World Health Organization's List Research Articles

A Survey of Availability and Affordability of Polypills for Cardiovascular Disease in Selected Countries.

The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally. We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised for marketing and/or included in EMLs and clinical guidelines. In each country, we collected retail and price data for polypills from at least one public-sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable if the lowest-paid worker spent more than a day's wage to purchase a monthly supply. Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. In the four countries, no surveyed public pharmacies stocked polypills. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Private sector availability was 100% in Argentina and Spain. Most combinations (n = 5) identified were in India. Combinations found in India and Spain were affordable in the local context. A lowest-paid government worker would spend between 0.2 (India) and 2.8 (Mauritius) days' wages to pay the price for one month's supply of the polypills. Polypills were likely to be affordable if they were manufactured in the same country. Low availability and affordability of polypills in the public sector suggest that implementation remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

Pleiotropic Effects of Heparin and its Monitoring in the Clinical Practice.

Unfractionated heparin (UFH) was uncovered in 1916, has been used as an anticoagulant since 1935, and has been listed in the World Health Organization's Model List of Essential Medicines. Despite the availability of many other anticoagulants, the use of heparin (either low molecular weight heparin [LMWH] or UFH) is still substantial. Heparin has pleotropic effects including anticoagulant and several nonanticoagulant properties such as antiproliferative, anti-inflammatory activity, and anticomplement effects. Although UFH has been widely replaced by LMWH, UFH is still the preferred anticoagulant of choice for patients undergoing cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, and patients with high-risk mechanical cardiac valves requiring temporary bridging with a parenteral anticoagulant. UFH is a highly negatively charged molecule and binds many positively charged molecules, hence has unpredictable pharmacokinetics, and variable anticoagulant effect on an individual patient basis. Therefore, anticoagulant effects of UFH may not be proportional to the dose of UFH given to any individual patient. In this review, we discuss the anticoagulant and nonanticoagulant activities of UFH, differences between UFH and LMWH, when to use UFH, different methods of monitoring the anticoagulant effects of UFH (including activated partial thromboplastin time, heparin anti-Xa activity level, and activated clotting time), while discussing pros and cons related to each method and comparison of clinical outcomes in patients treated with UFH monitored with different methods based on available evidence.

PmrAB, the two-component system of Acinetobacter baumannii, controls the phosphoethanolamine modification of lipooligosaccharide in response to metal ions.

Antimicrobial resistance (AMR) is a pressing global issue in human health. Acinetobacter baumannii is notably high on the World Health Organization's list of bacteria for which new antimicrobial agents are urgently needed. Colistin is one of the last-resort drugs used against extensively drug-resistant (XDR) Gram-negative bacteria. However, A. baumannii has become increasingly resistant to colistin, primarily by modifying its lipooligosaccharide (LOS) via activating mutations in the two-component system (TCS) PmrAB. This study comprehensively elucidates the detailed mechanism of drug resistance of PmrAB in A. baumannii as well as its biological functions. Understanding the molecular biology of these molecules, which serve as drug resistance factors and are involved in environmental recognition mechanisms in bacteria, is crucial for developing fundamental solutions to the AMR problem.

In Vitro Bactericidal Activity of Biogenic Copper Oxide Nanoparticles for Neisseria gonorrhoeae with Enhanced Compatibility for Human Cells.

Resistance to antibiotics and antimicrobial compounds is a significant problem for human and animal health globally. The development and introduction of new antimicrobial compounds are urgently needed, and copper oxide nanoparticles (CuO NPs) have found widespread application across various sectors including biomedicine, pharmacy, catalysis, cosmetics, and many others. What makes them particularly attractive is the possibility of their synthesis through biogenic routes. In this study, we synthesized biogenic green tea (GT, Camellia sinensis)-derived CuO NPs (GT CuO NPs) and examined their biophysical properties, in vitro toxicity for mammalian cells in culture, and then tested them against Neisseria gonorrhoeae, an exemplar Gram-negative bacterium from the World Health Organization's Priority Pathogen List. We compared our synthesized GT CuOP NPs with commercial CuO NPs (Com CuO NPs). Com CuO NPs were significantly more cytotoxic to mammalian cells (IC50 of 7.32 μg/mL) than GT CuO NPs (IC50 of 106.1 μg/mL). GT CuO NPs showed no significant increase in bax, bcl2, il6, and il1β mRNA expression from mammalian cells, whereas there were notable rises after treatment with Com CuO NPs. GT-CuO NPs required concentrations of 0.625 and 3.125 μg/mL to kill 50 and 100% of bacteria, respectively, whereas Com-CuO NPs needed concentrations of 15.625 and 30 μg/mL to kill 50 and 100% of bacteria, and the antibiotic ceftriaxone killed 50 and 100% with 3.125 and 30 μg/mL. Gonococci could be killed within 30 min of exposure to GT CuO NPs and the NPs could kill up to 107 within 1 h. In summary, this is the first report to our knowledge that describes the bioactivity of biogenic CuO NPs against N. gonorrhoeae. Our data suggest that biogenic nanoparticle synthesis has significant advantages over traditional chemical routes of synthesis and highlights the potential of GT-CuO NPs in addressing the challenges posed by multidrug-resistant Neisseria gonorrhoeae infections.

The Rapid Emergence of Hypervirulent Klebsiella Species and Burkholderia pseudomallei as Major Health Threats in Southeast Asia: The Urgent Need for Recognition as Neglected Tropical Diseases.

The World Health Organization (WHO)'s list of neglected tropical diseases (NTDs) highlights conditions that are responsible for devastating health, social and economic consequences, and yet, they are overlooked and poorly resourced. The NTD list does not include conditions caused by Gram-negative bacilli (GNB). Infections due to GNB cause significant morbidity and mortality and are prevalent worldwide. Southeast Asia is a WHO region of low- and middle-income countries carrying the largest burden of NTDs. Two significant health threats in Southeast Asia are Burkholderia pseudomallei (causing melioidosis) and hypervirulent Klebsiella pneumoniae (HvKp). Both diseases have high mortality and increasing prevalence, yet both suffer from a lack of awareness, significant under-resourcing, incomplete epidemiological data, limited diagnostics, and a lack of evidence-based treatment. Emerging evidence shows that both melioidosis and HvKp are spreading globally, including in high-income countries, highlighting the potential future global threat they pose. In this article, we review both conditions, identifying current trends and challenges in Southeast Asia and areas for future research. We also argue that melioidosis and HvKp merit inclusion as NTDs, and that mandatory global surveillance and reporting systems should be established, and we make an urgent call for research to better understand, detect, and treat these neglected diseases.

Arsenic Contamination Needs Serious Attention: An Opinion and Global Scenario

Arsenic (As) contamination is a serious global concern, polluting our natural resources, including water and soil, and posing a danger to the environment and public health. Arsenic is present in the groundwater of several countries and this contaminated water is used for irrigation, drinking, and food preparation, which poses the greatest threat to public health. Nearly 106 countries are affected by groundwater arsenic contamination and an estimated 230 million individuals worldwide are exposed to its adverse health effects, including increased cancer risks, associated cardiovascular disease and diabetes, skin lesions, neurological effects, kidney damage, and foetal or cognitive-development-related complications. Arsenic is highly toxic and ranked first in the priority list of ATSDR (Agency for Toxic Substances and Disease Registry, 2022) and among the 10 chemicals of major public health concern on the World Health Organization (WHO) list. The maximum permissible level of arsenic in drinking water has been established at 10 µg/L by WHO, as well as by the Environmental Protection Agency (EPA) and European Union (EU). These regulatory standards underscore the gravity of the problem, and actions to prioritise the development of effective detection, mitigation strategies, and collaborative initiatives are necessary. This opinion article covers (i) arsenic footprints—global scenario and impact, (ii) awareness and education and (iii) mitigation approaches (detection and removal strategies) and future perspectives, which collectively will help in controlling and preventing As contamination of our global water resources. Regulatory and legislative bodies and development agencies are crucial for raising awareness and countering this alarming concern by implementing collaborative actions to protect our environment and public health and to provide safe drinking water for all.

Antibodies anti-rFilF protein has anti-biofilm activity against carbapenem-resistant Acinetobacter baumannii

Acinetobacter baumannii is an opportunistic bacterium that causes infection in several sites. Carbapenem-resistant A. baumannii strains (CRAb) lead the World Health Organization's list of 12 pathogens considered a priority for developing new antimicrobials. The pathogenicity of A. baumannii is related to the different virulence factors employed in the colonization of biotic and abiotic surfaces, biofilm formation and multidrug resistance. We analyze the outer membrane protein FilF from A. baumannii in silico and produce it in recombinant form (rFilF). rFilF protein was successfully expressed in Escherichia coli BL21 Star in an insoluble form. Immunization with rFilF induced significant anti-rFilF IgG antibody production in mice, detected by indirect enzyme-linked immunosorbent assay, since the first evaluation until 49th. On the last experimentation day, the predominant immunoglobulin found was IgG1 followed by IgG2a, IgG2b, IgM, IgG3, and IgA. We observe that interleukins 4 and 10 show significant production after the 28th day of experimentation in mice immunized with rFilF. Anti-rFilF pAbs were able to inhibit biofilm formation in nine CRAb strains evaluated, and in the standard strain ATCC® 19606. These results demonstrate the anti-biofilm activity of anti-rFilF antibodies, promising in the development of a non-antibiotic approach based on the control of CRAb strains.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Antifibrinolytics

The use of strategies to reduce blood loss and transfusions is essential in the treatment of surgical patients, including in complex cardiac surgeries and those that use cardiopulmonary bypass. Antifibrinolytics, such as epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), are widely used in these procedures, as well as in other types of surgeries. These medicines are included in the World Health Organization (WHO) list of ‘essential medicines’. Scientific evidence demonstrates the effectiveness of EACA in reducing bleeding and the need for transfusions in heart surgery. EACA is highly recommended for use in heart surgery by the American Society of Anesthesiology Task Force on Perioperative Blood Management. Regarding the safety of EACA, there is no robust evidence of any significant thrombotic potential. TXA has also been shown to be effective in reducing the use of blood transfusions in cardiac and non-cardiac surgeries and is considered safer than other antifibrinolytic agents. There is no evidence of any increased risk of thromboembolic events with TXA, but doses greater than 2 g per day have been associated with an increased risk of seizures. It is also important to adjust the dose in patients with renal impairment. In conclusion, antifibrinolytics, such as EACA and TXA, are effective in reducing blood loss and transfusion use in cardiac and non-cardiac surgeries, without causing serious adverse effects.

PERSPECTIVE OF THE DOCTORS IN A NEW MEDICAL COLLEGE OF NORTH-EAST INDIA REGARDING THE NATIONAL LIST OF ESSENTIAL MEDICINES

Objectives: To collate the perspectives of doctors regarding the national list of essential medicines (NLEM) and thus assess the factors affecting adaptation and implementation of NLEM at the state or institution level. Methods: This is a cross-sectional questionnaire-based study conducted among the doctors of Tomo Riba Institute of Health and Medical Sciences, which is a new medical college and a tertiary care hospital in Naharlagun, Arunachal Pradesh. The study was carried out for 6 months. The participants were explained the purpose of the study and requested to fill out the questionnaire and return it immediately. Data analysis was performed using simple statistical methods such as percentages and proportions. Results: Out of 73 participants, 63% were aware of NLEM, while 37% were unaware of the term NLEM. Only 17.8% of the doctors are satisfied that the drugs in the latest NLEM suffice for most of the medical conditions they come across in their daily practices. Only about 39.7% of the doctors frequently prescribed the drugs from the NLEM list in their routine practice. The majority (61.6%) of them agree that there should be a separate essential drug list supplementary to the World Health Organization list in every tertiary care medical college. Conclusion: The concept of NLEM offers the most cost-effective solution to healthcare needs. The selection of the medicines in the list or a separate state or institutional list according to the needs of the regional population can cater to most of the healthcare needs.

A mRNA Vaccine for Crimean-Congo Hemorrhagic Fever Virus Expressing Non-Fusion GnGc Using NSm Linker Elicits Unexpected Immune Responses in Mice.

Crimean-Congo hemorrhagic fever (CCHF), caused by Crimean-Congo Hemorrhagic virus (CCHFV), is listed in the World Health Organization's list of priority diseases. The high fatality rate in humans, the widespread distribution of CCHFV, and the lack of approved specific vaccines are the primary concerns regarding this disease. We used microfluidic technology to optimize the mRNA vaccine delivery system and demonstrated that vaccination with nucleoside-modified CCHFV mRNA vaccines encoding GnNSmGc (vLMs), Gn (vLMn), or Gc (vLMc) induced different immune responses. We found that both T-cell and B-cell immune responses induced by vLMc were better than those induced by vLMn. Interestingly, immune responses were found to be lower for vLMs, which employed NSm to link Gn and Gc for non-fusion expression, compared to those for vLMc. In conclusion, our results indicated that NSm could be a factor that leads to decreased specific immune responses in the host and should be avoided in the development of CCHFV vaccine antigens.

Evolution of the Quinoline Scaffold for the Treatment of Leishmaniasis: A Structural Perspective.

Since the beginning of the XXI century, Leishmaniasis has been integrated into the World Health Organization's list of the 20 neglected tropical diseases, being considered a public health issue in more than 88 countries, especially in the tropics, subtropics, and the Mediterranean area. Statistically, this disease presents a world prevalence of 12 million cases worldwide, with this number being expected to increase shortly due to the 350 million people considered at risk and the 2-2.5 million new cases appearing every year. The lack of an appropriate and effective treatment against this disease has intensified the interest of many research groups to pursue the discovery and development of novel treatments in close collaboration with the WHO, which hopes to eradicate it shortly. This paper intends to highlight the quinoline scaffold's potential for developing novel antileishmanial agents and provide a set of structural guidelines to help the research groups in the medicinal chemistry field perform more direct drug discovery and development programs. Thus, this review paper presents a thorough compilation of the most recent advances in the development of new quinoline-based antileishmanial agents, with a particular focus on structure-activity relationship studies that should be considerably useful for the future of the field.

Exploring self-care and cervical cancer prevention attitudes and practices among Moroccan and Pakistani immigrant women in Catalonia, Spain: a comparative qualitative study.

Self-care and preventive health strategies may trigger health inequities when individuals' cultural values and health beliefs are not fully understood and considered. In the case of cervical cancer (CC) screening programs immigrant women have shown lower attendance compared with native women, which increases the risk of late diagnosis and, consequently, a lower probability of survival. HPV self-sampling for CC screening has been recently added to the World Health Organization's (WHO) list of self-care interventions as a promising tool to reduce this disparity and improve screening coverage. In Catalonia, Spain, the introduction of HPV self-sampling as a part of the new population-based CC screening program, is a significant step. However, there is a lack of research addressing self-care and prevention among immigrant populations in this region. This study aims to fill this gap exploring self-care and prevention attitudes and practices among Moroccan and Pakistani women. We conducted focus groups and individual interviews with 36 Moroccan and 37 Pakistani women in Barcelona, Spain. The topic guide of the focus groups included case vignettes to stimulate the discussion and a semi-structured questionnaire was used for the interviews. Our findings show that most Moroccan and Pakistani women do not prioritize self-care and prevention. They seek care for symptom treatment rather than disease prevention. In this sense, they reported not having the habit of doing regular check-ups and their self-care and prevention attitudes and practices seemed to be conditioned by cultural values. The implementation of an effective call and recall system could enhance the engagement of these populations with CC screening services. This study provides evidence on how universal concepts of self-care and prevention may not aligned with more collectivist societies, emphasizing the limited applicability and motivation of global self-care interventions guidelines for individuals with different cultural backgrounds and values. Therefore, the successful implementation of CC screening programs or any other self-care intervention requires the adoption of culturally appropriate strategies.

Comparing antipseudomonal effects of honey samples with different geographical and botanical origin

Pseudomonas aeruginosa, resistant to all broad-spectrum antibiotics, is on the World Health Organization's list of first-priority critical pathogens. Using reserve antibiotics, such as colistin, highlights the imperative for safer, more effective alternatives to combat these superbugs.Medical-grade honey, known for its antibacterial properties and efficacy in wound healing, emerges as a promising candidate.This study analyzed eleven honey samples, diverse in geographical, botanical, and entomological origins, for their antipseudomonal activity using the agar well-diffusion method. Zones of inhibition growth were measured in mm. The function switch was used to approximate the zones of inhibition values for antibacterial activity expressed as minimal inhibitory concentrations MIC99, MIC90, and MIC80, the lowest concentration, killing 99 %, 90 %, and 80 % of organisms, respectively. The authenticity and quality of honey samples complied with the European Commission, Codex Alimentarius, and Serbia Rulebook standards for honey. Melissopalynological analysis ensured the botanical authenticity of tested honey samples. A unique aspect of this research is that it included a honey sample from Serbia's Zlatar mountain region, harvested from Apis mellifera carnica bee colonies. The study's findings reveal that wild-type and multidrug-resistant Pseudomonas clinical isolates were susceptible to the tested honey samples. Honeydew honey from Zlatar showed the highest antibacterial activity on both tested bacteria. Honeydew and buckwheat honey from Zlatar yielded larger inhibition zones than manuka honey. Artificial honey showed no antibacterial effect.In conclusion, this research suggests the potential of honey, particularly from Zlatar, as an alternative therapy for treating infected wounds, warranting further investigation into its antimicrobial efficacy.

Novel drug candidates against antibiotic-resistant microorganisms: A review.

Antibiotic resistance is fast spreading globally, leading to treatment failures and adverse clinical outcomes. This review focuses on the resistance mechanisms of the top five threatening pathogens identified by the World Health Organization's global priority pathogens list: carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin, vancomycin-resistant Staphylococcus aureus. Several novel drug candidates have shown promising results from in vitro and in vivo studies, as well as clinical trials. The novel drugs against carbapenem-resistant bacteria include LCB10-0200, apramycin, and eravacycline, while for Enterobacteriaceae, the drug candidates are LysSAP-26, DDS-04, SPR-206, nitroxoline, cefiderocol, and plazomicin. TNP-209, KBP-7072, and CRS3123 are agents against E. faecium, while Debio 1450, gepotidacin, delafloxacin, and dalbavancin are drugs against antibiotic-resistant S. aureus. In addition to these identified drug candidates, continued in vitro and in vivo studies are required to investigate small molecules with potential antibacterial effects screened by computational receptor docking. As drug discovery progresses, preclinical and clinical studies should also be extensively conducted on the currently available therapeutic agents to unravel their potential antibacterial effect and spectrum of activity, as well as safety and efficacy profiles.

Possible Outbreak of Newcastle Virus Infection in the Face of Increasing Trend of Backyard Poultry Farm Management Interface in Nigeria: A Public Health and Food Security Threat

Introduction: Newcastle disease is a highly contagious illness and one of the "notifiable illnesses" on the World Health Organization list for Animal Health (OIE) Outcome. There are constantly new cases being reported as new NDV isolates from around the world. Newcastle disease poses a significant global economic threat to the poultry sector, causing highly contagious and transmissible diseases in birds with huge food security threat among the weak and vulnerable developing and underdeveloped countries Aim: The aim of this article borders on bringing to light the risk of possible Newcastle disease outbreak in Nigeria due to increasing poor management of poultry farms and poultry waste product. Furthermore, it will also underscore and outline various ways which can be adopted to prevent this poultry disease which is of great public health, economic and food security protection importance. Method/Methodology: This is a systematic review of published research articles focusing on Newcastle disease, epidemiology, pathogenicity, transmission and factors that can play important roles in the possible outbreak of the disease in poultries. Studies reviewed comprise of cross-sectional, prospective, longitudinal and observational studies. The study approach follows the systematic review of peer-reviewed published articles as well as online publications and articles derived from various databases with search keywords relevant to the topic of discourse. Findings and Results: The findings in this study highlight the endemicity of Newcastle virus disease in various part of the country, and how the severity of the disease is influenced by host characteristics, viral properties, and environmental factors. The study pointed out critical evidence-based possible reasons that could promote a new round of Newcastle disease epidemic outbreak as a result of poor poultry management practices such as high bird densities, poor poultry infrastructure, lack of quarantine of sick birds, mixed species rearing, free range system of poultry, poor waste disposal, lack of expertise, and insufficient biosecurity outcomes. However, the lack of education and awareness among farmers exacerbates the problem, hindering preventive measures. The complexity is increased by difficulties with vaccination, unrestrained bird movement through trading with neighboring countries and interstate, and a lack of diagnostic facilities. The consequences of an outbreak extends beyond financial losses to potential disruptions in the poultry supply chain, food security risks, and public health concerns. Conclusion and Recommendation: The growing difficulties in poultry management methods increases the serious public health concern posed by a possible Newcastle Virus epidemic outbreak in Nigeria. A paradigm shift in poultry farming practices is necessary to address this problem. A comprehensive strategy that incorporates infrastructural development, regulatory frameworks, and education in order to strengthen the poultry industry is needed, so as to address and prevent the looming public health and food security crises that may break out from the above scenario

Developments in the chemistry and biology of 1,2,3-triazolyl-C-nucleosides.

In the last 50 years, nucleoside analogs have been introduced to drug therapy as antivirals for different types of cancer due to their interference in cellular proliferation. Among the first line of nucleoside treatment drugs, ribavirin (RBV) is a synthetic N-nucleoside with a 1,2,4-triazole moiety that acts as a broad-spectrum antiviral. It is on the World Health Organization (WHO) list of essential medicines. However, this important drug therapy causes several side effects due to its nonspecific mechanism of action. There is thus a need for a continuous study of its scaffold. A particular approach consists of connecting d-ribose to the nitrogen-containing base with a C-C bond. It provides more stability against enzymatic action and a better pharmacologic profile. The coronavirus disease (COVID) pandemic has increased the need for more solutions for the treatment of viral infections. Among these solutions, remdesivir, the first C-nucleoside, has been approved by the Food and Drug Administration (FDA) for clinical use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It drew attention to the study of the C-nucleoside scaffold. Different C-nucleoside patterns have been synthesized over the years. They show many important activities against viruses and cancer cell lines. 1,2,3-Triazolyl-C-nucleoside derivatives are a prolific and efficient subclass of RBV analogs close to the already-known RBV with a C-C bond modification. These compounds are often prepared by alkynylation of the d-ribose ring followed by azide-alkyne cycloaddition. They are reported to be active against the Crimean-Congo hemorrhagic fever virus and several tumoral cell lines, showing promising biological potential. In this review, we explore such approaches to 1,2,3-triazolyl-C-nucleosides and their evolution over the years.

A Phase 1 Study of Subcutaneous Rituximab Hyaluronidase Combined with Local Standard-of-Care Chemotherapy for the Treatment of Diffuse Large B-Cell Lymphoma in Uganda

Background: Patients with Diffuse Large B-Cell Lymphoma (DLBCL) who are treated in low-resource settings have inferior outcomes compared to those in high-resource settings, with 12-month overall survival (OS) rates typically under 50% with standard chemotherapy (Gopal et al. [PMID:26934054]). Rituximab, an anti-CD20 monoclonal antibody, when combined with chemotherapy, improves OS for DLBCL and is the standard of care for patients with CD20+ DLBCL in resource-rich settings. Despite receiving FDA approval over 25 years ago and its subsequent inclusion in the World Health Organization's List of Essential Medicines, IV rituximab is not readily available or routinely used in sub-Saharan Africa (SSA). This is in part due to cost and the limited availability of infusion centers in SSA. Subcutaneous rituximab hyaluronidase (sqR) is a potential solution, but its safety is not established in these settings. Here, we evaluated the safety and efficacy of a fixed dose of 1400 mg sqR in combination with standard-of-care chemotherapy in Ugandan adults with CD20+ DLBCL. Methods: This open-label phase I study, conducted at the Uganda Cancer Institute [(UCI) Kampala, Uganda], enrolled patients age ≥ 18 with newly diagnosed CD20+ DLBCL with measurable disease, and an ECOG performance status of < 2. Patients living with HIV were eligible if they were receiving antiretroviral therapy and had CD4+ T-cell count >200 cells/uL. The first cohort (n=6) received IV rituximab, 375mg/m 2 on day 1 of cycle 1 plus CHOP chemotherapy (IV cyclophosphamide 750 mg/m 2, IV doxorubicin 50 mg/m 2, IV vincristine 1·4 mg/m 2 (maximum 2 mg/m 2) on day 1, and oral prednisone 100 mg on days 1-5). This cohort received sqR (1400 mg) for subsequent cycles. The second cohort (n=12) received sqR plus CHOP for all cycles. Safety and tolerability were evaluated by monitoring adverse events and graded by Common Terminology Criteria for Adverse Events (CTCAE) version 5; secondary outcomes included response rates and treatment completion. We used Kaplan-Meier methods to estimate OS and progression-free survival (PFS), defined as disease progression or death, with 95% confidence intervals (95% CIs) at 12 months from initiation of treatment. Results: Between October 25 th, 2019 and October 7, 2022, 38 patients were assessed for eligibility; 19 patients met the criteria and were enrolled. One patient was not given the study treatment due to UCI-mandated COVID-19 restrictions. Of the 18 participants, median age was 36.5 years (IQR 25.2-50.0), 10 (56%) were male and 10 (56%) presented with advanced stage (III/IV) disease. Three (16.7%) participants were living with HIV and their median CD4 count was 311. Participants completed a median of 6 cycles of therapy. Grade 3 or 4 hematologic toxicities were reported in 11 (61%) participants; grade 3 or 4 non-hematologic toxicities were reported in 4 (22%). The most common hematologic toxicity was neutropenia (n=9, 50%); the most common non-hematologic toxicities were anorexia (n=7; 39%) and hyponatremia (n=7; 39%). Fifteen of the 18 participants completed treatment; 3 died during treatment. Of the 15 who completed treatment, 14 (93.3%) patients achieved a complete response (CR) and 1 patient (6.7%) had a partial response (PR). The patient who had a PR subsequently developed progressive disease, as did 2 patients who initially had a CR after therapy (Figure 1). The OS and PFS at 12 months was 83% (95% CI, 68-100%) and 66% (95% CI 47-92%) respectively. Conclusion: As demonstrated in other parts of the world, sqR together with CHOP chemotherapy was safe, well-tolerated, and efficacious among Ugandan patients with DLBCL. The very high CR, PFS, and OS rates are nearly double that of historical controls at the UCI, and comparable to outcomes expected in resource-rich settings. Colleagues have previously demonstrated the safety and efficacy of an oral chemotherapy regimen for aggressive non-Hodgkin's lymphoma in East Africa (Mwanda et al. [PMID: 19470940]). Given the results of this study, the potential for a safe and effective regimen, which precludes the need for IV therapy, for the treatment of DLBCL exists. Additionally, this trial strengthened the clinical trial research infrastructure in Uganda; trials conducted locally are critical to determining pragmatic and optimal treatment strategies. We anticipate that this research will improve care for DLBCL patients not only in Uganda but in other resource-limited settings as well.

The World Health Organisation's list of essential medicines and haemophilia treatment products.

The World Health Organisation's list of essential medicines and haemophilia treatment products.

Histoplasma Seropositivity in TB Patients in The Gambia: Evidence to Drive Research on a High-Priority Fungal Pathogen.

Inclusion of Histoplasma in the World Health Organization's first Fungal Priority Pathogens List under "high-priority" fungal species highlights the need for robust surveillance of Histoplasma spp. in endemic and underrepresented regions. Despite increasing reports of histoplasmosis in Africa, data on the burden of this fungal disease are sparse in The Gambia. This baseline study examined the human seroprevalence of anti-Histoplasma antibody in a TB patient group in The Gambia, explored associations between seropositivity and demographic and clinical variables, and proposes future research directions. Biobanked plasma samples were selected from active TB cases with variable HIV infection status. Latex agglutination tests were performed on samples from 52 study participants to detect the presence of anti-Histoplasma antibodies. Potential risk factors for Histoplasma exposure were explored using logistic regression analysis. The sample seroprevalence of anti-Histoplasma antibody was 28.8% (n = 15/52; 95% CI, 17.1%-43.1%). Multivariable logistic regression analysis identified a statistically significant association between Histoplasma seropositivity and age (odds ratio, 0.91; 95% CI, 0.84-0.98; P = .008). This baseline study provides evidence of Histoplasma seropositivity in TB patients in The Gambia and explores risk factors for exposure. The small sample size and use of the LAT in TB and HIV-positive patient groups are significant study limitations. Future research directions are proposed to ascertain the burden of Histoplasma in general and patient populations and explore the context-specific risk factors for exposure and infection in The Gambia.

Can alcohol policy prevent harms to women and children from men's alcohol consumption? An overview of existing literature and suggested ways forward.

The World Health Organization's list of cost-effective alcohol control policies is a widely-used resource that highlights strategies to address alcohol-related harms. However, there is more evidence on how recommended policies impact harms to people who drink alcohol-such as physical health problems caused by heavy alcohol use-than on secondhand harms inflicted on someone other than the person drinking alcohol, i.e., alcohol's harms to others. In this essay, we describe evidence of impacts of alcohol policy on harms to women and children resulting from men's alcohol consumption, as well as options for making policies more relevant for reducing intimate partner violence and child abuse. We begin with an overview of harms to women and children resulting from men's alcohol consumption and review cost-effective alcohol policies with potential to reduce these harms based on likely mechanisms of action. Next, we present a rapid review of reviews to describe existing evidence of impacts of these policies on the outcomes of physical violence, sexual violence, and child abuse and neglect. We found little evidence of systematic evaluation of impacts of these important alcohol policies on harms to women and children. Thus, we advocate for increased attention in evaluation research to the impacts of alcohol policies on harms experienced by women and children who are exposed to men who drink alcohol. We also argue for more consideration of a broader range of policies and interventions to reduce these specific types of harm. Finally, we present a conceptual model illustrating how alcohol policies may be supplemented with other interventions specifically tailored to reduce alcohol-related harms commonly experienced by women and children as a result of men's alcohol use.