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Coronaviruses in Brazilian bats: A matter of concern?

PLoS Neglected Tropical Diseases News - 26 October 2020 - 9:00pm

by Samuel Cibulski, Francisco Esmaile Sales de Lima, Paulo Michel Roehe

<i>Schistosoma japonicum</i> cathepsin B2 (SjCB2) facilitates parasite invasion through the skin

PLoS Neglected Tropical Diseases News - 26 October 2020 - 9:00pm

by Bingkuan Zhu, Fang Luo, Yi Shen, Wenbin Yang, Chengsong Sun, Jipeng Wang, Jian Li, Xiaojin Mo, Bin Xu, Xumin Zhang, Yongdong Li, Wei Hu

Cercariae invasion of the human skin is the first step in schistosome infection. Proteases play key roles in this process. However, little is known about the related hydrolytic enzymes in Schistosoma japonicum. Here, we investigated the biochemical features, tissue distribution and biological roles of a cathepsin B cysteine protease, SjCB2, in the invasion process of S. japonicum cercariae. Enzyme activity analysis revealed that recombinant SjCB2 is a typical cysteine protease with optimum temperature and pH for activity at 37°C and 4.0, respectively, and can be totally inhibited by the cysteine protease inhibitor E-64. Immunoblotting showed that both the zymogen (50 kDa) and mature enzyme (30.5 kDa) forms of SjCB2 are expressed in the cercariae. It was observed that SjCB2 localized predominantly in the acetabular glands and their ducts of cercariae, suggesting that the protease could be released during the invasion process. The protease degraded collagen, elastin, keratin, fibronectin, immunoglobulin (A, G and M) and complement C3, protein components of the dermis and immune system. In addition, proteomic analysis demonstrated that SjCB2 can degrade the human epidermis. Furthermore, it was showed that anti-rSjCB2 IgG significantly reduced (22.94%) the ability of the cercariae to invade the skin. The cysteine protease, SjCB2, located in the acetabular glands and their ducts of S. japonicum cercariae. We propose that SjCB2 facilitates skin invasion by degrading the major proteins of the epidermis and dermis. However, this cysteine protease may play additional roles in host-parasite interaction by degrading immunoglobins and complement protein.

Utility of entomological indices for predicting transmission of dengue virus: secondary analysis of data from the Camino Verde trial in Mexico and Nicaragua

PLoS Neglected Tropical Diseases News - 26 October 2020 - 9:00pm

by Arcadio Morales-Pérez, Elizabeth Nava-Aguilera, Carlos Hernández-Alvarez, Víctor Manuel Alvarado-Castro, Jorge Arosteguí, José Legorreta-Soberanis, Miguel Flores-Moreno, Liliana Morales-Nava, Eva Harris, Robert J. Ledogar, Neil Andersson, Anne Cockcroft

Background

Dengue vector entomological indices are widely used to monitor vector density and disease control activities. But the value of these indices as predictors of dengue infection is not established. We used data from the impact assessment of a trial of community mobilization for dengue prevention (Camino Verde) to examine the associations between vector indices and evidence of dengue infection and their value for predicting dengue infection levels. In 150 clusters in Mexico and Nicaragua, two entomological surveys, three months apart, allowed calculation of the mean Container Index, Breteau index, Pupae per Household Index, and Pupae per Container Index across the two surveys. We measured recent dengue virus infection in children, indicated by a doubling of dengue antibodies in paired saliva samples over the three-month period. We examined the associations between each of the vector indices and evidence of dengue infection at household level and at cluster level, accounting for trial intervention status. To examine the predictive value for dengue infection, we constructed receiver operating characteristic (ROC) curves at household and cluster level, considering the four vector indices as continuous variables, and calculated the positive and negative likelihood ratios for different levels of the indices. None of the vector indices was associated with recent dengue infection at household level. The Breteau Index was associated with recent infection at cluster level (Odds ratio 1.36, 95% confidence interval 1.14–1.61). The ROC curve confirmed the weak predictive value for dengue infection of the Breteau Index at cluster level. Other indices showed no predictive value. Conventional vector indices were not useful in predicting dengue infection in Mexico and Nicaragua. The findings are compatible with the idea of sources of infection outside the household which were tackled by community action in the Camino Verde trial.

Spatiotemporal transmission dynamics of co-circulating dengue, Zika, and chikungunya viruses in Fortaleza, Brazil: 2011–2017

PLoS Neglected Tropical Diseases News - 26 October 2020 - 9:00pm

by Lilit Kazazian, Antonio S. Lima Neto, Geziel S. Sousa, Osmar José do Nascimento, Marcia C. Castro

The mosquito-borne viruses dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV), now co-endemic in the Americas, pose growing threats to health worldwide. However, it remains unclear whether there exist interactions between these viruses that could shape their epidemiology. This study advances knowledge by assessing the transmission dynamics of co-circulating DENV, ZIKV, and CHIKV in the city of Fortaleza, Brazil. Spatiotemporal transmission dynamics of DENV, ZIKV, and CHIKV were analyzed using georeferenced data on over 210,000 reported cases from 2011 to 2017 in Fortaleza, Brazil. Local spatial clustering tests and space-time scan statistics were used to compare transmission dynamics across all years. The transmission of co-circulating viruses in 2016 and 2017 was evaluated at fine spatial and temporal scales using a measure of spatiotemporal dependence, the τ-statistic. Results revealed differences in the diffusion of CHIKV compared to previous DENV epidemics and spatially distinct transmission of DENV/ZIKV and CHIKV during the period of their co-circulation. Significant spatial clustering of viruses of the same type was observed within 14-day time intervals at distances of up to 6.8 km (p<0.05). These results suggest that arbovirus risk is not uniformly distributed within cities during co-circulation. Findings may guide outbreak preparedness and response efforts by highlighting the clustered nature of transmission of co-circulating arboviruses at the neighborhood level. The potential for competitive interactions between the arboviruses should be further investigated.

Sugar feeding patterns of New York <i>Aedes albopictus</i> mosquitoes are affected by saturation deficit, flowers, and host seeking

PLoS Neglected Tropical Diseases News - 26 October 2020 - 9:00pm

by Kara Fikrig, Sonile Peck, Peter Deckerman, Sharon Dang, Kimberly St Fleur, Henry Goldsmith, Sophia Qu, Hannah Rosenthal, Laura C. Harrington

Background

Sugar feeding is an important behavior which may determine vector potential of female mosquitoes. Sugar meals can reduce blood feeding frequency, enhance survival, and decrease fecundity, as well as provide energetic reserves to fuel energy intensive behaviors such as mating and host seeking. Sugar feeding behavior can be harnessed for vector control (e.g. attractive toxic sugar baits). Few studies have addressed sugar feeding of Aedes albopictus, a vector of arboviruses of public health importance, including dengue and Zika viruses. To address this knowledge gap, we assessed sugar feeding patterns of Ae. albopictus for the first time in its invasive northeastern USA range.

Methodology/Principal findings

Using the cold anthrone fructose assay with robust sample sizes, we demonstrated that a large percentage of both male (49.6%) and female (41.8%) Ae. albopictus fed on plant or homopteran derived sugar sources within 24 hrs prior to capture. Our results suggest that sugar feeding behavior increases when environmental conditions are dry (high saturation deficit) and may vary by behavioral status (host seeking vs. resting). Furthermore, mosquitoes collected on properties with flowers (>3 blooms) had higher fructose concentrations compared to those collected from properties with few to no flowers (0–3).

Conclusions/Significance

Our results provide the first evidence of Ae. albopictus sugar feeding behavior in the Northeastern US and reveal relatively high rates of sugar feeding. These results suggest the potential success for regional deployment of toxic sugar baits. In addition, we demonstrate the impact of several environmental and mosquito parameters (saturation deficit, presence of flowers, host seeking status, and sex) on sugar feeding. Placing sugar feeding behavior in the context of these environmental and mosquito parameters provides further insight into spatiotemporal dynamics of feeding behavior for Ae. albopictus, and in turn, provides information for evidence-based control decisions.

The economic impact and cost-effectiveness of combined vector-control and dengue vaccination strategies in Thailand: results from a dynamic transmission model

PLoS Neglected Tropical Diseases News - 23 October 2020 - 9:00pm

by Gerhart Knerer, Christine S. M. Currie, Sally C. Brailsford

Background and aims

Dengue fever is a major public health problem in tropical/subtropical regions. Prior economic analyses have predominantly evaluated either vaccination or vector-control programmes in isolation and do not really consider the incremental benefits and cost-effectiveness of mixed strategies and combination control. We estimated the cost-effectiveness of single and combined approaches in Thailand.

Methods

The impacts of different control interventions were analysed using a previously published mathematical model of dengue epidemiology and control incorporating seasonality, age structure, consecutive infection, cross protection, immune enhancement and combined vector-host transmission. An economic model was applied to simulation results to estimate the cost-effectiveness of 4 interventions and their various combinations (6 strategies): i) routine vaccination of 1-year olds; ii) chemical vector control strategies targeting adult and larval stages separately; iii) environmental management/ public health education and awareness [EM/ PHEA]). Payer and societal perspectives were considered. The health burden of dengue fever was assessed using disability-adjusted life-years (DALYs) lost. Costs and effects were assessed for 10 years. Costs were discounted at 3% annually and updated to 2013 United States Dollars. Incremental cost-effectiveness analysis was carried out after strategies were rank-ordered by cost, with results presented in a table of incremental analysis. Sensitivity and scenario analyses were undertaken; and the impact and cost-effectiveness of Wolbachia was evaluated in exploratory scenario analyses.

Results

From the payer and societal perspectives, 2 combination strategies were considered optimal, as all other control strategies were dominated. Vaccination plus adulticide plus EM/ PHEA was deemed cost-effective according to multiple cost-effectiveness criteria. From the societal perspective, incremental differences vs. adulticide and EM/ PHEA resulted in costs of $157.6 million and DALYs lost of 12,599, giving an expected ICER of $12,508 per DALY averted. Exploratory scenario analyses showed Wolbachia to be highly cost-effective ($343 per DALY averted) vs. other single control measures.

Conclusions

Our model shows that individual interventions can be cost-effective, but that important epidemiological reductions and economic impacts are demonstrated when interventions are combined as part of an integrated approach to combating dengue fever. Exploratory scenario analyses demonstrated the potential epidemiological and cost-effective impact of Wolbachia when deployed at scale on a nationwide basis. Our findings were robust in the face of sensitivity analyses.

Meta-analysis of predictive symptoms for Ebola virus disease

PLoS Neglected Tropical Diseases News - 23 October 2020 - 9:00pm

by Vageesh Jain, Andre Charlett, Colin S. Brown

Introduction

One of the leading challenges in the 2013–2016 West African Ebola virus disease (EVD) outbreak was how best to quickly identify patients with EVD, separating them from those without the disease, in order to maximise limited isolation bed capacity and keep health systems functioning.

Methodology

We performed a systematic literature review to identify all published data on EVD clinical symptoms in adult patients. Data was dual extracted, and random effects meta-analysis performed for each symptom to identify symptoms with the greatest risk for EVD infection.

Results

Symptoms usually presenting late in illness that were more than twice as likely to predict a diagnosis of Ebola, were confusion (pOR 3.04, 95% CI 2.18–4.23), conjunctivitis (2.90, 1.92–4.38), dysphagia (1.95, 1.13–3.35) and jaundice (1.86, 1.20–2.88). Early non-specific symptoms of diarrhoea (2.99, 2.00–4.48), fatigue (2.77, 1.59–4.81), vomiting (2.69, 1.76–4.10), fever (1.97, 1.10–4.52), muscle pain (1.65, 1.04–2.61), and cough (1.63, 1.24–2.14), were also strongly associated with EVD diagnosis.

Conclusions

The existing literature fails to provide a unified position on the symptoms most predictive of EVD, but highlights some early and late stage symptoms that in combination will be useful for future risk stratification. Confirmation of these findings across datasets (or ideally an aggregation of all individual patient data) will aid effective future clinical assessment, risk stratification tools and emergency epidemic response planning.

Molecular xenomonitoring of diurnally subperiodic <i>Wuchereria bancrofti</i> infection in <i>Aedes (Downsiomyia) niveus</i> (Ludlow, 1903) after nine rounds of Mass Drug Administration in Nancowry Islands, Andaman and Nicobar Islands, India

PLoS Neglected Tropical Diseases News - 23 October 2020 - 9:00pm

by Addepalli Premkumar, Ananganallur Nagarajan Shriram, Kaliannagounder Krishnamoorthy, Swaminathan Subramanian, Venkatesan Vasuki, Paluru Vijayachari, Purushothaman Jambulingam

A group of four human inhabited Nancowry Islands in Nicobar district in the Andaman and Nicobar Islands, India having a population of 7674 is the lone focus of diurnally sub-periodic Wuchereria bancrofti (DspWB) that is transmitted by Aedes niveus (Ludlow). Microfilaria (Mf) prevalence was above 1% even after nine rounds of Mass Drug Administration (MDA) with DEC and albendazole. Molecular xenomonitoring (MX) was conducted to identify appropriate vector sampling method and assess the impact. BioGents Sentinel traps, gravid traps and human baited double bed nettraps were used in three locations in each village to collect Aedes niveus female mosquitoes. Subsequently daytime man landing collections (MLC) were carried out in all the 25 villages in the islands. Collections were compared in terms of the number of vector mosquitoes captured per trap collection. Females of Ae. niveus were pooled, dried and processed for detecting filarial parasite DNA using RT-PCR assay. Vector infection rate was estimated using PoolScreen software. Only 393 female mosquitoes including 44 Ae. niveus (11.2%) were collected from 459 trap collections using three trapping devices. From 151 MLCs, 2170 Ae. niveus female mosquitoes were collected. The average prevalence of W. bancrofti DNA was 0.43%. Estimated upper 95% CI exceeded the provisional prevalence threshold of 0.1% in all the villages, indicating continued transmission as observed in Mf survey. MLCs could be the choice, for now, to sample Ae. niveus mosquitoes. The PCR assay used in MX for nocturnally periodic bancroftian filariasis could be adopted for DspWB. The vector-parasite MX, can be used to evaluate interventions in this area after further standardization of the protocol.

Body location of “New World” cutaneous leishmaniasis lesions and its impact on the quality of life of patients in Suriname

PLoS Neglected Tropical Diseases News - 23 October 2020 - 9:00pm

by Ricardo V. P. F. Hu, Sahienshadebie Ramdas, Pythia Nieuwkerk, Ria Reis, Rudy F. M. Lai A Fat, Henry J. C. de Vries, Henk D. F. H. Schallig

Cutaneous leishmaniasis (CL) is a chronic skin infection caused by Leishmania parasites, causing single or multiple skin nodules and ulcers on the exposed body locations. Healing of lesions is followed by scar formation. Active and healed CL lesions may affect patient’s health related quality of life (HRQL). The aim of this study was to determine whether the body location of the leishmaniasis lesions affects the HRQL of localized CL patients in Suriname. The HRQL of 163 patients with CL was assessed by Skindex-29 and EQ-5D/VAS questionnaires. Forty-six patients out of the total study population also participated in a qualitative anthropological study involving in depth interviews. All patients were allocated in 4 groups in the following hierarchy: head and face, upper limbs, lower limbs and trunk. Patients with lesions on the lower limbs had significantly higher Skindex-29 scores, indicating worse HRQL, in the symptom scale compared to lesions on head/face and trunk. The lower limb group was more likely to report problems in the dimensions self-care, mobility, daily activities and pain/discomfort of the EQ-5D. Little to no social stigma was reported in the in-depth interviews. The findings of this study indicate that Surinamese patients with CL lesions located on the lower limbs had more impairment in HRQL than on other body locations. Stigma related to CL seems to be virtually absent in Suriname.

Elimination of STH morbidity in Zimbabwe: Results of 6 years of deworming intervention for school-age children

PLoS Neglected Tropical Diseases News - 23 October 2020 - 9:00pm

by Nicholas Midzi, Antonio Montresor, Masceline J. Mutsaka-Makuvaza, Claudio Fronterre, Portia Manangazira, Isaac Phiri, Olatunji Johnson, Gibson Mhlanga, Peter J. Diggle

This paper reports the prevalence and intensity of soil-transmitted helminth (STH) infections measured in Zimbabwe before and after a control intervention based on annual deworming of school-age children (SAC) conducted from 2012 to 2018. In 2010, epidemiological data were collected from 13 195 SAC in 255 randomly selected schools in all districts nationwide using, as diagnostic methods, the Kato–Katz and the formal ether stool concentration technique. At follow up, conducted in 2017, only Kato–Katz was performed; specimens were collected from 13 352 children in 336 schools. The data were evaluated using a geospatial approach. The national prevalence of STH infection in SAC was estimated at 5.8% at baseline, with 0.8% of infections of moderate and heavy intensity. Preventive chemotherapy (PC) targeted all 2.5 million children of school age enrolled in Zimbabwe, with coverage ranging from 49% to 85%. At follow up, national prevalence of STH in SAC was estimated at 0.8%; infections of moderate and heavy intensity almost disappeared (0.1% prevalence). As a result, Zimbabwe can suspend deworming activities in 54 districts and reduce the frequency of PC in the remaining six districts. The total amount of albendazole tablets needed will be approximately 100 000 a year.

Prostaglandins regulate humoral immune responses in <i>Aedes aegypti</i>

PLoS Neglected Tropical Diseases News - 23 October 2020 - 9:00pm

by Ana Beatriz Ferreira Barletta, Thiago Luiz Alves e Silva, Octavio A. C. Talyuli, Tatiana Luna-Gomes, Shuzhen Sim, Yesseinia Angleró-Rodríguez, George Dimopoulos, Christianne Bandeira-Melo, Marcos H. Ferreira Sorgine

Prostaglandins (PGs) are immuno-active lipids that mediate the immune response in invertebrates and vertebrates. In insects, PGs play a role on different physiological processes such as reproduction, ion transport and regulation of cellular immunity. However, it is unclear whether PGs play a role in invertebrate's humoral immunity, and, if so, which immune signaling pathways would be modulated by PGs. Here, we show that Aedes aegypti gut microbiota and Gram-negative bacteria challenge induces prostaglandin production sensitive to an irreversible inhibitor of the vertebrate cyclooxygenase, acetylsalicylic acid (ASA). ASA treatment reduced PG synthesis and is associated with decreased expression of components of the Toll and IMD immune pathways, thereby rendering mosquitoes more susceptible to both bacterial and viral infections. We also shown that a cytosolic phospholipase (PLAc), one of the upstream regulators of PG synthesis, is induced by the microbiota in the midgut after blood feeding. The knockdown of the PLAc decreased prostaglandin production and enhanced the replication of Dengue in the midgut. We conclude that in Ae. aegypti, PGs control the amplitude of the immune response to guarantee an efficient pathogen clearance.

Development of a multiplex microsphere immunoassay for the detection of antibodies against highly pathogenic viruses in human and animal serum samples

PLoS Neglected Tropical Diseases News - 23 October 2020 - 9:00pm

by Rebecca Surtees, Daniel Stern, Katharina Ahrens, Nicole Kromarek, Angelika Lander, Petra Kreher, Sabrina Weiss, Roger Hewson, Emma K. Punch, John N. Barr, Peter T. Witkowski, Emmanuel Couacy-Hymann, Andrea Marzi, Brigitte G. Dorner, Andreas Kurth

Surveillance of highly pathogenic viruses circulating in both human and animal populations is crucial to unveil endemic infections and potential zoonotic reservoirs. Monitoring the burden of disease by serological assay could be used as an early warning system for imminent outbreaks as an increased seroprevalance often precedes larger outbreaks. However, the multitude of highly pathogenic viruses necessitates the need to identify specific antibodies against several targets from both humans as well as from potential reservoir animals such as bats. In order to address this, we have developed a broadly reactive multiplex microsphere immunoassay (MMIA) for the detection of antibodies against several highly pathogenic viruses from both humans and animals. To this aim, nucleoproteins (NP) of Ebola virus (EBOV), Marburg virus (MARV) and nucleocapsid proteins (NP) of Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus and Dobrava-Belgrade hantavirus were employed in a 5-plex assay for IgG detection. After optimisation, specific binding to each respective NP was shown by testing sera from humans and non-human primates with known infection status. The usefulness of our assay for serosurveillance was shown by determining the immune response against the NP antigens in a panel of 129 human serum samples collected in Guinea between 2011 and 2012 in comparison to a panel of 88 sera from the German blood bank. We found good agreement between our MMIA and commercial or in-house reference methods by ELISA or IIFT with statistically significant higher binding to both EBOV NP and MARV NP coupled microspheres in the Guinea panel. Finally, the MMIA was successfully adapted to detect antibodies from bats that had been inoculated with EBOV- and MARV- virus-like particles, highlighting the versatility of this technique and potentially enabling the monitoring of wildlife as well as human populations with this assay. We were thus able to develop and validate a sensitive and broadly reactive high-throughput serological assay which could be used as a screening tool to detect antibodies against several highly pathogenic viruses.

How to choose the best control strategy? Mathematical models as a tool for pre-intervention evaluation on a macroparasitic disease

PLoS Neglected Tropical Diseases News - 22 October 2020 - 9:00pm

by Elisa Fesce, Claudia Romeo, Eleonora Chinchio, Nicola Ferrari

During the last century, emerging diseases have increased in number, posing a severe threat for human health. Zoonoses, in particular, represent the 60% of emerging diseases, and are a big challenge for public health due to the complexity of their dynamics. Mathematical models, by allowing an a priori analysis of dynamic systems and the simulation of different scenarios at once, may represent an efficient tool for the determination of factors and phenomena involved in zoonotic infection cycles, but are often underexploited in public health. In this context, we developed a deterministic mathematical model to compare the efficacy of different intervention strategies aimed at reducing environmental contamination by macroparasites, using raccoons (Procyon lotor) and their zoonotic parasite Bayilsascaris procyonis as a model system. The three intervention strategies simulated are raccoon depopulation, anthelmintic treatment of raccoons and faeces removal. Our results show that all these strategies are able to eliminate the parasite egg population from the environment, but they are effective only above specific threshold coverages. Host removal and anthelmintic treatment showed the fastest results in eliminating the egg population, but anthelmintic treatment requires a higher effort to reach an effective result compared to host removal. Our simulations show that mathematical models can help to shed light on the dynamics of communicable infectious diseases, and give specific guidelines to contain B. procyonis environmental contamination in native, as well as in new, areas of parasite emergence. In particular, the present study highlights that identifying in advance the appropriate treatment coverage is fundamental to achieve the desired results, allowing for the implementation of cost- and time-effective intervention strategies.

Inducible nitric oxide synthase blockade with aminoguanidine, protects mice infected with <i>Nocardia brasiliensis</i> from actinomycetoma development

PLoS Neglected Tropical Diseases News - 22 October 2020 - 9:00pm

by Mario C. Salinas-Carmona, Ossian Longoria-Lozano, Humberto R. Garza-Esquivel, Juan López-Ulloa, Jorge Reyes-Carrillo, Anna Velia Vázquez-Marmolejo

Mycetoma is a chronic infectious disease that can be caused by fungi or bacteria, Madurella mycetomatis and Nocardia brasiliensis are frequent etiologic agents of this disease. Mycetoma produced by bacteria is known as actinomycetoma. In mycetoma produced by fungi (eumycetoma) and actinomycetoma, diagnosis of the disease is based on clinical findings: severe inflammation, with deformities of affected tissues, abscesses, fistulae, sinuses and discharge of purulent material that contains micro colonies of the etiologic agent. Microscopic examination of infected tissue is similar regardless of the offending microbe; hallmark of infected tissue is severe inflammation with abundant neutrophils around micro colonies and granuloma formation with macrophages, lymphocytes, dendritic and foamy cells. Even though medical treatment is available for mycetoma patients, amputation, or surgical intervention is frequently needed. The pathogenesis of actinomycetoma is little known, most information was obtained from experimental animal models infected with bacteria. In other experimental mice infections with different microbes, it was demonstrated that nitric oxide is responsible for the intracellular killing of Mycobacterium tuberculosis by activated macrophages. Nitric oxide is a free radical with potent stimulatory and suppressive effects in innate and adaptive immunity. The unstable nitric oxide molecule is produced by action of nitric oxide synthases on L-arginine. There are three nitric oxide synthases expressed in different cells and tissues, two are constitutively expressed one in neurons, and the other in endothelial cells and one that is inducible in macrophages. Aminoguanidine is a competitive inhibitor of inducible nitric oxide synthase. Its administration in experimental animals may favor or harm them. We used aminoguanidine in mice infected with Nocardia brasiliensis, and demonstrated that all treated animals were protected from actinomycetoma development. Anti N. brasiliensis antibodies and T cell proliferation were not affected, but inflammation was reduced.

Development of a bio-inkjet printed LAMP test kit for detecting human African trypanosomiasis

PLoS Neglected Tropical Diseases News - 22 October 2020 - 9:00pm

by Kyoko Hayashida, Peter Nambala, Nick Van Reet, Philippe Büscher, Naoko Kawai, Mable Mwale Mutengo, Janelisa Musaya, Boniface Namangala, Chihiro Sugimoto, Junya Yamagishi

Human African trypanosomiasis (HAT) is one of the neglected tropical diseases in sub-Saharan Africa. Early diagnosis and treatment prior to disease progression are crucial for the survival of HAT patients. We had previously established a loop-mediated isothermal amplification (LAMP) method for HAT diagnosis in which the reagents were dried for field-use purposes. In this study, we used a semi-automated process to produce the test tubes using a bio-inkjet printer to achieve an accurate production. The performance of the inkjet printer-produced dried LAMP test (CZC-LAMP) was found to be stable after storage for up to 180 days at 30 °C. The diagnostic accuracy of CZC-LAMP HAT was evaluated using DNA samples that were extracted from 116 Trypanosoma brucei gambiense patients and 66 T. b. rhodesiense patients. The sensitivity was 72% for T. b. gambiense (95%CI: 63%–80%) and 80% for T. b. rhodesiense (95%CI: 69%–89%). The specificity determined using DNA from 116 endemic control DNA samples was 95% (95%CI: 89%–98%). The performance of the CZC-LAMP HAT and CZC-LAMP rHAT were also evaluated using 14 crude blood lysate samples obtained from T. b. rhodesiense patients and endemic control samples collected from Rumphi District in Malawi. The sensitivity and specificity were both 100% (95%CI: 77%–100%). As the developed CZC-LAMP test does not require a cold chain or a sophisticated laboratory, it holds promise for use as a routine simple molecular tool for point-of-care HAT diagnosis in endemic areas.

Animal models of congenital zika syndrome provide mechanistic insight into viral pathogenesis during pregnancy

PLoS Neglected Tropical Diseases News - 22 October 2020 - 9:00pm

by Harish Narasimhan, Anna Chudnovets, Irina Burd, Andrew Pekosz, Sabra L. Klein

In utero Zika virus (ZIKV; family Flaviviridae) infection causes a distinct pattern of birth defects and disabilities in the developing fetus and neonate that has been termed congenital zika syndrome (CZS). Over 8,000 children were affected by the 2016 to 2017 ZIKV outbreak in the Americas, many of whom developed CZS as a result of in utero exposure. To date, there is no consensus about how ZIKV causes CZS; animal models, however, are providing mechanistic insights. Using nonhuman primates, immunocompromised mice, immunocompetent mice, and other animal models (e.g., pigs, sheep, guinea pigs, and hamsters), studies are showing that maternal immunological responses, placental infection and inflammation, as well as viral genetic factors play significant roles in predicting the downstream consequences of in utero ZIKV infection on the development of CZS in offspring. There are thousands of children suffering from adverse consequences of CZS. Therefore, the animal models developed to study ZIKV-induced adverse outcomes in offspring could provide mechanistic insights into how other viruses, including influenza and hepatitis C viruses, impact placental viability and fetal growth to cause long-term adverse outcomes in an effort to identify therapeutic treatments.

The neglected challenge: Vaccination against rickettsiae

PLoS Neglected Tropical Diseases News - 22 October 2020 - 9:00pm

by Anke Osterloh

Over the last decades, rickettsioses are emerging worldwide. These diseases are caused by intracellular bacteria. Although rickettsioses can be treated with antibiotics, a vaccine against rickettsiae is highly desired for several reasons. Rickettsioses are highly prevalent, especially in poor countries, and there are indications of the development of antibiotic resistance. In addition, some rickettsiae can persist and cause recurrent disease. The development of a vaccine requires the understanding of the immune mechanisms that are involved in protection as well as in immunopathology. Knowledge about these immune responses is accumulating, and efforts have been undertaken to identify antigenic components of rickettsiae that may be useful as a vaccine. This review provides an overview on current knowledge of adaptive immunity against rickettsiae, which is essential for defense, rickettsial antigens that have been identified so far, and on vaccination strategies that have been used in animal models of rickettsial infections.

Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses

PLoS Neglected Tropical Diseases News - 22 October 2020 - 9:00pm

by James Fisher, Galen Card, Lynn Soong

Scrub typhus and spotted fever rickettsioses (SFR) are understudied, vector-borne diseases of global significance. Over 1 billion individuals are at risk for scrub typhus alone in an endemic region, spanning across eastern and southern Asia to Northern Australia. While highly treatable, diagnostic challenges make timely antibiotic intervention difficult for these diseases. Delayed therapy may lead to severe outcomes affecting multiple organs, including the central nervous system (CNS), where infection and associated neuroinflammation may be lethal or lead to lasting sequelae. Meningitis and encephalitis are prevalent in both scrub typhus and SFR. Additionally, case reports detailing focal neurological deficits have come to light, with attention to both acute and chronic sequelae of infection. Despite the increasing number of clinical reports outlining neurologic consequences of these diseases, relatively little research has examined underlying mechanisms of neuroinflammation. Animal models of scrub typhus have identified cerebral T-cell infiltration and vascular damage associated with endothelial infection and neuropathogenesis. Differential gene expression analysis of brain tissues during murine scrub typhus have revealed selective increases in CXCR3 ligands, proinflammatory and type-1 cytokines and chemokines, and cytotoxicity molecules, as well as alterations in the complement pathway. In SFR, microglial expansion and macrophage infiltration contribute to neurological disease progression. This narrative Review highlights clinical neurologic features of scrub typhus and SFR and evaluates our current understanding of basic research into neuroinflammation for both diseases in animal models. Further investigation into key mediators of neuropathogenesis may yield prognostic markers and treatment regimens for severe patients.

Quantifying and mapping the burden of human and animal rabies in Iraq

PLoS Neglected Tropical Diseases News - 22 October 2020 - 9:00pm

by Mashair Z. Ismail, Najlaa K. AL- Hamdi, Ali N. AL- Amery, Denise A. Marston, Lorraine McElhinney, Emma Taylor, Victor del Rio Vilas, Thani M. Dadan, Anthony R. Fooks, Daniel L. Horton

Rabies was first reported in ancient Iraqi civilizations, yet it remains a poorly quantified and important public health threat in the region. Efforts to control rabies in Iraq including dog population control, and vaccination of livestock and dogs, have increased since 2010. Officially reported data on human rabies, dog bites, and animal rabies cases between 2012 and 2017 are analysed here to assess the effect of existing control efforts, to inform future strategies, and to highlight gaps in surveillance and reporting. The results of molecular characterization of 32 viruses from animal cases from throughout Iraq are presented, to improve the understanding of rabies dynamics in the animal reservoir. Although annual numbers of reported human cases were lower in the period between 2012 and 2017 than prior to 2010, human cases continue. There was a distinct gender and age bias among human cases with nine cases in males for every one female and twice as many cases in children than adults. Spatial clustering analysis and phylogenetic evidence suggests rabies is endemic throughout the country, with no regional variation in risk, but better surveillance and reporting is required to underpin control strategies.

What are the implications of Zika Virus for infant feeding? A synthesis of qualitative evidence concerning Congenital Zika Syndrome (CZS) and comparable conditions

PLoS Neglected Tropical Diseases News - 21 October 2020 - 9:00pm

by Christopher Carroll, Andrew Booth, Fiona Campbell, Clare Relton

If a mother contracts the Zika Virus before or during pregnancy, then there is a risk of the child developing Congenital Zika Syndrome (CZS). An infant can then experience problems feeding due to the specific physical and developmental consequences of Congenital Zika Syndrome (CZS), such as microcephaly, dysphagia and an increased likelihood of choking. This qualitative evidence synthesis accesses direct and indirect evidence to inform WHO infant feeding guidelines. We conducted a qualitative evidence synthesis of the values and preferences of relevant stakeholders (e.g. pregnant women, mothers, family members and health practitioners) concerning infant (0–2 years) feeding in the presence of: 1) CZS (the‘direct evidence’); 2) severe disability and nonprogressive, chronic encephalopathies (‘indirect evidence’), which present with similar problems. Authors’ findings were extracted, synthesised using thematic synthesis techniques, and confidence in the findings were assessed using GRADE-CERQual. Six CZS-specific studies (all from Brazil) were included in the direct evidence, with a further eight indirect studies reporting feeding difficulties in infants with severe disability and nonprogressive, chronic encephalopathies. Included studies highlighted: breast-feeding represented the preference for all mothers in the studies in both reviews, and the inability to do so affected bonding between parents and child, and generated fear and anxiety relating to feeding choices, especially around the risks of choking and swallowing; the perception that health professionals were often unable to offer appropriate advice; the potential value of training; and a strong desire to achieve individual maternal autonomy in infant feeding decisions. Confidence in most findings ranged from low to moderate. The evidence base has limitations, but consistently reported that parents of children with feeding difficulties due to Congenital Zika Syndrome, or similar, need information, advice and counselling, and substantial emotional support. Parents perceive that these needs are often neither recognised nor satisfied; optimal feeding and support strategies for this population have not yet been identified.

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