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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Antimicrobials are widely used in food animal production, and use is rapidly increasing.
In an era of growing demand for animal products, there is an increasing trend towards the industrial production of food animals, especially in lower- and middle-income countries (LMICs). One hallmark of this me...thod of animal production is the
use of antimicrobial drugs, which in the majority of cases are administered to healthy animals for purposes other than
treating or controlling disease (termed “therapeutic uses”)
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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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9 April 2020
WHO has published the guidance “Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected” This document is intended for clinicians taking care of hospitalized adult and paediatric patients with severe acute respiratory infection (SARI) whe...n COVID-19 infection is suspected. Optimized supportive care should be provided to ensure the best possible chance for survival of COVID-19 patients as described in the WHO guidance:
1. Management of severe COVID-19 requires oxygen therapy and monitoring. Supplemental oxygen therapy should be given immediately to patients with SARI and respiratory distress, hypoxaemia or shock.
2. Management of critical COVID-19 (acute respiratory distress syndrome (ARDS)) requires advanced oxygen/ventilatory support.
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Viral hepatitis is defined as inflammation of the liver cells due to viral infection. The burden of liver disease in South Africa is mostly underestimated as viral hepatitis, in particular chronic infection, is a silent and neglected cause of morbidity and mortality. However, the burden of disease i...s likely substantial given the prevalence of chronic viral hepatitis. This burden is further compounded by the lack of screening and access to care and treatment as well as inadequate disease surveillance, human and financial resources.
The National Guidelines for the Management of Viral Hepatitis were developed, with the purpose to:
inform healthcare workers in the public and private sectors about the disease, its epidemiology in South Africa and current methods of diagnosis and therapy
strengthen the healthcare response to viral hepatitis
empower communicable diseases workers and stakeholders to make informed decisions regarding appropriate and cost effective interventions
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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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Buruli ulcer caused by Mycobacterium ulcerans is a neglected tropical disease characterized by extensive ulceration involving predominantly the upper and lower limbs of patients. The disease is common in rural tropical communities in West and Central Africa, where access to proper health care is lim...ited. Pathogenesis of the characteristic painless ulcers is linked to the elaboration by M. ulcerans of a lipid toxin called mycolactone that has potent cytopathic, immunosuppressive, and analgesic effects on a host of cells in cutaneous tissues. Mycolactone is known to profoundly inhibit secretion of a plethora of proteins that are essential for wound healing. Even though a combination antibacterial therapy of streptomycin and rifampicin for 8 weeks is effective for treatment, it relies on good and appropriate wound management to prevent secondary bacterial infections and improve healing. Evidence-based interventions for wound care in Buruli ulcer disease are often lacking and have relied on expert advice and recommendations. Surgical interventions are limited to debridement of necrotic tissue and grafting of extensive ulcers, usually after antibiotic therapy. Patients’ rehabilitation is an important component of care to reduce disabilities associated with the disease and proper integration into the community after 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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Parasites & Vectors volume 11, Article number: 264 (2018)
Dengue creates a staggering epidemiological and economic burden for endemic countries. Without a specific therapy and with a commercial vaccine that presents some problems relative to its full effectiveness, initiatives to improve vector... control strategies, early disease diagnostics and the development of vaccines and antiviral drugs are priorities. In this study, we present the probable origins of dengue in America and the trajectories of its spread. Overall, dengue diagnostics are costly, making the monitoring of dengue epidemiology more difficult and affecting physicians’ therapeutic decisions regarding dengue patients, especially in developing countries. This review also highlights some recent and important findings regarding dengue in Brazil and the Americas. We also summarize the existing DENV polymerase chain reaction (PCR) diagnostic tests to provide an improved reference since these tests are useful and accurate at discriminating DENV from other flaviviruses that co-circulate in the Americas. Additionally, these DENV PCR assays ensure virus serotyping, enabling epidemiologic monitoring.
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This document focuses on the management of patients affected by gambiense HAT and
constitutes an update to the WHO therapeutic guidance issued in 2013. The main changes in recommendations concern the criteria and methods for deciding the treatment among the new set of therapeutic options and the pa...rticular conditions that apply to treatment with fexinidazole, as outlined below. Because HAT is a serious, life-threatening disease and because the efficacy of fexinidazole depends on swallowing the medicine after an appropriate intake of food as well as on completing the full 10-day
treatment schedule, the recommendations regarding fexinidazole administration are considered key elements that must be carefully followed. When the conditions listed in these guidelines are not met for any individual patient, the alternative available treatments should be prescribed.
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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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In the Indian state of Bihar, visceral leishmaniasis (VL) is a major public health issue that has been aggravated by the rising incidence of new Human immunodeficiency virus (HIV) infections. In endemic areas, the risk of VL infections in patients living with HIV (PLHIV) is higher. It is important t...o investigate the disease-related knowledge, attitude, and practices (KAP) of PLHIV in Bihar in order to monitor HIV/VL co-infection. Adequate knowledge, a positive attitude, and good practices for VL control are essential to stamp out the disease. This study investigated the KAP towards VL in HIV patients attending antiretroviral therapy (ART) clinic at ICMR-RMRIMS, Patna.
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Chikungunya virus (CHIKV) is a re-emerging mosquito borne alphavirus responsible
for the recent outbreak in the Americas. Immunologically naïve population in the Americas favors the spread of epidemics. Chikungunya fever is characterized by an abrupt febrile illness, polyarthralgia and maculopapul...ar rash. In chikungunya fever, shock or severe hemorrhage is very rarely observed; the onset is more acute and the duration of fever is shorter than dengue disease. The pain is much more pronounced and localized to the joints and tendons in chikungunya fever, in comparison to dengue fever. There is no specific and effective antiviral therapy and vaccines are still in trails. The only effective preventive measures consist of individual protection against mosquito bites and vector control. Disease prevention is important due to the
economic burden it entails. Clinicians need to distinguish chikungunya fever between dengue fever and other diseases to give a successful treatment and prevent disease spreading.
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The previous report of the WHO Expert Committee on this disease
followed a meeting in 1995. Intensive, coordinated efforts against HAT during
the intervening 18 years have resulted in a decrease in incidence to a point at
which elimination is considered feasible. This report provides informati...on about
new diagnostic approaches, new therapeutic regimens and better understanding
of the distribution of the disease with high-quality mapping. The roles of human
and animal reservoirs and the tsetse fly vectors that transmit the parasites are
emphasized. The new information has formed the basis for an integrated strategy
with which it is hoped that elimination of HAT will be achieved. The report also
contains recommendations on the approaches that will lead to elimination of the
disease.
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The updates are based on evidence emerging from the: Ongoing monitoring of the disease. Protection that the population already developed against COVID-19 through previous infection or vaccination. Epidemiological situation, availability of diagnostic tests and access to therapeutic options.
Leishmaniasis is a vector-borne tropical/subtropical disease caused by an intracellular parasite transmitted to humans by sand fly bite. It is endemic in Asia, Africa, the Americas, and the Mediterranean region. Worldwide reports include 1.5–2 million new cases each year, more than 300 million at ...risk of acquiring the disease, and 70,000 deaths per year. Clinical features depend on the Leishmania species and immune response of the host, varying from localized cutaneous disease to visceral form with potentially fatal outcome; however, the common presentation is either cutaneous, mucocutaneous, or visceral leishmaniasis. Many therapeutic agents are being used in Leishmania treatment, but the only effective treatment is achieved with current pentavalent antimonials. WHO considers Leishmaniasis as one of the “Neglected Tropical Diseases” that continues to be prevalent despite international, national, and local efforts towards its control and elimination over the last decade. This chapter reviews the global perspective of Leishmaniasis with increasing recognition of emerging “Atypical forms” and new surge of disease across the world mainly due to increasing conflicts in endemic areas leading to forced migration among other causes. All these challenges related to environment, disease, and vector pose major implications on WHO’s leishmaniasis control and elimination plan.
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WHO has updated its guidelines for COVID-19 therapeutics, with revised recommendations for patients with non-severe COVID-19. This is the 13th update to these guidelines.
Updated risk rates for hospital admission in patients with non-severe COVID-19
The guidance includes updated risk rates for... hospital admission in patients with non-severe COVID-19.
The current COVID-19 virus variants tend to cause less severe disease while immunity levels are higher due to vaccination, leading to lower risks of severe illness and death for most patients.
This update includes new baseline risk estimates for hospital admission in patients with non-severe COVID-19. The new ‘moderate risk’ category now includes people previously considered to be high risk including older people and/or those with chronic conditions, disabilities, and comorbidities of chronic disease. The updated risk estimates will assist healthcare professionals to identify individuals at high, moderate or low risk of hospital admission, and to tailor treatment according to WHO guidelines:
**High: **People who are immunosuppressed remain at higher risk if they contract COVID-19, with an estimated hospitalization rate of 6%.
**Moderate: **People over 65 years old, those with conditions like obesity, diabetes and/or chronic conditions including chronic obstructive pulmonary disease, kidney or liver disease, cancer, people with disabilities and those with comorbidities of chronic disease are at moderate risk, with an estimated hospitalization rate of 3%.
Low: Those who are not in the high or moderate risk categories are at low risk of hospitalization (0.5%). Most people are low risk.
Review of COVID-19 treatments for people with non-severe COVID-19
WHO continues to strongly recommend nirmatrelvir-ritonavir (also known by its brand name ‘Paxlovid’) for people at high-risk and moderate risk of hospitalization. The recommendations state that nirmatrelvir-ritonavir is considered the best choice for most eligible patients, given its therapeutic benefits, ease of administration and fewer concerns about potential harms. Nirmatrelvir-ritonavir was first recommended by WHO in April 2022.
If nirmatrelvir-ritonavir is not available to patients at high-risk of hospitalization, WHO suggests the use of molnupiravir or remdesivir instead.
WHO suggests against the use of molnupiravir and remdesivir for patients at moderate risk, judging the potential harms to outweigh the limited benefits in patients at moderate risk of hospital admission.
For people at low risk of hospitalization, WHO does not recommend any antiviral therapy. Symptoms like fever and pain can continue to be managed with analgesics like paracetamol.
WHO also recommends against use of a new antiviral (VV116) for patients, except in clinical trials.
The update also includes a strong recommendation against the use of ivermectin for patients with non-severe COVID-19. WHO continues to advise that in patients with severe or critical COVID-19, ivermectin should only be used in clinical trials.
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Cardiovascular diseases (CVD) represent the highest burden of disease globally. Medicines are a critical intervention used to prevent and treat CVD. This review describes access to medication for CVD from a health system perspective and strategies that have been used to promote access, including pro...viding medicines at lower cost, improving medication supply, ensuring medicine quality, promoting appropriate use, and managing intellectual property issues. Using key evidence in published and gray literature and systematic reviews, we summarize advances in access to cardiovascular medicines using the 5 health system dimensions of access: availability, affordability, accessibility, acceptability, and quality of medicines. There are multiple barriers to access of CVD medicines, particularly in low- and middle-income countries. Low availability of CVD medicines has been reported in public and private healthcare facilities. When patients lack insurance and pay out of pocket to purchase medicines, medicines can be unaffordable. Accessibility and acceptability are low for medicines used in secondary prevention; increasing use is positively related to country income. Fixed-dose combinations have shown a positive effect on adherence and intermediate outcome measures such as blood pressure and cholesterol. We have a new opportunity to improve access to CVD medicines by using strategies such as efficient procurement of low-cost, quality-assured generic medicines, development of fixed-dose combination medicines, and promotion of adherence through insurance schemes that waive copayment for long-term medications. Monitoring progress at all levels, institutional, regional, national, and international, is vital to identifying gaps in access and implementing adequate policies.
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Heart failure (HF) is a leading global public health problem with >64 million prevalent cases globally. Patients with HF with reduced ejection fraction (HFrEF) from low- and middle-income countries experience a 22% to 58% higher 1-year mortality rate than those in high-income countries.1 Guideline-d...irected medical therapy (GDMT) consisting of ACE (angiotensin-converting enzyme) inhibitors or ARB (angiotensin receptor blockers) or ARNI (angiotensin receptor-neprilysin inhibitors), β-blockers, MRA (mineralocorticoid receptor antagonists), and SGLT2 (sodium-glucose cotransporter 2) inhibitors substantially reduces mortality among patients with HFrEF. These medicines are among the most cost-effective interventions and are thus included as the highest priority health system interventions recommended by the Disease Control Priorities Project.2 Despite this high-quality evidence, GDMT remains widely underutilized in low- and middle-income countries resulting in widespread undertreatment of patients with HFrEF due to health system-, provider-, and patient-level barriers.1 National essential medicines lists (EMLs) promoted by the World Health Organization (WHO) guide countries on which medications to purchase in the setting of limited resources and have resulted in higher procurement and availability of essential medicines in the public sector.3 We provide a cross-sectional analysis of national EMLs in 53 low- and middle-income countries, and availability, price, and affordability of GDMT in select countries to identify potential barriers to access to these essential medicines for patients with HFrEF.
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The article "Can we prevent cardiovascular diseases in low- and middle-income countries?" by Claude Lenfant discusses the growing threat of cardiovascular diseases (CVDs) in developing countries. It highlights that while CVD is already the leading cause of death globally, low- and middle-income coun...tries are now facing rising CVD rates due to lifestyle changes associated with urbanization and economic growth. Lenfant advocates for a dual approach: identifying and treating high-risk individuals and promoting broad, population-wide prevention efforts focused on lifestyle changes such as reducing smoking, lowering salt intake, and increasing physical activity. He emphasizes that early, affordable preventive measures are essential to mitigate the impending CVD epidemic in these countries and prevent significant healthcare and economic strain.
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