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Detection of Crimean-Congo Haemorrhagic Fever cases in a severe undifferentiated febrile illness outbreak in the Federal Republic of Sudan: a retrospective epidemiological and diagnostic cohort study

PLoS Neglected Tropical Diseases News - 10 July 2019 - 9:00pm

by Hilary Bower, Mubarak El Karsany, Mazza Alzain, Benedict Gannon, Rehab Mohamed, Iman Mahmoud, Mawahib Eldegail, Rihab Taha, Abdalla Osman, Salim Mohamednour, Amanda Semper, Barry Atkinson, Daniel Carter, Stuart Dowall, Jenna Furneaux, Victoria Graham, Jack Mellors, Jane Osborne, Steven T. Pullan, Gillian S. Slack, Tim Brooks, Roger Hewson, Nicholas J. Beeching, Jimmy Whitworth, Daniel G. Bausch, Tom E. Fletcher

Background

Undifferentiated febrile illness (UFI) is one of the most common reasons for people seeking healthcare in low-income countries. While illness and death due to specific infections such as malaria are often well-quantified, others are frequently uncounted and their impact underappreciated. A number of high consequence infectious diseases, including Ebola virus, are endemic or epidemic in the Federal Republic of Sudan which has experienced at least 12 UFI outbreaks, frequently associated with haemorrhage and high case fatality rates (CFR), since 2012. One of these occurred in Darfur in 2015/2016 with 594 cases and 108 deaths (CFR 18.2%). The aetiology of these outbreaks remains unknown.

Methodology/Principal findings

We report a retrospective cohort study of the 2015/2016 Darfur outbreak, using a subset of 65 of 263 outbreak samples received by the National Public Health Laboratory which met selection criteria of sufficient sample volume and epidemiological data. Clinical features included fever (95.8%), bleeding (95.7%), headache (51.6%) and arthralgia (42.2%). No epidemiological patterns indicative of person-to-person transmission or health-worker cases were reported. Samples were tested at the Public Health England Rare and Imported Pathogens Laboratory using a bespoke panel of likely pathogens including haemorrhagic fever viruses, arboviruses and Rickettsia, Leptospira and Borrelia spp. Seven (11%) were positive for Crimean-Congo haemorrhagic fever virus (CCHFV) by real-time reverse transcription PCR. The remaining samples tested negative on all assays.

Conclusions/Significance

CCHFV is an important cause of fever and haemorrhage in Darfur, but not the sole major source of UFI outbreaks in Sudan. Prospective studies are needed to explore other aetiologies, including novel pathogens. The presence of CCHFV has critical infection, prevention and control as well as clinical implications for future response. Our study reinforces the need to boost surveillance, lab and investigative capacity to underpin effective response, and for local and international health security.

Isolation and characterization of trypanosomatids, including <i>Crithidia mellificae</i>, in bats from the Atlantic Forest of Rio de Janeiro, Brazil

PLoS Neglected Tropical Diseases News - 10 July 2019 - 9:00pm

by Diana Azeredo Rangel, Cristiane Varella Lisboa, Roberto Leonan Morim Novaes, Bruno Alves Silva, Renan de França Souza, Ana Maria Jansen, Ricardo Moratelli, André Luiz Rodrigues Roque

We studied infection by Trypanosomatidae in bats captured in two areas with different degradation levels in the Atlantic Forest of Rio de Janeiro state: Reserva Ecológica de Guapiaçu (REGUA) and Estação Fiocruz Mata Atlântica (EFMA). Furthermore, we evaluated whether the diversity of trypanosomatids changes according to bat diversity and the different levels of preservation in the region. The results showed no influence of the level of preservation on bat species richness (15 and 14 species, respectively), with similar chiropterofauna and higher abundance of two common fruit-eating bat species in the tropics: Carollia perspicillata and Artibeus lituratus. Of the 181 bat specimens analyzed by LIT/Schneider hemoculture, we detected 24 infected individuals (13%), including one positive Sturnira lilium individual that was also positive by fresh blood examination. Molecular characterization using nested PCR targeting the 18 SSU rRNA-encoding gene fragment showed similar trypanosomatid infection rates in bats from the two areas: 15% in REGUA and 11% in EFMA (p = 0.46). Trypanosoma dionisii was the most frequently detected parasite (54%), followed by T. cruzi DTUs TcI and TcIV and Trypanosoma sp., in Neotropical phyllostomid bats (RNMO63 and RNMO56); mixed infections by T. dionisii/T. cruzi TcIII and T. dionisii/T. cruzi TcI were also observed. The T. cruzi DTUs TcI and TcIV are the genotypes currently involved in cases of acute Chagas disease in Brazil, and T. dionisii was recently found in the heart tissue of an infected child. Surprisingly, we also describe for the first time Crithidia mellificae, a putative monoxenous parasite from insects, infecting a vertebrate host in the Americas. Bats from the Atlantic Forest of Rio de Janeiro state harbor a great diversity of trypanosomatids, maintaining trypanosomatid diversity in this sylvatic environment.

The monetary burden of cysticercosis in Mexico

PLoS Neglected Tropical Diseases News - 10 July 2019 - 9:00pm

by Rachana Bhattarai, Hélène Carabin, Jefferson V. Proaño, Jose Flores-Rivera, Teresa Corona, Ana Flisser, Leith León-Maldonado, Christine M. Budke

Background

Taenia solium cysticercosis is a public health and agricultural problem in many low and middle-income countries where health education, sanitation, pig management practices and meat inspection infrastructure are insufficient. Cysticercosis affects both human and animal health and has important economic consequences. Very few studies have been conducted to evaluate the monetary burden of cysticercosis. This study aimed at estimating the 2015 costs associated with cysticercosis in humans and pigs in Mexico.

Methods

The monetary burden of human cysticercosis was estimated based on costs incurred by living with and treating epilepsy and severe chronic headaches associated with neurocysticercosis (NCC). The estimated cost of porcine cysticercosis took into consideration losses due to the reduction in the price of cysticercosis-infected animals. Epidemiologic and economic data were obtained from the published literature, government reports, and setting-specific questionnaires. Latin hypercube sampling methods were employed to sample the distributions of uncertain parameters and to estimate 95% credible regions (95% CRs). All results are reported in 2015 U.S.$.

Findings

The overall monetary burden associated with NCC morbidity was estimated at U.S.$215,775,056 (95% CR U.S.$109,309,560 –U.S.$361,924,224), with U.S.$436 (95% CR: U.S.$296 –U.S.$604) lost per patient. If loss of future years of income and productivity due to NCC-associated deaths was included, this value increased by U.S.$54.26 million, assuming that these individuals earned Mexico’s median wage salary. An additional U.S.$19,507,171 (95% CR U.S.$5,734,782 –U.S.$35,913,487) was estimated to be lost due to porcine cysticercosis.

Conclusions

This study suggests that T. solium cysticercosis results in considerable monetary losses to Mexico.

Modelling targeted rabies vaccination strategies for a domestic dog population with heterogeneous roaming patterns

PLoS Neglected Tropical Diseases News - 8 July 2019 - 9:00pm

by Emily G. Hudson, Victoria J. Brookes, Salome Dürr, Michael P. Ward

Australia is currently canine rabies free. However, communities located on the northern coastline–such as the Northern Peninsula Area (NPA), Queensland–are at risk of an incursion due to their large populations of susceptible free-roaming dogs and proximity to rabies-infected Indonesian islands. A rabies-spread model was used to simulate potential outbreaks and evaluate various disease control strategies. A heterogeneous contact structure previously described in the population of interest–explorer dogs, roamer dogs and stay-at-home dogs–was incorporated into the model using six spatial kernels describing contacts between dog roaming categories. Twenty-seven vaccination strategies were investigated based on a complete block design of 50%, 70% and 90% coverage for each of the three roaming categories to simulate various targeted vaccination strategies. The 27 strategies were implemented in four population structures in which the proportion of dogs in each category varied–explorer dominant, roamer dominant, stay-at-home dominant and a field population (based on field estimates of population structure). The overall vaccination coverage varied depending on the subpopulation targeted for vaccination and the population structure modelled. A total of 108 scenarios were simulated 2000 times and the model outputs (outbreak size and duration) were compared to Strategy 14 (a standard recommended overall 70% vaccination coverage). In general, targeting explorer dogs–and to a lesser extent roamer dogs–produced similar outbreaks to Strategy 14 but with a lower overall vaccination coverage. Similarly, strategies that targeted stay-at-home dogs required a higher vaccination coverage to produce significantly smaller and shorter outbreaks. This study provides some theoretical evidence that targeting subpopulations of dogs for vaccination based on their roaming behaviours (and therefore risk of rabies transmission) could be more efficient than blanket 70% vaccination campaigns. Such information can be used in preparedness planning to help improve control of a potential rabies incursion in Australia.

Absence of accessory genes in a divergent simian T-lymphotropic virus type 1 isolated from a bonnet macaque (<i>Macaca radiata</i>)

PLoS Neglected Tropical Diseases News - 8 July 2019 - 9:00pm

by Philippe V. Afonso, Zahra Fagrouch, Martin Deijs, Henk Niphuis, Willy Bogers, Antoine Gessain, Lia van der Hoek, Ernst J. Verschoor

Background

Primate T-lymphotropic viruses type 1 (PTLV-1) are complex retroviruses infecting both human (HTLV-1) and simian (STLV-1) hosts. They share common epidemiological, clinical and molecular features. In addition to the canonical gag, pol, env retroviral genes, PTLV-1 purportedly encodes regulatory (i.e. Tax, Rex, and HBZ) and accessory proteins (i.e. P12/8, P13, P30). The latter have been found essential for viral persistence in vivo.

Methodology/Principal findings

We have isolated a STLV-1 virus from a bonnet macaque (Macaca radiata–Mra18C9), a monkey from India. The complete sequence was obtained and phylogenetic analyses were performed. The Mra18C9 strain is highly divergent from the known PTLV-1 strains. Intriguingly, the Mra18C9 lacks the 3 accessory open reading frames. In order to determine if the absence of accessory proteins is specific to this particular strain, a comprehensive analysis of the complete PTLV-1 genomes available in Genbank was performed and found that the lack of one or many accessory ORF is common among PTLV-1.

Conclusion

This study raises many questions regarding the actual nature, role and importance of accessory proteins in the PTLV-1 biology.

The impact of acute adenolymphangitis in podoconiosis on caregivers: A case study in Wayu Tuka woreda, Oromia, Western Ethiopia. ‘<i>If she was healthy</i>, <i>I would be free</i>.’

PLoS Neglected Tropical Diseases News - 8 July 2019 - 9:00pm

by Clare Phillips, Abdi Samuel, Gemechu Tiruneh, Kebede Deribe, Gail Davey

Background

Podoconiosis, also known as mossy foot or endemic non-filarial elephantiasis, is a preventable form of lower-leg lymphoedema caused by prolonged (typically barefoot) exposure to soil derived from volcanic rocks. Acute adenolymphangitis (also called ‘acute attack’) is a serious complication of podoconiosis resulting in significant symptoms and worsening disability. Despite the well-known morbidity associated with podoconiosis, to date there have been no studies looking at the impact, or burden, of podoconiosis on caregivers. This study explored the experiences and impact of acute attacks on the caregivers of those with podoconiosis in one endemic district of Ethiopia.

Methods/Principal findings

This qualitative study was based in Wayu Tuka woreda (district), Oromia, Western Ethiopia. 27 semi-structured interviews of those with podoconiosis and their caregivers were conducted in June 2018. Here we report the findings from the caregiver’s interviews. Data were analysed using NVivo 12. Directed content analysis, a qualitative approach related to thematic analysis, was used to analyse the results. This study highlights a previously unreported impact of acute attacks on the caregivers of those affected by podoconiosis. The findings demonstrate the significant social and financial pressures placed on podoconiosis-affected families which are exacerbated during acute attacks. This study also highlighted the emotional burden experienced by caregivers, the range of care activities placed on them and the limited support available.

Conclusions

This study found a significant impact on the caregivers of those with podoconiosis, especially during acute attacks, in in Wayu Tuka woreda. It also highlighted the limited support available to caregivers. Further research is needed to understand whether this impact applies to podoconiosis caregivers across Ethiopia, and beyond, and to establish if there are wider implications of this important consequence of podoconiosis, for example on the economy and caregivers’ mental and physical health.

Development of multiplex PCR for neglected infectious diseases

PLoS Neglected Tropical Diseases News - 8 July 2019 - 9:00pm

by Nutchanart Sea-liang, Amornpun Sereemaspun, Kanitha Patarakul, Jariyanart Gaywee, Wuttikon Rodkvamtook, Nattachai Srisawat, Supaporn Wacharaplusadee, Thiravat Hemachudha

Scrub typhus, murine typhus, and leptospirosis are widely neglected infectious diseases caused by Orientia tsutsugamushi, Rickettsia typhi, and pathogenic Leptospira spp., respectively. Patients usually present with non-specific symptoms and therefore are commonly diagnosed with acute undifferentiated febrile illness. Consequently, patients face delayed treatment and increased mortality. Antibody-based serological test currently used as gold standard has limitations due to insufficient antibody titers, especially in the early phase of infection. In this study, we aimed to develop multiplex PCR to combine 3 primer pairs that target specific genes encoding 56-kDa TSA of O. tsutsugamushi, 17-kDa antigen of R. typhi, and LipL32 of L. Interrogans and evaluate its performance in comparison to the standard serological tests. Using EDTA blood samples of known patients, the sensitivity and specificity of our multiplex PCR was 100% and 70%, respectively. In addition, the assay was able to diagnose the co-infection of scrub typhus and leptospirosis. The assay may be useful in identifying causative agents during the early phase of these diseases, enabling prompt and appropriate treatment.

Immunoproteomic analysis of a Chikungunya poxvirus-based vaccine reveals high HLA class II immunoprevalence

PLoS Neglected Tropical Diseases News - 5 July 2019 - 9:00pm

by Elena Lorente, Alejandro Barriga, Eilon Barnea, Concepción Palomo, Juan García-Arriaza, Carmen Mir, Mariano Esteban, Arie Admon, Daniel López

Background

Efficient adaptive antiviral cellular and humoral immune responses require previous recognition of viral antigenic peptides bound to human leukocyte antigen (HLA) class I and II molecules, which are exposed on the surface of infected and antigen presenting cells, respectively. The HLA-restricted immune response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe chronic polyarthralgia and polyarthritis, is largely unknown.

Methodology/Principal findings

In this study, a high-throughput mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of human cells infected with a vaccinia virus (VACV) recombinant expressing CHIKV structural proteins was carried out. Twelve viral ligands from the CHIKV polyprotein naturally presented by different HLA-A, -B, and -C class I, and HLA-DR and -DP class II molecules were identified.

Conclusions/Significance

The immunoprevalence of the HLA class II but not the HLA class I-restricted cellular immune response against the CHIKV structural polyprotein was greater than that against the VACV vector itself. In addition, most of the CHIKV HLA class I and II ligands detected by mass spectrometry are not conserved compared to its closely related O'nyong-nyong virus. These findings have clear implications for analysis of both cytotoxic and helper immune responses against CHIKV as well as for the future studies focused in the exacerbated T helper response linked to chronic musculoskeletal disorders in CHIKV patients.

Potential effects of heat waves on the population dynamics of the dengue mosquito <i>Aedes albopictus</i>

PLoS Neglected Tropical Diseases News - 5 July 2019 - 9:00pm

by Lu Liang, Pengfei Jia, Xiaoyue Tan, Jin Chen, Xiang Chen

Extreme weather events affect the development and survival of disease pathogens and vectors. Our aim was to investigate the potential effects of heat waves on the population dynamics of Asian tiger mosquito (Aedes albopictus), which is a major vector of dengue and Zika viruses. We modeled the population abundance of blood-fed mosquito adults based on a mechanistic population model of Ae. albopictus with the consideration of diapause. Using simulated heat wave events derived from a 35-year historical dataset, we assessed how the mosquito population responded to different heat wave characteristics, including the onset day, duration, and the average temperature. Two important observations are made: (1) a heat wave event facilitates the population growth in the early development phase but tends to have an overall inhibitive effect; and (2) two primary factors affecting the development are the unusual onset time of a heat wave and a relatively high temperature over an extended period. We also performed a sensitivity analysis using different heat wave definitions, justifying the robustness of the findings. The study suggests that particular attention should be paid to future heat wave events with an abnormal onset time or a lasting high temperature in order to develop effective strategies to prevent and control Ae. albopictus-borne diseases.

Responses of <i>Glossina fuscipes fuscipes</i> to visually attractive stationary devices baited with 4-methylguaiacol and certain repellent compounds in waterbuck odour

PLoS Neglected Tropical Diseases News - 5 July 2019 - 9:00pm

by Njelembo J. Mbewe, Rajinder K. Saini, Janet Irungu, Abdullahi A. Yusuf, Christian W. W. Pirk, Baldwyn Torto

Background

A blend of compounds (pentanoic acid, guaiacol, δ-octalactone and geranylacetone) identified in waterbuck (Kobus defassa) body odour referred to as waterbuck repellent compounds (WRC) and a synthetic repellent 4-methylguaiacol have previously been shown to repel tsetse flies from the morsitans group. However, these repellents have not been evaluated on palpalis group tsetse flies. In this study, we evaluated the effect of these repellents on catches of Glossina fuscipes fuscipes (major vector of human sleeping sickness) in biconical traps and on sticky small targets which are visually attractive to palpalis group flies. The attractive devices were baited with different doses and blends of the repellent compounds. We also assessed the effect of removal of individual constituents in the synthetic blend of WRC on catches of G. f. fuscipes.

Methodology/Principal findings

The study was conducted in western Kenya on four islands of Lake Victoria namely Big Chamaunga, Small Chamaunga, Manga and Rusinga. The tsetse fly catches from the treatments were modeled using a negative binomial regression to determine their effect on catches. In the presence of WRC and 4-methylguaiacol (released at ≈2 mg/h and ≈1.4 mg/h respectively), catches of G. f. fuscipes were significantly reduced by 33% (P<0.001) and 22% (P<0.001) respectively in biconical traps relative to control. On sticky small targets the reduction in fly catches were approximately 30% (P<0.001) for both 4-methylguiacol and WRC. In subtractive assays, only removal of geranylacetone from WRC significantly increased catches (by 1.8 times; P <0.001) compared to the complete blend of WRC.

Conclusions/Significance

We conclude that WRC and 4-methylguaiacol reduce catches of G. f. fuscipes at stationary visually attractive traps and suggest that they may serve as broad spectrum repellents for Glossina species. We recommend further studies to investigate the effects of these compounds on reduction of G. f. fuscipes attracted to human hosts as this may lead to development of new strategies of reducing the prevalence and incidence of sleeping sickness.

Improved assessment of mass drug administration and health district management performance to eliminate lymphatic filariasis

PLoS Neglected Tropical Diseases News - 5 July 2019 - 9:00pm

by Carmen Maroto-Camino, Pilar Hernandez-Pastor, Naomi Awaca, Lebon Safari, Janet Hemingway, Marilia Massangaie, Donald Whitson, Caroline Jeffery, Joseph J. Valadez

Lymphatic filariasis (LF) elimination as a public health problem requires the interruption of transmission by administration of preventive mass drug administration (MDA) to the eligible population living in endemic districts. Suboptimal MDA coverage leads to persistent parasite transmission with consequential infection, disease and disability, and the need for continuing MDA rounds, requiring considerable investment. Routine coverage reports must be verified in each MDA implementation unit (IU) due to incorrect denominators and numerators used to calculate coverage estimates with administrative data. IU are usually the health districts. Coverage is verified so IU teams can evaluate their outreach and take appropriate action to improve performance. Mozambique and the Democratic Republic of Congo (DRC) have conducted MDA campaigns for LF since 2009 and 2014, respectively. To verify district reports and assess the declared achievement using administrative data of the minimum 80% coverage of eligible people (or 65% of the total population), both countries conducted rapid probability surveys using Lot Quality Assurance Sampling (LQAS)(n = 1102) in 2015 and 2016 in 58 IU in 49 districts. The surveys identified IU with suboptimal coverage, reasons for not residents did not take the medication, place where the medication was received, information sources, and knowledge about diseases prevented by the MDA. LQAS identified four inadequately covered IU triggering district team performance reviews with provincial and national teams and district retreatment. Provincial estimates using probability samples (weighted by populations sizes) were 10 and 17 percentage points lower than reported coverage in DRC and Mozambique. The surveys identified: absence from home during annual MDA rounds as the main reason for low performance and provided valuable information about pre-campaign and campaign activities resulting in improved strategies and continued progress towards elimination of LF and co-endemic Neglected Tropical Diseases.

<i>Anopheles</i> mosquito surveillance in Madagascar reveals multiple blood feeding behavior and <i>Plasmodium</i> infection

PLoS Neglected Tropical Diseases News - 5 July 2019 - 9:00pm

by Riley E. Tedrow, Tovonahary Rakotomanga, Thiery Nepomichene, Rosalind E. Howes, Jocelyn Ratovonjato, Arséne C. Ratsimbasoa, Gavin J. Svenson, Peter A. Zimmerman

Background

The Madagascar National Strategic Plan for Malaria Control 2018 (NSP) outlines malaria control pre-elimination strategies that include detailed goals for mosquito control. Primary surveillance protocols and mosquito control interventions focus on indoor vectors of malaria, while many potential vectors feed and rest outdoors. Here we describe the application of tools that advance our understanding of diversity, host choice, and Plasmodium infection in the Anopheline mosquitoes of the Western Highland Fringe of Madagascar.

Methodology/Principal findings

We employed a modified barrier screen trap, the QUadrant Enabled Screen Trap (QUEST), in conjunction with the recently developed multiplex BLOOdmeal Detection Assay for Regional Transmission (BLOODART). We captured a total of 1252 female Anopheles mosquitoes (10 species), all of which were subjected to BLOODART analysis. QUEST collection captured a heterogenous distribution of mosquito density, diversity, host choice, and Plasmodium infection. Concordance between Anopheles morphology and BLOODART species identifications ranged from 93–99%. Mosquito feeding behavior in this collection frequently exhibited multiple blood meal hosts (single host = 53.6%, two hosts = 42.1%, three hosts = 4.3%). The overall percentage of human positive bloodmeals increased between the December 2017 and the April 2018 timepoints (27% to 44%). Plasmodium positivity was frequently observed in the abdomens of vectors considered to be of secondary importance, with an overall prevalence of 6%.

Conclusions/Significance

The QUEST was an efficient tool for sampling exophilic Anopheline mosquitoes. Vectors considered to be of secondary importance were commonly found with Plasmodium DNA in their abdomens, indicating a need to account for these species in routine surveillance efforts. Mosquitoes exhibited multiple blood feeding behavior within a gonotrophic cycle, with predominantly non-human hosts in the bloodmeal. Taken together, this complex feeding behavior could enhance the role of multiple Anopheline species in malaria transmission, possibly tempered by zoophilic feeding tendencies.

Susceptibility of spotted doves (<i>Streptopelia chinensis</i>) to experimental infection with the severe fever with thrombocytopenia syndrome phlebovirus

PLoS Neglected Tropical Diseases News - 5 July 2019 - 9:00pm

by Zhifeng Li, Changjun Bao, Jianli Hu, Chengfeng Gao, Nan Zhang, Huo Xiang, Carol J. Cardona, Zheng Xing

Background

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging human pathogen naturally transmitted by ticks, has spread widely since it was first detected in 2010. Although SFTSV-specific antibodies have been detected in wild birds, these natural reservoir and amplifying hosts for the virus have not been well studied.

Methodology/Principle findings

Here we report an experimental infection of spotted doves (Streptopelia chinensis) with two strains of SFTSV, JS2010-14, a Chinese lineage strain, and JS2014-16, a Japanese lineage strain, which represent the main viral genotypes currently circulating in East Asia. In these studies, we have determined that spotted doves are susceptible to SFTSV and the severity of the viremia is dose-dependent. When challenged with 107 and 105 PFU, all doves developed viremia which peaked 3–5 days post infection (dpi). Only a subset (25–62.5%) of the birds developed viremia when challenged at 103 PFU. Virulence of SFTSV in spotted doves was strain dependent. Infection with 107 PFU of strain JS2014-16 resulted in 12.5% mortality over 6.8 days and mean peak viremia titers of 106.9 PFU/mL in experimentally inoculated birds. All doves inoculated with 107 PFU of the JS2010-14 strain survived infection with relatively lower mean viremia titers (105.6 PFU/mL at peak) over 6.1 days.

Conclusions/Significance

Our results suggest that spotted doves, one of the most abundant bird species in China, could be a competent amplifying host for SFTSV and play an important role in its ecology. Between the two SFTSV strains, the strain of the Japanese lineage caused mortality, higher viremia titers in infected birds over a longer time period than did the Chinese strain. Our observations shed light on the ecology of SFTSV, which could benefit the implementation of surveillance and control programs.

Concerns for efficacy of a 30-valent M-protein-based <i>Streptococcus pyogenes</i> vaccine in regions with high rates of rheumatic heart disease

PLoS Neglected Tropical Diseases News - 3 July 2019 - 9:00pm

by Philip M. Giffard, Steven Y. C. Tong, Deborah C. Holt, Anna P. Ralph, Bart J. Currie

The prevalence of rheumatic heart disease (RHD) in the Aboriginal population of the Australian Northern Territory is high, and Streptococcus pyogenes skin infections likely contribute to this. A promising candidate S. pyogenes “30mer” vaccine is composed of 30 pharyngitis associated type-specific antigens from the S. pyogenes M protein. Cross opsonisation experiments suggest that 30mer vaccine protection may extend to non-cognate emm types. A new “emm cluster” scheme for classifying M protein is based on the full-length coding sequence, and correlates with functional and immunological properties, and anatomical tropism. Twenty-seven years of research in the Northern Territory has yielded 1810 S. pyogenes isolates with clinical and emm type data. The primary aim was to analyse these data with reference to the emm cluster scheme and cross opsonisation information, to inform estimation of 30mer vaccine efficacy in the Northern Territory. The isolates encompass 101 emm types. Variants of cluster A-C were enriched in throat isolates, and variants of emm cluster D enriched in skin isolates. Throat isolates were enriched for 30mer vaccine cognate emm types in comparison with skin isolates of which only 25% were vaccine emm types. While cross opsonisation data indicates potential for enhancing 30mer vaccine coverage, more than one third of skin isolates were within 38 emm types untested for cross opsonisation. Emm cluster D variants, in particular emm cluster D4, were not only all non-cognate with the vaccine, but were abundant and diverse, and less likely to be cross-opsonisation positive than other emm clusters. Long term persistence of many emm types in the study area was revealed. It was concluded that the 30mer vaccine efficacy in the Northern Territory will likely require both cross protection, and additional measures to elicit immunity against variants of emm cluster D.

Contrasting the value of targeted versus area-wide mosquito control scenarios to limit arbovirus transmission with human mobility patterns based on different tropical urban population centers

PLoS Neglected Tropical Diseases News - 3 July 2019 - 9:00pm

by Chris M. Stone, Samantha R. Schwab, Dina M. Fonseca, Nina H. Fefferman

Vector control is still our primary intervention for both prevention and mitigation of epidemics of many vector-borne diseases. Efficiently targeting control measures is important since control can involve substantial economic costs. Targeting is not always straightforward, as transmission of vector-borne diseases is affected by various types of host movement. Here we assess how taking daily commuting patterns into consideration can help improve vector control efforts. We examine three tropical urban centers (San Juan, Recife, and Jakarta) that have recently been exposed to Zika and/or dengue infections and consider whether the distribution of human populations and resulting commuting flows affects the optimal scale at which control interventions should be implemented. We developed a stochastic, spatial model and investigated four control scenarios. The scenarios differed in the spatial extent of their implementation and were: 1) a response at the level of an individual neighborhood; 2) a response targeted at a neighborhood in which infected humans were detected and the one with which it was most strongly connected by human movement; 3) a limited area-wide response where all neighborhoods within a certain radius of the focal area were included; and 4) a collective response where all participating neighborhoods implemented control. The relative effectiveness of the scenarios varied only slightly between different settings, with the number of infections averted over time increasing with the scale of implementation. This difference depended on the efficacy of control at the neighborhood level. At low levels of efficacy, the scenarios mirrored each other in infections averted. At high levels of efficacy, impact increased with the scale of the intervention. As a result, the choice between scenarios will not only be a function of the amount of effort decision-makers are willing to invest, but largely epend on the overall effectiveness of vector control approaches.

Development and validation of an <i>Onchocerca ochengi</i> adult male worm gerbil model for macrofilaricidal drug screening

PLoS Neglected Tropical Diseases News - 1 July 2019 - 9:00pm

by Fidelis Cho-Ngwa, Glory Enjong Mbah, Rene Bilingwe Ayiseh, Emmanuel Menang Ndi, Elvis Monya, Irene Memeh Tumanjong, Evans Ngandung Mainsah, Judy Sakanari, Sara Lustigman

Background

Onchocerciasis currently afflicts an estimated 15 million people and is the second leading infectious cause of blindness world-wide. The development of a macrofilaricide to cure the disease has been hindered by the lack of appropriate small laboratory animal models. This study therefore, was aimed at developing and validating the Mongolian gerbil, as an Onchocerca ochengi (the closest in phylogeny to O. volvulus) adult male worm model.

Methodology/Principal findings

Mongolian gerbils (Meriones unguiculatus) were each implanted with 20 O. ochengi male worms (collected from infected cattle), in the peritoneum. Following drug or placebo treatments, the implanted worms were recovered from the animals and analyzed for burden, motility and viability. Worm recovery in control gerbils was on average 35%, with 89% of the worms being 100% motile. Treatment of the gerbils implanted with male worms with flubendazole (FBZ) resulted in a significant reduction (p = 0.0021) in worm burden (6.0% versus 27.8% in the control animals); all recovered worms from the treated group had 0% worm motility versus 91.1% motility in control animals. FBZ treatment had similar results even after four different experiments. Using this model, we tested a related drug, oxfendazole (OFZ), and found it to also significantly (p = 0.0097) affect worm motility (22.7% versus 95.0% in the control group).

Conclusions/Significance

We have developed and validated a novel gerbil O. ochengi adult male worm model for testing new macrofilaricidal drugs in vivo. It was also used to determine the efficacy of oxfendazole in vivo.

<i>Leishmania major</i> degrades murine CXCL1 – An immune evasion strategy

PLoS Neglected Tropical Diseases News - 1 July 2019 - 9:00pm

by Matthew S. Yorek, Barun Poudel, Lalita Mazgaeen, R. Marshall Pope, Mary E. Wilson, Prajwal Gurung

Leishmaniasis is a global health problem with an estimated report of 2 million new cases every year and more than 1 billion people at risk of contracting this disease in endemic areas. The innate immune system plays a central role in controlling L. major infection by initiating a signaling cascade that results in production of pro-inflammatory cytokines and recruitment of both innate and adaptive immune cells. Upon infection with L. major, CXCL1 is produced locally and plays an important role in the recruitment of neutrophils to the site of infection. Herein, we report that L. major specifically targets murine CXCL1 for degradation. The degradation of CXCL1 is not dependent on host factors as L. major can directly degrade recombinant CXCL1 in a cell-free system. Using mass spectrometry, we discovered that the L. major protease cleaves at the C-terminal end of murine CXCL1. Finally, our data suggest that L. major metalloproteases are involved in the direct cleavage and degradation of CXCL1, and a synthetic peptide spanning the CXCL1 cleavage site can be used to inhibit L. major metalloprotease activity. In conclusion, our study has identified an immune evasion strategy employed by L. major to evade innate immune responses in mice, likely reservoirs in the endemic areas, and further highlights that targeting these L. major metalloproteases may be important in controlling infection within the reservoir population and transmittance of the disease.

Intestinal parasitic infection alters bone marrow derived dendritic cell inflammatory cytokine production in response to bacterial endotoxin in a diet-dependent manner

PLoS Neglected Tropical Diseases News - 1 July 2019 - 9:00pm

by Stacey L. Burgess, Akihiko Oka, Bo Liu, David T. Bolick, David Noah Oakland, Richard L. Guerrant, Luther Bartelt

Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, is associated with debilitating chronic intestinal and extra-intestinal sequelae. In previously healthy adults, a primary sporadic Giardia infection can lead to gut dysfunction and fatigue. These symptoms correlate with markers of inflammation that persist well after the infection is cleared. In contrast, in endemic settings, first exposure occurs in children who are frequently malnourished and also co-infected with other enteropathogens. In these children, Giardia rarely causes symptoms and associates with several decreased markers of inflammation. Mechanisms underlying these disparate and potentially enduring outcomes following Giardia infection are not presently well understood. A body of work suggests that the outcome of experimental Giardia infection is influenced by the nutritional status of the host. Here, we explore the consequences of experimental Giardia infection under conditions of protein sufficiency or deficiency on cytokine responses of ex vivo bone marrow derived dendritic cells (BMDCs) to endotoxin stimulation. We show that BMDCs from Giardia- challenged mice on a protein sufficient diet produce more IL-23 when compared to uninfected controls whereas BMDCs from Giardia challenged mice fed a protein deficient diet do not. Further, in vivo co-infection with Giardia attenuates robust IL-23 responses in endotoxin-stimulated BMDCs from protein deficient mice harboring enteroaggregative Escherichia coli. These results suggest that intestinal Giardia infection may have extra-intestinal effects on BMDC inflammatory cytokine production in a diet dependent manner, and that Giardia may influence the severity of the innate immune response to other enteropathogens. This work supports recent findings that intestinal microbial exposure may have lasting influences on systemic inflammatory responses, and may provide better understanding of potential mechanisms of post-infectious sequelae and clinical variation during Giardia and enteropathogen co-infection.

Evaluation of methods for detection of asymptomatic individuals infected with <i>Leishmania infantum</i> in the state of Piauí, Brazil

PLoS Neglected Tropical Diseases News - 1 July 2019 - 9:00pm

by Gabriane Nascimento Porcino, Kátia Silene Souza Carvalho, Débora Cavalcante Braz, Vladimir Costa Silva, Carlos Henrique Nery Costa, Isabel Kinney Ferreira de Miranda Santos

Background

Visceral Leishmaniasis in humans presents with fever, anemia, and splenomegaly and can be lethal if not treated. Nevertheless, the majority of Leishmania infantum-infected individuals does not manifest symptoms and remain so provided they are not immunosuppressed. In this work, the performance of different tests was evaluated to detect asymptomatic individuals who were living in Teresina, Piauí state, Brazil, an endemic area for VL.

Methodology

L. infantum-specific antibodies were detected by ELISA and two different rapid immunochromatographic (IC) diagnostic tests, Kalazar Detect and OnSite, and parasitic loads were detected by real time PCR [qPCR]. Additionally, we measured levels of the biomarkers monokine induced by IFN-γ (MIG) and IFN-γ-induced protein 10 (IP-10) before and after stimulation of whole blood with soluble Leishmania antigen [SLA].

Principal findings

Kalazar Detect and OnSite detected, respectively, 76% and 64% of patients presenting with active Visceral Leishmaniasis; 50% and 57% of patients remained positive in these tests, respectively, after treatment. Of the healthy participants in the study who were living in the endemic area, only 1.7% were positive with both of the IC tests. On the other hand, reactivity in ELISA tests revealed that 13% of these individuals presented asymptomatic infections; among VL patients, 84% presenting with active disease were reactive in ELISA, and after treatment, 55.5% were seropositive. L. infantum DNA was present in the blood of 37.9% of infected individuals living in the endemic area, while IP-10 and MIG biomarkers were detected in 26.7% of them. The greatest concordance of positivity occurred between ELISA and qPCR.

Conclusion

The association of different techniques can detect asymptomatic infections, however, more research is necessary to develop ideal biomarkers that are simple to use in the clinic and in field studies in areas endemic for Visceral Leishmaniasis.

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