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.

Self-Assessed Severity as a Determinant of Coronavirus Disease 2019 Symptom Specificity: A Longitudinal Cohort Study.

Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%-66.7%) to 31.5% (95% CI, 25.7%- 38.0%) but increased specificity from 77.5% (95% CI, 75.3%-79.5%) to 93.8% (95% CI, 92.7%-94.8%).

Community Perceptions of Village Health Workers in Kisoro, Uganda.

Background: Village health workers (VHWs) can serve as a valuable resource to address public health needs in resource-limited settings such as Uganda. However, the successful implementation of VHW programs can be limited by poor acceptability among community members. Kisoro District Hospital (KDH) in Kisoro District, Uganda operates a VHW program and, at the time of the study, was expanding its services to 11 additional villages. Objective: The objective of this study was to evaluate community perceptions of VHWs in villages of Kisoro District with no prior exposure to the KDH VHW program in order to improve community acceptance when expanding the program to additional villages. Methods: We administered surveys to 658 community members from 11 villages to evaluate their perceptions of VHWs prior to receiving VHW services. Additionally, we conducted focus group discussions among 97 participants to explore perceptions of VHWs in further depth. Findings: Community members were generally accepting of VHWs. They preferred that VHWs provide both curative and preventive services across a broad range of health domains as opposed to a single disease. Expectations of the responsibilities of a VHW were influenced by agricultural occupational and household responsibilities, particularly for women. Participants expressed a preference to be actively involved in the selection and oversight of VHWs and that VHWs receive compensation. Conclusions: 1) Community members' expectations of VHWs are shaped by environmental, cultural, and social factors. 2) Active community engagement in the VHW program is key. 3) Aligning a VHW program with community perceptions may improve acceptance, in turn influencing effectiveness and sustainability. These findings were used to expand the KDH VHW Program into the participating villages in a manner consistent with community preferences. Our findings may provide guidance on enhancing the uptake of community-based VHW programs for VHW stakeholders and policymakers in other settings.

Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination.

The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of disease-modifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time. The infectious side-effect profile as well as the route and frequency of administration of each therapeutic agent should be carefully considered when selecting a new treatment or deciding on risk mitigation strategies for existing therapy. More importantly, the impact of each agent on the future severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccine should be carefully considered in treatment decisions. Moreover, some multiple sclerosis therapies may have beneficial antiviral effects against SARS-CoV-2 while others may have beneficial immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease. Conventional injectables have a favorable immune profile without an increased exposure risk and therefore may be suitable for mild multiple sclerosis during the pandemic. However, moderate and highly active multiple sclerosis will continue to require treatment with oral or intravenous high-potency agents but a number of risk mitigation strategies may have to be implemented. Immune-modulating therapies such as the fumerates, sphinogosine-1P modulators, and natalizumab may be anecdotally preferred over cell-depleting immunosuppressants during the pandemic from the immune profile standpoint. Within the cell-depleting agents, selective (ocrelizumab) or preferential (cladribine) depletion of B cells may be relatively safer than non-selective depletion of lymphocytes and innate immune cells (alemtuzumab). Patients who develop severe iatrogenic or idiosyncratic lymphopenia should be advised to maintain social distancing even in areas where lockdown has been removed or ameliorated. Patients with iatrogenic hypogammaglobulinemia may require prophylactic intravenous immunoglobulin therapy in certain situations. When the future SARS-CoV-2 vaccine becomes available, patients with multiple sclerosis should be advised that certain therapies may interfere with mounting a protective immune response to the vaccine and that serological confirmation of a response may be required after vaccination. They should also be aware that most multiple sclerosis therapies are incompatible with live vaccines if a live SARS-CoV-2 vaccine is developed. In this article, we review and compare disease-modifying therapies in terms of their effect on the immune system, published infection rates, potential impact on SARS-CoV-2 susceptibility, and vaccine-related implications. We propose risk mitigation strategies and practical approaches to disease-modifying therapy during the COVID-19 pandemic.

Chagas Disease in the New York City Metropolitan Area.

BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, once considered a disease confined to Mexico, Central America, and South America, is now an emerging global public health problem. An estimated 300 000 immigrants in the United States are chronically infected with T. cruzi. However, awareness of Chagas disease among the medical community in the United States is poor. METHODS: We review our experience managing 60 patients with Chagas disease in hospitals throughout the New York City metropolitan area and describe screening, clinical manifestations, EKG findings, imaging, and treatment. RESULTS: The most common country of origin of our patients was El Salvador (n = 24, 40%), and the most common detection method was by routine blood donor screening (n = 21, 35%). Nearly half of the patients were asymptomatic (n = 29, 48%). Twenty-seven patients were treated with either benznidazole or nifurtimox, of whom 7 did not complete therapy due to side effects or were lost to follow-up. Ten patients had advanced heart failure requiring device implantation or organ transplantation. CONCLUSIONS: Based on our experience, we recommend that targeted screening be used to identify at-risk, asymptomatic patients before progression to clinical disease. Evaluation should include an electrocardiogram, echocardiogram, and chest x-ray, as well as gastrointestinal imaging if relevant symptoms are present. Patients should be treated if appropriate, but providers should be aware of adverse effects that may prevent patients from completing treatment.

Orf virus infection after Eid al-Adha.

Human orf, also called ecthyma contagiosum, is a zoonotic infection that causes self-resolving skin lesions after contact with infected livestock. We present the case of a 45-year-old Moroccan-born man who developed multiple painful erythematous, violaceous plaques on his hands after butchering a sheep to celebrate the Muslim holiday Eid al-Adha. The diagnosis of orf virus infection was established based on exposure history, histopathology, and classic skin lesions. Although orf virus infection is traditionally seen in individuals with frequent animal contact such as farmers and veterinarians, clinicians evaluating suspicious lesions in patients without occupational risk factors should consider additional cultural practices that may expose the patient to orf virus.

Current and emerging therapeutics for neuromyelitis optica spectrum disorder: Relevance to the COVID-19 pandemic.

Neuromyelitis optica spectrum disorder (NMOSD) can lead to immobility and bulbar weakness. This, in addition to the older age of onset and the higher rate of hospitalization compared to multiple sclerosis, makes this patient group a potential target for complicated COVID-19 infection. Moreover, many of the commonly used preventive therapies for NMOSD are cell-depleting immunouppsressants with increased risk of viral and bacterial infections. The emergence of several new NMOSD therapeutics, including immune-modulating agents, concurrently with the worldwide spread of the COVID-19 global pandemic call for careful therapeutic planning and add to the complexity of NMOSD management. Altering the common therapeutic approach to NMOSD during the pandemic may be necessary to balance both efficacy and safety of treatment. Selection of preventive therapy should take in consideration the viral exposure risk related to the route and frequency of administration and, most importantly, the immunological properties of each therapeutic agent and its potential impact on the risk of SARS-CoV-2 susceptibility and severity of infection. The impact of the therapeutic agent on the immune response against the future SARS-CoV-2 vaccine should also be considered in the clinical decision-making. In this review, we will discuss the immune response against SARS-CoV-2 and evaluate the potential impact of the current and emerging NMOSD therapeutics on infection risk, infection severity, and future SARS-CoV-2 vaccination. We propose a therapeutic approach to NMOSD during the COVID-19 pandemic based on analysis of the mechanism of action, route of administration, and side effect profile of each therapeutic agent.

A Performance-Based Incentives System for Village Health Workers in Kisoro, Uganda.

BACKGROUND: Village health worker (VHW) programs in Uganda have achieved limited success, due in part to a reliance on volunteerism and a lack of standardized incentive mechanisms. However, how to best incentivize VHWs remains unclear. Doctors for Global Health developed a performance-based incentives (PBI) system to pay its VHWs in Kisoro, Uganda, based on performance of tasks or achievement of targets. OBJECTIVES: 1. To describe the development of a PBI system used to compensate VHWs. 2. To report cost and health services delivery outcomes under a PBI system. 3. To provide qualitative analysis on the successes and challenges of PBI. METHODS: Internal organization records from May 2016 to April 2017 were retrospectively reviewed. The results of descriptive and analytic statistics were reported. Qualitative analysis was performed by the authors. FINDINGS: In one year, 42 VHWs performed 23,703 remunerable health actions, such as providing care of minor ailments and chronic disease. VHWs earned on average $237. The total cost to maintain the program was $29,844, or $0.72 per villager. There was 0% VHW attrition. Strengths of PBI included flexibility, accountability, higher VHW earnings, and improved monitoring and evaluation. CONCLUSIONS: PBI is a feasible and sustainable model of compensating VHWs. At a time where VHW programs are sorely needed to address limitations in healthcare resources, yet are facing challenges with workforce compensation, PBI may serve as a model for others in Uganda and around the world.

Let's Join the Lane: The Role of Infectious Diseases Physicians in Preventing Gun Violence.

On November 7, 2018, the National Rifle Association (NRA) issued a tweet advising "self-important anti-gun doctors to stay in their lane." The tweet has galvanized physicians to share their experiences with gun violence through the grassroots #ThisISOurLane campaign. Infectious diseases physicians are regularly called upon to manage complications such as infected wounds and osteomyelitis in gunshot victims. Yet, Infectious Diseases as a specialty has been poorly represented in the national dialogue on gun violence. Over 80 medical societies have endorsed statements on gun violence, including the American College of Physicians (ACP) and the American College of Cardiology; the Infectious Diseases Society of America has not. We argue that gun violence does affect the Infectious Diseases community and issue a call to action to engage in the conversation, advocate for our patients, and join with other medical societies in affirming a commitment to gun violence prevention.

Complications of Silicone Cosmetic Procedures Among Medical Tourists from the Bronx, New York: A Retrospective Analysis.

Hundreds of thousands of Americans travel abroad each year for medical care, such as cosmetic silicone procedures. However, medical tourists risk encountering unqualified providers and receiving injectable or implantable cosmetic materials of questionable purity. We performed a retrospective chart review of patients treated at a multisite academic center in the Bronx, New York, between the years 2008 and 2017, and identified 12 patients who developed complications following silicone procedures performed in a foreign country, Puerto Rico, or the United States by an unlicensed provider. Procedures included silicone injections or implants in the breasts, buttocks, and face. Destination countries included the Dominican Republic, Guatemala, Venezuela, and Mexico. The patients in our study suffered significant morbidity, with complications including infection, implant rupture, and silicone migration. Laboratory and radiographic findings demonstrated nonspecific markers of inflammation. The management of silicone complications can be difficult and prolonged, and can place a large financial burden on the healthcare system as well as have significant and long-term negative consequences for the patient. Clinicians should be aware of the risks for adverse events, such as the ones described here following silicone injection and/or implant procedures, in patients who, whether for financial, cultural, or other reasons, chose to undergo cosmetic procedures in another country or by an unlicensed practictioner in the US. It is important that clinicians recognize the considerable and diverse morbidity of such patients and treat them with sensitivity and empathy to ensure optimal outcomes.

The BDNF Val66Met Prodomain Disassembles Dendritic Spines Altering Fear Extinction Circuitry and Behavior.

A human variant in the BDNF gene (Val66Met; rs6265) is associated with impaired fear extinction. Using super-resolution imaging, we demonstrate that the BDNF Met prodomain disassembles dendritic spines and eliminates synapses in hippocampal neurons. In vivo, ventral CA1 (vCA1) hippocampal neurons undergo similar morphological changes dependent on their transient co-expression of a SorCS2/p75NTR receptor complex during peri-adolescence. BDNF Met prodomain infusion into the vCA1 during this developmental time frame reduces dendritic spine density and prelimbic (PL) projections, impairing cued fear extinction. Adolescent BdnfMet/Met mice display similar spine and PL innervation deficits. Using fiber photometry, we found that, in wild-type mice, vCA1 neurons projecting to the PL encode extinction by enhancing neural activity in threat anticipation and rapidly subsiding their response. This adaptation is absent in BDNFMet/Met mice. We conclude that the BDNF Met prodomain renders vCA1-PL projection neurons underdeveloped, preventing their capacity for subsequent circuit modulation necessary for fear extinction. VIDEO ABSTRACT.

Sickle Cell Crisis Complicated by Synthetic Cannabinoid Abuse: A Case Report.

We describe a case of delirium occurring in a hospitalized sickle cell patient. Following admission for a typical pain crisis, the patient continued to report unrelieved pain with marked agitation for several days, despite escalating doses of opioid analgesia, and ultimately required intubation following development of acute chest syndrome (ACS). After some delay, it was discovered that he had been using a synthetic cannabinoid (K2) which may have precipitated his pain crisis and, with hindsight, explained his prolonged period of delirium. Delayed recognition was due to multiple factors, notably the absence of an index of suspicion for this novel drug, the presence of alternate explanations for the patient's altered mental status, and the fact that reliable laboratory screening for synthetic cannabinoids is currently not widely available.