Traditional management of ear, nose and throat (ENT) diseases in Central Kenya

Diseases of ear, nose and throat (ENT) often have serious consequences including hearing impairment, and emotional strain that lower the quality of life of patients. In Kenya, upper respiratory infections are among the most common infections encountered in outpatient facilities. Some of these infections are becoming difficult to control because some of the causing microorganisms have acquired antibiotic resistance and hence the need to develop new drugs with higher efficacy. Ethnobotanical studies have now been found to be instrumental in improving chances of discovering plants with antimicrobial activity in new drug development. In Kenya the majority of local people are turning to herbal remedies for primary health care needs. In most cases the sources of these remedies are undocumented and the knowledge about them passed orally form generation to generation, hence under threat of disappearing with current rates of modernisation. This study explored the traditional remedies used in managing various ENT diseases in seven districts of the Central Province of Kenya. The most common ENT conditions managed using traditional therapies include: common cold, cough, tonsillitis, otitis-media, chest pains and asthma. The results indicate that 67 species belonging to 36 plant families were utilized in this region. These plants were of varying habits; herbs (37.3%), shrubs (34.4%), trees (25.4%) as well as some grasses and sedges (3%). The traditional preparations were found to be made mainly from leaves (49%), roots (20.5%) and barks (12.5%). For each of the ENT conditions multiple species are utilized mainly as individual preparations but occasionally as polyherbal concoctions. In the case of common cold for example, 30 different species are used. Plants reported in this survey are important candidates for antimicrobial tests against ENT disease causing micro-organisms, especially those with antibiotic resistance

Sociocultural and Health System Factors Associated With Mortality Among Febrile Inpatients in Tanzania: A Prospective Social Biopsy Cohort Study

Introduction Communicable diseases are the leading causes of death in Tanzania despite the existence of effective treatment tools. We aimed to assess the sociocultural and health system factors associated with mortality from febrile illness in northern Tanzania. Methods We interviewed febrile inpatients to determine prevalence of barriers in seeking or receiving care and grouped these barriers using the Three Delays model (delays at home, in transport and at healthcare facilities). We assessed 6-week mortality and, after matching on age, gender and severity of illness, measured the association between delays and mortality using conditional logistic regression. Results We enrolled 475 children, of whom 18 (3.8%) died, and 260 adults, of whom 34 (13.0%) died. For children, home delays were not associated with mortality. Among adults, a delay in care-seeking due to not recognising severe symptoms was associated with mortality (OR: 3.01; 95% CI 1.24 to 7.32). For transport delays, taking \u3e1 hour to reach a facility increased odds of death in children (OR: 3.27; 95% CI 1.11 to 9.66) and adults (OR: 3.03; 95% CI 1.32 to 6.99). For health system delays, each additional facility visited was associated with mortality for children (OR: 1.59; 95% CI 1.06 to 2.38) and adults (OR: 2.00; 95% CI 1.17 to 3.41), as was spending \u3e4 days between the first facility visit and reaching tertiary care (OR: 4.39; 95% CI 1.49 to 12.93). Conclusion Our findings suggest that delays at home, in transport and in accessing tertiary care are risk factors for mortality from febrile illness in northern Tanzania. Interventions that may reduce mortality include community education regarding severe symptoms, expanding transportation infrastructure and streamlining referrals to tertiary care for the sickest patients

Non-communicable Diseases Week: Best Practices in Addressing the NCDs Burden from Tanzania

Background: Five million people die every year from non-communicable diseases (NCDs) globally. In Tanzania, more than two-thirds of deaths are NCD-related. The country is investing in preventive and advocacy activities as well as interventions to reduce the burden. Of particular interest, the Ministry of Health (MoH) commemorates NCDs’ week using a multisectoral and multi-stakeholders’ approach. This paper highlights activities conducted during NCDs week with the aim of sharing lessons for other countries with similar context and burdens. Methods: A thorough review of official reports and the national strategic plans for NCDs was done including the 2020 and 2021 National NCDs’ week reports, the National Strategic Plan for NCDs 2015–2020, and the National NCDs agenda. Findings: NCDs week is commemorated annually throughout the country involving the five key activities. First, community awareness and participation are encouraged through media engagement and community-based preventive and advocacy activities. Second, physical activities and sports festivals are implemented with a focus on developing and renovating infrastructures for sports and recreation. Third, health education is provided in schools to promote healthy behaviors for secondary school adolescents in transition to adulthood. Fourth, health service provision and exhibitions are conducted involving screening for hypertension, diabetes, obesity, alcohol use, and physical activities. The targeted screening of NCDs identified 10% of individuals with at least one NCD in 2020. In 2021, a third of all screened individuals were newly diagnosed with hypertension, and 3% were found to have raised blood glucose levels. Fifth, the national NCDs scientific conferences conducted within the NCDs week provide an avenue for stakeholders to discuss scientific evidence related to NCDs and recommend strategies to mitigate NCDs burden. Conclusion: The initiation of NCDs week has been a cornerstone in advocating for NCDs control and prevention in the country. It has created awareness on NCDs, encourage healthy lifestyles and regular screening for NCDs. The multi-stakeholder and multi-sectoral approaches have made the implementation of the mentioned activities feasible and impactful. This has set an example for the united efforts toward NCD control and prevention at national, regional, and global platforms while considering contextual factors during adoption and implementation

Natural products as starting points for future anti-malarial therapies: going back to our roots?

Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal medicinal products already used by the community. This first step forms a solid basis of observations, before moving to in vivo pharmacological characterization and ultimately identifying the active ingredient. A large part of the population uses herbal medicinal products despite limited numbers of well-controlled clinical studies. Increased awareness by the regulators and public health bodies of the need for safety information on herbal medicinal products also lends support to obtaining more clinical data on such products. Conclusions The relative paucity of new herbal medicinal product scaffolds active against malaria results discovered in recent years suggest it is time to re-evaluate the ‘smash and grab’ approach of randomly testing purified natural products and replace it with a patient-data led approach. This will require a change of perspective form many in the field. It will require an investment in standardisation in several areas, including: the ethnopharmacology and design and reporting of clinical observation studies, systems for characterizing anti-malarial activity of patient plasma samples ex vivo followed by chemical and pharmacological characterisation of extracts from promising sources. Such work falls outside of the core mandate of the product development partnerships, such as MMV, and so will require additional support. This call is timely, given the strong interest from researchers in disease endemic countries to support the research arm of a malaria eradication agenda. Para-national institutions such as the African Network for Drugs and Diagnostics Innovation (ANDi) will play a major role in facilitating the development of their natural products patrimony and possibly clinical best practice to bring forward new therapeutics. As in the past, with quinine, lapinone and artemisinin, once the activity of herbal medicinal products in humans is characterised, it can be used to identify new molecular scaffolds which will form the basis of the next generation of anti-malarial therapies.</p

The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Introduction Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the cost‐effectiveness of this enhanced‐prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced‐prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced‐prophylaxis components. Enhanced‐prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced‐prophylaxis still conveyed health gains in CrAg‐negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost‐effective unless the price of CrAg testing fell below US$2.30. Conclusions The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation