Haem iron versus ferrous iron salts to treat iron deficiency anaemia in Gambian children: protocol for randomised controlled trial {1}.

BACKGROUND: The World Health Organization recommends universal iron supplementation for children aged 6-23 months in countries where anaemia is seen in over 40% of the population. Conventional ferrous salts have low efficacy due to low oral absorption in children with inflammation. Haem iron is more bioavailable, and its absorption may not be decreased by inflammation. This study aims to compare daily supplementation with haem iron versus ferrous sulphate on haemoglobin concentration and serum ferritin concentration after 12 weeks of supplementation. METHODS: This will be a two-arm, randomised controlled trial. Gambian children aged 6-12 months with anaemia will be recruited within a predefined geographical area and recruited by trained field workers. Eligible participants will be individually randomised using a 1:1 ratio within permuted blocks to daily supplementation for 12 weeks with either 10.0 mg of elemental iron as haem or ferrous sulphate. Safety outcomes such as diarrhoea and infection-related adverse events will be assessed daily by the clinical team (see Bah et al. Additional file 4_Adverse event eCRF). Linear regression will be used to analyse continuous outcomes, with log transformation to normalise residuals as needed. Binary outcomes will be analysed by binomial regression or logistic regression, Primary analysis will be by modified intention-to-treat (i.e., those randomised and who ingested at least one supplement dose of iron), with multiple imputations to replace missing data. Effect estimates will be adjusted for baseline covariates (C-reactive protein, alpha-1-acid glycoprotein, haemoglobin, ferritin, soluble transferrin receptor). DISCUSSION: This study will determine if therapeutic supplementation with haem iron is more efficacious than with conventional ferrous sulphate in enhancing haemoglobin and ferritin concentrations in anaemic children aged 6-12 months. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR202210523178727.

Early iron supplementation in exclusively breastfed Gambian infants: a randomized controlled trial.

Objective: To investigate the effect of daily iron supplementation for 14 weeks on the serum iron concentration and other markers of iron status in exclusively breastfed infants in Gambia. Methods: A placebo-controlled, randomized, double-blind trial was performed in rural Gambia between 3 August 2021 and 9 March 2022. Overall, 101 healthy, exclusively breastfed infants aged 6 to 10 weeks were recruited at vaccination clinics and through community health workers. Infants were randomized to receive iron supplementation (7.5 mg/day as ferrous sulfate in sorbitol solution) or placebo for 98 days. Venous blood samples were collected at baseline and on day 99 to assess the serum iron concentration and other markers of iron and haematological status. Findings: At day 99, the serum iron concentration was significantly higher in the iron supplementation group than the placebo group (crude difference in means: 2.5 µmol/L; 95% confidence interval: 0.6 to 4.3) and there were significant improvements in other iron and haematological markers. There were 10 serious adverse events (five in each group), 106 non-serious adverse events (54 with iron supplementation; 52 with placebo) and no deaths. There was no marked difference between the groups in maternally reported episodes of diarrhoea, fever, cough, skin infection, eye infection or nasal discharge. Conclusion: In exclusively breastfed Gambian infants, iron supplementation from 6 weeks of age was associated with a significant improvement in markers of iron status at around 6 months of age. There was no indication of adverse effects on growth or infections.

Prevalence and mortality rate of abdominal surgical emergencies in Sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Abdominal surgical emergencies remain prevalent in various healthcare settings, particularly in regions with limited access to basic surgical care, such as Africa. The aim of this literature review is to systematically assess publications on abdominal surgical emergencies in adults in sub-Saharan Africa to estimate their prevalence and mortality rate. METHODOLOGY: A systematic review was conducted. The latest search was performed on October 31, 2022. We estimated the pooled prevalence with a 95% confidence interval (CI) for each abdominal surgical emergency, as well as overall postoperative mortality and morbidity rates. RESULTS: A total of 78 studies were included, and 55.1% were single-center retrospective and monocentric studies. The mean age of the patients was 32.5 years, with a sex ratio of 1.94. The prevalence of each abdominal surgical emergency among all of them was as follows: appendicitis: 30.0% (95% CI: 26.1-33.9); bowel obstruction: 28.6% (95% CI: 25.3-31.8); peritonitis: 26.6% (95% CI: 22.2-30.9); strangulated hernias: 13,4% (95% CI: 10,3-16,5) and abdominal trauma: 9.4% (95% CI: 7.5-11.3). The prevalence of complications was as follows: mortality rate: 7.4% (95% CI: 6.0-8.8); overall postoperative morbidity: 24.2% (95% CI: 19.4-29.0); and surgical site infection 14.4% (95% CI: 10.86-18.06). CONCLUSION: Our study revealed a high prevalence of postoperative complications associated with abdominal surgical emergencies in sub-Saharan Africa. More research and efforts should be made to improve access and quality of patient care.

Host Interactions with Engineered T-cell Micropharmacies.

Genetically engineered, cytotoxic, adoptively transferred T cells localize to antigen-positive cancer cells inside patients, but tumor heterogeneity and multiple immune escape mechanisms have prevented the eradication of most solid tumor types. More effective, multifunctional engineered T cells are in development to overcome the barriers to the treatment of solid tumors, but the interactions of these highly modified cells with the host are poorly understood. We previously engineered prodrug-activating enzymatic functions into chimeric antigen receptor (CAR) T cells, endowing them with a killing mechanism orthogonal to conventional T-cell cytotoxicity. These drug-delivering cells, termed Synthetic Enzyme-Armed KillER (SEAKER) cells, demonstrated efficacy in mouse lymphoma xenograft models. However, the interactions of an immunocompromised xenograft with such complex engineered T cells are distinct from those in an immunocompetent host, precluding an understanding of how these physiologic processes may affect the therapy. Herein, we expanded the repertoire of SEAKER cells to target solid-tumor melanomas in syngeneic mouse models using specific targeting with T-cell receptor (TCR)-engineered T cells. We demonstrate that SEAKER cells localized specifically to tumors, and activated bioactive prodrugs, despite host immune responses. We additionally show that TCR-engineered SEAKER cells were efficacious in immunocompetent hosts, demonstrating that the SEAKER platform is applicable to many adoptive cell therapies.

Host-cell Interactions of Engineered T cell Micropharmacies.

Genetically engineered, cytotoxic, adoptive T cells localize to antigen positive cancer cells inside patients, but tumor heterogeneity and multiple immune escape mechanisms have prevented the eradication of most solid tumor types. More effective, multifunctional engineered T cells are in development to overcome the barriers to the treatment of solid tumors, but the interactions of these highly modified cells with the host are poorly understood. We previously engineered prodrug-activating enzymatic functions into chimeric antigen receptor (CAR) T cells, endowing them with an orthogonal killing mechanism to conventional T-cell cytotoxicity. These drug-delivering cells, termed Synthetic Enzyme-Armed KillER (SEAKER) cells, demonstrated efficacy in mouse lymphoma xenograft models. However, the interactions of an immunocompromised xenograft with such complex engineered T cells are distinct from those in an immunocompetent host, precluding an understanding of how these physiologic processes may affect the therapy. Here, we also expand the repertoire of SEAKER cells to target solid-tumor melanomas in syngeneic mouse models using specific targeting with TCR-engineered T cells. We demonstrate that SEAKER cells localize specifically to tumors, and activate bioactive prodrugs, despite host immune responses. We additionally show that TCR-engineered SEAKER cells are efficacious in immunocompetent hosts, demonstrating that the SEAKER platform is applicable to many adoptive cell therapies.

Black in Cancer: Two Years of Empowering the Next Generation.

In the 2 years since the inception of Black in Cancer, we have modeled an action-oriented commitment to improving Black representation across all levels of the cancer spectrum. We reflect on our successes and consider new ways to innovate and inspire the cancer community.

Water vapor thermal therapy for indwelling urinary catheter removal in frail patients.

PURPOSE: To report the efficacy and safety of water vapor thermal therapy to achieve catheter removal in frail patients with refractory acute urinary retention. METHODS: Data from consecutive frail patients with indwelling urinary catheter undergoing the Rezum™ therapy (Boston Scientific Corporation, Marlborough, MA) at a single center between October 2017 and June 2021 were prospectively collected. The included patients were deemed unfit or at high risk of complications for conventional benign prostatic hyperplasia (BPH) surgery. Prostate volumes up to 120 mL were considered eligible. The primary endpoint was successful cessation of catheter dependency, assessed postoperatively and up to 1 year of follow-up. RESULTS: A total of 24 men met our inclusion criteria. The median age, Charlson comorbidity index, and duration of preoperative catheterization were 77 years (IQR 67-86), 6 (IQR 3-7), and 113 days (IQR 87-159), respectively. Two cases (8.3%) of postoperative complications were recorded (Clavien II and Clavien IIIa). After a median postoperative catheterization time of 21 days (IQR 11-32), all patients regained spontaneous voiding. During follow-up, two patients died and a total of 22 patients completed the 1 year follow-up. All patients maintained spontaneous voiding without recurrence of urinary retention. No surgical retreatment was performed. In terms of pharmacological management, 22/24 patients (91.7%) had a BPH medication pre-Rezum™; this decreased to 8/22 patients (36.3%) post-Rezum™ (p < 0.001). CONCLUSIONS: In this single-institution, prospective, and observational study, water vapor thermal therapy was found to be effective and safe in restoring successful spontaneous voiding in a cohort of elderly and frail patients.

Institutional determinants of insurance penetration in Africa.

This paper investigates the institutional determinants of insurance demand in Africa. We used a panel of 42 countries over the period 1996-2017. A system GMM approach was used for the estimations. Consistent with previous results, we find that institutional quality has positive and significant effects on insurance penetration in Africa. Specifically, regulatory quality, rule of law, control of corruption, political stability and absence of violence, and government effectiveness are the five institutional quality indicators that have positive and significant effects on the demand for total insurance and life insurance. However, only regulatory quality, control of corruption and government effectiveness are positively associated with non-life insurance demand. This indicates that governments should improve the business environment and strengthen the political environment to boost insurance development in Africa. Supplementary Information: The online version contains supplementary material available at 10.1057/s41288-022-00278-2.

Engineered DNA-encoded monoclonal antibodies targeting Plasmodium falciparum circumsporozoite protein confer single dose protection in a murine malaria challenge model.

Novel approaches for malaria prophylaxis remain important. Synthetic DNA-encoded monoclonal antibodies (DMAbs) are a promising approach to generate rapid, direct in vivo host-generated mAbs with potential benefits in production simplicity and distribution coupled with genetic engineering. Here, we explore this approach in a malaria challenge model. We engineered germline-reverted DMAbs based on human mAb clones CIS43, 317, and L9 which target a junctional epitope, major repeat, and minor repeat of the Plasmodium falciparum circumsporozoite protein (CSP) respectively. DMAb variants were encoded into a plasmid vector backbone and their expression and binding profiles were characterized. We demonstrate long-term serological expression of DMAb constructs resulting in in vivo efficacy of CIS43 GL and 317 GL in a rigorous mosquito bite mouse challenge model. Additionally, we engineered an Fc modified variant of CIS43 and L9-based DMAbs to ablate binding to C1q to test the impact of complement-dependent Fc function on challenge outcomes. Complement knockout variant DMAbs demonstrated similar protection to that of WT Fc DMAbs supporting the notion that direct binding to the parasite is sufficient for the protection observed. Further investigation of DMAbs for malaria prophylaxis appears of importance.

Stratification at the health district level for targeting malaria control interventions in Mali.

Malaria is the leading cause of morbidity and mortality in Mali. Between 2017 and 2020, the number of cases increased in the country, with 2,884,827 confirmed cases and 1454 reported deaths in 2020. We performed a malaria risk stratification at the health district level in Mali with a view to proposing targeted control interventions. Data on confirmed malaria cases were obtained from the District Health Information Software 2, data on malaria prevalence and mortality in children aged 6-59 months from the 2018 Demographic and Health Survey, entomological data from Malian research institutions working on malaria in the sentinel sites of the National Malaria Control Program (NMCP), and environmental data from the National Aeronautics and Space Administration. A stratification of malaria risk was performed. Targeted malaria control interventions were selected based on spatial heterogeneity of malaria incidence, malaria prevalence in children, vector resistance distribution, health facility usage, child mortality, and seasonality of transmission. These interventions were discussed with the NMCP and the different funding partners. In 2017-2019, median incidence across the 75 health districts was 129.34 cases per 1000 person-years (standard deviation = 86.48). Risk stratification identified 12 health districts in very low transmission areas, 19 in low transmission areas, 20 in moderate transmission areas, and 24 in high transmission areas. Low health facility usage and increased vector resistance were observed in high transmission areas. Eight intervention combinations were selected for implementation. Our work provides an updated risk stratification using advanced statistical methods to inform the targeting of malaria control interventions in Mali. This stratification can serve as a template for continuous malaria risk stratifications in Mali and other countries.

DNA immunotherapy targeting BARF1 induces potent anti-tumor responses against Epstein-Barr-virus-associated carcinomas.

Latent Epstein-Barr virus (EBV) infection is associated with several types of cancer. Several clinical studies have targeted EBV antigens as immune therapeutic targets with limited efficacy of EBV malignancies, suggesting that additional targets might be important. BamHI-A rightward frame 1 (BARF1) is an EBV antigen that is highly expressed in EBV+ nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC). BARF1 antigen can transform human epithelial cells in vivo. BARF1-specific antibodies and cytotoxic T cells were detected in some EBV+ NPC patients. However, BARF1 has not been evaluated as an antigen in the context of therapeutic immunization. Its possible importance in this context is unclear. Here, we developed a synthetic-DNA-based expression cassette as immunotherapy targeting BARF1 (pBARF1). Immunization with pBARF1 induced potent antigen-specific humoral and T cell responses in vivo. Immunization with pBARF1 plasmid impacted tumor progression through the induction of CD8+ T cells in novel BARF1+ carcinoma models. Using an in vivo imaging system, we observed that pBARF1-immunized animals rapidly cleared cancer cells. We demonstrated that pBARF1 can induce antigen-specific immune responses that can impact cancer progression. Further study of this immune target is likely important as part of therapeutic approaches for EBV+ malignancies.

Iron supplementation of breastfed Gambian infants from 6 weeks to 6 months of age: protocol for a randomised controlled trial.

Background: A recent analysis showed that plasma iron concentrations decline rapidly from birth in Gambian infants, irrespective of sex or birthweight, to concentrations well below normal expected values for iron-replete children older than two months of age (typically >10 µmol/L). The development and function of neural and immune cells may thus be compromised before the minimum age at which children should receive iron supplementation as per World Health Organisation recommendations. Methods: This study is a two-arm, double-blind, placebo-controlled, randomised superiority trial. Infants will be randomised to receive iron drops (7.5mg/day of iron as ferrous sulphate) or placebo daily for 98 days, to test the impact on serum iron concentrations in healthy, breastfed infants (n = 100) aged 6-10 weeks at enrolment. Participants will be visited daily and supplemented by the field team. Daily health and weekly breastfeeding questionnaires will be administered. Anthropometry, and venous blood and faecal samples will be collected at enrolment and after 98 days of supplementation with serum iron as the primary endpoint. Low birthweight (less than 2.5kg at birth) and infants born prematurely (< 37 weeks) will not be excluded. Formula-fed and infants with any illness will be excluded. An additional study exploring maternal stakeholder perspectives of the intervention will be conducted by means of maternal interviews and four focus group discussions with local stakeholders. Discussion: Most breast-fed Gambian infants have very low circulating iron levels by five months of age. This study will introduce iron supplements much earlier in infancy than has previously been attempted in a low-income setting with the primary aim of increasing serum iron concentration. Trial registration: Clincaltrials.gov ( NCT04751994); 12 th February 2021.

Effect of Salicylic Acid in the Yield of Ricinine in Ricinus communis under Greenhouse Condition.

Castor bean (Ricinus communis) seeds contain ricinine, an alkaloid with insecticidal and insectistatic activities. Elicitation with salicylic acid (SA) has proven to stress R. communis and might modify the ricinine concentration. The aim of this study was to evaluate the concentration of ricinine in the bagasse of seeds from R. communis elicited with exogenous SA under greenhouse conditions. Plants were grown and divided into five groups, which were sprayed with SA and drench with 50 mL 60 days after sowing with concentrations of SA (0, 100, 300, 600 and 900 µM). Clusters were mixed and separated according to the treatment, and dried. The seeds were ground, the oil was extracted by Soxhlet with hexane, and then the bagasse was extracted with methanol. Ricinine was determined by HPLC. Elicitation did not change the plant height or diameter; the control group had 9.17 µg mL-1 of ricinine; and the concentrations followed a hormesis curve with the peak at 300 µM of SA that had a ricinine concentration of 18.25 µg mL-1. Elicitation with SA might be a cost-effective technique to increase ricinine from R. communis bagasse.

Strategic Variants of CSP Delivered as SynDNA Vaccines Demonstrate Heterogeneity of Immunogenicity and Protection from Plasmodium Infection in a Murine Model.

Malaria infects millions of people every year, and despite recent advances in controlling disease spread, such as vaccination, it remains a global health concern. The circumsporozoite protein (CSP) has long been acknowledged as a key target in antimalarial immunity. Leveraging the DNA vaccine platform against this formidable pathogen, the following five synthetic DNA vaccines encoding variations of CSP were designed and studied: 3D7, GPI1, ΔGPI, TM, and DD2. Among the single CSP antigen constructs, a range of immunogenicity was observed with ΔGPI generating the most robust immunity. In an intravenous (i.v.) sporozoite challenge, the best protection among vaccinated mice was achieved by ΔGPI, which performed almost as well as the monoclonal antibody 311 (MAb 311) antibody control. Further analyses revealed that ΔGPI develops high-molecular-weight multimers in addition to monomeric CSP. We then compared the immunity generated by ΔGPI versus synDNA mimics for the antimalaria vaccines RTS,S and R21. The anti-CSP antibody responses induced were similar among these three immunogens. T cell responses demonstrated that ΔGPI induced a more focused anti-CSP response. In an infectious mosquito challenge, all three of these constructs generated inhibition of liver-stage infection as well as immunity from blood-stage parasitemia. This study demonstrates that synDNA mimics of complex malaria immunogens can provide substantial protection as can a novel synDNA vaccine ΔGPI.

Synthetic DNA Delivery of an Optimized and Engineered Monoclonal Antibody Provides Rapid and Prolonged Protection against Experimental Gonococcal Infection.

Monoclonal antibody (MAb) 2C7 recognizes a lipooligosaccharide epitope expressed by most clinical Neisseria gonorrhoeae isolates and mediates complement-dependent bactericidal activity. We recently showed that a recombinant human IgG1 chimeric variant of MAb 2C7 containing an E430G Fc modification (2C7_E430G), which enhances complement activation, outperformed the parental MAb 2C7 (2C7_WT) in vivo Because natural infection with N. gonorrhoeae often does not elicit protective immunity and reinfections are common, approaches that prolong bacterial control in vivo are of great interest. Advances in DNA-based approaches have demonstrated the combined benefit of genetic engineering, formulation optimizations, and facilitated delivery via CELLECTRA-EP technology, which can induce robust in vivo expression of protective DNA-encoded monoclonal antibodies (DMAbs) with durable serum activity relative to traditional recombinant MAb therapies. Here, we created optimized 2C7-derived DMAbs encoding the parental Fc (2C7_WT) or complement-enhancing Fc variants (2C7_E430G and 2C7_E345K). 2C7 DMAbs were rapidly generated and detected throughout the 4-month study. While all complement-engaging 2C7 variants facilitated rapid clearance following primary N. gonorrhoeae challenge (day 8 after DMAb administration), the complement-enhancing 2C7_E430G variant demonstrated significantly higher potency against mice rechallenged 65 days after DMAb administration. Passive intravenous transfer of in vivo-produced, purified 2C7 DMAbs confirmed the increased potency of the complement-enhancing variants. This study highlights the ability of the DMAb platform to launch the in vivo production of antibodies engineered to promote and optimize downstream innate effector mechanisms such as complement-mediated killing, leading to hastened bacterial elimination.IMPORTANCENeisseria gonorrhoeae has become resistant to most antibiotics in clinical use. Currently, there is no safe and effective vaccine against gonorrhea. Measures to prevent the spread of gonorrhea are a global health priority. A monoclonal antibody (MAb) called 2C7, directed against a lipooligosaccharide glycan epitope expressed by most clinical isolates, displays complement-dependent bactericidal activity and hastens clearance of gonococcal vaginal colonization in mice. Fc mutations in a human IgG1 chimeric version of MAb 2C7 further enhance complement activation, and the resulting MAb displays greater activity than wild-type MAb 2C7 in vivo Here, we utilized a DNA-encoded MAb (DMAb) construct designed to launch production and assembly of "complement-enhanced" chimeric MAb 2C7 in vivo The ensuing rapid and sustained MAb 2C7 expression attenuated gonococcal colonization in mice at 8 days as well as 65 days postadministration. The DMAb system may provide an effective, economical platform to deliver MAbs for durable protection against gonorrhea.

Gametocyte carriage after seasonal malaria chemoprevention in Plasmodium falciparum infected asymptomatic children.

BACKGROUND: Treatment of clinical Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) is associated with increased post-treatment gametocyte carriage. The effect of seasonal malaria chemoprevention (SMC) with SP and AQ on gametocyte carriage was assessed in asymptomatic P. falciparum infected children. METHODS: The study was carried out in eastern Gambia. Asymptomatic P. falciparum malaria infected children aged 24-59 months old who were eligible to receive SMC (SMC group) and children 5-8 years that were not eligible to receive SMC (comparison group) were recruited. Gametocytaemia was determined by molecular methods before and after SMC administration. Gametocyte carriage between the groups was compared using the chi-squared test and within-person using conditional logistic regression. RESULTS: During the 2017 and 2018 malaria transmission seasons, 65 and 75 children were recruited in the SMC and comparison groups, respectively. Before SMC administration, gametocyte prevalence was 10.7% (7/65) in the SMC group and 13.3% (10/75) in the comparison group (p = 0.64). At day 13 (IQR 12, 13) after SMC administration, this was 9.4% (5/53) in children who received at least the first dose of SMC treatment and 12.7% (9/71) for those in the comparison group (p = 0.57). Similarly, there was no difference in prevalence of gametocytes between children that adhered to all 3-day doses of SMC treatment 15.6% (5/32) and those in the comparison group (p = 0.68). In the SMC group, within-group gametocyte carriage was similar before and after SMC administration in children that received at least the first dose of SMC treatment (OR 0.6, 95% CI 0.14-2.51; p = 0.48) and in those that adhered to all 3-day doses of SMC treatment (OR 1.0, 95% CI 0.20-4.95; p = 1.0). CONCLUSION: In this study with relative low gametocyte prevalence prior to SMC treatment, no evidence was observed that SMC treatment increased gametocyte carriage in asymptomatic P. falciparum malaria infected children.

Implementation of DHIS2 for Disease Surveillance in Guinea: 2015-2020.

A robust epidemic-prone disease surveillance system is a critical component of public health infrastructure and supports compliance with the International Health Regulations (IHR). One digital health platform that has been implemented in numerous low- and middle-income countries is the District Health Information System Version 2 (DHIS2). In 2015, in the wake of the Ebola epidemic, the Ministry of Health in Guinea established a strategic plan to strengthen its surveillance system, including adoption of DHIS2 as a health information system that could also capture surveillance data. In 2017, the DHIS2 platform for disease surveillance was piloted in two regions, with the aim of ensuring the timely availability of quality surveillance data for better prevention, detection, and response to epidemic-prone diseases. The success of the pilot prompted the national roll-out of DHIS2 for weekly aggregate disease surveillance starting in January 2018. In 2019, the country started to also use the DHIS2 Tracker to capture individual cases of epidemic-prone diseases. As of February 2020, for aggregate data, the national average timeliness of reporting was 72.2%, and average completeness 98.5%; however, the proportion of individual case reports filed was overall low and varied widely between diseases. While substantial progress has been made in implementation of DHIS2 in Guinea for use in surveillance of epidemic-prone diseases, much remains to be done to ensure long-term sustainability of the system. This paper describes the implementation and outcomes of DHIS2 as a digital health platform for disease surveillance in Guinea between 2015 and early 2020, highlighting lessons learned and recommendations related to the processes of planning and adoption, pilot testing in two regions, and scale up to national level.

Sero-epidemiological evaluation of malaria transmission in The Gambia before and after mass drug administration.

BACKGROUND: As The Gambia aims to achieve malaria elimination by 2030, serological assays are a useful surveillance tool to monitor trends in malaria incidence and evaluate community-based interventions. METHODS: Within a mass drug administration (MDA) study in The Gambia, where reduced malaria infection and clinical disease were observed after the intervention, a serological sub-study was conducted in four study villages. Spatio-temporal variation in transmission was measured with a panel of recombinant Pf antigens on a multiplexed bead-based assay. Village-level antibody levels were quantified as under-15 sero-prevalence, sero-conversion rates, and age-adjusted antibody acquisition rates. Antibody levels prior to MDA were assessed for association with persistent malaria infection after community chemoprophylaxis. RESULTS: Seasonal changes in antibodies to Etramp5.Ag1 were observed in children under 15 years in two transmission settings-the West Coast and Upper River Regions (4.32% and 31.30% Pf prevalence, respectively). At the end of the malaria season, short-lived antibody responses to Etramp5.Ag1, GEXP18, HSP40.Ag1, EBA175 RIII-V, and Rh2.2030 were lower amongst 1-15 year olds in the West Coast compared to the Upper River, reflecting known differences in transmission. Prior to MDA, individuals in the top 50th percentile of antibody levels had two-fold higher odds of clinical malaria during the transmission season, consistent with previous findings from the Malaria Transmission Dynamics Study, where individuals infected before the implementation of MDA had two-fold higher odds of re-infection post-MDA. CONCLUSIONS: Serological markers can serve dual functions as indicators of malaria exposure and incidence. By monitoring age-specific sero-prevalence, the magnitude of age-stratified antibody levels, or identifying groups of individuals with above-average antibody responses, these antigens have the potential to complement conventional malaria surveillance tools. Further studies, particularly cluster randomised trials, can help establish standardised serological protocols to reliably measure transmission across endemic settings.

[Dissection of the abdominal aorta revealing Takayasu´s disease: about a case in Guinea]. / Dissection de l´aorte abdominale révélatrice de la maladie de Takayasu: à propos d´un cas en Guinée.

Takayasu´s disease (TD) is a chronic inflammatory arteriopathy affecting the aorta, its main branches and the pulmonary arteries. It was first described in 1908 by the Japanese ophthalmologist Mikito Takayasu. The study involved a 78-year-old patient with no known history of cardiovascular disease, admitted with abdominal pain, pain in the right lower limb when walking, insomnia. These symptoms had progressed over 1 year. Physical examination showed normal heart rate of 87 beats per minute without pathological noises, with absence of right pedal pulse, blood pressure 120/78 mmhg, free lungs, flexible abdomen, and a beating mass in the right iliac fossa whose auscultation showed continuous murmur. The remainder of the physical examination was normal. Abdominal CT angiography confirmed extensive aortic dissection at the abdominal aorta with synchronous opacification of both channels, thrombotic aneurysm of the primitive iliac arteries measuring 48mmx100mm on the right and 38mm x 90mm on the left, with no visible fissurization. We report a case abdominal aorta dissection associated with thrombus formation in the primary iliac arteries revealing Takayashu´s disease treated in the Department of Cardiology at the Ignace Deen National Hospital. The rate of abdominal aorta dissection in patients with Takayasu´s disease is rare. It is most often diagnosed in the occlusive phase. Prognosis depends on possible complications.

Antibody responses to a suite of novel serological markers for malaria surveillance demonstrate strong correlation with clinical and parasitological infection across seasons and transmission settings in The Gambia.

BACKGROUND: As malaria transmission declines, sensitive diagnostics are needed to evaluate interventions and monitor transmission. Serological assays measuring malaria antibody responses offer a cost-effective detection method to supplement existing surveillance tools. METHODS: A prospective cohort study was conducted from 2013 to 2015 in 12 villages across five administrative regions in The Gambia. Serological analysis included samples from the West Coast Region at the start and end of the season (July and December 2013) and from the Upper River Region in July and December 2013 and April and December 2014. Antigen-specific antibody responses to eight Plasmodium falciparum (P. falciparum) antigens-Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175 RIII-V, PfMSP119, PfAMA1, and PfGLURP.R2-were quantified using a multiplexed bead-based assay. The association between antibody responses and clinical and parasitological endpoints was estimated at the individual, household, and population level. RESULTS: Strong associations were observed between clinical malaria and concurrent sero-positivity to Etramp5.Ag1 (aOR 4.60 95% CI 2.98-7.12), PfMSP119 (aOR 4.09 95% CI 2.60-6.44), PfAMA1 (aOR 2.32 95% CI 1.40-3.85), and PfGLURP.R2 (aOR 3.12, 95% CI 2.92-4.95), while asymptomatic infection was associated with sero-positivity to all antigens. Village-level sero-prevalence amongst children 2-10 years against Etramp5.Ag1, HSP40.Ag1, and PfMSP119 showed the highest correlations with clinical and P. falciparum infection incidence rates. For all antigens, there were increased odds of asymptomatic P. falciparum infection in subjects residing in a compound with greater than 50% sero-prevalence, with a 2- to 3-fold increase in odds of infection associated with Etramp5.Ag1, GEXP18, Rh2.2030, PfMSP119, and PfAMA1. For individuals residing in sero-positive compounds, the odds of clinical malaria were reduced, suggesting a protective effect. CONCLUSIONS: At low transmission, long-lived antibody responses could indicate foci of malaria transmission that have been ongoing for several seasons or years. In settings where sub-patent infections are prevalent and fluctuate below the detection limit of polymerase chain reaction (PCR), the presence of short-lived antibodies may indicate recent infectivity, particularly in the dry season when clinical cases are rare. Serological responses may reflect a persistent reservoir of infection, warranting community-targeted interventions if individuals are not clinically apparent but have the potential to transmit. Therefore, serological surveillance at the individual and household level may be used to target interventions where there are foci of asymptomatically infected individuals, such as by measuring the magnitude of age-stratified antibody levels or identifying areas with clustering of above-average antibody responses across a diverse range of serological markers.