Dolutegravir HIV drug resistance (HIVDR) data from Africa remain sparse. We reviewed HIVDR results of Malawians on
dolutegravir-based antiretroviral therapy (November 2020– September 2021). Of 6462 eligible clients, 33 samples were submitted to South Africa, 27 were sequenced successfully, and 8 ...(30%) had dolutegravir HIVDR. Malawi urgently requires adequate HIVDR testing capacity.
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Ivermectin is an antiparasitic drug approved for the treatment of parasitic infections, including strongyloidiasis and onchocerciasis in humans. There is a reported increase in the use of ivermectin for the prevention and treatment of COVID-19 by the public in African Union Member States.
Currently..., there is:
1. No scientific evidence from pre-clinical studies on the therapeutic effect of ivermectin for the management of COVID-19;
2. No evidence of its clinical efficacy for the management of patients with asymptomatic, mild, moderate or severe COVID-19; and
3. No safety data regarding the use of ivermectin for COVID-19 in the majority of the published studies.
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Expert Consensus Validation 2018.
This innovative approach aimed at improving and facilitating the screening, prescribing and monitoring of drug therapy for older patients, is currently being further developed in the area of Clinical Pharmacology at the University of Heidelberg in Mannheim. This ap...proach represents another advance in worldwide research efforts aimed at adding a new dimension to already-existing classification systems and negative listings of potentially inappropriate medications for the elderly.
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The pamphlet "What is Addiction" explains addiction as a chronic, relapsing brain disease characterized by compulsive drug seeking and use, despite harmful consequences. It highlights the dangers of different drug categories, including sedatives, stimulants, and hallucinogens, and their potential he...alth and behavioral impacts. The document emphasizes the importance of combined medication and behavioral therapy in the treatment process, including detoxification, ongoing therapy, and relapse prevention. Additionally, it provides contact information for addiction treatment resources.
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We systematically reviewed Medline as well as the references of published review articles for relevant studies of adherence to multidrug treatment of both drug-susceptible and drug-resistant TB through February 3, 2018. We included randomized controlled trials (RCTs) as well as prospective and retro...spective cohort studies (CSs) with an internal or external control group that evaluated any adherence intervention and conducted a meta-analysis of their impact on TB treatment outcomes. Our search identified 7,729 articles, of which 129 met the inclusion criteria for quantitative analysis. Seven adherence categories were identified, including DOT offered by different providers and at various locations, reminders and tracers, incentives and enablers, patient education, digital technologies (short message services [SMSs] via mobile phones and video-observed therapy [VOT]), staff education, and combinations of these interventions.
https://doi.org/10.1371/journal.pmed.1002595
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sthma prevalence is increasing worldwide, and surveys indicate that most patients in developed and developing countries, including South Africa, do not receive optimal care and are therefore not well controlled. Standard management guidelines adapted to in-country realities are important to support ...optimal care. The South African Thoracic Society (SATS) first published a guideline for the management of chronic persistent asthma in 1992, which has subsequently been revised several times.
The main aim of the present document was to revise and update SATS’ statement on the suggested management of chronic asthma, based on the need to promote optimal care and control of asthma, together with the incorporation of new concepts and drug developments. This revised document reinforces optimal care and incorporates the following primary objectives to achieve the recent advances in asthma care:
• continued emphasis on the use of inhaled corticosteroids (ICS) as the foundation of asthma treatment
• to reduce the reliance on short-acting beta-2 agonist (SABA) monotherapy for asthma symptoms
• to incorporate the evidence and strategy for the use of the combination of an ICS and formoterol for acute symptom relief (instead of a SABA)
• to incorporate the evidence and strategy for the use of as-needed ICS-long-acting beta agonists (LABA) for patients with infrequent symptoms or ‘mild’ asthma
• to incorporate the evidence and strategy for the use of a long-acting muscarinic antagonist (LAMA) in combination with ICS-LABA; and
• to incorporate the evidence and strategy for the use of and management with a biologic therapy in severe asthma.
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These guidelines are based on the 3rd Edition of the WHO Guidelines (Published 2015) World Health Organization’s Guidelines for the treatment of malaria. Additional literature surveys have been undertaken. Factors that were considered in the choice of therapeutic options included effectiveness, sa...fety, and impact on malaria transmission and on the emergence and spread of antimalarial drug resistance. On-going surveillance is critical given the spread of artemisinin resistance in Southeast Asia, although not yet confirmed anywhere in Africa. The guidelines on the treatment of malaria in South Africa aim to facilitate effective, appropriate and timeous treatment of malaria, thereby reducing the burden of this disease in our communities. This is essential to further reduce the malaria case fatality rates currently recorded in South Africa, to decrease malaria transmission and to limit resistance to antimalarial drugs.
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This report provides an update on the key facets of HIV treatment access, including the latest HIV treatment guidelines from World Health Organization (WHO), an overview on pricing for first-line, second-line, and salvage regimens, and a summary of the opportunities for – and threats to – expand...ing access to affordable antiretroviral therapy (ART).
The report is supplemented by 11 drug profiles that contain more detailed information on pricing trends and patent barriers for key antiretroviral drugs and fixed-dose combinations. Also included is an annex of conditions that define eligibility for reduced prices from 15 pharmaceutical companies.
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Co-trimoxazole is a fixed-dose combination of two antimicrobial drugs (sulfamethoxazole and trimethoprim) that covers a variety of bacterial, fungal and protozoan infections. Co-trimoxazole preventive therapy is a feasible, well tolerated and inexpensive intervention for people living with HIV to re...duce HIV-related morbidity and mortality. Further, co-trimoxazole is an off-patent drug and widely available in resource-limited settings.
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Antimicrobial resistance represents a big threat to public health. The Centers for Disease Control and Prevention (CDC) estimate that every year two million Americans are infected with a (multi-)drug resistant bacterium, resulting in 23,000 deaths. The WHO has repeatedly drawn attention to this majo...r health issue. In the worst-case scenario, we will shortly run out of effective antibiotics. Surgery and cancer therapy will then become very dangerous due to the risk of infection associated with such treatments. (Organ) transplantation will become close to impossible as the immunosuppression necessary for transplant patients makes them highly vulnerable to infections. Some infections we can easily treat today could turn deadly. It is therefore conceivable that infectious diseases once again become the leading cause of death as in early 20th century.
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Human African Trypanosomiasis (HAT, sleeping sickness) and Animal African Trypanosomiasis (AAT) are neglected tropical diseases generally caused by the same etiological agent, Trypanosoma brucei. Despite important advances in the reduction or disappearance of HAT cases, AAT represents a risky reserv...oir of the infections. There is a strong need to control AAT, as is claimed by the European Commission in a recent document on the reservation of antimicrobials for human use. Control of AAT is considered part of the One Health approach established by the FAO program against African Trypanosomiasis. Under the umbrella of the One Health concepts, in this work, by analyzing the pharmacological properties of the therapeutic options against Trypanosoma brucei spp., we underline the need for clearer and more defined guidelines in the employment of drugs designed for HAT and AAT. Essential requirements are addressed to meet the challenge of drug use and drug resistance development. This approach shall avoid inter-species cross-resistance phenomena and retain drugs therapeutic activity.
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Clinical guideline, Methods, Evidence and Recommendations
In this guideline the following is covered: information needs of people with chronic hep
titis B and their carers; where children, young people and adults with chronic hepatitis B a-
should be assessed; assessment of liver disease, includi...ng the use of non-invasive tests and genotype testing; criteria for offering antiviral treatment; the efficacy, safety and cost effectiveness of currently available treatments; selection of first-line therapy; management of treatment failure or drug resistance; prophylactic treatment during im-
munosuppressive therapy; and monitoring for treatment response
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This study was aimed to ascertain the clinical profile and management of patients with ischemic heart disease (IHD) and/or peripheral artery disease (PAD). In this observational and cross-sectional study developed in 80 hospitals throughout Spain, consecutive adults with stable IHD and/or PAD were i...ncluded. A total of 1089 patients were analyzed, of whom 65.3% had only IHD, 17.8% PAD and 16.9% both. A total of 80.6% were taking only one antiplatelet agent, and 18.2% were on dual antiplatelet therapy (mainly aspirin/clopidogrel). Almost all patients were taking ≥1 lipid lowering drug, mainly moderate-to-high intensity statins. IHD patients took ezetimibe more commonly than PAD (43.9% vs. 12.9%; p < 0.001). There were more patients with IHD that achieved blood pressure targets compared to PAD (<140/90 mmHg: 67.9% vs. 43.0%; p < 0.001; <130/80 mmHg: 34.1% vs. 15.7%; p < 0.001), LDL-cholesterol (<70 mg/dL: 53.1% vs. 41.5%; p = 0.033; <55 mg/dL: 26.5% vs. 16.0%; p = 0.025), and diabetes (HbA1c < 7%, with SGLT2i/GLP1-RA: 21.7% vs. 8.8%; p = 0.032). Modifications of antihypertensive agents and lipid-lowering therapy were performed in 69.0% and 82.3% of patients, respectively, without significant differences between groups. The use of SGLT2i/GLP1-RA was low. In conclusion, cardiovascular risk factors control remains poor among patients with IHD, PAD, or both. A higher use of combined therapy is warranted.
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Schistosomiasis and soil-transmitted helminths (STH) infections are major public health problems. We aimed to study the 6-mo impact of mass drug administration with praziquantel and albendazole on urinary schistosomiasis and STH.We examined children (aged 2–15 y) from one hamlet, who provided urin...e and faeces samples at baseline (n=197), 1 mo (n=102) and 6 mo (n=92); 67 completed the protocol.At baseline, 47/67 (70.1%) children presented Schistosoma haematobium (75.8% in the baseline total sample) and 12/67 (17.9%) with STH (30.5% in the initial sample, p=0.010). Among the children, 47.3% had heavy Schistosoma haematobium infection. The most frequent STH was Trichuris trichiura in 9.0%. We also found Hymenolepis nana (13.2%) and Plasmodium falciparum (9.1%) infections and anaemia (82.1%). One mo after chemotherapy there was a significant (p=0.013) reduction of Schistosoma haematobium prevalence (23.5%) and a high egg reduction rate (86.9%). Considering the sample of 67 children, the mean egg concentration was 498 at baseline, 65 at 1 mo and 252 at 6 mo (p<0.05). We also observed a reduction in STH infections, 50% in Ascaris lumbricoides, 33.3% in T. trichiura and 50% in hookworms. At 6 mo, the prevalence of Schistosoma haematobium (76.1%) was similar to the baseline and the STH reduction was not significant.Longitudinal studies have reported many losses in these settings, but we were able to show that mass drug administration for control of schistosomiasis and STH present low effectiveness, that reinfections occur rapidly and that stand alone anthelmintic therapy is not a sustainable choice.
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After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenge...s of the clinical trials of fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules. In cell culture, fexinidazole has an IC50 of around 1 µM against Trypanosoma brucei and is more than 100-fold less toxic to mammalian cells. In the mouse model, fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT). This greatly facilitates the diagnosis and treatment algorithm for gHAT, increasing the attainable coverage and paving the way towards the envisaged goal of zero transmission by 2030.
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The mandate of the National Tuberculosis Control Programme is to provide leadership and stewardship to accelerate intense and coordinated efforts to reduce the adult TB burden of 290 per 100,000 population recently established in the 2013 National TB Prevalence Survey. Other key challenges are low T...B case notification, unacceptably high TB death rates, low antiretroviral therapy (ART) coverage among TB/HIV patients and low drug-resistant notification and treatment.
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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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Cardiovascular disease is a major cause of disability and premature death throughout the world, and contributes substantially to the escalating costs of health care. The underlying pathology is atherosclerosis, which develops over many years and is usually advanced by the time symptoms occur, genera...lly in middle age. Acute coronary and cerebrovascular events frequently occur suddenly, and are often fatal before medical care can be given. Modification of risk factors has been shown to reduce mortality and morbidity in people with diagnosed or undiagnosed cardiovascular disease.
This publication provides guidance on reducing disability and premature deaths from coronary heart disease, cerebrovascular disease and peripheral vascular disease in people at high risk, who have not yet experienced a cardiovascular event. People with established cardiovascular disease are at very high risk of recurrent events and are not the subject of these guidelines. They have been addressed in previous WHO guidelines.
Several forms of therapy can prevent coronary, cerebral and peripheral vascular events. Decisions about whether to initiate specific preventive action, and with what degree of intensity, should be guided by estimation of the risk of any such vascular event. The risk prediction charts that accompany these guidelinesb allow treatment to be targeted accord-
ing to simple predictions of absolute cardiovascular risk.
Recommendations are made for management of major cardiovascular risk factors through changes in lifestyle and prophylactic drug therapies. The guidelines provide a framework for the development of national guidance on prevention of cardiovascular disease that takes into account the particular political, economic, social and medical circumstances.
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The Western Pacific Region is the largest and most diverse region in the world, made up of 37 countries and territories in the Pacific, Oceania and parts of Asia, with a population of more than 1.9 billion people stretching over an area from China and Mongolia in the north to New Zealand in the sout...h. In 1999, 22 countries and territories in the Pacific joined together and launched the Pacific Programme to Eliminate Lymphatic Filariasis. Shortly after, the Global Programme to Eliminate Lymphatic Filariasis was launched in 2000. In 2004, 12 countries in the Asia subregion of the Western Pacific Region and Southeast Asian Region joined and developed the Mekong-Plus Strategic Plan for Elimination of Lymphatic Filariasis. Since then, significant efforts have been made by all endemic countries, with annual mass drug administration (MDA) as a principal strategy, through strong partnership with the WHO and other donors and partners. As a result, by the end of 2019, 10 of 22 endemic countries in the region, including 8 of 16 countries in the Pacific and 2 countries in the Asia subregion, achieved WHO validation for elimination of lymphatic filariasis (LF) as a public health problem. All the other countries are either progressing with post-MDA surveillance or accelerating efforts by adoption of the new triple drug therapy strategy and enhancement of MDA campaigns to tackle persistent transmission. Some 85% of the originally endemic implementation units have stopped MDA and the number of people requiring MDA for LF in the Western Pacific Region was reduced by 72% from 2000 to 2018. This paper reviews the progress, key success factors and remaining challenges and indicates the way forward to achieve LF elimination in the Western Pacific Region.
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Non-communicable diseases (NCDs) pose a substantial threat to many health systems, especially in low-income and middle-income countries (LMICs) where they are already overstretched. In the past few decades, deaths from NCDs in LMICs have spiked, whereas numbers in high-income countries have stabilis...ed. Worryingly, a large proportion of deaths from NCDs (29%) in LMICs occur among people younger than 60 years compared with the proportion in high-income countries (13%). This finding has been attributed to poor access to effective and equitable health-care services in most LMICs. The threat of NCDs in LMICs was recognised by the UN 2011 High-Level Meeting, and is now featured in Sustainable Development Goal 3 in the form of reducing premature mortality from NCDs by one-third before 2030. Cardiovascular diseases (CVDs) are the leading cause of deaths from NCDs (ie, 48% of all NCDs deaths). Therefore, substantial reductions in CVDs will have a major impact on reducing the overall burden of NCDs globally. The good news is that most CVDs can be prevented by addressing the key underlying behavioural risk factors, such as physical inactivity, unhealthy diet, tobacco use, and harmful use of alcohol, through population-wide approaches. Among individuals with or at high risk of CVD, early detection and effective management with appropriate counselling and medicines can reduce cardiovascular deaths substantially.
The importance of effective treatment for CVD has been recognised in the Global NCD Action Plan 2013–20, for which one of the nine global targets is that at least 50% of eligible individuals should receive drug therapy and counselling to prevent heart attacks and strokes by 2025.5 Although admirable, this is a hard target to achieve given that secondary prevention strategies in LMICs are often unaffordable or unavailable.
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