA+ capB + lef , and BAPA+ lef + capB , all demonstrated 100.0% specificity and 98.7% accuracy, while maintaining a sensitivity of 96.6%. Using Ba-1+BAPA+ lef + capB , as well as Ba-1+BAPA+ lef with molecular diagnosis accurately detects B . anthracis in the absence of bacterial culture. Systematically combining microscopy and molecular markers holds promise for notably reducing false positives. This significantly enhances the detection and surveillance of diseases like anthrax in southern Africa and beyond and reduces the need for propagation of the bacteria in culture.

PLoS Neglected Tropical Diseases↗
USGS2025

Population genomics of Aedes albopictus across remote Pacific islands for genetic biocontrol considerations

Remote Pacific islands (RPI) are characterized by ecological isolation, diverse endemic species, and vulnerability to invasive organisms due to globalization-driven connectivity. Among these species, Aedes albopictus , a highly invasive vector of flaviviruses, has spread extensively across the RPI via human-mediated dispersal, posing significant health and economic burdens. While the population structure and the degree of gene flow between mosquito populations can inform the dispersal pathways critical for disease vector management, the population genetics of Ae. albopictus in Northern RPI remains understudied. The present work investigated the population structure and connectivity of Ae. albopictus populations from Guam, Hawaiian Islands, and the Republic of the Marshall Islands (RMI) to inform disease and vector-based biosecurity risks and develop targeted management strategies. This is the first assessment to develop and analyze whole genome sequences of Ae. albopictus for RPI, enabling more accurate estimates of differentiation, admixture, and ancestry. We found distinct genetic clustering between regions, distinct ancestry of populations across RPI, and potential invasions that originated from Hawaii and spread into the RMI, and invasions from North America that spread to Guam. These findings can inform biosecurity protocols to limit the invasion of Ae. albopictus and their associated diseases within Hawaii and around the Pacific. Given the significant degree of genetic differentiation, we found between islets, islands, and regions, the genome data from this study can be used to enable the development of locally confined geographically isolated gene drives. These drives may be used to prevent and control outbreaks of dengue, chikungunya, and Zika, diseases that have had devastating consequences in these remote island communities.

PLoS Neglected Tropical Diseases↗
USGS2016

Global assessment of schistosomiasis control over the past century shows targeting the snail intermediate host works best

Background Despite control efforts, human schistosomiasis remains prevalent throughout Africa, Asia, and South America. The global schistosomiasis burden has changed little since the new anthelmintic drug, praziquantel, promised widespread control. Methodology We evaluated large-scale schistosomiasis control attempts over the past century and across the globe by identifying factors that predict control program success: snail control (e.g., molluscicides or biological control), mass drug administrations (MDA) with praziquantel, or a combined strategy using both. For data, we compiled historical information on control tactics and their quantitative outcomes for all 83 countries and territories in which: (i) schistosomiasis was allegedly endemic during the 20 th century, and (ii) schistosomiasis remains endemic, or (iii) schistosomiasis has been "eliminated," or is "no longer endemic," or transmission has been interrupted. Principal Findings Widespread snail control reduced prevalence by 92 ± 5% (N = 19) vs. 37 ± 7% (N = 29) for programs using little or no snail control. In addition, ecological, economic, and political factors contributed to schistosomiasis elimination. For instance, snail control was most common and widespread in wealthier countries and when control began earlier in the 20 th century. Conclusions/Significance Snail control has been the most effective way to reduce schistosomiasis prevalence. Despite evidence that snail control leads to long-term disease reduction and elimination, most current schistosomiasis control efforts emphasize MDA using praziquantel over snail control. Combining drug-based control programs with affordable snail control seems the best strategy for eliminating schistosomiasis.

PLoS Neglected Tropical Diseases↗
USGS2017

Characterization of Monkeypox virus infection in African rope squirrels (Funisciurus sp.)

Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is caused by Monkeypox virus (MPXV), the most virulent Orthopoxvirus affecting humans since the eradication of Variola virus (VARV). Many aspects of the MPXV transmission cycle, including the natural host of the virus, remain unknown. African rope squirrels ( Funisciurus spp .) are considered potential reservoirs of MPXV, as serosurveillance data in Central Africa has confirmed the circulation of the virus in these rodent species . In order to understand the tissue tropism and clinical signs associated with infection with MPXV in these species, wild-caught rope squirrels were experimentally infected via intranasal and intradermal exposure with a recombinant MPXV strain from Central Africa engineered to express the luciferase gene. After infection, we monitored viral replication and shedding via in vivo bioluminescent imaging, viral culture and real time PCR. MPXV infection in African rope squirrels caused mortality and moderate to severe morbidity, with clinical signs including pox lesions in the skin, eyes, mouth and nose, dyspnea, and profuse nasal discharge. Both intranasal and intradermal exposures induced high levels of viremia, fast systemic spread, and long periods of viral shedding. Shedding and luminescence peaked at day 6 post infection and was still detectable after 15 days. Interestingly, one sentinel animal, housed in the same room but in a separate cage, also developed severe MPX disease and was euthanized. This study indicates that MPXV causes significant pathology in African rope squirrels and infected rope squirrels shed large quantities of virus, supporting their role as a potential source of MPXV transmission to humans and other animals in endemic MPX regions.

PLoS Neglected Tropical Diseases↗
USGS2022

A recombinant rabies vaccine that prevents viral shedding in rabid common vampire bats (Desmodus rotundus)

Vampire bat transmitted rabies (VBR) is a continuing burden to public health and agricultural sectors in Latin America, despite decades-long efforts to control the disease by culling bat populations. Culling has been shown to disperse bats, leading to an increased spread of rabies. Thus, non-lethal strategies to control VBR, such as vaccination, are desired. Here, we evaluated the safety and efficacy of a viral-vectored recombinant mosaic glycoprotein rabies vaccine candidate (RCN-MoG) in vampire bats ( Desmodus rotundus ) of unknown history of rabies exposure captured in México and transported to the United States. Vaccination with RCN-MoG was demonstrated to be safe, even in pregnant females, as no evidence of lesions or adverse effects were observed. We detected rabies neutralizing antibodies in 28% (8/29) of seronegative bats post-vaccination. Survival proportions of adult bats after rabies virus (RABV) challenge ranged from 55–100% and were not significantly different among treatments, pre- or post-vaccination serostatus, and route of vaccination, while eight pups (1–2.5 months of age) used as naïve controls all succumbed to challenge (P<0.0001). Importantly, we found that vaccination with RCN-MoG appeared to block viral shedding, even when infection proved lethal. Using real-time PCR, we did not detect RABV nucleic acid in the saliva samples of 9/10 vaccinated bats that succumbed to rabies after challenge (one was inconclusive). In contrast, RABV nucleic acid was detected in saliva samples from 71% of unvaccinated bats (10/14 sampled, plus one inconclusive) that died of the disease, including pups. Low seroconversion rates post-vaccination and high survival of non-vaccinated bats, perhaps due to earlier natural exposure, limited our conclusions regarding vaccine efficacy. However, our findings suggest a potential transmission-blocking effect of vaccination with RCN-MoG that could provide a promising strategy for controlling VBR in Latin America beyond longstanding culling programs.

San Luis Potosi↗
USGS2020

Linking mosquito surveillance to dengue fever through Bayesian mechanistic modeling

Our ability to effectively prevent the transmission of the dengue virus through targeted control of its vector, Aedes aegypti , depends critically on our understanding of the link between mosquito abundance and human disease risk. Mosquito and clinical surveillance data are widely collected, but linking them requires a modeling framework that accounts for the complex non-linear mechanisms involved in transmission. Most critical are the bottleneck in transmission imposed by mosquito lifespan relative to the virus’ extrinsic incubation period, and the dynamics of human immunity. We developed a differential equation model of dengue transmission and embedded it in a Bayesian hierarchical framework that allowed us to estimate latent time series of mosquito demographic rates from mosquito trap counts and dengue case reports from the city of Vitória, Brazil. We used the fitted model to explore how the timing of a pulse of adult mosquito control influences its effect on the human disease burden in the following year. We found that control was generally more effective when implemented in periods of relatively low mosquito mortality (when mosquito abundance was also generally low). In particular, control implemented in early September (week 34 of the year) produced the largest reduction in predicted human case reports over the following year. This highlights the potential long-term utility of broad, off-peak-season mosquito control in addition to existing, locally targeted within-season efforts. Further, uncertainty in the effectiveness of control interventions was driven largely by posterior variation in the average mosquito mortality rate (closely tied to total mosquito abundance) with lower mosquito mortality generating systems more vulnerable to control. Broadly, these correlations suggest that mosquito control is most effective in situations in which transmission is already limited by mosquito abundance.

Espírito Santo↗
USGS2015

Laboratory investigations of African Pouched Rats ( Cricetomys gambianus ) as a potential reservoir host species for Monkeypox Virus

Monkeypox is a zoonotic disease endemic to central and western Africa, where it is a major public health concern. Although Monkeypox virus (MPXV) and monkeypox disease in humans have been well characterized, little is known about its natural history, or its maintenance in animal populations of sylvatic reservoir(s). In 2003, several species of rodents imported from Ghana were involved in a monkeypox outbreak in the United States with individuals of three African rodent genera ( Cricetomys , Graphiurus , Funisciurus ) shown to be infected with MPXV. Here, we examine the course of MPXV infection in Cricetomys gambianus (pouched Gambian rats) and this rodent species&rsquo; competence as a host for the virus. We obtained ten Gambian rats from an introduced colony in Grassy Key, Florida and infected eight of these via scarification with a challenge dose of 4X10 4 plaque forming units (pfu) from either of the two primary clades of MPXV: Congo Basin (C-MPXV: n = 4) or West African (W-MPXV: n = 4); an additional 2 animals served as PBS controls. Viral shedding and the effect of infection on activity and physiological aspects of the animals were measured. MPXV challenged animals had significantly higher core body temperatures, reduced activity and increased weight loss than PBS controls. Viable virus was found in samples taken from animals in both experimental groups (C-MPXV and W-MPXV) between 3 and 27 days post infection (p.i.) (up to 1X10 8 pfu/ml), with viral DNA found until day 56 p.i. The results from this work show that Cricetomys gambianus (and by inference, probably the closely related species, Cricetomys emini ) can be infected with MPXV and shed viable virus particles; thus suggesting that these animals may be involved in the maintenance of MPXV in wildlife mammalian populations. More research is needed to elucidate the epidemiology of MPXV and the role of Gambian rats and other species.

PLoS Neglected Tropical Diseases↗
USGS2015

Further assessment of Monkeypox Virus infection in Gambian pouched rats ( Cricetomys gambianus ) using in vivo bioluminescent imaging

Monkeypox is a zoonosis clinically similar to smallpox in humans. Recent evidence has shown a potential risk of increased incidence in central Africa. Despite attempts to isolate the virus from wild rodents and other small mammals, no reservoir host has been identified. In 2003, Monkeypox virus (MPXV) was accidentally introduced into the U.S. via the pet trade and was associated with the Gambian pouched rat ( Cricetomys gambianus ). Therefore, we investigated the potential reservoir competence of the Gambian pouched rat for MPXV by utilizing a combination of in vivo and in vitro methods. We inoculated three animals by the intradermal route and three animals by the intranasal route, with one mock-infected control for each route. Bioluminescent imaging (BLI) was used to track replicating virus in infected animals and virological assays (e.g. real time PCR, cell culture) were used to determine viral load in blood, urine, ocular, nasal, oral, and rectal swabs. Intradermal inoculation resulted in clinical signs of monkeypox infection in two of three animals. One severely ill animal was euthanized and the other affected animal recovered. In contrast, intranasal inoculation resulted in subclinical infection in all three animals. All animals, regardless of apparent or inapparent infection, shed virus in oral and nasal secretions. Additionally, BLI identified viral replication in the skin without grossly visible lesions. These results suggest that Gambian pouched rats may play an important role in transmission of the virus to humans, as they are hunted for consumption and it is possible for MPXV-infected pouched rats to shed infectious virus without displaying overt clinical signs.

PLoS Neglected Tropical Diseases↗
USGS2021

Schistosome infection in Senegal is associated with different spatial extents of risk and ecological drivers for Schistosoma haematobium and S. mansoni

Schistosome parasites infect more than 200 million people annually, mostly in sub-Saharan Africa, where people may be co-infected with more than one species of the parasite. Infection risk for any single species is determined, in part, by the distribution of its obligate intermediate host snail. As the World Health Organization reprioritizes snail control to reduce the global burden of schistosomiasis, there is renewed importance in knowing when and where to target those efforts, which could vary by schistosome species. This study estimates factors associated with schistosomiasis risk in 16 villages located in the Senegal River Basin, a region hyperendemic for Schistosoma haematobium and S . mansoni . We first analyzed the spatial distributions of the two schistosomes’ intermediate host snails ( Bulinus spp. and Biomphalaria pfeifferi , respectively) at village water access sites. Then, we separately evaluated the relationships between human S . haematobium and S . mansoni infections and (i) the area of remotely-sensed snail habitat across spatial extents ranging from 1 to 120 m from shorelines, and (ii) water access site size and shape characteristics. We compared the influence of snail habitat across spatial extents because, while snail sampling is traditionally done near shorelines, we hypothesized that snails further from shore also contribute to infection risk. We found that, controlling for demographic variables, human risk for S . haematobium infection was positively correlated with snail habitat when snail habitat was measured over a much greater radius from shore (45 m to 120 m) than usual. S . haematobium risk was also associated with large, open water access sites. However, S . mansoni infection risk was associated with small, sheltered water access sites, and was not positively correlated with snail habitat at any spatial sampling radius. Our findings highlight the need to consider different ecological and environmental factors driving the transmission of each schistosome species in co-endemic landscapes.

PLoS Neglected Tropical Diseases↗