HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: a systematic review and meta-analysis protocol

Background: Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial. This review aims at summarizing current knowledge on HIV-1 Gag gene mutations that are selected under PI/r pressure and their distribution according to viral subtypes. Materials and methods: Randomized and non-randomized trials, cohort and cross-sectional studies evaluating HIV-1 Gag gene mutations and protease resistance associated mutations, will all be included. Searches will be conducted (from January 2000 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. Genotypic profiles of both Gag gene and the protease region as well as viral subtypes (especially B vs. non B) will all serve as comparators. Primary outcomes will be the "prevalence of Gag mutations" and the "prevalence of PI/r resistance associated mutations". Secondary outcomes will be the "rate of treatment failure" and the distribution of Gag mutations according to subtypes. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. This study will be reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses. Discussion: This systematic review will help identify HIV-1 Gag gene mutations associated to PI/r-based regimen according to viral subtypes. Findings of this review will help to better understand the implications of the Gag gene mutations in PI/r treatment failure. This may later justify considerations of Gag-genotyping within HIV drug resistance interpretation algorithms in the clinical management of patients receiving PI/r regimens. Systematic review registration: PROSPERO: CRD42019114851

HIV-1 integrase resistance associated mutations and the use of dolutegravir in Sub-Saharan Africa: a systematic review and meta-analysis protocol

Background: Sub-Saharan Africa carries the greatest burden of HIV-infection with increasing drug resistance burden, which requires improved patient management and monitoring. Current WHO recommendations suggest transitioning to dolutegravir-based (adults) or raltegravir-based-regimens (neonates) for initial antiretroviral therapy (ART) and as a suitable alternative in cases of multi-resistance in resource-limited settings. This review aims at synthesizing the current knowledge on dolutegravir use and integrase resistance-associated mutations found before the wide use of dolutegravir-based regimens. Methods: This systematic review will include randomized and non-randomized trials, cohort, and cross-sectional studies published on dolutegravir use or integrase resistance-associated mutations in Sub-Saharan Africa. Searches will be conducted (from 2007 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. We will include studies of adults and/or children exposed to integrase inhibitors-based therapies; especially dolutegravir or raltegravir (which is our intervention of interest as compared to other antiretroviral regimens). We will exclude studies of patients with specific co-morbidities such as tuberculosis or opportunistic infections. Primary outcomes will be "the rate of viral suppression" and "the level of drug resistance" on integrase inhibitor-based regimens among patients in Sub-Saharan Africa. Secondary outcomes will be "the effect of baseline viremia on viral suppression," "the effect of treatment duration on viral suppression," "the proportion of patients with immune recovery," "the rate of non-adherence," "rate of adverse events;" "drug resistance according to different integrase inhibitor-based regimens," and "drug resistance according to viral subtypes/recombinants." Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., age, sex, baseline viremia, CD4 following treatment, treatment duration, and adherence level). Discussion: This review will help to strengthen evidence on the effectiveness of integrase strand transfer inhibitors by contributing to current knowledge on the use of dolutegravir and/or raltegravir (especially for neonates) in Sub-Saharan Africa. Results will therefore help in setting-up baseline data for an optimal management of people living with HIV as Sub-Saharan African countries are transitioning to dolutegravir-based regimens. Evidence will also support HIV/AIDS programs in identifying gaps and actions to be undertaken for improved long-term care and treatment of people living with HIV in Sub-Saharan Africa. Systematic review registration: PROSPERO CRD42019122424

Reporting quality of systematic reviews of interventions aimed at improving vaccination coverage: compliance with PRISMA guidelines

Systematic reviews have become increasingly important for informing clinical practice and policy; however, little is known about the reporting characteristics and quality of SRs of interventions to improve immunization coverage in different settings. The aim of this study was to assess the reporting quality of systematic reviews of interventions aimed at improving vaccination coverage using the recommended Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. PubMed and Cochrane Library were searched to identify SRs of interventions to improve immunization coverage, indexed up to May 2016. Two authors independently screened the search output, assessed study eligibility, and extracted data from eligible SRs using a 27-item data collection form derived from PRISMA. Discrepancies in reviews assessments were resolved by discussion and consensus. A total of 57 reviews were included in this study with a mean percentage of applicable PRISMA items that were met across all studies of 66% (range 19–100%) and median compliance of 70%. 39 out of the 57 reviews were published after the release of the PRISMA statement in 2009. Highest compliance was observed in items related to the “description of rational”, “description of eligibility criteria”, “synthesis of results” and “provision of a general interpretation of the results” (items #3, #6, #14 and #26, respectively). Compliance was poorest in the items “describing summary of evidence” (item 24, 19%), “describing indication of review protocol and registration” (item 5, 26%) and “describing results of risk of bias across studies (item 22, 33%). The overall reporting quality of systematic reviews of interventions to improve vaccination coverage requires significant improvement. There remains a need for additional research targeted at addressing potential barriers to compliance and strategies to improve compliance with PRISMA guideline

Assessing the methodological quality of systematic reviews of interventions aimed at improving vaccination coverage using AMSTAR and ROBIS checklists

Introduction: Systematic reviews (SRs) are the backbone of evidence-based health care, but no gold standard exists to assess their methodological quality. Although the AMSTAR tool is accepted for analyzing the quality of SRs, the ROBIS instrument was recently developed. This study compared the capacity of both instruments to capture the quality of SRs of interventions for improving vaccination coverage. Methods: We conducted a comprehensive literature search in the Cochrane Library and PubMed. Two reviewers independently screened the search output, assessed study eligibility, and extracted data from eligible SRs; resolving differences through consensus. We conducted Principal Component Analysis (PCA) in Stata 14 to determine similarities and differences between AMSTAR and ROBIS. Results: A total of 2322 records were identified through the search and 75 full-text publications were assessed for eligibility, of which 57 met inclusion criteria. Using AMSTAR, we found 32%, 60% and 9% of SRs to have high, moderate and low quality, respectively. With ROBIS, we judged 74%, 14% and 12% of SRs to have low, unclear and high risk of bias. PCA showed that SRs with low risk of bias in ROBIS clustered together with SRs having high-quality in AMSTAR, and SRs with high risk of bias in ROBIS clustered with low-quality SRs in AMSTAR. Conclusions: Our findings suggest that there is an association between methodological quality and risk of bias in SRs of interventions focused on improving vaccination coverage. Therefore, either AMSTAR or ROBIS checklists can be used to evaluate methodological quality of SRs in vaccinology

A systematic review and meta-analysis of the effects of educating parents on the benefits and schedules of childhood vaccinations in low and middle-income countries

Public health benefits of childhood vaccinations risk being derailed by low vaccination coverage in low and middle-income countries. One reason for the low coverage is poor parental knowledge of the importance of completing vaccination schedules. We therefore assessed the effects on childhood vaccination coverage, of educating parents and other persons assuming the parental role. We prospectively registered the systematic review, published the protocol, and used standard Cochrane methods to collect and synthesise the evidence. We found six eligible randomised trials with 4248 participants. Three trials assessed health-facility based education of mothers on the importance of completing vaccination schedules; immediately after birth and three months later (one study) or during the first vaccination visit (two studies). The other trials assessed community-based education, including information campaigns on the importance of vaccines using audiotaped presentations and leaflet distributions (one study); structured group discussions on benefits and costs of childhood vaccination and local action plans for improving vaccine uptake (one study); and home-based information sessions using graphic cards showing benefits and costs of childhood vaccinations and location of vaccination centres (one study). Combining the data shows that these interventions lead to substantial improvements in childhood vaccination coverage (relative increase 36%, 95% confidence interval 14% to 62%). There was no difference between the effects of community-based and facility-based education. Therefore, education in communities and health facilities on the importance of childhood vaccinations should be integrated into all vaccination programmes in low and middle-income countries; accompanied by robust monitoring of impacts and use of data for action

Epidemiology of rubella infection in Cameroon : a 7-year experience of measles and rubella case-based surveillance, 2008–2014

CITATION: Nimpa Mengouo, M. et al. 2017. Epidemiology of rubella infection in Cameroon: a 7-year experience of measles and rubella case-based surveillance, 2008–2014. BMJ Open, 7(4):e012959. doi:10.1136/bmjopen-2016-012959.The original publication is available at https://bmjopen.bmj.com/Objective The aim of this study was to estimate the proportion of rubella disease in a measles case-based surveillance in Cameroon prior to rubella vaccine introduction into the national immunisation programme. Design This was a cross-sectional study for rubella infection in Cameroon for the period 2008 to 2014. Setting Patients suspected with measles from the 10 regions of Cameroon were recruited according to the WHO measles case definition and were tested for rubella IgM antibodies accompanied with the case report/investigation forms. Participants All persons with rash and fever within 14 days of onset of rash according to the standard WHO African Regional Office (WHO/AFRO) case definition for a suspected measles case. Outcome measures Descriptive analyses and simple logistic regressions were performed. OR were estimated. Results A total of 9907 serum samples from people with fever and rash were received in the laboratory from 2008 to 2014. A total of 7489 (75.59%) measles-negative samples were tested for rubella; 699 (9.3%) were positive for rubella IgM antibodies. Logistic regression analysis was done using IgM antibodies detection as the outcome variable. Age, sex and setting were explanatory variables. Logistic regression analysis revealed that, comparing the proportion of rubella IgM seropositivity status by age, the association to a positive rubella IgM increased with age from 1 to 4 years (OR 7.11; 95% CI 4.35 to 12.41; p<0.0001), through 5 to 9 years (OR 13.07; 95% CI 7.93 to 22.93; p<0.001), to 10 to 14 years of age (OR 13.86; 95% CI 8.06 to 25.12; p<0.001). Persons aged ≥15 years were also more likely to have rubella infection than children under one (OR 3.69; 95% CI 1.85 to 7.48; p=0.0001). There were also significant associations with sex, with males being less associated to a positive rubella serology than females (OR 1.33; 95% CI 1.14 to 1.56; p=0.0001). No statistically significant difference in proportion of rubella cases was observed between urban and rural populations (OR 1.11; 95% CI 0.94 to 1.31; p=0.208). Conclusions This study reveals that rubella virus circulates in Cameroon, with important number of cases in children under 15 years. This finding supports the planned introduction of rubella-containing vaccines into the Expanded Program on Immunization.publishers versio

Seroprevalence of rubella virus antibodies among pregnant women in the Center and South-West regions of Cameroon.

Rubella infection in early pregnancy can lead to miscarriages, fetal death, or birth of an infant with congenital rubella syndrome (CRS). In Cameroon, like in many developing countries, rubella surveillance is not well-established. The aim of this study was to determine the prevalence of rubella virus specific antibodies among pregnant Cameroonians. We conducted a cross-sectional study for rubella infection among pregnant women attending antenatal clinics in the Center and South-West regions of Cameroon. Demographic data and blood were collected and tested for rubella specific antibodies (IgG and IgM), and for the IgM positive cases, IgG avidity and real time PCR was done. From December 2015 to July 2017, 522 serum samples were collected and tested from pregnant women. The seroprevalence of rubella specific IgG was 94.4%, presumably due to immunity induced by wild-type rubella virus. The seroprevalence of rubella specific IgM was 5.0%, possibly indicating rubella infection. However, IgG avidity testing of the IgM positive cases detected high avidity IgGs, ranging from 52.37% to 87.70%, indicating past rubella infection. 5.6% (29/522) of the participants had negative results for IgG to rubella virus, indicating susceptibility to rubella infection. None of the participants had received a rubella containing vaccine (RCV), but 51% (266/522) of the pregnant women lived in a house with a child with records of at least one dose of RCV. Rubella virus RNA was not detected in the urine of any IgM positive case. Findings from this study show that rubella infection is significant in Cameroon. Some pregnant women are still susceptible to rubella infection. For a better management of rubella infection in pregnancy in Cameroon, consideration should be taken to investigate for IgG-avidity test in cases with positive rubella IgM result to distinguish between recent from past rubella infection

Data from: DNA of diverse adenoviruses detected in Cameroonian rodent and shrew species

Rodent adenoviruses are important models for human disease. In contrast to the over 70 adenovirus types isolated from humans, few rodent adenoviruses are known, despite the vast diversity of rodent species. PCR and Sanger sequencing were used to investigate adenovirus diversity in wild rodents and shrews in Cameroon. Adenovirus DNA was detected in 13.8% of animals (n=218). All detected sequences differ from known adenovirus types by more than 10% on the amino acid level, thus indicating up to 14 novel adenovirus species. These results highlight the diversity of rodent adenoviruses, their phylogeny, and opportunities for studying alternative adenovirus rodent models