Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 70 Records) |
Query Trace: Pillay A[original query] |
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Near-universal resistance to macrolides of treponema pallidum in North America
Lieberman NAP , Reid TB , Cannon CA , Nunley BE , Berzkalns A , Cohen SE , Newman LM , Aldrete S , Xu LH , Thornlund CP , Pettus K , Lundy S , Kron M , Soge OO , Workowski K , Perlowski C , Hook EW 3rd , Dionne JA , Golden MR , Lieberman JA , Lee MK , Morshed M , Naidu P , Cao W , Pillay A , Giacani L , Greninger AL . N Engl J Med 2024 390 (22) 2127-2128 |
CDC laboratory recommendations for syphilis testing, United States, 2024
Papp JR , Park IU , Fakile Y , Pereira L , Pillay A , Bolan GA . MMWR Recomm Rep 2024 73 (1) 1-32 This report provides new CDC recommendations for tests that can support a diagnosis of syphilis, including serologic testing and methods for the identification of the causative agent Treponema pallidum. These comprehensive recommendations are the first published by CDC on laboratory testing for syphilis, which has traditionally been based on serologic algorithms to detect a humoral immune response to T. pallidum. These tests can be divided into nontreponemal and treponemal tests depending on whether they detect antibodies that are broadly reactive to lipoidal antigens shared by both host and T. pallidum or antibodies specific to T. pallidum, respectively. Both types of tests must be used in conjunction to help distinguish between an untreated infection or a past infection that has been successfully treated. Newer serologic tests allow for laboratory automation but must be used in an algorithm, which also can involve older manual serologic tests. Direct detection of T. pallidum continues to evolve from microscopic examination of material from lesions for visualization of T. pallidum to molecular detection of the organism. Limited point-of-care tests for syphilis are available in the United States; increased availability of point-of-care tests that are sensitive and specific could facilitate expansion of screening programs and reduce the time from test result to treatment. These recommendations are intended for use by clinical laboratory directors, laboratory staff, clinicians, and disease control personnel who must choose among the multiple available testing methods, establish standard operating procedures for collecting and processing specimens, interpret test results for laboratory reporting, and counsel and treat patients. Future revisions to these recommendations will be based on new research or technologic advancements for syphilis clinical laboratory science. |
Round bodies detected by treponema pallidum immunohistochemical stain in two cases of cutaneous syphilitic gummata
Birmingham SW , Saeed L , Thurlow CM , Vilfort K , Pillay A , Rojek NW , Doan LT , Lee BA . Am J Dermatopathol 2023 46 (1) 31-35 Tertiary syphilis may present a diagnostic challenge due to negative nontreponemal serologies in up to 30% of cases and frequent lack of identifiable spirochetes on histopathology or other direct detection tests. We report 2 cases of round bodies staining with Treponema pallidum immunohistochemistry by light microscopy in biopsies from cutaneous syphilitic gummata. In 1 case, the finding was validated 3 times by 2 independent laboratories; in the other case, T. pallidum was detected by polymerase chain reaction in the biopsy sample. Spirochete round bodies have previously been reported in the setting of electron microscopy and fluorography, but to the best of our knowledge, have not been reported by light microscopy in a routine skin biopsy. Although the clinical implications are unclear, this may represent a helpful new paradigm for the diagnosis of tertiary syphilis. |
Recommendations on data sharing in HIV drug resistance research
Inzaule SC , Siedner MJ , Little SJ , Avila-Rios S , Ayitewala A , Bosch RJ , Calvez V , Ceccherini-Silberstein F , Charpentier C , Descamps D , Eshleman SH , Fokam J , Frenkel LM , Gupta RK , Ioannidis JPA , Kaleebu P , Kantor R , Kassaye SG , Kosakovsky Pond SL , Kouamou V , Kouyos RD , Kuritzkes DR , Lessells R , Marcelin AG , Mbuagbaw L , Minalga B , Ndembi N , Neher RA , Paredes R , Pillay D , Raizes EG , Rhee SY , Richman DD , Ruxrungtham K , Sabeti PC , Schapiro JM , Sirivichayakul S , Steegen K , Sugiura W , van Zyl GU , Vandamme AM , Wensing AMJ , Wertheim JO , Gunthard HF , Jordan MR , Shafer RW . PLoS Med 2023 20 (9) e1004293 Author summary • Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV. |
Molecular investigation of Treponema pallidum strains associated with ocular syphilis in the United States, 2016-2020
Pillay A , Vilfort K , Debra A , Katz SS , Thurlow CM , Joseph SJ , Lundy S , Ji A , Jaeyoung H , Workowski KA , Barrow RY , Danavall D , Pettus K , Chi KH , Kersh EN , Cao W , Chen CY . Microbiol Spectr 2024 e0058124 Ocular syphilis is a serious complication of Treponema pallidum infection that can occur at any stage of syphilis and affect any eye structure. It remains unknown if certain T. pallidum strains are associated with ocular infections; therefore, we performed genotyping and whole genome sequencing (WGS) to characterize strains from patients with ocular syphilis. Seventy-five ocular or non-ocular specimens from 55 ocular syphilis patients in 14 states within the United States were collected between February 2016 and November 2020. Sufficient T. pallidum DNA was available from nine patients for genotyping and three for WGS. Genotyping was done using the augmented Centers for Disease Control and Prevention typing scheme, and WGS was performed on Illumina platforms. Multilocus sequence typing allelic profiles were predicted from whole genome sequence data. T. pallidum DNA was detected in various specimens from 17 (30.9%) of the 55 patients, and typing was done on samples from 9 patients. Four complete strain types (14d10/g, 14b9/g, 14d9/g, and 14e9/f) and five partial types were identified. WGS was successful on samples from three patients and all three strains belonged to the SS14 clade of T. pallidum. Our data reveal that multiple strain types are associated with ocular manifestations of syphilis. While genotyping and WGS were challenging due to low amounts of T. pallidum DNA in specimens, we successfully performed WGS on cerebrospinal fluid, vitreous fluid, and whole blood.IMPORTANCESyphilis is caused by the spirochete Treponema pallidum. Total syphilis rates have increased significantly over the past two decades in the United States, and the disease remains a public health concern. In addition, ocular syphilis cases has also been on the rise, coinciding with the overall increase in syphilis rates. We conducted a molecular investigation utilizing traditional genotyping and whole genome sequencing over a 5-year period to ascertain if specific T. pallidum strains are associated with ocular syphilis. Genotyping and phylogenetic analysis show that multiple T. pallidum strain types are associated with ocular syphilis in the United States. |
Population-level viremia predicts HIV incidence at the community level across the Universal Testing and Treatment Trials in eastern and southern Africa
Larmarange J , Bachanas P , Skalland T , Balzer LB , Iwuji C , Floyd S , Mills LA , Pillay D , Havlir D , Kamya MR , Ayles H , Wirth K , Dabis F , Hayes R , Petersen M . PLOS Glob Public Health 2023 3 (7) e0002157 Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV). We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression-defined as plasma HIV RNA >500 or >400 copies/mL-among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation. HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY. Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression). Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level. |
Selective whole genome amplification as a tool to enrich specimens with low Treponema pallidum genomic DNA copies for whole genome sequencing (preprint)
Thurlow CM , Joseph SJ , Ganova-Raeva L , Katz SS , Pereira L , Chen C , Debra A , Vilfort K , Workowski K , Cohen SE , Reno H , Sun Y , Burroughs M , Sheth M , Chi KH , Danavall D , Philip SS , Cao W , Kersh EN , Pillay A . bioRxiv 2021 10 Downstream next generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome, and the capture and removal of CpG-methylated host DNA using the NEBNext Microbiome DNA Enrichment Kit followed by MDA with the REPLI-g Single Cell Kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93-98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit propagated isolates, containing >14 T. pallidum genomic copies/ul of sample for SWGA and >129 genomic copies/ul for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens, showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which have been challenging until now. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Investigating the quality of HIV rapid testing practices in public antenatal health care facilities, South Africa
Nsibande DF , Woldesenbet SA , Puren A , Barron P , Maduna VI , Lombard C , Cheyip M , Mogashoa M , Pillay Y , Magasana V , Ramraj T , Kufa T , Kindra G , Goga A , Chirinda W . PLoS One 2022 17 (8) e0268687 Monitoring HIV prevalence using antenatal HIV sentinel surveillance is important for efficient epidemic tracking, programme planning and resource allocation. HIV sentinel surveillance usually employs unlinked anonymous HIV testing which raises ethical, epidemiological and public health challenges in the current era of universal test and treat. The World Health Organization (WHO) recommends that countries should consider using routine prevention of mother-to-child transmission of HIV (PMTCT) data for surveillance. We audited antenatal care clinics to assess the quality of HIV rapid testing practices as the first step to assess whether South Africa is ready to utilize PMTCT programme data for antenatal HIV surveillance. In 2017, we conducted a cross-sectional survey in 360 randomly sampled antenatal care clinics using the adapted WHO Stepwise-Process-for-Improving-the-Quality-of-HIV-Rapid-Testing (SPI-RT) checklist. We calculated median percentage scores within a domain (domain-specific median score), and across all domains (overall median percentage scores). The latter was used to classify sites according to five implementation levels; (from 0:<40% to 4: 90% or higher). Of 346 (96.1%) facilities assessed, an overall median percentage score of 62.1% (inter-quartile range (IQR): 50.8-71.9%) was obtained. The lowest domain-specific median percentage scores were obtained under training/certification (35% IQR: 10.0-50.0%) and external quality assurance (12.5% IQR: 0.0-50.0%), respectively. The majority (89%) of sites had an overall median score at level 2 or below; of these, 37% required improvement in specific areas and 6.4% in all areas. Facilities in districts implementing the HIV Rapid Test Quality Improvement Initiative and supported by the President's Emergency Plan for AIDS Relief (PEPFAR) had significantly higher median overall scores (65.6% IQR: 53.9-74.2%) (P-value from rank sum test: <0.001) compared with non-PEPFAR-supported facilities (56.6% IQR:47.7-66.0%). We found sub-optimal implementation of HIV rapid testing practices. We recommend the expansion of the PEPFAR-funded Rapid Test Continuous Quality Improvement (RTCQI) support to all antenatal care testing sites. |
Selective Whole-Genome Amplification as a Tool to Enrich Specimens with Low Treponema pallidum Genomic DNA Copies for Whole-Genome Sequencing.
Thurlow CM , Joseph SJ , Ganova-Raeva L , Katz SS , Pereira L , Chen C , Debra A , Vilfort K , Workowski K , Cohen SE , Reno H , Sun Y , Burroughs M , Sheth M , Chi KH , Danavall D , Philip SS , Cao W , Kersh EN , Pillay A . mSphere 2022 7 (3) e0000922 Downstream next-generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole-genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome and the capture and removal of 5'-C-phosphate-G-3' (CpG) methylated host DNA using the NEBNext Microbiome DNA enrichment kit followed by MDA with the REPLI-g single cell kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93 to 98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit-propagated isolates, containing >14 T. pallidum genomic copies/μL of sample for SWGA and >129 genomic copies/μL for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole-genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which has been challenging until now. IMPORTANCE Syphilis is a sexually transmitted, disseminated acute and chronic infection caused by the bacterial pathogen Treponema pallidum subspecies pallidum. Primary syphilis typically presents as single or multiple mucocutaneous lesions and, if left untreated, can progress through multiple stages with various clinical manifestations. Molecular studies often rely on direct amplification of DNA sequences from clinical specimens; however, this can be impacted by inadequate samples due to disease progression or timing of patients seeking clinical care. While genotyping has provided important data on circulating strains over the past 2 decades, WGS data are needed to better understand strain diversity, perform evolutionary tracing, and monitor antimicrobial resistance markers. The significance of our research is the development of an SWGA DNA enrichment method that expands the range of clinical specimens that can be directly sequenced to include samples with low numbers of T. pallidum. |
Evaluation of a laboratory-developed multiplex real-time PCR assay for diagnosis of syphilis, herpes and chancroid genital ulcers in four public health laboratories in the USA.
Koralur M , Chen CY , Pillay A , White B , Pettus K , Chi KH , Stringer J , Aroh C , Dasu T , Bhattacharyya S , Perkins K , Chen J , Riner D , Soehnlen M , Cao W , Gaynor AM , Kersh EN . Sex Transm Infect 2021 98 (6) 448-450 OBJECTIVE: To evaluate the field performance of a multiplex PCR (M-PCR) assay for detection of herpes simplex virus (HSV)-1 and HSV-2, Treponema pallidum (T. pallidum) and Haemophilus ducreyi (H. ducreyi) in genital ulcer disease (GUD) specimens. METHODS: GUD M-PCR was performed on 186 remnant specimens, previously collected for HSV testing, by four public health laboratories (PHLs) and the Laboratory Reference and Research Branch (LRRB) at the Centers for Disease Control and Prevention. The results from the PHLs were compared with those of LRRB, which served as the reference testing method, and percentage agreement was calculated. RESULTS: HSV was detected in 31 of 52 (59.6%), 20 of 40 (50%), 43 of 44 (97.7%) and 19 of 50 (38.0%) specimens from PHL1, PHL2, PHL3 and PHL4, respectively. There were seven discrepant results for HSV, and the overall percent agreement between the PHLs and the LRRB was 94%-100%, with a kappa value of 0.922, which demonstrates high agreement. T. pallidum was identified in 7 of 51 (13.7%) specimens from PHL1 with 94.1% agreement and in 2 of 40 (5.0%) specimens from PHL2 with 100% agreement. The LRRB identified three additional T. pallidum-positive specimens from PHL1. The kappa value (0.849) for T. pallidum testing suggests good agreement. Consistent with the LRRB results, no T. pallidum was detected in specimens from PHL3 and PHL4, and H. ducreyi was not detected at any of the study sites. CONCLUSIONS: The GUD M-PCR assay performed well in four independent PHLs and 12 suspected syphilis cases were identified in this study. The M-PCR assay could provide improved diagnostic options for GUD infections in state and local PHLs. |
The importation and establishment of community transmission of SARS-CoV-2 during the first eight weeks of the South African COVID-19 epidemic.
McCarthy KM , Tempia S , Kufa T , Kleynhans J , Wolter N , Jassat W , Ebonwu J , von Gottberg A , Erasmus L , Muchengeti M , Walaza S , Ntshoe G , Shonhiwa AM , Manana PN , Pillay Y , Moonasar D , Muthivhi T , Mngemane S , Mlisana K , Chetty K , Blumberg LH , Cohen C , Govender NP . EClinicalMedicine 2021 39 101072 BACKGROUND: We describe the epidemiology of COVID-19 in South Africa following importation and during implementation of stringent lockdown measures. METHODS: Using national surveillance data including demographics, laboratory test data, clinical presentation, risk exposures (travel history, contacts and occupation) and outcomes of persons undergoing COVID-19 testing or hospitalised with COVID-19 at sentinel surveillance sites, we generated and interpreted descriptive statistics, epidemic curves, and initial reproductive numbers (Rt). FINDINGS: From 4 March to 30 April 2020, 271,670 SARS-CoV-2 PCR tests were performed (462 tests/100,000 persons). Of these, 7,892 (2.9%) persons tested positive (median age 37 years (interquartile range 28-49 years), 4,568 (58%) male, cumulative incidence of 13.4 cases/100,000 persons). Hospitalization records were found for 1,271 patients (692 females (54%)) of whom 186 (14.6%) died. Amongst 2,819 cases with data, 489/2819 (17.3%) travelled internationally within 14 days prior to diagnosis, mostly during March 2020 (466 (95%)). Cases diagnosed in April compared with March were younger (median age, 37 vs. 40 years), less likely female (38% vs. 53%) and resident in a more populous province (98% vs. 91%). The national initial R(t) was 2.08 (95% confidence interval (CI): 1.71-2.51). INTERPRETATION: The first eight weeks following COVID-19 importation were characterised by early predominance of imported cases and relatively low mortality and transmission rates. Despite stringent lockdown measures, the second month following importation was characterised by community transmission and increasing disease burden in more populous provinces. |
Detection of Lymphogranuloma Venereum- associated Chlamydia trachomatis L2 Serovars in Remnant Rectal Specimens Collected from Seven United States Public Health Laboratories
Chi KH , de Voux A , Morris M , Katz SS , Pillay A , Danavall D , Bowden KE , Gaynor AM , Kersh EN . Sex Transm Dis 2021 49 (1) e26-e28 The frequency of lymphogranuloma venereum (LGV) or invasive Chlamydia trachomatis (CT) infection with serovar L1, L2 or L3 is unknown in the United States. While no diagnostic test is commercially available, we used a laboratory-developed test and detected LGV-associated serovar L2 in 14% of 132 remnant CT-positive rectal swabs. |
Antibody responses to two recombinant treponemal antigens (rp17 and TmpA) before and after azithromycin treatment for yaws in Ghana and Papua New Guinea
Parameswaran N , Mitjà O , Bottomley C , Kwakye C , Houinei W , Pillay A , Danavall D , Chi KH , Ballard RC , Solomon AW , Chen CY , Bieb SV , Adu-Sarkodie Y , Mabey DC , Asiedu K , Marks M , Martin D . J Clin Microbiol 2021 59 (5) WHO and its partners aim to interrupt yaws transmission in endemic countries and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical.We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6-15 years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semi-quantitative bead-based immunoassay.Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold-change. These data demonstrate that responses to TmpA decrease markedly within 6 months of treatment whereas (as expected) those to rp17 do not.Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping. |
Impact of breastfeeding, maternal antiretroviral treatment and health service factors on 18-month vertical transmission of HIV and HIV-free survival: results from a nationally representative HIV-exposed infant cohort, South Africa
Goga AE , Lombard C , Jackson D , Ramokolo V , Ngandu NK , Sherman G , Puren A , Chirinda W , Bhardwaj S , Makhari N , Ramraj T , Magasana V , Singh Y , Pillay Y , Dinh TH . J Epidemiol Community Health 2020 74 (12) 1069-1077 BACKGROUND: We analysed the impact of breastfeeding, antiretroviral drugs and health service factors on cumulative (6 weeks to 18 months) vertical transmission of HIV (MTCT) and 'MTCT-or-death', in South Africa, and compared estimates with global impact criteria to validate MTCT elimination: (1) <5% final MTCT and (2) case rate ≤50 (new paediatric HIV infections/100 000 live births). METHODS: 9120 infants aged 6 weeks were enrolled in a nationally representative survey. Of 2811 HIV-exposed uninfected infants (HEU), 2644 enrolled into follow-up (at 3, 6, 9, 12, 15 and 18 months). Using Kaplan-Meier analysis and weighted survey domain-based Cox proportional hazards models, we estimated cumulative risk of MTCT and 'MTCT or death' and risk factors for time-to-event outcomes, adjusting for study design and loss-to-follow-up. RESULTS: Cumulative (final) MTCT was 4.3% (95% CI 3.7% to 5.0%); case rate was 1290. Postnatal MTCT (>6 weeks to 18 months) was 1.7% (95% CI 1.2% to 2.4%). Cumulative 'MTCT-or-death' was 6.3% (95% CI 5.5% to 7.3%); 81% and 62% of cumulative MTCT and 'MTCT-or-death', respectively, occurred by 6 months. Postnatal MTCT increased with unknown maternal CD4-cell-count (adjusted HR (aHR 2.66 (1.5-5.6)), undocumented maternal HIV status (aHR 2.21 (1.0-4.7)) and exclusive (aHR 2.3 (1.0-5.2)) or mixed (aHR 3.7 (1.2-11.4)) breastfeeding. Cumulative 'MTCT-or death' increased in households with 'no refrigerator' (aHR 1.7 (1.1-2.9)) and decreased if infants used nevirapine at 6 weeks (aHR 0.4 (0.2-0.9)). CONCLUSIONS: While the <5% final MTCT target was met, the case rate was 25-times above target. Systems are needed in the first 6 months post-delivery to optimise HEU health and fast-track ART initiation in newly diagnosed mothers. |
Molecular and Direct Detection Tests for Treponema pallidum Subspecies pallidum: A Review of the Literature, 1964-2017.
Theel ES , Katz SS , Pillay A . Clin Infect Dis 2020 71 S4-s12 Direct detection methods for Treponema pallidum include dark-field microscopy (DFM), direct fluorescence antibody (DFA) testing, immunohistochemistry (IHC), and nucleic acid amplification tests (NAATs). Here, we reviewed the relevant syphilis diagnostic literature to address 2 main questions with respect to T. pallidum direct detection techniques: "What are the performance characteristics for each direct detection test for T. pallidum and what are the optimal specimen types for each test?" and "What options are available for T. pallidum molecular epidemiology?" To answer these questions, we searched 5 electronic databases (OVID Medline, OVID Embase, CINAHL, Cochrane Library, and Scopus) from 1964 to 2017 using relevant search terms and identified 1928 articles, of which 37 met our inclusion criteria. DFM and DFA sensitivities ranged from 73% to 100% in cases of primary syphilis; and while sensitivity using silver stain histopathology for T. pallidum was generally low (0%-41%), higher performance characteristics were observed for T. pallidum-specific IHC (49-92%). Different genes have been targeted by T. pallidum-specific NAATs, with the majority of studies indicating that sensitivity is primarily dependent on the type of collected biological sample, with highest sensitivity observed in primary lesion exudate (75-95%). Given the rising incidence of syphilis, the development of direct, Food and Drug Administration-cleared T. pallidum NAATs should be considered an immediate priority. |
Awareness of HIV-positive status and linkage to treatment prior to pregnancy in the "test and treat" era: A national antenatal sentinel survey, 2017, South Africa
Woldesenbet S , Kufa T , Cheyip M , Ayalew K , Lombard C , Manda S , Nadol P , Barron P , Chirombo B , Igumbor E , Pillay Y , Puren A . PLoS One 2020 15 (3) e0229874 INTRODUCTION: Knowledge of HIV status in South Africa (SA) is reported to be 90% among people living with HIV. National level estimates could mask population-specific levels, which are critical to monitor program coverage and potential impact. Using data from the 2017 national antenatal sentinel survey, we assessed knowledge of HIV-positive status, initiation of antiretroviral therapy (ART), and socio-demographic characteristics associated with knowledge of HIV-positive status prior to the current pregnancy among women attending antenatal care. METHODS: Between 1 October and 15 November 2017, a nationally representative sample of 32,716 pregnant women were enrolled from 1,595 public health facilities selected from all districts of SA. Data on age, gravidity, knowledge of HIV-positive status and ART initiation prior to pregnancy were extracted from medical records. A blood sample was collected from each woman regardless of prior knowledge of HIV status or ART history, and tested for HIV in the laboratory. All HIV-positive pregnant women enrolled in the survey were eligible for inclusion in the analysis. Multivariable survey logistic regression was used to examine factors associated with knowledge of HIV-positive status prior to the current pregnancy. RESULTS: Of 10,065 eligible HIV-positive women, 60.8% (95% confidence interval (CI):59.9%-61.7%) knew their HIV status prior to the current pregnancy, of whom 91.1% (95% CI: 90.4%-91.7%) initiated ART prior to the current pregnancy. Knowledge of HIV-positive status was lower among adolescent girls and young women (15-24 years) (38.9%) and primigravid women (40.5%) compared with older women (35-49 years) (75.5%) and multigravid women (64.7%). In a multivariable analysis, significant effect modification was found between gravidity and age (P value = 0.047). Being in the age group 15-24 years compared to the age group 35-49 years decreased the odds of knowing HIV-positive status by 80% (adjusted odds ratio (AOR): 0.2, 95% CI:0.1-0.4) among primigravid women and by 60%(AOR: 0.4, 95% CI:0.3-0.4) among multigravid women. CONCLUSION: Knowledge of HIV-positive status prior to the current pregnancy fell short of the target of 90% among pregnant women living with HIV. This was especially low among adolescent girls and young women, highlighting the gap in youth friendly reproductive health and HIV testing services. |
Updated assessment of risks and benefits of dolutegravir versus efavirenz in new antiretroviral treatment initiators in sub-Saharan Africa: modelling to inform treatment guidelines
Phillips AN , Bansi-Matharu L , Venter F , Havlir D , Pozniak A , Kuritzkes DR , Wensing A , Lundgren JD , Pillay D , Mellors J , Cambiano V , Jahn A , Apollo T , Mugurungi O , Ripin D , Da Silva J , Raizes E , Ford N , Siberry GK , Gupta RK , Barnabas R , Revill P , Cohn J , Calmy A , Bertagnolio S . Lancet HIV 2020 7 (3) e193-e200 BACKGROUND: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens. METHODS: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted. FINDINGS: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2.9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain. INTERPRETATION: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators. FUNDING: Bill & Melinda Gates Foundation. |
Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa.
Chimukangara B , Kharsany ABM , Lessells RJ , Naidoo K , Rhee SY , Manasa J , Graf T , Lewis L , Cawood C , Khanyile D , Diallo K , Ayalew KA , Shafer RW , Hunt G , Pillay D , Abdool SK , de Oliveira T . AIDS Res Hum Retroviruses 2019 35 (2) 129-138 There is evidence of increasing levels of pretreatment HIV drug resistance (PDR) in Southern Africa. We used data from two large population-based HIV surveillance studies to estimate prevalence of PDR in KwaZulu-Natal, the province with the highest HIV prevalence in South Africa. Sanger sequencing was performed on samples obtained from a longitudinal HIV surveillance program (study A, 2013-2014) and the HIV Incidence Provincial Surveillance System (study B, 2014-2015). Sequences were included for adult HIV positive participants (age >/=15 years for study A, age 15-49 years for study B) with no documented prior exposure to antiretroviral therapy (ART). Overall and drug class-specific PDR was estimated using the World Health Organization 2009 surveillance drug resistance mutation (SDRM) list, and phylogenetic analysis was performed to establish evidence of drug resistance transmission linkage. A total of 1,845 sequences were analyzed (611 study A; 1,234 study B). An overall PDR prevalence of 9.2% [95% confidence interval (CI) 7.0-11.7] was observed for study A and 11.0% (95% CI 8.9-13.2) for study B. In study B, the prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR exceeded 10% for sequences collected in 2014 (10.2%, 95% CI 7.5-12.9). The most prevalent SDRMs were K103NS (7.5%), M184VI (2.4%), and V106AM (1.4%). There was no evidence of large transmission chains of drug-resistant virus. High level NNRTI PDR (>10%) suggests a need to modify the standard first-line ART regimen and to focus attention on improving the quality of HIV prevention, treatment, and care. |
Successful isolation of Treponema pallidum strains from patients' cryopreserved ulcer exudate using the rabbit model.
Pereira LE , Katz SS , Sun Y , Mills P , Taylor W , Atkins P , Thurlow CM , Chi KH , Danavall D , Cook N , Ahmed T , Debra A , Philip S , Cohen S , Workowski KA , Kersh E , Fakile Y , Chen CY , Pillay A . PLoS One 2020 15 (1) e0227769 Clinical isolates of Treponema pallidum subspecies pallidum (T. pallidum) would facilitate study of prevalent strains. We describe the first successful rabbit propagation of T. pallidum from cryopreserved ulcer specimens. Fresh ulcer exudates were collected and cryopreserved with consent from syphilis-diagnosed patients (N = 8). Each of eight age-matched adult male rabbits were later inoculated with a thawed specimen, with two rabbits receiving 1.3 ml intratesticularly (IT), and six receiving 0.6 ml intravenously (IV) and IT. Monitoring of serology, blood PCR and orchitis showed that T. pallidum grew in 2/8 rabbits that were inoculated IV and IT with either a penile primary lesion specimen (CDC-SF003) or a perianal secondary lesion specimen (CDC-SF007). Rabbit CDC-SF003 was seroreactive by T. pallidum Particle Agglutination (TP-PA) and Rapid Plasma Reagin (RPR) testing, PCR+, and showed orchitis by week 6. Euthanasia was performed in week 7, with treponemal growth in the testes confirmed and quantified by qPCR and darkfield microscopy (DF). Serial passage of the extract in a second age-matched rabbit also yielded treponemes. Similarly, rabbit CDC-SF007 showed negligible orchitis, but was seroreactive and PCR+ by week 4 and euthanized in week 6 to yield T. pallidum, which was further propagated by second passage. Using the 4-component molecular typing system for syphilis, 3 propagated strains (CDC-SF003, CDC-SF007, CDC-SF008) were typed as 14d9f, 14d9g, and 14d10c, respectively. All 3 isolates including strain CDC-SF011, which was not successfully propagated, had the A2058G mutation associated with azithromycin resistance. Our results show that immediate cryopreservation of syphilitic ulcer exudate can maintain T. pallidum viability for rabbit propagation. |
Evaluation of the WHO/CDC Syphilis Serology Proficiency Programme to support the global elimination of mother-to-child transmission of syphilis: an observational cross-sectional study, 2008-2015
Hopkins AO , Trinh T , Fakile YF , Pillay A , Taylor MM , Kersh E , Kamb M . BMJ Open 2020 10 (1) e029434 OBJECTIVES: Syphilis morbidity is high among pregnant women in lower income countries with limited laboratory capacity. We evaluated a long-standing global Syphilis Serology Proficiency Programme (SSPP) that supports testing quality in national reference laboratories to determine if participation affects congenital syphilis elimination strategies. DESIGN: In this observational cross-sectional study, we calculated coverage on type, frequency and quality of syphilis testing reported by laboratories enrolled in the SSPP from 2008 to 2015. We used country-reported data to WHO on four congenital syphilis (CS) indicators and World Bank country economic data to compare coverage and completeness of reporting of indicators in lower income countries with and without an SSPP-enrolled laboratory. PARTICIPANTS: From 2008-2015, 78 laboratories from 51 countries participated in >1 SSPP evaluation; 56% were national reference laboratories, of which most (93%) participated for >3 years and 11 (22%) in all 24 cycles. RESULTS: Median proficiency performance score was >95% regardless of test conducted. Of the 51 countries with an SSPP-enrolled laboratory, 22 (43%) were lower-income countries, of which 21 reported CS data during 2008-2015. Comparing CS data from 87 (90% of total) lower income countries with and without an SSPP-enrolled laboratory, countries with an SSPP-laboratory had stronger reporting on antenatal syphilis testing (p=0.04). For 2015, an estimated 74% of prenatal syphilis tests and 63% of positive tests reported to WHO from countries with an SSPP-enrolled laboratory. CONCLUSION: The SSPP has focused well on national reference laboratories, but has been only partially successful in recruiting laboratories from lower income countries. The finding that over half of syphilis infections in pregnant women living in countries with SSPP-enrolled laboratories suggests wide reach of the current quality assurance programme. However, reach could expand with focussed recruitment of laboratories from lower income countries. |
Viral suppression and factors associated with failure to achieve viral suppression among pregnant women in South Africa: a national cross-sectional survey
Woldesenbet SA , Kufa T , Barron P , Chirombo BC , Cheyip M , Ayalew K , Lombard C , Manda S , Diallo K , Pillay Y , Puren AJ . AIDS 2019 34 (4) 589-597 OBJECTIVE: To describe viral load (VL) levels among pregnant women and factors associated with failure to achieve viral suppression (VL</=50 copies/mL) (VS) during pregnancy. DESIGN: Between 1 October and 15 November 2017, a cross-sectional survey was conducted among 15-49 year old pregnant women attending antenatal care (ANC) in 1,595 nationally representative public facilities. METHODS: Blood specimens were taken from each pregnant woman and tested for HIV. VL testing was done on all HIV-positive specimens. Demographic and clinical data were extracted from medical records or self-reported. Survey logistic regression examined factors associated with failure to achieve VS. RESULT: Of 10,052 HIV-positive participants with VL data, 56.2% were virally suppressed. Participants initiating ART prior to pregnancy had higher VS (71.0%) by their third trimester compared with participants initiating ART during pregnancy (59.3%). Booking for ANC during the third trimester vs earlier: (adjusted odds ratio (AOR) 1.8, 95% confidence interval (CI):1.4-2.3), low frequency of ANC visits (AOR for 2 ANC visits vs >/=4 ANC visits: 2.0, 95%CI:1.7-2.4), delayed initiation of ART (AOR for ART initiated at the second trimester vs before pregnancy:2.2, 95%CI:1.8-2.7), and younger age (AOR for 15-24years vs 35-49years: 1.4, 95%CI:1.2-1.8) were associated with failure to achieve VS at third trimester. CONCLUSION: Failure to achieve VS was primarily associated with late initiation of ANC and late initiation of ART. Efforts to improve early ANC booking and early ART initiation in the general population would help improve VS rates among pregnant women. In addition, the study found, despite initiating ART prior to pregnancy, more than one quarter of participants did not achieve VS in their third trimester. This highlights the need to closely monitor VL and strengthen counselling and support services for ART adherence. |
Assessment of readiness to transition from antenatal HIV surveillance surveys to PMTCT program data based HIV surveillance, in South Africa, the 2017 Antenatal Sentinel HIV Survey
Selamawit AW , Kufa T , Barron P , Ayalew K , Cheyip M , Chirombo BC , Lombard C , Manda S , Pillay Y , Puren AJ . Int J Infect Dis 2019 91 50-56 OBJECTIVE: South Africa has used antenatal HIV surveys for HIV surveillance in pregnant women since 1990. We assessed South Africa's readiness to transition to programme data based antenatal HIV surveillance with respect to PMTCT uptake, accuracy of point-of-care rapid testing (RT) and selection bias with using programme data in the context of the 2017 antenatal HIV survey. METHODS: Between 1 October and 15 November 2017, the national survey was conducted in 1,595 public antenatal facilities selected using stratified multistage cluster sampling method. Results of point-of-care RT were obtained from medical records. Blood samples were taken from eligible pregnant women and tested for HIV using immunoassays (IA) in the laboratory. Descriptive statistics were used to report on: PMTCT uptake; agreement between HIV point-of-care RT and laboratory-based HIV-1 IA; and selection bias associated with using programme data for surveillance. RESULTS: PMTCT HIV testing uptake was high (99.8%). The positive percent agreement (PPA) between RT and IA was lower than the World Health Organization (WHO) benchmark (97.6%) at 96.3% (95% confidence interval (CI):95.9%-96.6%). The negative percent agreement was above the WHO benchmark (99.5%), at 99.7%(95%CI:99.6%-99.7%) nationally. PPA markedly varied by province (92.9%-98.3%). Selection bias due to exclusion of participants with no RT results was within the recommended threshold at 0.3%. CONCLUSION: For the three components assessed, South Africa was close to meeting the WHO standard for transitioning to routine RT data for antenatal HIV surveillance. The wide variations in PPA across provinces should be addressed. |
What will it take for the Global Plan priority countries in Sub-Saharan Africa to eliminate mother-to-child transmission of HIV
Goga AE , Dinh TH , Essajee S , Chirinda W , Larsen A , Mogashoa M , Jackson D , Cheyip M , Ngandu N , Modi S , Bhardwaj S , Chirwa E , Pillay Y , Mahy M . BMC Infect Dis 2019 19 783 BACKGROUND: The 2016 'Start Free, Stay Free, AIDS Free' global agenda, builds on the 2011-2015 'Global Plan'. It prioritises 22 countries where 90% of the world's HIV-positive pregnant women live and aims to eliminate vertical transmission of HIV (EMTCT) and to keep mothers alive. By 2019, no Global Plan priority country had achieved EMTCT; however, 11 non-priority countries had. This paper synthesises the characteristics of the first four countries validated for EMTCT, and of the 21 Global Plan priority countries located in Sub-Saharan Africa (SSA). We consider what drives vertical transmission of HIV (MTCT) in the 21 SSA Global Plan priority countries. METHODS: A literature review, using PubMed, Science direct and the google search engine was conducted to obtain global and national-level information on current HIV-related context and health system characteristics of the first four EMTCT-validated countries and the 21 SSA Global Plan priority countries. Data representing only one clinic, hospital or region were excluded. Additionally, key global experts working on EMTCT were contacted to obtain clarification on published data. We applied three theories (the World Health Organisation's building blocks to strengthen health systems, van Olmen's Health System Dynamics framework and Baral's socio-ecological model for HIV risk) to understand and explain the differences between EMTCT-validated and non-validated countries. Additionally, structural equation modelling (SEM) and linear regression were used to explain associations between infant HIV exposure, access to antiretroviral therapy and two outcomes: (i) percent MTCT and (iii) number of new paediatric HIV infections per 100 000 live births (paediatric HIV case rate). RESULTS: EMTCT-validated countries have lower HIV prevalence, less breastfeeding, fewer challenges around leadership, governance within the health sector or country, infrastructure and service delivery compared with Global Plan priority countries. Although by 2016 EMTCT-validated countries and Global Plan priority countries had adopted a public health approach to HIV prevention, recommending lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and lactating women, EMCT-validated countries had also included contact tracing such as assisted partner notification, and had integrated maternal and child health (MCH) and sexual and reproductive health (SRH) services, with services for HIV infection, sexually transmitted infections, and viral hepatitis. Additionally, Global Plan priority countries have limited data on key SRH indicators such as unmet need for family planning, with variable coverage of antenatal care, HIV testing and triple antiretroviral therapy (ART) and very limited contact tracing. Structural equation modelling (SEM) and linear regression analysis demonstrated that ART access protects against percent MTCT (p<0.001); in simple linear regression it is 53% protective against percent MTCT. In contrast, SEM demonstrated that the case rate was driven by the number of HIV exposed infants (HEI) i.e. maternal HIV prevalence (p<0.001). In linear regression models, ART access alone explains only 17% of the case rate while HEI alone explains 81% of the case rate. In multiple regression, HEI and ART access accounts for 83% of the case rate, with HEI making the most contribution (coef. infant HIV exposure=82.8, 95% CI: 64.6, 101.1, p<0.001 vs coef. ART access=-3.0, 95% CI: -6.2, 0.3, p=0.074). CONCLUSION: Reducing infant HIV exposure, is critical to reducing the paediatric HIV case rate; increasing ART access is critical to reduce percent MTCT. Additionally, our study of four validated countries underscores the importance of contact tracing, strengthening programme monitoring, leadership and governance, as these are potentially-modifiable factors. |
A nonhuman primate model for rectally transmitted syphilis
Tansey C , Zhao C , Hopkins A , Ritter JM , Fakile YF , Pillay A , Katz SS , Pereira L , Mitchell J , Deyounks F , Kersh EN , McNicholl JM , Vishwanathan SA . J Infect Dis 2018 217 (7) 1139-1144 Among men who have sex with men (MSM), those with a diagnosis of syphilis or other rectal sexually transmitted infections (STIs) are at a higher risk for human immunodeficiency virus acquisition, which is concerning given the large increase in recently reported syphilis cases in the United States. We have developed the first nonhuman primate model for rectally transmitted syphilis by exposing simian/human immunodeficiency virus-infected and naive rhesus macaques to Treponema pallidum in the rectum. All animals showed mucosal lesions, systemic dissemination, and seroconversion (treponemal antibodies). This model would be valuable for studying the manifestations of and interventions for T. pallidum infection, with and without human immunodeficiency virus coinfection. |
Increased discrimination of Treponema pallidum strains by subtyping with a four-component system incorporating a mononucleotide tandem repeat in rspA.
Pillay A , Lee MK , Slezak T , Katz SS , Sun Y , Chi KH , Morshed M , Philip S , Ballard RC , Chen CY . Sex Transm Dis 2019 46 (4) e42-e45 A guanine mononucleotide repeat in the rpsA (tp0279) gene was evaluated for improved strain discrimination using 72 Treponema pallidum-positive specimens. The tandem repeat combined with the enhanced Centers for Disease Control and Prevention typing system resulted in increased discrimination and should be useful for molecular epidemiologic studies on syphilis especially in outbreaks and among men who have sex with men. |
Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis.
Chimukangara B , Lessells RJ , Rhee SY , Giandhari J , Kharsany ABM , Naidoo K , Lewis L , Cawood C , Khanyile D , Ayalew KA , Diallo K , Samuel R , Hunt G , Vandormael A , Stray-Pedersen B , Gordon M , Makadzange T , Kiepiela P , Ramjee G , Ledwaba J , Kalimashe M , Morris L , Parikh UM , Mellors JW , Shafer RW , Katzenstein D , Moodley P , Gupta RK , Pillay D , Abdool Karim SS , de Oliveira T . EClinicalMedicine 2019 9 26-34 Background: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa. Methods: We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect. Findings: We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4–11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13–1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05–1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). Interpretation: Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV. Source of Funding: This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package. Disclaimer: The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC. |
A case of inguinal lymphogranuloma venereum imitating malignancy on CT imaging
Promer K , Pillay A , Chi KH , Vahdat N , Katz SS , Chen CY , Fierer J . Radiol Case Rep 2019 14 (5) 581-583 Lymphogranuloma venereum is a sexually transmitted infection caused by serovars L1, L2, and L3 of Chlamydia trachomatis. We here report a case of Lymphogranuloma venereum, confirmed by PCR testing, which mimicked malignancy on CT imaging. |
Completeness of patient-held records: observations of the Road-to-Health Booklet from two national facility-based surveys at 6 weeks postpartum, South Africa
Ramraj T , Goga AE , Larsen A , Ramokolo V , Bhardwaj S , Chirinda W , Jackson D , Nsibande D , Ayalew K , Pillay Y , Lombard CJ , Ngandu NK . J Glob Health 2018 8 (2) 020901 Background: Continuity of care is important for child well-being in all settings where postnatal retention of mother-infant pairs in care remains a challenge. This analysis reports on completeness of patient-held infant Road to Health Booklets (RtHBs), amongst HIV exposed and unexposed infants during the first two years after the RtHB was launched country-wide in South Africa. Methods: Secondary data were analysed from two nationally representative, cross-sectional surveys, conducted in 2011-12 and 2012-13. These surveys aimed to measure early effectiveness of the national programme for preventing vertical HIV transmission. Participants were eligible for this analysis if they were 4-8 weeks old, receiving their six-week immunisation, not needing emergency care and had their RtHBs reviewed. Caregivers were interviewed and data abstracted from RtHBs. RtHB completeness across both surveys was defined as the proportion of RtHBs with any of the following indicators recorded: infant birth weight, BCG immunisation, maternal syphilis results and maternal HIV status. A partial proportional odds logistic regression model was used to identify factors associated with completeness. Survey sampling weights were included in all analyses. Results: Data from 10 415 (99.6%) participants in 2011-12 and 9529 (99.2%) in 2012-13 were analysed. Overall, recording of all four indicators increased from 23.1% (95% confidence interval (CI) = 22.2-24.0) in 2011-12 to 43.3% (95% CI = 42.3-44.4) in 2012-13. In multivariable models, expected RtHB completeness (ie, recording all four indicators vs recording of <4 indicators), was significantly (P<0.05) associated with survey year, marital status, socio-economic status, maternal antenatal TB screening, antenatal infant feeding counselling, delivery at a clinic or hospital and type of birth attendant. Conclusions: Routine patient-held infant health RtHB, a critical tool for continuity of care in high HIV/TB prevalence settings, was poorly completed, with less than 50% of the RtHB showing expected completeness. However, government efforts for improved usage of the booklet were evidenced by the near doubling of completeness from 2011 to 2013. Education about its importance and interventions aiming at optimising its use without violating user privacy should be continued. |
Molecular strain typing of the yaws pathogen, Treponema pallidum subspecies pertenue.
Katz SS , Chi KH , Nachamkin E , Danavall D , Taleo F , Kool JL , Addo KK , Ampofo W , Simpson SV , Ye T , Asiedu KB , Ballard RC , Chen CY , Pillay A . PLoS One 2018 13 (9) e0203632 Yaws is a neglected tropical disease caused by the bacterium Treponema pallidum subspecies pertenue. The disease primarily affects children under 15 years of age living in low socioeconomic conditions in tropical areas. As a result of a renewed focus on the disease owing to a recent eradication effort initiated by the World Health Organization, we have evaluated a typing method, adapted from and based on the enhanced Centers for Disease Control and Prevention typing method for T. pallidum subsp. pallidum, for possible use in epidemiological studies. Thirty DNA samples from yaws cases in Vanuatu and Ghana, 11 DNA samples extracted from laboratory strains, and 3 published genomic sequences were fully typed by PCR/RFLP analysis of the tpr E, G, and J genes and by determining the number of 60-bp repeats within the arp gene. Subtyping was performed by sequencing a homonucleotide "G" tandem repeat immediately upstream of the rpsA gene and an 84-bp region of tp0548. A total of 22 complete strain types were identified; two strain types in clinical samples from Vanuatu (5q11/ak and 5q12/ak), nine strain types in clinical samples from Ghana (3q12/ah, 4r12/ah, 4q10/j, 4q11/ah, 4q12/ah, 4q12/v, 4q13/ah, 6q10/aj, and 9q10/ai), and twelve strain types in laboratory strains and published genomes (2q11/ae, 3r12/ad, 4q11/ad, 4q12/ad, 4q12/ag, 4q12/v, 5r12/ad, 6r12/x, 6q11/af, 10q9/r, 10q12/r, and 12r12/w). The tpr RFLP patterns and arp repeat sizes were subsequently verified by sequencing analysis of the respective PCR amplicons. This study demonstrates that the typing method for subsp. pallidum can be applied to subsp. pertenue strains and should prove useful for molecular epidemiological studies on yaws. |
Centers for Disease Control and Prevention Syphilis Summit - diagnostics and laboratory issues
Pillay A . Sex Transm Dis 2018 45 S13-s16 Syphilis, caused by the bacterium Treponema pallidum, is on the rise in the United States particularly among men who have sex with men. The disease is complex with varied clinical manifestations and challenges remain in the laboratory diagnostic setting because T. pallidum is noncultivable and no single test can accurately diagnose all stages of the disease. There are missed opportunities for the use of direct detection tests in primary and secondary syphilis. The increasing use of different reverse sequence algorithms for serology testing without validation in populations with varying risks for syphilis makes the interpretation of test results difficult; this has led to concerns about diagnostic errors or overtreatment. On the other hand, the traditional algorithm may miss some early primary syphilis cases, which is of concern in high-risk populations. The potential utility of rapid syphilis serology tests in different settings or populations remains to be determined. The implementation of better tests and appropriate testing algorithms together with laboratory guidelines for test use in general will lead to better diagnostic options for syphilis. |
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