Search

Objectives : We implemented a project named MENINGSTOP in three countries of North Africa (Algeria, Morocco and Tunisia). The main objective was to use real-time PCR to detect, identify and type the three main agents (Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) responsible for invasive bacterial infections (IBI). Methods : The protocol of WHO and US CDC for real-time PCR was used to detect and type the three bacterial agents in clinical samples. We also designated two quality exercises using an external interlaboratory study and cross-testing of 10% of randomly selected samples. Results : Among the 752 samples tested, 18% were positive for one of the three agents. N. meningitidis was the most frequent globally reaching 9% of all samples (7% to 17% range) followed by S. pneumoniae 8% of all samples (6% to 15%). Group B meningococci was the most frequent (74% of all positive samples for meningococci and ranging from 50% to 90%). Quality assurance showed >85% correlation scores. Conclusions : Real-time PCR can help improving epidemiological surveillance. Data confirm the prevalence of meningococci B. Our project add a reliable tool to enhance surveillance and to help decision making in vaccination strategies against IBI.

The 2022 FIFA World Cup was the first major multi-continental sporting Mass Gathering Event (MGE) of the post COVID-19 era to allow foreign spectators. Such large-scale MGEs can potentially lead to outbreaks of infectious disease and contribute to the global dissemination of such pathogens. Here we adapt previous work and create a generalisable model framework for assessing the use of disease control strategies at such events, in terms of reducing infections and hospitalisations. This framework utilises a combination of meta-populations based on clusters of people and their vaccination status, Ordinary Differential Equation integration between fixed time events, and Latin Hypercube sampling. We use the FIFA 2022 World Cup as a case study for this framework. Pre-travel screenings of visitors were found to have little effect in reducing COVID-19 infections and hospitalisations. With pre-match screenings of spectators and match staff being more effective. Rapid Antigen (RA) screenings 0.5 days before match day outperformed RT-PCR screenings 1.5 days before match day. A combination of pre-travel RT-PCR and pre-match RA testing proved to be the most successful screening-based regime. However, a policy of ensuring that all visitors had a COVID-19 vaccination (second or booster dose) within a few months before departure proved to be much more efficacious. The State of Qatar abandoned all COVID-19 related travel testing and vaccination requirements over the period of the World Cup. Our work suggests that the State of Qatar may have been correct in abandoning the pre-travel testing of visitors. However, there was a spike in COVID-19 cases and hospitalisations within Qatar over the World Cup. The research outlined here suggests a policy requiring visitors to have had a recent COVID-19 vaccination may have prevented the increase in COVID-19 cases and hospitalisations during the world cup.Author summaryMass Gathering Events (MGEs) can potentially lead to outbreaks of infectious disease and facilitate the dissemination of such pathogens. We have adapted previous work to create a framework for simulating disease transmission and mitigation at such MGEs. We use the 2022 FIFA World Cup as a test case for this framework. A policy of Pre-travel screenings of visitors was found to have little effect in reducing COVID-19 cases and hospitalisations. Pre-match screenings of spectators and match staff was found to be more effective. The most effective policy was to ensure that all visitors had a COVID-19 vaccination (second or booster dose) within a few months before departure. Qatar abandoned all COVID-19 related travel testing and vaccination requirements over the period of the World Cup. Our work suggests that the State of Qatar may have been correct in abandoning the pre-travel testing of visitors. However, there was a spike in COVID-19 cases and hospitalisations within Qatar over the World Cup. Given our findings, we suggest a policy requiring visitors to have had a recent COVID-19 vaccination may have prevented the increase in COVID-19 cases and hospitalisations during the world cup.

International audience; Prostate cancer is the most common cancer in men. For patients with advanced or metastatic prostate cancer, available treatments can slow down its progression but cannot cure it. The development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2, a natural multifunctional antimicrobial peptide isolated from Amazonian frog skin, has been reported to possess antitumor activity. To improve its pharmacological properties and to decrease its peripheral toxicity and lethality we developed a hormonotoxin molecule composed of dermaseptin-B2 combined with d-Lys6-LHRH to target the LHRH receptor. This hormonotoxin has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of dermaseptin-B2. Its antitumor activity has been confirmed in vivo in a xenograft mouse model with PC3 tumors and appears to be better tolerated than dermaseptin-B2. Biophysical experiments showed that the addition of LHRH to dermaseptin-B2 did not alter its secondary structure or biological activity. The combination of different experimental approaches indicated that this hormonotoxin induces cell death by an apoptotic mechanism instead of necrosis, as observed for dermaseptin-B2. These results could explain the lower toxicity observed for this hormonotoxin compared to dermaseptin-B2 and may represent a promising targeting approach for cancer therapyY

ContextPrompt administration of post exposure prophylaxis (PEP) is one of the key strategies for ending human deaths from rabies. Delay in seeking first dose of rabies PEP or failure to complete the recommended PEP dosage may result in clinical rabies and death.ObjectivesTo assess the efficacy of short message system (SMS) phone texts on adherence to scheduled PEP doses among bite patients in rural eastern Kenya.Trial design and methodsWe conducted a single arm before-after field trial that compared adherence among bite patients presenting at Makueni Referral Hospital in October – December 2018 (control group) and January – March 2019 (intervention group that received an SMS reminder one day prior to their scheduled PEP doses). Data on demographics, socio-economic status, circumstances surrounding the bite, expenditures related to the bite were collected for all patients.ResultsA total of 186 bite patients were enrolled in the study, with 82 (44%) being in the intervention and 104 (56%) in the control group. The odds of PEP completion was three times (OR 3.37, 95% CI 1.28, 10.20) among patients that received the SMS reminder compared to those that did not. The intervention group had better compliance on the scheduled doses 2 to 5 with a mean deviation of 0.18 days compared to 0.79 days for the control group (p = 0.004). The main reasons for non-compliance included lack of funds (30%), forgetfulness (23%) on days for follow-up treatment, among others. Although the majority of bite patients (94%) were under the Makueni medical insurance cover and did not pay for PEP, nearly all (96%, n=179) the bite patients incurred indirect costs of transport at an average of 4 USD (0 - 45 USD) per visit.ConclusionThis study suggests integrating SMS reminders in healthcare service delivery increases compliance to PEP and may strengthen rabies control and elimination strategies.Trial registrationThe study trial is registered at US National Institute of Health (clinicalTrial.gov) identifier number NCT05350735. https://clinicaltrials.gov/ct2/show/NCT05350735

Prostate cancer represents the most common cancer in men. For patients with advanced or metastatic form, treatments will be able to slow down the progression but cannot cure it even with the used of new targeted therapies. In this context, the development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2 (DRS-B2), a natural multifunctional antimicrobial peptide isolated from the Amazonian frog skin, has been reported to possess antitumor and antiangiogenic activities. To improve DRS-B2 pharmacological properties and target prostate tumor cells more specifically, we have developed a chimeric molecule, called Hormonotoxin (H-B2) which is composed of a DRS-B2 combined with a hormonal analog, d-Lys6-LHRH, to target LHRH-Receptor which is overexpressed in more than 85% of prostate cancers. In vitro H-B2 has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of DRS-B2. The antitumor activity of H-B2 was confirmed in vivo in mouse model xenografted with PC3 tumors and appears to be better tolerated than DRS-B2. Biophysical experiments showed that the addition of the hormonal analog to DRS-B2 did not alter either its secondary structure or its biological activity. Combination of different experimental approaches indicated that H-B2 induces cell death by an apoptotic mechanism whereas DRS-B2 was shown to induce it by necrosis. These results could explain the H-B2 less toxicity compared to DRS-B2. H-B2 represents a promising targeting approach for cancer therapy.

Background Viral infections are often treated with empiric antibiotics due to suspected bacterial coinfections, leading to antibiotic overuse. We aimed to describe antibiotic resistance (ABR) trends and their association with the influenza season in ambulatory and inpatient settings in the United States. Methods We used the BD Insights Research Database to evaluate antibiotic susceptibility profiles in 30-day nonduplicate bacterial isolates collected from patients >17 years old at 257 US healthcare institutions from 2011 to 2019. We investigated ABR in Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) and Gram-negative (Enterobacterales [ENT], Pseudomonas aeruginosa [PSA], and Acinetobacter baumannii spp [ACB]) bacteria expressed as the proportion of isolates not susceptible ([NS], intermediate or resistant) and resistance per 100 admissions (inpatients only). Antibiotics included carbapenems (Carb), fluoroquinolones (FQ), macrolides, penicillin, extended-spectrum cephalosporins (ESC), and methicillin. Generalized estimating equations models were used to evaluate monthly trends in ABR outcomes and associations with community influenza rates. Results We identified 8 250 860 nonduplicate pathogens, including 154 841 Gram-negative Carb-NS, 1 502 796 Gram-negative FQ-NS, 498 012 methicillin-resistant S aureus (MRSA), and 44 131 NS S pneumoniae. All S pneumoniae rates per 100 admissions (macrolide-, penicillin-, and ESC-NS) were associated with influenza rates. Respiratory, but not nonrespiratory, MRSA was also associated with influenza. For Gram-negative pathogens, influenza rates were associated with the percentage of FQ-NS ENT, FQ-NS PSA, and Carb-NS ACB. Conclusions Our study showed expected increases in rates of ABR Gram-positive and identified small but surprising increases in ABR Gram-negative pathogens associated with influenza activity. These insights may help inform antimicrobial stewardship initiatives.

Additional file 1: Text 1 includes a detailed model description, Supplementary data, Supplementary results, FiguresS1, S2, and Tables S1-S9.

Background Invasive meningococcal disease (IMD) represents a global health burden. However, its epidemiology in the Eastern Mediterranean (EM) and North Africa (NA) regions is currently not well understood. This review had four key objectives: to describe asymptomatic meningococcal carriage, IMD epidemiology (e.g. serogroup prevalence, case-fatality rates [CFRs]), IMD presentation and management (e.g. clinical diagnosis, antibiotic treatments) and economic impact and evaluation (including health technology assessment [HTA] recommendations) in EM and NA. Methods A systematic literature search (MEDLINE and EMBASE) was conducted (January 2000 to February 2021). Search strings included meningococcal disease and the regions/countries of interest. Identified publications were screened sequentially by title/abstract, followed by screening of the full-text article; articles were also assessed on methodological quality. Literature reviews, genetic sequencing or diagnostic accuracy studies, or other non-pertinent publication type were excluded. An additional grey literature search (non-peer-reviewed sources; start date January 2000) was conducted to the end of April 2019. Results Of the 1745 publications identified, 79 were eligible for the final analysis (n = 61 for EM and n = 19 for NA; one study was relevant to both). Asymptomatic meningococcal carriage rates were 0–33% in risk groups (e.g. military personnel, pilgrims) in EM (no data in NA). In terms of epidemiology, serogroups A, B and W were most prevalent in EM compared with serogroups B and C in NA. IMD incidence was 0–20.5/100,000 in EM and 0.1–3.75/100,000 in NA (reported by 7/15 countries in EM and 3/5 countries in NA). CFRs were heterogenous across the EM, ranging from 0 to 57.9%, but were generally lower than 50%. Limited NA data showed a CFR of 0–50%. Data were also limited in terms of IMD presentation and management, particularly relating to clinical diagnosis/antibiotic treatment. No economic evaluation or HTA studies were found. Conclusions High-risk groups remain a significant reservoir of asymptomatic meningococcal carriage. It is probable that inadequacies in national surveillance systems have contributed to the gaps identified. There is consequently a pressing need to improve national surveillance systems in order to estimate the true burden of IMD and guide appropriate prevention and control programmes in these regions.

Seasonal influenza represents a huge health burden, resulting in significant mortality and morbidity. Following the 2009 H1N1 pandemic, focus has been directed on the burden of influenza globally. Country and regional disease burden estimates play important roles in helping inform decisions on national influenza intervention programmes. Despite improvements in influenza surveillance following the 2009 pandemic, many opportunities remain unexplored in the Eastern Mediterranean and North African (EMNA) region, which has a high prevalence of patients with chronic disease and thus a population at high risk of influenza complications. We conducted a systematic literature review of Embase, Medline, Scopus and the Cochrane Database of Systematic Reviews from 1 January 1998 to 31 January 2020 covering the EMNA region with the aim to describe the epidemiology of influenza in the region and assess the influenza epidemiological surveillance research landscape. Relevant data on study characteristics, population, clinical/virology characteristics and epidemiology were extracted and summarised descriptively. Of the 112 studies identified for inclusion, 90 were conducted in the Eastern Mediterranean region, 19 in North Africa and three across the EMNA region. Data were reported on 314,058 laboratory-confirmed influenza cases, 96 of which were derived from surveillance systems. Amongst the surveillance studies, the percentage of positive cases reported ranged from 1% to 100%. The predominantly identified influenza strain was strain A; H1N1 was the most prominent circulating subtype. Typing was performed in approximately 75% and subtyping in 50% of studies, respectively. Data on those considered most at risk for influenza complications were collected in 21% of studies, highlighting a regional gap for these data. Our review reveals existing gaps in regional estimates of influenza health and economic burden, hospitalisation rates and duration, and highlights the need for robust and high-quality epidemiology data to help inform public health interventions. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00534-3.

Most mass gathering events have been suspended due to the SARS-CoV-2 pandemic. However, with vaccination rollout, whether and how to organize some of these mass gathering events arises as part of the pandemic recovery discussions, and this calls for decision support tools. Hajj, one of the world's largest religious gatherings, was substantively scaled down in 2020 and it is still unclear if it will take place in 2021 and sub-sequent years. Considering the disease trends and vaccination conditions in the pilgrims’ country of origin, and the operational and logistical aspects of implementing public health measures, Hajj reopening conditions could be very complex. Simulating disease transmission dynamics during the Hajj season under differ-ent conditions can provide some insights for better decision-making. Since most disease risk assessment models require data on the number and nature of possible close contacts between individuals, we seek to use integrated agent-based modeling and discrete events simulation techniques to capture risky contacts among the pilgrims in one of the Hajj major sites, namely Masjid-Al-Haram. In particular, we assessed different scenarios concerning the total number of pilgrims and enforced physical distancing measures. Our simulation results show that a plethora of risky contacts may occur during the rituals. Also, as the total number of pilgrims increases at each site, the number of risky contacts increases, and physical distancing measures may be challenging to maintain beyond a certain number of pilgrims in the site.

Most mass gathering events have been suspended due to the SARS-CoV-2 pandemic. However, with vaccination rollout, whether and how to organize some of these mass gathering events arises as part of the pandemic recovery discussions, and this calls for decision support tools. Hajj, one of the world's largest religious gatherings, was substantively scaled down in 2020 and it is still unclear if it will take place in 2021 and subsequent years. Considering the disease trends and vaccination conditions in the pilgrims’ country of origin, and the operational and logistical aspects of implementing public health measures, Hajj reopening conditions could be very complex. Simulating disease transmission dynamics during the Hajj season under different conditions can provide some insights for better decision-making. Since most dis-ease risk assessment models require data on the number and nature of possible close contacts between individuals, we seek to use integrated agent-based modeling and discrete events simulation techniques to capture risky contacts among the pilgrims in one of the Hajj major sites, namely Masjid-Al-Haram. In particular, we assessed different scenarios concerning the total number of pilgrims and enforced physical distancing measures. Our simulation results show that a plethora of risky contacts may occur during the rituals. Also, as the total number of pilgrims increases at each site, the number of risky contacts increases, and physical distancing measures may be challenging to maintain beyond a certain number of pilgrims in the site.