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1.
Int J Tuberc Lung Dis ; 26(3): 224-231, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35197162

ABSTRACT

BACKGROUND: TB diagnosis in patients with HIV is challenging due to the lower sensitivities across tests. Molecular tests are preferred and the Xpert® MTB/RIF assay has limitations in lower-income settings. We evaluated the performance of loop-mediated isothermal amplification (LAMP) and the lipoarabinomannan (LAM) test in HIV-positive, ART-naïve clinic patients.METHODS: A total of 783 eligible patients were enrolled; three spot sputum samples of 646 patients were tested using TB-LAMP, Xpert, smear microscopy and culture, while 649 patients had TB-LAM testing. Sensitivity, specificity, and negative and positive predictive values were estimated with 95% confidence intervals.RESULTS: Sensitivities for smear microscopy, TB-LAMP and Xpert were respectively 50%, 63% and 74% compared to culture, with specificities of respectively 99.2%, 98.5% and 97.5%. An additional eight were positive on TB-LAM alone. Seventy TB patients (9%) were detected using standard-of-care testing, an additional 27 (3%) were detected using study testing. Treatment was initiated in 57/70 (81%) clinic patients, but only in 56% (57/97) of all those with positive TB tests; 4/8 multidrug-resistant samples were detected using Xpert.CONCLUSION: TB diagnostics continue to miss cases in this high-burden setting. TB-LAMP was more sensitive than smear microscopy, and if followed by culture and drug susceptibility testing as required, can diagnose TB in HIV-positive patients. TB-LAM is a useful add-in test and both tests at the point-of-care would maximise yield.


Subject(s)
HIV Infections , Mycobacterium tuberculosis , Tuberculosis , Humans , Anti-Retroviral Agents , HIV Infections/complications , HIV Infections/drug therapy , Microbial Sensitivity Tests , Sensitivity and Specificity , Sputum , Tuberculosis/diagnosis
2.
Public Health Action ; 11(3): 120-125, 2021 Sep 21.
Article in English | MEDLINE | ID: mdl-34567987

ABSTRACT

OBJECTIVE: To describe the medical, socio-economic and geographical profiles of patients with rifampicin-resistant TB (RR-TB) and the implications for the provision of patient-centred care. SETTING: Thirteen districts across three South African provinces. DESIGN: This descriptive study examined laboratory and healthcare facility records of 194 patients diagnosed with RR-TB in the third quarter of 2016. RESULTS: The median age was 35 years; 120/194 (62%) of patients were male. Previous TB treatment was documented in 122/194 (63%) patients and 56/194 (29%) had a record of fluoroquinolone and/or second-line injectable resistance. Of 134 (69%) HIV-positive patients, viral loads were available for 68/134 (51%) (36/68 [53%] had viral loads of >1000 copies/ml) and CD4 counts were available for 92/134 (69%) (20/92 [22%] had CD4 <50 cells/mm3). Patients presented with varying other comorbidities, including hypertension (13/194, 7%) and mental health conditions (11/194, 6%). Of 194 patients, 44 (23%) were reported to be employed. Other socio-economic challenges included substance abuse (17/194, 9%) and ill family members (17/194, 9%). Respectively 13% and 42% of patients were estimated to travel more than 20 km to reach their diagnosing and treatment-initiating healthcare facility. CONCLUSIONS: RR-TB patients had diverse medical and social challenges highlighting the need for integrated, differentiated and patient-centred healthcare to better address specific needs and underlying vulnerabilities of individual patients.


OBJECTIF: Décrire les profils médicaux, socioéconomiques et géographiques des patients atteints de TB résistante à la rifampicine (RR-TB) et les implications en matière de soins centrés sur le patient. CONTEXTE: Treize districts de trois provinces d'Afrique du Sud. MÉTHODE: Cette étude descriptive a analysé les dossiers médicaux et de laboratoire de 194 patients ayant reçu un diagnostic de RR-TB au troisième trimestre de 2016. RÉSULTATS: L'âge médian était de 35 ans ; 120/194 (62%) patients étaient des hommes. Un traitement antituberculeux antérieur était documenté chez 122/194 (63%) patients, et 56/194 (29%) avaient une résistance à la fluoroquinolone et/ou à un agent injectable de deuxième ligne documentée. Sur 134 (69%) patients infectés par le VIH, les charges virales étaient disponibles pour 68/134 (51%) patients (36/68 [53%] avaient des charges virales >1 000 copies/ml) et les taux de CD4 étaient disponibles pour 92/134 (69%) patients (20/92 [22%] avaient un taux de CD4 <50 cellules/mm3). Les patients présentaient diverses autres comorbidités, dont hypertension (13/194, 7%) et troubles psychiques (11/194, 6%). Sur les 194 patients, 44 (23%) avaient un emploi. Les autres problèmes socioéconomiques comprenaient la toxicomanie (17/194, 9%) et le fait d'avoir un membre de sa famille malade (17/194, 9%). Respectivement 13% et 42% des patients parcouraient plus de 20 km pour se rendre à leur centre de diagnostic et au centre de soins responsable de l'instauration du traitement. CONCLUSIONS: Les patients atteints de RR-TB avaient divers problèmes médicaux et sociaux. Ces résultats soulignent le besoin de soins intégrés, différenciés et centrés sur le patient afin de mieux répondre aux besoins spécifiques et aux vulnérabilités sous-jacentes de chaque patient.

3.
S Afr Med J ; 110(9): 842-845, 2020 07 17.
Article in English | MEDLINE | ID: mdl-32880264

ABSTRACT

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections , Immunologic Tests/methods , Pandemics , Pneumonia, Viral , Serologic Tests/methods , Betacoronavirus/genetics , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Clinical Laboratory Techniques/standards , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Reproducibility of Results , SARS-CoV-2 , Sensitivity and Specificity , Seroepidemiologic Studies , South Africa/epidemiology
4.
S Afr Med J ; 110(9): 872-876, 2020 Aug 31.
Article in English | MEDLINE | ID: mdl-32880271

ABSTRACT

BACKGROUND: Urinary tract infection (UTI) is one of the most common infections during pregnancy, which can lead to significant maternal and perinatal morbidity and mortality if left untreated. Challenges when treating UTIs in pregnancy include fetal protection and resistance development of uropathogens. Currently, the Essential Medicines List recommends nitrofurantoin to treat cystitis and ceftriaxone to treat pyelonephritis in pregnant women. OBJECTIVES: To determine common pathogens causing UTI in pregnancy and their antibiotic susceptibility patterns. METHODS: A retrospective analysis was performed of laboratory data for positive urine specimens from obstetric departments of 6 KwaZulu- Natal Province hospitals during 2011 - 2016. Identification and susceptibility testing were performed using the VITEK 2 system. Results were interpreted according to the breakpoints of the Clinical and Laboratory Standards Institute, USA. RESULTS: From 5 971 positive urine specimens, the most common isolate was Escherichia coli (n=3 236; 54.2%), followed by Klebsiella pneumoniae (n=770; 12.9%). Group B streptococcus (GBS) (n=239; 4.0%) and Enterococcus faecalis (n=251; 4.2%) were the most common Gram-positive pathogens. E. coli displayed significant resistance to trimethoprim-sulfamethoxazole (65.1%), cephalothin (38.3%), cefuroxime (27.3%), ciprofloxacin (16.9%) and amoxicillin-clavulanic acid (17.1%). Resistance to ceftriaxone and nitrofurantoin remained low ‒ 9.1% and 7.7%, respectively. Among Gram-positive pathogens, GBS displayed 100% penicillin susceptibility and E. faecalis showed 92.9% susceptibility to ampicillin. CONCLUSIONS: E. coli is unsurprisingly the most common cause of UTI in pregnancy in KwaZulu-Natal. Susceptibility to ceftriaxone and nitrofurantoin remains good. Among Gram positives, GBS is prevalent and susceptible to penicillin, while E. faecalis is susceptible to ampicillin. As antimicrobial resistance evolves, routine surveillance is necessary to modify recommended empirical antibiotic use.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Infections/microbiology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Pregnancy Complications, Infectious/microbiology , Urinary Tract Infections/microbiology , Candida albicans/isolation & purification , Enterococcus faecalis/drug effects , Enterococcus faecalis/isolation & purification , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Female , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Humans , Klebsiella pneumoniae/isolation & purification , Microbial Sensitivity Tests , Pregnancy , Proteus mirabilis/isolation & purification , Retrospective Studies , South Africa , Streptococcus agalactiae/drug effects , Streptococcus agalactiae/isolation & purification , Urine/microbiology
5.
Int J Tuberc Lung Dis ; 24(1): 83-91, 2020 01 01.
Article in English | MEDLINE | ID: mdl-32005310

ABSTRACT

SETTING: Thirteen districts in Eastern Cape (EC), KwaZulu-Natal (KZN) and Western Cape (WC) Provinces, South Africa.OBJECTIVE: To pilot a methodology for describing and visualising healthcare journeys among drug-resistant tuberculosis (DR-TB) patients using routine laboratory records.DESIGN: Laboratory records were obtained for 195 patients with laboratory-detected rifampicin-resistant TB (RR-TB) during July-September 2016. Health facility visits identified from these data were plotted to visualise patient healthcare journeys. Data were verified by facility visits.RESULTS: In the 9 months after the index RR-TB sample was collected, patients visited a mean of 2.3 health facilities (95% CI 2.1-2.6), with 9% visiting ≥4 facilities. The median distance travelled by patients from rural areas (116 km, interquartile range [IQR] 50-290) was greater than for urban patients (51 km, IQR 9-140). A median of 21% of patient's time was spent under the care of primary healthcare facilities: this was respectively 6%, 37% and 39% in KZN, EC and WC. Journey patterns were generally similar within districts. Some reflected a semi-centralised model of care where patients were referred to regional hospitals; other journeys showed greater involvement of primary care.CONCLUSION: Routine laboratory data can be used to explore DR-TB patient healthcare journeys and show how the use of healthcare services for DR-TB varies in different settings.


Subject(s)
Laboratories , Tuberculosis, Multidrug-Resistant , Humans , Patient Care , Pilot Projects , South Africa/epidemiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology
6.
S. Afr. med. j. (Online) ; 0:0(0): 1-4, 2020. ilus
Article in English | AIM (Africa) | ID: biblio-1271064

ABSTRACT

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies


Subject(s)
COVID-19 , Disease Outbreaks , Public Health , Severe acute respiratory syndrome-related coronavirus , Serologic Tests , South Africa
7.
Int J Tuberc Lung Dis ; 23(6): 720-727, 2019 06 01.
Article in English | MEDLINE | ID: mdl-31315705

ABSTRACT

BACKGROUND In KwaZulu-Natal, South Africa, the incidence of extensively drug-resistant tuberculosis (XDR-TB) is driven by the transmission of resistant strains. As data suggest that cases may be spatially clustered, we sought to identify 'hotspots' and describe these communities. METHODS We enrolled XDR-TB patients diagnosed from 2011 to 2014 in eThekwini. Global positioning system (GPS) coordinates for participant homes were collected and hotspots were identified based on population-adjusted XDR-TB incidence. The sociodemographic features of hotspots were characterised using census data. For a subset of participants, we mapped non-home XDR-TB congregate locations and compared these with results including only homes. RESULTS Among 132 participants, 75 (57%) were female and 87 (66%) lived in urban or suburban locations. Fifteen of 197 census tracts were identified as XDR-TB hotspots with ≥95% confidence. Four spatial mapping methods identified one large hotspot in northeastern eThekwini. Hotspot communities had higher proportions of low educational attainment (12% vs. 9%) and unemployment (29.3% vs. 20.4%), and lower proportion of homes with flush toilets (36.4% vs. 68.9%). The case density shifted towards downtown Durban when congregate locations (e.g., workplaces) for 43 (33%) participants were mapped. CONCLUSIONS In eThekwini, XDR-TB case homes were clustered into hotspots with more poverty indicators than non-hotspots. Prevention efforts targeting hotspot communities and congregate settings may be effective in reducing community transmission. .


Subject(s)
Extensively Drug-Resistant Tuberculosis/epidemiology , Tuberculosis, Pulmonary/epidemiology , Adult , Cities , Cross-Sectional Studies , Demography , Extensively Drug-Resistant Tuberculosis/etiology , Female , Geographic Information Systems , Humans , Incidence , Male , Socioeconomic Factors , South Africa/epidemiology , Tuberculosis, Pulmonary/etiology
9.
Int J Tuberc Lung Dis ; 21(10): 1154-1160, 2017 10 01.
Article in English | MEDLINE | ID: mdl-28911361

ABSTRACT

SETTING: In South Africa, KwaZulu-Natal is the epicentre of the human immunodeficiency virus (HIV) epidemic, where approximately 70% of people with tuberculosis (TB) are co-infected with HIV. Undiagnosed TB contributes to high mortality in HIV-infected patients. Delays in diagnosing TB and treatment initiation result in prolonged transmission and increased infectiousness. OBJECTIVE: To evaluate the LoopampTM MTBC Detection kit (TB-LAMP; based on the loop-mediated isothermal amplification assay), smear microscopy and Xpert test with the gold standard of mycobacterial culture. METHODS: Sputum samples were collected from 705 patients with symptoms of pulmonary TB attending a primary health care clinic. RESULTS: The TB-LAMP assay had significantly higher sensitivity than smear microscopy (72.6% vs. 45.4%, P < 0.001), whereas specificity was slightly lower (99% vs. 96.8%, P = 0.05), but significantly higher than Xpert (92.9%, P = 0.004). There was no significant difference in sensitivity of smear-positive, culture-positive and smear-negative, culture-positive sputum samples using TB-LAMP vs. Xpert (respectively 95.9%/55.9% vs. 97.6%/66.1%; P =0.65, P = 0.27). The positive predictive value of TB-LAMP was significantly higher than that of Xpert (87.5% vs. 77.0%; P = 0.02), but similar to that of smear microscopy (94.2%; P = 0.18). The negative predictive value was respectively 91.9%, 92.5% (P = 0.73) and 83.1% (P = 0.0001). CONCLUSION: Given its ease of operability, the TB-LAMP assay could be implemented as a point-of-care test in primary health care settings, and contribute to reducing treatment waiting times and TB prevalence.


Subject(s)
Mycobacterium tuberculosis/isolation & purification , Nucleic Acid Amplification Techniques/methods , Sputum/microbiology , Tuberculosis, Pulmonary/diagnosis , Adult , Coinfection , Female , HIV Infections/epidemiology , Humans , Male , Microscopy/methods , Middle Aged , Point-of-Care Systems , Predictive Value of Tests , Prevalence , Sensitivity and Specificity , South Africa
10.
Epidemiol Infect ; 145(10): 2100-2108, 2017 07.
Article in English | MEDLINE | ID: mdl-28478776

ABSTRACT

An outbreak of respiratory diphtheria occurred in two health districts in the province of KwaZulu-Natal in South Africa in 2015. A multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. Fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. Of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. The case fatality was 27%. Ninety-three household contacts, 981 school or work contacts and 595 healthcare worker contacts were identified and given prophylaxis against Corynebacterium diphtheriae infection. A targeted vaccination campaign for children aged 6-15 years was carried out at schools in the two districts. The outbreak highlighted the need to improve diphtheria vaccination coverage in the province and to investigate the feasibility of offering diphtheria vaccines to healthcare workers.


Subject(s)
Corynebacterium diphtheriae/physiology , Diphtheria/epidemiology , Disease Outbreaks , Respiratory Tract Infections/epidemiology , Adolescent , Adult , Child , Child, Preschool , Diphtheria/microbiology , Diphtheria/mortality , Female , Humans , Immunization/statistics & numerical data , Male , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/mortality , South Africa/epidemiology , Young Adult
11.
BMC Infect Dis ; 16: 27, 2016 Jan 25.
Article in English | MEDLINE | ID: mdl-26809736

ABSTRACT

BACKGROUND: Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies. METHODS: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31-69) until 2014. RESULTS: Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44 log10 copies/ml; SE = 0.18; p = 0.03) and higher CD4+ T-cell counts (+80 cells/µl; SE = 42; p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype. CONCLUSIONS: Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.


Subject(s)
HIV Infections/immunology , Receptors, KIR/genetics , Adult , Alleles , CD4-Positive T-Lymphocytes/immunology , Cohort Studies , Disease Progression , Female , HIV Infections/diagnosis , HLA-C Antigens , Haplotypes , Humans , Killer Cells, Natural/immunology , Prospective Studies , South Africa , Viral Load
12.
Vaccine ; 31(16): 2089-96, 2013 Apr 12.
Article in English | MEDLINE | ID: mdl-23370155

ABSTRACT

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 interviewer-administered 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.


Subject(s)
AIDS Vaccines/administration & dosage , Risk-Taking , Unsafe Sex/statistics & numerical data , AIDS Vaccines/immunology , Circumcision, Male/statistics & numerical data , Female , HIV Infections/immunology , HIV Infections/prevention & control , Humans , Male , Risk Reduction Behavior , Safe Sex/psychology , Safe Sex/statistics & numerical data , South Africa , Surveys and Questionnaires , Unsafe Sex/psychology
13.
J Virol ; 86(22): 12013-24, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22933291

ABSTRACT

HLA-B*81:01 and HLA-B*39:10 alleles have been associated with viremic control in HIV-1 subtype C infection. Both alleles restrict the TL9 epitope in p24 Gag, and cytotoxic-T-lymphocyte (CTL)-mediated escape mutations in this epitope have been associated with an in vitro fitness cost to the virus. We investigated the timing and impact of mutations in the TL9 epitope on disease progression in five B*81:01- and two B*39:10-positive subtype C-infected individuals. Whereas both B*39:10 participants sampled at 2 months postinfection had viruses with mutations in the TL9 epitope, in three of the five (3/5) B*81:01 participants, TL9 escape mutations were only detected 10 months after infection, taking an additional 10 to 15 months to reach fixation. In the two remaining B*81:01 individuals, one carried a TL9 escape variant at 2 weeks postinfection, whereas no escape mutations were detected in the virus from the other participant for up to 33 months postinfection, despite CTL targeting of the epitope. In all participants, escape mutations in TL9 were linked to coevolving residues in the region of Gag known to be associated with host tropism. Late escape in TL9, together with coevolution of putative compensatory mutations, coincided with a spontaneous increase in viral loads in two individuals who were otherwise controlling the infection. These results provide in vivo evidence of the detrimental impact of B*81:01-mediated viral evolution, in a single Gag p24 epitope, on the control of viremia.


Subject(s)
HIV Core Protein p24/genetics , HIV Infections/immunology , HIV Infections/virology , HIV-1/metabolism , HLA-B Antigens/genetics , Alleles , Cell Separation , Disease Progression , Epitopes/chemistry , Female , Flow Cytometry , Genotype , HIV Infections/genetics , Humans , Interferon-gamma/metabolism , Kinetics , Longitudinal Studies , Molecular Sequence Data , Mutation , South Africa , Time Factors , Toll-Like Receptor 9/genetics
14.
J Virol ; 85(14): 7070-80, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21613398

ABSTRACT

Molecular epidemiology studies have identified HLA-B 58:01 as a protective HIV allele. However, not all B 58:01-expressing persons exhibit slow HIV disease progression. We followed six HLA-B 58:01-positive, HIV subtype C-infected individuals for up to 31 months from the onset of infection and observed substantial variability in their clinical progression despite comparable total breadths of T cell responses. We therefore investigated additional immunological and virological factors that could explain their different disease trajectories. Cytotoxic T-lymphocyte (CTL) responses during acute infection predominantly targeted the TW10 and KF9 epitopes in p24(Gag) and Nef, respectively. Failure to target the TW10 epitope in one B 58:01-positive individual was associated with low CD4(+) counts and rapid disease progression. Among those targeting TW10, escape mutations arose within 2 to 15 weeks of infection. Rapid escape was associated with preexisting compensatory mutations in the transmitted viruses, which were present at a high frequency (69%) in the study population. At 1 year postinfection, B 58:01-positive individuals who targeted and developed escape mutations in the TW10 epitope (n = 5) retained significantly higher CD4(+) counts (P = 0.04), but not lower viral loads, than non-B 58:01-positive individuals (n = 17). The high population-level frequency of these compensatory mutations may be limiting the protective effect of the B 58:01 allele.


Subject(s)
HIV Infections/immunology , HIV Infections/virology , HLA-B Antigens/immunology , Amino Acid Sequence , Base Sequence , CD4 Lymphocyte Count , DNA Primers , Disease Progression , Enzyme-Linked Immunosorbent Assay , HIV-1 , HLA-B Antigens/genetics , Humans , Molecular Epidemiology , Molecular Sequence Data , Mutation , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino Acid , T-Lymphocytes, Cytotoxic/immunology , Viral Load
15.
Virology ; 396(2): 213-25, 2010 Jan 20.
Article in English | MEDLINE | ID: mdl-19913270

ABSTRACT

It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential "transmission signatures", we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection, we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission.


Subject(s)
HIV Infections/virology , HIV-1/genetics , HLA Antigens/immunology , Immune Evasion/genetics , Amino Acid Substitution , Disease Progression , Female , Genome, Viral/genetics , HIV Infections/immunology , HIV-1/immunology , Humans , Immune Evasion/immunology , Molecular Sequence Data , Mutation/genetics , Sequence Alignment , Sequence Analysis, Protein , Viral Envelope Proteins/genetics , Viral Envelope Proteins/immunology
16.
J Virol ; 83(8): 3556-67, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19193811

ABSTRACT

Identifying the specific genetic characteristics of successfully transmitted variants may prove central to the development of effective vaccine and microbicide interventions. Although human immunodeficiency virus transmission is associated with a population bottleneck, the extent to which different factors influence the diversity of transmitted viruses is unclear. We estimate here the number of transmitted variants in 69 heterosexual men and women with primary subtype C infections. From 1,505 env sequences obtained using a single genome amplification approach we show that 78% of infections involved single variant transmission and 22% involved multiple variant transmissions (median of 3). We found evidence for mutations selected for cytotoxic-T-lymphocyte or antibody escape and a high prevalence of recombination in individuals infected with multiple variants representing another potential escape pathway in these individuals. In a combined analysis of 171 subtype B and C transmission events, we found that infection with more than one variant does not follow a Poisson distribution, indicating that transmission of individual virions cannot be seen as independent events, each occurring with low probability. While most transmissions resulted from a single infectious unit, multiple variant transmissions represent a significant fraction of transmission events, suggesting that there may be important mechanistic differences between these groups that are not yet understood.


Subject(s)
Genetic Variation , HIV Infections/transmission , HIV Infections/virology , HIV-1/physiology , Adult , Cluster Analysis , Female , HIV-1/classification , HIV-1/genetics , Humans , Male , Molecular Sequence Data , Phylogeny , RNA, Viral/genetics , Sequence Analysis, DNA , Sequence Homology , Young Adult
17.
J Virol ; 81(12): 6187-96, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17409164

ABSTRACT

The study of the evolution and specificities of neutralizing antibodies during the course of human immunodeficiency virus type 1 (HIV-1) infection may be important in the discovery of possible targets for vaccine design. In this study, we assessed the autologous and heterologous neutralization responses of 14 HIV-1 subtype C-infected individuals, using envelope clones obtained within the first 2 months postinfection. Our data show that potent but relatively strain-specific neutralizing antibodies develop within 3 to 12 months of HIV-1 infection. The magnitude of this response was associated with shorter V1-to-V5 envelope lengths and fewer glycosylation sites, particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced (CD4i) epitopes developed to high titers in 12 participants, in most cases before the development of autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificity conferred neutralization breadth. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection.


Subject(s)
HIV Infections/immunology , HIV Infections/virology , HIV-1/metabolism , Acute Disease , Amino Acid Sequence , Antibody Formation , CD4-Positive T-Lymphocytes/immunology , Cloning, Molecular , Epitopes/chemistry , Female , Glycosylation , HIV-2/metabolism , Humans , Molecular Sequence Data , Neutralization Tests , Sequence Homology, Amino Acid
19.
S Afr Med J ; 86(4): 345-9, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8693369

ABSTRACT

OBJECTIVES: A study was undertaken to assess the prevalence of hepatitis B infection in selected residential child care facilities in Natal. DESIGN: All residents at three facilities in the Durban and Pietermaritzburg areas of KwaZulu-Natal were tested for markers of hepatitis B infection as part of a broader health status assessment. RESULTS: One hundred and ninety-five children between the ages of 3 and 194 months (78 +/- 47) were studied. Overall 66.2% of children had evidence of past exposure to hepatitis B virus. Of these 14.9% were positive for hepatitis B surface antigen, 13.3% for hepatitis B e antigen, 47.7% for hepatitis B surface antibody and 59.5% for hepatitis B core antibody. Relative rates of infection increased with age from 18.2%, 20% and 27.8% in the 1st, 2nd and 3rd years of life respectively to 72.2% and 88.2% in the 4th and 5th years of life. Relative rates of infection increased with duration of stay from 40% by the end of the 1st year to 100% by the end of the 5th year. CONCLUSIONS: This study has demonstrated a very high rate of infection with hepatitis B virus and a high prevalence of hepatitis B surface antigenaemia in residential care facilities. It has also shown that the infection is horizontally transmitted within these facilities, that infection increases with duration of stay, that there is a dramatic increase in infection rates after the 3rd year of life, that the highest carrier rates are occurring in children between the ages of 2 and 4 years, and that the vast majority of carriers are highly infectious. These children are not only at risk themselves for the long-term complications of this disease but also constitute an important reservoir of hepatitis B infection within the larger community. There is an urgent need for uniform national guidelines for the screening and management of children in residential care facilities and children being prepared for adoption or foster care. There is also a need for a wider investigation into conditions at residential care facilities previously designated for black children in this country.


Subject(s)
Adoption , Child, Institutionalized , Foster Home Care , Hepatitis B/epidemiology , Adolescent , Black or African American , Black People , Carrier State , Child , Child, Preschool , Female , Hepatitis B/ethnology , Hepatitis B/immunology , Hepatitis B Antibodies/analysis , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B e Antigens/immunology , Hepatitis B virus/immunology , Humans , Infant , Length of Stay , Male , Prevalence , South Africa/epidemiology
20.
Genitourin Med ; 71(2): 65-7, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7744414

ABSTRACT

OBJECTIVE: The aim of this study was to assess the prevalence of syphilis, human immunodeficiency virus (HIV), and hepatitis B virus (HBV) infections in women at the time of delivery, and to determine the seroconversion rates for syphilis and HIV infections from initial booking visit to delivery. SETTING: The labour ward of a typical tertiary hospital in a developing country and serving an indigent African population. METHOD: Four hundred and eighteen women presenting in labour were randomly selected and informed consent obtained for serological testing for syphilis and HBV infections in umbilical cord blood samples. The specimens were then given a study number, the gestational ages recorded and anonymously tested for HIV infection. RESULTS: Of the 191 women who had antenatal care, 13 (6.8%) were HIV antibody positive at the initial "booking" visit. An additional 4 were found to be HIV antibody positive at the time of delivery resulting in a seroconversion rate of 2.2%. The seroconversion rate for syphilis at the time of delivery was 2.7%. Hepatitis B surface antigens were detected in only 2 women, one of whom was antigen positive. CONCLUSION: The high seroconversion rates for both syphilis and HIV infection in pregnancy justifies re-screening for these conditions in endemic areas such as ours.


Subject(s)
HIV Seropositivity/epidemiology , Pregnancy Complications, Infectious/epidemiology , Syphilis/epidemiology , Delivery, Obstetric , Female , Fetal Blood/immunology , HIV Antibodies/analysis , HIV Seroprevalence , Hepatitis B/epidemiology , Hepatitis B Surface Antigens/analysis , Humans , Infant, Newborn , Mass Screening , Pregnancy , Prenatal Care , Prevalence , Syphilis, Congenital/prevention & control , Time Factors
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