SARS-CoV-2 has claimed several million lives since its emergence in late 2019. The ongoing evolution of the virus has resulted in the periodic emergence of new viral variants with distinct fitness ...advantages, including enhanced transmission and immune escape. While several SARS-CoV-2 variants of concern trace their origins back to the African continent-including Beta, Eta, and Omicron-most countries in Africa remain under-sampled in global genomic surveillance efforts. In an effort to begin filling these knowledge gaps, we conducted retrospective viral genomic surveillance in Guinea from October 2020 to August 2021. We found that SARS-CoV-2 clades 20A, 20B, and 20C dominated throughout 2020 until the coincident emergence of the Alpha and Eta variants of concern in January 2021. The Alpha variant remained dominant throughout early 2021 until the arrival of the Delta variant in July. Surprisingly, despite the small sample size of our study, we also found the persistence of the early SARS-CoV-2 clade 19B as late as April 2021. Together, these data help fill in our understanding of the SARS-CoV-2 population dynamics in West Africa early in the COVID-19 pandemic.
Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB), is composed of eight subspecies. TB in West Africa, in contrast to other geographical regions, is caused by ...Mycobacterium africanum (MAF) in addition to M. tuberculosis (MTB), with both infections presenting similar symptoms. Nevertheless, MAF is considered to be hypovirulent in comparison with MTB and less likely to progress to active disease. In this study, we asked whether MAF and MTB infected patients possess distinct intestinal microbiomes and characterized how these microbiota communities are affected by anti-tuberculosis therapy (ATT). Additionally, we assessed if the changes in microbiota composition following infection correlate with pathogen induced alterations in host blood-gene expression.
A longitudinal, clinical study of MAF infected, MTB infected patients assessed at diagnosis and two months after start of ATT, and healthy, endemic controls was conducted to compare compositions of the fecal microbiome as determined by 16S rRNA sequencing. A blood transcriptome analysis was also performed on a subset of subjects in each group by microarray and the results cross-compared with the same individual's microbiota composition.
MAF participants have distinct microbiomes compared with MTB patients, displaying decreased diversity and increases in Enterobacteriaceae with respect to healthy participants not observed in the latter patient group. Interestingly, this observed elevation in Enterobacteriaceae positively correlated with enhanced inflammatory gene expression in peripheral blood and was reversed after initiation of ATT.
Our findings indicate that MAF and MTB have distinct associations with the gut microbiome that may be reflective of the differential susceptibility of West Africans to these two co-endemic infections either as biomarkers or as a contributing determinant.
Low and middle income countries (LMICs) bear more than 50% of the current cervical cancer burden over the last decade with linkages to lack of HPV vaccination, high levels of poverty, illiteracy and ...nonexistent or poor screening programs. Governments of LMICs need enough convincing evidence that HPV vaccination will be more cost-effective in reducing the scourge of cervical cancer.
A systematic review to identify suitable studies from MEDLINE(via PubMed), EMBASE and Electronic search through GOOGLE for original and review articles from 2007 to 2014 on cost-effectiveness of human papilloma virus vaccination of pre-adolescent girls in LMICs was conducted. A total of 19 full articles were finally selected and reviewed after screening out those not consistent with the inclusion and exclusion criteria.
Most studies on cost-effectiveness of HPV vaccine in LMICs show that lowering cost of HPV vaccination with or without Pap smear screening is cost-effective in areas with high incidence of cervical cancer.
Xpert MTB/Rif (Xpert) is described as a game changer in tuberculosis (TB) control. We evaluated the impact of Xpert on diagnosis, time to treatment, and treatment outcome among patients with HIV ...associated TB in Nigeria.
Adults with HIV being evaluated for pulmonary TB (PTB) were consecutively enrolled into the study cohort. At baseline, expectorated sputa were examined using Xpert and smear microscopy for Mycobacterium tuberculosis (MTB) and acid fast bacilli, respectively. Patients diagnosed with TB were followed-up until 6 months post TB diagnosis. TB was defined as sputum positive by smear microscopy, Xpert detection of MTB (bacteriologically confirmed case), or clinician diagnosed TB with initiation of full TB treatment (clinical diagnosis). Time to treatment was time from first clinic presentation for TB evaluation to initiation of TB treatment. We examined the proportion PTB patients with a positive Xpert result and compared time to TB treatment and outcome of TB treatment in patients based on sputum test results.
A total of 310 adults with HIV were enrolled. The median CD4 cell count was 242 (interquartile range (IQR) 120-425) cells/mm
and 88.1% were receiving antiretroviral therapy (ART). PTB was diagnosed in 76 (24.5%) patients, with 71 (93.4%) being bacteriologically confirmed. Among patients with PTB, 56 (73.7%) were Xpert positive. Median time to treatment was 5 (IQR 2-8) days and 12 (IQR 5-35) days in patient with and without Xpert positive results, respectively; p = 0.005. Overall 73.1% had symptom free survival at 6 months post PTB treatment initiation with no significant differences observed based on TB test method. 10 (14.9%) died within 6 months of TB treatment initiation. In analysis adjusted for age, sex, and mode of diagnosis (Xpert positive or negative), only ART use independently predicted mortality (AOR 0.10; 95% CI 0.01-0.93).
The use of Xpert for routine care reduced time to PTB treatment, but did not improve survival in patients with HIV treated for susceptible PTB.
The COVID-19 pandemic has placed unprecedented stress on economies, food systems, and health care resources in Latin America and the Caribbean (LAC). Existing surveillance provides a proxy of the ...COVID-19 caseload and mortalities; however, these measures make it difficult to identify the dynamics of the pandemic and places where outbreaks are likely to occur. Moreover, existing surveillance techniques have failed to measure the dynamics of the pandemic.
This study aimed to provide additional surveillance metrics for COVID-19 transmission to track changes in the speed, acceleration, jerk, and persistence in the transmission of the pandemic more accurately than existing metrics.
Through a longitudinal trend analysis, we extracted COVID-19 data over 45 days from public health registries. We used an empirical difference equation to monitor the daily number of cases in the LAC as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. COVID-19 transmission rates were tracked for the LAC between September 30 and October 6, 2020, and between October 7 and 13, 2020.
The LAC saw a reduction in the speed, acceleration, and jerk for the week of October 13, 2020, compared to the week of October 6, 2020, accompanied by reductions in new cases and the 7-day moving average. For the week of October 6, 2020, Belize reported the highest acceleration and jerk, at 1.7 and 1.8, respectively, which is particularly concerning, given its high mortality rate. The Bahamas also had a high acceleration at 1.5. In total, 11 countries had a positive acceleration during the week of October 6, 2020, whereas only 6 countries had a positive acceleration for the week of October 13, 2020. The TAC displayed an overall positive trend, with a speed of 10.40, acceleration of 0.27, and jerk of -0.31, all of which decreased in the subsequent week to 9.04, -0.81, and -0.03, respectively.
Metrics such as new cases, cumulative cases, deaths, and 7-day moving averages provide a static view of the pandemic but fail to identify where and the speed at which SARS-CoV-2 infects new individuals, the rate of acceleration or deceleration of the pandemic, and weekly comparison of the rate of acceleration of the pandemic indicate impending explosive growth or control of the pandemic. Enhanced surveillance will inform policymakers and leaders in the LAC about COVID-19 outbreaks.
Seagrass meadows support complex species assemblages and provide ecosystem services with a multitude of socio-economic benefits. However, they are sensitive to anthropogenic pressures such as coastal ...development, agricultural run-off, and overfishing. The increasing prevalence of marine heatwaves (MHWs) due to climate change poses an additional and growing threat. In this study, we apply the environmental sensitivity mapping approach MESA (Mapping Environmentally Sensitive Assets) to explore the potential consequences of MHWs on the ecosystem services that Posidonia oceanica provides to coastal communities. Under the intermediate climate change scenario Representative Concentration Pathway 4.5, Mediterranean marine heatwaves will be severe by 2050, and will very likely increase mortality of P. oceanica. However, the societal risk of seagrass loss is not evenly distributed across the Mediterranean. The spatial distribution of socio-economic implications of seagrass loss is highlighted through two case studies on seagrass-dependent fisheries and coastal hazards. Coastal communities in Tunisia and Libya show very high sensitivity to a loss of fisheries due to a combination of increasingly intense and frequent MHWs, coupled with high proportions of regional seagrass-dependent fisheries catch. The coastlines of Italy, Tunisia, and Cyprus are shown to potentially be highly sensitive to loss of seagrass due to high levels of coastal hazards, and seagrass meadows susceptible to MHW-induced degradation. These coastlines are likely to suffer from reduced coastal protection services provided by intact seagrass meadows. We demonstrate the implications of MHWs for ecosystem service provision to coastal communities in the Mediterranean and the need for policy instruments to help mitigate and adapt to its effect. We also highlight the potential for environmental sensitivity mapping to help support policymakers with rapid screening tools to prioritize resources more effectively to areas where in-depth local planning is needed.
Display omitted
•Posidonia oceanica provides important ecosystem services for coastal communities.•P. oceanica is affected by magnifying marine heatwaves due to climate change.•MHWs will affect the provision of fishing and coastal protection services.•Areas that heavily rely on these services should prioritize adaptation planning.•Environmental Sensitivity Mapping is used here to prioritize adaptation responses.
COVID-19 transmission rates in South Asia initially were under control when governments implemented health policies aimed at controlling the pandemic such as quarantines, travel bans, and border, ...business, and school closures. Governments have since relaxed public health restrictions, which resulted in significant outbreaks, shifting the global epicenter of COVID-19 to India. Ongoing systematic public health surveillance of the COVID-19 pandemic is needed to inform disease prevention policy to re-establish control over the pandemic within South Asia.
This study aimed to inform public health leaders about the state of the COVID-19 pandemic, how South Asia displays differences within and among countries and other global regions, and where immediate action is needed to control the outbreaks.
We extracted COVID-19 data spanning 62 days from public health registries and calculated traditional and enhanced surveillance metrics. We use an empirical difference equation to measure the daily number of cases in South Asia as a function of the prior number of cases, the level of testing, and weekly shifts in variables with a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R.
Traditional surveillance metrics indicate that South Asian countries have an alarming outbreak, with India leading the region with 310,310 new daily cases in accordance with the 7-day moving average. Enhanced surveillance indicates that while Pakistan and Bangladesh still have a high daily number of new COVID-19 cases (n=4819 and n=3878, respectively), their speed of new infections declined from April 12-25, 2021, from 2.28 to 2.18 and 3.15 to 2.35 daily new infections per 100,000 population, respectively, which suggests that their outbreaks are decreasing and that these countries are headed in the right direction. In contrast, India's speed of new infections per 100,000 population increased by 52% during the same period from 14.79 to 22.49 new cases per day per 100,000 population, which constitutes an increased outbreak.
Relaxation of public health restrictions and the spread of novel variants fueled the second wave of the COVID-19 pandemic in South Asia. Public health surveillance indicates that shifts in policy and the spread of new variants correlate with a drastic expansion in the pandemic, requiring immediate action to mitigate the spread of COVID-19. Surveillance is needed to inform leaders whether policies help control the pandemic.
It is a well-documented fact that world-wide cancer incidence and mortality remains high in Human Immunodeficiency Virus (HIV) infected population despite potent antiretroviral therapy. With the ...current capture of HIV status of cancer patients in our cancer registry at Jos Nigeria, this study aims to assess the effect of HIV on cancer mortality outcomes.
We conducted a 2-year retrospective cohort study of cancer registry data from Jos, north central Nigeria. The cancers were grouped into cervical, breast, liver, hematologic, colonic, AIDS defining, prostate and others in this study. Patients were followed up to determine their patient time contribution from time at initiation of cancer treatment to death or the end of study period. Those lost to follow-up were censored at date of their last known follow-up in clinic.
Out of 930 cancer cases evaluated, 52 (5.6%) were HIV positive, 507 (54.5%) were HIV negative and 371 (39.9%) did not know their HIV status. After 525,223 person- days of follow-up, there were 232 deaths leading to a crude mortality rate of 4.3 per 10,000 person-days. Median survival probability for both HIV-infected and HIV uninfected patients were equal (1,013 days). Unadjusted hazard of death was associated with greater age, HR 0.99 (95% CI: 0.98,0.99,
= 0.002); hepatitis virus, HR 2.40 (95% CI: 1.69,3.43,
= 0.001); liver cancer, HR 2.25 (95% CI:1.11,4.55,
= 0.024); prostate cancer, HR 0.17 (95% CI: 0.06,0.393,
= 0.001). In an adjusted model, only prostate cancer AHR 0.23 (95% CI: 0.12, 0.42,
< 0.001) and liver cancer AHR 2.45 (95% CI: 1.78, 5.51,
< 0.001) remained significantly associated with death regardless of HIV status.
Having liver cancer increases risk for mortality among our cancer patients. Screening, early detection and treatment are therefore key to improving dismal outcomes.
Spinal muscular atrophy (SMA), which results from the loss of expression of the survival of motor neuron-1 (SMN1) gene, represents the most common genetic cause of pediatric mortality. A duplicate ...copy (SMN2) is inefficiently spliced, producing a truncated and unstable protein. We describe herein a potent, orally active, small-molecule enhancer of SMN2 splicing that elevates full-length SMN protein and extends survival in a severe SMA mouse model. We demonstrate that the molecular mechanism of action is via stabilization of the transient double-strand RNA structure formed by the SMN2 pre-mRNA and U1 small nuclear ribonucleic protein (snRNP) complex. The binding affinity of U1 snRNP to the 5' splice site is increased in a sequence-selective manner, discrete from constitutive recognition. This new mechanism demonstrates the feasibility of small molecule-mediated, sequence-selective splice modulation and the potential for leveraging this strategy in other splicing diseases.
PDF
