Pharmaco-virological outcomes and genotypic resistance profiles among children and adolescents receiving a DTG-based regimen in Togo.

BACKGROUND: Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (DTG) as HIV treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents. METHODS: A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-Generation Sequencing (NGS) of protease, Reverse Transcriptase (RT) and integrase was performed on all samples with viral load >200 c/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm. RESULTS: 264 participants were enrolled (median age=17 years), 226 received a DTG-based regimen for a median of 20.5 months. Among them, virological suppression at the 200 c/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (i.e., >640 ng/mL), suboptimal and below the limit of quantification in 74.1%, 6.7% and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of Nucleoside RT Inhibitors, Non-NRTIs, and protease inhibitors were found in 52%, 66% and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n=3/32, R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 c/mL. CONCLUSIONS: These first findings in such a large series of adolescents in a low-income country, showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of the virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.

Effect of the COVID-19 pandemic on HIV, malaria and tuberculosis indicators in Togo: an interrupted time series analysis.

BACKGROUND: Limited data are available on the effects of the COVID-19 pandemic on health-related indicators in sub-Saharan Africa. This study aimed to estimate the effect of the COVID-19 pandemic on nine indicators of HIV, malaria and tuberculosis (TB) in Togo. METHODS: For this interrupted time series analysis, national health information system data from January 2019 to December 2021 and TB programmatic data from the first quarter of 2018 to the fourth quarter of 2022 were analysed. Nine indicators were included. We used Poisson segmented regression to estimate the immediate impact of the pandemic and per-pandemic period trends through incidence rate ratios (IRRs) with 95% CIs. RESULTS: Overall, there was a decrease in six of the nine indicators, ranging from 19.3% (IRR 0.807, 95% CI 0.682 to 0.955, p=0.024) for the hospitalisation of patients for malaria to 36.9% (IRR 0.631, 95% CI 0.457 to 0.871, p=0.013) for TB diagnosis by Mycobacterium tuberculosis Xpert immediately after the declaration of the COVID-19 pandemic. A comparison of the observed and predicted trends showed that the trend remained constant between the prepandemic and pandemic periods of COVID-19 for all malaria indicators. A significant downward monthly trend was observed in antiretroviral therapy initiation (IRR 0.909, 95% CI 0.892 to 0.926, p<0.001) and positive TB microscopy (IRR 0.919, 95% CI 0.880 to 0.960, p=0.002). CONCLUSION: HIV, malaria and TB services were generally maintained over time in Togo despite the COVID-19 pandemic. However, given the decline in levels immediately after the onset of the pandemic, there is an urgent need to improve the preparedness of the healthcare system.

Safety and immunogenicity of a single dose of Tdap compared to Td in pregnant women in Mali and 3 its effect on infant immune responses: a single-centre, randomised, double-blind, active-controlled phase 2 study.

Background: While maternal pertussis vaccination is a strategy to reduce infant morbidity, safety and immunogenicity data are limited in sub-Saharan Africa. We aimed to evaluate the safety of a single dose of tetanus, diphtheria and acellular pertussis vaccine (Tdap) vaccine compared to tetanus and diphtheria vaccine (Td) vaccine in pregnant women in Bamako, Mali and to assess the pertussis toxin (PT) antibody response at birth. Methods: In this phase 2, single-centre, randomised, double-blind, active-controlled study, from 23 January 2019 to 10 July 2019, healthy 18-39 year old women in the second trimester of a singleton pregnancy were randomised 2:1 to receive Tdap or Td. Blood was tested for serum immunoglobulin G (IgG) against PT and other vaccine antigens using a qualified Meso Scale Discovery multiplex immunoassay. The co-primary objectives evaluated safety and birth anti-PT levels. Infant immune responses to whole-cell pertussis vaccine (DTwP) were assessed. Statistical analysis was descriptive. This trial is registered with clinicaltrials.gov, NCT03589768. Findings: 133 women received Tdap and 67 received Td, with 126 and 66 livebirths, respectively. In the Tdap group, 22 serious adverse events (SAEs) including one maternal death occurred in 20 participants (15·0%), with 10 SAEs in 10 participants (14·9%) in the Td group. Among infants, 18 events occurred among 13 participants (10.3%) and 8 SAEs in 6 participants (9.1%), including three and two infant deaths, occurred in Tdap and Td groups, respectively. None were related to study vaccines. Anti-PT geometric mean concentration (GMC) at birth in the Tdap group was higher than in the Td group (55.4 [46.2-66.6] IU/ml vs 7.9 [5.4-11.5] IU/ml). One month after the third dose of DTwP, the GMC in infants born to mothers in the Tdap group were lower compared to the Td group (20.2 [13.7-29.9] IU/ml vs 77.2 [32.2-184.8] IU/ml). By 6 months of age, the anti- PT GMCs were 17.3 [12.8-23.4] IU/ml and 67.1 [35.5-126.7] IU/ml in Tdap and Td groups, respectively. At birth, anti-tetanus toxin (TT) GMCs were higher in infants in the Td vs Tdap group (5.9 [5.0-7.0] IU/ml vs 4.1 [3.5-4.8] IU/ml). Anti-diphtheria toxin GMCs were similar in both groups. Interpretation: Tdap administered to pregnant women in Mali is safe and well-tolerated. Infants of mothers who received Tdap were born with high PT and protective anti-TT antibody levels. By six months of age, after primary vaccination, the PT levels were lower in the Tdap group compared to the Td group. The blunted immune responses to primary DTwP vaccination in the Tdap infant group warrant further study. Funding: This project was funded by National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under contract numbers 75N93021C00012 (The Emmes Company), and HHSN27220130000221 (University of Maryland, Baltimore). Dr. Susana Portillo was supported by NIH award no. T32AI007524. NIAID, NIH provided Tdap vaccine (BOOSTRIX).

ADHD medications use and risk of mortality and unintentional injuries: a population-based cohort study.

We assessed the association between the use of medications for attention-deficit/hyperactivity disorder (ADHD) and the risk of all-cause mortality and unintentional injuries leading to emergency department (ED) or hospital admission in individuals aged ≤24 years with ADHD. We conducted a population-based retrospective cohort study between 2000 and 2021 using Quebec health administrative data. Individuals were followed from the first ADHD diagnosis or ADHD medication claim until turning 25, death, or study end. Exposure was defined as mutually exclusive episodes of ADHD medication use and/or coverage under the public provincial drug plan (PDP): 1) covered and not treated with ADHD medication; 2) covered and treated with ADHD medication; and 3) not covered under the PDP. The risk of all-cause mortality and unintentional injuries associated with exposure episodes was estimated using multivariable survival analyses. The cohort included n = 217 192 individuals aged 1-24 years with a male to female ratio of close to 2:1. Compared to non-medication use, episodes of ADHD medication use, overall, were associated with reduced all-cause mortality (adjusted hazard ratio, aHR 0.61, 95% CI 0.48-0.76) and unintentional injury leading to ED (0.75, 0.74-0.77) or hospitalisation (0.71, 0.68-0.75). Episodes of stimulants were associated with a lower risk of all-cause mortality and reduced risk of unintentional injuries, while episodes with non-stimulants and with both stimulants and non-stimulants concomitantly were associated with reduced risk of unintentional injuries, but not of all-cause mortality. Although residual confounding cannot be excluded, stimulants may have a protective effect in terms of risk of all-cause mortality and both stimulants and non-stimulants for ADHD may reduce the risk of unintentional injuries. The findings of the current study should inform clinical decision making on the choice of starting a pharmacological treatment for ADHD, when a balance needs to be struck between expected benefits and possible risks.

Statistical analysis plan for the LAKANA trial: a cluster-randomized, placebo-controlled, double-blinded, parallel group, three-arm clinical trial testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1-11-month-old infants in Mali.

BACKGROUND: The Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1-11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP). METHODS/DESIGN: LAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1-11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1-11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering. CONCLUSION: The SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT04424511 . Registered on 11 June 2020.

"Be honest and gain trust": a population health study to understand the factors associated with building trust in local government related to COVID-19 and vaccination in three historically disinvested neighborhoods in New York City.

Background: Distrust in government among people of color is a response to generations of systemic racism that have produced preventable health inequities. Higher levels of trust in government are associated with better adherence to government guidelines and policies during emergencies, but factors associated with trust and potential actions to increase trust in local government are not well understood. Methods: The COVID-19 Community Recovery study sampled participants from the New York City (NYC) Department of Health and Mental Hygiene's NYC Health Panel, a probability-based survey panel who complete health surveys periodically. Participants who lived in one of three historically disinvested communities in NYC where the NYC Department of Health and Mental Hygiene has dedicated resources to reduce health inequities were included. The cross-sectional survey was fielded from September 30 to November 4, 2021 and could be self-administered online or conducted via CATI (Computer Assisted Telephone Interviewing) in English, Spanish, and Simplified Chinese (Mandarin and Cantonese by phone). Demographic data were summarized by descriptive statistics. Crude and adjusted logistic regression analyses were used to assess factors predictive of trust in local government as a source of information about COVID-19 vaccines. Open-ended responses about strengthening residents' trust in local government were coded using an iteratively generated codebook. Results: In total, 46% of respondents indicated NYC local government was a trusted source of information about COVID-19 vaccines, relatively high compared to other sources. In bivariate analyses, race/ethnicity, age group, educational attainment, length of time living in NYC, and household income were significantly associated with identifying NYC government as a trusted source of information about COVID-19 vaccines. In multivariable logistic regression, no variables remained significant predictors of selecting local government as a trusted source of information. Key recommendations for local government agencies to build residents' trust include communicating clearly and honestly, addressing socioeconomic challenges, and enhancing public COVID-19 protection measures. Conclusion: Study findings demonstrate that nearly half of residents in three historically divested NYC communities consider local government to be a trusted source of information about COVID-19 vaccines. Strategies to increase trust in local government can help reduce community transmission of COVID-19 and protect public health.

Disruption of Healthcare in New York City During the COVID-19 Pandemic: Findings From Residents Living in North and Central Brooklyn, the South Bronx, and East and Central Harlem.

INTRODUCTION: The COVID-19 pandemic has disproportionately affected some New York City (NYC) neighborhoods that primarily consist of Black, Indigenous, and Latinx residents. In comparison to the rest of NYC, these neighborhoods experienced high hospitalization and COVID-related death rates, which has been attributed to a longstanding history of structural racism and disinvestment. While stay-at-home orders were implemented to reduce the spread of COVID-19, this may have also affected access and utilization of non-COVID related healthcare services. This study aims to assess the prevalence of and reasons for the disruption of non-COVID related healthcare services during the first 18 months of the pandemic. METHODS: From September 30, 2021 to November 4, 2021, the NYC Health Department administered the COVID-19 Community Recovery Survey to a subset of residents who were part of the NYC Health Panel a probability-based survey panel. This cross-sectional survey, which included closed and open-ended questions, was either self-administered online or completed via CATI (Computer Assisted Telephone Interviewing) in English, Spanish, and Simplified Chinese. Descriptive statistics were used to summarize responses and unweighted, weighted, age-adjusted percentages, and 95% Confidence Intervals (CIs) were calculated. RESULTS: With a response rate of 30.3% (N = 1358), more than half of participants (54%) reported disruption to either routine physical healthcare or mental health services. Concern about getting COVID-19 (61%), stay-at-home policies (40%), belief that care could safely be postponed (35%), and appointment challenges (34%) were among reasons for delaying routine healthcare. Concern about getting COVID-19 (38%) and reduced hours of service (36%) were primary reasons for delaying mental healthcare. Reported reasons for the sustained delay of care past 18 months involved COVID concerns, appointment, and insurance challenges. CONCLUSIONS: Due to the pandemic, some disruption to healthcare was expected. However, most study participants either avoided or experienced a delay in healthcare. The delay of non-COVID related healthcare throughout the pandemic may result in the further widening of the health inequity gap among NYC residents dealing with a higher chronic disease burden before the start of the COVID-19 pandemic in March 2020. Findings from this study can support equitable COVID-19 recovery, and guide efforts with health promotion.

Safety and immunogenicity of quadrivalent meningococcal polysaccharide vaccine (MPV ACYW135) compared with quadrivalent meningococcal conjugate vaccine (Menactra®) in Malian children.

Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study compared the safety and immunogenicity of a quadrivalent meningococcal polysaccharide vaccine (MPV-4, MPV ACYW135) and quadrivalent meningococcal ACWY conjugate vaccine (MCV-4, Menactra®). Healthy, 2- to 10-year-old children in Bamako, Mali, were randomized 1:1 to receive one dose of MPV-4 or MCV-4. Safety outcomes were evaluated for 6 months post-immunization. Immunogenicity for all serogroups was assessed for non-inferiority between MPV-4 and MCV-4 30 days post immunization by serum bactericidal antibody assay using baby rabbit complement (rSBA). From December 2020 to July 2021, 260 healthy subjects were consented and randomized. At Day 30 post-immunization, the proportions of subjects with rSBA titers ≥ 128 for all serogroups in the MPV-4 group were non-inferior to those in MCV-4 group. The proportions of subjects with rSBA ≥ 4-fold increase and rSBA titers ≥ 8 for all serogroups were similar among vaccine groups (P > .05). Geometric Mean Titers and Geometric Mean Fold Increases for all serogroups in both vaccine groups were similar (P > .05). Few local and systemic post-immunization reactions of similar severity and duration were observed within 7 days and were similar in both groups (P > .05). All resolved without sequelae. Unsolicited adverse events were similar in both groups regarding relationship to study vaccine, severity and duration. No serious adverse events were reported during the study period. MPV ACYW135 showed a non-inferior immunogenicity profile and a comparable reactogenicity profile to MCV-4 in Malian children aged 2-10 years.Clinical Trial Registration: NCT04450498.

Optimizing next-generation RSV prevention in Mali: A cost-effectiveness analysis of pediatric vaccination, maternal vaccination, and extended half-life monoclonal antibody immunoprophylaxis.

Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children. We analyzed the health and economic impact of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios. We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. Incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months. At prices comparable to existing vaccine products, extended half-life RSV mAbs would be impactful and efficient components of prevention strategies in LMICs such as Mali.

Meningococcal ACWYX Conjugate Vaccine in 2-to-29-Year-Olds in Mali and Gambia.

BACKGROUND: An effective, affordable, multivalent meningococcal conjugate vaccine is needed to prevent epidemic meningitis in the African meningitis belt. Data on the safety and immunogenicity of NmCV-5, a pentavalent vaccine targeting the A, C, W, Y, and X serogroups, have been limited. METHODS: We conducted a phase 3, noninferiority trial involving healthy 2-to-29-year-olds in Mali and Gambia. Participants were randomly assigned in a 2:1 ratio to receive a single intramuscular dose of NmCV-5 or the quadrivalent vaccine MenACWY-D. Immunogenicity was assessed at day 28. The noninferiority of NmCV-5 to MenACWY-D was assessed on the basis of the difference in the percentage of participants with a seroresponse (defined as prespecified changes in titer; margin, lower limit of the 96% confidence interval [CI] above -10 percentage points) or geometric mean titer (GMT) ratios (margin, lower limit of the 98.98% CI >0.5). Serogroup X responses in the NmCV-5 group were compared with the lowest response among the MenACWY-D serogroups. Safety was also assessed. RESULTS: A total of 1800 participants received NmCV-5 or MenACWY-D. In the NmCV-5 group, the percentage of participants with a seroresponse ranged from 70.5% (95% CI, 67.8 to 73.2) for serogroup A to 98.5% (95% CI, 97.6 to 99.2) for serogroup W; the percentage with a serogroup X response was 97.2% (95% CI, 96.0 to 98.1). The overall difference between the two vaccines in seroresponse for the four shared serogroups ranged from 1.2 percentage points (96% CI, -0.3 to 3.1) for serogroup W to 20.5 percentage points (96% CI, 15.4 to 25.6) for serogroup A. The overall GMT ratios for the four shared serogroups ranged from 1.7 (98.98% CI, 1.5 to 1.9) for serogroup A to 2.8 (98.98% CI, 2.3 to 3.5) for serogroup C. The serogroup X component of the NmCV-5 vaccine generated seroresponses and GMTs that met the prespecified noninferiority criteria. The incidence of systemic adverse events was similar in the two groups (11.1% in the NmCV-5 group and 9.2% in the MenACWY-D group). CONCLUSIONS: For all four serotypes in common with the MenACWY-D vaccine, the NmCV-5 vaccine elicited immune responses that were noninferior to those elicited by the MenACWY-D vaccine. NmCV-5 also elicited immune responses to serogroup X. No safety concerns were evident. (Funded by the U.K. Foreign, Commonwealth, and Development Office and others; ClinicalTrials.gov number, NCT03964012.).

Model-estimated impacts of pediatric respiratory syncytial virus prevention programs in Mali on asthma prevalence.

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in young children and is associated with subsequent recurrent wheezing illness and asthma (wheeze/asthma). RSV prevention may therefore reduce wheeze/asthma prevalence. Objectives: We estimated the contribution of RSV LRTI and the impact of RSV prevention on recurrent wheeze/asthma in Mali. Methods: We simulated 12 consecutive monthly birth cohorts in Mali and estimated RSV LRTI cases through 2 years and recurrent wheeze/asthma prevalence at 6 years under different RSV prevention scenarios: status quo, seasonal birth-dose extended half-life mAb, and seasonal birth-dose extended half-life mAb followed by 2 doses of pediatric vaccine (mAb + vaccine). We used World Health Organization (WHO) Preferred Product Characteristics for RSV prevention, demographic and RSV epidemiologic data from Mali, regional recurrent wheeze/asthma prevalence, and relative risk of recurrent wheeze/asthma given early childhood RSV LRTI. Results: Among the simulated cohort of 778,680 live births, 10.0% had RSV LRTI by 2 years and 89.6% survived to 6 years. We estimated that 13.4% of all recurrent wheeze/asthma at 6 years was attributable to RSV LRTI. Recurrent wheeze/asthma prevalence at 6 years was 145.0 per 10,000 persons (RSV LRTI attributable) and 1084.2 per 10,000 persons (total). In mAb and mAb + vaccine scenarios, RSV LRTI cases decreased by 11.8% and 44.4%, respectively, and recurrent wheeze/asthma prevalence decreased by 11.8% and 44.4% (RSV LRTI attributable) and 1.6% and 5.9% (total). Conclusion: In Mali, RSV prevention programs may have a meaningful impact on chronic respiratory disease, strengthening the case for investment in RSV prevention.

Aid when 'there is nothing left to offer': Experiences of palliative care and palliative care needs in humanitarian crises.

Access to palliative care, and more specifically the alleviation of avoidable physical and psychosocial suffering is increasingly recognized as a necessary component of humanitarian response. Palliative approaches to care can meet the needs of patients for whom curative treatment may not be the aim, not just at the very end of life but alleviation of suffering more broadly. In the past several years many organizations and sectoral initiatives have taken steps to develop guidance and policies to support integration of palliative care. However, it is still regarded by many as unfeasible or aspirational in crisis contexts; particularly where care for persons with life threatening conditions or injuries is logistically, legally, and ethically challenging. This article presents a synthesis of findings from five qualitative sub-studies within a research program on palliative care provision in humanitarian crises that sought to better understand the ethical and practical dimensions of humanitarian organizations integrating palliative care into emergency responses. Our multi-disciplinary, multi-national team held 98 in-depth semi-structured interviews with people with experiences in natural disasters, refugee camps in Rwanda and Jordan, and in Ebola Treatment Centers in Guinea. Participants included patients, family members, health care workers, and other staff of humanitarian agencies. We identified four themes from descriptions of the struggles and successes of applying palliative care in humanitarian settings: justification and integration of palliative care into humanitarian response, contextualizing palliative care approaches to crisis settings, the importance of being attentive to the 'situatedness of dying', and the need for retaining a holistic approach to care. We discuss these findings in relation to the ideals embraced in palliative care and corresponding humanitarian values, concluding that palliative care in humanitarian response is essential for responding to avoidable pain and suffering in humanitarian settings.

Prevalence of HIV-1 Natural Polymorphisms and Integrase-Resistance-Associated Mutations in African Children.

Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.

Testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1-11-month-old infants in Mali (LAKANA): study protocol for a cluster-randomized, placebo-controlled, double-blinded, parallel-group, three-arm clinical trial.

BACKGROUND: Mass drug administration (MDA) of azithromycin (AZI) has been shown to reduce under-5 mortality in some but not all sub-Saharan African settings. A large-scale cluster-randomized trial conducted in Malawi, Niger, and Tanzania suggested that the effect differs by country, may be stronger in infants, and may be concentrated within the first 3 months after treatment. Another study found no effect when azithromycin was given concomitantly with seasonal malaria chemoprevention (SMC). Given the observed heterogeneity and possible effect modification by other co-interventions, further trials are needed to determine the efficacy in additional settings and to determine the most effective treatment regimen. METHODS: LAKANA stands for Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin. The LAKANA trial is designed to address the mortality and health impacts of 4 or 2 annual rounds of azithromycin MDA delivered to 1-11-month-old (29-364 days) infants, in a high-mortality and malaria holoendemic Malian setting where there is a national SMC program. Participating villages (clusters) are randomly allocated in a ratio of 3:2:4 to three groups: placebo (control):4-dose AZI:2-dose AZI. The primary outcome measured is mortality. Antimicrobial resistance (AMR) will be monitored closely before, during, and after the intervention and both among those receiving and those not receiving MDA with the study drugs. Other outcomes, from a subset of villages, comprise efficacy outcomes related to morbidity, growth and nutritional status, outcomes related to the mechanism of azithromycin activity through measures of malaria parasitemia and inflammation, safety outcomes (AMR, adverse and serious adverse events), and outcomes related to the implementation of the intervention documenting feasibility, acceptability, and economic aspects. The enrolment commenced in October 2020 and is planned to be completed by the end of 2022. The expected date of study completion is December 2024. DISCUSSION: If LAKANA provides evidence in support of a positive mortality benefit resulting from azithromycin MDA, it will significantly contribute to the options for successfully promoting child survival in Mali, and elsewhere in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT04424511. Registered on 11 June 2020.

Engaging businesses and faith-based organizations in public health interventions: Lessons learned from a COVID-19 and flu vaccine detailing program in the Northeast Bronx.

Objectives: The NYC Department of Health and Mental Hygiene conducted a COVID-19 and flu vaccine community detailing program to influential businesses and faith-based organizations in the Northeast Bronx in 2022 to increase COVID-19 and flu vaccine knowledge and uptake among residents of the area. Study design: program evaluation. Methods: The program was piloted in the Northeast Bronx, a geography selected based on prior low COVID-19 and flu vaccination rates and high COVID-19 case positivity rates. Barbershops, hair salons, beauty salons, nail salons and faith-based organizations were selected as potential partners because their owners or staff typically spend at least an hour in interactions with clients. From January 2022 through April 2022, two detailing visits were conducted by engagement staff: an initial visit to all potential partners in the selected geography, and a follow up visit to those who committed to be champions of health. Results: Out of 113 identified businesses/organizations, 70 met the criteria to be potential partners in the program. After being contacted by health department staff, 45 (64%) potential partners committed to be champions of health. During the four months of the pilot, zip codes with the highest level of program engagement experienced greater percent increases in COVID-19 vaccination rates during the program period compared to NYC and Bronx averages. Flu vaccination rates during the program period were not available. Conclusion: Supplementing other local public health efforts, the community detailing pilot program demonstrates a model of dissemination of health information through local business leaders, and provides lessons learned to increase champion commitment.

[Causes Of Death In The Medicine Department Of The Regional Hospital Of Sikasso]. / Causes De Décès Au Service De Médecine De l'Hôpital Régional De Sikasso.

The causes of death are of great importance in assessing the health status of the population and care'squality. Their study could guide health policies aimed at increasing life expectancy. OBJECTIVES: It was to determine the causes of death; to study the socio-demographic characteristics of deceased. MATERIALS AND METHODS: This was a retrospective and descriptive study of all deaths that occurred in the Medical Department of Sikasso Hospital from January 2018 to December 2020. RESULTS: Among 265 deaths recorded, the mean age was 45.12 ± 17.5 years. The sex ratio was 1.59. They were mostly city dwellers and 51.64% lived in Sikasso city. The mean length of hospitalization was 7.09 ± 6.38 days. Kidney failure was the first reason for hospitalization. HIV infection was the leading cause of death (29.8%), followed by renal failure (24.2%). The male sex was predominant in all causes of death except HIV infection and anemia. Deaths linked to kidney failure have increased fivefold from 2018 to 2020. CONCLUSION: Deaths related to HIV/AIDS remain in the lead despite their strong reduction; those related to kidney failure have increased fivefold.

Les causes de décès revêtent une grande importance dans l'évaluation de l'état de santé de la population et de la qualité des soins. Leur étude pourrait orienter les politiques de santé visant à accroître l'espérance de vie. OBJECTIFS: C'était de déterminer les causes de mort ; d'étudier les caractéristiques sociodémographiques des défunts. MATÉRIELS ET MÉTHODES: Il s'agissait d'une étude rétrospective et descriptive portant sur tous les décès survenus dans le service de Médecine de l'hôpital de Sikasso de Janvier 2018 à Décembre 2020. RÉSULTATS: Parmi 265 décès recensés, l'âge moyen était de 45,12±17,5 ans. Le sex-ratio était de 1,59. Il s'agissait en majorité de citadins et 51,64% résidaient à Sikasso ville. La durée moyenne d'hospitalisation était 7,09 ± 6,38 jours. L'insuffisance rénale constituait le 1er motif d'hospitalisation. L'infection à VIH était la 1ère cause de décès (29,8%), suivie de l'insuffisance rénale (24,2%). Le sexe masculin était majoritaire dans toutes les causes de décès hormis l'infection à VIH et l'anémie. Les décès liés à l'insuffisance rénale ont quintuplé de 2018 à 2020. CONCLUSION: Les décès liés au VIH/SIDA reste en tête malgré leur forte réduction ; ceux liés à l'insuffisance rénale ont quintuplé.

Causes de décès au service de médecine de l'hôpital régional de Sikasso / Causes of death in the medicine department of the regional hospital of Sikasso

Les causes de décès revêtent une grande importance dans l'évaluation de l'état de santé de la population et de la qualité des soins. Leur étude pourrait orienter les politiques de santé visant à accroître l'espérance de vie. Objectifs : C'était de déterminer les causes de mort ; d'étudier les caractéristiques sociodémographiques des défunts. Matériels et méthodes : Il s'agissait d'une étude rétrospective et descriptive portant sur tous les décès survenus dans le service de Médecine de l'hôpital de Sikasso de Janvier 2018 à Décembre 2020. Résultats : Parmi 265 décès recensés, l'âge moyen était de 45,12±17,5 ans. Le sex-ratio était de 1,59. Il s'agissait en majorité de citadins et 51,64% résidaient à Sikasso ville. La durée moyenne d'hospitalisation était 7,09 ± 6,38 jours. L'insuffisance rénale constituait le 1er motif d'hospitalisation. L'infection à VIH était la 1ère cause de décès (29,8%), suivie de l'insuffisance rénale (24,2%). Le sexe masculin était majoritaire dans toutes les causes de décès hormis l'infection à VIH et l'anémie. Les décès liés à l'insuffisance rénale ont quintuplé de 2018 à 2020. Conclusion : Les décès liés au VIH/SIDA reste en tête malgré leur forte réduction ; ceux liés à l'insuffisance rénale ont quintuplé

The causes of death are of great importance in assessing the health status of the population and care'squality. Their study could guide health policies aimed at increasing life expectancy. Objectives: It was to determine the causes of death; to study the socio-demographic characteristics of deceased. Materials and methods: This was a retrospective and descriptive study of all deaths that occurred in the Medical Department of Sikasso Hospital from January 2018 to December 2020. Results: Among 265 deaths recorded, the mean age was 45.12 ± 17.5 years. The sex ratio was 1.59. They were mostly city dwellers and 51.64% lived in Sikasso city. The mean length of hospitalization was 7.09 ± 6.38 days. Kidney failure was the first reason for hospitalization. HIV infection was the leading cause of death (29.8%), followed by renal failure (24.2%). The male sex was predominant in all causes of death except HIV infection and anemia. Deaths linked to kidney failure have increased fivefold from 2018 to 2020. Conclusion: Deaths related to HIV/AIDS remain in the lead despite their strong reduction; those related to kidney failure have increased fivefold

SARS-CoV-2 antibody seroprevalence in Togo: a national cross-sectional household survey, May-June, 2021.

BACKGROUND: The extent of SARS-CoV-2 circulation in African countries is still unclear. Seroprevalence studies are a common approach to epidemiological surveillance, allowing estimation of the proportion of people who have had contact with the virus. We aimed at estimating the seroprevalence of anti-SARS-CoV-2 antibodies and associated factors in Togo at the national level in 2021 according to age groups, gender, and place of residence (rural or urban). METHODS: From 15 May to 31 June 2021, we conducted a nationally representative cross-sectional serological survey in 12 health districts (two districts per health region) in the > 5 years old population in Togo. The Wantai SARS-CoV-2 total antibody assay S protein receptor-binding domain-based ELISA (Wantai Biological Pharmacy Enterprise Co.; Beijing, China) was used to determine the presence of SARS-CoV-2 total antibodies in plasma. Crude and weighted seroprevalences (weighted by age, sex and place of residence) were calculated and then weighted seroprevalences were adjusted according to sensitivity and specificity of the ELISA test. Finally, logistic regression models were performed in order to describe factors associated. RESULTS: Of the 7593 participants, the overall weighted and adjusted seroprevalence of total anti-SARS-CoV-2 antibodies was 65.5% (CI95%: 18.9-21.1). Urban dwellers, young adults (30-49 years) and vaccinated individuals were significantly more likely to be seropositive. CONCLUSION: The high seroprevalence we observed is consistent with observations across West Africa. Quantification of the level of immunity in the population is needed to know how close we are to herd immunity. In the meantime, vaccination against the COVID-19 remains necessary.

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries. Here, pre-pandemic samples from eight malaria endemic and non-endemic countries and four continents were tested by ELISA to measure SARS-CoV-2 Spike S1 subunit reactivity. Individuals with acute malaria infection generated substantial SARS-CoV-2 reactivity. Cross-reactivity was not associated with reactivity to other human coronaviruses or other SARS-CoV-2 proteins, as measured by peptide and protein arrays. ELISAs with deglycosylated and desialated Spike S1 subunits revealed that cross-reactive antibodies target sialic acid on N-linked glycans of the Spike protein. The functional activity of cross-reactive antibodies measured by neutralization assays showed that cross-reactive antibodies did not neutralize SARS-CoV-2 in vitro. Since routine use of glycosylated or sialated assays could result in false positive SARS-CoV-2 antibody results in malaria endemic regions, which could overestimate exposure and population-level immunity, we explored methods to increase specificity by reducing cross-reactivity. Overestimating population-level exposure to SARS-CoV-2 could lead to underestimates of risk of continued COVID-19 transmission in sub-Saharan Africa.