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Integrating testing for chronic strongyloidiasis within the Indigenous adult preventive health assessment system in endemic communities in the Northern Territory, Australia: An intervention study

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

by Wendy A. Page, Jenni A. Judd, David J. MacLaren, Petra Buettner

Background

The life-threatening clinical manifestations of strongyloidiasis are preventable with early detection and effective treatment. The aim of this study was to assess if there was an increase to the number and proportion of persons tested for chronic strongyloidiasis, as a result of integrating Strongyloides stercoralis serology into the existing preventive health assessment system in four Aboriginal health services in endemic communities.

Methodology

A prospective, longitudinal, before-and-after intervention study was conducted in four Aboriginal health services in remote endemically infected communities in the Northern Territory, Australia, from July 2012 to December 2016. The electronic patient information and recall systems enabled the integration of Strongyloides stercoralis serology into the adult preventive health assessment. Strongyloides reports for each health service were extracted half-yearly to examine the number and proportion of persons tested for chronic strongyloidiasis during the study and to measure the effect of the intervention.

Principal findings

The number and proportion of persons tested increased significantly during the study. From a total resident population of 3650 Indigenous adults over 15 years of age, 1686 persons (47.4%) were tested. The percentage of adults who had at least one serology test increased in all four health services to between 41% (446/1086) and 81.9% (172/210). Of the 1686 persons tested, 680 positive cases of chronic strongyloidiasis (40.3%) were identified.

Conclusions/Significance

This population health systems intervention increased the number and proportion of persons tested for chronic strongyloidiasis in four health services in endemically infected communities. This intervention is relevant to other health services with high-risk populations.

Patients infected with <i>Mycobacterium africanum</i> versus <i>Mycobacterium tuberculosis</i> possess distinct intestinal microbiota

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

by Sivaranjani Namasivayam, Bassirou Diarra, Seydou Diabate, Yeya dit Sadio Sarro, Amadou Kone, Bourahima Kone, Mohamed Tolofoudie, Bocar Baya, Mahamane T. Diakite, Ousmane Kodio, Keira Cohen, Jane Holl, Chad J. Achenbach, Soumya Chatterjee, Robert Leo Murphy, William Bishai, Souleymane Diallo, Alan Sher, Mamoudou Maiga

Background

Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB), is composed of eight subspecies. TB in West Africa, in contrast to other geographical regions, is caused by Mycobacterium africanum (MAF) in addition to M. tuberculosis (MTB), with both infections presenting similar symptoms. Nevertheless, MAF is considered to be hypovirulent in comparison with MTB and less likely to progress to active disease. In this study, we asked whether MAF and MTB infected patients possess distinct intestinal microbiomes and characterized how these microbiota communities are affected by anti-tuberculosis therapy (ATT). Additionally, we assessed if the changes in microbiota composition following infection correlate with pathogen induced alterations in host blood-gene expression.

Methods

A longitudinal, clinical study of MAF infected, MTB infected patients assessed at diagnosis and two months after start of ATT, and healthy, endemic controls was conducted to compare compositions of the fecal microbiome as determined by 16S rRNA sequencing. A blood transcriptome analysis was also performed on a subset of subjects in each group by microarray and the results cross-compared with the same individual’s microbiota composition.

Findings

MAF participants have distinct microbiomes compared with MTB patients, displaying decreased diversity and increases in Enterobacteriaceae with respect to healthy participants not observed in the latter patient group. Interestingly, this observed elevation in Enterobacteriaceae positively correlated with enhanced inflammatory gene expression in peripheral blood and was reversed after initiation of ATT.

Interpretation

Our findings indicate that MAF and MTB have distinct associations with the gut microbiome that may be reflective of the differential susceptibility of West Africans to these two co-endemic infections either as biomarkers or as a contributing determinant.

Tissue- and sex-specific lipidomic analysis of <i>Schistosoma mansoni</i> using high-resolution atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging

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

by Patrik Kadesch, Thomas Quack, Stefanie Gerbig, Christoph G. Grevelding, Bernhard Spengler

Schistosomes are human pathogens causing the neglected tropical disease schistosomiasis, which occurs worldwide in (sub-)tropical regions. This infectious disease is often associated with poverty, and more than 700 million people are at risk of infection. Exploitation of novel habitats and limited therapeutic options brought schistosomes into research focus. Schistosomes are the only trematodes that have evolved separate sexes. They are covered by their metabolically active tegument, a surface area representing the interface between male and female in their permanent mating contact but also between parasite and host. The tegument comprises, besides others, numerous specific lipid compounds. Limited information is available on the exact lipid composition and its spatial distribution. We used atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization (AP-SMALDI) mass spectrometry imaging (MSI) to characterize the Schistosoma mansoni tegument surface in comparison to tissue sections of whole worms or couples. We found that phosphatidylcholines (PC) and specific phosphatidylethanolamines (PE) are significantly more abundant inside the worm body compared to the tegument. On the other hand, the latter was found to be enriched in sphingomyelins (SM), phosphatidylserines (PS), lysophosphatidylcholines (LPC), and specific PE species. We further investigated lipid classes concerning number of carbon atoms in fatty acyl chains as well as the degree of unsaturation and found pronounced differences between the tegument and whole-worm body. Furthermore, differences between male and female teguments were found. The lipid composition of S. mansoni tissues has been investigated in an untargeted, spatially resolved manner for the first time.

A systematic review of alternative surveillance approaches for lymphatic filariasis in low prevalence settings: Implications for post-validation settings

PLoS Neglected Tropical Diseases News - 12 May 2020 - 9:00pm

by Nicholas Riches, Xavier Badia-Rius, Themba Mzilahowa, Louise A. Kelly-Hope

Due to the success of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) many countries have either eliminated the disease as a public health problem or are scheduled to achieve this elimination status in the coming years. The World Health Organization (WHO) recommend that the Transmission Assessment Survey (TAS) is used routinely for post-mass drug administration (MDA) surveillance but it is considered to lack sensitivity in low prevalence settings and not be suitable for post-validation surveillance. Currently there is limited evidence to support programme managers on the design of appropriate alternative strategies to TAS that can be used for post-validation surveillance, as recommended by the WHO. We searched for human and mosquito LF surveillance studies conducted between January 2000 and December 2018 in countries which had either completed MDA or had been validated as having eliminated LF. Article screening and selection were independently conducted. 44 papers met the eligibility criteria, summarising evidence from 22 countries and comprising 83 methodologically distinct surveillance studies. No standardised approach was reported. The most common study type was community-based human testing (n = 42, 47.2%), followed by mosquito xenomonitoring (n = 23, 25.8%) and alternative (non-TAS) forms of school-based human testing (n = 19, 21.3%). Most studies were cross-sectional (n = 61, 73.5%) and used non-random sampling methods. 11 different human diagnostic tests were described. Results suggest that sensitivity of LF surveillance can be increased by incorporating newer human diagnostic tests (including antibody tests) and the use of mosquito xenomonitoring may be able to help identify and target areas of active transmission. Alternative sampling methods including the addition of adults to routine surveillance methods and consideration of community-based sampling could also increase sensitivity. The evidence base to support post-validation surveillance remains limited. Further research is needed on the diagnostic performance and cost-effectiveness of new diagnostic tests and methodologies to guide policy decisions and must be conducted in a range of countries. Evidence on how to integrate surveillance within other routine healthcare processes is also important to support the ongoing sustainability of LF surveillance.

From importation to autochthonous transmission: Drivers of chikungunya and dengue emergence in a temperate area

PLoS Neglected Tropical Diseases News - 11 May 2020 - 9:00pm

by Frédéric Jourdain, David Roiz, Henriette de Valk, Harold Noël, Grégory L’Ambert, Florian Franke, Marie-Claire Paty, Anne Guinard, Jean-Claude Desenclos, Benjamin Roche

Background

The global spread of Aedes albopictus has exposed new geographical areas to the risk of dengue and chikungunya virus transmission. Several autochthonous transmission events have occurred in recent decades in Southern Europe and many indicators suggest that it will become more frequent in this region in the future. Environmental, socioeconomic and climatic factors are generally considered to trigger the emergence of these viruses. Accordingly, a greater knowledge of the determinants of this emergence in a European context is necessary to develop adapted surveillance and control strategies, and public health interventions.

Methodology/Principal findings

Using French surveillance data collected from between 2010 and 2018 in areas of Southern France where Ae. albopictus is already established, we assessed factors associated with the autochthonous transmission of dengue and chikungunya. Cases leading to autochthonous transmission were compared with those without subsequent transmission using binomial regression. We identified a long reporting delay (≥ 21 days) of imported cases to local health authorities as the main driver for autochthonous transmission of dengue and chikungunya in Southern France. The presence of wooded areas around the cases’ place of residence and the accumulation of heat during the season also increased the risk of autochthonous arbovirus transmission.

Conclusions

Our findings could inform policy-makers when developing strategies to the emerging threats of dengue and chikungunya in Southern Europe and can be extrapolated in this area to other viruses such as Zika and yellow fever, which share the same vector. Furthermore, our results allow a more accurate characterization of the environments most at risk, and highlight the importance of implementing surveillance systems which ensure the timely reporting and of imported cases and swift interventions.

Quantifying the localized relationship between vector containment activities and dengue incidence in a real-world setting: A spatial and time series modelling analysis based on geo-located data from Pakistan

PLoS Neglected Tropical Diseases News - 11 May 2020 - 9:00pm

by Nabeel Abdur Rehman, Henrik Salje, Moritz U G Kraemer, Lakshminarayanan Subramanian, Umar Saif, Rumi Chunara

Increasing urbanization is having a profound effect on infectious disease risk, posing significant challenges for governments to allocate limited resources for their optimal control at a sub-city scale. With recent advances in data collection practices, empirical evidence about the efficacy of highly localized containment and intervention activities, which can lead to optimal deployment of resources, is possible. However, there are several challenges in analyzing data from such real-world observational settings. Using data on 3.9 million instances of seven dengue vector containment activities collected between 2012 and 2017, here we develop and assess two frameworks for understanding how the generation of new dengue cases changes in space and time with respect to application of different types of containment activities. Accounting for the non-random deployment of each containment activity in relation to dengue cases and other types of containment activities, as well as deployment of activities in different epidemiological contexts, results from both frameworks reinforce existing knowledge about the efficacy of containment activities aimed at the adult phase of the mosquito lifecycle. Results show a 10% (95% CI: 1–19%) and 20% reduction (95% CI: 4–34%) reduction in probability of a case occurring in 50 meters and 30 days of cases which had Indoor Residual Spraying (IRS) and fogging performed in the immediate vicinity, respectively, compared to cases of similar epidemiological context and which had no containment in their vicinity. Simultaneously, limitations due to the real-world nature of activity deployment are used to guide recommendations for future deployment of resources during outbreaks as well as data collection practices. Conclusions from this study will enable more robust and comprehensive analyses of localized containment activities in resource-scarce urban settings and lead to improved allocation of resources of government in an outbreak setting.

Source reduction with a purpose: Mosquito ecology and community perspectives offer insights for improving household mosquito management in coastal Kenya

PLoS Neglected Tropical Diseases News - 11 May 2020 - 9:00pm

by Jenna E. Forsyth, Francis M. Mutuku, Lydiah Kibe, Luti Mwashee, Joyce Bongo, Chika Egemba, Nicole M. Ardoin, A. Desiree LaBeaud

Understanding mosquito breeding behavior as well as human perspectives and practices are crucial for designing interventions to control Aedes aegypti mosquito-borne diseases as these mosquitoes primarily breed in water-holding containers around people’s homes. The objectives of this study were to identify productive mosquito breeding habitats in coastal Kenya and to understand household mosquito management behaviors and their behavioral determinants. The field team conducted entomological surveys in 444 households and semi-structured interviews with 35 female caregivers and 37 children in Kwale County, coastal Kenya, between May and December 2016. All potential mosquito habitats with or without water were located, abundances of mosquito immatures measured and their characteristics recorded. Interviews explored household mosquito management behaviors and their behavioral determinants. 2,452 container mosquito habitats were counted containing 1,077 larvae and 390 pupae, predominantly Aedes species. More than one-third of the positive containers were found outside houses in 1 of the 10 villages. Containers holding water with no intended purpose contained 55.2% of all immature mosquitoes. Containers filled with rainwater held 95.8% of all immature mosquitoes. Interviews indicated that households prioritize sleeping under bednets as a primary protection against mosquito-borne disease because of concern about night-time biting, malaria-transmitting Anopheles mosquitoes. Respondents had limited knowledge about the mosquito life cycle, especially with respect to day-time biting, container-breeding Aedes mosquitoes. Therefore, respondents did not prioritize source reduction. Most mosquitoes breed in containers that have no direct or immediate purpose (“no-purpose containers”). These containers may be left unattended for several days allowing rainwater to collect, and creating ideal conditions for mosquito breeding. An intervention that requires little effort and targets only the most productive containers could effectively reduce mosquito indices and, relatedly, mosquito-borne disease risk.

Occupational exposure to <i>Brucella</i> spp.: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 11 May 2020 - 9:00pm

by Carine Rodrigues Pereira, João Vitor Fernandes Cotrim de Almeida, Izabela Regina Cardoso de Oliveira, Luciana Faria de Oliveira, Luciano José Pereira, Márcio Gilberto Zangerônimo, Andrey Pereira Lage, Elaine Maria Seles Dorneles

Brucellosis is a neglected zoonotic disease of remarkable importance worldwide. The focus of this systematic review was to investigate occupational brucellosis and to identify the main infection risks for each group exposed to the pathogen. Seven databases were used to identify papers related to occupational brucellosis: CABI, Cochrane, Pubmed, Scielo, Science Direct, Scopus and Web of Science. The search resulted in 6123 studies, of which 63 were selected using the quality assessment tools guided from National Institutes of Health (NIH) and Case Report Guidelines (CARE). Five different job-related groups were considered greatly exposed to the disease: rural workers, abattoir workers, veterinarians and veterinary assistants, laboratory workers and hunters. The main risk factors and exposure sources involved in the occupational infection observed from the analysis of the articles were direct contact with animal fluids, failure to comply with the use of personal protective equipment, accidental exposure to live attenuated anti-brucellosis vaccines and non-compliance with biosafety standards. Brucella species frequently isolated from job-related infection were Brucella melitensis, Brucella abortus, Brucella suis and Brucella canis. In addition, a meta-analysis was performed using the case-control studies and demonstrated that animal breeders, laboratory workers and abattoir workers have 3.47 [95% confidence interval (CI); 1.47–8.19] times more chance to become infected with Brucella spp. than others individuals that have no contact with the possible sources of infection. This systematic review improved the understanding of the epidemiology of brucellosis as an occupational disease. Rural workers, abattoir workers, veterinarians, laboratory workers and hunters were the groups more exposed to occupational Brucella spp. infection. Moreover, it was observed that the lack of knowledge about brucellosis among frequently exposed professionals, in addition to some behaviors, such as negligence in the use of individual and collective protective measures, increases the probability of infection.

Uncertainty and sensitivity analyses of extinction probabilities suggest that adult female mortality is the weakest link for populations of tsetse (<i>Glossina</i> spp)

PLoS Neglected Tropical Diseases News - 11 May 2020 - 9:00pm

by Elisha B. Are, John W. Hargrove

Background

A relatively simple life history allows us to derive an expression for the extinction probability of populations of tsetse, vectors of African sleeping sickness. We present the uncertainty and sensitivity analysis of the extinction probability, to offer key insights into factors affecting the control or eradication of tsetse populations.

Methods

We represent tsetse population growth as a branching process, and derive closed form estimates of population extinction from that model. Statistical and mathematical techniques are used to analyse the uncertainties in estimating extinction probability, and the sensitivity of the extinction probability to changes in input parameters representing the natural life history and vital dynamics of tsetse populations.

Results

For fixed values of input parameters, the sensitivity of extinction probability depends on the baseline parameter values. Extinction probability is most sensitive to the probability that a female is inseminated by a fertile male when daily pupal mortality is low, whereas the extinction probability is most sensitive to daily mortality rate for adult females when daily pupal mortality, and extinction probabilities, are high. Global uncertainty and sensitivity analysis show that daily mortality rate for adult females has the highest impact on the extinction probability.

Conclusions

The high correlation between extinction probability and daily female adult mortality gives a strong argument that control techniques which increase daily female adult mortality may be the single most effective means of ensuring eradication of tsetse population.

Incidence and epidemiological features of dengue in Sabah, Malaysia

PLoS Neglected Tropical Diseases News - 11 May 2020 - 9:00pm

by Amanda Murphy, Giri Shan Rajahram, Jenarun Jilip, Marilyn Maluda, Timothy William, Wenbiao Hu, Simon Reid, Gregor J. Devine, Francesca D. Frentiu

In South East Asia, dengue epidemics have increased in size and geographical distribution in recent years. We examined the spatiotemporal distribution and epidemiological characteristics of reported dengue cases in the predominantly rural state of Sabah, in Malaysian Borneo–an area where sylvatic and urban circulation of pathogens are known to intersect. Using a public health data set of routinely notified dengue cases in Sabah between 2010 and 2016, we described demographic and entomological risk factors, both before and after a 2014 change in the clinical case definition for the disease. Annual dengue incidence rates were spatially variable over the 7-year study period from 2010–2016 (state-wide mean annual incidence of 21 cases/100,000 people; range 5-42/100,000), but were highest in rural localities in the western districts of the state (Kuala Penyu, Nabawan, Tenom and Kota Marudu). Eastern districts exhibited lower overall dengue rates, although a high proportion of severe (haemorrhagic) dengue cases (44%) were focused in Sandakan and Tawau. Dengue incidence was highest for those aged between 10 and 29 years (24/100,000), and was slightly higher for males compared to females. Available vector surveillance data indicated that during large outbreaks in 2015 and 2016 the mosquito Aedes albopictus was more prevalent in both urban and rural households (House Index of 64%) than Ae. aegypti (15%). Demographic patterns remained unchanged both before and after the dengue case definition was changed; however, in the years following the change, reported case numbers increased substantially. Overall, these findings suggest that dengue outbreaks in Sabah are increasing in both urban and rural settings. Future studies to better understand the drivers of risk in specific age groups, genders and geographic locations, and to test the potential role of Ae. albopictus in transmission, may help target dengue prevention and control efforts.

Significant improvement in quality of life following surgery for hydrocoele caused by lymphatic filariasis in Malawi: A prospective cohort study

by Hannah Betts, Sarah Martindale, John Chiphwanya, Square Z. Mkwanda, Dorothy E. Matipula, Paul Ndhlovu, Charles Mackenzie, Mark J. Taylor, Louise A. Kelly-Hope

Background

Lymphatic filariasis (LF) is a mosquito-borne parasitic infection that causes significant disabling and disfiguring clinical manifestations. Hydrocoele (scrotal swelling) is the most common clinical condition, which affects an estimated 25 million men globally. The recommended strategy is surgical intervention, yet little is known about the impact of hydrocoele on men’s lives, and how it may change if they have access to surgery.

Methodology/Principal findings

We prospectively recruited and followed-up men who underwent surgery for hydrocoele at six hospitals in an LF endemic area of Malawi in December 2015. Men were interviewed at hospitals pre-surgery and followed-up at 3-months and 6-months post-surgery. Data on demographic characteristics, clinical condition, barriers to surgery, post-surgery symptoms/complications and quality of life indicators were collected and analysed pre- and post-surgery, by age group and stage of disease (mild/moderate vs. severe), using chi-square tests and student’s t test (paired).201 men were interviewed pre-surgery, 152 at 3-months and 137 at 6-months post-surgery. Most men had unilateral hydrocoeles (65.2%), mild/moderate stages (57.7%) with an average duration of 11.4 years. The most reported cause of hydrocoele was it being sexually transmitted (22.4%), and the main barrier to surgery was the cost (36.3%). Pre-surgery, a significant difference in the scrotum side affected was found by age group (X2 = 5.978, p = 0.05), and men with severe stage hydrocoele reported more problems with their quality of life those with mild/moderate stage (t = 2.793; p = 0.0006). Post-surgery, around half of the men reported some pain/discomfort (55.9%), swelling (8.6%), bleeding (3.3%) and infection (5.9%), most of which had resolved at 3-months when the most significant improvements in their quality of life were found (t = 21.3902; p = 0.000). Post-surgery at 6 months all men reported no physical, social, psychological problems and took no time off work.

Conclusion/Significance

Surgery had a significant positive impact on many aspects of a patient’s life, and the expansion of this treatment to all those affected in LF endemic areas would greatly improve the quality of men’s and their families’ lives, and greatly contribute to the global goal of providing universal health care.

Clinical findings of patients with coronavirus disease 2019 in Jiangsu province, China: A retrospective, multi-center study

by Rui Huang, Li Zhu, Leyang Xue, Longgen Liu, Xuebing Yan, Jian Wang, Biao Zhang, Tianmin Xu, Fang Ji, Yun Zhao, Juan Cheng, Yinling Wang, Huaping Shao, Shuqin Hong, Qi Cao, Chunyang Li, Xiang-an Zhao, Lei Zou, Dawen Sang, Haiyan Zhao, Xinying Guan, Xiaobing Chen, Chun Shan, Juan Xia, Yuxin Chen, Xiaomin Yan, Jie Wei, Chuanwu Zhu, Chao Wu

Limited data are available for clinical characteristics of patients with coronavirus disease 2019 (COVID-19) outside Wuhan. This study aimed to describe the clinical characteristics of COVID-19 and identify the risk factors for severe illness of COVID-19 in Jiangsu province, China. Clinical data of hospitalized COVID-19 patients were retrospectively collected in 8 hospitals from 8 cities of Jiangsu province, China. Clinical findings of COVID-19 patients were described and risk factors for severe illness of COVID-19 were analyzed. By Feb 10, 2020, 202 hospitalized patients with COVID-19 were enrolled. The median age of patients was 44.0 years (interquartile range, 33.0–54.0). 55 (27.2%) patients had comorbidities. At the onset of illness, the common symptoms were fever (156 [77.2%]) and cough (120 [59.4%]). 66 (32.7%) patients had lymphopenia. 193 (95.5%) patients had abnormal radiological findings. 11 (5.4%) patients were admitted to the intensive care unit and none of the patients died. 23 (11.4%) patients had severe illness. Severe illness of COVID-19 was independently associated with body mass index (BMI) ≥ 28 kg/m2 (odds ratio [OR], 9.219; 95% confidence interval [CI], 2.731 to 31.126; P<0.001) and a known history of type 2 diabetes (OR, 4.326; 95% CI, 1.059 to 17.668; P = 0.041). In this case series in Jiangsu Province, COVID-19 patients had less severe symptoms and had better outcomes than the initial COVID-19 patients in Wuhan. The BMI ≥ 28 kg/m2 and a known history of type 2 diabetes were independent risk factors of severe illness in patients with COVID-19.

The V410L knockdown resistance mutation occurs in island and continental populations of <i>Aedes aegypti</i> in West and Central Africa

by Constância F. J. Ayres, Gonçalo Seixas, Sílvia Borrego, Cátia Marques, Inilça Monteiro, Camila S. Marques, Bruna Gouveia, Silvania Leal, Arlete D. Troco, Filomeno Fortes, Ricardo Parreira, João Pinto, Carla A. Sousa

The extensive use of insecticides for vector control has led to the development of insecticide resistance in Aedes aegypti populations on a global scale, which has significantly compromised control actions. Insecticide resistance, and its underlying mechanisms, has been investigated in several countries, mostly in South American and Asian countries. In Africa, however, studies reporting insecticide resistance are rare and data on resistance mechanisms, notably knockdown resistance (kdr) mutations, is scarce. In this study, the recently described V410L kdr mutation is reported for the first time in old world Ae. aegypti populations, namely from Angola and Madeira island. Two additional kdr mutations, V1016I and F1534C, are also reported for the first time in populations from Angola and Cape Verde. Significant associations with the resistance phenotype were found for both V410L and V1016I individually as well as for tri-locus genotypes in the Angolan population. However, no association was found in Madeira island, probably due to the presence of a complex pattern of multiple insecticide resistance mechanisms in the local Ae. aegypti population. These results suggest that populations carrying the same kdr mutations may respond differently to the same insecticide, stressing the need for complementary studies when assessing the impact of kdr resistance mechanisms in the outcome of insecticide-based control strategies.

Eliminating yellow fever epidemics in Africa: Vaccine demand forecast and impact modelling

by Kévin Jean, Arran Hamlet, Justus Benzler, Laurence Cibrelus, Katy A. M. Gaythorpe, Amadou Sall, Neil M. Ferguson, Tini Garske

Background

To counter the increasing global risk of Yellow fever (YF), the World Health Organisation initiated the Eliminate Yellow fever Epidemics (EYE) strategy. Estimating YF burden, as well as vaccine impact, while accounting for the features of urban YF transmission such as indirect benefits of vaccination, is key to informing this strategy.

Methods and findings

We developed two model variants to estimate YF burden in sub-Saharan Africa, assuming all infections stem from either the sylvatic or the urban cycle of the disease. Both relied on an ecological niche model fitted to the local presence of any YF reported event in 34 African countries. We calibrated under-reporting using independent estimates of transmission intensity provided by 12 serological surveys performed in 11 countries. We calculated local numbers of YF infections, deaths and disability-adjusted life years (DALYs) lost based on estimated transmission intensity while accounting for time-varying vaccination coverage. We estimated vaccine demand and impact of future preventive mass vaccination campaigns (PMVCs) according to various vaccination scenarios.Vaccination activities conducted in Africa between 2005 and 2017 were estimated to prevent from 3.3 (95% CI 1.2–7.7) to 6.1 (95% CI 2.4–13.2) millions of deaths over the lifetime of vaccinees, representing extreme scenarios of none or maximal herd effects, respectively. By prioritizing provinces based on the risk of urban YF transmission in future PMVCs, an average of 37.7 million annual doses for PMVCs over eight years would avert an estimated 9,900,000 (95% CI 7,000,000–13,400,000) infections and 480,000 (180,000–1,140,000) deaths over the lifetime of vaccinees, corresponding to 1.7 (0.7–4.1) deaths averted per 1,000 vaccine doses.

Conclusions

By estimating YF burden and vaccine impact over a range of spatial and temporal scales, while accounting for the specificity of urban transmission, our model can be used to inform the current EYE strategy.

Molecular surveillance over 14 years confirms reduction of <i>Plasmodium vivax</i> and <i>falciparum</i> transmission after implementation of Artemisinin-based combination therapy in Papua, Indonesia

by Zuleima Pava, Agatha M. Puspitasari, Angela Rumaseb, Irene Handayuni, Leily Trianty, Retno A. S. Utami, Yusrifar K. Tirta, Faustina Burdam, Enny Kenangalem, Grennady Wirjanata, Steven Kho, Hidayat Trimarsanto, Nicholas M. Anstey, Jeanne Rini Poespoprodjo, Rintis Noviyanti, Ric N. Price, Jutta Marfurt, Sarah Auburn

Genetic epidemiology can provide important insights into parasite transmission that can inform public health interventions. The current study compared long-term changes in the genetic diversity and structure of co-endemic Plasmodium falciparum and P. vivax populations. The study was conducted in Papua Indonesia, where high-grade chloroquine resistance in P. falciparum and P. vivax led to a universal policy of Artemisinin-based Combination Therapy (ACT) in 2006. Microsatellite typing and population genetic analyses were undertaken on available isolates collected between 2004 and 2017 from patients with uncomplicated malaria (n = 666 P. falciparum and n = 615 P. vivax). The proportion of polyclonal P. falciparum infections fell from 28% (38/135) before policy change (2004–2006) to 18% (22/125) at the end of the study (2015–2017); p<0.001. Over the same period, polyclonal P. vivax infections fell from 67% (80/119) to 35% (33/93); p<0.001. P. falciparum strains persisted for up to 9 years compared to 3 months for P. vivax, reflecting higher rates of outbreeding in the latter. Sub-structure was observed in the P. falciparum population, but not in P. vivax, confirming different patterns of outbreeding. The P. falciparum population exhibited 4 subpopulations that changed in frequency over time. Notably, a sharp rise was observed in the frequency of a minor subpopulation (K2) in the late post-ACT period, accounting for 100% of infections in late 2016–2017. The results confirm epidemiological evidence of reduced P. falciparum and P. vivax transmission over time. The smaller change in P. vivax population structure is consistent with greater outbreeding associated with relapsing infections and highlights the need for radical cure to reduce recurrent infections. The study emphasizes the challenge in disrupting P. vivax transmission and demonstrates the potential of molecular data to inform on the impact of public health interventions.

COVID-19 in Latin America: Novel transmission dynamics for a global pandemic?

by Matthew J. Miller, Jose R. Loaiza, Anshule Takyar, Robert H. Gilman

Cystic echinococcosis in the Eastern Mediterranean region: Neglected and prevailing!

by Mehdi Borhani, Saeid Fathi, Samia Lahmar, Haroon Ahmed, Mohanad Faris Abdulhameed, Majid Fasihi Harandi

Cystic echinococcosis (CE) is distributed worldwide, extending from China to the Middle East and from Mediterranean countries to the sub-Saharan Africa and South America. According to WHO, one million people around the world are suffering from CE with an estimated burden of 183,573 DALYs. The annual monetary burden of the disease due to treatment costs and CE-related livestock losses has been estimated at US$ 3 billion. CE is endemic in all countries within the WHO Eastern Mediterranean Regional Office (EMRO). The region, which includes most of the Middle East and North Africa, is one of the most ancient foci of the domestic cycle of CE and is recognized as one of the major hotspots of CE. There are 22 countries in the EMRO, where about 688 million people are living at risk of CE. In many EMRO countries, little is known about CE epidemiology and transmission. WHO included echinococcosis in a list of 17 neglected tropical diseases (NTDs) and 12 neglected zoonotic diseases (NZDs). Accordingly, different regional offices of WHO organized several initiatives for CE control and prevention. WHO’s Western Pacific regional office considered echinococcosis as one of the region’s major health topics, and several preventive measures have been implemented in the American region with the support of Pan American Health Organization (PAHO) in Argentina, Peru, Uruguay, and Chile. Although CE is endemic in all 22 EMRO countries, surprisingly, CE is absent from the health topics list of diseases and conditions in this region. Therefore, CE clearly requires further attention in the WHO EMRO agenda, and the need for elaboration of specific measures for CE control is becoming apparent in EMRO countries, where substantial collaborations among the member states and WHO EMRO is of paramount importance. Major topics of collaborative activities include training programs and health communication on different aspects of CE control, analysis of CE burden, national and international surveillance and disease registry systems, technical support to promote epidemiological studies for collecting baseline data, cost–benefit analysis of control interventions, and intersectoral cooperation among the agriculture, veterinary, medical, and health sectors.

Extinction probabilities as a function of temperature for populations of tsetse (<i>Glossina</i> spp.)

by Elisha B. Are, John W. Hargrove

Significant reductions in populations of tsetse (Glossina spp) in parts of Zimbabwe have been attributed to increases in temperature over recent decades. Sustained increases in temperature might lead to local extinctions of tsetse populations. Extinction probabilities for tsetse populations have not so far been estimated as a function of temperature. We develop a time-homogeneous branching process model for situations where tsetse live at different levels of fixed temperature. We derive a probability distribution pk(T) for the number of female offspring an adult female tsetse is expected to produce in her lifetime, as a function of the fixed temperature at which she is living. We show that pk(T) can be expressed as a geometric series: its generating function is therefore a fractional linear type. We obtain expressions for the extinction probability, reproduction number, time to extinction and growth rates. The results are valid for all tsetse, but detailed effects of temperature will vary between species. No G. m. morsitans population can escape extinction if subjected, for extended periods, to temperatures outside the range 16°C–32°C. Extinction probability increases more rapidly as temperatures approach and exceed the upper and lower limits. If the number of females is large enough, the population can still survive even at high temperatures (28°C–31°C). Small decreases or increases in constant temperature in the neighbourhoods of 16°C and 31°C, respectively, can drive tsetse populations to extinction. Further study is needed to estimate extinction probabilities for tsetse populations in field situations where temperatures vary continuously.

Transcriptome of the parasitic flatworm <i>Schistosoma mansoni</i> during intra-mammalian development

by Arporn Wangwiwatsin, Anna V. Protasio, Shona Wilson, Christian Owusu, Nancy E. Holroyd, Mandy J. Sanders, Jacqueline Keane, Mike J. Doenhoff, Gabriel Rinaldi, Matthew Berriman

Schistosomes are parasitic blood flukes that survive for many years within the mammalian host vasculature. How the parasites establish a chronic infection in the hostile bloodstream environment, whilst evading the host immune response is poorly understood. The parasite develops morphologically and grows as it migrates to its preferred vascular niche, avoiding or repairing damage from the host immune system. In this study, we investigated temporal changes in gene expression during the intra-mammalian development of Schistosoma mansoni. RNA-seq data were analysed from parasites developing in the lung through to egg-laying mature adult worms, providing a comprehensive picture of in vivo intra-mammalian development. Remarkably, genes involved in signalling pathways, developmental control, and adaptation to oxidative stress were up-regulated in the lung stage. The data also suggested a potential role in immune evasion for a previously uncharacterised gene. This study not only provides a large and comprehensive data resource for the research community, but also reveals new directions for further characterising host–parasite interactions that could ultimately lead to new control strategies for this neglected tropical disease pathogen.

<i>Toxocara</i> species environmental contamination of public spaces in New York City

by Donna L. Tyungu, David McCormick, Carla Lee Lau, Michael Chang, James R. Murphy, Peter J. Hotez, Rojelio Mejia, Henry Pollack

Human toxocariasis has been identified as an under-diagnosed parasitic zoonosis and health disparity of significant public health importance in the United States due to its high seropositivity among socioeconomically disadvantaged groups, and possible links to cognitive and developmental delays. Through microscopy and quantitative PCR, we detected that Toxocara eggs are widespread in New York City public spaces, with evidence of significant levels of contamination in all five boroughs. The Bronx had the highest contamination rate (66.7%), while Manhattan had the lowest contamination rate (29.6%). Moreover, infective eggs were only found in the Bronx playgrounds, with over 70% of eggs recovered in embryonic form and the highest egg burden (p = 0.0365). All other boroughs had eggs in the pre-infectious, unembronyated form. Toxocara cati, the cat roundworm, was the predominant species. These results suggest that feral or untreated cats in New York City represent a significant source of environmental contamination. These findings indicate that human toxocariasis has emerged as an important health disparity in New York City, with ongoing risk of acquiring Toxocara infection in public spaces, especially in poorer neighborhoods. There is a need for reducing environmental Toxocara contamination. Additional rigorous public health interventions should explore further approaches to interrupt transmission to humans.

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