In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm

Anderson, Motswedi; Choga, Wonderful T.; Moyo, Sikhulile; Bell, Trevor Graham; Mbangiwa, Tshepiso; Phinius, Bonolo B.; Bhebhe, Lynette; Sebunya, Theresa K.; Makhema, Joseph; Marlink, Richard; Kramvis, Anna; Essex, Max; Musonda, Rosemary; Blackard, Jason T.; Gaseitsiwe, Simani

doi:10.3390/genes9090420

Cited by 8 publications

(6 citation statements)

References 98 publications

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“…It has also been associated with liver fibrosis, cirrhosis and hepatocellular cancers. 33,36 Prevalence of OBI varies from 1% to more than 15% amongst HIV-positive patients in the USA and South Africa. In Botswana, the prevalence of OBI was 26.5% amongst the HIV-positive treatment naïve patients which decreased to 1.5% after initiation of highly active antiretroviral therapy (HAART).…”

Section: Discussionmentioning

confidence: 99%

Seroprevalence and risk factors of hepatitis B, C and D virus infection amongst patients with features of hepatitis in a referral hospital in Botswana: A cross-sectional study

Souda

Mwita

Cainelli³

et al. 2021

Southern African Journal of Infectious Diseases

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Background: Viral hepatitis is a major global health problem. There is a paucity of data from Botswana on the seroprevalence of markers of hepatitis. The objective of the study was to determine the seroprevalence and risk factors of hepatitis B virus (HBV), hepatitis D virus (HDV) and hepatitis C virus (HCV) infections in patients with clinical features of hepatitis and/or altered liver function tests.Method: This cross-sectional study was done at Princess Marina Hospital (PMH) in Gaborone, Botswana, from February 2015 to July 2016. It involved 328 adult patients with any of the following: jaundice, history of liver disease and/or increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum bilirubin of 2 times the upper limit of normal (ULN).Results: Active or chronic active hepatitis (hepatitis B surface antigen [HBsAg] positive) was identified in 46.7% of patients. Antibodies to HDV infection were detected in 4.6% of the HBsAg-positive patients and antibodies to HCV infection in 4.3% of the study patients. Immunity against HBV infection was noted in 34.5% of patients. Human immunodeficiency virus (HIV) co-infection was self-reported by 42.7% of HBsAg-positive patients with known HIV status.Conclusion: High prevalence rate of HBV, HCV, HDV infection and HIV co-infection was observed in patients with liver disease attending PMH.

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Section: Discussionmentioning

confidence: 99%

Seroprevalence and risk factors of hepatitis B, C and D virus infection amongst patients with features of hepatitis in a referral hospital in Botswana: A cross-sectional study

Souda

Mwita

Cainelli³

et al. 2021

Southern African Journal of Infectious Diseases

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“…Overall, the investment that SANTHE received has directly benefited African-based researchers by raising their profile and that of their institutions, and enabling them to directly identify and address problems, set a research agenda, supervise students on these projects on site, promote their careers in the process, and directly impact local and international stakeholders. Crucially, one demonstration of the scientific impact of these efforts is that important discovery and policy impacting research has been performed within a short period of time [ 30 – 32 ].…”

Section: The Sub-saharan African Network For Tb/hiv Research Excellenmentioning

confidence: 99%

African-led health research and capacity building- is it working?

et al. 2020

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Background: Africa bears a disproportionately high burden of globally significant disease but has lagged in knowledge production to address its health challenges. In this contribution, we discuss the challenges and approaches to health research capacity strengthening in sub-Saharan Africa and propose that the recent shift to an African-led approach is the most optimal. Methods and findings: We introduce several capacity building approaches and recent achievements, explore why African-led research on the continent is a potentially paradigm-shifting and innovative approach, and discuss the advantages and challenges thereof. We reflect on the approaches used by the African Academy of Sciences (AAS)funded Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) consortium as an example of an effective African-led science and capacity building programme. We recommend the following as crucial components of future efforts: 1. Directly empowering African-based researchers, 2. Offering quality training and career development opportunities to large numbers of junior African scientists and support staff, and 3. Effective information exchange and collaboration. Furthermore, we argue that long-term investment from international donors and increasing funding commitments from African governments and philanthropies will be needed to realise a critical mass of local capacity and to create and sustain world-class research hubs that will be conducive to address Africa's intractable health challenges. Conclusions: Our experiences so far suggest that African-led research has the potential to overcome the vicious cycle of brain-drain and may ultimately lead to improvement of health and science-led economic transformation of Africa into a prosperous continent.

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“…SNAP2 [ 35 , 36 ], Phyre [ 37 ], and PolyPhen [ 38 ] were used to predict in silico the potential impact (deleterious or neutral) and nature of mutations located within the M pro region of SARS-CoV-2. The algorithm calibration was performed as previously described [ 39 , 40 ]. Subsequently, we validated the results by assessing the accuracy of predictions for known deleterious mutations reported in the literature.…”

Section: Methodsmentioning

confidence: 99%

Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana

Choga,

Bareng,

Moraka

et al. 2024

Open Forum Infectious Diseases

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Background We evaluated naturally occurring nirmatrelvir-ritonavir (NTV/r) resistance-associated mutations (RAMs)among SARS-CoV-2 strains from Botswana, a country with no NTV/r use to date, in order to recommend the usage of the agent for high-risk patients with COVID-19. Methods We conducted a retrospective analysis using 5254 complete SARS-CoV-2 sequences from Botswana (September 2020–September 2023). We evaluated the mutational landscape of the SARS-CoV-2 3-Chymotrypsin-like protease (3CLpro) relative to the highlighted list of RAMs provided by FDA emergency use authorization in 2023. Results The sequenced 5254 samples included Beta VOC (N = 323), Delta VOC (N = 1314), and Omicron VOC (N = 3354). Overall, 77.8% of the sequences exhibited at least one polymorphism within 76/306 amino acid positions in the nsp5 gene. NTV/rRAMs were identified in 34/5254 (0.65%, 95%CI:.43%–.87%), and occurred at five distinct positions. Amongst the NTV/r RAMS detected, A191 V was the most prevalent (24/34; 70.6%). Notably, T21I mutation had a prevalence of 20.6% (7/34) and co-existed with either K90R (n = 3) polymorphism in Beta sequences with RAMs or P132H (n = 3) polymorphism for Omicron sequences with RAMs. Other NTV/r RAMs detected include P108S with prevalence of 5.88% (2/34) and L50F prevalence of 2.94% (1/34).NTV/r RAMs were significantly higher (P < .001) in Delta (24/35) compared to either Beta (4/34) or Omicron (6/34) sequences. Conclusions The frequency of NTV/r RAMs in Botswana was low. Higher rates were observed in Delta VOC variants compared to in Omicron and Beta VOC. As NTV/r use expands globally, continuous surveillance for drug-resistant variants is essential, given the RAMs identified in our study.

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In Silico Analysis of Hepatitis B Virus Occult Associated Mutations in Botswana Using a Novel Algorithm

Cited by 8 publications

References 98 publications

Seroprevalence and risk factors of hepatitis B, C and D virus infection amongst patients with features of hepatitis in a referral hospital in Botswana: A cross-sectional study

Seroprevalence and risk factors of hepatitis B, C and D virus infection amongst patients with features of hepatitis in a referral hospital in Botswana: A cross-sectional study

African-led health research and capacity building- is it working?

Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana

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