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Background: The use of NSAIDs have caused stomach injury by inhibiting endogenous mucosal prostaglandin production. Cucumis melo is reported to possess antiulcer potential. This study investigates the mechanism underlying the antiulcer potentials of Cucumis melo (CUM). Methods: Thirty-five male Wistar rat were randomly assigned to each of seven groups; A(control given water and rat pellets), B(gastric ulcer induced with ibuprofen 400 mg/kg), C (Misoprotol 200 μg/kg), D to G (pretreated with different variation of CUM extract; 25 %, 50 %, 75 % and 100 % at a dose of 1 ml/kg for 3 weeks prior to gastric ulcer induction). Ulcer score, ulcer index and percentage inhibition, total gastric acidity was measured. Antioxidant activities, Malondialdehyde, H+/K+ ATPase, PGE2, TNF-α was done by spectrophotometry. Molecular docking investigation of Cucumis melo compounds against Prostaglandin E2 was carried out. Level of significance was tested at P ≤ 0.05 using Tukey post hoc. Result: Total gastric acidity, ulcer score, ulcer index, MDA, TNF-α significantly decreased after CUM treatment when compared to group B. The percentage inhibition, antioxidant activities, PGE2 concentration was significantly increased in all treatment groups compared to group B. Interactions of selected compounds of CUM with Prostaglandin E2 at various docking pockets showed folic acid has highest binding affinity followed by delta7-avenasterol and codisterol to PGE2 receptor. this study shows that one of the mechanisms by which CUM exhibits its antiulcer potential by enhancing Prostaglandin synthesis and antioxidant capacity. Therefore, Cucumis melo can therefore be explored as novel antiulcer agents.

The article assesses the effect of Betulinic acid (BA) indomethacin-induced peptic ulcer and anti-inflammatory properties in experimental albino rats. After the administration of BA orally, indomethacin is administered subcutaneously to all the animals in four groups. A progressive increase of paw oedema is noted after the rats were injected by carrageenin and the dose dependent inhibition of oedema decreases after BA and aspirin were administered. The BA is also noted responsible for the decrease in ulcer scores.

Introduction: Respiratory syncytial virus (RSV) incidence is known to be underestimated in adults due to its infrequent diagnostic testing and lower sensitivity of single nasal/nasopharyngeal swab PCR testing outside of the early childhood period. RSV can trigger acute cardiac events as well as cause respiratory disease. Consequently, we used a model-based study to estimate RSV-attributable hospitalization and mortality incidence among adults in Italy between 2015 and 2019., Methods: Through a database predisposed by CREA Sanità, by extracting monthly data from the Italian hospitalization collection data of the Ministry of Health and the Italian National Institute of Statistics (ISTAT) data (mortality), we estimated yearly RSV-attributable incidence of events for different cardiorespiratory outcomes. We used a quasi-Poisson regression model, which accounted for periodic and aperiodic time trends and viral activity proxies., Results: The yearly RSV-attributable cardiorespiratory hospitalization incidence increased with age and was highest among adults aged ≥ 75 years (1064-1527 cases per 100,000 person-years). Similarly, the RSV-attributable cardiorespiratory mortality rate was highest among persons aged ≥ 75 years (59-85 deaths per 100,000 person-years). Incidence rates for RSV-attributable hospitalizations and RSV-attributable mortality were on average 2-3 times higher for cardiorespiratory than respiratory disease alone. Incidence rate based on RSV-specific ICD codes only were 405-1729 times lower than modeled estimates accounting for untested events., Conclusion: RSV causes a substantial disease burden among adults in Italy and contributes to both respiratory and cardiovascular conditions. Our results emphasize the need for effective RSV prevention strategies, particularly among older adults., (© 2024. Pfizer Inc.)

Introduction: Diagnostics are an essential, undervalued part of the health-care system. For many diseases, molecular diagnostics are the gold standard, but are not easy to implement in Low- and Middle-Income Countries (LMIC). Sample-to-result (S2R) platforms combining all procedures in a closed system could offer a solution. In this paper, we investigated their suitability for implementation in LMIC., Areas Covered: A scorecard was used to evaluate different platforms on a range of parameters. Most platforms scored fairly on the platform itself, ease-of-use and test consumables; however, shortcomings were identified in cost, distribution and test panels tailored to LMIC needs. The diagnostic coverage for common infectious diseases was found to have a wider coverage in high-income countries (HIC) than LMIC. A literature study showed that in LMIC, these platforms are mainly used as diagnostic tools or evaluation of diagnostic performance, with a minority assessing the operational characteristics or the clinical utility. In this narrative review, we identified various points for adaptation of S2R platforms to LMIC conditions., Expert Opinion: For S2R platforms to be suitable for implementation in LMIC some modifications by the manufacturers could be considered. Furthermore, strengthening health systems and digitalization are vital; as are smaller, cheaper, faster, and sustainable technologies.

Background: Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing., Methods: We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance., Results: We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%., Conclusions: RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated., Competing Interests: Potential conflicts of interest. P95 was contracted by Pfizer to conduct this study. N. A., Z. A.-T., B. M., S. M., L. M. M., C. O., M. R., M. S., and H. V. are employees of P95, which received funding from Pfizer in connection with the development of this article. H. N. received grants from Innovative Medicine Initiative, National Institute of Health and Care Research, Bill and Melinda Gates Foundation, WHO, and Pfizer; and consultancy or honoraria and speaker fees from Sanofi, Merck, Novavax, ReViral, and GSK (all paid to institution). J. E. A., E. B., D. C., B. D. G., W. K., and M. R. are employees of Pfizer and may hold stock or stock options. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Most observational population-based studies identify respiratory syncytial virus (RSV) by nasal/nasopharyngeal swab reverse transcriptase real-time PCR (RT-PCR) only. We conducted a systematic review and meta-analyses to quantify specimen and diagnostic testing-based underascertainment of adult RSV infection., Methods: EMBASE, PubMed, and Web of Science were searched (January 2000-December 2021) for studies including adults using/comparing >1 RSV testing approach. We quantified test performance and RSV detection increase associated with using multiple specimen types., Results: Among 8066 references identified, 154 met inclusion. Compared to RT-PCR, other methods were less sensitive: rapid antigen detection test (RADT; pooled sensitivity, 64%), direct fluorescent antibody (DFA; 83%), and viral culture (86%). Compared to singleplex PCR, multiplex PCR's sensitivity was lower (93%). Compared to nasal/nasopharyngeal swab RT-PCR alone, adding another specimen type increased detection: sputum RT-PCR, 52%; 4-fold rise in paired serology, 44%; and oropharyngeal swab RT-PCR, 28%. Sensitivity was lower in estimates limited to only adults (for RADT, DFA, and viral culture), and detection rate increases were largely comparable., Conclusions: RT-PCR, particularly singleplex testing, is the most sensitive RSV diagnostic test in adults. Adding additional specimen types to nasopharyngeal swab RT-PCR testing increased RSV detection. Synergistic effects of using ≥3 specimen types should be assessed, as this approach may improve the accuracy of adult RSV burden estimates., Competing Interests: Potential conflicts of interest. P95 was contracted by Pfizer to conduct this study. C. O., L. M. M., S. M., B. M., M. S., N. A., M. R., Z. A.-T., and H. V. are employees of P95. D. C., W. K., J. E. A., B. D. G., M. R., and E. B. are employees of Pfizer and may hold stock or stock options. H. N. declares no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Hyperglycaemia is a risk factor for tuberculosis. Evidence of changes in blood glucose levels during and after tuberculosis treatment is unclear., Objective: To compile evidence of changes in blood glucose during and after tuberculosis treatment and the effects of elevated blood glucose changes on treatment outcomes in previously normoglycaemic patients., Methods: Original research studies (1980 to 2021) were identified in PubMed, Web of Science, CINAHL and Embase databases., Results: Of the 1,277 articles extracted, 14 were included in the final review. All the studies were observational and 50% were prospective. Fasting blood sugar was the most common clinical test (64%), followed by the glycated haemoglobin test and the oral glucose tolerance test (each 50%). Most tests were conducted at baseline and in the third month of treatment. Twelve studies showed that the prevalence of hyperglycaemia in previously normoglycaemic patients decreased from baseline to follow-up and end of treatment. Three studies showed successful treatment outcomes of 64%, 75% and 95%. Patients with hyperglycaemia at baseline were more likely to develop cavitary lung lesions and poor treatment outcomes and had higher post-treatment mortality. There was no difference in outcomes by human immunodeficiency virus (HIV) status., Conclusion: Elevated blood glucose in normoglycaemic patients receiving treatment for tuberculosis decreased by the end of treatment. Positive HIV status did not affect glucose changes during treatment. Further research is needed to investigate post-treatment morbidity in patients with baseline hyperglycaemia and the effects of HIV on the association between blood glucose and tuberculosis.

In 2020, WHO recognised the importance of strongyloidiasis alongside soil-transmitted helminths (STH) in their 2021-30 roadmap, which aspires to target Strongyloides stercoralis with preventive chemotherapy by use of ivermectin. Combination treatment with both albendazole, the primary drug used to treat STH, and ivermectin, would improve the efficiency of mass drug administration targeting both STH and S stercoralis. In this Personal View, we discuss the challenges and opportunities towards the development of an efficient control programme for strongyloidiasis, particularly if it is to run concurrently with STH control. We argue the need to define the prevalence threshold to implement preventive chemotherapy for S stercoralis, the target populations and optimal dosing schedules, and discuss the added benefits of a fixed-dose coformulation of ivermectin and albendazole. Implementation of an efficient control programme will require improvements to current diagnostics, and validation of new diagnostics, to target and monitor S stercoralis infections, and consideration of the challenges of multispecies diagnostics for S stercoralis and STH control. Finally, the evolution of ivermectin resistance represents a credible risk to control S stercoralis; we argue that genome-wide approaches, together with improved genome resources, are needed to characterise and prevent the emergence of resistance. Overcoming these challenges will help to reduce strongyloidiasis burden and enhance the feasibility of controlling it worldwide., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Before the introduction of vaccination to protect children from pneumonia, Streptococcus pneumoniae and Haemophilus influenzae type B (HiB) were the most frequent aetiological agents causing bacterial pneumonia in children under five years old. However, the etiology of childhood pneumonia appears to be changing and nonvaccine- type S. pneumoniae , non-typeable H. influenzae , and Staphylococcus aureus are becoming more relevant., Objective: We conducted a systematic review aimed at identifying the common causes of bacterial pneumonia in children in sub-Saharan Africa., Methods: We searched PubMed, Web of Science and African Index Medicus and included primary studies conducted since January 2010 that reported on the bacterial causes of pneumonia in children under five from sub-Saharan Africa. We extracted data items (about the study setting, pneumonia diagnosis, sampling, microbiological methods, and etiological agents) as well as study quality indicators., Results: Streptococcus pneumoniae was the most common bacteria in blood cultures from children with pneumonia (8%, 95% CI: 4-14%), and H. influenzae was second (3%, 95% CI: 1-17%). Children's nasopharynx commonly contained S. pneumoniae (66%), Moraxella catarrhalis (62%), and H. influenzae (44%)., Conclusion: S. pneumoniae and H. influenzae cause bacterial pneumonia in sub-Saharan African children. Our review also highlights the prevalence of potentially pathogenic bacteria in the nasopharynx of children under five and calls for more research into how nasopharyngeal colonization causes pneumonia., (©Copyright: the Author(s).)

Background: The rollout of GeneXpert aimed at increasing early diagnosis of tuberculosis to improve treatment outcomes and global tuberculosis targets., Objective: This study evaluated trends in tuberculosis diagnosis and outcomes pre- and post-introduction of GeneXpert in three African countries - the Democratic Republic of the Congo (DRC), Nigeria and South Africa., Methods: Data from 2001 to 2019 were extracted from the World Health Organization's data repository. Descriptive analysis, paired t -tests and interrupted time series models were used., Results: Estimated tuberculosis incidence decreased from 327/100 000 to 324/100 000 in the DRC, and from 1220/100 000 to 988/100 000 in South Africa. Incidence remained at 219/100 000 in Nigeria. The tuberculosis case notification rate did not change significantly. Increases in the new case treatment success rates were statistically significant (DRC: p = 0.0201; Nigeria: p = 0.0001; South Africa: p = 0.0017); decreases in mortality were also statistically significant (DRC: p = 0.0264; Nigeria: p = 0.0001; South Africa: p < 0.0001). Time series models showed insignificant increases in new tuberculosis cases in DRC ( n = 1856, p = 0.085) and Nigeria ( n = 785, p = 0.555) from 2011 to 2019; and a statistically significant decrease in South Africa ( n = 15 269, p = 0.006)., Conclusion: Improvements in tuberculosis treatment outcomes were achieved, but little progress has been made in new case notification due to varied implementation and scale-up of GeneXpert across the three countries. Implementation barriers need to be addressed to achieve the required tuberculosis targets., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2022. The Authors.)

There is limited capacity and infrastructure in sub-Saharan Africa to conduct clinical trials for the identification of efficient and effective new prevention, diagnostic and treatment modalities to address the disproportionate burden of disease. This paper reports on the process to establish locally driven infrastructure for multicentre research and trials in Nigeria known as the Nigeria Implementation Science Alliance Model Innovation and Research Centres (NISA-MIRCs). We used a participatory approach to establish a research network of 21 high-volume health facilities selected from all 6 geopolitical zones in Nigeria capable of conducting clinical trials, implementation research using effectiveness-implementation hybrid designs and health system research. The NISA-MIRCs have a cumulative potential to recruit 60 000 women living with HIV and an age-matched cohort of HIV-uninfected women. We conducted a needs assessment, convened several stakeholder outreaches and engagement sessions, and established a governance structure. Additionally, we selected and trained a core research team, developed criteria for site selection, assessed site readiness for research and obtained ethical approval from a single national institutional review board. We used the Exploration, Preparation, Implementation, Sustainment framework to guide our reporting of the process in the development of this network. The NISA-MIRCs will provide a nationally representative infrastructure to initiate new studies, support collaborative research, inform policy decisions and thereby fill a significant research infrastructure gap in Africa's most populous country., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Asymptomatic Leishmania infection may play an important role in the transmission of the parasite in endemic areas. At present there is no consensus on the definition of asymptomatic Leishmania infection, nor is there a safe and accessible gold standard test for its identification., Methods: This paper presents a scoping review to summarize definitions of asymptomatic Leishmania infection found in the literature, as well as to detail the approach (molecular, serological, cellular, and/or parasitological tests) used by researchers to identify this asymptomatic population. A scoping review of published and gray literature related to asymptomatic Leishmania infection was conducted; retrieved citations were screened based on predefined eligibility criteria, and relevant data items were extracted from eligible articles. The analysis is descriptive and is presented using tables, figures, and thematic narrative synthesis., Results: We conducted a screening of 3008 articles, of which 175 were selected for the full review. Of these articles, we selected 106 that met the inclusion criteria. These articles were published between 1991 and 2021, and in the last 5 years, up to 38 articles were reported. Most of the studies were conducted in Brazil (26%), Spain (14%), India (12%), Bangladesh (10%), and Ethiopia (7%). Of the studies, 84.9% were conducted in the immunocompetent population, while 15.1% were conducted in the immunosuppressed population (HIV, immunosuppressive drugs, and organ transplantation population). We report 14 different techniques and 10 strategies employed by researchers to define asymptomatic Leishmania infection in an endemic area., Conclusions: The definition of asymptomatic Leishmania infection is not unified across the literature, but often includes the following criteria: residence (or extended stay) in a Leishmania-endemic area, no reported signs/symptoms compatible with leishmaniasis, and positive on a combination of serological, molecular, cellular, and/or parasitological tests. Caution is recommended when comparing results of different studies on the subject of asymptomatic infections, as the reported prevalence cannot be confidently compared between areas due to the wide variety of tests employed by research groups. More research on the importance of asymptomatic immunosuppressed and immunocompetent Leishmania-positive populations in leishmaniasis epidemiology is required., (© 2021. The Author(s).)

Background: Nigeria has low antiretroviral therapy (ART) coverage among HIV-positive pregnant women. In a previous cluster-randomized trial in Nigeria, Baby Shower events resulted in higher HIV testing coverage and linkage of pregnant women to ART; here, we assess outcomes of Baby Shower events in a non-research setting., Methods: Baby Shower events, including a prayer ceremony, group education, music, gifting of a "mama pack" with safe delivery supplies, and HIV testing with ART linkage support for HIV-positive pregnant women, were conducted in eighty sites in Benue State, Nigeria. Client questionnaires (including demographics, ANC attendance, and HIV testing history), HIV test results, and reported linkage to ART were analyzed. Descriptive data on HIV testing and ART linkage data for facility-based care at ANC clinics in Benue State were also analyzed for comparison., Results: Between July 2016 and October 2017, 10,056 pregnant women and 6,187 male partners participated in Baby Shower events; 61.5% of women attended with a male partner. Nearly half of female participants (n = 4515, 44.9%) were not enrolled in ANC for the current pregnancy, and 22.3% (n = 2,241) of female and 24.8% (n = 1,532) of male participants reported they had never been tested for HIV. Over 99% (n = 16,240) of participants had their HIV status ascertained, with 7.2% of females (n = 724) and 4.0% of males (n = 249) testing HIV-positive, and 2.9% of females (n = 274) and 2.3% of males (n = 138) receiving new HIV-positive diagnoses. The majority of HIV-positive pregnant women (93.0%, 673/724) were linked to ART. By comparison, at health facilities in Benue State during a similar time period, 99.7% of pregnant women had HIV status ascertained, 8.4% had a HIV-positive status, 2.1% were newly diagnosed HIV-positive, and 100% were linked to ART., Conclusion: Community-based programs such as the faith-based Baby Shower intervention complement facility-based approaches and can reach individuals who would not otherwise access facility-based care. Future Baby Showers implementation should incorporate enhanced support for ART linkage and retention to maximize the impact of this intervention on vertical HIV transmission., Competing Interests: No authors have competing interests.

Objective: The declaration of the coronavirus disease (COVID-19), a pandemic in early 2020, has seen an upsurge in research globally to fill gaps in the epidemiology of the SARS-CoV-2 virus impact on health care and clinical management, as well as possible prevention and treatment modalities. Published literature on the different types of COVID-19 research conducted globally is varied and is particularly limited in Africa. This study sets out to describe the COVID-19-related research registered and conducted on the African continent., Methods: This is a cross-sectional study of all COVID-19-related studies available in the WHO's International Clinical Trials Registry Platform (ICTRP) repository. We extracted studies registered from March 1, 2020, to July 15, 2021. A descriptive analysis of the extracted data was performed, and the findings were presented., Results: At extraction, a total of 12,533 COVID-19-related studies were listed on the ICTRP portal. We included 9803 studies, after excluding 2060 duplicate records and 686 records without a site/country. While 9347 studies (96%) were conducted outside of Africa, only 456 studies (4%) were conducted in the African continent, of which 270 (59.2%) were interventional studies, and 184 (40.4%) were observational studies. About 80% of the studies were conducted in Egypt and South Africa, and most of these involved testing of drugs and biologicals., Conclusion: The African continent hosts considerably fewer COVID-19-related research compared to other parts of the world. This may have implications on scientific evidence available for implementing COVID-19 control efforts. There is, therefore, a need for local funding and ownership of research projects and north-south collaboration in research., (© 2021. The Author(s).)

Objective: Prospective registration of clinical trials is an ethical, scientific, and legal requirement that serves several functions, including minimising research wastage and publication bias. Sub-Saharan Africa (SSA) is increasingly hosting clinical trials over the past few years, and there is limited literature on trends in clinical trial registration and reporting in SSA. Therefore, we set out to determine the trends in clinical trials registered in SSA countries between 2010 and July 2020., Methods: A cross-sectional study design was used to describe the type of clinical trials that are conducted in SSA from 1 January 2010 to 31 July 2020. The registries searched were ClinicalTrials.gov (CTG), the Pan African Clinical Trials Register (PACTR), and the International Standard Randomized Controlled Trial Number (ISRCTN). Data were extracted into Excel and imported into STATA for descriptive analysis., Results: CTG had the highest number of registered trials at 2622, followed by PACTR with 1501 and ISRCTN with 507 trials. Trials were observed to increase gradually from 2010 and peaked at 2018-2019. Randomised trials were the commonest type, accounting for at least 80% across the three registries. Phase three trials investigating drugs targeted at infections/infestations were the majority. Few completed trials had their results posted: 58% in ISRCTN and 16.5% in CTG, thus suggesting reporting bias., Conclusion: Despite the gradual increase in clinical trials registered during the period, recent trends suggest a drop in the number of trials registered across the region. Strengthening national and regional regulatory capacity will improve clinical trial registration and minimise reporting bias in completed clinical trials., (© 2021. The Author(s).)

Background: An affordable pneumococcal conjugate vaccine (PCV) is needed to ensure sustainable access in low-income and middle-income countries. This trial examined the immunogenicity and safety of a novel ten-valent PCV (SIIPL-PCV) containing serotypes 1, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, and 23F compared with the pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix; GlaxoSmithKline; Brentford, UK)., Methods: In this single-centre, randomised, double-blind, phase 3, non-inferiority trial in The Gambia, healthy, PCV-naive infants aged 6-8 weeks were enrolled and assigned using permuted block randomisation to receive one of three lots of SIIPL-PCV or to PHiD-CV in a ratio of 2:2:2:3. Parents and all staff assessing study outcomes were masked to group assignment. Vaccines (0·5 mL SIIPL-PCV or 0·5 mL PHiD-CV) were administered at ages 6, 10, and 14 weeks by intramuscular injection. Primary immunogenicity outcomes, measured at age 18 weeks, were serotype-specific IgG geometric mean concentrations (GMCs) and seroresponse rates (IgG ≥ 0·35 μg/mL). Lot-to-lot equivalence (objective 1) was shown if the upper and lower bounds of the two-sided 95% CI around the GMC ratio for each pairwise lot-to-lot comparison was between the 0·5 and 2·0 equivalence margins for all ten serotypes. The immunogenicity of SIIPL-PCV was defined as being non-inferior to that of PHiD-CV (objective 2) if, for at least seven of the ten serotypes in SIIPL-PCV, the lower bound of the 97·5% CI for the GMC ratio was greater than 0·5, or the lower bound of the 97·5% CI for differences in seroresponse rate was greater than -10%. The GMC and seroresponse rates to serotypes 6A and 19A, which are not in PHiD-CV, were compared with those of the serotype in PHiD-CV that had the lowest seroresponse rate. Non-inferiority of the immune responses to antigens in the co-administered Expanded Programme on Immunization (EPI) vaccines (objective 3) was declared if the lower bound of the 95% CI for the difference between SIIPL-PCV and PHiD-CV in seroresponse rates, or GMC ratios for pertussis antigens, was greater than -10% (or 0·5 for pertussis antigens) for all vaccine antigens. Safety data were assessed according to treatment received at the first visit in infants who received at least one dose of study vaccine and for whom at least some post-vaccination safety data were available. The primary immunogenicity analysis was in the per-protocol immunogenicity population, which included infants who received all study vaccines and had immunogenicity measurements after vaccination and no major protocol deviations. This trial is registered at ClinicalTrials.gov (NCT03197376)., Findings: Between June 21, 2017, and Jan 29, 2018, 2250 infants were enrolled and randomly assigned to receive SIIPL-PCV (n=1503; 502 to lot 1, 501 to lot 2, and 500 to lot 3) or PHiD-CV (n=747). 1458 (97·0%) infants assigned to SIIPL-PCV and 724 (96·9%) assigned to PHiD-CV were included in the per-protocol primary immunogenicity analysis. Lot-to-lot equivalence was shown, with the lowest lower bound of the 95% CI for the GMC ratio being 0·52 (for serotype 6B in lot 2 vs lot 3) and the highest upper bound being 1·69 (for serotype 6B in lot 1 vs lot 2). SIIPL-PCV was non-inferior to PHiD-CV in terms of immunogenicity: the lower bound of the 97·5% CI for the GMC ratio was greater than 0·5 (the lowest being 0·67 for serotype 19F) and the lower bound of the 97·5% CI for the difference in seroresponse rate was greater than -10% (the lowest being -2·2% for serotype 6B) for all ten serotypes in SIIPL-PCV. The lowest seroresponse rate after PHiD-CV was to serotype 6B (76·7% [95% CI 73·4-79·7]). This serotype was therefore used for the comparisons with serotype 6A and 19A in SIIPL-PCV. Non-inferiority of immune responses to the EPI vaccines after co-administration with SIIPL-PCV compared with after co-administration with PHiD-CV was shown for all vaccine antigens included in the primary series. The lowest lower bound of the 95% CI for the difference in seroresponse rates was -7·1% for rotavirus antibody and for the GMC ratio for pertussis antigens was 0·62 for anti-pertussis toxoid. 1131 (75·2%) of 1503 infants in the SIIPL-PCV group and 572 (76·6%) of 747 in the PHiD-CV group had at least one unsolicited adverse event. 36 (2·4%) participants in the SIIPL-PCV group and 18 (2·4%) in the PHiD-CV group had a serious adverse event; none were considered related to vaccination. In infants who were selected to have solicited adverse events recorded, injection-site induration after primary vaccinations occurred in 27 (4·9%) of 751 infants who received SIIPL-PCV versus 34 (9·4%) of 364 who received PHiD-CV (p=0·0032). There were no other notable differences in the safety profiles of the two vaccines. One infant in the SIIPL-PCV group and two in the PHiD-CV group died during the study. The deaths were not considered to be related to study vaccination or study participation., Interpretation: The immunogenicity of SIIPL-PCV was non-inferior to that of PHiD-CV, for which efficacy and effectiveness data against pneumococcal disease are available. The vaccine is safe and can be co-administered with routine EPI vaccines. The data generated in this trial have supported the licensure and pre-qualification of SIIPL-PCV, making the vaccine available for introduction into national immunisation programmes. Generating post-implementation data confirming vaccine impact remains important., Funding: Bill & Melinda Gates Foundation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background : This study aimed to summarise the evidence on the impact of routine administration of 10-valent and 13-valent pneumococcal conjugate vaccines on pneumonia in children under five years of age in sub-Saharan Africa. Methods: A systematic search of the literature was conducted including primary research reporting on the impact of 10- or 13-valent pneumococcal vaccines on childhood pneumonia in a sub-Saharan African country. Case-control, cohort, pre-post and time-series study designs were eligible for inclusion. Thematic narrative synthesis was carried out to summarise the findings. Results: Eight records were included in the final analysis, 6 records were pre-post or time-series studies, 1 was a case-control study and 1 report combined pre-post and case-control studies. Vaccine impact on clinical pneumonia measured as percentage reduction in risk (%RR) was mostly non-significant. The reduction in risk was more consistent in radiological and pneumococcal pneumonia. Conclusions: Evidence of the positive impact of routine infant pneumococcal vaccination on clinical pneumonia incidence in sub-Saharan Africa is inconclusive. Ongoing surveillance and further research is required to establish the long term trend in pneumonia epidemiology and aetiology after PCV introduction. PROSPERO registration : CRD42019142369 30/09/19., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Onwuchekwa C et al.)

In the African meningitis belt (region from Senegal to Ethiopia), there are around 30,000 reported cases of meningococcal disease per year. The main aetiological agent is Neisseria meningitidis of serogroup A. Since 2010, vaccination efforts have increased and hundreds of millions of people have been vaccinated. There are indications that the epidemiology of meningococcal disease is changing. This is the protocol of a scoping review, the objective of which is to describe the extent and nature of the research evidence about the impact of vaccination on meningitis frequency. Primary studies and reviews are eligible for inclusion in the review if they assess the impact of interventions that include N. meningitidis vaccination in countries of the African meningitis belt, report meningitis frequencies, and include an element of comparison. The sources of records are electronic databases (MEDLINE, Cochrane register of clinical trials, African Index Medicus, and clinicaltrials.gov), surveillance reports at country level, online resources of large stakeholders involved in vaccination, reference lists of included records, and experts in the field. The search strategy is based on the combination of the condition of interest, the intervention, and the geographical region. The findings of this review will be presented using figures, tables, and thematic narrative synthesis. This review will not produce a pooled estimate of what the impact of vaccination is, but will give insight in how the authors of the included records assessed the impact., Competing Interests: Competing interests: Three members of the review team work for the Finlay institute in Cuba, a centre for vaccine research and production. The topic of the review was proposed by staff of the Finlay Institute. Sponsors and institutes played no other role in the development and content of the protocol or the decision to submit., (Copyright: © 2019 Molina N et al.)

Background: Zinc has been reported to mediate cellular responses to injury by producing cytoprotection via the scavenging of reactive oxygen species. Anti-stress medications are generally anti-psychotic drugs and anti- depressants. Some Anti-psychotic drugs such as risperidone have been reported to possess anti-ulcer activity. Risperidone as an antipsychotic drug blocks several neurotransmitter systems including dopaminergic, adrenergic, histaminergic and serotonergic pathways., Method: The study investigated the antiulcer activity of Zinc Chloride (ZnCl(2)) in combination with risperidone in male Wistar rats. The animals were divided into two groups of twenty animals each for ZnCl(2) and risperidone groups. Each group was further divided into four subgroups. ZnCl(2) was administered orally at 20mg/kg, 40mg/kg and 80mg/kg to a subgroup, while 80mg/kg of ZnCl(2) was administered in combination with risperidone (0.1mg/kg, 0.3mg/kg and 0.5mg/kg) orally once daily for 21 days. The controls were treated with distilled water. Ulcer was induced using indomethacin. Histology of the stomach tissues was prepared with PAS and H& E stains. Ulcer score and ulcer area were assessed using standard methods. Data were analysed using student t-test and Graphpad Prism 5., Results: There were decreases in ulcer scores using the different doses of ZnCl, (20mg/kg, 40mg/kg and 80mg/kg). Also using the highest dose ZnCl(2) (80mg/ kg) and different doses of risperidone there were decreases in ulcer scores compared to the control. This effect of the risperidone showed a significant dose- dependent reduction. The effect ZnCl(2), and risperidone were also reflected in the ulcer area and in the histology., Conclusion: These findings suggest that ZnCl(2), enhances the gastroprotective activity ofrisperidone in indomethacin- induced gastric ulcer. However, more detailed studies are necessary to confirm the relevance of this finding and its implications in clinical settings.

Betulinic acid (BA) is a lupane-type triterpene that has been identified and isolated from various plant species used in ethnomedicine in various cultures across the world. This study was undertaken to elucidate the mechanisms underlying the anti-ulcer effect of Betulinic acid. The effect of BA on indomethacin-induced ulcer, gastric mucus secretion, gastric mucus cells count, basal and histamine-induced gastric acid secretion and levels of malondialdehyde formation were studied using dose of 0.5, 1.5, and 3.0 mg/kg. The results showed that BA reduced indomethacin-induced ulceration significantly and significantly increased  gastric mucus secretion in the 1.5 mg/kg and 3.0 mg/kg BA treated rats compared to the control rats. There was a significant increase  in the mucus cells count in all the treated groups which is in a dose- dependent manner compared to the control group. There was significant decrease  in gastric acid secretion in each of the BA treated groups compared to the control. Malondialdehyde concentration significantly decrease in all the treated groups compared to the control. The anti-gastric ulcer effect of BA may be mediated via decreasing gastric acid secretion, increasing gastric mucus secretions, increasing the number of gastric mucus cells and also by reducing the level of MDA concentration.

Calcium channel blockers (CCBs) are widely used as therapeutic agents, for the treatment of cardiovascular disorders. However, the discovery that CCBs bind to various regions of the brain suggest that they might also offer some beneficial effects in the treatment of neuropsychiatry disorders. This study was carried out to evaluate the anti-psychotic and sedative effects of two notable calcium channel blockers, verapamil and nifedipine in mice. The anti-psychotic effects of the CCBs were studied in the animal model of amphetamine-induced stereotyped behavioral disorders. The sedative effect was assessed utilizing the prolongation of the time of sleep, induced by thiopentone. The ability of CCBs to produce catalepsy in mice was also evaluated in the study. Graded doses of verapamil (5.0-20.0 mg/kg, i.p) significantly (p<0.05) suppressed stereotyped behaviour induced by amphetamine (10.0 mg/kg, i.p). In contrast, nifedipine (5.0-20.0 mg/kg, i.p) did not exhibit anti-psychotic effect, as it could not significantly reduce stereotypy caused by amphetamine. In the test for sedation, both verapamil (5.0-20.0 mg/kg, i.p) and nifedipine (10.0-20.0 mg/kg) significantly (p<0.05) prolonged the sleeping time induced by thiopentone (50.0 mg/kg, i.p). However, neither verapamil (5.0-20.0 mg/kg, i.p.) nor nifedipine (5.0-20.0 mg/kg, i.p.) at the tested doses produced any cataleptic behaviour in the animals. The results of the study suggest that verapamil has both anti-psychotic and sedative effects without inducing the side effect of catalepsy and might be relevant in the treatment of psychosis.