Kaposi Sarcoma-associated Herpesvirus Glycoprotein H is Indispensable for Infection of Epithelial, Endothelial, and Fibroblast Cell Types

Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and is the causative infectious agent of Kaposi sarcoma and two malignancies of B cell origin. To date, there is no licensed KSHV vaccine. Development of an effective vaccine against KSHV continues to be limited by a poor understanding of how the virus initiates acute primary infection in vivo in diverse human cell types. The role of glycoprotein H (gH) in herpesvirus entry mechanisms remains largely unresolved. To characterize the requirement for KSHV gH in the viral life cycle and in determination of cell tropism, we generated and characterized a mutant KSHV in which expression of gH was abrogated. Using a bacterial artificial chromosome containing a complete recombinant KSHV genome and recombinant DNA technology, we inserted stop codons into the gH coding region. We used electron microscopy to reveal that the gH-null mutant virus assembled and exited from cells normally, compared to wild-type virus. Using purified virions, we assessed infectivity of the gH-null mutant in diverse mammalian cell types in vitro Unlike wild-type virus or a gH-containing revertant, the gH-null mutant was unable to infect any of the epithelial, endothelial, or fibroblast cell types tested. However, its ability to infect B cells was equivocal, and remains to be investigated in vivo due to generally poor infectivity in vitro Together, these results suggest that gH is critical for KSHV infection of highly permissive cell types including epithelial, endothelial, and fibroblasts. MPORTANCE: All homologues of herpesvirus gH studied to date have been implicated in playing an essential role in viral infection of diverse permissive cell types. However, the role of gH in the mechanism of KSHV infection remains largely unresolved. In this study, we generated a gH-null mutant KSHV and provided evidence that deficiency of gH expression did not affect viral particle assembly or egress. Using the gH-null mutant, we showed that gH was indispensable for KSHV infection of epithelial, endothelial, and fibroblast cells in vitro. This suggests that gH is an important target for the development of a KSHV prophylactic vaccine to prevent initial viral infection

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Heart failure in sub-Saharan Africa.

The heart failure syndrome has been recognized as a significant contributor to cardiovascular disease burden in sub-Saharan African for many decades. Seminal knowledge regarding heart failure in the region came from case reports and case series of the early 20th century which identified infectious, nutritional and idiopathic causes as the most common. With increasing urbanization, changes in lifestyle habits, and ageing of the population, the spectrum of causes of HF has also expanded resulting in a significant burden of both communicable and non-communicable etiologies. Heart failure in sub-Saharan Africa is notable for the range of etiologies that concurrently exist as well as the healthcare environment marked by limited resources, weak national healthcare systems and a paucity of national level data on disease trends. With the recent publication of the first and largest multinational prospective registry of acute heart failure in sub-Saharan Africa, it is timely to review the state of knowledge to date and describe the myriad forms of heart failure in the region. This review discusses several forms of heart failure that are common in sub-Saharan Africa (e.g., rheumatic heart disease, hypertensive heart disease, pericardial disease, various dilated cardiomyopathies, HIV cardiomyopathy, hypertrophic cardiomyopathy, endomyocardial fibrosis, ischemic heart disease, cor pulmonale) and presents each form with regard to epidemiology, natural history, clinical characteristics, diagnostic considerations and therapies. Areas and approaches to fill the remaining gaps in knowledge are also offered herein highlighting the need for research that is driven by regional disease burden and needs

Primary Causes and Direct Medical Cost of Heart Failure Among Adults Admitted with Acute Decompensated Heart Failure in a Public Tertiary Hospital, Kenya

Background: Heart failure (HF) is a major contributor to cardiovascular morbidity and mortality. Adversely impacting health outcomes in Kenya and other developing countries, data on the direct medical cost of HF hospitalization remain limited. Methods: This was a prospective study conducted at Moi Teaching and Referral Hospital. Patients with HF were identified by sequential medical chart abstraction. Primary causes were extracted from echocardiogram reports and adjudicated by a cardiologist. Direct medical cost of hospitalization was derived using activity-based and micro-costing methods, adopting payers’ system perspective. Drivers of overall cost were explored using linear regression models. Results: 142 participants were consecutively recruited from September to November 2022. 51.4% were females, and the mean age was 54 (SD 20). The leading primary causes were cor pulmonale (CP), 28.9%; dilated cardiomyopathy (DCM), 26.1%; rheumatic heart disease (RHD), 19.7%; hypertensive heart disease (HHD), 16.9%; ischaemic heart disease (IHD), 6.3%; and pericardial disease (PD), 2.1%. Overall direct cost of HF hospitalization was KES 11,470.94 (SD 8,289.57) [USD 93.49 (67.56)] per patient per day, with the mean length of hospital stay of 10.1 (SD 7.1). RHD incurred the highest costs, KES 15,299.08 (SD 13,196.89) [USD 124.70 (107.56)] per patient per day; IHD, KES 12,966.47 (SD 6656.49) [USD 105.68 (54.25)]; and DCM, KES 12,268.08 (SD 7,816.12) [USD 99.99 (63.71)]. The cost of medications was the leading driver, β = 0.56 (0.55 – 0.56), followed by inpatient fees, β = 0.27 (0.27 – 0.28), and laboratory investigations, β = 0.19 (0.18 – 0.19). Conclusion: Cor pulmonale, CM, RHD, and HHD were the major causes of HF. The overall direct medical cost of hospitalization was extremely expensive compared with the Kenyan average monthly household income per capita. Widespread comprehensive health insurance coverage is therefore recommended to cushion families against such catastrophic health expenditures besides public health measures aimed at addressing primary causes of HF

May Measurement Month 2019: an analysis of blood pressure screening results from Kenya

Abstract Elevated blood pressure (BP) is the leading cause of global mortality, but control rates remain poor because most patients, especially in Africa, are unaware. May Measurement Month (MMM) is an annual global BP screening campaign that was initiated by the International Society of Hypertension (ISH) in 2017 to raise awareness of raised BP. Following participation in 2017 and 2018, Kenya participated again in 2019 and the results are reported here. Screening was carried out in 30 sites by volunteers coordinated by the Kenya Cardiac Society. Participants had three BP readings by standard methods with the last two being averaged and recorded. Heart rate, weight, height, socio-demographic parameters, and co-morbidities were documented. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or a diastolic BP (DBP) ≥90 mmHg or being on treatment with at least one antihypertensive medication. A total of 33 992 participants were screened, mean age was 42.5 (SD 16.8) years and 58.7% of participants were female. Only 27.3% had their BPs checked within the preceding 12 months. After multiple imputation, 26.1% were hypertensive, of whom 34.5% were aware of their hypertension and 31.5% were on treatment. Of those on treatment, 59.7% were controlled translating to 18.8% of all hypertensives. Being on treatment for hypertension, overweight, obese or having had hypertension in previous pregnancy were associated with increased SBP and DBP, while diabetes was associated with raised SBP. Two-thirds of hypertensives were unaware. Only a third of those aware were on treatment, with about 60% of these controlled. Lack of awareness remains a significant barrier to BP control. Programmes to raise awareness such as MMM are significant in raising population awareness.</jats:p

Abstract 16597: Outcomes of a Randomized Controlled Trial of Integrated Cardiac Rehabilitation Among Heart Failure Patients in Kenya

Background: Cardiac rehabilitation (CR) is an evidence based, cost effective treatment for heart failure (HF). Globally, access to CR is limited, especially in low- and middle-income countries. An integrated model of institutional and home-based CR has been proposed as a solution to access barriers. However, the efficacy of integrated CR in this region is unknown. We performed a randomized controlled trial of integrated CR compared to usual care (no CR) among patients with stable HF in western Kenya. Methods: Patients with class II or III NYHA symptoms were enrolled from the Moi Teaching and Referral Hospital. Participants with arrhythmias, congenital heart disease, or stenotic valvular heart disease were excluded. Integrated CR comprised of counseling and supervised aerobic exercises 3 times a week for 1 month, followed by 2 months of monitored home-based exercises prescribed weekly via phone. Participants in both arms received health lifestyle education and wore triaxial hip pedometers. The primary outcome, change in 6-minute walk time distance (6MWTD), as well as weekly step counts were compared using the Student’s t-test. Results: Eighty-two participants were randomized (Figure). 6MWTD improved significantly more among the 41 patients receiving CR (45 ± 67m from baseline), compared to the usual care arm (18 ± 49m in, p&lt;0.05), (Table). There was no significant difference in change by age, gender, BMI, ejection fraction or reported HF cause. Conclusions: Integrated CR improves 6MWTD among patients with HF. The findings are limited to a single center. Future studies on long-term outcomes and mechanistic processes responsible for improvement are needed. </jats:p