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Disproportionate impact of the COVID-19 pandemic on immigrant communities in the United States

PLoS Neglected Tropical Diseases News - 13 July 2020 - 9:00pm

by Eva Clark, Karla Fredricks, Laila Woc-Colburn, Maria Elena Bottazzi, Jill Weatherhead

Melioidosis DS rapid test: A standardized serological dipstick assay with increased sensitivity and reliability due to multiplex detection

PLoS Neglected Tropical Diseases News - 13 July 2020 - 9:00pm

by Gabriel E. Wagner, Esther Föderl-Höbenreich, Karoline Assig, Michaela Lipp, Andreas Berner, Christian Kohler, Sabine Lichtenegger, Julia Stiehler, Wisansanee Karoonboonyanan, Nida Thanapattarapairoj, Chidchanok Promkong, Sirikamon Koosakulnirand, Panjaporn Chaichana, Ralf Ehricht, Anne-Marie Gad, Hans H. Söffing, Susanna J. Dunachie, Narisara Chantratita, Ivo Steinmetz

Background

Melioidosis, caused by Burkholderia pseudomallei, is a severe infectious disease with high mortality rates, but is under-recognized worldwide. In endemic areas, there is a great need for simple, low-cost and rapid diagnostic tools. In a previous study we showed, that a protein multiplex array with 20 B. pseudomallei-specific antigens detects antibodies in melioidosis patients with high sensitivity and specificity. In a subsequent study the high potential of anti-B. pseudomallei antibody detection was confirmed using a rapid Hcp1 single protein-based assay. Our protein array also showed that the antibody profile varies between patients, possibly due to a combination of host factors but also antigen variations in the infecting B. pseudomallei strains. The aim of this study was to develop a rapid test, combining Hcp1 and the best performing antigens BPSL2096, BPSL2697 and BPSS0477 from our previous study, to take advantage of simultaneous antibody detection.

Methods and principal findings

The 4-plex dipstick was validated with sera from 75 patients on admission plus control groups, achieving 92% sensitivity and 97–100% specificity. We then re-evaluated melioidosis sera with the 4-plex assay that were previously misclassified by the monoplex Hcp1 rapid test. 12 out of 55 (21.8%) false-negative samples were positive in our new dipstick assay. Among those, 4 sera (7.3%) were Hcp1 positive, whereas 8 (14.5%) sera remained Hcp1 negative but gave a positive reaction with our additional antigens.

Conclusions

Our dipstick rapid test represents an inexpensive, standardized and simple diagnostic tool with an improved serodiagnostic performance due to multiplex detection. Each additional band on the test strip makes a false-positive result more unlikely, contributing to its reliability. Future prospective studies will seek to validate the gain in sensitivity and specificity of our multiplex rapid test approach in different melioidosis patient cohorts.

Performance of a rapid diagnostic test for the detection of <i>Cryptosporidium</i> spp. in African children admitted to hospital with diarrhea

PLoS Neglected Tropical Diseases News - 13 July 2020 - 9:00pm

by Gedéon Prince Manouana, Eva Lorenz, Mirabeau Mbong Ngwese, Paul Alvyn Nguema Moure, Oumou Maiga Ascofaré, Charity Wiafe Akenten, John Amuasi, Njari Rakotozandrindrainy, Raphael Rakotozandrindrainy, Joyce Mbwana, John Lusingu, Natalie Byrne, Sophia Melhem, Jeannot Frejus Zinsou, Roméo Bayodé Adegbite, Benedikt Hogan, Doris Winter, Jurgen May, Peter Gottfried Kremsner, Steffen Borrmann, Daniel Eibach, Ayola Akim Adegnika

Background

Cryptosporidium is a protozoan parasite that causes mild to severe diarrhoeal disease in humans. To date, several commercial companies have developed rapid immunoassays for the detection of Cryptosporidium infection. However, the challenge is to identify an accurate, simple and rapid diagnostic tool for the estimation of cryptosporidiosis burden. This study aims at evaluating the accuracy of CerTest Crypto, a commercialized rapid diagnostic test (RDT) for the detection of Cryptosporidium antigens in the stool of children presenting with diarrhoea.

Methods

A cross-sectional study was conducted in four study sites in Sub-Saharan Africa (Gabon, Ghana, Madagascar, and Tanzania), from May 2017 to April 2018. Stool samples were collected from children under 5 years with diarrhoea or a history of diarrhoea within the last 24 hours. All specimens were processed and analyzed using CerTest Crypto RDT against a composite diagnostic panel involving two polymerase chain reaction (PCR) tests (qPCR and RFLP-PCR,) as the gold standard.

Results

A total of 596 stool samples were collected. Evaluation of the RDT yielded a very low overall sensitivity of 49.6% (confidence interval (CI) 40.1–59.0), a specificity of 92.5% (CI 89.8–94.7), positive predictive value of 61.3% (CI 50.6–71.2), and negative predictive value of 88.5% (85.3–91.1) when compared to the composite reference standard of qPCR and RFLP-PCR for the detection of Cryptosporidium species. Moreover, the performance of this test varied across different sites.

Conclusion

The weak performance of the studied RDT suggests the need to carefully evaluate available commercial RDTs before their use as standard tools in clinical trials and community survey of Cryptosporidium infections in pediatric cohorts.

<i>Phlebotomus papatasi</i> sand fly predicted salivary protein diversity and immune response potential based on <i>in silico</i> prediction in Egypt and Jordan populations

PLoS Neglected Tropical Diseases News - 13 July 2020 - 9:00pm

by Catherine M. Flanley, Marcelo Ramalho-Ortigao, Iliano V. Coutinho-Abreu, Rami Mukbel, Hanafi A. Hanafi, Shabaan S. El-Hossary, Emadeldin Y. Fawaz, David F. Hoel, Alexander W. Bray, Gwen Stayback, Douglas A. Shoue, Shaden Kamhawi, Scott Emrich, Mary Ann McDowell

Phlebotomus papatasi sand flies inject their hosts with a myriad of pharmacologically active salivary proteins to assist with blood feeding and to modulate host defenses. In addition, salivary proteins can influence cutaneous leishmaniasis disease outcome, highlighting the potential of the salivary components to be used as a vaccine. Variability of vaccine targets in natural populations influences antigen choice for vaccine development. Therefore, the objective of this study was to investigate the variability in the predicted protein sequences of nine of the most abundantly expressed salivary proteins from field populations, testing the hypothesis that salivary proteins appropriate to target for vaccination strategies will be possible. PpSP12, PpSP14, PpSP28, PpSP29, PpSP30, PpSP32, PpSP36, PpSP42, and PpSP44 mature cDNAs from field collected P. papatasi from three distinct ecotopes in the Middle East and North Africa were amplified, sequenced, and in silico translated to assess the predicted amino acid variability. Two of the predicted sequences, PpSP12 and PpSP14, demonstrated low genetic variability across the three geographic isolated sand fly populations, with conserved multiple predicted MHCII epitope binding sites suggestive of their potential application in vaccination approaches. The other seven predicted salivary proteins revealed greater allelic variation across the same sand fly populations, possibly precluding their use as vaccine targets.

Correction: Plague in Zimbabwe from 1974 to 2018: A review article

PLoS Neglected Tropical Diseases News - 10 July 2020 - 9:00pm

by Amon Munyenyiwa, Moses Zimba, Tamuka Nhiwatiwa, Maxwell Barson

<i>Schistosoma mansoni</i> immunomodulatory molecule Sm16/SPO-1/SmSLP is a member of the trematode-specific helminth defence molecules (HDMs)

PLoS Neglected Tropical Diseases News - 9 July 2020 - 9:00pm

by Jenna Shiels, Krystyna Cwiklinski, Raquel Alvarado, Karine Thivierge, Sophie Cotton, Bibiana Gonzales Santana, Joyce To, Sheila Donnelly, Clifford C. Taggart, Sinead Weldon, John P. Dalton

Background

Sm16, also known as SPO-1 and SmSLP, is a low molecular weight protein (~16kDa) secreted by the digenean trematode parasite Schistosoma mansoni, one of the main causative agents of human schistosomiasis. The molecule is secreted from the acetabular gland of the cercariae during skin invasion and is believed to perform an immune-suppressive function to protect the invading parasite from innate immune cell attack.

Methodology/Principal findings

We show that Sm16 homologues of the Schistosomatoidea family are phylogenetically related to the helminth defence molecule (HDM) family of immunomodulatory peptides first described in Fasciola hepatica. Interrogation of 69 helminths genomes demonstrates that HDMs are exclusive to trematode species. Structural analyses of Sm16 shows that it consists predominantly of an amphipathic alpha-helix, much like other HDMs. In S. mansoni, Sm16 is highly expressed in the cercariae and eggs but not in adult worms, suggesting that the molecule is of importance not only during skin invasion but also in the pro-inflammatory response to eggs in the liver tissues. Recombinant Sm16 and a synthetic form, Sm16 (34–117), bind to macrophages and are internalised into the endosomal/lysosomal system. Sm16 (34–117) elicited a weak pro-inflammatory response in macrophages in vitro but also suppressed the production of bacterial lipopolysaccharide (LPS)-induced inflammatory cytokines. Evaluation of the transcriptome of human macrophages treated with a synthetic Sm16 (34–117) demonstrates that the peptide exerts significant immunomodulatory effects alone, as well as in the presence of LPS. Pathways most significantly influenced by Sm16 (34–117) were those involving transcription factors peroxisome proliferator-activated receptor (PPAR) and liver X receptors/retinoid X receptor (LXR/RXR) which are intricately involved in regulating the cellular metabolism of macrophages (fatty acid, cholesterol and glucose homeostasis) and are central to inflammatory responses.

Conclusions/Significance

These results offer new insights into the structure and function of a well-known immunomodulatory molecule, Sm16, and places it within a wider family of trematode-specific small molecule HDM immune-modulators with immuno-biotherapeutic possibilities.

Instability of aquaglyceroporin (AQP) 2 contributes to drug resistance in <i>Trypanosoma brucei</i>

PLoS Neglected Tropical Diseases News - 9 July 2020 - 9:00pm

by Juan F. Quintana, Juan Bueren-Calabuig, Fabio Zuccotto, Harry P. de Koning, David Horn, Mark C. Field

Defining mode of action is vital for both developing new drugs and predicting potential resistance mechanisms. Sensitivity of African trypanosomes to pentamidine and melarsoprol is predominantly mediated by aquaglyceroporin 2 (TbAQP2), a channel associated with water/glycerol transport. TbAQP2 is expressed at the flagellar pocket membrane and chimerisation with TbAQP3 renders parasites resistant to both drugs. Two models for how TbAQP2 mediates pentamidine sensitivity have emerged; that TbAQP2 mediates pentamidine translocation across the plasma membrane or via binding to TbAQP2, with subsequent endocytosis and presumably transport across the endosomal/lysosomal membrane, but as trafficking and regulation of TbAQPs is uncharacterised this remains unresolved. We demonstrate that TbAQP2 is organised as a high order complex, is ubiquitylated and is transported to the lysosome. Unexpectedly, mutation of potential ubiquitin conjugation sites, i.e. cytoplasmic-oriented lysine residues, reduced folding and tetramerization efficiency and triggered ER retention. Moreover, TbAQP2/TbAQP3 chimerisation, as observed in pentamidine-resistant parasites, also leads to impaired oligomerisation, mislocalisation and increased turnover. These data suggest that TbAQP2 stability is highly sensitive to mutation and that instability contributes towards the emergence of drug resistance.

A spatio-temporal approach to short-term prediction of visceral leishmaniasis diagnoses in India

PLoS Neglected Tropical Diseases News - 9 July 2020 - 9:00pm

by Emily Sara Nightingale, Lloyd A. C. Chapman, Sridhar Srikantiah, Swaminathan Subramanian, Purushothaman Jambulingam, Johannes Bracher, Mary M. Cameron, Graham F. Medley

Background

The elimination programme for visceral leishmaniasis (VL) in India has seen great progress, with total cases decreasing by over 80% since 2010 and many blocks now reporting zero cases from year to year. Prompt diagnosis and treatment is critical to continue progress and avoid epidemics in the increasingly susceptible population. Short-term forecasts could be used to highlight anomalies in incidence and support health service logistics. The model which best fits the data is not necessarily most useful for prediction, yet little empirical work has been done to investigate the balance between fit and predictive performance.

Methodology/Principal findings

We developed statistical models of monthly VL case counts at block level. By evaluating a set of randomly-generated models, we found that fit and one-month-ahead prediction were strongly correlated and that rolling updates to model parameters as data accrued were not crucial for accurate prediction. The final model incorporated auto-regression over four months, spatial correlation between neighbouring blocks, and seasonality. Ninety-four percent of 10-90% prediction intervals from this model captured the observed count during a 24-month test period. Comparison of one-, three- and four-month-ahead predictions from the final model fit demonstrated that a longer time horizon yielded only a small sacrifice in predictive power for the vast majority of blocks.

Conclusions/Significance

The model developed is informed by routinely-collected surveillance data as it accumulates, and predictions are sufficiently accurate and precise to be useful. Such forecasts could, for example, be used to guide stock requirements for rapid diagnostic tests and drugs. More comprehensive data on factors thought to influence geographic variation in VL burden could be incorporated, and might better explain the heterogeneity between blocks and improve uniformity of predictive performance. Integration of the approach in the management of the VL programme would be an important step to ensuring continued successful control.

Prolonged intermittent fever and massive splenomegaly in a miner working in the tropical jungle, China

PLoS Neglected Tropical Diseases News - 9 July 2020 - 9:00pm

by Yanbin Liu, Zhiyong Zong

Prolonged fever is a particular challenge. A 47-year-old man with 5-year intermittent fever and remarkable splenomegaly was diagnosed as chronic melioidosis after splenectomy. The case would help clinicians to raise awareness and include chronic melioidosis in the differential diagnosis for patients with the travel history in melioidosis endemic regions.

Severe leptospirosis after rat bite: A case report

PLoS Neglected Tropical Diseases News - 9 July 2020 - 9:00pm

by Thais Faggion Vinholo, Guilherme S. Ribeiro, Nanci F. Silva, Jaqueline Cruz, Mitermayer G. Reis, Albert I. Ko, Federico Costa

Genetic diversity and neutral selection in <i>Plasmodium vivax</i> erythrocyte binding protein correlates with patient antigenicity

PLoS Neglected Tropical Diseases News - 9 July 2020 - 9:00pm

by Jin-Hee Han, Jee-Sun Cho, Jessica J. Y. Ong, Ji-Hoon Park, Myat Htut Nyunt, Edwin Sutanto, Hidayat Trimarsanto, Beyene Petros, Abraham Aseffa, Sisay Getachew, Kanlaya Sriprawat, Nicholas M. Anstey, Matthew J. Grigg, Bridget E. Barber, Timothy William, Gao Qi, Yaobao Liu, Richard D. Pearson, Sarah Auburn, Ric N. Price, Francois Nosten, Laurent Rénia, Bruce Russell, Eun-Taek Han

Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development. In this study, we focus on another member of EBL protein family, P. vivax erythrocyte binding protein (PvEBP). PvEBP was first identified in Cambodian (C127) field isolates and has subsequently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight countries including China (n = 4), Ethiopia (n = 24), Malaysia (n = 53), Myanmar (n = 10), Papua New Guinea (n = 16), Republic of Korea (n = 10), Thailand (n = 174), and Vietnam (n = 25). PvEBP gene exhibited four different phenotypic clusters based on the insertion/deletion (indels) variation. PvEBP-RII (179–479 aa.) showed highest polymorphism similar to other EBL family proteins in various Plasmodium species. Whereas even though PvEBP-RIII-V (480–690 aa.) was the most conserved domain, that showed strong neutral selection pressure for gene purifying with significant population expansion. Antigenicity of both of PvEBP-RII (16.1%) and PvEBP-RIII-V (21.5%) domains were comparatively lower than other P. vivax antigen which expected antigens associated with merozoite invasion. Total IgG recognition level of PvEBP-RII was stronger than PvEBP-RIII-V domain, whereas total IgG inducing level was stronger in PvEBP-RIII-V domain. These results suggest that PvEBP-RII is mainly recognized by natural IgG for innate protection, whereas PvEBP-RIII-V stimulates IgG production activity by B-cell for acquired immunity. Overall, the low antigenicity of both regions in patients with vivax malaria likely reflects genetic polymorphism for strong positive selection in PvEBP-RII and purifying selection in PvEBP-RIII-V domain. These observations pose challenging questions to the selection of EBP and point out the importance of immune pressure and polymorphism required for inclusion of PvEBP as a vaccine candidate.

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