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Category: publications

Young Adults in Endemic Areas: An Untreated Group in Need of School-Based Preventive Chemotherapy for Schistosomiasis Control and Elimination

Abstract

Parasitologic surveys of young adults in college and university settings are not commonly done, even in areas known to be endemic for schistosomiasis and soil-transmitted helminths. We have done a survey of 291 students and staff at the Kisumu National Polytechnic in Kisumu, Kenya, using the stool microscopy Kato-Katz (KK) method and the urine point-of-care circulating cathodic antigen (POC-CCA) test. Based on three stools/two KK slides each, in the 208 participants for whom three consecutive stools were obtained, Schistosoma mansoni prevalence was 17.8%. When all 291 individuals were analyzed based on the first stool, as done by the national neglected tropical disease (NTD) program, and one urine POC-CCA assay (n = 276), the prevalence was 13.7% by KK and 23.2% by POC-CCA. Based on three stools, 2.5% of 208 participants had heavy S. mansoni infections (≥400 eggs/gram feces), with heavy S. mansoni infections making up 13.5% of the S. mansoni cases. The prevalence of the soil-transmitted helminths (STH: Ascaris lumbricoidesTrichuris trichiura and hookworm) by three stools was 1.4%, 3.1%, and 4.1%, respectively, and by the first stool was 1.4%, 2.4% and 1.4%, respectively. This prevalence and intensity of infection with S. mansoni in a college setting warrants mass drug administration with praziquantel. This population of young adults is ‘in school’ and is both approachable and worthy of inclusion in national schistosomiasis control and elimination programs.

Harrison K. Korir, Diana K. Riner, Emmy Kavere, Amos Omondi, Jasmine Landry, Nupur Kittur, Eric M. Ndombi, Bartholomew N. Ondigo, W. Evan Secor, Diana M. S. Karanja and Daniel G. Colley. 2018. Trop. Med. Infect. Dis.; 3(3):100. https://doi.org/10.3390/tropicalmed3030100

Antiplasmodial flavanones and a stilbene from Carpha glomerata

graphical abstract

Abstract

Bioassay-guided fractionation of an extract of Carpha glomerata (Cyperaceae) led to the isolation of seven compounds. Compounds 1 (carphorin A), 3 (carphorin C), 4(carphorin D), and 5 (carphabene) are new compounds, and compound 2 (8-(3″-hydroxyisoamyl)-naringenin) was isolated for the first time as a natural product. All structures were elucidated based on analyses of their HR-ESIMS and 1D and 2D NMR data. Compounds 12, and 6, which have prenyl or hydroxyprenyl side chains, exhibited antiplasmodial activities with IC50 values of 5.2 ± 0.6, 3.4 ± 0.4, and 6.7 ± 0.8 µM against the drug-resistant Dd2 strain of Plasmodium falciparum. In addition the prenylated stilbene 5 also showed good activity, with IC50 5.8 ± 0.7 µM.

Namki Cho, Ana Lisa Valenciano, Yongle Du, Jason Clement, Maria B. Cassera, Michael Goetz, David G. I. Kingston. 2018. Bioorganic & Medicinal Chemistry Letters; 28(20):3368-3371. https://doi.org/10.1016/j.bmcl.2018.09.003

Spatio-temporal spillover risk of yellow fever in Brazil

Abstract

Background: Yellow fever virus is a mosquito-borne flavivirus that persists in an enzoonotic cycle in non-human primates (NHPs) in Brazil, causing disease in humans through spillover events. Yellow fever (YF) re-emerged in the early 2000s, spreading from the Amazon River basin towards the previously considered low-risk, southeastern region of the country. Previous methods mapping YF spillover risk do not incorporate the temporal dynamics and ecological context of the disease, and are therefore unable to predict seasonality in spatial risk across Brazil. We present the results of a bagged logistic regression predicting the propensity for YF spillover per municipality (administrative sub-district) in Brazil from environmental and demographic covariates aggregated by month. Ecological context was incorporated by creating National and Regional models of spillover dynamics, where the Regional model consisted of two separate models determined by the regions’ NHP reservoir species richness (high vs low).

Results: Of the 5560 municipalities, 82 reported YF cases from 2001 to 2013. Model accuracy was high for the National and low reservoir richness (LRR) models (AUC = 0.80), while the high reservoir richness (HRR) model accuracy was lower (AUC = 0.63). The National model predicted consistently high spillover risk in the Amazon, while the Regional model predicted strong seasonality in spillover risk. Within the Regional model, seasonality of spillover risk in the HRR region was asynchronous to the LRR region. However, the observed seasonality of spillover risk in the LRR Regional model mirrored the national model predictions.

Conclusions: The predicted risk of YF spillover varies with space and time. Seasonal trends differ between regions indicating, at times, spillover risk can be higher in the urban coastal regions than the Amazon River basin which is counterintuitive based on current YF risk maps. Understanding the spatio-temporal patterns of YF spillover risk could better inform allocation of public health services.

RajReni B. Kaul, Michelle V. Evans, Courtney C. Murdock and John M. Drake. 2018. Parasites & Vectors; 11:488. https://doi.org/10.1186/s13071-018-3063-6

Estimating the effects of variation in viremia on mosquito susceptibility, infectiousness, and R0 of Zika in Aedes aegypti

Abstract

Zika virus (ZIKV) is an arbovirus primarily transmitted by Aedes mosquitoes. Like most viral infections, ZIKV viremia varies over several orders of magnitude, with unknown consequences for transmission. To determine the effect of viral concentration on ZIKV transmission risk, we exposed field-derived Aeaegypti mosquitoes to four doses (103, 104, 105, 106 PFU/mL) representative of potential variation in the field. We demonstrate that increasing ZIKV dose in the blood-meal significantly increases the probability of mosquitoes becoming infected, and consequently disseminating virus and becoming infectious. Additionally, we observed significant interactions between dose and days post-infection on dissemination and overall transmission efficiency, suggesting that variation in ZIKV dose affects the rates of midgut escape and salivary gland invasion. We did not find significant effects of dose on mosquito mortality. We also demonstrate that detecting virus using RT-qPCR approaches rather than plaque assays potentially over-estimates key transmission parameters, including the time at which mosquitoes become infectious and viral burden. Finally, using these data to parameterize an R0 model, we showed that increasing viremia from 104 to 106 PFU/mL increased relative R0 3.8-fold, demonstrating that variation in viremia substantially affects transmission risk.

Blanka Tesla, Leah R. Demakovsky, Hannah S. Packiam, Erin A. Mordecai, Américo D. Rodríguez, Matthew H. Bonds, Melinda A. Brindley, Courtney C. Murdock. 2018. PLOS Neglected Tropical Diseases; 12(8): e0006733. https://doi.org/10.1371/journal.pntd.0006733

Temperature drives Zika virus transmission: evidence from empirical and mathematical models

Abstract

Temperature is a strong driver of vector-borne disease transmission. Yet, for emerging arboviruses we lack fundamental knowledge on the relationship between transmission and temperature. Current models rely on the untested assumption that Zika virus responds similarly to dengue virus, potentially limiting our ability to accurately predict the spread of Zika. We conducted experiments to estimate the thermal performance of Zika virus (ZIKV) in field-derived Aedes aegypti across eight constant temperatures. We observed strong, unimodal effects of temperature on vector competence, extrinsic incubation period and mosquito survival. We used thermal responses of these traits to update an existing temperature-dependent model to infer temperature effects on ZIKV transmission. ZIKV transmission was optimized at 29°C, and had a thermal range of 22.7°C–34.7°C. Thus, as temperatures move towards the predicted thermal optimum (29°C) owing to climate change, urbanization or seasonality, Zika could expand north and into longer seasons. By contrast, areas that are near the thermal optimum were predicted to experience a decrease in overall environmental suitability. We also demonstrate that the predicted thermal minimum for Zika transmission is 5°C warmer than that of dengue, and current global estimates on the environmental suitability for Zika are greatly over-predicting its possible range.

Blanka Tesla, Leah R. Demakovsky, Erin A. Mordecai, Sadie J. Ryan, Matthew H. Bonds, Calistus N. Ngonghala, Melinda A. Brindley, and Courtney C. Murdock. 2018. Proceedings of the Royal Society B; 285(1884):0962-8452. https://doi.org/10.1098/rspb.2018.0795

When Should the Emphasis on Schistosomiasis Control Move to Elimination?

Abstract

The stated goal of the World Health Organization’s program on schistosomiasis is paraphrased as follows: to control morbidity and eliminate transmission where feasible. Switching from a goal of controlling morbidity to interrupting transmission may well be currently feasible in some countries in the Caribbean, some areas in South America, northern Africa, and selected endemic areas in sub-Saharan Africa where there have been improvements in sanitation and access to clean water. However, in most of sub-Saharan Africa, where programmatic interventions still consist solely of annual mass drug administration, such a switch in strategies remains premature. There is a continued need for operational research on how best to reduce transmission to a point where interruption of transmission may be achievable. The level of infection at which it is feasible to transition from control to elimination must also be defined. In parallel, there is also a need to develop and evaluate approaches for achieving and validating elimination. There are currently neither evidence-based methods nor tools for breaking transmission or verifying that it has been accomplished. The basis for these statements stems from numerous studies that will be reviewed and summarized in this article; many, but not all of which were undertaken as part of SCORE, the Schistosomiasis Consortium for Operational Research and Evaluation

W. Evan Secor and Daniel G. Colley. 2018. Trop. Med. Infect. Dis.; 3(3):85. https://doi.org/10.3390/tropicalmed3030085

Characterization of Two EF-hand Domain-containing Proteins from Toxoplasma gondii

The universal role of calcium (Ca2+ ) as a second messenger in cells depends on a large number of Ca2+ -binding proteins (CBP), which are able to bind Ca2+ through specific domains. Many CBPs share a type of Ca2+ -binding domain known as the EF-hand. The EF-hand motif has been well studied and consists of a helix-loop-helix structural domain with specific amino acids in the loop region that interact with Ca2+ . In Toxoplasma gondii a large number of genes (approximately 68) are predicted to have at least one EF-hand motif. The majority of these genes have not been characterized. We report the characterization of two EF-hand motif-containing proteins, TgGT1_216620 and TgGT1_280480, which localize to the plasma membrane and to the rhoptry bulb, respectively. Genetic disruption of these genes by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) resulted in mutant parasite clones (Δtg216620 and Δtg280480) that grew at a slower rate than control cells. Ca2+ measurements showed that Δtg216620 cells did not respond to extracellular Ca2+ as the parental controls while Δtg280480 cells appeared to respond as the parental cells. Our hypothesis is that TgGT1_216620 is important for Ca2+ influx while TgGT1_280480 may be playing a different role in the rhoptries. This article is protected by copyright. All rights reserved.