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High prevalence and diversity of Bartonella in small mammals from the biodiverse Western Ghats

PLoS Neglected Tropical Diseases News - 11 March 2021 - 2:00pm

by B. R. Ansil, Ian H. Mendenhall, Uma Ramakrishnan

Bartonella species are recognized globally as emerging zoonotic pathogens. Small mammals such as rodents and shrews are implicated as major natural reservoirs for these microbial agents. Nevertheless, in several tropical countries, like India, the diversity of Bartonella in small mammals remain unexplored and limited information exists on the natural transmission cycles (reservoirs and vectors) of these bacteria. Using a multi-locus sequencing approach, we investigated the prevalence, haplotype diversity, and phylogenetic affinities of Bartonella in small mammals and their associated mites in a mixed-use landscape in the biodiverse Western Ghats in southern India. We sampled 141 individual small mammals belonging to eight species. Bartonella was detected in five of the eight species, including three previously unknown hosts. We observed high interspecies variability of Bartonella prevalence in the host community. However, the overall prevalence (52.5%) and haplotype diversity (0.9) was high for the individuals tested. Of the seven lineages of Bartonella identified in our samples, five lineages were phylogenetically related to putative zoonotic species–B. tribocorum, B. queenslandensis, and B. elizabethae. Haplotypes identified from mites were identical to those identified from their host species. This indicates that these Bartonella species may be zoonotic, but further work is necessary to confirm whether these are pathogenic and pose a threat to humans. Taken together, these results emphasize the presence of hitherto unexplored diversity of Bartonella in wild and synanthropic small mammals in mixed-use landscapes. The study also highlights the necessity to assess the risk of spillover to humans and other incidental hosts.

Preventing vector-borne diseases at major sport events: Addressing the challenges for FIFA 22 in Qatar

PLoS Neglected Tropical Diseases News - 11 March 2021 - 2:00pm

by Francis Schaffner, Devendra Bansal, Mohammed Hamad J. Al-Thani, Hamad Al-Romaihi, Elmoubasher Abu Baker Abd Farag

Use-case scenarios for an anti-<i>Cryptosporidium</i> therapeutic

PLoS Neglected Tropical Diseases News - 11 March 2021 - 2:00pm

by Paul G. Ashigbie, Susan Shepherd, Kevin L. Steiner, Beatrice Amadi, Natasha Aziz, Ujjini H. Manjunatha, Jonathan M. Spector, Thierry T. Diagana, Paul Kelly

Cryptosporidium is a widely distributed enteric parasite that has an increasingly appreciated pathogenic role, particularly in pediatric diarrhea. While cryptosporidiosis has likely affected humanity for millennia, its recent “emergence” is largely the result of discoveries made through major epidemiologic studies in the past decade. There is no vaccine, and the only approved medicine, nitazoxanide, has been shown to have efficacy limitations in several patient groups known to be at elevated risk of disease. In order to help frontline health workers, policymakers, and other stakeholders translate our current understanding of cryptosporidiosis into actionable guidance to address the disease, we sought to assess salient issues relating to clinical management of cryptosporidiosis drawing from a review of the literature and our own field-based practice. This exercise is meant to help inform health system strategies for improving access to current treatments, to highlight recent achievements and outstanding knowledge and clinical practice gaps, and to help guide research activities for new anti-Cryptosporidium therapies.

Anti-<i>Leptospira</i> immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization

PLoS Neglected Tropical Diseases News - 11 March 2021 - 2:00pm

by Frédérique Vernel-Pauillac, Gerald L. Murray, Ben Adler, Ivo G. Boneca, Catherine Werts

Leptospira interrogans is a pathogenic spirochete responsible for leptospirosis, a neglected, zoonotic reemerging disease. Humans are sensitive hosts and may develop severe disease. Some animal species, such as rats and mice can become asymptomatic renal carriers. More than 350 leptospiral serovars have been identified, classified on the basis of the antibody response directed against the lipopolysaccharide (LPS). Similarly to whole inactivated bacteria used as human vaccines, this response is believed to confer only short-term, serogroup-specific protection. The immune response of hosts against leptospires has not been thoroughly studied, which complicates the testing of vaccine candidates. In this work, we studied the immunoglobulin (Ig) profiles in mice infected with L. interrogans over time to determine whether this humoral response confers long-term protection after homologous challenge six months post-infection. Groups of mice were injected intraperitoneally with 2×107 leptospires of one of three pathogenic serovars (Manilae, Copenhageni or Icterohaemorrhagiae), attenuated mutants or heat-killed bacteria. Leptospira-specific immunoglobulin (IgA, IgM, IgG and 4 subclasses) produced in the first weeks up to 6 months post-infection were measured by ELISA. Strikingly, we found sustained high levels of IgM in mice infected with the pathogenic Manilae and Copenhageni strains, both colonizing the kidney. In contrast, the Icterohaemorrhagiae strain did not lead to kidney colonization, even at high dose, and triggered a classical IgM response that peaked at day 8 post-infection and disappeared. The virulent Manilae and Copenhageni serovars elicited high levels and similar profiles of IgG subclasses in contrast to Icterohaemorrhagiae strains that stimulated weaker antibody responses. Inactivated heat-killed Manilae strains elicited very low responses. However, all mice pre-injected with leptospires challenged with high doses of homologous bacteria did not develop acute leptospirosis, and all antibody responses were boosted after challenge. Furthermore, we showed that 2 months post challenge, mice pre-infected with the attenuated M895 Manilae LPS mutant or heat-killed bacterin were completely protected against renal colonization. In conclusion, we observed a sustained IgM response potentially associated with chronic leptospiral renal infection. We also demonstrated in mice different profiles of protective and cross-reactive antibodies after L. interrogans infection, depending on the serovar and virulence of strains.

Louse-borne relapsing fever—A systematic review and analysis of the literature: Part 2—Mortality, Jarisch–Herxheimer reaction, impact on pregnancy

PLoS Neglected Tropical Diseases News - 11 March 2021 - 2:00pm

by Pascal Kahlig, Andreas Neumayr, Daniel H. Paris

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease’s causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus corporis. Since the disease was at its peak before the days of modern medicine, many of its aspects have never been formally studied and to date remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF since the recognition of its mode of transmission in 1907, and summarized the existing data on mortality, Jarisch–Herxheimer reaction (JHR), and impact on pregnancy. Publications were identified by using a predefined search strategy of electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases. The high mortality rates often found in literature are confined to extreme scenarios. The case fatality rate (CFR) of untreated cases is on average significantly lower than frequently assumed. In recent years, a rise in the overall CFRs is documented, for which reasons remain unknown. Lacking standardized criteria, a clear diagnostic threshold defining antibiotic treatment-induced JHR does not exist. This explains the wide range of occurrence rates found in literature. Pre-antibiotic era data suggest the existence of a JHR-like reaction also in cases treated with arsenicals and even in untreated cases. LBRF-related adverse outcomes are observed in 3 out of 4 pregnancies.

Louse-borne relapsing fever—A systematic review and analysis of the literature: Part 1—Epidemiology and diagnostic aspects

PLoS Neglected Tropical Diseases News - 11 March 2021 - 2:00pm

by Pascal Kahlig, Daniel H. Paris, Andreas Neumayr

Louse-borne relapsing fever (LBRF) is a classical epidemic disease, which in the past was associated with war, famine, poverty, forced migration, and crowding under poor hygienic conditions around the world. The disease’s causative pathogen, the spirochete bacterium Borrelia recurrentis, is confined to humans and transmitted by a single vector, the human body louse Pediculus humanus. Since the disease has had its heyday before the days of modern medicine, many of its aspects have never been formally studied and to date, remain incompletely understood. In order to shed light on some of these aspects, we have systematically reviewed the accessible literature on LBRF, since the recognition of its mode of transmission in 1907, and summarized the existing data on epidemiology and diagnostic aspects of the disease. Publications were identified by using a predefined search strategy on electronic databases and a subsequent review of the reference lists of the obtained publications. All publications reporting patients with a confirmed diagnosis of LBRF published in English, French, German, and Spanish since 1907 were included. Data extraction followed a predefined protocol and included a grading system to judge the certainty of the diagnosis of reported cases. Historically, Ethiopia is considered a stronghold of LBRF. The recognition of LBRF among East African migrants (originating from Somalia, Eritrea, and Ethiopia) arriving to Europe in the course of the recent migration flow from this region suggests that this epidemiological focus ostensibly persists. Currently, there is neither evidence to support or refute active transmission foci of LBRF elsewhere on the African continent, in Latin America, or in Asia. Microscopy remains the most commonly used method to diagnose LBRF. Data are lacking on sensitivity and specificity of most diagnostic methods.

Derivation of the first clinical diagnostic models for dehydration severity in patients over five years with acute diarrhea

PLoS Neglected Tropical Diseases News - 10 March 2021 - 2:00pm

by Adam C. Levine, Meagan A. Barry, Monique Gainey, Sabiha Nasrin, Kexin Qu, Christopher H. Schmid, Eric J. Nelson, Stephanie C. Garbern, Mahmuda Monjory, Rochelle Rosen, Nur H. Alam

Diarrheal diseases lead to an estimated 1.3 million deaths each year, with the majority of those deaths occurring in patients over five years of age. As the severity of diarrheal disease can vary widely, accurately assessing dehydration status remains the most critical step in acute diarrhea management. The objective of this study is to empirically derive clinical diagnostic models for assessing dehydration severity in patients over five years with acute diarrhea in low resource settings. We enrolled a random sample of patients over five years with acute diarrhea presenting to the icddr,b Dhaka Hospital. Two blinded nurses independently assessed patients for symptoms/signs of dehydration on arrival. Afterward, consecutive weights were obtained to determine the percent weight change with rehydration, our criterion standard for dehydration severity. Full and simplified ordinal logistic regression models were derived to predict the outcome of none (<3%), some (3–9%), or severe (>9%) dehydration. The reliability and accuracy of each model were assessed. Bootstrapping was used to correct for over-optimism and compare each model’s performance to the current World Health Organization (WHO) algorithm. 2,172 patients were enrolled, of which 2,139 (98.5%) had complete data for analysis. The Inter-Class Correlation Coefficient (reliability) was 0.90 (95% CI = 0.87, 0.91) for the full model and 0.82 (95% CI = 0.77, 0.86) for the simplified model. The area under the Receiver-Operator Characteristic curve (accuracy) for severe dehydration was 0.79 (95% CI: 0.76–0.82) for the full model and 0.73 (95% CI: 0.70, 0.76) for the simplified model. The accuracy for both the full and simplified models were significantly better than the WHO algorithm (p<0.001). This is the first study to empirically derive clinical diagnostic models for dehydration severity in patients over five years. Once prospectively validated, the models may improve management of patients with acute diarrhea in low resource settings.

Epidemiological and clinical features in patients with coronavirus disease 2019 outside of Wuhan, China: Special focus in asymptomatic patients

PLoS Neglected Tropical Diseases News - 10 March 2021 - 2:00pm

by Ping Liu, Ruichao Niu, Jie Chen, Yuling Tang, Wenfang Tang, Linyan Xu, Juntao Feng

Objectives

In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan City and rapidly spread across the world. The clinical characteristics of affected patients in different regions and populations may differ. Thus, this study aimed to identify the characteristics of the disease to provide an insight about the prevention and treatment of COVID-19.

Methods

Data on the demographic characteristics and clinical findings of the patients admitted at the First Hospital of Changsha from January 1, 2020 to February 10, 2020 were assessed.

Results

In this study, there were 8 (3.8%) asymptomatic, 21 (10.0%) mild upper respiratory tract infection (URTI), and 180 (86.1%) pneumonia cases. In total, 47 (22.5%) patients resided in Wuhan, and 45 (21.5%) had recently traveled to Wuhan before disease onset. Moreover, 19 (9.1%) had contact with people from Wuhan, and 69 (33.0%) were family cluster cases. The median incubation period was approximately 6.3 (range: 1.0–20.0) days. Fever and cough were the most common initial symptoms: 99 (49.3%) patients presented with fever, without cough; 59 (29.4%) with cough, without fever; and 33 (16.4%) with both fever and cough.

Conclusion

The symptoms of patients with COVID-19 were relatively mild outside Wuhan, and family cluster was a remarkable epidemic characteristic. Special attention should be paid to asymptomatic patients.

Dog ownership practices and responsibilities for children’s health in terms of rabies control and prevention in rural communities in Tanzania

PLoS Neglected Tropical Diseases News - 10 March 2021 - 2:00pm

by Lwitiko Sikana, Tiziana Lembo, Katie Hampson, Kennedy Lushasi, Sally Mtenga, Maganga Sambo, Daniel Wight, Jane Coutts, Katharina Kreppel

Interventions tackling zoonoses require an understanding of healthcare patterns related to both human and animal hosts. The control of dog-mediated rabies is a good example. Despite the availability of effective control measures, 59,000 people die of rabies every year worldwide. In Tanzania, children are most at risk, contributing ~40% of deaths. Mass dog vaccination can break the transmission cycle, but reaching the recommended 70% coverage is challenging where vaccination depends on willingness to vaccinate dogs. Awareness campaigns in communities often target children, but do not consider other key individuals in the prevention chain. Understanding factors related to dog ownership and household-level responsibility for dog vaccination and child health is critical to the design of vaccination strategies. We investigated who makes household decisions about dogs and on health care for children in rural Tanzania. In the Kilosa district, in-depth interviews with 10 key informants were conducted to inform analysis of data from a household survey of 799 households and a survey on Knowledge Attitudes and Practices of 417 households. The in-depth interviews were analysed using framework analysis. Descriptive analysis showed responsibilities for household decisions on dogs’ and children’s health. Multivariate analysis determined factors associated with the probability of dogs being owned and the number of dogs owned, as well as factors associated with the responsibility for child health. Dog ownership varied considerably between villages and even households. The number of dogs per household was associated with the size of a household and the presence of livestock. Children are not directly involved in the decision to vaccinate a dog, which is largely made by the father, while responsibility for seeking health care if a child is bitten lies with the mother. These novel results are relevant for the design and implementation of rabies interventions. Specifically, awareness campaigns should focus on decision-makers in households to improve rabies prevention practices and on the understanding of processes critical to the control of zoonoses more broadly.

Insights into the molecular basis of tick-borne encephalitis from multiplatform metabolomics

PLoS Neglected Tropical Diseases News - 10 March 2021 - 2:00pm

by YanDan Du, ZhiHui Mi, YaPing Xie, DeSheng Lu, HaiJun Zheng, Hui Sun, Meng Zhang, YiQing Niu

Background

Tick-borne encephalitis virus (TBEV) is the most prevalent arbovirus, with a tentative estimate of 10,000 to 10,500 infections occurring in Europe and Asia every year. Endemic in Northeast China, tick-borne encephalitis (TBE) is emerging as a major threat to public health, local economies and tourism. The complicated array of host physiological changes has hampered elucidation of the molecular mechanisms underlying the pathogenesis of this disease.

Methodology/Principle findings

System-level characterization of the serum metabolome and lipidome of adult TBEV patients and a healthy control group was performed using liquid chromatography tandem mass spectrometry. By tracking metabolic and lipid changes during disease progression, crucial physiological changes that coincided with disease stages could be identified. Twenty-eight metabolites were significantly altered in the sera of TBE patients in our metabolomic analysis, and 14 lipids were significantly altered in our lipidomics study. Among these metabolites, alpha-linolenic acid, azelaic acid, D-glutamine, glucose-1-phosphate, L-glutamic acid, and mannose-6-phosphate were altered compared to the control group, and PC(38:7), PC(28:3;1), TAG(52:6), etc. were altered based on lipidomics. Major perturbed metabolic pathways included amino acid metabolism, lipid and oxidative stress metabolism (lipoprotein biosynthesis, arachidonic acid biosynthesis, leukotriene biosynthesis and sphingolipid metabolism), phospholipid metabolism and triglyceride metabolism. These metabolites were significantly perturbed during disease progression, implying their latent utility as prognostic markers.

Conclusions/Significance

TBEV infection causes distinct temporal changes in the serum metabolome and lipidome, and many metabolites are potentially involved in the acute inflammatory response and immune regulation. Our global analysis revealed anti- and pro-inflammatory processes in the host and changes to the entire metabolic profile. Relationships between metabolites and pathologies were established. This study provides important insight into the pathology of TBE, including its pathology, and lays the foundation for further research into putative markers of TBE disease.

Optimising predictive modelling of Ross River virus using meteorological variables

PLoS Neglected Tropical Diseases News - 9 March 2021 - 2:00pm

by Iain S. Koolhof, Simon M. Firestone, Silvana Bettiol, Michael Charleston, Katherine B. Gibney, Peter J. Neville, Andrew Jardine, Scott Carver

Background

Statistical models are regularly used in the forecasting and surveillance of infectious diseases to guide public health. Variable selection assists in determining factors associated with disease transmission, however, often overlooked in this process is the evaluation and suitability of the statistical model used in forecasting disease transmission and outbreaks. Here we aim to evaluate several modelling methods to optimise predictive modelling of Ross River virus (RRV) disease notifications and outbreaks in epidemiological important regions of Victoria and Western Australia.

Methodology/Principal findings

We developed several statistical methods using meteorological and RRV surveillance data from July 2000 until June 2018 in Victoria and from July 1991 until June 2018 in Western Australia. Models were developed for 11 Local Government Areas (LGAs) in Victoria and seven LGAs in Western Australia. We found generalised additive models and generalised boosted regression models, and generalised additive models and negative binomial models to be the best fit models when predicting RRV outbreaks and notifications, respectively. No association was found with a models’ ability to predict RRV notifications in LGAs with greater RRV activity, or for outbreak predictions to have a higher accuracy in LGAs with greater RRV notifications. Moreover, we assessed the use of factor analysis to generate independent variables used in predictive modelling. However, this approach did not result in as many best fit models than when not using this approach.

Conclusions/Significance

We demonstrate that models which are developed and used for predicting disease notifications may not be suitable for predicting disease outbreaks, or visa versa. Furthermore, poor predictive performance in modelling disease transmissions may be the result of inappropriate model selection methods. Our findings provide approaches and methods to facilitate the selection of the best fit statistical model for predicting mosquito-borne disease notifications and outbreaks used for disease surveillance.

Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load

PLoS Neglected Tropical Diseases News - 9 March 2021 - 2:00pm

by Pedro Henrique Lopes da Silva, Katherine Kelda Gomes de Castro, Mayara Abud Mendes, Thyago Leal Calvo, Júlia Monteiro Pereira Leal, Mariana de Andréa Vilas-Boas Hacker, José Augusto da Costa Nery, Euzenir Nunes Sarno, Roberto Alves Lourenço, Milton Ozório Moraes, Flávio Alves Lara, Danuza Esquenazi

Background

Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy.

Methodology/Principal findings

87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark’s microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase.

Conclusions/Significance

We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.

Seropositivity and geographical distribution of <i>Strongyloides stercoralis</i> in Australia: A study of pathology laboratory data from 2012–2016

PLoS Neglected Tropical Diseases News - 9 March 2021 - 2:00pm

by Jennifer Shield, Sabine Braat, Matthew Watts, Gemma Robertson, Miles Beaman, James McLeod, Robert W. Baird, Julie Hart, Jennifer Robson, Rogan Lee, Stuart McKessar, Suellen Nicholson, Johanna Mayer-Coverdale, Beverley-Ann Biggs

Background

There are no national prevalence studies of Strongyloides stercoralis infection in Australia, although it is known to be endemic in northern Australia and is reported in high risk groups such as immigrants and returned travellers. We aimed to determine the seropositivity (number positive per 100,000 of population and percent positive of those tested) and geographical distribution of S. stercoralis by using data from pathology laboratories.

Methodology

We contacted all seven Australian laboratories that undertake Strongyloides serological (ELISA antibody) testing to request de-identified data from 2012–2016 inclusive. Six responded. One provided positive data only. The number of people positive, number negative and number tested per 100,000 of population (Australian Bureau of Statistics data) were calculated including for each state/territory, each Australian Bureau of Statistics Statistical Area Level 3 (region), and each suburb/town/community/locality. The data was summarized and expressed as maps of Australia and Greater Capital Cities.

Principal findings

We obtained data for 81,777 people who underwent serological testing for Strongyloides infection, 631 of whom were from a laboratory that provided positive data only. Overall, 32 (95% CI: 31, 33) people per 100,000 of population were seropositive, ranging between 23/100,000 (95% CI: 19, 29) (Tasmania) and 489/100,000 population (95%CI: 462, 517) (Northern Territory). Positive cases were detected across all states and territories, with the highest (260-996/100,000 and 17–40% of those tested) in regions across northern Australia, north-east New South Wales and north-west South Australia. Some regions in Greater Capital Cities also had a high seropositivity (112-188/100,000 and 17–20% of those tested). Relatively more males than females tested positive. Relatively more adults than children tested positive. Children were under-represented in the data.

Conclusions/Significance

The study confirms that substantial numbers of S. stercoralis infections occur in Australia and provides data to inform public health planning.

Control of cystic echinococcosis in the Middle Atlas, Morocco: Field evaluation of the EG95 vaccine in sheep and cesticide treatment in dogs

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Fatimaezzahra Amarir, Abdelkbir Rhalem, Abderrahim Sadak, Marianne Raes, Mohamed Oukessou, Aouatif Saadi, Mohammed Bouslikhane, Charles G. Gauci, Marshall W. Lightowlers, Nathalie Kirschvink, Tanguy Marcotty

Background

Cystic echinococcosis (CE) is an important cause of human morbidity and mortality worldwide, particularly in Morocco and other North African countries.

Methodology/Principal findings

We investigated the potential of three strategies to reduce Echinococcus granulosus transmission: (1) 4-monthly treatment of dogs with praziquantel, (2) vaccination of sheep with the EG95 vaccine and (3) a combination of both measures. These measures were implemented during four consecutive years in different areas of the Middle Atlas Mountains in Morocco. The outcome of the interventions was assessed through hydatid cyst (viable and non-viable) counts in liver and lungs using necropsy or in vivo ultrasound examination of the liver. A total of 402 lambs were recruited for annual vaccination with the EG95 anti-E. granulosus vaccine and 395 similar lambs were selected as non-vaccinated controls.At approximately four years of age the relative risk (estimated as odds ratio) for vaccinated sheep to have viable hydatid cysts compared with non-vaccinated controls was 3% (9.37% of the vaccinated sheep were found infected while 72.82% of the controls were infected; p = 0.002). The number of viable cysts in vaccinated animals was reduced by approximately 97% (mean counts were 0.28 and 9.18 respectively; p<0.001). An average of 595 owned dogs received 4-monthly treatment during the 44 months trial, corresponding to 91% of the owned dog population. Approximately, 5% of them were examined for E. granulosus adult worms by arecoline purge or eggs in feces (confirmed by PCR). The proportion of infected dogs significantly decreased after treatment (12% versus 35%; p<0.001). Post-treatment incidence of re-infestation corresponded to a monthly risk of 4% (95% CI: 3–6%). Treatment of owned dogs on a 4-monthly basis did not reduce the level of transmission of E. granulosus to sheep, nor did it enhance the level of control generated by vaccination of sheep with EG95, possibly because of unowned dogs and wild canids were not treated.

Conclusions/Significance

These data suggest that vaccination of sheep with EG95 has the potential to reduce the level of CE in Morocco and in other parts of the world with similar transmission dynamics. Under the epidemiological circumstances existing in the trial area, 4-monthly treatment of owned dogs with praziquantel was insufficient to have a major impact of E. granulosus transmission to sheep.

Zika-related adverse outcomes in a cohort of pregnant women with rash in Pernambuco, Brazil

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Ricardo Arraes de Alencar Ximenes, Demócrito de Barros Miranda-Filho, Ulisses Ramos Montarroyos, Celina Maria Turchi Martelli, Thalia Velho Barreto de Araújo, Elizabeth Brickley, Maria de Fátima Pessoa Militão de Albuquerque, Wayner Vieira Souza, Liana O. Ventura, Camila V. Ventura, Adriana L. Gois, Mariana C. Leal, Danielle Maria da Silva Oliveira, Sophie Helena Eickmann, Maria Durce C. G. Carvalho, Paula F. S. da Silva, Maria Angela Wanderley Rocha, Regina Coeli Ferreira Ramos, Sinval Pinto Brandão-Filho, Marli Tenorio Cordeiro, Luciana Caroline Albuquerque Bezerra, George Dimech, Sandra Valongueiro, Pedro Pires, Priscila Mayrelle da Silva Castanha, Rafael Dhalia, Ernesto Torres Azevedo Marques-Júnior, Laura C. Rodrigues, on behalf of the Microcephaly Epidemic Research Group (MERG)

Background

While Zika virus (ZIKV) is now widely recognized as a teratogen, the frequency and full spectrum of adverse outcomes of congenital ZIKV infection remains incompletely understood.

Methods

Participants in the MERG cohort of pregnant women with rash, recruited from the surveillance system from December/2015-June/2017. Exposure definition was based on a combination of longitudinal data from molecular, serologic (IgM and IgG3) and plaque reduction neutralization tests for ZIKV. Children were evaluated by a team of clinical specialists and by transfontanelle ultrasound and were classified as having microcephaly and/or other signs/symptoms consistent with congenital Zika syndrome (CZS). Risks of adverse outcomes were quantified according to the relative evidence of a ZIKV infection in pregnancy.

Findings

376 women had confirmed and suspected exposure to ZIKV. Among evaluable children born to these mothers, 20% presented with an adverse outcome compatible with exposure to ZIKV during pregnancy. The absolute risk of microcephaly was 2.9% (11/376), of calcifications and/or ventriculomegaly was 7.2% (13/180), of additional neurologic alterations was 5.3% (13/245), of ophthalmologic abnormalities was 7% (15/214), and of dysphagia was 1.8% (4/226). Less than 1% of the children experienced abnormalities across all of the domains simultaneously. Interpretation: Although approximately one-fifth of children with confirmed and suspected exposure to ZIKV in pregnancy presented with at least one abnormality compatible with CZS, the manifestations presented more frequently in isolation than in combination. Due to the rare nature of some outcomes and the possibility of later manifestations, large scale individual participant data meta-analysis and the long-term evaluation of children are imperative to identify the full spectrum of this syndrome and to plan actions to reduce damages.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Areli Martínez-Gamboa, María Dolores Niembro-Ortega, Pedro Torres-González, Janeth Santiago-Cruz, Nancy Guadalupe Velázquez-Zavala, Andrea Rangel-Cordero, Brenda Crabtree-Ramírez, Armando Gamboa-Domínguez, Edgardo Reyes-Gutiérrez, Gustavo Reyes-Terán, Víctor Hugo Lozano-Fernandez, Víctor Hugo Ahumada-Topete, Pedro Martínez-Ayala, Marisol Manríquez-Reyes, Juan Pablo Ramírez-Hinojosa, Patricia Rodríguez-Zulueta, Christian Hernández-León, Jesús Ruíz-Quiñones, Norma Eréndira Rivera-Martínez, Alberto Chaparro-Sánchez, Jaime Andrade-Villanueva, Luz Alicia González-Hernández, Sofia Cruz-Martínez, Oscar Flores-Barrientos, Jesús Enrique Gaytán-Martínez, Martín Magaña-Aquino, Axel Cervantes-Sánchez, Antonio Olivas-Martínez, Javier Araujo-Meléndez, María del Rocío Reyes-Montes, Esperanza Duarte-Escalante, María Guadalupe Frías-De León, José Antonio Ramírez, María Lucia Taylor, Alfredo Ponce de León-Garduño, José Sifuentes-Osornio

Background

The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine.

Methodology/Principal findings

We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA.The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively.

Conclusions/Significance

The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.

Sporadic outbreaks of crimean-congo haemorrhagic fever in Uganda, July 2018-January 2019

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Bernadette Basuta Mirembe, Angella Musewa, Daniel Kadobera, Esther Kisaakye, Doreen Birungi, Daniel Eurien, Luke Nyakarahuka, Stephen Balinandi, Alex Tumusiime, Jackson Kyondo, Sophia Mbula Mulei, Jimmy Baluku, Benon Kwesiga, Steven Ndugwa Kabwama, Bao-Ping Zhu, Julie R. Harris, Julius Julian Lutwama, Alex Riolexus Ario

Introduction

Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne, zoonotic viral disease that causes haemorrhagic symptoms. Despite having eight confirmed outbreaks between 2013 and 2017, all within Uganda’s ‘cattle corridor’, no targeted tick control programs exist in Uganda to prevent disease. During a seven-month-period from July 2018-January 2019, the Ministry of Health confirmed multiple independent CCHF outbreaks. We investigated to identify risk factors and recommend interventions to prevent future outbreaks.

Methods

We defined a confirmed case as sudden onset of fever (≥37.5°C) with ≥4 of the following signs and symptoms: anorexia, vomiting, diarrhoea, headache, abdominal pain, joint pain, or sudden unexplained bleeding in a resident of the affected districts who tested positive for Crimean-Congo haemorrhagic fever virus (CCHFv) by RT-PCR from 1 July 2018–30 January 2019. We reviewed medical records and performed active case-finding. We conducted a case-control study and compared exposures of case-patients with age-, sex-, and sub-county-matched control-persons (1:4).

Results

We identified 14 confirmed cases (64% males) with five deaths (case-fatality rate: 36%) from 11 districts in western and central region. Of these, eight (73%) case-patients resided in Uganda’s ‘cattle corridor’. One outbreak involved two case-patients and the remainder involved one. All case-patients had fever and 93% had unexplained bleeding. Case-patients were aged 6–36 years, with persons aged 20–44 years more affected (AR: 7.2/1,000,000) than persons ≤19 years (2.0/1,000,000), p = 0.015. Most (93%) case-patients had contact with livestock ≤2 weeks before symptom onset. Twelve (86%) lived <1 km from grazing fields compared with 27 (48%) controls (ORM-H = 18, 95% CI = 3.2-∞) and 10 (71%) of 14 case-patients found ticks attached to their bodies ≤2 weeks before symptom onset, compared to 15 (27%) of 56 control-persons (ORM-H = 9.3, 95%CI = 1.9–46).

Conclusions

CCHF outbreaks occurred sporadically during 2018–2019, both within and outside ‘cattle corridor’ districts of Uganda. Most cases were associated with tick exposure. The Ministry of Health should partner with the Ministry of Agriculture, Animal Industry and Fisheries to develop joint nationwide tick control programs and strategies with shared responsibilities through a One Health approach.

The role of livestock movements in the spread of Rift Valley fever virus in animals and humans in Mayotte, 2018–19

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Younjung Kim, Raphaëlle Métras, Laure Dommergues, Chouanibou Youssouffi, Soihibou Combo, Gilles Le Godais, Dirk U. Pfeiffer, Catherine Cêtre-Sossah, Eric Cardinale, Laurent Filleul, Hassani Youssouf, Marion Subiros, Guillaume Fournié

Rift Valley fever (RVF) is a vector-borne viral disease of major animal and public health importance. In 2018–19, it caused an epidemic in both livestock and human populations of the island of Mayotte. Using Bayesian modelling approaches, we assessed the spatio-temporal pattern of RVF virus (RVFV) infection in livestock and human populations across the island, and factors shaping it. First, we assessed if (i) livestock movements, (ii) spatial proximity from communes with infected animals, and (iii) livestock density were associated with the temporal sequence of RVFV introduction into Mayotte communes’ livestock populations. Second, we assessed whether the rate of human infection was associated with (a) spatial proximity from and (b) livestock density of communes with infected animals. Our analyses showed that the temporal sequence of RVFV introduction into communes’ livestock populations was associated with livestock movements and spatial proximity from communes with infected animals, with livestock movements being associated with the best model fit. Moreover, the pattern of human cases was associated with their spatial proximity from communes with infected animals, with the risk of human infection sharply increasing if livestock in the same or close communes were infected. This study highlights the importance of understanding livestock movement networks in informing the design of risk-based RVF surveillance programs.

Effects of a combined water and sanitation intervention on biomarkers of child environmental enteric dysfunction and associations with height-for-age z-score: A matched cohort study in rural Odisha, India

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Sheela S. Sinharoy, Heather E. Reese, Ira Praharaj, Howard H. Chang, Thomas Clasen

Poor water, sanitation and hygiene (WaSH) conditions are hypothesized to contribute to environmental enteric dysfunction (EED), a subclinical condition that may be associated with chronic undernutrition and impaired linear growth. We evaluated the effect of a combined water and sanitation intervention on biomarkers of EED, and then assessed associations of biomarkers of EED with height-for-age z-scores (HAZ), in children under five. We conducted a sub-study within a matched cohort study of a household-level water and sanitation infrastructure intervention in rural Odisha, India, in which we had observed an effect of the intervention on HAZ. We collected stool samples (N = 471) and anthropometry data (N = 209) for children under age 5. We analyzed stool samples for three biomarkers of EED: myeloperoxidase (MPO), neopterin (NEO), and α1-anti-trypsin (AAT). We used linear mixed models to estimate associations between the intervention and each biomarker of EED and between each biomarker and HAZ. The intervention was inversely associated with AAT (-0.25 log μg/ml, p = 0.025), suggesting a protective effect on EED, but was not associated with MPO or NEO. We observed an inverse association between MPO and HAZ (-0.031 per 1000 ng/ml MPO, p = 0.0090) but no association between either NEO or AAT and HAZ. Our results contribute evidence that a transformative WaSH infrastructure intervention may reduce intestinal permeability, but not intestinal inflammation and immune activation, in young children. Our study also adds to observational evidence of associations between intestinal inflammation and nutritional status, as measured by HAZ, in young children. Trial Registration: ClinicalTrials.gov (NCT02441699).

Early onset of neurological features differentiates two outbreaks of Lassa fever in Ebonyi state, Nigeria during 2017–2018

PLoS Neglected Tropical Diseases News - 8 March 2021 - 2:00pm

by Nneka M. Chika-Igwenyi, Rebecca E. Harrison, Christina Psarra, Julita Gil-Cuesta, Maria Gulamhusein, Emeka O. Onwe, Robinson C. Onoh, Uche S. Unigwe, Nnennaya A. Ajayi, Ugochukwu U. Nnadozie, Chiedozie K. Ojide, Damian U. Nwidi, Obumneme Ezeanosike, Emeka Sampson, Azuka S. Adeke, Collins N. Ugwu, Uchenna Anebonam, Jacques K. Tshiang, Jacob Maikere, Anthony Reid

Lassa fever (LF) is an acute viral haemorrhagic illness with various non-specific clinical manifestations. Neurological symptoms are rare at the early stage of the disease, but may be seen in late stages, in severely ill patients.The aim of this study was to describe the epidemiological evolution, socio-demographic profiles, clinical characteristics, and outcomes of patients seen during two Lassa fever outbreaks in Ebonyi State, between December 2017 and December 2018. Routinely collected clinical data from all patients admitted to the Virology Centre of the hospital during the period were analysed retrospectively.Out of a total of 83 cases, 70(84.3%) were RT-PCR confirmed while 13(15.7%) were probable cases. Sixtynine(83.1%) patients were seen in outbreak 1 of whom 53.6% were urban residents, while 19%, 15%, and 10% were farmers, students and health workers respectively. There were 14(16.8%)patients, seen in second outbreak with 92.9% rural residents. There were differences in clinical symptoms, signs and laboratory findings between the two outbreaks. The case fatality rates were 29.9% in outbreak 1 and 85.7% for outbreak 2. Neurological features and abnormal laboratory test results were associated with higher mortality rate, seen in outbreak 2. This study revealed significant differences between the two outbreaks. Of particular concern was the higher case fatality during the outbreak 2 which may be from a more virulent strain of the Lassa virus. This has important public health implications and further molecular studies are needed to better define its characteristics.

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