Kinetoplastid parasites have caused human disease for millennia. Significant achievements have been made toward developing new treatments for leishmaniasis (particularly on the Indian subcontinent) and for human African trypanosomiasis (HAT). Moreover, the sustained decrease in the incidence of HAT... has made the prospect of elimination a tantalizing reality. Despite the gains, no new chemical or biological entities to treat kinetoplastid diseases have been registered in more than three decades, and more work is needed to discover safe and effective therapies for patients with Chagas disease and leishmaniasis. Advances in tools for drug discovery and novel insights into the biology of the host−parasite interaction may provide opportunities for accelerated progress. Here, we summarize the output from a gathering of scientists and physicians who met to discuss the current status and future directions in drug discovery for kinetoplastid diseases.
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Preventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, ...we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d'Ivoire, using two different diagnostic tests.
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Background: The human helminth infections include ascariasis, trichuriasis, hookworm infections, schistosomiasis, lymphatic filariasis (LF) and onchocerciasis. It is estimated that almost 2 billion people worldwide are infected with helminths. Whilst the WHO treatment guidelines for helminth infecti...ons are mostly aimed at controlling morbidity, there has been a recent shift with some countries moving towards goals of disease elimination through mass drug administration, especially for LF and onchocerciasis. However, as prevalence is driven lower, treating entire populations may no longer be the most efficient or cost-effective strategy. Instead, it may be beneficial to identify individuals or demographic groups who are persistently infected, often termed as being “predisposed” to infection, and target treatment at them.
Methods: The authors searched Embase, MEDLINE, Global Health, and Web of Science for all English language, humanbased papers investigating predisposition to helminth infections published up to October 31st, 2017. The varying definitions used to describe predisposition, and the statistical tests used to determine its presence, are summarised. Evidence for predisposition is presented, stratified by helminth species, and risk factors for predisposition to infection are identified and discussed.
Results: In total, 43 papers were identified, summarising results from 34 different studies in 23 countries. Consistent evidence of predisposition to infection with certain species of human helminth was identified. Children were regularly found to experience greater predisposition to Ascaris lumbricoides, Schistosoma mansoni and S. haematobium than adults. Females were found to be more predisposed to A. lumbricoides infection than were males. Household clustering of infection was identified for A. lumbricoides, T. trichiura and S. japonicum. Ascaris lumbricoides and T. trichiura also showed evidence of familial predisposition. Whilst strong evidence for predisposition to hookworm infection was identified, findings with regards to which groups were affected were considerably more varied than for other helminth species.
Conclusion: This review has found consistent evidence of predisposition to heavy (and light) infection for certain human helminth species. However, further research is needed to identify reasons for the reported differences between demographic groups. Molecular epidemiological methods associated with whole genome sequencing to determine ‘who infects whom’ may shed more light on the factors generating predisposition.
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Chagas heart disease (CHD) affects approximately 30% of patients chronically infected with the protozoa Trypanosoma cruzi. CHD is classified into four stages of increasing severity according to electrocardiographic, echocardiographic, and clinical criteria. CHD presents with a myriad of clinical man...ifestations, but its main complications are sudden cardiac death, heart failure, and stroke. Importantly, CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies, and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies. Among patients with CHD, approximately 90% of deaths can be attributed to complications of Chagas disease. Sudden cardiac death is the most common cause of death (55%-60%), followed by heart failure (25%-30%) and stroke (10%-15%). The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with. Therefore, the management of CHD is challenging, and in this review, we present the most updated available data to help clinicians and cardiologists in the care of these patients. We describe the clinical manifestations, diagnosis and classification criteria, risk stratification, and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.
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Background: East African trypanosomiasis is an uncommon, potentially lethal disease if not diagnosed and treated in a timely manner. South Africa, as a centre for emergency medical evacuations from much of sub-Saharan Africa, receives a high proportion of these patients, mostly tourists and expatria...te residents.
Methods: The cases of East African trypanosomiasis patients evacuated to South Africa, for whom diagnostic and clinical management advice was provided over the years 2004–2018, were reviewed, using the authors’ own records and those of collaborating clinicians.
Results: Twenty-one cases were identified. These originated in Zambia, Malawi, Zimbabwe, Tanzania, and Uganda. Nineteen cases (90%) had stage 1 (haemolymphatic) disease; one of these patients had fatal myocarditis. Of the two patients with stage 2 (meningoencephalitic) disease, one died of melarsoprol encephalopathy. Common problems were delayed diagnosis, erroneous assessment of severity, and limited access to treatment.
Conclusions: The key to early diagnosis is recognition of the triad of geographic exposure, tsetse fly bites, and trypanosomal chancre, plus good microscopy. Elements for successful management are rapid access to specific drug treatment, skilled intensive care, and good laboratory facilities. Clinical experience and the local stock of antitrypanosomal drugs from the World Health Organization have improved the chance of a successful outcome in the management of East African trypanosomiasis in South Africa; the survival rate over the period was 90.5%.
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Despite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported ...serious adverse events (SAEs).
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This article considers the current public health perspective on cutaneous leishmaniasis (CL) and its implications for incidence, prevalence, and global burden of disease calculations. CL is the most common form of leishmaniasis and one of a small number of infectious diseases increasing in incidence... worldwide [1] due to conflict and environmental factors in the Middle East (“Old World”) and the Americas (“New World”)—regions where it is most prevalent.
Recently, the disease has reached hyperendemic levels in the conflict zones of the Syrian Arab Republic, Iraq, and Afghanistan while simultaneously affecting refugees from those regions . Nevertheless, CL is not seen as a priority for policymakers because it is not life limiting. This is evidenced by a lack of commitment in recent years to preventive campaigns and patient provision (limited diagnostic capacity, knowledge of treatment, drug availability) in a number
of endemic countries.
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Antibiotics 2022, 11(3), 329; https://doi.org/10.3390/antibiotics11030329.
The authors found that the most-represented antibiotics on the Rwandan market were amoxicillin, co-trimoxazole and cloxacillin. No counterfeit antibiotics were found in this study. However, substandard batches with moderate ...deviations were found, suggesting that regular quality control of antibiotics is needed in Rwanda.
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Buruli ulcer is a disease of skin and soft tissue with the potential to leave sufferers scarred and disabled. It is caused by an environmental pathogen, Mycobacterium
ulcerans, that produces a destructive toxin. The exact mode of transmission is unclear. The main burden of disease falls on childre...n living in sub-Saharan Africa, but healthy people of all ages, races, and socioeconomic classes are susceptible.
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Soil-transmitted helminths (STH) affect 1.45 billion people worldwide, and high intensity infections are associated with anemia, undernutrition and impaired cognition, particularly among children. Mathematical models suggest it may be possible to interrupt the transmission of STH in a community by e...xpanding mass drug administration (MDA) from targeted high-risk groups (primarily school-aged children and women of child-bearing age) to all community members with high coverage. The DeWorm3 Project will test the feasibility of this approach to interrupting the transmission of STH using a series of cluster randomized trials in Benin, India and Malawi. Each study area (population 80,000) will be divided into 40 clusters and randomized to community-wide or standard-of-care targeted MDA for three years. Two years following the final round of MDA, prevalence of STH will be compared between arms and transmission interruption assessed in each cluster. The DeWorm3 trials will provide stakeholders with information regarding the potential to switch from STH control to a more ambitious and sustainable strategy.
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Human African trypanosomiasis (HAT) is a lethal neglected tropical disease (NTD) transmitted by the bite of infected tsetse flies. The disease is also known as “sleeping sickness”. During the 20th century it caused enormous suffering in the endemic areas in sub-Saharan Africa. HAT transmission l...ast soared in the late 1990s, triggering a renewed, coordinated and very successful control effort. In this paper, we present achievements towards HAT elimination, with a focus on the WHO road map targets for 2020. In particular, reported cases continue to decline, from over 30,000 cases per year at the turn of the century to 663 cases in 2020. Despite the impact of the COVID-19 pandemic, HAT surveillance was largely sustained, and the network of health facilities able to diagnose and treat the disease further expanded. Looking to the future, the World Health Organization (WHO) set bold new targets for HAT in its 2021–2030 road map for NTDs, namely: the elimination of transmission of gambiense HAT, which occurs in western and central Africa, and the elimination as a public health problem of rhodesiense HAT, which is found in eastern and southern Africa. The strong commitment of national health authorities and the international community will be essential if these goals are to be achieved.
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The aim of this toolkit is to guide countries on how to best estimate their current burden of dengue by combining existing data from dengue surveillance systems with on-going research efforts to measure the community burden
of dengue.
PLoS Neglected Tropical diseases August 16, 2021 https://doi.org/10.1371/journal.pntd.0009697
Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease transmitted by triatomine insects, first identified in 1909. Chagas disease affects approximately 6–7 million peop...le globally and is highly prevalent in Latin America where most cases are reported. However, there is increasing evidence that Chagas disease is now an important public health issue outside the “classical” endemic countries due to population migration. Our understanding of Chagas disease, including its pathologies and factors relating to progression, remains to date limited, and is also challenged by lack of diagnosis and highly effective treatment. This systematic review aims to describe studies with Chagas patients receiving antiparasitic treatment. Databases were searched for relevant studies published after 1997, and the results of these searches were screened.
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Contemporary data for causes of vision impairment and blindness form an important basis of recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modelling of cause of vision loss data from 1990 to 2015, further disaggregat...ion by cause, and forecasts to 2020.
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Ein Leitfaden für Fachkräfte in sozialen, pädagogischen und medizinischen Berufen
PLOS One November 20, 2020 https://doi.org/10.1371/journal.pone.0241799 . The first autochthonous case of chikungunya virus (CHIKV) infection in Brazil was in September 2014 in the State of Amapá, and from there it rapidly spread across the country. The present study was conducted in 2016 in the st...ate of Rio Grande do Norte, and the aims were to describe the epidemiological and the clinical aspects of the CHIKV outbreak.
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Chikungunya virus (CHIKV) is currently one of the most relevant arboviruses to public health. It is a member of the Togaviridae family and alphavirus genus and causes an arthritogenic disease known as chikungunya fever (CHIKF). It is characterized by a multifaceted disease, which is distinguished fr...om other arbovirus infections by the intense and debilitating arthralgia that can last for months or years in some individuals. Despite the great social and economic burden caused by CHIKV infection, there is no vaccine or specific antiviral drugs currently available. Recent outbreaks have shown a change in the severity profile of the disease in which atypical and severe manifestation lead to hundreds of deaths, reinforcing the necessity to understand the replication and pathogenesis processes. CHIKF is a complex disease resultant from the infection of a plethora of cell types. Although there are several in vivo models for studying CHIKV infection, none of them reproduces integrally the disease signature observed in humans, which is a challenge for vaccine and drug development. Therefore, understanding the potentials and limitations of the state-of-the-art experimental models is imperative to advance in the field. In this context, the present review outlines the present knowledge on CHIKV epidemiology, replication, pathogenesis, and immunity and also brings a critical perspective on the current in vitro and in vivo state-of-the-art experimental models of CHIKF.
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Analysis of microfilaria prevalence data from 430 communities
Version 4
The purpose of these standard operating procedures (SOPs) is to offer policy guidance and to provide performance standards on how to respond to any type of poliovirus outbreak or event in a timely and effective manner, and specifically, to stop an outbrea...k within 120 days.
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