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Genetic dynamics of the Duffy antigen receptor for chemokines gene and Plasmodium vivax circulation within sub-Saharan Africa
Get PDFINTRODUCTION: Duffy antigen receptor for chemokines (DARC) is a transmembrane receptor (glycoprotein) expressed on human red blood cells. Sub-Saharan Africa (sSA) individuals, who suffer the most of the global malaria burden, predominantly carry a Duffy negative phenotype. Expression of this gene (found among Duffy-positive individuals) is known to be essential for P. vivax invasion of RBCs. While P. falciparum is the predominant Plasmodium in sSA, the upward trend in P. vivax infection is a major threat to the malaria eradication programme in the region. Since Duffy null individuals (homozygous negative) lack DARC expression, we investigated the DARC gene dynamics in relation to the emerging presence of P. vivax infections in a previously predominant P. falciparum endemic region. METHODS: A total of 223 DARC genes were retrieved from the NCBI database across various countries, Nigeria, Cameroon, Ethiopia, Madagascar and South Africa and were used for population dynamic analysis using different population genetic metrics. FINDINGS: Among these sSA countries, South Africa showed the most haplotype and nucleotide diversity compared to other parts of sSA. Various selection pressures were observed in Western Africa and the Central African Republic. Population structure analysis revealed DARC population clustering of Cameroon, Nigeria and Ethiopia (despite Ethiopia's geographic distance), suggestive of shared ancestry and minimal DARC locus divergence. Conversely, South Africa and Madagascar showed a distinct genetic lineage reflecting differences in evolutionary pressures. CONCLUSION: Our analysis suggests minimal genetic diversity within sSA with evidence of selection potentially attributed to the recent emergence of P. vivax infections. However, greater diversity was observed in South Africa. Evidence of selection of this gene and detection of P. vivax among Duffy-null individuals in the other regions is truly a public health concern.</p
Feasibility, acceptability, and effectiveness of community interventions to increase the uptake of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in sub-Saharan Africa
No full textAre malaria rapid diagnostic test results stable over time to support verification of surveillance data?
No full textBackground: Rapid diagnostic tests (RDTs) have improved malaria case management by enabling point-of-care confirmation of infection, particularly in low-resource settings. In addition to clinical use, RDT results recorded in health facility registers are a critical component of national malaria surveillance systems. Recently, national programmes have explored using stored RDT cassettes to validate register data. However, manufacturers caution that results should be read within 15–30 min, raising concerns about result validity after this period. This study evaluated the stability of RDT results over a one-month period to assess whether stored cassettes can reliably reflect initial test outcomes. Methods: A prospective, observational study was conducted in 48 health facilities across Benin, Nigeria, and Uganda from June to September 2023. A digital artificial intelligence (AI)-powered RDT reader (HealthPulse, Audere, Seattle WA USA) was used to photograph RDTs immediately after interpretation by health workers and again at one week and one month. RDTs were stored under typical health facility conditions during the study. Images were independently interpreted by a trained panel, with results categorized as positive, negative, invalid, or uninterpretable. Only RDTs with valid interpretations at all three time points were included in the final analysis. Positive and negative predictive values (PPV and NPV) were calculated to measure the accuracy of results from stored RDTs relative to the initial interpretation. Results: Out of 54,251 RDTs captured, 45,155 (83.2%) met inclusion criteria. At one month, 95.1% of initially positive RDTs remained positive, and 95.3% of initially negative RDTs remained negative. The PPV of a positive result at one month was 96.3% (95% CI 96.1, 96.5), while the NPV of a negative result was 93.8% (95% CI 93.4, 94.1). Most result changes occurred within the first week. Faint lines were associated with higher rates of change in both directions; 26.8% changing from positive to negative and 48.1% changing from negative to positive. Stability of results also varied across RDT products and specific test lines. Conclusions: Stored RDT cassettes maintain high result stability over one month and can serve as a reliable reference to verify health facility records. Result changes were linked to premature interpretation, faint lines or product- or line-specific characteristics. Adherence to manufacturer-recommended read times may reduce the proportion of RDTs that change from negative to positive. These findings support the utility of stored RDTs in improving data quality and rational antimalarial use in malaria-affected settings.</p
Maintenance of the Brugia malayi life cycle in Mongolian gerbils
Get PDFThe Mongolian gerbil or jird (Meriones unguiculatus) is a rodent belonging to the subfamily Gerbillinae. They are commonly used as models for a variety of infectious diseases such as Hepatitis E virus and Giardia lamblia. At the LSTM/University of Liverpool (UoL) these gerbils (Figure 3) are infected with Brugia malayi, a laboratory strain of a human parasitic nematode, that causes Lymphatic Filariasis (LF) (Figure 1). To maintain this lifecycle (Figure 2) we need to harvest juvenile larval stages known as microfilaria by abdominal lavage. Previously microfilaria were harvested from the peritoneal cavity by using a needle and syringe on anaesthetised gerbils held vertically. This method often resulted in low yields of parasites due to the low volume of media recovered and carried the risk of damaging the abdominal organs. A refinement of this technique is to use a gravity assisted method (Figure 4) with a 20G catheter and a 5ml syringe to inject and aspirate warm sterile RPMI media, containing 1% Penicillin/Streptomycin and Amphotericin B. This refinement allows the gerbil to lay horizontally during lavage, which reduces the risk of damage to internal organs. This improves the welfare of the gerbil and results in an increased number of microfilaria (Figure 5) which typically can yield between 400,000 to more than 1,000,000 mf/ml.</p
Association between social frailty and quality of life in older patients with chronic heart failure: sequential multiple mediating effects of family insufficiency and social networks
Get PDFBackground and objectives: Older patients with chronic heart failure have severe somatic symptoms, which lead to high levels of social frailty and loss of quality of life. Understanding the demographic and disease factors of quality of life and its relationship with social frailty is beneficial to overall health for older patients with chronic heart failure. This study aims to explore the relationship between social frailty and quality of life in older patients with chronic heart failure and to verify whether family insufficiency and social networks moderate this relationship. Methods: A multi-centre cross-sectional study was conducted on 443 older patients with chronic heart failure from three tertiary hospitals in China. The study questionnaire included a general information questionnaire, the HALFT scale (social frailty), the Family APGAR Index (family insufficiency), the LSNS-6 (social networks), and the MLHFQ (quality of life). Hierarchical regression analysis was used to assess the factors influencing quality of life; the SPSS PROCESS Marco Plug-in was employed to conduct mediation analysis. Results: The results showed that age, the number of hospitalizations, and NYHA classification influenced the quality of life in older patients with chronic heart failure. Social frailty, family insufficiency, and social networks were related, and family insufficiency and social networks mediated the relationship between social frailty and quality of life, with mediating effect sizes of 25.87, 99.5 and 58.97%, respectively.Conclusion: This study shows that high levels of social frailty are associated with reduced quality of life in older patients with chronic heart failure. Decreasing family insufficiency and extending social networks help alleviate social frailty’s adverse effects on the quality of life in older patients with chronic heart failure.</p
Microscopic detection and genetic characterisation of schistosome eggs within cervicovaginal lavage sediments from cases of female genital schistosomiasis
Get PDFControl of female genital schistosomiasis (FGS) has gained significant international attention, driven in part, as a newly appreciated underlying aetiological risk factor for HIV, HPV and cervical dysplasia. Whilst diagnosis and clinical staging of FGS typically relies upon colposcopy, alternative methods of incrimination have grown, particularly upon application of PCR diagnostic assays that detect schistosome DNA within tissue biopsy, genital (self-)swab and/or cervicovaginal lavage (CVL). With regard to the latter, we present novel evidence that microscopy alone of CVL sediments can be sufficient to incriminate FGS and CVL sediment provides an original source of (viable) schistosome eggs and miracidia for later genetic analysis. Upon a pilot examination of 55 adult women from Malawi with previously proven urogenital schistosomiasis by egg-patent urine microscopy, 25.5% (95% CI = 14.7 - 39.0) were found to have schistosome eggs within CVL, with one woman having more than 50 eggs observed. After praziquantel treatments and upon re-examination one year later, the prevalence of egg-patent CVLs reduced to 14.5% (95% CI = 6.5 - 26.7) although the same woman again presented with more than 50 observable eggs. Molecular DNA analysis by real-time PCR of extracted DNA from CVL sediments and CVL hatched miracidia (and eggs) revealed the dominance of Schistosoma haematobium within the samples, noting a fifth with Schistosoma mattheei co-infections and the singular presence of a putative S. haematobium x mattheei hybrid miracidium. Viable schistosome eggs shed from cervicovaginal surfaces likely represent a minor environmental transmission route, thus promoting secure menstrual hygiene management is needed.</p
Neuronavigation-assisted stereotactic minimally invasive puncture with tenecteplase for the treatment of acute spontaneous deep intracerebral haemorrhage (NAS-TNK):Rationale and design of a multicentre randomised trial
Get PDFIntroduction: Minimally invasive puncture surgery followed by thrombolysis has been proven to be an effective approach for managing hypertensive intracerebral haemorrhage (ICH). Nevertheless, its impact on improving neurological outcomes remains controversial. The integration of neuronavigation-assisted stereotactic (NAS) technology will significantly help enhance the accuracy of catheter placement, while tenecteplase (TNK), a third-generation thrombolytic agent, offers stronger capabilities in breaking down platelet-rich clots and demonstrates increased fibrin selectivity, which could enhance the overall effectiveness of thrombolytic treatment. However, the efficacy and safety of combining NAS-assisted minimally invasive puncture with TNK (NAS-TNK) in reducing disability and mortality rates among patients with acute spontaneous deep ICH remain unknown. Aim: To describe the rationale and design of the NAS-TNK trial for the treatment of acute spontaneous deep ICH. Design: NAS-TNK is a randomised, open-label, outcome-blinded multicentre trial, involving 732 participants with acute basal ganglia or thalamic haemorrhage with a haematoma volume ranging from 20 to 50 mL. This study will evaluate the efficacy and safety of NAS-TNK, administered every 24 hours at a dose of 0.009 mg/mL of haematoma volume, compared with participants receiving standard medical care. Each patient will undergo follow-up evaluations for a period of 180 days. Study outcomes: The main measure of effectiveness is the percentage of participants achieving a modified Rankin Scale Score ranging from 0 to 3 at the 180-day mark. The primary safety outcome is the all-cause death at 30 days. Discussion and conclusion: The NAS-TNK study will help improve our understanding of the benefits of NAS-TNK in patients with acute spontaneous deep ICH.</p
Overcoming barriers to NHS adoption of innovative IPC products: A qualitative study of SMEs in the Liverpool city region
Get PDFHealthcare-associated infections (HAIs) result in prolonged hospital stays and an increased incidence of infections caused by antimicrobial-resistant bacteria. Small and Medium Enterprises (SMEs) play a crucial role in developing innovative Infection Prevention and Control (IPC) solutions, but they face substantial challenges in navigating the complex NHS procurement system. This study, carried out in the Liverpool City Region in 2022, investigated these barriers. The methodology involved qualitative data collection through an online survey and five semi-structured interviews with SMEs involved in IPC innovation. The survey targeted 114 SMEs, and the interviews were conducted remotely with management teams. Data were analysed thematically using NVivo software, allowing for the identification of key barriers and recurring themes across the dataset. Key challenges identified included high market-entry costs, navigating complex regulatory and procurement frameworks, and limited access to key NHS stakeholders. These issues were compounded by fragmented decision-making processes within NHS Trusts, making it difficult for SMEs to secure product adoption. Despite these barriers, SMEs remain committed to innovating IPC solutions, driven by the potential to improve patient care and address antimicrobial resistance. This report recommends streamlining support mechanisms for SMEs, improving access to NHS decision-makers, and advocating for policy reforms to simplify the procurement process. By facilitating collaboration between SMEs, the NHS, and other stakeholders, the adoption of innovative IPC products can be accelerated, ultimately benefiting patients and addressing the significant public health threats posed by HAIs and antimicrobial resistance.</p
Systematic review of antimycobacterial therapy for Bacille Calmette-Guérin infection in hosts without significant immunocompromise
Get PDFObjectivesThis systematic review aims to synthesise the best available evidence on antimycobacterial management of Bacille Calmette-Guérin (BCG) infection in hosts without significant immunocompromise.MethodsWe performed a systematic review searching Medline, Scopus, Cinahl, Global Health and Clinicaltrials.gov, including the best available evidence on antimycobacterial management of BCG infection after any route of BCG administration. We analysed these subgroups: local and disseminated infection after intravesical instillation, osteitis after vaccination and central nervous system (CNS) infection.Results17 studies were included with 131 patients (one prospective and 16 retrospective cohort). For infection after intravesical instillation, in line with the Summary of Product Characteristics, triple therapy was most common in disseminated infection (75.0%, (38/52)), but for local infection only 37.5% (6/16) of patients received dual therapy. Osteitis was usually managed with a dual regimen ((68.3%, 43/63); although cure rates were high, 33.3% (21/63) of patients experienced an adverse outcome. CNS infections were typically treated with a quinolone-based three- or four-drug regimen.ConclusionsTriple therapy for disseminated infection after intravesical instillation is likely sufficient but we are unable to conclude an optimal regimen for local infection. Although cure rates were high for dual therapy in osteitis, further work is needed to understand morbidity. Future studies should be of higher quality and include standardised reporting of clinical outcomes
Provider costs of professional COVID-19 rapid antigen testing in low-income settings
Get PDFWorld Health Organization recommends antigen rapid diagnostic tests (RDT) as point of care tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in suspected outbreaks when polymerase-chain-reaction testing is not accessible; to trace the extent of outbreaks; and in areas with widespread community transmission. Annual economic costs were estimated for professional SARS-CoV-2 testing as part of several COVID-19 testing use cases in Malawi, Nigeria and Zimbabwe. Symptom screening and antigen-based RDT was implemented as part of a multi-country, Unitaid/STAR 3ACP (Africa, Asia, America COVID-19 Prevention) funded project (April 2022-June 2023). Testing services were provided through trained health providers in outpatient departments of primary care facilities (Malawi and Nigeria) and two primary non governmental organisation (NGO) use cases separately targeting key population (KP) and the general population in Zimbabwe. Combined financial expenditure analysis and on-site micro-costing took the provider/health system perspective in 2025 US9.73 (range across sites: 29.90) in Malawi, 11.64-US10.11 (209.09) and 10.76-521 (800) in Malawi; 202.66-1,125 ( 1,762) and 161-9.73 in Malawi, 10.70 and $9.79 in Zimbabwe. Integrating COVID-19 testing into existing sites can reach people at high risk of severe illness at a reasonable cost. For resource-limited settings where programmes are threatened by low fiscal space, costs might be reduced when scaling up, through greater spreading of startup and capital costs.</p