Systematic Review of Scales for Measuring Infectious Disease-Related Stigma.

Infectious disease outbreaks are associated with substantial stigma, which can have negative effects on affected persons and communities and on outbreak control. Thus, measuring stigma in a standardized and validated manner early in an outbreak is critical to disease control. We reviewed existing scales used to assess stigma during outbreaks. Our findings show that many different scales have been developed, but few have been used more than once, have been adequately validated, or have been tested in different disease and geographic contexts. We found that scales were usually developed too slowly to be informative early during an outbreak and were published a median of 2 years after the first case of an outbreak. A rigorously developed, transferable stigma scale is needed to assess and direct responses to stigma during infectious disease outbreaks.

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.

Go.Data as a digital tool for case investigation and contact tracing in the context of COVID-19: a mixed-methods study.

BACKGROUND: A manual approach to case investigation and contact tracing can introduce delays in response and challenges for field teams. Go.Data, an outbreak response tool developed by the World Health Organization (WHO) in collaboration with the Global Outbreak Alert and Response Network, streamlines data collection and analysis during outbreaks. This study aimed to characterize Go.Data use during COVID-19, elicit shared benefits and challenges, and highlight key opportunities for enhancement. METHODS: This study utilized mixed methods through qualitative interviews and a quantitative survey with Go.Data implementors on their experiences during COVID-19. Survey data was analyzed for basic univariate statistics. Interview data were coded using deductive and inductive reasoning and thematic analysis of categories. Overarching themes were triangulated with survey data to clarify key findings. RESULTS: From April to June 2022, the research team conducted 33 interviews and collected 41 survey responses. Participants were distributed across all six WHO regions and 28 countries. While most implementations represented government actors at national or subnational levels, additional inputs were collected from United Nations agencies and universities. Results highlighted WHO endorsement, accessibility, adaptability, and flexible support modalities as main enabling factors. Formalization and standardization of data systems and people processes to prepare for future outbreaks were a welcomed byproduct of implementation, as 76% used paper-based reporting prior and benefited from increased coordination around a shared platform. Several challenges surfaced, including shortage of the appropriate personnel and skill-mix within teams to ensure smooth implementation. Among opportunities for enhancements were improved product documentation and features to improve usability with large data volumes. CONCLUSIONS: This study was the first to provide a comprehensive picture of Go.Data implementations during COVID-19 and what joint lessons could be learned. It ultimately demonstrated that Go.Data was a useful complement to responses across diverse contexts, and helped set a reproducible foundation for future outbreaks. Concerted preparedness efforts across the domains of workforce composition, data architecture and political sensitization should be prioritized as key ingredients for future Go.Data implementations. While major developments in Go.Data functionality have addressed some key gaps highlighted during the pandemic, continued dialogue between WHO and implementors, including cross-country experience sharing, is needed ensure the tool is reactive to evolving user needs.

Seroprevalence of anti-Lassa Virus IgG antibodies in three districts of Sierra Leone: A cross-sectional, population-based study.

BACKGROUND: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The prevalence of exposure to LASV in Sierra Leone is crudely estimated and largely unknown. This cross-sectional study aimed to establish a baseline point seroprevalence of IgG antibodies to LASV in three administrative districts of Sierra Leone and identify potential risk factors for seropositivity and LASV exposure. METHODOLOGY AND PRINCIPAL FINDINGS: Between 2015 and 2018, over 10,642 participants from Kenema, Tonkolili, and Port Loko Districts were enrolled in this cross-sectional study. Previous LASV and LF epidemiological studies support classification of these districts as "endemic," "emerging," and "non-endemic", respectively. Dried blood spot samples were tested for LASV antibodies by ELISA to determine the seropositivity of participants, indicating previous exposure to LASV. Surveys were administered to each participant to assess demographic and environmental factors associated with a higher risk of exposure to LASV. Overall seroprevalence for antibodies to LASV was 16.0%. In Kenema, Port Loko, and Tonkolili Districts, seroprevalences were 20.1%, 14.1%, and 10.6%, respectively. In a multivariate analysis, individuals were more likely to be LASV seropositive if they were living in Kenema District, regardless of sex, age, or occupation. Environmental factors contributed to an increased risk of LASV exposure, including poor housing construction and proximity to bushland, forested areas, and refuse. CONCLUSIONS AND SIGNIFICANCE: In this study we determine a baseline LASV seroprevalence in three districts which will inform future epidemiological, ecological, and clinical studies on LF and the LASV in Sierra Leone. The heterogeneity of the distribution of LASV and LF over both space, and time, can make the design of efficacy trials and intervention programs difficult. Having more studies on the prevalence of LASV and identifying potential hyper-endemic areas will greatly increase the awareness of LF and improve targeted control programs related to LASV.

Fertility decision-making during the Zika virus epidemic in Brazil: Where is the decision?

BACKGROUND: In 2016, a Public Health Emergency of International Concern (PHEIC) was declared in response to the rise of microcephaly cases among newborns in Northeastern Brazil. A common reactionary measure by public health authorities was to recommend women postpone pregnancy to avoid the possible perinatal transmission of Zika virus (ZIKV). METHODS: The purpose of this study was to assess how women in Fortaleza, Brazil conceptualize pregnancy; experience facilitators and barriers to pregnancy avoidance; perceive the authorities' recommendation to postpone pregnancy due to the ZIKV outbreak; and recall their experiences during the ZIKV epidemic. Qualitative methods, specifically a Rapid Anthropological Assessment (RAA), were utilized in this study. Data collection included semi-structured interviews, triangulated with observations and informal interviews with community members. RESULTS: The sample included 35 women (18-39 years old) who exclusively utilized the national public health care system. Findings indicated that all participants perceived the ZIKV pregnancy-postponement recommendation to be counter-cultural to Brazilian social norms. Overall women's self-perceived agency to prevent pregnancy was low due to social expectations and lack of trust for contraceptives. ZIKV prevention was not seen as a reason to utilize contraceptives. Interestingly, only women who self-perceived as more affluent were willing to attempt pregnancy prevention for educational, occupational, or financial opportunity. CONCLUSION: Pregnancy postponement as a response to a ZIKV epidemic ignores gaps in reproductive agency and defies social norms, making it unrealistic and counter-cultural. Future ZIKV health recommendations must be culturally aligned with the population, and address barriers and motivators for family planning.

Exploring perceived risk for COVID-19 and its role in protective behavior and COVID-19 vaccine hesitancy: a qualitative study after the first wave.

BACKGROUND: The novel coronavirus pandemic (COVID-19) has had severe impacts on morbidity and mortality globally. METHODS: This study was set in rural central Kentucky and included participants recruited from public spaces. Fifteen qualitative interviews about personal experiences during the COVID-19 pandemic were conducted by phone from July 3 to July 24, 2020. Interviews were recorded, transcribed, and coded using a grounded theory approach. RESULTS: Participants who perceived COVID-19 to be a severe risk tended to have personal health concerns and therefore reported taking protective measures for themselves. A slightly smaller proportion of participants reported taking measures to protect others (particularly family). A minority of participants had an ambivalent attitude towards the risk and only took measures if required. COVID-19 vaccine acceptability was low with most participants expressing concerns regarding their need for a vaccine, safety of this vaccine, the value of personal rights, or future vaccine supply. CONCLUSIONS: Most participants perceived some risk of COVID-19 and took steps to prevent infections in themselves and others. Mandates for mask use in certain locations were additionally useful for those who had an ambivalent attitude towards the risk of illness. There was surprisingly little connection between perceiving COVID-19 risk and a desire for the COVID-19 vaccine. In this setting, vaccine acceptability was low, with vaccine concerns outweighing perceived potential benefits. In conclusion, because the risk was often constructed in terms of worries for themselves and others, the framing of health education materials for protective behaviors in these terms may be effective. Furthermore, future COVID-19 vaccine education should address vaccine knowledge and concerns, such as the need for a vaccine and its safety, and emphasize how a vaccination would reduce their chances of severe disease if they were to get sick.

How Fear Appeal Approaches in COVID-19 Health Communication May Be Harming the Global Community.

As health professionals develop health communication for coronavirus disease 2019 (COVID-19), we implore that these communication approaches do not include fear appeals. Fear appeals, also known as scare tactics, have been widely used to promote recommended preventive behaviors. We contend that unintended negative outcomes can result from fear appeals that intensify the already complex pandemic and efforts to contain it. We encourage public health professionals to reevaluate their desire to use fear appeals in COVID-19 health communication and recommend that evidence-based health communication be utilized to address the needs of a specific community, help people understand what they are being asked to do, explain step-by-step how to complete preventative behaviors, and consider external factors needed to support the uptake of behaviors. To aid health professionals in redirecting away from the use of fear appeals, we offer a phased approach to creating health communication messages during the COVID-19 crisis.

Author Correction: Impacts of environmental and socio-economic factors on emergence and epidemic potential of Ebola in Africa.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Impacts of environmental and socio-economic factors on emergence and epidemic potential of Ebola in Africa.

Recent outbreaks of animal-borne emerging infectious diseases have likely been precipitated by a complex interplay of changing ecological, epidemiological and socio-economic factors. Here, we develop modelling methods that capture elements of each of these factors, to predict the risk of Ebola virus disease (EVD) across time and space. Our modelling results match previously-observed outbreak patterns with high accuracy, and suggest further outbreaks could occur across most of West and Central Africa. Trends in the underlying drivers of EVD risk suggest a 1.75 to 3.2-fold increase in the endemic rate of animal-human viral spill-overs in Africa by 2070, given current modes of healthcare intervention. Future global change scenarios with higher human population growth and lower rates of socio-economic development yield a fourfold higher likelihood of epidemics occurring as a result of spill-over events. Our modelling framework can be used to target interventions designed to reduce epidemic risk for many zoonotic diseases.

Human Monkeypox in Sierra Leone after 44-Year Absence of Reported Cases.

We note the reemergence of human monkeypox in Sierra Leone following a 44-year absence of reported disease. The persons affected were an 11-month-old boy and, several years later, a 35-year-old man. The reappearance of monkeypox in this country suggests a need for renewed vigilance and awareness of the disease and its manifestations.

Understanding the cryptic nature of Lassa fever in West Africa.

Lassa fever (LF) is increasingly recognized by global health institutions as an important rodent-borne disease with severe impacts on some of West Africa's poorest communities. However, our knowledge of LF ecology, epidemiology and distribution is limited, which presents barriers to both short-term disease forecasting and prediction of long-term impacts of environmental change on Lassa virus (LASV) zoonotic transmission dynamics. Here, we synthesize current knowledge to show that extrapolations from past research have produced an incomplete picture of the incidence and distribution of LF, with negative consequences for policy planning, medical treatment and management interventions. Although the recent increase in LF case reports is likely due to improved surveillance, recent studies suggest that future socio-ecological changes in West Africa may drive increases in LF burden. Future research should focus on the geographical distribution and disease burden of LF, in order to improve its integration into public policy and disease control strategies.

Local disease-ecosystem-livelihood dynamics: reflections from comparative case studies in Africa.

This article explores the implications for human health of local interactions between disease, ecosystems and livelihoods. Five interdisciplinary case studies addressed zoonotic diseases in African settings: Rift Valley fever (RVF) in Kenya, human African trypanosomiasis in Zambia and Zimbabwe, Lassa fever in Sierra Leone and henipaviruses in Ghana. Each explored how ecological changes and human-ecosystem interactions affect pathogen dynamics and hence the likelihood of zoonotic spillover and transmission, and how socially differentiated peoples' interactions with ecosystems and animals affect their exposure to disease. Cross-case analysis highlights how these dynamics vary by ecosystem type, across a range from humid forest to semi-arid savannah; the significance of interacting temporal and spatial scales; and the importance of mosaic and patch dynamics. Ecosystem interactions and services central to different people's livelihoods and well-being include pastoralism and agro-pastoralism, commercial and subsistence crop farming, hunting, collecting food, fuelwood and medicines, and cultural practices. There are synergies, but also tensions and trade-offs, between ecosystem changes that benefit livelihoods and affect disease. Understanding these can inform 'One Health' approaches towards managing ecosystems in ways that reduce disease risks and burdens.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'.

Contact tracing performance during the Ebola virus disease outbreak in Kenema district, Sierra Leone.

Contact tracing in an Ebola virus disease (EVD) outbreak is the process of identifying individuals who may have been exposed to infected persons with the virus, followed by monitoring for 21 days (the maximum incubation period) from the date of the most recent exposure. The goal is to achieve early detection and isolation of any new cases in order to prevent further transmission. We performed a retrospective data analysis of 261 probable and confirmed EVD cases in the national EVD database and 2525 contacts in the Contact Line Lists in Kenema district, Sierra Leone between 27 April and 4 September 2014 to assess the performance of contact tracing during the initial stage of the outbreak. The completion rate of the 21-day monitoring period was 89% among the 2525 contacts. However, only 44% of the EVD cases had contacts registered in the Contact Line List and 6% of probable or confirmed cases had previously been identified as contacts. Touching the body fluids of the case and having direct physical contact with the body of the case conferred a 9- and 20-fold increased risk of EVD status, respectively. Our findings indicate that incompleteness of contact tracing led to considerable unmonitored transmission in the early months of the epidemic. To improve the performance of early outbreak contact tracing in resource poor settings, our results suggest the need for prioritized contact tracing after careful risk assessment and better alignment of Contact Line Listing with case ascertainment and investigation.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.

A Unified Framework for the Infection Dynamics of Zoonotic Spillover and Spread.

A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.e. transmission of pathogens from animals to humans, and 'stuttering transmission', i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir.

Clinical validation trial of a diagnostic for Ebola Zaire antigen detection: Design rationale and challenges to implementation.

The current Ebola outbreak in West Africa has affected more people than all previous outbreaks combined. The current diagnostic method of choice, quantitative polymerase chain reaction, requires specialized conditions as well as specially trained technicians. Insufficient testing capacity has extended the time from sample collection to results. These delays have led to further delays in the transfer and treatment to Ebola Treatment Units. A sensitive and specific point-of-care device that could be used reliably in low-resource settings by healthcare workers with minimal training would increase the efficiency of triage and appropriate transfer of care. This article describes a study designed to validate the sensitivity and specificity of the ReEBOVTM Rapid Diagnostic Test using venous whole blood and capillary blood obtained via fingerprick. We present the scientific and clinical rationale for the decisions made in the design of a diagnostic validation study to be conducted in an outbreak setting. The multi-site strategy greatly complicated implementation. In addition, a decrease in cases in one geographic area along with a concomitant increase in other areas made site selection challenging. Initiation of clinical trials during rapidly evolving outbreaks requires significant cooperation on a national level between research teams implementing studies and clinical care providers. Coordination and streamlining of approval process are essential if trials are to be implemented in a timely fashion.

Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.

The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT.

Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.

The 2013-2015 Ebola virus disease (EVD) epidemic is caused by the Makona variant of Ebola virus (EBOV). Early in the epidemic, genome sequencing provided insights into virus evolution and transmission and offered important information for outbreak response. Here, we analyze sequences from 232 patients sampled over 7 months in Sierra Leone, along with 86 previously released genomes from earlier in the epidemic. We confirm sustained human-to-human transmission within Sierra Leone and find no evidence for import or export of EBOV across national borders after its initial introduction. Using high-depth replicate sequencing, we observe both host-to-host transmission and recurrent emergence of intrahost genetic variants. We trace the increasing impact of purifying selection in suppressing the accumulation of nonsynonymous mutations over time. Finally, we note changes in the mucin-like domain of EBOV glycoprotein that merit further investigation. These findings clarify the movement of EBOV within the region and describe viral evolution during prolonged human-to-human transmission.

Understanding the emergence of ebola virus disease in sierra leone: stalking the virus in the threatening wake of emergence.

Since Ebola Virus Disease (EVD) was first identified in 1976 in what is now the Democratic Republic of Congo, and despite the numerous outbreaks recorded to date, rarely has an epidemic origin been identified. Indeed, among the twenty-one most documented EVD outbreaks in Africa, an index case has been identified four times, and hypothesized in only two other instances. The initial steps of emergence and spread of a virus are critical in the development of a potential outbreak and need to be thoroughly dissected and understood in order to improve on preventative strategies. In the current West African outbreak of EVD, a unique index case has been identified, pinpointing the geographical origin of the epidemic in Guinea. Herein, we provide an accounting of events that serve as the footprint of EVD emergence in Sierra Leone and a road map for risk mitigation fueled by lessons learned.

Sequence variability and geographic distribution of Lassa virus, Sierra Leone.

Lassa virus (LASV) is endemic to parts of West Africa and causes highly fatal hemorrhagic fever. The multimammate rat (Mastomys natalensis) is the only known reservoir of LASV. Most human infections result from zoonotic transmission. The very diverse LASV genome has 4 major lineages associated with different geographic locations. We used reverse transcription PCR and resequencing microarrays to detect LASV in 41 of 214 samples from rodents captured at 8 locations in Sierra Leone. Phylogenetic analysis of partial sequences of nucleoprotein (NP), glycoprotein precursor (GPC), and polymerase (L) genes showed 5 separate clades within lineage IV of LASV in this country. The sequence diversity was higher than previously observed; mean diversity was 7.01% for nucleoprotein gene at the nucleotide level. These results may have major implications for designing diagnostic tests and therapeutic agents for LASV infections in Sierra Leone.

Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of lassa fever.

BACKGROUND: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost [Formula: see text] of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals ('super-spreaders'), as we found only [Formula: see text] of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) [Formula: see text], with a maximum value up to [Formula: see text]. CONCLUSIONS/SIGNIFICANCE: This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.