Research Articles (University of Pretoria)

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Molecular evidence of Brucella abortus circulating in cattle, goats, and humans in Central Equatoria State, South Sudan
(Nature Research, 2025-04) Lita, Emmanuel P.; Mkupasi, Ernatus M.; Ochi, Erneo B.; Misinzo, Gerald; Van Heerden, Henriette; Katani, Robab; Godfroid, Jacques; Mathew, Coletha
Brucellosis is a neglected zoonotic disease in most developing countries, including South Sudan. Precise identification of Brucella species is crucial for addressing public health and epidemiological concerns associated with brucellosis. The study aimed to identify Brucella species using real-time polymerase chain reaction (qPCR) from seropositive samples that were acquired from an earlier investigation. A total of 143 genomic DNA samples were extracted from brucellosis Rose Bengal plate test (RBPT) seropositive samples from humans (n = 7), cattle (n = 103) and goats (n = 33). The samples were collected from Terekeka and Juba counties, Central Equatoria State (CES), South Sudan. The qPCR targeting the Brucella-specific IS711 insertion gene at the genus level was performed. Samples with a cycle threshold (Ct) of ≤ 35 were considered positive and subjected to further Brucella speciation assays. Out of 143 DNA samples tested for genus-specific Brucella, 15 (10.5%) were positive including 4 (2.8%) from humans, 10 (6.9%) from cattle, and 1 (0.7%) from goats. Brucella abortus was identified in 5 (33.3%) of the positive samples at the genus level. The overall individual species infection rates with B. abortus were 6.6% (1/15) in humans, 20% (3/15) in cattle, and 6.6% (1/15) in goats. There was no B. melitensis detected in this study. This study identified B. abortus in cattle, goats and humans in CES, South Sudan. The findings suggest that cattle are probably the primary reservoirs for transmission of B. abortus, with infections occurring in goats and humans primarily resulting from cattle spillover.
Integrated profiling of adiponectin and cytokine signaling pathways in high-fat diet-induced MASLD reveals early markers of disease progression
(Nature Research, 2025-06) Johnson, Rabia; Shabalala, Samukelisiwe; Mabasa, Lawrence; Kotze-Hoerstmann, Liske; Sangweni, Nonhlakanipho; Ramharack, Pritika; Sharma, Jyoti; Pheiffer, Carmen; Arowolo, Afolake; Sadie-Van Gijsen, Hanel
Metabolic dysfunction-associated steatotic liver disease (MASLD), which affects a significant portion of the global population, is linked to high-fat diets (HFD) and characterized by abnormal lipid accumulation and activation of inflammatory pathways in hepatocytes. The precise mechanisms underlying MASLD, especially the involvement of inflammatory cytokines in its pathophysiology, remain unclear. This study evaluated the changes and interactions of steatotic liver and inflammatory markers in an animal model of MASLD by feeding male Wistar rats a high-fat diet (HFD) for 17 weeks. After this period, the serum lipid profiles were assessed, along with liver enzymes, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The changes in liver morphology and triglyceride levels were determined by histology and a colorimetric assay, respectively. Steatotic liver and inflammatory markers were measured using a RT2 ProfilerTMPCRArray and validated with quantitative real-time PCR (qRT-PCR). Histological evaluations indicated that HFD livers exhibited macrovesicular steatosis and lobular inflammation. The HFD-fed group had significantly higher hepatic triglyceride levels than the controls (383 ± 23 mg/dL vs. 100 ± 9 mg/dL) and elevated serum lipid levels (p < 0.0001), along with increased liver aminotransferase levels. Gene expression analysis showed decreased adiponectin signaling (AdipoR2, p < 0.001) and upregulated de novo lipogenesis (Srebf1, p < 0.05). Notably, pro-inflammatory cytokines (Cxcl10, Ccl2, Ilβ, p < 0.001; TNF-α, p < 0.01) were significantly elevated, correlating with reduced hepatic glucose transporter Glut2 expression (p < 0.05), as confirmed by STRING analysis. These findings demonstrate that HFD consumption alters key genes and pathways involved in adiponectin and insulin signalling, lipogenesis, and inflammatory responses, thereby contributing to the pathogenesis of MASLD. Additionally, it identifies a comprehensive chemokine expression profile, highlighting potential therapeutic targets for MASLD.
Insights into the effects of geographical sourcing area on nutrient composition and sensory attributes of nine edible insects
(Nature Research, 2025-05) Ishara, Jackson; Matendo, Rehema; Ng'ang'a, Jeremiah; Niassy, Saliou; Katcho, Karume; Kinyuru, John
With the rapidly growing world population, climate change uncertainties and depletion of our natural resources, edible insects are seen as sustainable and viable bioresources for food and feed to tackle global food and nutritional security issues, for their nutritional value, taste, and environmental sustainability. In this study, we investigated the effect of geographical distribution on the nutrient composition and sensory attributes of commonly consumed edible insects, namely Acheta domesticus, Apis mellifera, Gnathocera trivittata, Gryllotalpa africana, Imbrasia oyemensis, Locusta migratoria, Macrotermes subhylanus, Nomadacris septemfasciata, and Rhyncophorus phoenicis collected from six different geographical areas namely Fizi, Kabare, Kalehe, Idjwi, Mwenge and Walungu, in the Eastern D. R. Congo. Depending on edible insect species, geographical sourcing area affected significantly macronutrient composition and mineral profile as well as sensory attributes of investigated commonly edible insects. A principal component analysis (PCA-Biplot) indicated that the two axes accounted for up to 97.7% of the observed variability in the nutrient composition and sensory attributes of commonly consumed edible insects sourced from different geographical area. Visualized results after cluster analysis using non-metric multidimensional scaling (NMDS) indicated that the geographical sourcing area has substantial and significant effect on the nutrient composition as well as sensory attributes of the studied commonly edible with a stress value of 0.185.
Genomic relatedness of colonizing and invasive disease Klebsiella pneumoniae isolates in South African infants
(Nature Research, 2025-03) Olwagen, Courtney P.; Izu, Alane; Khan, Shama; Van der Merwe, Lara; Dean, Nicholas J.; Mabena, Fikile C.; Jones, Stephanie; Kwatra, Gaurav; Andrew, Lubomira; Rajyaguru, Urvi; Donald, Robert G.K.; Simon, Raphael; Said, Mohamed; Nakwa, Firdose L.; Wadula, Jeannette; Strehlau, Renate; Van Niekerk, Anika M.; Naidoo, Niree; Ramsamy, Yogandree; Velaphi, Sithembiso C.; Dangor, Ziyaad; Madhi, Shabir A.
Klebsiella pneumoniae (KPn) colonizes multiple anatomical sites and is a leading cause of invasive disease and death in African children; however, there is no comparative genomic analysis between colonizing and invasive strains. This study investigated the genomic relatedness of KPn colonizing and invasive isolates in South African infants; and evaluated the relative invasiveness of KPn isolates based on sequence types (ST), capsular (KL), and lipopolysaccharide (O) loci by calculating case-carrier ratios (CCRs). There was less genomic diversity amongst invasive (22 ST, 17 K-loci) than colonizing isolates (31 ST, 29 K-loci), with invasive isolates being 8.59-fold and 3.49-fold more likely to harbour genes encoding for multi-drug resistance and yersiniabactin production compared with colonizing isolates. The CCRs for KL102 and O1/O2v2 were > 1, and < 1 for KL8, ST1414, and O1O2v1. Identifying high-risk strains, including KL102 and O1O2v2, that may have a higher potential to cause invasive disease, could enhance risk assessment and management strategies in vulnerable populations.
Multinational cross-sectional study and meta-analysis on radicular grooves, C-shaped canals, and taurodontism in mandibular first premolars across 20 countries
(Nature Research, 2025-05) Pertek Hatipoglu, Fatma; Magat, Gueldane; Karobari, Mohmed Isaqali; Buchanan, Glynn Dale; Kopbayeva, Maira; Taha, Nessrin; Fernandez-Grisales, Rafael; Bekjanova, Olga; Luu, Peter; Buerklein, Sebastian; Mufadhal, Abdulbaset; Petridis, Xenos; Mora, Maria Fernanda; Sugumaran, Surendar; Allawi, Safaa; Ivica, Anja; Lim, Wen Yi; Fadag, Abdulrahman; Jagtap, Rohan; Kulczyk, Tomasz; Alfirjani, Suha; Palma, Paulo J.; Hatipoglu, Oemer
The success of root canal therapy is fully predicated upon a complete understanding of root and canal morphology and all the anatomical variations that can complicate the endodontic treatment. Of these morphological variations, taurodontism, RGs, and C-shaped canals are of note due to their implications on diagnosis, treatment planning, and endodontic success. This study aimed to investigate the prevalence and regional variations of C-shaped canals, RGs, and taurodontism across 20 countries using CBCT imaging and meta-analytic methods. A multicenter, cross-sectional study analyzed CBCT datasets from 6,000 participants (12,000 teeth) distributed equally across 20 countries. Standardized evaluation arrangements were utilized to identify RGs (RG), taurodontism, and C-shaped canals with their prevalence stratified by region, gender, and age. Statistical analyses cover subgroup comparisons, correlation studies, and sensitivity analysis using Cramer’s V. RGs had a pooled global prevalence of 20%, with high-rised rates in Africa. C-shaped canals reported a 10% global prevalence, mainly in Asia, On the Other hand taurodontism was lowest prevalent at 7%, with markable regional variability. Prominent bilateral symmetry was noticed for all features, and taurodontism showed the highest rate (98.33%). Important correlations existed among C-shaped canals, grooves, and taurodontism showing shared developmental pathways. The current study points out the significant prevalence, including anatomical variations of RGs, taurodontism, and C-shaped canals in mandibular 1st premolars, with substantial demographic and regional differences. The findings highlight the importance of perception of these features’ morphological interrelationships along with bilateral symmetry to increase diagnostic accuracy, clinical outcomes, and treatment planning.
Opportunistic bacterial pathogens in bioaerosols emitted at municipal wastewater treatment plants, South Africa
(Nature Research, 2025-03) Poopedi, Evida; Pierneef, Rian Ewald; Singh, Tanusha; Gomba, Annancietar
Aeration tanks at wastewater treatment plants (WWTPs) emit significant amounts of bioaerosols containing potentially hazardous infectious material. Occupational exposure to airborne pathogens can pose health risks to WWTP workers. Bioaerosol samples collected at aeration tanks of two typical municipal WWTPs that use different aeration modes were analysed to investigate the composition and diversity of airborne bacteria in wastewater environments, using the Illumina MiSeq platform. Thirty-six potential airborne bacterial pathogens were identified in the air samples, and these were dominated by Bacillus, Enterococcus, Clostridium, Streptococcus, Acinetobacter, Enterobacter, Pseudomonas, Bacteroides fragilis, Acinetobacter baumannii, and Escherichia/Shigella. Bioaerosols from mechanical aeration tanks (72%, 26/36) had a relatively higher richness and diversity of airborne bacterial pathogens than diffused aeration tanks (17%, 6/36). Furthermore, most of the identified airborne bacterial pathogens (78%, 28/36) were classified as Risk Group 2 according to the revised South African Regulation for Hazardous Biological Agents, 2022, and up to 70% of these were gram-negative bacteria. The presence of potentially pathogenic bacteria in the ambient air at WWTPs suggests an elevated risk of bioaerosol exposure for workers. Therefore, further research and site-specific risk assessments are recommended to guide the implementation of effective bioaerosol strategies to protect workers’ health, with special attention paid to WWTPs that use mechanical aerators.
Comparative analysis of predictors of child mortality in Ethiopia via frequentist and Bayesian approaches
(Nature Research, 2025-08) Aguade, Aragaw Eshetie; Chen, Ding-Geng (Din)
The child mortality rate is a leading factor in the well-being and development of a nation. It measures the quality of life for a given population. This study aimed to determine the effects of under-five child mortality in Ethiopia. The authors used a cross-sectional study design via the 2019 Ethiopian Demographic and Health Survey. For our study, we used 3837 births recorded by mothers in seven regions of Ethiopia. In this study, the author employed the Bayesian and classical logistic regression models. The study found that the household size, number of under-five children, Sex of child, twin, births in the last five years, and breastfeeding status are significant predictors of child mortality in Ethiopia. Consequently, governmental, non-governmental, and other concerned bodies should focus on targeted healthcare interventions for mothers and children by updating their health intervention policies. In addition, improved health services are needed for better health care for children and mothers. Education should be given to mothers during pregnancy and after birth. This helps improve health for mothers and children, along with addressing other risk factors.
Root and canal configurations of maxillary first premolars in 22 countries using two classification systems : a multinational cross-sectional study
(Nature Research, 2025-06) Tulegenova, Indira; Hatipoglu, Omer; Taha, Nessrin; Makahleh, Nisrein; Fernandez-Grisales, Rafael; Bekjanova, Olga; Rahimi, Mehdi;; Donnermeyer, David; Madfa, Ahmed A.; Petridis, Xenos; Intriago, Martha Gallegos; Shah, Tanvi; Allawi, Safaa; Ivica, Anja; Lim, Wen Yi; Hamouda, Abdelrahman; Jagtap, Rohan; Martin-Biedma, Benjamin; Lehmann, Anna Paulina; Alfirjani, Suha; Palma, Paulo J.; Buchanan, Glynn Dale
Please read abstract in the article.
SARS-CoV-2 seroprevalence and COVID-19 vaccination coverage in two states of Nigeria from a population based household survey
(Nature Research, 2025-08) Enyereibe, Nwachukwu William; Ilori, Elsie; Steinhardt, Laura; Stafford, Kristen; Dan-Nwafor, Chioma; Ochu, Chinwe Lucia; Ibrahim, Dalhatu; Alagi, Matthias; Ibrahim, Baffa Sule; Iwara, Iwara Emem; Mba, Nwand; Ibrahim, Zainab; Ahmed, Rabiatu Aliyu; Botson, Iliya; Ogbonna, Stanley Uche; Igumbor, Ehimario Uche; Abubakar, Jafiya; Ahmed, Nasir; Nwiyi, Gloria Ogochukwu; Ihemeje, Chima Emmanuel; Okoi, Catherine; John, Doris; Ashikeni, Matthew; Muhammad, Basheer Lawan; Iriemenam, Nnaemeka C.; Okunoye, Olumide; Greby, Stacie M.; Bassey, Orji; Okoye, Mcpaul; Blanco, Natalia; Mitchell, Andrew; Ipadeola, Oladipupo; Antonza, Gladys S.; Mpamugo, Augustine; Makava, Favour; Charurat, Manhattan; Adebajo, Sylvia; Swaminathan, Mahesh; Ifedayo, Adetifa; Ihekweazu, Chikwe
SARS-CoV-2 population-based seroprevalence surveys are useful for estimating the extent of SARS-CoV-2 infections, which may be underestimated by COVID-19 case counts. Surveys conducted in October 2020 in four Nigerian states showed that SARS-CoV-2 seroprevalence ranged from 9.3% in Gombe (northeast) to 25.2% in Enugu (southeast) after the first COVID-19 wave, more than 100 and 700 times higher than the official number of COVID-19 cases in these two states, respectively. We conducted a serosurvey after the second COVID-19 wave to evaluate the extent of SARS-CoV-2 infections, attitudes to COVID-19 vaccines, and COVID-19 vaccination coverage in two regions of Nigeria. Using the World Health Organization (WHO) Unity protocol, 34 enumeration areas (EAs) each in the Federal Capital Territory (FCT) (Northcentral Zone) and Kano State (Northwest Zone) were sampled in June 2021, using probability proportional to estimated size; 20 households in one EA were randomly selected. All consenting and assenting members of a household were asked about risk behaviors; adults who were 18 years and above (the eligible population for COVID-19 vaccination in Nigeria) responded to questions on COVID-19 vaccine attitudes and receipt. Blood and nasal/oropharyngeal samples were taken from all consenting and assenting household members. Blood samples collected were tested with the Luminex xMAP® SARS-CoV-2 Multi-Antigen IgG Assay and swabs by reverse-transcriptase-PCR (RT-PCR). Overall response rates were 76.8% in the FCT (n = 1,505 blood draws) and 80.4% in Kano State (n = 2,178 blood draws). Following the second COVID-19 wave in Nigeria, more than 40% of residents in the FCT (40.3%, 95% CI: 34.7–45.9) and Kano State (42.6%, 95% CI: 39.4–45.8) had evidence of prior SARS-CoV-2 infection. There were no active SARS-CoV-2 infections detected by RT-PCR in either the FCT or Kano State. In the FCT and Kano State, 3.4% and 1.6% of people surveyed reported receipt of any COVID-19 vaccine, three months after vaccines were available in country. In the FCT, 77.5% of adults were aware of COVID-19 vaccines, of whom 46.9% reported willingness to receive them. In Kano State, 48.7% of adults were aware of COVID-19 vaccines, of whom 61.1% were willing to receive them. In both regions, about 84% of those reporting unwillingness to accept COVID-19 vaccines cited concerns over vaccine safety. “Serosurvey findings revealed that SARS-CoV-2 infection was far more widespread in both the Federal Capital Territory and Kano State than indicated by reported case numbers. Despite high awareness, COVID-19 vaccine uptake remained low, primarily due to concerns about vaccine safety. These results highlight the urgent need for targeted risk communication to address vaccine hesitancy and improve coverage. Serosurveys provide valuable insights that can guide public health interventions and future pandemic preparedness in Nigeria.”
Sensitive and modular amplicon sequencing of Plasmodium falciparum diversity and resistance for research and public health
(Nature Portfolio, 2025-03) Aranda-Diaz, Andres; Vickers, Eric Neubauer; Murie, Kathryn; Palmer, Brian; Hathaway, Nicholas; Gerlovina, Inna; Boene, Simone; Garcia-Ulloa, Manuel; Cistero, Pau; Katairo, Thomas; Semakuba, Francis Ddumba; Nsengimaana, Bienvenu; Gwarinda, Hazel; Garcia-Fernandez, Carla; Louie, William; Esayas, Endashaw; Da Silva, Clemente; Datta, Debayan; Kiyaga, Shahiid; Wiringilimaana, Innocent; Feleke, Sindew Mekasha; Bennett, Adam; Smith, Jennifer L.; Gadisa, Endalamaw; Parr, Jonathan B.; Conrad, Melissa D.; Raman, Jaishree; Tukwasibwe, Stephen; Ssewanyana, Isaac; Rovira-Vallbona, Eduard; Tato, Cristina M.; Briggs, Jessica; Mayor, Alfredo; Greenhouse, Bryan
Please read abstract in the article.
Negotiating the boundaries of farmerhood : class, race, and identity in the new rural South Africa
(Routledge, 2025) Dyzenhaus, Alex; Holmes, Carolyn E.
Farmers play a veto role in democratization because of their economic standing and their symbolic status as keepers of a conservative rural space. In South Africa, the classification of “farmer” was historically reserved for white land-owners, but democratization promised land reform and rural integration. This paper examines the ways the category of “farmer” has changed with these reforms. Using qualitative interviews with white and Black farmers, the paper finds distinct variation in the levels of integration of the category of “farmer” between white English-speaking and white Afrikaans-speaking farmers. Despite their reputation for liberality, there is less meaningful integration within English-speaking farming communities. Afrikaans-speaking farmers, who have a reputation for conservatism, have higher barriers to entry, but emerging farmers who meet these criteria are more meaningfully integrated into the farming community. These findings elucidate the complex interactions of threat, class, and politics that create rural identity in democratic transitions.
Outbreaks of H5N1 high pathogenicity avian influenza in South Africa in 2023 were caused by two distinct sub-genotypes of clade 2.3.4.4b viruses
(MDPI, 2024-06) Abolnik, Celia; Roberts, Laura Christl; Strydom, Christine; Snyman, Albert; Roberts, David Gordon; celia.abolnik@up.ac.za
In 2023, South Africa continued to experience sporadic cases of clade 2.3.4.4b H5N1 high-pathogenicity avian influenza (HPAI) in coastal seabirds and poultry. Active environmental surveillance determined that H5Nx, H7Nx, H9Nx, H11Nx, H6N2, and H12N2, amongst other unidentified subtypes, circulated in wild birds and ostriches in 2023, but that H5Nx was predominant. Genome sequencing and phylogenetic analysis of confirmed H5N1 HPAI cases determined that only two of the fifteen sub-genotypes that circulated in South Africa in 2021-2022 still persisted in 2023. Sub-genotype SA13 remained restricted to coastal seabirds, with accelerated mutations observed in the neuraminidase protein. SA15 caused the chicken outbreaks, but outbreaks in the Paardeberg and George areas, in the Western Cape province, and the Camperdown region of the KwaZulu-Natal province were unrelated to each other, implicating wild birds as the source. All SA15 viruses contained a truncation in the PB1-F2 gene, but in the Western Cape SA15 chicken viruses, PA-X was putatively expressed as a novel isoform with eight additional amino acids. South African clade 2.3.4.4b H5N1 viruses had comparatively fewer markers of virulence and pathogenicity compared to European strains, a possible reason why no spillover to mammals has occurred here yet.
Low-level viremia among adults living with HIV on dolutegravir-based first-line antiretroviral therapy is a predictor of virological failure in Botswana
(MDPI, 2024-05-01) Bareng, Ontlametse T.; Moyo, Sikhulile; Mudanga , Mbatshi; Sebina , Kagiso; Koofhethile , Catherine K.; Choga, Wonderful T.; Moraka , Natasha O.; Maruapula , Dorcas; Gobe , Irene; Motswaledi, Modisa S.; Musonda, Rosemary; Nkomo , Bornapate; Ramaabya , Dinah; Chebani , Tony; Makuruetsa, Penny; Makhema , Joseph; Shapiro , Roger; Lockman, Shahin; Gaseitsiwe, Simani
We evaluated subsequent virologic outcomes in individuals experiencing low-level virem ia (LLV) on dolutegravir (DTG)-based first-line antiretroviral therapy (ART) in Botswana. We used a national dataset from 50,742 adults who initiated on DTG-based first-line ART from June 2016-December 2022. Individuals with at least two viral load (VL) measurements post three months on DTG-based first-line ART were evaluated for first and subsequent episodes of LLV (VL:51-999 copies/mL). LLV was sub-categorized as low-LLV (51-200 copies/mL), medium-LLV (201-400 copies/mL) and high-LLV (401-999 copies/mL). The study outcome was virologic failure (VF) (VL ≥ 1000 copies/mL): virologic non-suppression defined as single-VF and confirmed-VF defined as two-consecutive VF measurements after an initial VL < 1000 copies/mL. Cox regression analysis identified predictive factors of subsequent VF. The prevalence of LLV was only statistically different at timepoints >6-12 (2.8%) and >12-24 (3.9%) (p-value < 0.01). LLV was strongly associated with both virologic non-suppression (adjusted hazards ratio [aHR] = 2.6; 95% CI: 2.2-3.3, p-value ≤ 0.001) and confirmed VF (aHR = 2.5; 95% CI: 2.4-2.7, p-value ≤ 0.001) compared to initially virally suppressed PLWH. High-LLV (HR = 3.3; 95% CI: 2.9-3.6) and persistent-LLV (HR = 6.6; 95% CI: 4.9-8.9) were associated with an increased hazard for virologic non-suppression than low-LLV and a single-LLV episode, respectively. In a national cohort of PLWH on DTG-based first-line ART, LLV > 400 copies/mL and persistent-LLV had a stronger association with VF. Frequent VL testing and adherence support are warranted for individuals with VL > 50 copies/mL.
High prevalence of hepatitis B virus drug resistance mutations to lamivudine among people with HIV/HBV coinfection in rural and peri-urban communities in Botswana
(MDPI, 2024-04-11) Phinius , Bonolo B.; Anderson , Motswedi; Gobe , Irene; Mokomane , Margaret; Choga, Wonderful T.; Phakedi , Basetsana; Ratsoma , Tsholofelo; Mpebe , Gorata; Makhema , Joseph; Shapiro, Roger; Lockman , Shahin; Musonda, Rosemary; Moyo, Sikhulile; Gaseitsiwe, Simani
BACKGROUND : We aimed to determine the prevalence of hepatitis B virus (HBV) resistance-associated mutations (RAMs) in people with HBV and human immunodeficiency virus (HBV/HIV) in Botswana. METHODS : We sequenced HBV deoxyribonucleic acid (DNA) from participants with HBV/HIV from the Botswana Combination Prevention Project study (2013-2018) using the Oxford Nanopore GridION platform. Consensus sequences were analyzed for genotypic and mutational profiles. RESULTS : Overall, 98 HBV sequences had evaluable reverse transcriptase region coverage. The median participant age was 43 years (IQR: 37, 49) and 66/98 (67.4%) were female. Most participants, i.e., 86/98 (87.8%) had suppressed HIV viral load (VL). HBV RAMs were identified in 61/98 (62.2%) participants. Most RAMs were in positions 204 (60.3%), 180 (50.5%), and 173 (33.3%), mostly associated with lamivudine resistance. The triple mutations rtM204V/L180M/V173L were the most predominant (17/61 [27.9%]). Most participants (96.7%) with RAMs were on antiretroviral therapy for a median duration of 7.5 years (IQR: 4.8, 10.5). Approximately 27.9% (17/61) of participants with RAMs had undetectable HBV VL, 50.8% (31/61) had VL < 2000 IU/mL, and 13/61 (21.3%) had VL ≥ 2000 IU/mL. CONCLUSIONS : The high prevalence of lamivudine RAMs discourages the use of ART regimens with 3TC as the only HBV-active drug in people with HIV/HBV.
Detection of Dengue virus 1 and mammalian orthoreovirus 3, with novel reassortments, in a South African family returning from Thailand, 2017
(MDPI, 2024-08-09) Jansen van Vuren, Petrus; Parry, Rhys H.; Paweska, Janusz Tadeusz
In July 2017, a family of three members, a 46-year-old male, a 45-year-old female and their 8-year-old daughter, returned to South Africa from Thailand. They presented symptoms consistent with mosquito-borne diseases, including fever, headache, severe body aches and nausea. Mosquito bites in all family members suggested recent exposure to arthropod-borne viruses. Dengue virus 1 (Genus Orthoflavivirus) was isolated (isolate no. SA397) from the serum of the 45-year-old female via intracerebral injection in neonatal mice and subsequent passage in VeroE6 cells. Phylogenetic analysis of this strain indicated close genetic identity with cosmopolitan genotype 1 DENV1 strains from Southeast Asia, assigned to major lineage K, minor lineage 1 (DENV1I_K.1), such as GZ8H (99.92%) collected in November 2018 from China, and DV1I-TM19-74 isolate (99.72%) identified in Bangkok, Thailand, in 2019. Serum samples from the 46-year-old male yielded a virus isolate that could not be confirmed as DENV1, prompting unbiased metagenomic sequencing for virus identification and characterization. Illumina sequencing identified multiple segments of a mammalian orthoreovirus (MRV), designated as Human/SA395/SA/2017. Genomic and phylogenetic analyses classified Human/SA395/SA/2017 as MRV-3 and assigned a tentative genotype, MRV-3d, based on the S1 segment. Genomic analyses suggested that Human/SA395/SA/2017 may have originated from reassortments of segments among swine, bat, and human MRVs. The closest identity of the viral attachment protein σ1 (S1) was related to a human isolate identified from Tahiti, French Polynesia, in 1960. This indicates ongoing circulation and co-circulation of Southeast Asian and Polynesian strains, but detailed knowledge is hampered by the limited availability of genomic surveillance. This case represents the rare concurrent detection of two distinct viruses with different transmission routes in the same family with similar clinical presentations. It highlights the complexity of diagnosing diseases with similar sequelae in travelers returning from tropical areas.
Comparative effects of efavirenz and dolutegravir on metabolomic and inflammatory profiles, and platelet activation of people living with HIV
(MDPI, 2024-09-14) Roux, Crystal Gayle; Mason, Shayne; Du Toit, Louise; Nel, Jan-Gert; Rossouw, Theresa M.; Steel, Helen Carolyn; u04672365@tuks.co.za
Antiretroviral therapy (ART) has reduced the mortality and morbidity associated with HIV. However, irrespective of treatment, people living with HIV remain at a higher risk of developing non-AIDS-associated diseases. In 2019, the World Health Organization recommended the transition from efavirenz (EFV)- to dolutegravir (DTG)-based ART. Data on the impact of this transition are still limited. The current study therefore investigated the metabolic profiles, cytokine inflammatory responses, and platelet activation before and after the treatment transition. Plasma samples from nine virally suppressed adults living with HIV and sixteen healthy, HIV-uninfected individuals residing in Gauteng, South Africa were compared. Metabolite and cytokine profiles, and markers associated with platelet activation, were investigated with untargeted proton magnetic resonance metabolomics, multiplex suspension bead array immunoassays, and sandwich enzyme-linked immunosorbent assays, respectively. In those individuals with normal C-reactive protein levels, the transition to a DTG-based ART regimen resulted in decreased concentrations of acetoacetic acid, creatinine, adenosine monophosphate, 1,7-dimethylxanthine, glycolic acid, 3-hydroxybutyric acid, urea, and lysine. Moreover, increased levels of formic acid, glucose, lactic acid, myo-inositol, valine, glycolic acid, and 3-hydroxybutyric acid were observed. Notably, levels of interleukin-6, platelet-derived growth factor-BB, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, soluble cluster of differentiation 40 ligand, as well as regulated on activation, normal T-cell expressed and secreted (RANTES) reached levels close to those observed in the healthy control participants. The elevated concentration of macrophage inflammatory protein-1 alpha was the only marker indicative of elevated levels of inflammation associated with DTG-based treatment. The transition from EFV- to DTG-based regimens therefore appears to be of potential benefit with metabolic and inflammatory markers, as well as those associated with cardiovascular disease and other chronic non-AIDS-related diseases, reaching levels similar to those observed in individuals not living with HIV.
Attempted transmission of Marburg virus by bat-associated fleas Thaumapsylla breviceps breviceps (Ischnopsyllidae: Thaumapsyllinae) to the Egyptian Rousette bat (Rousettus aegyptiacus)
(MDPI, 2024-07-25) Paweska, Janusz Tadeusz; Storm, Nadia; Jansen van Vuren, Petrus; Markotter, Wanda; Kemp, Alan; wanda.markotter@up.ac.za
Egyptian rousette bats (ERBs) are implicated as reservoir hosts for Marburg virus (MARV), but natural mechanisms involved in maintenance of MARV in ERB populations remain undefined. A number of hematophagous ectoparasites, including fleas, parasitize bats. Subcutaneous (SC) inoculation of ERBs with MARV consistently results in viremia, suggesting that infectious MARV could be ingested by blood-sucking ectoparasites during feeding. In our study, MARV RNA was detected in fleas that took a blood meal during feeding on viremic bats on days 3, 7, and 11 after SC inoculation. Virus concentration in individual ectoparasites was consistent with detectable levels of viremia in the blood of infected host bats. There was neither seroconversion nor viremia in control bats kept in close contact with MARV-infected bats infested with fleas for up to 40 days post-exposure. In fleas inoculated intracoelomically, MARV was detected up to 14 days after intracoelomic (IC) inoculation, but the virus concentration was lower than that delivered in the inoculum. All bats that had been infested with inoculated, viremic fleas remained virologically and serologically negative up to 38 days after infestation. Of 493 fleas collected from a wild ERB colony in Matlapitsi Cave, South Africa, where the enzootic transmission of MARV occurs, all tested negative for MARV RNA. While our findings seem to demonstrate that bat fleas lack vectorial capacity to transmit MARV biologically, their role in mechanical transmission should not be discounted. Regular blood-feeds, intra- and interhost mobility, direct feeding on blood vessels resulting in venous damage, and roosting behaviour of ERBs provide a potential physical bridge for MARV dissemination in densely populated cave-dwelling bats by fleas. The virus transfer might take place through inoculation of skin, mucosal membranes, and wounds when contaminated fleas are squashed during auto- and allogrooming, eating, biting, or fighting.
A standardized pipeline for assembly and annotation of African swine fever virus genome
(MDPI, 2024-08-13) Spinard , Edward; Dinhobl , Mark; Erdelyan, Cassidy N.G.; O’Dwyer , James; Fenster , Jacob; Birtley , Hillary; Tesler, Nicolas; Calvelage , Sten; Leijon , Mikael; Steinaa , Lucilla; O’Donnell , Vivian; Blome, Sandra; Bastos, Armanda D.S.; Ramirez-Medina , Elizabeth; Lacasta , Anna; Stahl, Karl; Qiu , Huaji; Nilubol , Dachrit; Tennakoon , Chandana; Maesembe , Charles; Faburay, Bonto; Ambagala , Aruna; Williams , David; Ribeca , Paolo; Borca , Manuel V.; Gladue, Douglas P.
Obtaining a complete good-quality sequence and annotation for the long double-stranded DNA genome of the African swine fever virus (ASFV) from next-generation sequencing (NGS) technology has proven difficult, despite the increasing availability of reference genome sequences and the increasing affordability of NGS. A gap analysis conducted by the global African swine fever research alliance (GARA) partners identified that a standardized, automatic pipeline for NGS analysis was urgently needed, particularly for new outbreak strains. Whilst there are several diagnostic and research labs worldwide that collect isolates of the ASFV from outbreaks, many do not have the capability to analyze, annotate, and format NGS data from outbreaks for submission to NCBI, and some publicly available ASFV genomes have missing or incorrect annotations. We developed an automated, standardized pipeline for the analysis of NGS reads that directly provides users with assemblies and annotations formatted for their submission to NCBI. This pipeline is freely available on GitHub and has been tested through the GARA partners by examining two previously sequenced ASFV genomes; this study also aimed to assess the accuracy and limitations of two strategies present within the pipeline: reference-based (Illumina reads) and de novo assembly (Illumina and Nanopore reads) strategies.
Emergence of Omicron FN.1 a descendent of BQ.1.1 in Botswana
(Oxford University Press, 2024-11) Choga, Wonderful T.; Gustani-Buss, Emanuele; Tegally, Houriiyah; Maruapula, Dorcas; Yu, Xiaoyu; Moir, Monika; Zuze, Boitumelo J.L; James, San Emmanuel; Ndlovu, Nokuthula S.; Seru, Kedumetse; Motshosi, Patience; Blenkinsop , Alexandra; Gobe , Irene; Baxter, Cheryl; Manasa, Justen; Lockman , Shahin; Shapiro, Roger; Makhema , Joseph; Wilkinson, Eduan; Blackard, Jason T.; Lemey , Phillipe; Lessells, Richard J.; Martin, Darren P.; De Oliveira , Tulio; Gaseitsiwe, Simani; Moyo, Sikhulile
Botswana, like the rest of the world, has been significantly impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In December 2022, we detected a monophyletic cluster of genomes comprising a sublineage of the Omicron variant of concern (VOC) designated as B.1.1.529.5.3.1.1.1.1.1.1.74.1 (alias FN.1, clade 22E). These genomes were sourced from both epidemiologically linked and unlinked samples collected in three close locations within the district of Greater Gaborone. In this study, we assessed the worldwide prevalence of the FN.1 lineage, evaluated its mutational profile, and conducted a phylogeographic analysis to reveal its global dispersal dynamics. Among approximately 16 million publicly available SARS-CoV-2 sequences generated by 30 September 2023, only 87 were of the FN.1 lineage, including 22 from Botswana, 6 from South Africa, and 59 from the UK. The estimated time to the most recent common ancestor of the 87 FN.1 sequences was 22 October 2022 [95% highest posterior density: 2 September 2022—24 November 2022], with the earliest of the 22 Botswana sequences having been sampled on 7 December 2022. Discrete trait reconstruction of FN.1 identified Botswana as the most probable place of origin. The FN.1 lineage is derived from the BQ.1.1 lineage and carries two missense variants in the spike protein, S:K182E in NTD and S:T478R in RDB. Among the over 90 SARS-CoV-2 lineages circulating in Botswana between September 2020 and July 2023, FN.1 was most closely related to BQ.1.1.74 based on maximum likelihood phylogenetic inference, differing only by the S:K182E mutation found in FN.1. Given the early detection of numerous novel variants from Botswana and its neighbouring countries, our study underscores the necessity of continuous surveillance to monitor the emergence of potential VOCs, integrating molecular and spatial data to identify dissemination patterns enhancing preparedness efforts.
Rabies in cats—an emerging public health issue
(MDPI, 2024-10-19) Fehlner-Gardiner , Christine; Gongal , Gyanendra; Tenzin, Tenzin; Sabeta, Claude Taurai; De Benedictis , Paola; Rocha , Silene Manrique; Vargas , Alexander; Cediel-Becerra, Natalia; Gomez , Luis Carlos; Maki , Joanne; Rupprecht, Charles E.; claude.sabeta@up.ac.za
Human rabies cases today are predominantly associated with infection from rabid domestic dogs. Unlike dogs, a common global reservoir species that perpetuates rabies viruses (RABV) within their populations, domestic cats are much less frequently reported or vaccinated. Epidemiologically, cats are important vectors of lyssaviruses but are not viral reservoirs. Typically, cats are incidental hosts only, infected with the predominant lyssavirus in their geographic locale. Human cases associated with rabid cats have occurred in Africa, Asia, Europe and throughout the Americas. As adept, solitary hunters, wild and domestic felids are at risk of lyssavirus infection based upon interactions with infected prey, such as bats, or from transmission by other mesocarnivores, such as rabid dogs, foxes, jackals, raccoons, and skunks. Current veterinary vaccines provide safe and effective immunity in cats against phylogroup I lyssaviruses, such as RABV, but not against divergent lyssaviruses in phylogroups II-IV. With the focus upon the global elimination of canine rabies, the emergence of rabies in cats represents a concerning trend. Clearly, education about the occurrence of rabies in cats needs to be improved, as well as the routine vaccination of cats to reduce the associated risks to public health, agriculture, and conservation biology from a One Health perspective.

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