Plasmodium falciparum genetic diversity and multiplicity of infection based on msp-1, msp-2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17. RESULTS: The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51-0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of msp-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%, MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For msp-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurp was 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88-2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56-70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%). CONCLUSION: The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.

Contribution of the one health approach to strengthening health security in Uganda: a case study.

BACKGROUND: The One Health approach is key in implementing International Health Regulations (IHR, 2005) and the Global Health Security Agenda (GHSA). Uganda is signatory to the IHR 2005 and in 2017, the country conducted a Joint External Evaluation (JEE) that guided development of the National Action Plan for Health Security (NAPHS) 2019-2023. AIM: This study assessed the contribution of the One Health approach to strengthening health security in Uganda. METHODS: A process evaluation between 25th September and 5th October 2020, using a mixed-methods case study. Participants were Subject Matter Experts (SMEs) from government ministries, departments, agencies and implementing partners. Focus group discussions were conducted for five technical areas (workforce development, real-time surveillance, zoonotic diseases, national laboratory systems and emergency response operations), spanning 18 indicators and 96 activities. Funding and implementation status from the NAPHS launch in August 2019 to October 2020 was assessed with a One Health lens. RESULTS: Full funding was available for 36.5% of activities while 40.6% were partially funded and 22.9% were not funded at all. Majority (65%) of the activities were still in progress, whereas 8.6% were fully implemented and14.2% were not yet done. In workforce development, several multisectoral trainings were conducted including the frontline public health fellowship program, the One Health fellowship and residency program, advanced field epidemiology training program, in-service veterinary trainings and 21 district One Health teams' trainings. Real Time Surveillance was achieved through incorporating animal health events reporting in the electronic integrated disease surveillance and response platform. The national and ten regional veterinary laboratories were assessed for capacity to conduct zoonotic disease diagnostics, two of which were integrated into the national specimen referral and transportation network. Multisectoral planning for emergency response and the actual response to prioritized zoonotic disease outbreaks was done jointly. CONCLUSIONS: This study demonstrates the contribution of 'One Health' implementation in strengthening Uganda's health security. Investment in the funding gaps will reinforce Uganda's health security to achieve the IHR 2005. Future studies could examine the impacts and cost-effectiveness of One Health in curbing prioritized zoonotic disease outbreaks.

COVID-19 and the law in Uganda: a case study on development and application of the public health act from 2020 to 2021.

BACKGROUND: Despite the discovery of vaccines, the control, and prevention of Coronavirus disease 2019 (COVID-19) relied on non-pharmaceutical interventions (NPIs). This article describes the development and application of the Public Health Act to implement NPIs for COVID-19 pandemic control in Uganda. METHODS: This is a case study of Uganda's experience with enacting COVID-19 Rules under the Public Health Act Cap. 281. The study assessed how and what Rules were developed, their influence on the outbreak progress, and litigation. The data sources reviewed were applicable laws and policies, Presidential speeches, Cabinet resolutions, statutory instruments, COVID-19 situation reports, and the registry of court cases that contributed to a triangulated analysis. RESULTS: Uganda applied four COVID-19 broad Rules for the period March 2020 to October 2021. The Minister of Health enacted the Rules, which response teams, enforcement agencies, and the general population followed. The Presidential speeches, their expiry period and progress of the pandemic curve led to amendment of the Rules twenty one (21) times. The Uganda Peoples Defense Forces Act No. 7 of 2005, the Public Finance Management Act No. 3 of 2015, and the National Policy for Disaster Preparedness and Management supplemented the enacted COVID-19 Rules. However, these Rules attracted specific litigation due to perceived infringement on certain human rights provisions. CONCLUSIONS: Countries can enact supportive legislation within the course of an outbreak. The balance of enforcing public health interventions and human rights infringements is an important consideration in future. We recommend public sensitization about legislative provisions and reforms to guide public health responses in future outbreaks or pandemics.

Persistence of chloroquine resistance alleles in malaria endemic countries: a systematic review of burden and risk factors.

BACKGROUND: Chloroquine, a previous highly efficacious, easy to use and affordable anti-malarial agent was withdrawn from malaria endemic regions due to high levels of resistance. This review collated evidence from published-reviewed articles to establish prevalence of Pfcrt 76T and Pfmdr-1 86Y alleles in malaria affected countries following official discontinuation of chloroquine use. METHODS: A review protocol was developed, registered in PROSPERO (#CRD42018083957) and published in a peer-reviewed journal. Article search was done in PubMed, Scopus, Lilacs/Vhl and Embase databases by two experienced librarians (AK, RS) for the period 1990-to-Febuary 2018. Mesh terms and Boolean operators (AND, OR) were used. Data extraction form was designed in Excel spread sheet 2007. Data extraction was done by three reviewers (NL, BB and MO), discrepancies were resolved by discussion. Random effects analysis was done in Open Meta Analyst software. Heterogeneity was established using I2-statistic. RESULTS: A total of 4721 citations were retrieved from article search (Pubmed = 361, Lilac/vhl = 28, Science Direct = 944, Scopus = 3388). Additional targeted search resulted in three (03) eligible articles. After removal of duplicates (n = 523) and screening, 38 articles were included in the final review. Average genotyping success rate was 63.6% (18,343/28,820) for Pfcrt K76T and 93.5% (16,232/17,365) for Pfmdr-1 86Y mutations. Prevalence of Pfcrt 76T was as follows; East Africa 48.9% (2528/5242), Southern Africa 18.6% (373/2163), West Africa 58.3% (3321/6608), Asia 80.2% (1951/2436). Prevalence of Pfmdr-1 86Y was; East Africa 32.4% (1447/5722), Southern Africa 36.1% (544/1640), West Africa 52.2% (1986/4200), Asia 46.4% (1276/2217). Over half, 52.6% (20/38) of included studies reported continued unofficial chloroquine use following policy change. Studies done in Madagascar and Kenya reported re-emergence of chloroquine sensitive parasites (IC50 < 30.9 nM). The average time (years) since discontinuation of chloroquine use to data collection was 8.7 ± 7.4. There was high heterogeneity (I2 > 95%). CONCLUSION: The prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites have steadily declined since discontinuation of chloroquine use. However, Pfcrt K76T and Pfmdr-1 N86Y mutations still persist at moderate frequencies in most malaria affected countries.

Antidepressants for depression in adults with HIV infection.

BACKGROUND: Rates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population. OBJECTIVES: To assess the efficacy of antidepressant therapy for treatment of depression in PLWH. SEARCH METHODS: We searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017. SELECTION CRITERIA: We included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach. MAIN RESULTS: We included 10 studies with 709 participants in this review. Of the 10 studies, eight were conducted in high income countries (USA and Italy), seven were conducted prior to 2000 and seven had predominantly men. Seven studies assessed antidepressants versus placebo, two compared different antidepressant classes and one had three arms comparing two antidepressant classes with placebo.Antidepressant therapy may result in a greater improvement in depression compared to placebo. There was a moderate improvement in depression when assessed with the Hamilton Depression Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to 0.96; participants = 357; studies = 6; I2 = 62%, low quality evidence). However, there was no evidence of improvement when this was assessed with HAM-D score as a dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies = 5; I2 = 0%, low quality evidence) or Clinical Global Impression of Improvement (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I2 = 29%, low quality evidence). There was little to no difference in the proportion of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants = 306; studies = 4; I2 = 0%, moderate quality evidence).The methods of reporting adverse events varied substantially between studies, this resulted in very low quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21; participants = 167; studies = 2; I2 = 34%; very low quality evidence). Based on this, we were unable to determine if there was a difference in the proportion of participants experiencing adverse events in the antidepressant versus placebo arms. However, sexual dysfunction was reported commonly in people receiving selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic antidepressants (TCAs) frequently reported anticholinergic adverse effects such as dry mouth and constipation. There were no reported grade 3 or 4 adverse events in any study group.There was no evidence of a difference in follow-up CD4 count at study termination (MD -6.31 cells/mm3, 95% CI -72.76 to 60.14; participants = 176; studies = 3; I2 = 0%; low quality evidence). Only one study evaluated quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies = 1; very low quality evidence), due to the poor quality evidence we could not draw conclusions for this outcome.There were few studies comparing different antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to 4.47; participants = 14; studies = 1; very low quality evidence). There was some evidence that mirtazapine resulted in a greater improvement in depression compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies = 1; low quality evidence); however, this finding was not consistent for all measures of improvement in depression for this comparison.No studies reported on virological suppression or any other HIV specific outcomes.The studies included in this review had an overall unclear or high risk of bias due to under-reporting of study methods, high risk of attrition bias and inadequate sequence generation methods. Heterogeneity between studies and the limited number of participants, and events lead to downgrading of the quality of the evidence for several outcomes. AUTHORS' CONCLUSIONS: This review demonstrates that antidepressant therapy may be more beneficial than placebo for the treatment of depression in PLWH. The low quality of the evidence contributing to this assessment and the lack of studies representing PLWH from generalized epidemics in low- to middle-income countries make the relevance of these finding in today's context limited. Future studies that evaluate the effectiveness of antidepressant therapy should be designed and conducted rigorously. Such studies should incorporate evaluation of stepped care models and health system strengthening interventions in the study design. In addition, outcomes related to HIV care and antiretroviral therapy should be reported.

A comparision of the yield of three tuberculosis screening modalities among people living with HIV: a retrospective quasi-experiemental study.

BACKGROUND: The Intensified Case Finding (ICF) tool was approved for TB screening in 2011; however there is still paucity of robust data comparing yields of the different ICF screening modalities. We compared yields of three different screening modalities for TB among Patients Living with HIV (PLHIV) in Uganda in order to inform National TB Programs on the most effective TB screening method. METHODS: This was a retrospective quasi-experimental study conducted at an Out-Patient HIV/AIDS clinic in Uganda. We set out to determine yields of three different TB screening modalities at three time periods: 2006/07 where Passive Case Finding (PCF) was used. Here, no screening questions were administered; the clinician depended on the patient's self report. In 2008/09 embedded Intensified Case Finding Tool (e-ICF) was used; here a data capture field was added to the patient clinical encounter forms to compel clinicians to screen for TB symptoms. In 2010/11 Independent Intensified Case Finding Tool (i-ICF) was used; here a screening data collection form, was used, it had the same screening questions as e-ICF. Routine clinical data, including TB status, were collected and entered into an electronic clinical care database. Analysis was done in STATA and the main outcome estimated was the proportional yield of TB cases for each screening modality. RESULTS: The overall yield of TB cases was 11.18 % over the entire period of the study (2006 - 2011). The intervention-specific yields were 1.86 % for PCF, 14.95 % for e-ICF and 12.47 % for i-ICF. Use of either e-ICF (OR: 9.2, 95 % CI: 4.81-17.73) or i- ICF (OR: 7.7, 95 % CI: 4.02-14.78) significantly detected more TB cases compared to PCF (P <0.001). While the yields of the Active Case Finding modalities (e-ICF & i-ICF) were not significantly different (OR: 0.98, 95 % CI 0.76-1.27, P = 0.89). CONCLUSION: The active screening modalities (e-ICF & i-ICF) had a comparable TB yield and were eight to nine times more efficient in identifying TB cases when compared to the PCF. Cost effectiveness studies would be informative.

Chest closure without drainage after open patent ductus arteriosus ligation in Ugandan children: A non blinded randomized controlled trial.

BACKGROUND: There is clinical equipoise regarding post-operative management of patients with patent ductus arteriosus (PDA) without insertion of a chest drain. This study evaluated post operative outcomes of chest closure with or without a drain following Patent Ductus Arteriosus ligation among childen at Uganda Heart Instritute (UHI). METHODS: This was an open label randomized controlled trial of 62 children 12 years of age and below diagnosed with patent ductus arteriosus at Mulago National Teaching and Referral Hospital, Uganda. Participants were randomized in the ratio of 1:1 with surgical ligation of patent ductus arteriosus to either thoracotomy closure with a chest tube or without a chest tube. All participants received standard care and were monitored hourly for 24 hours then until hospital discharge. The combined primary endpoint consisted of significant pleural space accumulation of fluid or air, higher oxygen need or infection of the surgical site. Analysis was conducted by multivariable logistic regression analysis at 5 % significance level. RESULTS: We enrolled 62 participants, 46 (74 %) of whom were females. Their median age was 12 months (IQR: 8-36). Participants in the no-drain arm significantly had less post-operative complications compared to the drain arm (Unadjusted odds ratio [uOR]: 0.21, 95 % CI: 0.06-0.73, p = 0.015). This "protective effect" remained without statistical significance in the multivariable regression model (Adjusted odds ratio [aOR]: 0.07, 95 % CI: 0.00-2.50, p = 0.144). CONCLUSION: Children aged below 6 years with patent ductus arterious can safely and effectively have thoracotomy closure without using a drain in uncomplicated surgical ligation of the PDA. Chest drain was associated with post-operative complications. TRIAL REGISTRATION: The trial was registered in the Pan African Clinical Trials registry on 1st/July/2012, retrospectively registered. Identifier number PACTR201207000395469 .

Household antimicrobial self-medication: a systematic review and meta-analysis of the burden, risk factors and outcomes in developing countries.

BACKGROUND: Antimicrobial self-medication is common in most low and middle income countries (LMICs). However there has been no systematic review on non-prescription antimicrobial use in these settings. This review thus intended to establish the burden, risk factors and effects of antimicrobial self-medication in Low and Middle Income Countries. METHODS: In 2012, we registered a systematic review protocol in PROSPERO (CRD42012002508). We searched PubMed, Medline, Scopus, and Embase databases using the following terms; "self-medication", "non-prescription", 'self-treatment', "antimicrobial", "antimalarial", "antibiotic", "antibacterial" "2002-2012" and combining them using Boolean operators. We performed independent and duplicate screening and abstraction of study administrative data, prevalence, determinants, type of antimicrobial agent, source, disease conditions, inappropriate use, drug adverse events and clinical outcomes of antibiotic self-medication where possible. We performed a Random Effects Meta-analysis. RESULTS: A total of thirty four (34) studies involving 31,340 participants were included in the review. The overall prevalence of antimicrobial self-medication was 38.8 % (95 % CI: 29.5-48.1). Most studies assessed non-prescription use of antibacterial (17/34: 50 %) and antimalarial (5/34: 14.7 %) agents. The common disease symptoms managed were, respiratory (50 %), fever (47 %) and gastrointestinal (45 %). The major sources of antimicrobials included, pharmacies (65.5 %), leftover drugs (50 %) and drug shops (37.5 %). Twelve (12) studies reported inappropriate drug use; not completing dose (6/12) and sharing of medicines (4/12). The main determinants of antimicrobial self-medication include, level of education, age, gender, past successful use, severity of illness and income. Reported negative outcomes of antimicrobial self-medication included, allergies (2/34: 5.9 %), lack of cure (4/34: 11.8 %) and causing death (2/34: 5.9 %). The commonly reported positive outcome was recovery from illness (4/34: 11.8 %). CONCLUSION: The prevalence of antimicrobial self-medication is high and varies in different communities as well as by social determinants of health and is frequently associated with inappropriate drug use.

World Health Organization group 5 drugs for the treatment of drug-resistant tuberculosis: unclear efficacy or untapped potential?

BACKGROUND: Treatment of multidrug-resistant or extensively drug-resistant tuberculosis (DR-tuberculosis) is challenging because commonly used second-line drugs are poorly efficacious and highly toxic. Although World Health Organization group 5 drugs are not recommended for routine use because of unclear activity, some may have untapped potential as more efficacious or better tolerated alternatives. METHODS: We conducted an exhaustive review of in vitro, animal, and clinical studies of group 5 drugs to identify critical research questions that may inform their use in current treatment of DR-tuberculosis and clinical trials of new DR-tuberculosis regimens. RESULTS: Clofazimine may contribute to new short-course DR-tuberculosis regimens. Beta-lactams merit further evaluation-specifically optimization of dose and schedule. Linezolid appears to be effective but is frequently discontinued due to toxicity. Thiacetazone is too toxic to warrant further evaluation. Mycobacterium tuberculosis has intrinsic inducible resistance to clarithromycin. CONCLUSIONS: Clofazimine and beta-lactams may have unrealized potential in the treatment of DR-tuberculosis and warrant further study. Serious toxicities or intrinsic resistance limit the utility of other group 5 drugs. For several group 5 compounds, better understanding of structure-toxicity relationships may lead to better-tolerated analogs.

Prevalence of Oropharyngeal Candidiasis and distribution of Candida species among People Living with Human Immunodeficiency Virus in Africa: a systematic review and meta-analysis.

Background: The incidence of oropharyngeal candidiasis among people living with human immunodeficiency virus in Africa is on the rise. Oropharyngeal candidiasis is mainly caused by C.albicans; however, a shift in the etiology towards non-Candida albicans species is increasing. In addition, there are variations in the epidemiological distribution of Candida species causing oropharyngeal candidiasis among people living with human immunodeficiency virus in Africa. Objective: This review aimed to determine the prevalence of oropharyngeal candidiasis and the distribution of Candida species among people living with human immunodeficiency virus in Africa. Materials and Methods: This systematic review protocol was registered in the base PROSPERO database prior to its conduct (CRD42021254473). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines (PRISMA-P) were followed for this study. The PubMed, Scopus and EMBASE databases were searched to identify published studies published between 1st January 2000 and 8th October 2022. The eligible studies were included in the meta-analysis and analyzed using a random effects model. The risk of bias of the included studies was assessed using the Joanna Briggs Institute quality assessment tool for prevalence studies. Results: The database search yielded 370 titles from PubMed (n=192), EMBASE (n=162) and SCOPUS (n=16). Fourteen studies with a total of 3,863 participants were included in the meta-analysis. The pooled prevalence of oropharyngeal candidiasis was 49.0% (95% CI: 37% - 62%). A total of 2,688 Candida isolates were reported; approximately 76.6% (n=2,060) were C. albicans, and 21.7% (n=582) were non-C. albicans. Among the non-Candida albicans species, C. glabrata was the most common isolate (29.6%), followed by C. tropicalis (27.7%), C. krusei (17.0%), C. parapsilosis (8.1%) and C. dubliniensis (5.2%). Out of 14 studies, 7 (50.0%) had a low risk of bias, 5 (35.7%) had a moderate risk of bias, and 2 (14.3%) had a high risk of bias. Conclusion: Almost half of people living with HIV in Africa have oropharyngeal candidiasis, and C. albicans remains the most frequent cause of oropharyngeal candidiasis.

The diagnostic accuracy of serum and plasma microRNAs in detection of cervical intraepithelial neoplasia and cervical cancer: A systematic review and meta-analysis.

Studies suggest a need for new diagnostic approaches for cervical cancer including microRNA technology. In this review, we assessed the diagnostic accuracy of microRNAs in detecting cervical cancer and Cervical Intraepithelial Neoplasia (CIN). We performed a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis guideline for protocols (PRISMA-P). We searched for all articles in online databases and grey literature from 01st January 2012 to 16th August 2022. We used the quality assessment of diagnostic accuracy studies tool (QUADAS-2) to assess the risk of bias of included studies and then conducted a Random Effects Meta-analysis. We identified 297 articles and eventually extracted data from 24 studies. Serum/plasma concentration miR-205, miR-21, miR-192, and miR-9 showed highest diagnostic accuracy (AUC of 0.750, 0.689, 0.980, and 0.900, respectively) for detecting CIN from healthy controls. MicroRNA panels (miR-21, miR-125b and miR-370) and (miR-9, miR-10a, miR-20a and miR-196a and miR-16-2) had AUC values of 0.897 and 0.886 respectively for detecting CIN from healthy controls. For detection of cervical cancer from healthy controls, the most promising microRNAs were miR-21, miR-205, miR-192 and miR-9 (AUC values of 0.723, 0.960, 1.00, and 0.99 respectively). We report higher diagnostic accuracy of upregulated microRNAs, especially miR-205, miR-9, miR-192, and miR-21. This highlights their potential as stand-alone screening or diagnostic tests, either with others, in a new algorithm, or together with other biomarkers for purposes of detecting cervical lesions. Future studies could standardize quantification methods, and also study microRNAs in higher prevalence populations like in sub-Saharan Africa and South Asia. Our review protocol was registered in PROSPERO (CRD42022313275).

Prevalence and risk factors of gross neurologic deficits in children after severe malaria: a systematic review protocol.

Background: Children exposed to severe malaria may recover with gross neurologic deficits (GND). Several risk factors for GND after cerebral malaria (CM), the deadliest form of severe malaria, have been identified in children. However, there is inconsistency between previously reported and more recent findings. Although CM patients are the most likely group to develop GND, it is not clear if other forms of severe malaria (non-CM) may also contribute to the malaria related GND. The aim of this systematic review is to synthesize evidence on the prevalence and risk factors for GND in children following CM and map the changes in patterns over time. In addition, this review will synthesize evidence on the reported prevalence and risk factors of gross neurologic deficits following other forms of severe malaria. Methods: The systematic review will be conducted according to recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P). Relevant research articles will be identified using relevant search terms from the following databases: MEDLINE, Embase, Web of Science and Global Index Medicus (GIM). The articles will be screened at title and abstract, then at full text for inclusion using a priori eligibility criteria. Data extraction will be done using a tool developed and optimized in Excel spreadsheet. Risk of bias assessment will be done using appropriate tools including ROBINS-E ('Risk Of Bias In Non-randomized Studies of Exposure') tool, while publication bias will be assessed using funnel plot. A random-effects meta-analysis and structured narrative synthesis of the outcomes will be performed and results presented. Discussion: Findings from this systematic review will inform policy makers on planning, design and implementation of interventions targeting the treatment and rehabilitation of GND following severe malaria in children. Systematic review registration: The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42022297109.

Sensitivity and specificity of clinician administered screening instruments in detecting depression among HIV-positive individuals in Uganda.

Depressive disorders are highly prevalent in Africa where diseases such as HIV/AIDS are common. The aim of this study was to assess the validity of commonly used depression screening instruments in a setting characterized by low literacy, where patients may not be able to self-administer depression scales. We explored the validity of the Patient Health Questionaire-9 (PHQ-9), Centre for Epidemiological Surveys for Depression (CES-D), and the Kessler-10 (K-10), using the Mini International Neuropsychiatric Instrument (MINI) as a gold standard in 368 persons living with HIV/AIDS (PLWHA) in Uganda. The shorter versions of the K-10 and PHQ-9 were extracted to assess their performance in comparison to the longer versions. We used STATA 11.2 to analyze the data. The prevalence of a MINI defined depression in this patient sample was 17.4%. The three instruments all performed well, with areas under the curve (AUC) ranging from 0.82 to 0.96. The PHQ-9 showed the best performance characteristics with an AUC of 0.96, a sensitivity of 91.6%, and specificity 81.2%. The extracted versions performed more modestly. All three instruments showed good properties as screening tools; the PHQ-9 has particularly high sensitivity and specificity, and so can be considered useful for screening HIV-positive patients for depression.

Efficacy of antimalarial herbal medicines used by communities in malaria affected regions globally: a protocol for systematic review and evidence and gap map.

INTRODUCTION: With the rising resistance to artemisinin-based combination treatments, there is a need to hasten the discovery and development of newer antimalarial agents. Herbal medicines are key for the development of novel drugs. Currently, herbal medicine usage in communities for treatment of malaria symptoms is common as an alternative to conventional (modern) antimalarial agents. However, the efficacy and safety of most of the herbal medicines has not yet been established. Therefore, this systematic review and evidence gap map (EGM) is intended to collate and map the available evidence, identify the gaps and synthesise the efficacy of herbal antimalarial medicines used in malaria affected regions globally. METHODS AND ANALYSIS: The systematic review and EGM will be done following PRISMA and Campbell Collaboration guidelines respectively. This protocol has been registered in PROSPERO. Data sources will include PubMed, MEDLINE Ovid, EMBASE, Web of Science, Google Scholar and grey literature search. Data extraction will be done in duplicate using a data extraction tool tailored in Microsoft Office excel for herbal antimalarials discovery research questions following the PICOST framework. The Risk of Bias and overall quality of evidence will be assessed using Cochrane risk of bias tool (clinical trials), QUIN tool (in vitro studies), Newcastle-Ottawa tool (observational studies) and SYRCLE's risk of bias tool for animal studies (in vivo studies). Data analysis will be done using both structured narrative and quantitative synthesis. The primary review outcomes will be clinically important efficacy and adverse drug reactions. Laboratory parameters will include Inhibitory Concentration killing 50% of parasites, IC50; Ring Stage Assay, RSA0-3 hou; Trophozoite Survival Assay, TSA50. ETHICS AND DISSEMINATION: The review protocol was approved by the School of Biomedical Science Research Ethics Committee, Makerere University College of Health Sciences (SBS-2022-213). PROSPERO REGISTRATION NUMBER: CRD42022367073.

The diagnostic accuracy of serum microRNAs in detection of cervical cancer: a systematic review protocol.

BACKGROUND: Cervical cancer remains a public health problem worldwide, especially in sub-Saharan Africa. There are challenges in timely screening and diagnosis for early detection and intervention. Therefore, studies on cervical cancer and cervical intraepithelial neoplasia suggest the need for new diagnostic approaches including microRNA technology. Plasma/serum levels of microRNAs are elevated or reduced compared to the normal state and their diagnostic accuracy for detection of cervical neoplasms has not been rigorously assessed more so in low-resource settings such as Uganda. The aim of this systematic review was therefore to assess the diagnostic accuracy of serum microRNAs in detecting cervical cancer. METHODS: We will perform a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. We will search for all articles in MEDLINE/PubMed, Web of Science, Embase, and CINAHL, as well as grey literature from 2012 to 2022. Our outcomes will be sensitivity, specificity, negative predictive values, positive predictive values or area under the curve (Nagamitsu et al, Mol Clin Oncol 5:189-94, 2016) for each microRNA or microRNA panel. We will use the quality assessment of diagnostic accuracy studies (Whiting et al, Ann Intern Med 155:529-36, 2011) tool to assess the risk of bias of included studies. Our results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy studies (PRISMA-DTA). We will summarise studies in a flow chart and then describe them using a structured narrative synthesis. If possible, we shall use the Lehmann model bivariate approach for the meta analysis USE OF THE REVIEW RESULTS: This systematic review will provide information on the relevance of microRNAs in cervical cancer. This information will help policy makers, planners and researchers in determining which particular microRNAs could be employed to screen or diagnose cancer of the cervix. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered in PROSPERO under registration number CRD42022313275.

Efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models: a systematic review protocol.

BACKGROUND: Wounds inflict pain and affect human health causing high expenditure on treatment and management. Herbal crude extracts are used in traditional medicine as a treatment for wounds and other illnesses. However, the progress in the use of plants has been deterred due to their poor solubility and poor bioavailability requiring administration at high doses. It has been established that nanoencapsulation of herbal products in nanocarriers (size 1 nm to 100 nm) such as nanofibers, nanoparticles, nanospheres, and nanoliposomes greatly improves their efficacy. Due to their small and large surface area, nanocarriers are more biologically active, improve bioavailability, protect the drug from deterioration, and release it to the targeted site in a sustainable manner. AIM: The review aims to collate and appraise evidence on the efficacy of nano encapsulated herbal extracts in the treatment of induced wounds in animal models. METHODS: The review will be protocol-driven and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISMA-P) and protocol guidelines for systematic review and meta-analysis for animal intervention studies. The final review will be conducted and reported with reference to PRISMA 2020 statement. Studies will be searched in Pub Med, ProQuest, Web of Science, Medline Ovid, EMBASE, and Google Scholar. The PRISMA flow criteria will be followed in screening the articles for inclusion. Data extraction form will be designed in Excel spreadsheet 2013 and data extracted based on the primary and secondary outcomes. Risk of bias assessment will be done using SYRCLE's risk of bias tool for animal studies. Data analysis will be done using narrative and quantitative synthesis. EXPECTED RESULTS: We hope to make meaningful comparisons between the effectiveness of the herb-loaded nanomaterials and other interventions (controls) in the selected studies, based on the primary and secondary outcome measures. We expect that these findings to inform clinical practice on whether preclinical studies show enough quality evidence on the efficacy and safety of herbal-loaded nanomaterials that can be translated into clinical trials and further research. SYSTEMIC REVIEW REGISTRATION: PROSPERO 330330. The protocol was submitted on the 11th of May 2022.

Protocol for scoping review to identify and characterise surgery, obstetric, trauma and anaesthesia care in Ugandan health policy databases.

INTRODUCTION: Diseases addressed by surgical, obstetric, trauma and anaesthesia (SOTA) care are rising globally due to an anticipated rise in the burden of non-communicable diseases and road traffic accidents. Low- and middle-income countries (LMICs) disproportionately bear the brunt. Evidence-based policies and political commitment are required to reverse this trend. The Lancet Commission of Global Surgery proposed National Surgical and Obstetric and Anaesthesia Plans (NSOAPs) to alleviate the respective SOTA burdens in LMICs. NSOAPs success leverages comprehensive stakeholder engagement and appropriate health policy analyses and recommendations. As Uganda embarks on its NSOAP development, policy prioritisation in Uganda remains unexplored. We, therefore, seek to determine the priority given to SOTA care in Uganda's healthcare policy and systems-relevant documents. METHODS AND ANALYSIS: We will conduct a scoping review of SOTA health policy and system-relevant documents produced between 2000 and 2022 using the Arksey and O'Malley methodological framework and additional guidance from the Joanna Briggs Institute Reviewer's manual. These documents will be sought from the websites of SOTA stakeholders by hand searching. We shall also search from Google Scholar and PubMed using well-defined search strategies. The Knowledge Management Portal for the Ugandan Ministry of Health, which was created to provide evidence-based decision-making data, is the primary source. The rest of the sources will include the following: other repositories like websites of relevant government institutions, international and national non-governmental organisations, professional associations and councils, and religious and medical bureaus. Data retrieved from the eligible policy and decision-making documents will include the year of publication, the global surgery specialty mentioned, the NSOAP surgical system domain, the national priority area involved and funding. The data will be collected in a preformed extraction sheet. Two independent reviewers will screen the collected data, and results will be presented as counts and their respective proportions. The findings will be reported narratively using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. ETHICS AND DISSEMINATION: This study will generate evidence-based information on the state of SOTA care in Uganda's health policy, which will inform NSOAP development in this nation. The review's findings will be presented to the Ministry of Health planning task force. The study will also be disseminated through a peer-reviewed publication; oral and poster presentations at local, regional, national and international conferences and over social media.

Data sharing practices in collaborative human genomic research in low- and middle-income countries: A systematic review protocol.

INTRODUCTION: The practice of creating large databases has become increasingly common by combining research participants' data into larger repositories. Funders now require that data sharing be considered in newly funded research project, unless there are justifiable reasons not to do so. Access to genomic data brings along a host of ethical concerns as well as fairness and equity in the conduct of collaborative research between researchers from high- income and low-and middle-income countries. MATERIALS AND METHODS: This systematic review protocol will be developed in line with PRISMA -guidelines which refers to Open Science Framework, registered in PROSPERO (https://www.crd.york.ac.uk/prospero/) record CRD42022297984 and published in a peer reviewed journal. Data sources will include PubMed, google scholar, EMBASE, Web of science and MEDLINE. Both published and grey literature will be searched. Subject matter experts including bioethicists, principal investigators of genomic research projects and research administrators will be contacted. After de-duplication, titles and abstracts will be screened for eligibility. Data extraction will be undertaken using a piloted form designed in EPPI-Reviewer software before conducting risk of bias assessments by a pair of reviewers, acting independently. Any discrepancies will be resolved by consensus. Analysis will be done using a structured narrative synthesis and where feasible metanalysis. This review will attempt to highlight the context of data sharing practices in the global North-South and South-South collaborative human genomic research in low- and middle-income countries. This review will enhance the body of evidence on ethical, legal and social implications of data sharing in international collaborative genomic research setting criteria for data sharing. The full report will be shared with relevant stakeholders including universities, civil society, funders, and departments of genomic research to ensure an adequate reach in low-and middle-income countries (LMICs).

A scoping review establishes need for consensus guidance on reporting health equity in observational studies.

OBJECTIVES: To evaluate the support from the available guidance on reporting of health equity in research for our candidate items and to identify additional items for the Strengthening Reporting of Observational studies in Epidemiology-Equity extension. STUDY DESIGN AND SETTING: We conducted a scoping review by searching Embase, MEDLINE, CINAHL, Cochrane Methodology Register, LILACS, and Caribbean Center on Health Sciences Information up to January 2022. We also searched reference lists and gray literature for additional resources. We included guidance and assessments (hereafter termed "resources") related to conduct and/or reporting for any type of health research with or about people experiencing health inequity. RESULTS: We included 34 resources, which supported one or more candidate items or contributed to new items about health equity reporting in observational research. Each candidate item was supported by a median of six (range: 1-15) resources. In addition, 12 resources suggested 13 new items, such as "report the background of investigators". CONCLUSION: Existing resources for reporting health equity in observational studies aligned with our interim checklist of candidate items. We also identified additional items that will be considered in the development of a consensus-based and evidence-based guideline for reporting health equity in observational studies.

Comparing the accuracy of brief versus long depression screening instruments which have been validated in low and middle income countries: a systematic review.

BACKGROUND: Given the high prevalence of depression in primary health care (PHC), the use of screening instruments has been recommended. Both brief and long depression screening instruments have been validated in low and middle income countries (LMIC), including within HIV care settings. However, it remains unknown whether the brief instruments validated in LMIC are as accurate as the long ones. METHODS: We conducted a search of PUBMED, the COCHRANE library, AIDSLINE, and PSYCH-Info from their inception up to July 2011, for studies that validated depression screening instruments in LMIC. Data were extracted into tables and analyzed using RevMan 5.0 and STATA 11.2 for the presence of heterogeneity. RESULTS: Nineteen studies met our inclusion criteria. The reported prevalence of depression in LMIC ranged from 11.1 to 53%. The area under curve (AUC) scores of the validated instruments ranged from 0.69-0.99. Brief as well as long screening instruments showed acceptable accuracy (AUC≥0.7). Five of the 19 instruments were validated within HIV settings. There was statistically significant heterogeneity between the studies, and hence a meta-analysis could not be conducted to completion. Heterogeneity chi-squared = 189.23 (d.f. = 18) p<.001. CONCLUSION: Brief depression screening instruments in both general and HIV-PHC are as accurate as the long ones. Brief scales may have an edge over the longer instruments since they can be administered in a much shorter time. However, because the ultra brief scales do not include the whole spectrum of depression symptoms including suicide, their use should be followed by a detailed diagnostic interview.