A practical tool to help health workers in the clinical and operational management of multidrug-resistant tuberculosis with special focus on the introduction, implementation and management of the nine-month treatment regimen.
DOI: 10.5772/intechopen.102891Little progress has been made since the 1960s and 19. 70s to widen the therapeutic arsenal against Trypanosoma cruzi, the causative pathogen of Chagas disease, which remains a frustrating and perplexing infectious disease. This chapter focuses on the strategic and opera...tional challenges in the clinical drug development of a novel antitrypanosomal agent for Chagas disease. The various elements that contribute to a robust assessment of treatment effect including dose selection, choice of patient population, trial methodology, endpoint measures, and regulatory perspectives are discussed. The learnings herein should serve as resource to help researchers and other stakeholders optimize their clinical development plans and speed delivery of new medicines to patients with Chagas disease.
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The recommendations in these guidelines promote the use of simple, non-invasive diagnostic tests to assess the stage of liver disease and eligibility for treatment; prioritize treatment for those with most advanced liver disease and at greatest risk of mortality; and recommend the preferred use of n...ucleos(t)ide analogues with a high barrier to drug resistance (tenofovir and entecavir, and entecavir in children aged 2–11 years) for first- and second-line treatment. Recommendations for the treatment of HBV/HIV-coinfected persons are based on the WHO 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, which will be updated in 2015.
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Chagas disease affects 8-10 million people worldwide, mainly in Latin America. The current therapy for Chagas disease is limited to nifurtimox and benznidazole, which are effective in treating only the acute phase of the disease but with severe side effects. Therefore, there is an unmet need for new... drugs and for the exploration of innovative approaches which may lead to the discovery of new effective and safe drugs for its treatment.
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PLOS Glob Public Health 4(12): e0004035. https://doi. org/10.1371/journal.pgph.0004035.
A new formulation of praziquantel, arpraziquantel (arPZQ), has been developed for preschool-
aged children (PSAC) to fill the treatment gap for this age group in schistosomiasis control and
elimination program...s. There is now a priority to ensure that the drug reaches all at-risk PSAC
in endemic areas, including hard-to-reach areas and populations. This study aimed to deter-
mine schistosomiasis treatment-related contextual factors among fishermen and island popu-
lations in Homa Bay County, Kenya, and to identify a suitable platform to deliver arPZQ.
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The purpose of this document is to stop to irrational use/ over prescription of this reserve/
experimental/ emergency use authorisation drug Remdesivir. For this reason, Joint
Monitoring Group under Chairmanship of DGHS took into consideration findings of the
followi...ng studies to issue this advisory:
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The protozoan parasite Trypanosoma cruzi causes Chagas disease, an important public health problem throughout Latin America. Current therapeutic options are characterised by limited efficacy, long treatment regimens and frequent toxic side-effects. Advances in this area have been compromised by gaps... in our knowledge of disease pathogenesis, parasite biology and drug activity. Nevertheless, several factors have come together to create a more optimistic scenario. Drug-based research has become more systematic, with increased collaborations between the academic and commercial sectors, often within the framework of not-for-profit consortia. High-throughput screening of compound libraries is being widely applied, and new technical advances are helping to streamline the drug development pipeline. In addition, drug repurposing and optimisation of current treatment regimens, informed by laboratory research, are providing a basis for new clinical trials. Here, we will provide an overview of the current status of Chagas disease drug development, highlight those areas where progress can be expected, and describe how fundamental research is helping to underpin the process.
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Nat Commun 9, 5370 (2018). https://doi.org/10.1038/s41467-018-07804-8. Mycobacterium ulcerans is the causative agent of Buruli ulcer, a neglected tropical skin disease that is most commonly found in children from West and Central Africa. Despite the severity of the infection, therapeutic options are... limited to antibiotics with severe side effects. Here, we show that M. ulcerans is susceptible to the anti-tubercular drug Q203 and related compounds targeting the respiratory cytochrome bc1:aa3. While the cytochrome bc1:aa3 is the primary terminal oxidase in Mycobacterium tuberculosis, the presence of an alternate bd-type terminal oxidase limits the bactericidal and sterilizing potency of Q203 against this bacterium. M. ulcerans strains found in Buruli ulcer patients from Africa and Australia lost all alternate terminal electron acceptors and rely exclusively on the cytochrome bc1:aa3 to respire. As a result, Q203 is bactericidal at low dose against M. ulcerans replicating in vitro and in mice, making the drug a promising candidate for Buruli ulcer treatment.
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Specific measures are being taken within the National Tuberculosis Control Programme (NTP) to address the MDR TB problem through appropriate management of patients and strategies to prevent the propagation and dissemination of MDR TB.
The term "Programmatic Management of Drug Resistant TB" (PMD...T) refers to programme based MDR TB diagnosis, management and treatment. This guideline promotes full integration of basic TB control and PMDT activities under the NTP, so that patients with TB are evaluated for drug resistance and are placed on the appropriate treatment regimen and properly managed from the outset of treatment, or as early as possible. The guidelines also integrate the identification and treatment of more severe forms of drug resistance, such as extensively drug resistant TB (XDR TB).
At the end, the guideline introduces new standards for registering, monitoring and reporting outcomes of multidrug resistant TB cases.
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Effective malaria case management requires quick access to diagnostics and antimalarial treatments to reduce illness and death. Artemisinin-based combination therapy (ACT) has been essential to malaria treatment since 2001, as it combines artemisinin for rapid parasite reduction with a partner drug ...to ensure complete cure. However, resistance to antimalarial drugs, where parasites survive standard doses, threatens malaria control.
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HIV, viral hepatitis and STI epidemics, particularly among people who inject drugs and other key populations, continue to be fuelled by laws and policies criminalizing sex work; drug use or possession; diverse forms of gender expression and sexuality; stigma and discrimination; gender discrimination...; violence; lack of community empowerment and other violations of human rights. These sociostructural factors limit access to health services, constrain how these services are
delivered and diminish their effectiveness.
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Meeting Report 27-29 October 2020
The overall goal of the meeting was to discuss recent changes in treatment regimens and diagnostics for drug-resistant TB and to determine how these impact on the definition of XDR-TB, with a view to revising this definition. The pre-existing definition of XDR-TB w...as formulated in 2006 at a meeting of the Global Taskforce on XDR-TB, convened by WHO, and has been in use for clinical and surveillance purposes, since this time.
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The "Pocket Manual for the Diagnosis and Treatment of Malaria", published by the Ministry of Health of the Sultanate of Oman, provides practical guidance for healthcare professionals on how to identify, manage, and treat malaria cases. It emphasizes parasitological confirmation before treatment, out...lines standard protocols for treating uncomplicated and severe malaria—including P. falciparum, P. vivax, and mixed infections—and specifies drug regimens based on patient weight and age. The manual also includes recommendations for travelers on malaria chemoprophylaxis and highlights the importance of prevention, especially for high-risk groups like children and pregnant women.
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The goal of this addendum is to help management and staff
minimize the risk of TB transmission at facilities in resource limited settings in which a.) HIV-infected persons receive diagnosis, care, treatment,
and/or support, and b.) there is a high prevalence of HIV infection, both known
and... undiagnosed, in settings such as prisons, jails, other
detention centers, and drug rehabilitation centers.
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This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospita...ls in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included.
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Of the more than 10 million people estimated to have fallen ill with tuberculosis (TB) in 2022, just over 400 000 people developed TB resistant to rifampicin (RIF), and 1.3 million people developed TB resistant isoniazid (INH). Drug resistance must be detected rapidly and accurately to initiate appr...opriate and effective treatment.
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This publication seeks to describe the best treatments and practices based on the scientific evidence available at the time of writing as evaluated by the authors and may change as a result of new research. Readers need to apply this knowledge to patients in accordance with the guidelines and laws o...f their country of practice. Some medications may not be available in some countries and readers should consult the specific drug information since not all the unwanted effects of medications are mentioned.
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In 2019, an estimated 10 million individuals fell ill with tuberculosis (TB) and 3 million of them were not reported to have beendiagnosed and notified. The gap is proportionately even wider for drug-resistant TB. Of the estimated 465 000 patients with rifampicin-resistant and multi-drug resistant T...B (RR/MDR-TB), only 206 030 (44%) were diagnosed and notified.For the first time, the World Health Organization (WHO) has provided global estimates of the incidence of isoniazid resistance: in 2019, there were 1.4 million incident cases of isoniazid-resistant TB, of which 1.1 million were susceptible to rifampicin. Most of these people were not diagnosed with drug-resistant TB and did not receive appropriate treatment.
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WHO recommends artemisinin-based combination therapies for treating uncomplicated malaria, alongside studies to monitor treatment effectiveness. Given the threat of antimalarial resistance, including partial resistance in several African countries, molecular tools are vital for tracking resistance. ...In 2015, WHO launched the External Quality Assessment scheme for nucleic acid amplification testing to ensure reliable lab results. Coordinated by WHO and operated by the United Kingdom National External Quality Assessment Service for Parasitology, the scheme provides quality-controlled specimens and reports to help improve testing accuracy. Experts recently discussed expanding the scheme to include antimalarial resistance markers.
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Malaria and HIV, two of the world’s most deadly diseases, are widespread, but their distribution overlaps greatly in sub-Saharan Africa. Consequently, malaria and HIV coinfection (MHC) is common in the region. In this paper, pertinent publications on the prevalence, impact, and treatment strategie...s of MHC obtained by searching major electronic databases (PubMed, PubMed Central, Google Scholar, ScienceDirect, and Scopus) were reviewed, and it was found that the prevalence of MHC in SSA was 0.7%–47.5% overall. Prevalence was 0.7%–47.5% in nonpregnant adults, 1.2%–27.8% in children, and 0.94%–37% in pregnant women. MHC was associated with an increased frequency of clinical parasitemia and severe malaria, increased parasite and viral load, and impaired immunity to malaria in nonpregnant adults, children, and pregnant women, increased in placental malaria and related outcomes in pregnant women, and impaired antimalarial drug efficacy in nonpregnant adults and pregnant women. Although a few cases of adverse events have been reported in coinfected patients receiving antimalarial and antiretroviral drugs concurrently, available data are very limited and have not prompted major revision in treatment guidelines for both diseases. Artemisinin-based combination therapy and cotrimoxazole are currently the recommended drugs for treatment and prevention of malaria in HIV-infected children and adults. However, concurrent administration of cotrimoxazole and sulfadoxine–pyrimethamine in HIV-infected pregnant women is not recommended, because of high risk of sulfonamide toxicity. Further research is needed to enhance our understanding of the impact of malaria on HIV, drug–drug interactions in patients receiving antimalarials and antiretroviral drugs concomitantly, and the development of newer, safer, and more cost-effective drugs and vaccines to prevent malaria in HIV-infected pregnant women.
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