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1.
AIDS Behav ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415616

RESUMO

South Africa processes 5.1 million HIV CD4, viral load (VL), and tuberculosis (TB) tests annually. This pilot non-randomized trial in South Africa explored an intervention ("MatlaMobile") to deliver laboratory results via mobile phone. Adults completing CD4, VL, and/or TB laboratory tests were enrolled-either receiving results by returning to clinic (control, n = 174) or mobile phone (intervention, n = 226). Study staff instructed control participants to return within 6 days (standard-of-care). MatlaMobile instructed intervention participants with clinically actionable results requiring intervention or treatment change (i.e., < 200 CD4 cells per milliliter, ≥ 400 viral copies per milliliter, or TB positive) to return immediately. A greater proportion of intervention participants than controls saw their results within 7 days of enrollment (73% vs. 8.6%, p < 0.001). Among participants instructed to return, more intervention participants (20%, n = 14/70) returned than controls (8.6%, n = 15/174, p = 0.02). MatlaMobile demonstrated that patients can quickly receive and respond appropriately to digital delivery of health information.

2.
Lancet Infect Dis ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32178764

RESUMO

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per µL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A.

4.
PLoS One ; 15(3): e0230376, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182274

RESUMO

INTRODUCTION: Household contacts of patients with active pulmonary tuberculosis (TB) often have latent TB infection, and are at risk of progression to disease. We set out to investigate whether index TB case HIV status was linked to a higher probability of latent TB infection among household contacts. MATERIALS AND METHODS: Data were collected prospectively from participants in the intervention arm of a household cluster-randomised trial in two South Africa provinces (Mangaung, Free State, and Capricorn, Limpopo). In intervention group households, TB contacts underwent HIV testing and tuberculin skin testing (TST). TST induration was estimated at two cut-offs (≥5mm, ≥10mm). Multilevel Bayesian regression models estimated posterior distributions of the percentage of household contacts with TST induration ≥5mm and ≥10mm by age group, and compared the odds of latent TB infection by key risk factors including HIV status index case age and study province. RESULTS: A total of 2,985 household contacts of 924 index cases were assessed, with most 2,725 (91.3%) undergoing TST. HIV prevalence in household contacts was 14% and 10% in Mangaung and Capricorn respectively. Overall, 16.8% (458/2,725) had TST induration of ≥5mm and 13.1% (359/2,725) ≥10mm. In Mangaung, children aged 0-4 years had a high TST positivity prevalence compared to their peers in Capricorn (22.0% vs. 7.6%, and 20.5% vs. 2.3%, using TST thresholds of ≥5mm and ≥10mm respectively). Compared to contacts from Capricorn, household contacts living in Mangaung were more likely to have TST induration ≥5mm (odds ratio [OR]: 3.08, 95% credibility interval [CI]: 2.13-4.58) and ≥10mm (OR: 4.52, 95% CI: 3.03-6.97). There was a 90% and 92% posterior probability that the odds of TST induration ≥5mm (OR: 0.79, 95% CI: 0.56-1.14) and ≥10mm (OR: 0.77, 95% CI: 0.53-1.10) respectively were lower in household contacts of HIV-positive compared to HIV-negative index cases. CONCLUSIONS: High TST induration positivity, especially among young children and people living in Mangaung indicates considerable TB transmission despite high antiretroviral therapy coverage. Household contact of HIV-positive index TB cases were less likely to have evidence of latent TB infection than contacts of HIV-negative index cases.

5.
Infect Genet Evol ; 80: 104216, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32006707

RESUMO

Bone marrow stromal cell antigen 2 (BST2 or tetherin) is a host-encoded, interferon-inducible antiviral restriction factor which blocks the release of enveloped viruses. Few studies have assessed the role of BST2 polymorphisms on HIV-1 acquisition or disease progression in sub-Saharan Africa. This study investigated the frequency of four HIV-1-associated BST2 variants rs3217318, rs12609479, rs10415893 and rs113189798 in uninfected and HIV-1 infected black South Africans. Homozygosity for the rs12609479-A minor allele, previously associated with decreased HIV-1 acquisition risk, was underrepresented in HIV-1 uninfected black South Africans (2%) compared to reference African (9%) and in particular European populations (61%) (p = .047 and p < .0001, respectively). To determine if any of these gene variants influenced HIV-1 control in the absence of antiretroviral treatment (ART), we compared HIV-1 infected ART-naïve progressors [n = 72] and controllers [n = 71], the latter includes elite controllers [EC: n = 23; VL < 50 RNA copies/ml]. Heterozygosity for the rs12609479 SNP (G/A) was enriched in progressors compared to ECs (47.2% vs 21.7%, OR = 3.50 [1.16-10.59], p = .03), while rs113189798 heterozygosity (A/G) showed a strong trend of overrepresentation in ECs compared to progressors (47.8% vs 26.4%, OR = 0.39 [0.14-1.04], p = .07). Heterozygosity for the promoter indel rs3217318 (i19/Δ19) was associated with a faster rate of CD4+ T-cell decline in progressors (p = .0134). Carriage of the rs3217318 (i19/Δ19), rs12609479 (G/G), rs10415893(G/A) and rs113189798 (A/G) combined genotype, denoted as i19Δ19 GG GA AG, was associated with significantly higher CD4+ T-cell counts in progressors (p = .03), a finding predominantly driven by the _GG_AG combination. Our data suggest that the possession of select BST2 genotype combinations may be implicated in HIV-1 disease progression and natural spontaneous control.

6.
Mucosal Immunol ; 13(1): 118-127, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31619762

RESUMO

We compared outer and inner foreskin tissue from adolescent males undergoing medical male circumcision to better understand signals that increase HIV target cell availability in the foreskin. We measured chemokine gene expression and the impact of sexually transmitted infections (STIs) on the density and location of T and Langerhans cells. Chemokine C-C ligand 27 (CCL27) was expressed 6.94-fold higher in the inner foreskin when compared with the outer foreskin. We show that the density of CD4+CCR5+ cells/mm2 was higher in the epithelium of the inner foreskin, regardless of STI status, in parallel with higher CCL27 gene expression. In the presence of STIs, there were higher numbers of CD4+CCR5+ cells/mm2 cells in the sub-stratum of the outer and inner foreskin with concurrently higher number of CD207+ Langerhans cells (LC) in both tissues, with the latter cells being closer to the keratin surface of the outer FS in the presence of an STI. When we tested the ability of exogenous CCL27 to induce T-cell migration in foreskin tissue, CD4 + T cells were able to relocate to the inner foreskin epithelium in response. We provide novel insight into the impact CCL27 and STIs on immune and HIV-1 target cell changes in the foreskin.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31844002

RESUMO

Tuberculosis is an important cause of maternal morbidity, but little is known about the effects of pregnancy on antituberculosis drug concentrations. We developed population pharmacokinetic models to describe drug dispositions of isoniazid, pyrazinamide, and ethambutol in pregnant women with tuberculosis and HIV. HIV-positive pregnant women with tuberculosis receiving standard first-line tuberculosis treatment and participating in Tshepiso, a prospective cohort study in Soweto, South Africa, underwent sparse pharmacokinetic sampling at >36 weeks of gestation and 7 weeks postpartum. The effects of pregnancy on the pharmacokinetics of isoniazid, pyrazinamide, and ethambutol were investigated via population pharmacokinetic modeling. Isoniazid, pyrazinamide, and ethambutol concentrations were available for 29, 18, and 18 women, respectively. Their median weight was 66 kg while pregnant and 64 kg postpartum. No significant differences were observed in drug clearance, volume of distribution, or bioavailability during and after pregnancy. The model-estimated isoniazid, pyrazinamide, and ethambutol area under the concentration-time curve from 0 to 24 h (AUC0-24) medians were, respectively, 6.88, 419, and 16.5 mg · h/liter during pregnancy versus 5.01, 407, and 19.0 mg · h/liter postpartum. The model-estimated maximum concentration (C max) medians for isoniazid, pyrazinamide, and ethambutol were, respectively, 1.39, 35.9, and 1.82 mg/liter during pregnancy versus 1.43, 34.5, and 2.11 mg/liter postpartum. A posteriori power calculations determined that our analysis was powered 91.8%, 59.2%, and 90.1% at a P of <0.01 to detect a 40% decrease in the AUCs of isoniazid, pyrazinamide, and ethambutol, respectively. Pregnancy does not appear to cause relevant changes in the exposure to isoniazid, pyrazinamide, and ethambutol. Additional studies of antituberculosis drugs in pregnancy are needed.

8.
AIDS ; 34(1): 63-71, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31567163

RESUMO

OBJECTIVES: Tuberculosis preventive therapy for people living with HIV is effective, widely recommended, and increasingly prescribed, but completion rates are less than ideal, and adherence is not typically monitored. We sought to quantify adherence to isoniazid preventive therapy using a urine metabolite assay. DESIGN: Two cross-sectional surveys. SETTING: Rio de Janeiro, Brazil, 2008-2009; and Northwest Province, South Africa, 2018-2019. PARTICIPANTS: Two hundred and three Brazilian and 93 South African patients attending HIV clinics with active prescriptions for isoniazid preventive therapy MAIN OUTCOME MEASURES:: Self-reported isoniazid adherence, paired with semiquantitative measurement of urine isoniazid metabolites. RESULTS: By self-report, 90% of patients [95% confidence interval (CI) 86-93%] reported having taken a dose of isoniazid on the day of enrollment or the preceding day, and 91% (95% CI 87-94%) reported missing an average of one dose or fewer per week. By urine testing, only 65% (95% CI 59-70%) of all patients, and 69% (95% CI 63-74%) of those who reported having taken isoniazid on the current or preceding day, had detectable urine metabolites (expected in 95% of patients at 24 h). Longer time since starting preventive therapy was independently associated with a negative urine test for isoniazid metabolites (adjusted prevalence ratio 1.11 per month of isoniazid, 95% CI 1.05-1.18). CONCLUSION: Adherence to isoniazid preventive therapy among patients with HIV in Brazil and South Africa is inadequate, is overestimated by self-report, and declines with time on treatment. Shorter regimens for TB preventive therapy may improve adherence and completion, but adherence support for all patients may be necessary.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31733411

RESUMO

SETTING: Tshepong Hospital multidrug resistant (MDR) unit between April 2011 and February 2014. OBJECTIVE: Rifampicin resistant (RR) tuberculosis (TB) on X-pert MTB/Rif is assumed a surrogate for MDR TB. Following a RR result, a second specimen is taken for confirmatory culture and drug susceptibility testing (DST). We compare the initial diagnostic X-pert MTB/RIF result to the confirmatory DST in a high HIV seroprevalence setting. DESIGN: We retrospectively reviewed records analyzing demographics, HIV serostatus, prior TB treatments and DST results. RESULTS: Of 604 patients with X-pert MTB/RIF RR, 374(61.9%) had a DST and were included. The mean age was 36.9 years and 82% were HIV-infected. Following DST, MDR was confirmed in 49% and Rif mono-resistant (RMR) TB in 36%. Amongst RMR TB, 84% were HIV-infected and amongst those with CD4 < 50 versus those 50-350 cells/mm3 RMR TB was noted in 51% versus 33% (p = 0.012). Primary DR was diagnosed in 43% (61% MDR and 33% RMR). CONCLUSION: RR detected on a diagnostic X-pert MTB/Rif assay did not always predict MDR. RMR is emerging amongst those with HIV co - infection and low CD4 count (<50cells/mm3) and research is needed to reduce the number of drugs and treatment durations for RMR TB.

10.
BMC Infect Dis ; 19(1): 839, 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606032

RESUMO

BACKGROUND: Household contact tracing of index TB cases has been advocated as a key part of TB control for many years, but has not been widely implemented in many low-resource setting because of the current dearth of high quality evidence for effectiveness. Innovative strategies for earlier, more effective treatment are particularly important in contexts with hyper-endemic levels of HIV, where levels of TB infection remain extremely high. METHODS: We present the design of a household cluster-randomised controlled trial of interventions aimed at improving TB-free survival and reducing childhood prevalence of Mycobacterium tuberculosis infection among household contacts of index TB cases diagnosed in two provinces of South Africa. Households of index TB cases will be randomly allocated in a 1:1 ratio to receive either an intensified home screening and linkage for TB and HIV intervention, or enhanced standard of care. The primary outcome will compare between groups the TB-free survival of household contacts over 15 months. All participants, or their next-of-kin, will provide written informed consent to participate. DISCUSSION: Evidence from randomised trials is required to identify cost-effective approaches to TB case-finding that can be applied at scale in sub-Saharan Africa. TRIAL REGISTRATION: ISRCTN16006202 (01/02/2017: retrospectively registered) and NHREC4399 (11/04/2016: prospectively registered). Protocol version: 4.0 (date: 18th January 2018).


Assuntos
Busca de Comunicante/métodos , Tuberculose/prevenção & controle , Adulto , Criança , Análise Custo-Benefício , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Estudos Retrospectivos , Risco , África do Sul/epidemiologia , Padrão de Cuidado , Resultado do Tratamento , Teste Tuberculínico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Carga Viral
11.
Clin Infect Dis ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631221

RESUMO

BACKGROUND: Both pregnancy and HIV increase the risk of tuberculosis disease which results in poor maternal, pregnancy, and infant outcomes. Isoniazid preventive therapy (IPT) reduces mortality among HIV-infected individuals in high-burden settings, but has recently been associated with adverse pregnancy outcomes when initiated during pregnancy. METHODS: In this secondary analysis, we used multivariable logistic regression to evaluate the association between IPT exposure and adverse pregnancy outcomes (fetal demise, prematurity, low birth weight and congenital anomaly) in HIV-infected pregnant women enrolled as controls in the Tshepiso study, a prospective observational cohort of HIV-infected pregnant women with and without TB disease in Soweto, South Africa from 2011-2014. RESULTS: There were 151 women enrolled with known pregnancy outcomes; 69 (46%) reported IPT initiation during pregnancy. Of the 69 IPT-exposed participants, 11 (16%) had an adverse pregnancy outcome compared to 23 of 82 (23%) IPT-unexposed participants. The adjusted odds of having an adverse pregnancy outcome was 2.5 (95%CI: 1.0, 6.5; p=0.048) times higher in IPT-unexposed women compared to IPT-exposed women after controlling for maternal age, CD4 count, viral load, antiretroviral regimen, body mass index and anemia. CONCLUSIONS: IPT exposure during pregnancy was not negatively associated with pregnancy outcomes after controlling for relevant demographic, clinical and HIV-related factors. These results may provide some reassurance that IPT can be safely used in the second or third trimester of pregnancy. Additional research is needed to confirm both the safety of IPT and new short-course TB preventive therapies during pregnancy.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31631667

RESUMO

Understanding of the burden of HIV infection and comorbid conditions in older adults is limited, especially in low- and middle-income countries. Antiretroviral therapy (ART) has increased longevity of HIV-positive individuals, making age-related comorbidities more likely. This study aimed to compare the demographic and disease profiles, including chronic comorbid conditions of inpatients, at least 50 years of age, by HIV status, admitted to a regional hospital in South Africa. Adults, 50 years of age and older, admitted to internal medicine wards from November 2015 to February 2016 were approached to participate. Sociodemographic data, laboratory results, anthropometric data, discharge diagnoses, and HIV status were collected and compared by HIV serostatus. Overall, 151 participants were enrolled. Their median age was 61 years (IQR: 56-68 years); 89 (58.9%) were women. Overall, 47 (31.1%) were HIV positive, of whom 10 (6.6%) were first diagnosed during the admission. HIV-positive inpatients were younger than HIV-negative patients. The leading discharge diagnoses of all participants were acute gastroenteritis (11.5%) and community-acquired pneumonia (11.5%). Hypertension and type 2 diabetes mellitus (T2DM) were the leading comorbidities in both HIV-negative and HIV-positive participants. Prevalence of hypertension was 75.0% in seronegative, 59.5% in those with a prior diagnosis of HIV, and 40.0% in newly diagnosed; similarly, prevalence of T2DM was 22.1% in HIV-negative and 24.3% in known HIV-positive participants. Similar proportions died during admission; 11.3% of HIV-negative and 12.7% of HIV-positive admitted inpatients died. Almost one third of patients admitted were HIV positive. In HIV-positive older admitted to hospital, the leading cause for hospitalization was coinfections. In the ART era, irrespective of HIV status, older patients have similar age-related chronic illnesses and similar mortality rates, despite younger age at admission.

13.
N Engl J Med ; 381(25): 2429-2439, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31661198

RESUMO

BACKGROUND: Results of an earlier analysis of a trial of the M72/AS01E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity. METHODS: From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with M. tuberculosis infection (defined by positive results on interferon-γ release assay) without evidence of active tuberculosis disease at centers in Kenya, South Africa, and Zambia. Participants were randomly assigned in a 1:1 ratio to receive two doses of either M72/AS01E or placebo, administered 1 month apart. The primary objective was to evaluate the efficacy of M72/AS01E to prevent active pulmonary tuberculosis disease according to the first case definition (bacteriologically confirmed pulmonary tuberculosis not associated with human immunodeficiency virus infection). Participants were followed for 3 years after the second dose. Participants with clinical suspicion of tuberculosis provided sputum samples for polymerase-chain-reaction assay, mycobacterial culture, or both. Humoral and cell-mediated immune responses were evaluated until month 36 in a subgroup of 300 participants. Safety was assessed in all participants who received at least one dose of M72/AS01E or placebo. RESULTS: A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01E or placebo, and 3330 received both planned doses. Among the 3289 participants in the according-to-protocol efficacy cohort, 13 of the 1626 participants in the M72/AS01E group, as compared with 26 of the 1663 participants in the placebo group, had cases of tuberculosis that met the first case definition (incidence, 0.3 vs. 0.6 cases per 100 person-years). The vaccine efficacy at month 36 was 49.7% (90% confidence interval [CI], 12.1 to 71.2; 95% CI, 2.1 to 74.2). Among participants in the M72/AS01E group, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T cells increased after the first dose and were sustained throughout the follow-up period. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS: Among adults infected with M. tuberculosis, vaccination with M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598.).


Assuntos
Imunogenicidade da Vacina , Tuberculose Latente/terapia , Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose Pulmonar/prevenção & controle , Adolescente , Adulto , África , Progressão da Doença , Método Duplo-Cego , Feminino , Seguimentos , Soronegatividade para HIV , Humanos , Tuberculose Latente/imunologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Adulto Jovem
14.
AIDS Behav ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31549265

RESUMO

Isoniazid preventive therapy (IPT) reduces the risk of active tuberculosis among people living with HIV, but implementation of IPT in South Africa and elsewhere remains slow. The objective of this study was to examine both nurse perceptions of clinical mentorship and patient perceptions of in-queue health education for promoting IPT uptake in Potchefstroom, South Africa. We measured adoption, fidelity, acceptability, and sustainability of the interventions using both quantitative and qualitative methods. Adoption, fidelity, and acceptability of the interventions were moderately high. However, nurses believed they could not sustain their increased prescriptions of IPT, and though many patients intended to ask nurses about IPT, few did. Most patients attributed their behavior to an imbalance of patient-provider power. National IPT guidelines should be unambiguous and easily implemented after minimal training on patient eligibility and appropriate medication durations, nurse-patient dynamics should empower the patient, and district-level support and monitoring should be implemented.

15.
BMC Urol ; 19(1): 65, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296191

RESUMO

BACKGROUND: The past four years has seen a rapid roll-out of male medical circumcision services in South Africa in response to clinical trials showing circumcision prevents HIV acquisition in heterosexual men. Clinics conduct substantial numbers of circumcisions per day. We report three cases of glans amputation in adolescents attending high volume clinics where modified Models of Optimising Volume and Efficiency (MOVE) are implemented. CASE PRESENTATIONS: Three cases of glans amputation in young healthy men that presented for voluntary medical male circumcision. The procedures were performed by highly experienced medical officers in two cases. All these cases shared characteristics: younger males with immature genitalia, forceps guided circumcision, and likely operator fatigue. Voluntary male medical circumcision programs should include regular monitoring and evaluation and training of operators to ensure high quality surgical techniques such as working in clean areas and taking frequent breaks. CONCLUSION: Circumcision is a relatively simple medical procedure, however regular training and quality control in high volume Male Medical Circumcision sites is essential to prevent rare catastrophic adverse events.


Assuntos
Amputação Traumática/diagnóstico , Amputação Traumática/etiologia , Circuncisão Masculina/efeitos adversos , Pênis , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Adolescente , Criança , Humanos , Masculino , Instrumentos Cirúrgicos/efeitos adversos , Carga de Trabalho
16.
AIDS Care ; : 1-5, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31298566

RESUMO

In South Africa, high attrition rates throughout the care continuum present major barriers to controlling the HIV epidemic. Mobile health (mHealth) interventions may provide innovative opportunities for efficient healthcare delivery and improving retention in care. In this formative research, we interviewed 11 patients and 28 healthcare providers in North West Province, South Africa, to identify perceived benefits, concerns and suggestions for a future mHealth program to deliver HIV Viral Load and CD4 Count test results directly to patients via mobile phone. Thematic analysis found that reduced workload for providers, reduced wait times for patients, potential expanded uses and patient empowerment were the main perceived benefits of an mHealth program. Perceived concerns included privacy, disseminating distressing results through text messages and patients' inability to interpret results. Participants felt that an mHealth program should complement face-to-face interactions and educational information to interpret results is needed. Providers identified logistical considerations and suggested protocols be developed. An mHealth program to deliver HIV test results directly to patients could mitigate multiple barriers to care but needs to be tested for efficacy. Concerns identified by patients and providers must be addressed in designing the program to successfully integrate with health facility workflow and ensure its sustainability.

17.
PLoS One ; 14(7): e0218902, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269056

RESUMO

BACKGROUND: Additional approaches are needed to identify and provide targeted interventions to populations at continued risk for HIV-associated mortality. We sought to describe care utilization and mortality following an index hospitalization for people with HIV in South Africa. METHODS: We conducted a prospective cohort study among hospitalized patients admitted to medicine wards at a single hospital serving a large catchment area. Participants were followed to 6 months post-discharge. Hospital records were used to describe overall admission numbers and inpatient mortality. Poisson regression was used to assess for associations between readmission or death and independent variables. RESULTS: Of 124 enrolled participants, 121 lived to hospital discharge. At the time of discharge the median length of stay of sampled patients was 5.5 days and 105 (87%) participants were referred for follow-up, most within 2 weeks of discharge. By 6 months post-discharge, only 18% of participants had attended the clinic to which they were referred and within the referred timeframe; 64 (53%) had been readmitted at least once and 31 (26%) had died. Self-reported skipping care due to difficulty in access (relative risk 1.3, p = 0.02) and not attending follow-up care on time or at the scheduled clinic or not attending clinic at all (relative risk 1.8 and 2.4, respectively, p = 0.001) were associated with readmission or mortality. CONCLUSIONS: The post-hospital period is a period of medical vulnerability and high mortality. Improving post-hospital retention in care may reduce post-hospital mortality.


Assuntos
Infecções por HIV/mortalidade , Mortalidade Hospitalar , Mortalidade , Readmissão do Paciente , Adulto , Idoso , Feminino , Infecções por HIV/patologia , Hospitalização , Humanos , Pacientes Internados , Pessoa de Meia-Idade , Alta do Paciente , Fatores de Risco , África do Sul/epidemiologia
18.
BMC Public Health ; 19(1): 898, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286953

RESUMO

BACKGROUND: HIV diagnosis is a critical step in linking HIV-infected individuals to care and treatment and linking HIV-uninfected persons to prevention services. However, the uptake of HIV testing remains low in many countries. HIV self-screening (HIVSS) is acceptable to adults, but there is limited data on HIVSS feasibility in community programmes. This study aimed to evaluate the feasibility of HIVSS in South Africa. METHODS: We conducted a prospective study that enrolled participants through mobile site, homebased, workplace and sex worker programmes in two townships from May to November 2017. Following an information session on HIVSS, interested participants were offered one of three methods of HIVSS testing: supervised, semi-supervised, and unsupervised. Participants who opted for unsupervised testing and those who tested HIV positive after semi- or supervised HIVSS were followed up telephonically or with a home visit one week after receipt of the test kit to confirm results and linkages to care. Follow-up visits were concluded when the participant indicated that they had used the kit or had accessed a confirmatory HIV test. RESULTS: Of the 2061 people approached, 88.2% (1818/2061) received HIV testing information. Of this group, 89% (1618/1818) were enrolled in the study and 70.0% (1133/1618) were tested for HIV with the kit. The median age was 28 (IQR:23-33) years with an even gender distribution. Of those enrolled, 43.0% (696/1618) were identified through homebased outreach, 42.5% (687/1618) through mobile sites, 7.3% (118/1618) at their workplace and 7.2% (117/1618) from sex worker programmes. A total of 68.7% (1110/1616) selected unsupervised HIVSS, whereas 6.3% (101/1616) opted for semi-supervised and 25.0% ((405/1616) chose supervised HIVSS. Overall, the HIV prevalence using the HIVSS test was 8.2% (93/1129). Of those newly diagnosed with HIV, 16% (12/75) were initiated on ART. Almost half (48.0%; 543/1131) of those tested were linked to a primary HIV test as follows: supervised (85.2%; 336/394); semi-supervised (93.8%; 91/97) and unsupervised (18.1%; 116/640). CONCLUSION: Unsupervised HIVSS was by far the most selected and utilised HIVSS method. Linkages to primary and confirmatory testing for the unsupervised HIVSS and further care were low, despite home visits and telephonic reminders.


Assuntos
Infecções por HIV/diagnóstico , Programas de Rastreamento/métodos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Autocuidado/métodos , Testes Sorológicos/métodos , Adulto , Estudos de Viabilidade , Feminino , HIV , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos , Masculino , Programas de Rastreamento/psicologia , Prevalência , Estudos Prospectivos , Autocuidado/psicologia , Testes Sorológicos/psicologia , Profissionais do Sexo , África do Sul/epidemiologia , Adulto Jovem
19.
Pharmacogenet Genomics ; 29(7): 167-178, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31162291

RESUMO

BACKGROUND: African populations are characterised by high genetic diversity, which provides opportunities for discovering and elucidating novel variants of clinical importance, especially those affecting therapeutic outcome. Significantly more knowledge is however needed before such populations can take full advantage of the advances in precision medicine. Coupled with the need to concisely map and better understand the pharmacological implications of genetic diversity in populations of sub-Sharan African ancestry, the aim of this study was to identify and characterize known and novel variants present within 65 important absorption, distribution, metabolism and excretion genes. PATIENTS AND METHODS: Targeted ultra-deep next-generation sequencing was used to screen a cohort of 40 South African individuals of Bantu ancestry. RESULTS: We identified a total of 1662 variants of which 129 are novel. Moreover, out of the 1662 variants 22 represent potential loss-of-function variants. A high level of allele frequency differentiation was observed for variants identified in this study when compared with other populations. Notably, on the basis of prior studies, many appear to be pharmacologically important in the pharmacokinetics of a broad range of drugs, including antiretrovirals, chemotherapeutic drugs, antiepileptics, antidepressants, and anticoagulants. An in-depth analysis was undertaken to interrogate the pharmacogenetic implications of this genetic diversity. CONCLUSION: Despite the new insights gained from this study, the work illustrates that a more comprehensive understanding of population-specific differences is needed to facilitate the development of pharmacogenetic-based interventions for optimal drug therapy in patients of African ancestry.

20.
Tuberculosis (Edinb) ; 116: 17-21, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31153513

RESUMO

SETTING: Mycobacterial sputum culture is a key diagnostic and research tool. OBJECTIVE: To compare mycobacterial culture outcomes of three sputum collection methods. DESIGN: We compared culture results within sets of three sputum samples collected from 18 HIV-infected adult tuberculosis patients at regular intervals up to 84 days after treatment initiation. The first sputum was collected at home and brought to the clinic, where a second and third sputum were consecutively collected under supervision following mouthwash with bottled water and chlorhexidine solution respectively. All sputa were processed for liquid culture in duplicate. RESULTS: Out of 556 cultures 430 (77.3%), 91 (16.4%) and 35 (6.3%) were positive, negative or contaminated, respectively. The odds of contamination were higher with home collection and with water rinse than with chlorhexidine rinse (OR: 12.5, p < 0.001 and OR: 6.7, p = 0.015). Chlorhexidine rinse increased the odds of a negative culture compared to water rinse (OR: 3.5, p = 0.002). The odds of a positive culture were greater with water rinse than with home collection (OR: 2.5, p = 0.005). Water rinse significantly reduced time to culture positivity. CONCLUSION: Compared to sputum collected at home, chlorhexidine rinse reduces culture contamination and water rinse increases the rate and viable mycobacterial load of positive cultures.


Assuntos
Técnicas Bacteriológicas , Mycobacterium tuberculosis/isolamento & purificação , Manejo de Espécimes/métodos , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Antituberculosos/uso terapêutico , Clorexidina/administração & dosagem , Coinfecção , Água Potável , Feminino , Infecções por HIV/diagnóstico , Humanos , Masculino , Viabilidade Microbiana , Antissépticos Bucais/administração & dosagem , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
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