Browsing by Author "Gaseitsiwe, Simani"

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    Afri-Can Forum 2
    (Biomed Central, 2016-07-12) Mukudu, Hillary; Martinson, Neil; Sartorius, Benn; Coetzee, Jenny; Dietrich, Janan; Mokgatswana, Kgaugelo; Jewkes, Rachel; Gray, Glenda E.; Dugas, Marylene; Behanzin, Luc; Guedou, Fernand A.; Gagnon, Marie-Pierre; Alary, Michel; Rutakumwa, Rwamahe; Mbonye, Martin; Kiwanuka, Thadeus; Nakamanya, Sarah; Muhumuza, Richard; Nalukenge, Winfred; Seeley, Janet; Atujuna, Millicent; Wallace, Melissa; Brown, Ben; Bekker, Linda G.; Newman, Peter A.; Harryparsad, Rushil; Olivier, Abraham J.; Jaspan, Heather B.; Wilson, Douglas; Dietrich, Janan; Martinson, Neil; Mukudu, Hillary; Mkhize, Nonhlanhla; Morris, Lynn; Cianci, Gianguido; Dinh, Minh; Hope, Thomas; Passmore, Jo-Ann S.; Gray, Clive M.; Henrick, Bethany M.; Yao, Xiao-Dan; Rosenthal, Kenneth L.; Henrick, Bethany M.; Yao, Xiao-Dan; Drannik, Anna G.; Rosenthal, Kenneth L.; Chanzu, Nadia; Mwanda, Walter; Oyugi, Julius; Anzala, Omu; Mbow, Moustapha; Jallow, Sabelle; Thiam, Moussa; Davis, Alberta; Diouf, Assane; Ndour, Cheikh T.; Seydi, Moussa; Dieye, Tandakha N.; Mboup, Souleymane; Goodier, Martin; Rilley, Eleanor; Jaye, Assan; Yao, Xiao-Dan; Omange, R. W.; Henrick, Bethany M.; Lester, Richard T.; Kimani, Joshua; Ball, T. B.; Plummer, Francis A.; Rosenthal, Kenneth L.; Behanzin, Luc; Guedou, Fernand A.; Geraldo, Nassirou; Mastetse, Ella G.; Sossa, Jerome C.; Zannou, Marcel D.; Alary, Michel; Osawe, Sophia; Okpokoro, Evaezi; Okolo, Felicia; Umaru, Stephen; Abimiku, Rebecca; Audu, Sam; Datong, Pam; Abimiku, Alashle; Nyange, Jacquelyn; Olenja, Joyce; Mutua, Gaudensia; Jaoko, Walter; Omosa-Manyonyi, Gloria; Farah, Bashir; Khaniri, Maureen; Anzala, Omu; Cockcroft, Anne; Tonkin, Kendra; Girish, Indu; Mhati, Puna; Cunningham, Ashley; Andersson, Neil; Farah, Bashir; Indangasi, Jackton; Jaoko, Walter; Mutua, Gaudensia; Khaniri, Maureen; Nyange, Jacquelyn; Anzala, Omu; Diphoko, Thabo; Gaseitsiwe, Simani; Maiswe, Victoria; Iketleng, Thato; Maruapula, Dorcas; Bedi, Keabetswe; Moyo, Sikhulile; Musonda, Rosemary; Wainberg, Mark; Makhema, Joseph; Novitsky, Vladimir; Marlink, Richard; Essex, Max; Okoboi, Stephen; Ssali, Livingstone; Kalibala, Sam; Birungi, Josephine; Egessa, Aggrey; Wangisi, Jonathan; Okullu, Lyavala J.; Bakanda, Celestin; Obare, Francis; Boer, I. M. S.; Semvua, Hadija H.; Van den Boogaard, Jossy; Kiwango, Krisanta W.; Ngowi, Kennedy M.; Nieuwkerk, Pythia T.; Aarnoutse, Rob E.; Kiwelu, Ireen; Muro, Eva; Kibiki, Gibson S.; Datiri, Ruth; Choji, Grace; Osawe, Sophia; Okpokoro, Evaezi; Okolo, Felicia; Umaru, Stephen; Abimiku, Rebecca; Datong, Pam; Abimiku, Alashle; Fomsgaard, A.; Karlsson, I.; Jensen, K. J; Jensen, S. S.; Leo-Hansen, C.; Jespersen, S.; Da Silva Te, D.; Rodrigues, C. M.; Da Silva, Z. J.; Janitzek, C. M.; Gerstoft, J.; Kronborg, G.; Okpokoro, Evaezi; Osawe, Sophia; Daitiri, Ruth; Choji, Grace; Umaru, Stephen; Okolo, Felicia; Datong, Pam; Emily, Nyariki; Joyce, Olenja; Robert, Lorway R.; Anzala, Anzala; Viljoen, Katie; Wendoh, Jerome; Kidzeru, Elvis; Karaoz, Ulas; Brodie, Eoin; Botha, Gerrit; Mulder, Nicola; Gray, Clive; Cameron, William; Stintzi, Alain; Jaspan, Heather; Levett, Paul N.; Alexander, David; Gulzar, Naveed; Grewal, Prabvir S.; Poon, Art F Y.; Brumme, Zabrina; Harrigan, P. R.; Brooks, James I.; Sandstrom, Paul A.; Calvez, Stryker; Sanche, Stephen E.; Scott, Jamie K.; Swartz, Leslie; Kagee, Ashraf; Lesch, Anthea; Kafaar, Zuhayr; De Wet, Anneliese; Okpokoro, Evaezi; Osawe, Sophia; Daitiri, Ruth; Choji, Grace; Umaru, Stephen; Okolo, Felicia; Datong, Pam; Abimiku, Alashle; Dietrich, Janan; Smith, Tricia; Cotton, Laura; Hornschuh, Stefanie; Van der Watt, Martin; Miller, Cari L.; Gray, Glenda; Smit, Jenni; Jaggernath, Manjeetha; Ndungu, Thumbi; Brockman, Mark; Kaida, Angela; Akolo, Maureen; Kimani, Joshua; Gelmon, Larry; Chitwa, Michael; Osero, Justus; Cockcroft, Anne; Marokoane, Nobantu; Kgakole, Leagajang; Maswabi, Boikhutso; Mpofu, Neo; Ansari, Umaira; Andersson, Neil; Nakinobe, Elizabeth; Miiro, George M.; Zalwango, Flavia; Nakiyingi-Miiro, Jessica; Kaleebu, Potiano; Semwanga, John R.; Nyanzi, Emily; Musoke, Saidat N.; Nakinobe, Elizabeth; Miiro, George; Mbidde, Edward K.; Lutalo, Tom; Kaleebu, Pontiano; Handema, Ray; Chianzu, Graham P.; Thiam, Moussa; Diagne-Gueye, Diabou; Ndiaye, Mame K.; Mbow, Moustapha; Ndiaye, Birahim P.; Traore, Ibrahima; Dia, Mamadou C.; Thomas, Gilleh; Tour-Kane, Coumba; Mboup, Souleymane; Jaye, Assan; Nyanzi, Emily; Mbidde, Edward K.; Kaleebu, Pontiano; Mpendo, Juliet; Kimani, Joshua; Birungi, Josephine; Muyindike, Winnie; Kambugu, Andrew; Sebastian, Hachizovu; Ray, Handema; Mike, Chaponda; Bertin, Kabuya J.; Modest, Mulenga; Thiam, Moussa; Janha, Omar; Davis, Alberta; Amambua-Ngwa, Alfred; Nwakanma, Davis C.; Mboup, Souleymane; Jaye, Assan; Jespersen, Sanne; Hønge, Bo L.; Esbjornsson, Joakim; Medina, Candida; Te, David Da Silva; Correira, Faustino G.; Laursen, Alex L.; Ostergaard, Lars; Andersen, Andreas; Aaby, Peter; Erikstrup, Christian; Wejse, Christian; Dieye, Siry; Sarr, Moussa; Sy, Haby; Mbodj, Helene D.; Ndiaye, Marianne; Ndiaye, Amy; Moussa, Seydi; Jaye, Assan; Mboup, Souleymane; Nyombi, Balthazar M.; Shao, Elichilia R.; Chilumba, Innocent B.; Moyo, Sikhulile; Gaseitsiwe, Simani; Musonda, Rosemary; Datong, Pam; Inyang, Bucky; Osawe, Sophia; Izang, Abel; Cole, Chundung; Okolo, Felicia; Cameron, Bill; Rosenthal, Kenneth; Gray, Clive; Jaspan, Heather; Seraise, Boitumelo; Andrea-Marobela, Kerstin; Moyo, Sikhulile; Musonda, Rosemary; Makhema, Joseph; Essex, Max; Gaseitsiwe, Simani
    ENGLISH ABSTRACT: We are pleased to present peer reviewed forum proceedings of the 2nd synchronicity forum of GHRI/CHVIfunded Canadian and African HIV prevention and vaccine teams Forum objectives ∙GHRI-funded capacity building and HIV prevention research teams presented highlights of achievements ∙Teams discussed how to jointly build on achievements for sustainability ∙Provided an opportunity for inter-team collaboration, synchronize best approach to capacity building, mentoring of new researchers and building leadership ∙Provided opportunities for informal discussions and networking among the teams. ∙Teams learnt about recent advances in the area of African regulatory and ethics review process ∙The forum proceedings was a special supplement in an openaccess journal was produced
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    Analysis of viral diversity in relation to the recency of HIV-1C infection in Botswana
    (Public Library of Science, 2016) Moyo, Sikhulile; Vandormael, Alain; Wilkinson, Eduan; Engelbrecht, Susan; Gaseitsiwe, Simani; Kotokwe, Kenanao P.; Musonda, Rosemary; Tanser, Frank; Essex, Max; Novitsk, Vladimir; De Oliveira, Tulio
    Background: Cross-sectional, biomarker methods to determine HIV infection recency present a promising and cost-effective alternative to the repeated testing of uninfected individuals. We evaluate a viral-based assay that uses a measure of pairwise distances (PwD) to identify HIV infection recency, and compare its performance with two serologic incidence assays, BED and LAg. In addition, we assess whether combination BED plus PwD or LAg plus PwD screening can improve predictive accuracy by reducing the likelihood of a false-recent result. Methods: The data comes from 854 time-points and 42 participants enrolled in a primary HIV-1C infection study in Botswana. Time points after treatment initiation or with evidence of multiplicity of infection were excluded from the final analysis. PwD was calculated from quasispecies generated using single genome amplification and sequencing. We evaluated the ability of PwD to correctly classify HIV infection recency within <130, <180 and <360 days post-seroconversion using Receiver Operator Characteristics (ROC) methods. Following a secondary PwD screening, we quantified the reduction in the relative false-recency rate (rFRR) of the BED and LAg assays while maintaining a sensitivity of either 75, 80, 85 or 90%. Results: The final analytic sample consisted of 758 time-points from 40 participants. The PwD assay was more accurate in classifying infection recency for the 130 and 180-day cut-offs when compared with the recommended LAg and BED thresholds. A higher AUC statistic confirmed the superior predictive performance of the PwD assay for the three cut-offs. When used for combination screening, the PwD assay reduced the rFRR of the LAg assay by 52% and the BED assay by 57.8% while maintaining a 90% sensitivity for the 130 and 180-day cut-offs respectively. Conclusion: PwD can accurately determine HIV infection recency. A secondary PwD screening reduces misclassification and increases the accuracy of serologic-based assays.
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    Deciphering multiplicity of HIV-1C infection : transmission of closely related multiple viral lineages
    (Public Library of Science, 2016-11-28) Novitsky, Vlad; Moyo, Sikhulile; Wang, Rui; Gaseitsiwe, Simani; Essex, M.
    Background: A single viral variant is transmitted in the majority of HIV infections. However, about 20% of heterosexually transmitted HIV infections are caused by multiple viral variants. Detection of transmitted HIV variants is not trivial, as it involves analysis of multiple viral sequences representing intra-host HIV-1 quasispecies. Methodology: We distinguish two types of multiple virus transmission in HIV infection: (1) HIV transmission from the same source, and (2) transmission from different sources. Viral sequences representing intra-host quasispecies in a longitudinally sampled cohort of 42 individuals with primary HIV-1C infection in Botswana were generated by single-genome amplification and sequencing and spanned the V1C5 region of HIV-1C env gp120. The Maximum Likelihood phylogeny and distribution of pairwise raw distances were assessed at each sampling time point (n = 217; 42 patients; median 5 (IQR: 4–6) time points per patient, range 2–12 time points per patient). Results: Transmission of multiple viral variants from the same source (likely from the partner with established HIV infection) was found in 9 out of 42 individuals (21%; 95 CI 10–37%). HIV super-infection was identified in 2 patients (5%; 95% CI 1–17%) with an estimated rate of 3.9 per 100 person-years. Transmission of multiple viruses combined with HIV super-infection at a later time point was observed in one individual. Conclusions: Multiple HIV lineages transmitted from the same source produce a monophyletic clade in the inferred phylogenetic tree. Such a clade has transiently distinct sub-clusters in the early stage of HIV infection, and follows a predictable evolutionary pathway. Over time, the gap between initially distinct viral lineages fills in and initially distinct sub-clusters converge. Identification of cases with transmission of multiple viral lineages from the same source needs to be taken into account in cross-sectional estimation of HIV recency in epidemiological and population studies
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    Detection of second line drug resistance among drug resistant Mycobacterium tuberculosis isolates in Botswana
    (MDPI, 2019-10-28) Mogashoa, Tuelo; Melamu, Pinkie; Derendinger, Brigitta; Ley, Serej D.; Streicher, Elizabeth M.; Iketleng, Thato; Mupfumi, Lucy; Mokomane, Margaret; Kgwaadira, Botshelo; Rankgoane-Pono, Goabaone; Tsholofelo, Thusoyaone T.; Kasvosve, Ishmael; Moyo, Sikhulile; Warren, Robin M.; Gaseitsiwe, Simani
    ENGLISH ABSTRACT: The emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) Mycobacterium tuberculosis (M.tb) strains is a threat to global tuberculosis (TB) control. The early detection of drug resistance is critical for patient management. The aim of this study was to determine the proportion of isolates with additional second-line resistance among rifampicin and isoniazid resistant and MDR-TB isolates. A total of 66 M.tb isolates received at the National Tuberculosis Reference Laboratory between March 2012 and October 2013 with resistance to isoniazid, rifampicin or both were analyzed in this study. The genotypes of the M.tb isolates were determined by spoligotyping and second-line drug susceptibility testing was done using the Hain Genotype MTBDRsl line probe assay version 2.0. The treatment outcomes were defined according to the Botswana national and World Health Organization (WHO) guidelines. Of the 57 isolates analyzed, 33 (58%) were MDR-TB, 4 (7%) were additionally resistant to flouroquinolones and 3 (5%) were resistant to both fluoroquinolones and second-line injectable drugs. The most common fluoroquinolone resistance-conferring mutation detected was gyrA A90V. All XDR-TB cases remained smear or culture positive throughout the treatment. Our study findings indicate the importance of monitoring drug resistant TB cases to ensure rapid detection of second-line drug resistance.
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    Genetic diversity of Mycobacterium tuberculosis strains circulating in Botswana
    (PLoS, 2019-05-07) Mogashoa, Tuelo; Melamu, Pinkie; Ley, Serej D.; Streicher, Elizabeth M.; Iketleng, Thato; Kelentse, Nametso; Mupfumi, Lucy; Mokomane, Margaret; Kgwaadira, Botshelo; Novitsky, Vladimir; Kasvosve, Ishmael; Moyo, Sikhulile; Warren, Robin M.; Gaseitsiwe, Simani
    Background: Molecular typing of Mycobacterium tuberculosis (M.tb) isolates can inform Tuberculosis (TB) control programs on the relative proportion of transmission driving the TB epidemic. There is limited data on the M. tb genotypes that are circulating in Botswana. The aim of this study was to generate baseline data on the genetic diversity of M.tb isolates circulating in the country. Methods: A total of 461 M.tb isolates received at the Botswana National Tuberculosis Reference Laboratory between March 2012 and October 2013 were included in this study. Drug susceptibility testing was conducted using the BD BACTEC MGIT 960 System. M.tb strains were genotyped using spoligotyping and spoligotype patterns were compared with existing patterns in the SITVIT Web database. A subset of drug resistant isolates which formed spoligo clusters (n = 65) was additionally genotyped with 12-loci MIRU. Factors associated with drug resistance and clustering were evaluated using logistic regression. Results: Of the 461 isolates genotyped, 458 showed 108 distinct spoligotype patterns. The predominant M.tb lineages were Lineage 4 (81.9%), Lineage 2 (9%) and Lineage 1 (7.2%). The predominant spoligotype families within Lineage 4 were LAM (33%), S (14%), T (16%), X (16%). Three hundred and ninety-two (86%) isolates could be grouped into 44 clusters (2– 46 isolates per cluster); giving a clustering rate of 76%. We identified 173 (37.8%) drug resistant isolates, 48 (10.5%) of these were multi-drug resistant. MIRU typing of the drug resistant isolates allowed grouping of 46 isolates into 14 clusters, giving a clustering rate of 49.2%. There was no association between age, sex, treatment category, region and clustering. Conclusions: This study highlights the complexity of the TB epidemic in Botswana with multiple strains contributing to disease and provides baseline data on the population structure of M.tb strains in Botswana.
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    HIV-1C env and gag variation in the cerebrospinal fluid and plasma of patients with HIV-associated cryptococcal meningitis in Botswana
    (MDPI, 2020-12-07) Kelentse, Nametso; Moyo, Sikhulile; Mogwele, Mompati L.; Ditshwanelo, Doreen; Mokaleng, Baitshepi; Moraka, Natasha O.; Lechiile, Kwana; Leeme, Tshepo B.; Lawrence, David S.; Musonda, Rosemary; Kasvosve, Ishmael; Harrison, Thomas S.; Jarvis, Joseph N.; Gaseitsiwe, Simani
    ENGLISH ABSTRACT: HIV-1 compartmentalization in reservoir sites remains a barrier to complete HIV eradication. It is unclear whether there is variation in HIV-1 env and gag between cerebrospinal fluid (CSF) and plasma of individuals with HIV-associated cryptococcal meningitis (CM). We compared HIV-1 env characteristics and the gag cytotoxic T-lymphocyte (CTL) escape mutations from CSF and plasma samples. Employing population-based Sanger sequencing, we sequenced HIV-1 env from CSF of 25 patients and plasma of 26 patients. For gag, 15 CSF and 21 plasma samples were successfully sequenced. Of these, 18 and 9 were paired env and gag CSF/plasma samples, respectively. There was no statistically significant difference in the proportion of CCR5-using strains in the CSF and plasma, (p = 0.50). Discordant CSF/plasma virus co-receptor use was found in 2/18 pairs (11.1%). The polymorphisms in the HIV-1 V3 loop were concordant between the two compartments. From the HIV-1 gag sequences, three pairs had discordant CTL escape mutations in three different epitopes of the nine analyzed. These findings suggest little variation in the HIV-1 env between plasma and CSF and that the CCR5-using strains predominate in both compartments. HIV-1 gag CTL escape mutations also displayed little variation in CSF and plasma suggesting similar CTL selective pressure.
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    Identifying recent HIV infections : from serological assays to genomics
    (MDPI, 2015-10-23) Moyo, Sikhulile; Wilkinson, Eduan; Novitsky, Vladimir; Vandormael, Alain; Gaseitsiwe, Simani; Essex, Max; Engelbrecht, Susan; De Oliveira, Tulio
    In this paper, we review serological and molecular based methods to identify HIV infection recency. The accurate identification of recent HIV infection continues to be an important research area and has implications for HIV prevention and treatment interventions. Longitudinal cohorts that follow HIV negative individuals over time are the current gold standard approach, but they are logistically challenging, time consuming and an expensive enterprise. Methods that utilize cross-sectional testing and biomarker information have become an affordable alternative to the longitudinal approach. These methods use well-characterized biological makers to differentiate between recent and established HIV infections. However, recent results have identified a number of limitations in serological based assays that are sensitive to the variability in immune responses modulated by HIV subtypes, viral load and antiretroviral therapy. Molecular methods that explore the dynamics between the timing of infection and viral evolution are now emerging as a promising approach. The combination of serological and molecular methods may provide a good solution to identify recent HIV infection in cross-sectional data. As part of this review, we present the advantages and limitations of serological and molecular based methods and their potential complementary role for the identification of HIV infection recency.