Nova Reader - Subject

Alternative approaches to lymphoedema care in lymphatic filariasis

2021-04-29T00:00

Multiplexed assays reveal effects of missense variants in MSH2 and cancer predisposition

2021-04-22T00:00

Leprosy postexposure prophylaxis with single-dose rifampicin: Nepalese dermatologist’s dilemma

2021-04-08T00:00

Quantitative PCR in soil-transmitted helminth epidemiology and control programs: Toward a universal standard

2021-03-04T00:00

Call to action: A literature review of Chagas disease risk in California 1916–2018

2021-02-25T00:00

Approaches for implementing society-led community interventions to mitigate snakebite envenoming burden: The SHE-India experience

2021-02-25T00:00

A New Approach to the Development of Disease‐Modifying Therapies for PD; Fighting Another Pandemic

2020-10-07T00:00

A disease‐modifying therapy that slows disease progression and development of disability is the major unmet need in the treatment of Parkinson's disease. Recent scientific advances suggest many promising and exciting new interventions. However, despite these opportunities, the cost, time and uncertainty of being able to receive an indication as a disease‐modifying therapy has caused many pharmaceutical companies to abandon development of potentially disease‐modifying drugs. We propose a new approach to development of these agents that will reduce the cost and facilitate approval of putative disease‐modifying drugs that should prove acceptable to pharmaceutical companies and regulatory agencies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Stress and Mindfulness in Parkinson's Disease: Clinical Effects and Potential Underlying Mechanisms

2020-10-23T00:00

Patients with Parkinson's disease (PD) are very vulnerable to the negative effects of psychological distress: neuropsychiatric symptoms, such as anxiety and depression, are highly prevalent in PD; motor symptoms (such as tremor) typically worsen in stressful situations; and dopaminergic medication is less effective. Furthermore, animal studies of PD suggest that chronic stress may accelerate disease progression. Adequate self‐management strategies are therefore essential to reduce the detrimental effects of chronic stress on PD. Mindfulness‐based interventions encourage individuals to independently self‐manage and adapt to the challenges created by their condition. In PD, emerging clinical evidence suggests that mindfulness‐based interventions may reduce psychological distress and improve clinical symptoms, but insight into the underlying mechanisms is lacking. In this viewpoint, we provide a systematic overview of existing mindfulness trials in PD. Furthermore, we discuss the cerebral mechanisms involved in acute and chronic stress, and the impact of mindfulness‐based interventions on these networks. In addition, we delineate a hypothetical mechanistic framework of how chronic stress may increase the susceptibility for neuropsychiatric symptoms in PD and may potentially even influence disease progression. We end with offering recommendations for future research. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Drugs that target early stages of Onchocerca volvulus: A revisited means to facilitate the elimination goals for onchocerciasis

2021-02-18T00:00

Several issues have been identified with the current programs for the elimination of onchocerciasis that target only transmission by using mass drug administration (MDA) of the drug ivermectin. Alternative and/or complementary treatment regimens as part of a more comprehensive strategy to eliminate onchocerciasis are needed. We posit that the addition of “prophylactic” drugs or therapeutic drugs that can be utilized in a prophylactic strategy to the toolbox of present microfilaricidal drugs and/or future macrofilaricidal treatment regimens will not only improve the chances of meeting the elimination goals but may hasten the time to elimination and also will support achieving a sustained elimination of onchocerciasis. These “prophylactic” drugs will target the infective third- (L3) and fourth-stage (L4) larvae of Onchocerca volvulus and consequently prevent the establishment of new infections not only in uninfected individuals but also in already infected individuals and thus reduce the overall adult worm burden and transmission. Importantly, an effective prophylactic treatment regimen can utilize drugs that are already part of the onchocerciasis elimination program (ivermectin), those being considered for MDA (moxidectin), and/or the potential macrofilaricidal drugs (oxfendazole and emodepside) currently under clinical development. Prophylaxis of onchocerciasis is not a new concept. We present new data showing that these drugs can inhibit L3 molting and/or inhibit motility of L4 at IC₅₀ and IC₉₀ that are covered by the concentration of these drugs in plasma based on the corresponding pharmacological profiles obtained in human clinical trials when these drugs were tested using various doses for the therapeutic treatments of various helminth infections.

The impact of COVID-19 pandemic on AIDS-related mycoses and fungal neglected tropical diseases: Why should we worry?

2021-02-09T00:00

The World Health Organization (WHO) considers mycetoma, chromoblastomycosis, and paracoccidioidomycosis to be fungal neglected tropical diseases (FNTDs). Depending on climatic, cultural, and economic contexts, these diseases have a similar geographical distribution as many other diseases, particularly tuberculosis (TB) and malaria, but are often less targeted by the national and many international healthcare systems. Another subgroup of fungal infections, such as candidiasis, cryptococcosis, pneumocystosis, histoplasmosis, and to a lesser extent, aspergillosis, are known as AIDS-related mycoses. Although antiretroviral therapy (ART) has been able to decrease the mortality rate of these diseases, particularly cryptococcosis, the disproportionately low distribution of funds to their diagnosis and treatment remains an obstacle in saving and improving the lives of patients affected. A new wave of viral diseases dubbed the Coronavirus Disease 2019 (COVID-19) hit the world at the end of 2019. Due to progressive symptoms and high mortality rates of COVID-19 compared to fungal infections, particularly the FNTDs, funding is currently allocated predominantly for diagnostic and therapeutic research on COVID-19. As a result, advances in FNTDs and AIDS-related mycosis care are considerably reduced. This paper explores the association between COVID-19, FNTDs, and AIDS-related mycoses with a predictive perspective.

China’s COVID-19 response for the protection of rural communities

2021-02-02T00:00

Tracing the source of infection of cystic and alveolar echinococcosis, neglected parasitic infections with long latency: The shaky road of “evidence” gathering

2021-01-21T00:00

The clarifying role of time series data in the population genetics of HIV

2021-01-14T00:00

HIV can evolve remarkably quickly in response to antiretroviral therapies and the immune system. This evolution stymies treatment effectiveness and prevents the development of an HIV vaccine. Consequently, there has been a great interest in using population genetics to disentangle the forces that govern the HIV adaptive landscape (selection, drift, mutation, and recombination). Traditional population genetics approaches look at the current state of genetic variation and infer the processes that can generate it. However, because HIV evolves rapidly, we can also sample populations repeatedly over time and watch evolution in action. In this paper, we demonstrate how time series data can bound evolutionary parameters in a way that complements and informs traditional population genetic approaches. Specifically, we focus on our recent paper (Feder et al., 2016, eLife), in which we show that, as improved HIV drugs have led to fewer patients failing therapy due to resistance evolution, less genetic diversity has been maintained following the fixation of drug resistance mutations. Because soft sweeps of multiple drug resistance mutations spreading simultaneously have been previously documented in response to the less effective HIV therapies used early in the epidemic, we interpret the maintenance of post-sweep diversity in response to poor therapies as further evidence of soft sweeps and therefore a high population mutation rate (θ) in these intra-patient HIV populations. Because improved drugs resulted in rarer resistance evolution accompanied by lower post-sweep diversity, we suggest that both observations can be explained by decreased population mutation rates and a resultant transition to hard selective sweeps. A recent paper (Harris et al., 2018, PLOS Genetics) proposed an alternative interpretation: Diversity maintenance following drug resistance evolution in response to poor therapies may have been driven by recombination during slow, hard selective sweeps of single mutations. Then, if better drugs have led to faster hard selective sweeps of resistance, recombination will have less time to rescue diversity during the sweep, recapitulating the decrease in post-sweep diversity as drugs have improved. In this paper, we use time series data to show that drug resistance evolution during ineffective treatment is very fast, providing new evidence that soft sweeps drove early HIV treatment failure.

Scabies-infested pregnant women: A critical therapeutic challenge

2021-01-07T00:00

COVID-19, leprosy, and neutrophils

2021-01-07T00:00

Coronavirus Disease 2019 (COVID-19), a disease caused by the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has only recently emerged, while Mycobacterium leprae, the etiological agent of leprosy, has endured for more than 2,000 years. As soon as the initial reports of COVID-19 became public, several entities, including the Brazilian Leprosy Society, warned about the possible impact of COVID-19 on leprosy patients. It has been verified that COVID-19 carriers can be either asymptomatic or present varying degrees of severe respiratory failure in association with cytokine storm and death, among other diseases. Severe COVID-19 patients show increased numbers of neutrophils and serum neutrophil extracellular trap (NET) markers, in addition to alterations in the neutrophil-to-lymphocyte ratio (NLR). The absence of antiviral drugs and the speed of COVID-19 transmission have had a major impact on public health systems worldwide, leading to the almost total collapse of many national and local healthcare services. Leprosy, an infectious neurological and dermatological illness, is widely considered to be the most frequent cause of physical disabilities globally. The chronic clinical course of the disease may be interrupted by acute inflammatory episodes, named leprosy reactions. These serious immunological complications, characterized by cytokine storms, are responsible for amplifying peripheral nerve damage. From 30% to 40% of all multibacillary leprosy (MB) patients experience erythema nodosum leprosum (ENL), a neutrophilic immune-mediated condition. ENL patients often present these same COVID-19-like symptoms, including high levels of serum NET markers, altered NLR, and neutrophilia. Moreover, the consequences of a M. leprae–SARS-CoV-2 coinfection have yet to be fully investigated. The goal of the present viewpoint is to describe some of the similarities that may be found between COVID-19 and leprosy disease in the context of neutrophilic biology.

Time for a diagnostic sea-change: Rethinking neglected tropical disease diagnostics to achieve elimination

2020-12-31T00:00

Mild manifestations of COVID-19 in healthcare workers

2020-12-22T00:00

Medical staff treating Coronavirus Disease 2019 (COVID-19) patients are at high risk for exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and many have been infected, which may cause panic among medical workers, their relatives, health professionals, and government leaders. We report the epidemiologic and clinical characteristics of healthcare workers and that the majority of infected medical staff had milder symptoms/conditions with a better prognosis than admitted patients. Timely improvement to medical staff’s working conditions such as allowing adequate rest and providing sufficient medical protection is extremely important.