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Papers by Maphoshane Nchabeleng

Research paper thumbnail of Bacterial vaginosis and vaginal microorganisms in pregnant women with a history of adverse pregnancy outcomes at Dr George Mukhari Academic Hospital, Pretoria, South Africa

International Journal of Infectious Diseases, 2014

Background: In many developing countries, little is known about the prevalence of genital Chlamyd... more Background: In many developing countries, little is known about the prevalence of genital Chlamydia trachomatis infections and complications, such as infertility, thus preventing any policy from being formulated regarding screening for C. trachomatis of patients at risk for infertility. The objective of the present study was to determine the prevalence of C. trachomatis and evaluate the diagnostic utility of serological markers namely anti-C. trachomatis IgG and IgA antibodies in women attending an infertility clinic. Methods & Materials: Two commercial species-specific ELISA to determine serum IgG and IgA antibodies to C. trachomatis, PCR on vaginal swabs specimens and Hysterosalpingography (HSG) was performed on Serum and vaginal swab specimens of 303 women presenting with infertility to the infertility clinic of the Kigali University Teaching Hospital and 312 fertile controls in subfertile women. Results: The prevalence of C. trachomatis infection by PCR and serological test (IgG and IgA) were relatively low in both subfertile and fertile women and no significant differences in overall prevalence rates of C. trachomatis among both groups were observed. The only factor associated with C. trachomatis infection in our study population was age 25 years. Evidence of tubal pathology identified by HSG was found in 185 patients in the subfertile group (67.8%). All the serological markers measured in this study had very low sensitivities and negative predictive values in predicting tubal pathology. The specificities for ANILabsystems IgG, Vircell IgG, Anilabsystem IgA and positive C. trachomatis DNA to predict tubal pathology were 84, 86, 95 and 98%, respectively, whereas their respective positive predictive values were 73, 76, 81 and 80%. Conclusion: The prevalence of C. trachomatis in our study population in Rwanda appears to be low and women aged 25 years are more likely to have genital infection with C. trachomatis. Since serological testing for Chlamydia shows an excellent negative predictive value for lower genital tract infection, specific peptide-based serological assays may be of use for screening in low prevalence settings. Our data suggest that C. trachomatis is not the primary pathogen responsible for tubal pathology in Rwandan women.

Research paper thumbnail of Molecular characterisation of group A streptococcus isolates recovered from the north-west of Pretoria, South Africa

South African Medical Journal, Apr 30, 2021

Group A streptococcus (GAS) is a pathogen responsible for a wide range of invasive and non-invasi... more Group A streptococcus (GAS) is a pathogen responsible for a wide range of invasive and non-invasive infections. [1-3] Pharyngitis caused by GAS may have complications such as acute rheumatic fever (ARF), which may subsequently lead to rheumatic heart disease (RHD). [4,5] RHD affects millions of children and young adults in developing countries and continues to result in high morbidity and mortality, with 349 000 deaths estimated annually worldwide. [6] Antibiotics alone, although GAS remains susceptible to them, fail to control the burden of RHD, so other strategies such as preventive vaccines are required. [7-9] Various GAS vaccine candidates are being developed. [10] These are broadly divided into M-proteinbased and non-M-protein-based vaccines. [10] M-protein is a major virulence factor of GAS, encoded by the emm gene. [11] A 30-valent (SteptAnova) vaccine currently at clinical trials stage consists of 4 recombinant subunits each containing 7 or 8 N-terminal fused peptides of 30 different emm types. [8] However, the major drawback is that there are more than 220 emm types worldwide, and a single vaccine design with all emm types is not practical. [8] Potential vaccine coverage will rely on geographical molecular information of the GAS emm types circulating. [8,10,12,13] There are currently limited data on the circulating emm types in South Africa (SA). GAS emm typing technique has helped to identify and estimate the diversity of GAS strains that are circulating. [13] This technique is based on amplification of the emm gene, followed by sequencing of 160-600 bases from the 5′ portion of the gene. [13] The molecular epidemiology of GAS emm types is the information required for the development of an effective globally relevant vaccine. [8,14,15] Objectives To characterise the GAS isolates and determine the emm types circulating in northwest Pretoria, SA, in order to assess the local relevance of the 30-valent vaccine currently under development. This was an extension of a study conducted in Vanguard in Cape Town by Engel et al. [16] Methods Ethical considerations The study was approved by the Sefako Makgatho Health Sciences University Research and Ethics Committee (ref. no. SMUREC/M/154/2017: PG) and the Gauteng Provincial Ethics Committee. Permission was obtained from the management of the Dr George Mukhari (DGM) tertiary diagnostic laboratory, National Health Laboratory Service. Consent was obtained from the patients, parents and patient carers where necessary. Assent was obtained from the patients, where possible. This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Research paper thumbnail of Case-fatality and sequelae following acute bacterial meningitis in South Africa, 2016 through 2020

International Journal of Infectious Diseases

Research paper thumbnail of Prolonged shedding of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA among patients with coronavirus disease 2019 (COVID-19)

Infection Control & Hospital Epidemiology, 2020

Early reports from China indicate that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) ... more Early reports from China indicate that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA may persist in the respiratory tracts of patients with coronavirus disease 2019 (COVID-19) for several weeks after symptom onset. 1-3 However, the duration of SARS-CoV-2 RNA shedding has not been systematically studied in a large cohort of patients.

Research paper thumbnail of Sexually transmitted infections amongst men who have sex with men (MSM) in South Africa

PLOS Global Public Health

There is limited data about bacterial STIs in MSM populations in sub-Saharan Africa. Our retrospe... more There is limited data about bacterial STIs in MSM populations in sub-Saharan Africa. Our retrospective analysis used data from the HVTN 702 HIV vaccine clinical trial (October 2016 to July 2021). We evaluated multiple variables. Polymerase chain reaction testing was conducted on urine and rectal samples to detect Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) every 6 months. Syphilis serology was conducted at month 0 and thereafter every 12 months. We calculated STI prevalence and the associated 95% confidence intervals until 24 months of follow-up. The trial enrolled 183 participants who identified as male or transgender female, and of homosexual or bisexual orientation. Of these, 173 had STI testing done at month 0, median age was 23 (IQR 20–25) years, with median 20.5 (IQR 17.5–24.8) months follow-up (FU). The clinical trial also enrolled and performed month 0 STI testing on 3389 female participants, median age 23 (IQR 21–27) years, median 24.8 (IQR 18.8–24.8) months FU...

Research paper thumbnail of HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4+ T cell increases in antiretroviral-treated South African volunteers: a randomized phase II clinical trial

Retrovirology, 2016

BACKGROUND. Although combined antiretroviral therapy (cART) has saved millions of lives, it is in... more BACKGROUND. Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The Transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate 3 with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. METHODS. The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 μg) given intradermally, 3 times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4 + T-cell counts ≥200 cells/µL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4 + T-cell counts and therapy compliance. RESULTS. Immunization was safe and well-tolerated and induced durable, high titers anti-Tat Bclade antibodies in 97% vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade Envelope (Env) in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4 + T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4 + T-cell numbers over study entry levels as compared to placebo. CONCLUSIONS. The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. TRIAL REGISTRATION. ClinicalTrials.gov NCT01513135, 01/23/2012.

Research paper thumbnail of History of medicine : the Hamilton Naki Clinical Scholarship, 2007-2011

Research paper thumbnail of Antigenic distribution of Streptococcus agalactiae isolates from pregnant women at Garankuwa hospital – South Africa

GERMS, 2015

Streptococcus agalactiae (group B streptococcus; GBS) is globally recognised as one of the leadin... more Streptococcus agalactiae (group B streptococcus; GBS) is globally recognised as one of the leading causes of neonatal sepsis and meningitis. It also causes adverse pregnancy outcomes such as stillbirth and miscarriages. Incidence of invasive disease is increasing in non-pregnant adults with underlying medical conditions (e.g., diabetes mellitus). Epidemiological studies of GBS infections are based on capsular serotyping. Genotyping of the surface anchored protein genes is also becoming an important tool for GBS studies. Currently ten different GBS serotypes have been identified. This study was performed to determine the prevalence of GBS capsular types (CTs) and surface anchored protein genes in isolates from colonized pregnant women attending antenatal clinic, at Dr George Mukhari Academic Hospital, Garankuwa, Pretoria, South Africa. The samples were collected over 11 months and cultured on selective media. GBS was identified using different morphological and biochemical tests. Capsular typing was done using latex agglutination test and conventional PCR. Multiplex PCR with specific primers was used to detect the surface anchored protein genes. Of the 413 pregnant women recruited, 128 (30.9%) were colonized with GBS. The capsular polysaccharide (CPS) typing test showed that CPS type III (29.7%) was the most prevalent capsular type followed by CPS type Ia (25.8%), II (15.6%), IV (8.6%), V (10.9%) and Ib (8.6%); 0.7% of the isolates were nontypeable. Multiplex PCR revealed that the surface proteins genes were possessed by all the capsular types: rib (44.5%), bca (24.7%), alp2/3 (17.9%), epsilon (8.6%) and alp4 (4.7%). The common capsular types found in this study are Ia, III, and II. The most common protein genes identified were rib and bca, and the distribution of the surface protein genes among the isolates of different capsular types showed similar trends to the distribution reported from previous studies.

Research paper thumbnail of Molecular characterisation and associated drug susceptibility patterns of Mycobacterium tuberculosis isolates from South African children

Southern African Journal of Infectious Diseases, 2015

Research paper thumbnail of Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men

PloS one, 2015

The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of ... more The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models. Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo ...

Research paper thumbnail of Antibiotic resistance of Streptococcus agalactiae isolated from pregnant women in Garankuwa, South Africa

BMC Research Notes, 2015

Background: This study was undertaken to determine the susceptibility profile and the mechanism o... more Background: This study was undertaken to determine the susceptibility profile and the mechanism of antibiotic resistance in Group B streptococcus (GBS) isolates detected in vaginal and rectal swabs from pregnant women attending Dr George Mukhari Academic Hospital, a University Teaching Hospital in Pretoria, South Africa. Methods: The samples were collected over an 11-month period, cultured on selective media (colistin and nalidixic acid agar and Todd-Hewitt broth), and GBS positively identified by using different morphological and biochemical tests. The susceptibility testing was done using the Kirby-Bauer and E test methods according to CLSI guidelines 2012. The D test method was used for the detection of inducible clindamycin resistance. Multiplex PCR with specific primers was used to detect different genes coding for resistance. Results: Out of 413 samples collected, 128 (30.9 %) were positive with GBS. The susceptibility testing revealed that 100 % of isolates were sensitive to penicillin, ampicillin, vancomycin and high level gentamicin. Erythromycin and clindamycin resistance was 21.1 and 17.2 %, respectively, in which 69 % had harboured constitutive macrolide, lincosamide and streptogramin B (MLS B), 17.4 % had inducible MLS B. The M and L phenotypes were present in 6.8 % each. The methylation of target encoded by ermB genes was the commonest mechanism of resistance observed in 55 % of isolates, 38 % of isolates had both ermB and linB genes and efflux pump mediated by mefA genes was also distributed among the isolates. Conclusions: The study reaffirmed the appropriateness of penicillin as the antibiotic of choice for treating GBS infection. However it identified the challenges of resistance to macrolides and lincosamides used as alternative drugs for individuals allergic to penicillin. More GBS treatment options for penicillin allergic patients need to be researched on.

Research paper thumbnail of Bacteraemia in HIV-positive children in a rural Kwazulu/Natal hospital /

ABSTRACT Thesis (MMed)-University of Natal, 1998.

Research paper thumbnail of The Hamilton Naki Scholarship, 2007-2011

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, Jan 14, 2012

Thandinkosi E Madiba, University of KwaZulu-Natal, Abolade A Awotedu, Walter Sisulu University, D... more Thandinkosi E Madiba, University of KwaZulu-Natal, Abolade A Awotedu, Walter Sisulu University, Dion du Plessis, Netcare Ltd, Maphoshane Nchabeleng, University of Limpopo, Mike M Sathekge, University of Pretoria, Sithembiso C Velaphi, University of the ...

Research paper thumbnail of HIV vaccine trial safety and retention among 18-20 year olds in the HVTN 503/Phambili study support the inclusion of adolescents in future trials

Research paper thumbnail of Incident Herpes Simplex Virus Type 2 Associated with HIV Infection in Phambili

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Vaccine Enhancement Confirmed among Men in HVTN 503-S, Final Results from a Recall Study of Phambili Participants

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Self-reported Benefits of Study Participation in HVTN 503, “Phambili”

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef Vaccine Induced Immune Responses

PLoS ONE, 2014

Background: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine... more Background: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. Methods: Vaccine-induced immunogenicity was ascertained by interferon-c ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. Results: Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500). Conclusions: Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity).

Research paper thumbnail of P14-07. Offering new prevention modalities in HIV vaccine trials: Experience with male circumcision in the Phambili trial

Research paper thumbnail of Does participation in an HIV vaccine efficacy trial affect risk behaviour in South Africa?

Vaccine, 2013

Background: Increased sexual risk behaviour in participants enrolled in HIV prevention trials has... more Background: Increased sexual risk behaviour in participants enrolled in HIV prevention trials has been a concern. The HVTN 503/Phambili study, a phase 2B study of the Merck Ad-5 multiclade HIV vaccine in South Africa, suspended enrollment and vaccinations following the results of the Step study. Participants were notified of their treatment allocation and continue to be followed. We investigated changes in risk behaviour over time and assessed the impact of study unblinding. Methods: 801 participants were enrolled. Risk behaviours were assessed with an intervieweradministered questionnaire at 6-month intervals. We assessed change from enrolment to the first 6-month assessment pre-unblinding and between enrolment and at least 6 months post-unblinding on all participants with comparable data. A one-time unblinding risk perception questionnaire was administered post-unblinding. Results: A decrease in participants reporting unprotected sex was observed in both measured time periods for men and women, with no differences by treatment arm. At 6 months (pre-unblinding), 29.6% of men and 35.8% of women reported changing from unprotected to protected sex (p < 0.0001 for each). Men (22%) were more likely than women (14%) to report behaviour change after unblinding (p = 0.009). Post-enrolment, 142 (45%) of 313 previously uncircumcised men underwent medical circumcision. 663 participants completed the unblinding questionnaire. More vaccine (24.6%) as compared to placebo recipients (12.0%) agreed that they were more likely to get HIV than most people (p < 0.0001), and attributed this to receiving the vaccine. Conclusion: We did not find evidence of risk compensation during this clinical trial. Some risk behaviour reductions including male circumcision were noted irrespective of treatment allocation.

Research paper thumbnail of Bacterial vaginosis and vaginal microorganisms in pregnant women with a history of adverse pregnancy outcomes at Dr George Mukhari Academic Hospital, Pretoria, South Africa

International Journal of Infectious Diseases, 2014

Background: In many developing countries, little is known about the prevalence of genital Chlamyd... more Background: In many developing countries, little is known about the prevalence of genital Chlamydia trachomatis infections and complications, such as infertility, thus preventing any policy from being formulated regarding screening for C. trachomatis of patients at risk for infertility. The objective of the present study was to determine the prevalence of C. trachomatis and evaluate the diagnostic utility of serological markers namely anti-C. trachomatis IgG and IgA antibodies in women attending an infertility clinic. Methods & Materials: Two commercial species-specific ELISA to determine serum IgG and IgA antibodies to C. trachomatis, PCR on vaginal swabs specimens and Hysterosalpingography (HSG) was performed on Serum and vaginal swab specimens of 303 women presenting with infertility to the infertility clinic of the Kigali University Teaching Hospital and 312 fertile controls in subfertile women. Results: The prevalence of C. trachomatis infection by PCR and serological test (IgG and IgA) were relatively low in both subfertile and fertile women and no significant differences in overall prevalence rates of C. trachomatis among both groups were observed. The only factor associated with C. trachomatis infection in our study population was age 25 years. Evidence of tubal pathology identified by HSG was found in 185 patients in the subfertile group (67.8%). All the serological markers measured in this study had very low sensitivities and negative predictive values in predicting tubal pathology. The specificities for ANILabsystems IgG, Vircell IgG, Anilabsystem IgA and positive C. trachomatis DNA to predict tubal pathology were 84, 86, 95 and 98%, respectively, whereas their respective positive predictive values were 73, 76, 81 and 80%. Conclusion: The prevalence of C. trachomatis in our study population in Rwanda appears to be low and women aged 25 years are more likely to have genital infection with C. trachomatis. Since serological testing for Chlamydia shows an excellent negative predictive value for lower genital tract infection, specific peptide-based serological assays may be of use for screening in low prevalence settings. Our data suggest that C. trachomatis is not the primary pathogen responsible for tubal pathology in Rwandan women.

Research paper thumbnail of Molecular characterisation of group A streptococcus isolates recovered from the north-west of Pretoria, South Africa

South African Medical Journal, Apr 30, 2021

Group A streptococcus (GAS) is a pathogen responsible for a wide range of invasive and non-invasi... more Group A streptococcus (GAS) is a pathogen responsible for a wide range of invasive and non-invasive infections. [1-3] Pharyngitis caused by GAS may have complications such as acute rheumatic fever (ARF), which may subsequently lead to rheumatic heart disease (RHD). [4,5] RHD affects millions of children and young adults in developing countries and continues to result in high morbidity and mortality, with 349 000 deaths estimated annually worldwide. [6] Antibiotics alone, although GAS remains susceptible to them, fail to control the burden of RHD, so other strategies such as preventive vaccines are required. [7-9] Various GAS vaccine candidates are being developed. [10] These are broadly divided into M-proteinbased and non-M-protein-based vaccines. [10] M-protein is a major virulence factor of GAS, encoded by the emm gene. [11] A 30-valent (SteptAnova) vaccine currently at clinical trials stage consists of 4 recombinant subunits each containing 7 or 8 N-terminal fused peptides of 30 different emm types. [8] However, the major drawback is that there are more than 220 emm types worldwide, and a single vaccine design with all emm types is not practical. [8] Potential vaccine coverage will rely on geographical molecular information of the GAS emm types circulating. [8,10,12,13] There are currently limited data on the circulating emm types in South Africa (SA). GAS emm typing technique has helped to identify and estimate the diversity of GAS strains that are circulating. [13] This technique is based on amplification of the emm gene, followed by sequencing of 160-600 bases from the 5′ portion of the gene. [13] The molecular epidemiology of GAS emm types is the information required for the development of an effective globally relevant vaccine. [8,14,15] Objectives To characterise the GAS isolates and determine the emm types circulating in northwest Pretoria, SA, in order to assess the local relevance of the 30-valent vaccine currently under development. This was an extension of a study conducted in Vanguard in Cape Town by Engel et al. [16] Methods Ethical considerations The study was approved by the Sefako Makgatho Health Sciences University Research and Ethics Committee (ref. no. SMUREC/M/154/2017: PG) and the Gauteng Provincial Ethics Committee. Permission was obtained from the management of the Dr George Mukhari (DGM) tertiary diagnostic laboratory, National Health Laboratory Service. Consent was obtained from the patients, parents and patient carers where necessary. Assent was obtained from the patients, where possible. This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Research paper thumbnail of Case-fatality and sequelae following acute bacterial meningitis in South Africa, 2016 through 2020

International Journal of Infectious Diseases

Research paper thumbnail of Prolonged shedding of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA among patients with coronavirus disease 2019 (COVID-19)

Infection Control & Hospital Epidemiology, 2020

Early reports from China indicate that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) ... more Early reports from China indicate that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA may persist in the respiratory tracts of patients with coronavirus disease 2019 (COVID-19) for several weeks after symptom onset. 1-3 However, the duration of SARS-CoV-2 RNA shedding has not been systematically studied in a large cohort of patients.

Research paper thumbnail of Sexually transmitted infections amongst men who have sex with men (MSM) in South Africa

PLOS Global Public Health

There is limited data about bacterial STIs in MSM populations in sub-Saharan Africa. Our retrospe... more There is limited data about bacterial STIs in MSM populations in sub-Saharan Africa. Our retrospective analysis used data from the HVTN 702 HIV vaccine clinical trial (October 2016 to July 2021). We evaluated multiple variables. Polymerase chain reaction testing was conducted on urine and rectal samples to detect Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) every 6 months. Syphilis serology was conducted at month 0 and thereafter every 12 months. We calculated STI prevalence and the associated 95% confidence intervals until 24 months of follow-up. The trial enrolled 183 participants who identified as male or transgender female, and of homosexual or bisexual orientation. Of these, 173 had STI testing done at month 0, median age was 23 (IQR 20–25) years, with median 20.5 (IQR 17.5–24.8) months follow-up (FU). The clinical trial also enrolled and performed month 0 STI testing on 3389 female participants, median age 23 (IQR 21–27) years, median 24.8 (IQR 18.8–24.8) months FU...

Research paper thumbnail of HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4+ T cell increases in antiretroviral-treated South African volunteers: a randomized phase II clinical trial

Retrovirology, 2016

BACKGROUND. Although combined antiretroviral therapy (cART) has saved millions of lives, it is in... more BACKGROUND. Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The Transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate 3 with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. METHODS. The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 μg) given intradermally, 3 times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4 + T-cell counts ≥200 cells/µL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4 + T-cell counts and therapy compliance. RESULTS. Immunization was safe and well-tolerated and induced durable, high titers anti-Tat Bclade antibodies in 97% vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade Envelope (Env) in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4 + T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4 + T-cell numbers over study entry levels as compared to placebo. CONCLUSIONS. The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. TRIAL REGISTRATION. ClinicalTrials.gov NCT01513135, 01/23/2012.

Research paper thumbnail of History of medicine : the Hamilton Naki Clinical Scholarship, 2007-2011

Research paper thumbnail of Antigenic distribution of Streptococcus agalactiae isolates from pregnant women at Garankuwa hospital – South Africa

GERMS, 2015

Streptococcus agalactiae (group B streptococcus; GBS) is globally recognised as one of the leadin... more Streptococcus agalactiae (group B streptococcus; GBS) is globally recognised as one of the leading causes of neonatal sepsis and meningitis. It also causes adverse pregnancy outcomes such as stillbirth and miscarriages. Incidence of invasive disease is increasing in non-pregnant adults with underlying medical conditions (e.g., diabetes mellitus). Epidemiological studies of GBS infections are based on capsular serotyping. Genotyping of the surface anchored protein genes is also becoming an important tool for GBS studies. Currently ten different GBS serotypes have been identified. This study was performed to determine the prevalence of GBS capsular types (CTs) and surface anchored protein genes in isolates from colonized pregnant women attending antenatal clinic, at Dr George Mukhari Academic Hospital, Garankuwa, Pretoria, South Africa. The samples were collected over 11 months and cultured on selective media. GBS was identified using different morphological and biochemical tests. Capsular typing was done using latex agglutination test and conventional PCR. Multiplex PCR with specific primers was used to detect the surface anchored protein genes. Of the 413 pregnant women recruited, 128 (30.9%) were colonized with GBS. The capsular polysaccharide (CPS) typing test showed that CPS type III (29.7%) was the most prevalent capsular type followed by CPS type Ia (25.8%), II (15.6%), IV (8.6%), V (10.9%) and Ib (8.6%); 0.7% of the isolates were nontypeable. Multiplex PCR revealed that the surface proteins genes were possessed by all the capsular types: rib (44.5%), bca (24.7%), alp2/3 (17.9%), epsilon (8.6%) and alp4 (4.7%). The common capsular types found in this study are Ia, III, and II. The most common protein genes identified were rib and bca, and the distribution of the surface protein genes among the isolates of different capsular types showed similar trends to the distribution reported from previous studies.

Research paper thumbnail of Molecular characterisation and associated drug susceptibility patterns of Mycobacterium tuberculosis isolates from South African children

Southern African Journal of Infectious Diseases, 2015

Research paper thumbnail of Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men

PloS one, 2015

The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of ... more The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models. Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo ...

Research paper thumbnail of Antibiotic resistance of Streptococcus agalactiae isolated from pregnant women in Garankuwa, South Africa

BMC Research Notes, 2015

Background: This study was undertaken to determine the susceptibility profile and the mechanism o... more Background: This study was undertaken to determine the susceptibility profile and the mechanism of antibiotic resistance in Group B streptococcus (GBS) isolates detected in vaginal and rectal swabs from pregnant women attending Dr George Mukhari Academic Hospital, a University Teaching Hospital in Pretoria, South Africa. Methods: The samples were collected over an 11-month period, cultured on selective media (colistin and nalidixic acid agar and Todd-Hewitt broth), and GBS positively identified by using different morphological and biochemical tests. The susceptibility testing was done using the Kirby-Bauer and E test methods according to CLSI guidelines 2012. The D test method was used for the detection of inducible clindamycin resistance. Multiplex PCR with specific primers was used to detect different genes coding for resistance. Results: Out of 413 samples collected, 128 (30.9 %) were positive with GBS. The susceptibility testing revealed that 100 % of isolates were sensitive to penicillin, ampicillin, vancomycin and high level gentamicin. Erythromycin and clindamycin resistance was 21.1 and 17.2 %, respectively, in which 69 % had harboured constitutive macrolide, lincosamide and streptogramin B (MLS B), 17.4 % had inducible MLS B. The M and L phenotypes were present in 6.8 % each. The methylation of target encoded by ermB genes was the commonest mechanism of resistance observed in 55 % of isolates, 38 % of isolates had both ermB and linB genes and efflux pump mediated by mefA genes was also distributed among the isolates. Conclusions: The study reaffirmed the appropriateness of penicillin as the antibiotic of choice for treating GBS infection. However it identified the challenges of resistance to macrolides and lincosamides used as alternative drugs for individuals allergic to penicillin. More GBS treatment options for penicillin allergic patients need to be researched on.

Research paper thumbnail of Bacteraemia in HIV-positive children in a rural Kwazulu/Natal hospital /

ABSTRACT Thesis (MMed)-University of Natal, 1998.

Research paper thumbnail of The Hamilton Naki Scholarship, 2007-2011

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, Jan 14, 2012

Thandinkosi E Madiba, University of KwaZulu-Natal, Abolade A Awotedu, Walter Sisulu University, D... more Thandinkosi E Madiba, University of KwaZulu-Natal, Abolade A Awotedu, Walter Sisulu University, Dion du Plessis, Netcare Ltd, Maphoshane Nchabeleng, University of Limpopo, Mike M Sathekge, University of Pretoria, Sithembiso C Velaphi, University of the ...

Research paper thumbnail of HIV vaccine trial safety and retention among 18-20 year olds in the HVTN 503/Phambili study support the inclusion of adolescents in future trials

Research paper thumbnail of Incident Herpes Simplex Virus Type 2 Associated with HIV Infection in Phambili

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Vaccine Enhancement Confirmed among Men in HVTN 503-S, Final Results from a Recall Study of Phambili Participants

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Self-reported Benefits of Study Participation in HVTN 503, “Phambili”

AIDS Research and Human Retroviruses, 2014

Research paper thumbnail of Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef Vaccine Induced Immune Responses

PLoS ONE, 2014

Background: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine... more Background: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. Methods: Vaccine-induced immunogenicity was ascertained by interferon-c ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. Results: Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500). Conclusions: Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity).

Research paper thumbnail of P14-07. Offering new prevention modalities in HIV vaccine trials: Experience with male circumcision in the Phambili trial

Research paper thumbnail of Does participation in an HIV vaccine efficacy trial affect risk behaviour in South Africa?

Vaccine, 2013

Background: Increased sexual risk behaviour in participants enrolled in HIV prevention trials has... more Background: Increased sexual risk behaviour in participants enrolled in HIV prevention trials has been a concern. The HVTN 503/Phambili study, a phase 2B study of the Merck Ad-5 multiclade HIV vaccine in South Africa, suspended enrollment and vaccinations following the results of the Step study. Participants were notified of their treatment allocation and continue to be followed. We investigated changes in risk behaviour over time and assessed the impact of study unblinding. Methods: 801 participants were enrolled. Risk behaviours were assessed with an intervieweradministered questionnaire at 6-month intervals. We assessed change from enrolment to the first 6-month assessment pre-unblinding and between enrolment and at least 6 months post-unblinding on all participants with comparable data. A one-time unblinding risk perception questionnaire was administered post-unblinding. Results: A decrease in participants reporting unprotected sex was observed in both measured time periods for men and women, with no differences by treatment arm. At 6 months (pre-unblinding), 29.6% of men and 35.8% of women reported changing from unprotected to protected sex (p < 0.0001 for each). Men (22%) were more likely than women (14%) to report behaviour change after unblinding (p = 0.009). Post-enrolment, 142 (45%) of 313 previously uncircumcised men underwent medical circumcision. 663 participants completed the unblinding questionnaire. More vaccine (24.6%) as compared to placebo recipients (12.0%) agreed that they were more likely to get HIV than most people (p < 0.0001), and attributed this to receiving the vaccine. Conclusion: We did not find evidence of risk compensation during this clinical trial. Some risk behaviour reductions including male circumcision were noted irrespective of treatment allocation.