A packaged intervention to improve viral load monitoring within a deeply rural health district of South Africa.

BACKGROUND: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. METHODS: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. RESULTS: Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p < 0·01). VL suppression rates similarly increased overall by 39·3% and 36·2% (RR 1·84 and 1·70, p < 0·01). The Chart Intervention phase showed significant increases in fidelity 16 months after implementation. CONCLUSIONS: The packaged intervention improved VL performance and suppression rates overall but was significant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.

An isolated outbreak of diphtheria in South Africa, 2015.

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.

Clinical evaluation of the OneStep Gonorrhea RapiCard InstaTest for detection of Neisseria gonorrhoeae in symptomatic patients from KwaZulu-Natal, South Africa.

We evaluated a point-of-care test for the detection of Neisseria gonorrhoeae in patients attending a public health clinic in KwaZulu-Natal, South Africa. The test showed a low sensitivity against PCR and culture (<40%); however, a higher specificity was observed (>95%). This test is unsuitable as a screening tool for gonorrhea.

Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

OBJECTIVE: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. DESIGN: A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. RESULTS: In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. CONCLUSION: This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

OBJECTIF: Identifier les indicateurs d'alerte précoce au niveau individuel de l'échec virologique chez les patients séropositifs recevant un traitement antirétroviral (TAR) en Afrique du Sud. MÉTHODE: Une étude cas-témoins appariée de personnes avec et sans échec virologique (FV, pour l'anglais « virologic failure ¼) (>5 mois sous ART et charge virale plasmatique du VIH-1 >1 000 copies/ml) a été menée entre juin 2014 et juin 2018. Sur les 1 000 participants inscrits dans la cohorte parente, 96 ont présenté une FV et 199 témoins supplémentaires ont été identifiés dans la cohorte parentale et appariés 1:2 (certains appariés 1:3) pour le sexe, l'âge, la durée du TAR et le site. Les participants ont été interrogés pendant que des données cliniques, de renouvellement de pharmacie, de laboratoire et pharmacologiques objectives ont été obtenues. Des modèles de régression logistique conditionnelle multivariée ont été construits à l'aide d'une sélection de modèles pour identifier les facteurs associés à la FV. Les déterminants significatifs de la FV ont été identifiés à l'aide d'un niveau alpha de 0,05. RÉSULTATS: Dans un modèle conditionnel complet, une observance cumulative plus élevée du TAR, quantifiée à l'aide des concentrations de ténofovir-diphosphate dans les gouttes de sang séché (OR 0,26) et du ratio de possession de médicaments (OR 0,98) protégeait contre la FV, tandis qu'une augmentation du score de dépression totale (OR 1,20) était prédictive de la FV. CONCLUSION: Cette analyse démontre l'importance de la dépression en tant qu'indicateur précoce clé au niveau individuel de la FV. Les efforts visant à résoudre les problèmes de santé mentale chez les personnes vivant avec le VIH pourraient améliorer la suppression virologique.

International spread of MDR TB from Tugela Ferry, South Africa.

We describe a death associated with multidrug-resistant tuberculosis and HIV infection outside Africa that can be linked to Tugela Ferry (KwaZulu-Natal, South Africa), the town most closely associated with the regional epidemic of drug-resistant tuberculosis. This case underscores the international relevance of this regional epidemic, particularly among health care workers.

Venous thromboembolic disease in adults admitted to hospital in a setting with a high burden of HIV and TB.

BACKGROUND: HIV and tuberculosis (TB) independently cause an increased risk for venous thromboembolic disease (VTE): deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Data from high HIV and TB burden settings describing VTE are scarce. The Wells' DVT and PE scores are widely used but their utility in these settings has not been reported on extensively. OBJECTIVES: To evaluate new onset VTE, compare clinical characteristics by HIV status, and the presence or absence of TB disease in our setting. We also calculate the Wells' score for all patients. METHODS: A prospective cohort of adult in-patients with radiologically confirmed VTE were recruited into the study between September 2015 and May 2016. Demographics, presence of TB, HIV status, duration of treatment, CD4 count, viral load, VTE risk factors, and parameters to calculate the Wells' score were collected. RESULTS: We recruited 100 patients. Most of the patients were HIV-infected (n=59), 39 had TB disease and 32 were HIV/TB co-infected. Most of the patients had DVT only (n=83); 11 had PE, and 6 had both DVT and PE. More than a third of patients on antiretroviral treatment (ART) (43%; n=18/42) were on treatment for <6 months. Half of the patients (51%; n=20/39) were on TB treatment for <1 month. The median (interquartile range (IQR)) DVT and PE Wells' score in all sub-groups was 3.0 (1.0 - 4.0) and 3.0 (2.5 - 4.5), respectively. CONCLUSION: HIV/TB co-infection appears to confer a risk for VTE, especially early after initiation of ART and/or TB treatment, and therefore requires careful monitoring for VTE and early initiation of thrombo-prophylaxis.

Protocol for a randomised feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression in South Africa: the POwER study.

INTRODUCTION: Access to HIV viral load testing remains difficult for many people on antiretroviral therapy (ART) in low-income and middle-income countries. Weak laboratory and clinic systems often delay the detection and management of viraemia, which can lead to morbidity, drug resistance and HIV transmission. Point-of-care testing could overcome these challenges. We aim to assess whether it is feasible to conduct a randomised trial of point-of-care viral load testing to manage viraemia. METHODS AND ANALYSIS: We will conduct an open-label, single-site, individually randomised, feasibility study of Point-Of-care HIV viral load testing to Enhance Re-suppression, in Durban, South Africa. We will enrol approximately 100 people living with HIV who are aged ≥18 years, receiving first-line ART but with recent viraemia ≥1000 copies/mL, and randomise them 1:1 to receive point-of-care viral load or standard laboratory viral load monitoring, after 12 weeks. All participants will continue to receive care from public sector healthcare workers following South African HIV management guidelines. Participants with persistent viraemia ≥1000 copies/mL will be considered for switching to second-line ART. We will compare the proportion in each study arm who achieve the primary outcome of viral suppression <50 copies/mL at 24 weeks after enrolment. Additional outcomes include proportions retained in the study, proportions with HIV drug resistance, time to viral load results and time to switching to second-line ART. We will assess implementation of point-of-care viral load testing using process evaluation data, and through interviews and focus groups with healthcare workers. ETHICS AND DISSEMINATION: University of Oxford Tropical Research Ethics Committee and the Biomedical Research Ethics Committee of the University of KwaZulu-Natal have approved the study. We will present results to stakeholders, and through conferences and open-access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: PACTR202001785886049.

Comparative analyses of published cost effectiveness models highlight critical considerations which are useful to inform development of new models.

Background: Comparative analyses of published cost effectiveness models provide useful insights into critical issues to inform the development of new cost effectiveness models in the same disease area.Objective: The purpose of this study was to describe a comparative analysis of cost-effectiveness models and highlight the importance of such work in informing development of new models. This research uses genotypic antiretroviral resistance testing after first line treatment failure for Human Immunodeficiency Virus (HIV) as an example.Method: A literature search was performed, and published cost effectiveness models were selected according to predetermined eligibility criteria. A comprehensive comparative analysis was undertaken for all aspects of the models.Results: Five published models were compared, and several critical issues were identified for consideration when developing a new model. These include the comparator, time horizon and scope of the model. In addition, the composite effect of drug resistance prevalence, antiretroviral therapy efficacy, test performance and the proportion of patients switching to second-line ART potentially have a measurable effect on model results. When considering CD4 count and viral load, dichotomizing patients according to higher cost and lower quality of life (AIDS) versus lower cost and higher quality of life (non-AIDS) status will potentially capture differences between resistance testing and other strategies, which could be confirmed by cross-validation/convergent validation. A quality adjusted life year is an essential outcome which should be explicitly explored in probabilistic sensitivity analysis, where possible.Conclusions: Using an example of GART for HIV, this study demonstrates comparative analysis of previously published cost effectiveness models yields critical information which can be used to inform the structure and specifications of new models.

Extensively drug-resistant tuberculosis 'hotspots' and sociodemographic associations in Durban, South Africa.

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. 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. 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. 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. .

Low effectiveness of syndromic treatment services for curable sexually transmitted infections in rural South Africa.

OBJECTIVES: Syndromic sexually transmitted infection (STI) treatment remains a cost-saving HIV prevention intervention in many countries in Africa. We estimate the effectiveness of syndromic treatment for curable STIs in rural KwaZulu-Natal, South Africa, and the trend in STI prevalences before and after the introduction of syndromic treatment in 1995. METHODS: Data were available from various clinical studies, surveys of public and private health providers, the general population and women attending antenatal, family planning and child immunisation clinics in rural northern KwaZulu-Natal between 1987 and 2004. Overall effectiveness was defined as the estimated proportion of the annual number of symptomatic curable STI episodes cured by syndromic treatment based on separate estimates for six curable STI aetiologies by gender. RESULTS: Median overall effectiveness was 13.1% (95% CI 8.9 to 17.8%) of symptomatic curable STI episodes cured. Effectiveness increased to 25.0% (95% CI 17.3 to 33.8%), 47.6% (95% CI 44.5 to 50.8%) or 14.3% (95% CI 9.9 to 19.4%) if 100% treatment seeking, 100% correct treatment provision or 100% cure were assumed, respectively. Time-trends were difficult to assess formally but there was little evidence of decreasing STI prevalences. Including incurable but treatable herpes simplex virus (HSV)-2 ulcers in the effectiveness calculation would halve the proportion of ulcers cured or correctly treated, but this reduction could be entirely countered by including episodic antiviral treatment in the national guidelines. CONCLUSION: Overall effectiveness of syndromic treatment for curable STIs in rural KwaZulu-Natal remains low and there is little evidence of reduced curable STI prevalences. As syndromic treatment is likely to be a cost-saving HIV prevention intervention in South Africa, innovative strategies are urgently needed to increase rates of treatment seeking and correct treatment provision.

High-risk sexual behaviour in men attending a sexually transmitted infection clinic in Durban, South Africa.

OBJECTIVES: A study of men with genital ulcer disease (GUD) in Durban, South Africa, at the start of the local HIV epidemic in 1988/1989 found that 36% of men with GUD continued with sexual intercourse despite symptoms. The aim of this study was to determine whether this high-risk behaviour was still prevalent and to enquire about similar risk behaviours with other sexually transmitted infection (STI)-related problems. METHODS: 650 Men attending the main Durban STI clinic with a new complaint were enrolled. A standard questionnaire was administered. Polymerase chain reaction (PCR) tests were performed to diagnose genital herpes from ulcer specimens and gonorrhoea and chlamydia from those with urethral discharge and/or dysuria. Serology tests were performed for HIV, herpes simplex virus type 2 (HSV-2) and syphilis. RESULTS: Sex since the start of symptoms was reported by between 33.3% and 43.9% of men with GUD, herpetic ulcers, gonorrhoea and/or chlamydia or dysuria. The incidence of condom use was very low in all groups having sex despite symptoms. In 87 men with genital ulcers confirmed positive for genital herpes by PCR testing, 30 (34.4%) had had sex since the start of symptoms, 28 (93.3%) of whom had had unprotected sex. CONCLUSIONS: There is a high level of risk behaviour in this group of men in whom genital herpes is the most common cause of GUD. This risky sexual behaviour could reflect disinhibition, possibly because so many have already been infected with HSV-2, lack of education or other unknown factors. Syndromic STI management should be strengthened with intensive health education to promote community awareness of both genital ulceration and genital herpes and their role in facilitating HIV transmission. The low level of condom use indicates that condom promotion programmes still have much to achieve.

A comparison of private and public sector intensive care unit infrastructure in South Africa.

BACKGROUND: Intensive care units (ICUs) are designed to care for patients who are often at increased risk of acquiring healthcare-associated infections. The structure of ICUs should be optimally designed to facilitate the care of these critically ill patients, and minimise their risk of infection. National regulations (R158) were developed to govern the building and registration of private hospitals, and until recently equivalent regulations were not available for public hospitals. OBJECTIVE: To assess and compare the compliance of ICUs in the private and public sectors with the R158 regulations. METHODS: A cross-sectional study design was used to assess the infrastructure of 25 private sector and 6 public sector ICUs in eThekwini Health District, KwaZulu-Natal Province, South Africa. We used the R158 checklist, which was developed by the KwaZulu-Natal Department of Health Private Licensing Unit and Infection Prevention and Control Unit. The aspects covered in the R158 checklist were categorised into the design, general safety and patient services of the ICUs. RESULTS: Most of the ICUs in both sectors met the general safety requirements. There were varying levels of compliance with the design criteria. Only 7 (28.0%) and 1 (16.7%) of the private and public ICUs, respectively, had sufficient space around the beds. Twenty-two private ICUs (88.0%) and 4 public ICUs (66.7%) had isolation rooms, but only some of these isolation rooms (15 private and 2 public) had appropriate mechanical ventilation. None of the ICUs had clinical hand-wash basins in the nurse stations and dirty utility rooms. The majority of the ICUs had the required number of oxygen and electric outlets at the bedside. None of the public ICUs met the light intensity requirement over the bed area. CONCLUSIONS: Adequate spacing in ICUs is an issue in many cases. Interventions need to be put in place to ensure that ICUs meet the relevant design standards. There is an urgent need to revise the R158 regulations to reflect current best practices, particularly with regard to infection control. The same standards should be applied to ICUs in the private and public health sectors to maintain quality of care to patients.

CTX-M-37 in Salmonella enterica serotype Isangi from Durban, South Africa.

Beta-lactamase-mediated resistance was investigated in 59 putative extended-spectrum beta-lactamase (ESBL)-positive Salmonella spp. from the paediatric ward of a tertiary hospital in Durban, South Africa. Three Salmonella enterica serotype Isangi cultured from stool samples were multidrug resistant, with susceptibility only to meropenem, piperacillin/tazobactam and cefoxitin. Isoelectric focusing revealed beta-lactamases with isoelectric points of pI 5.8, 6.8 and 7.2. Sequencing identified beta-lactamases CTX-M-37 and TEM-1. To our knowledge, this is the first report of CTX-M-37 from S. enterica serotype Isangi in South Africa.

Aetiology of male urethritis in patients recruited from a population with a high HIV prevalence.

The aetiology of urethritis, the significance of potential pathogens and the relation of urethritis to HIV infection were determined in 335 men (cases) with and 100 men (controls) without urethral symptoms. Urethral swab specimens were tested for different organisms by PCR or by culture for Neisseria gonorrhoeae. The prevalence of N. gonorrhoeae and Chlamydia trachomatis was 52 and 16%, respectively. The potential pathogens: Mycoplasma genitalium, Ureaplasma urealyticum, Trichomonas vaginalis and herpes simplex virus (HSV), were present in 5, 36, 6 and 6% of the cases respectively. M. genitalium was the only potential pathogen associated with microscopic urethritis. After excluding gonococcal infections, U. urealyticum was more frequent in symptomatic patients, while the prevalence of T. vaginalis was similar among cases and controls. These results strongly suggest an a etiological role for M. genitalium in male urethritis, a possible role for U. urealyticum, but not for T. vaginalis. The control group, with 97% genital ulcer disease patients, was not suitable for the investigation of the role of HSV. The sero-prevalence of HIV was 45%. Current infections were not associated with HIV. However, a history of previous urethral discharge was associated with HIV in a multivariate analysis and supported the hypothesis that non-ulcerative sexually transmitted diseases facilitate HIV transmission.

Failure of clonidine treatment in benzodiazepine withdrawal.

Six subjects, dependent on benzodiazepines for at least 2 years, were gradually withdrawn, using placebo substitution, while taking clonidine. After withdrawal was complete, subjects were switched to clonidine-placebo. Despite administration of clonidine at doses sufficient to produce a fall in blood pressure, an abstinence syndrome was seen in five of the subjects. In none of these cases was the withdrawal syndrome exacerbated by changing from clonidine to clonidine-placebo. Scores of depression, subjective anxiety, observed anxiety and somatic symptoms did not change throughout the study.

Computed axial brain tomograms in long-term benzodiazepine users.

Computed axial brain tomograms were recorded in four groups of subjects: (a) subjects who had never taken benzodiazepines (n = 25); (b) subjects who had taken them in the past for less than a year (n = 9); (c) patients currently taking benzodiazepines (n = 30); and (d) patients who had taken benzodiazepines in the past for at least a year and who had been withdrawn from medication for at least 6 months (n = 17). Ventricle-to-brain ratios and tissue absorption to X-rays were computed. No overall differences were found between the main groups. However, a few brain regions differed in density between nonusers and heavy users, particularly those taking lorazepam.

Identification of women at high STD risk among STD clinic attendees: implications for STD programmes.

We showed an association between current infection with a recognized sexually transmitted infection (STI) pathogen and HIV infection in women but not in men with non-ulcerative genital disease. While the accuracy of recognition of male urethritis and genital ulcer syndromes is high, this is significantly less for non-ulcerative STIs in women. The symptoms associated with the latter have a broad differential diagnosis including conditions of a non-STI nature. Local sexually transmitted disease (STD) clinic attendees often comprise patients with and without STIs. We hypothesized that this may be responsible for the association of current STI pathogens and HIV in women. To identify a group of women that would be representative of a true STD clinic population we looked at those with a past history of treated genital ulcers. When we analysed in this subset the association of current STI pathogen and HIV infection, a pattern emerged that was comparable with that in men.

Diagnosis of bacterial vaginosis on self-collected vaginal tampon specimens.

A vaginal tampon specimen was previously shown to be suitable for the molecular diagnosis of non-ulcerative sexually transmitted infections (STIs). Different tampon fluid preparations were evaluated for the diagnosis of bacterial vaginosis (BV). Women with pregnancy related problems were enrolled. Two observers evaluated the different tampon fluid preparations and vaginal smears collected during speculum examination using the Nugent score. Using the Amsel criteria, 21% of the 84 women enrolled were diagnosed with BV. Results of the tampon fluid preparations and vaginal smears showed excellent agreement for both observers (Spearman >0.80). The overall sensitivity and specificity was 91.7% (95% CI: 81.6-96.5) and 79.3% (95% CI: 67.2-87.8), respectively, using the Amsel criteria as reference standard. The tampon provides a specimen for the combined diagnosis of non-ulcerative STIs and BV. This non-invasively collected specimen may facilitate self-initiated testing and population-based studies as well as longitudinal studies that are necessary to gain insight in the epidemiology of BV related to STIs and HIV.

Bacterial vaginosis and associated infections in pregnancy.

OBJECTIVE: To assess the role of bacterial vaginosis (BV) on pregnancy complications in a developing community where mixed cervico-vaginal infections are common. SETTING: The antenatal clinic at King Edward VIII Hospital (KEH), Durban, South Africa, which is a large urban tertiary hospital serving mainly a Black underprivileged population of KwaZulu/Natal. METHODS: Asymptomatic pregnant women < or = 30 weeks gestation were recruited at their first antenatal visit. Clinical data including the sexual history were recorded. Swab specimens were collected from the vagina and endocervix for diagnosing BV, trichomoniasis, candidiasis, gonorrhea and chlamydial infection. Venous blood specimens were tested for antibody to syphilis and human immunodeficiency virus (HIV). All women continued standard antenatal care and hospital records were reviewed following delivery to evaluate pregnancy outcome. RESULTS: BV was found in 52% of the women studied and was the commonest infection diagnosed. Mixed vaginal infections of BV and trichomoniasis were diagnosed in 14%. Only 29% of asymptomatic women did not have any microbiological evidence of a lower genital tract infection. A total of 46% of women studied had poor pregnancy outcome as measured by obstetrical complications, pregnancy loss and/or neonatal morbidity. There was a significant difference in outcome in women with BV (55 of 88) compared to those having infections other than BV (13 of 31), or no infection (5 of 9)-P = 0.005. This difference was for obstetrical complications of preterm delivery, premature rupture of membranes and intrauterine infection, but not for pregnancy losses and neonatal morbidity. CONCLUSIONS: The high prevalence of BV and concomitant lower genital tract infections among asymptomatic pregnant women and the resultant adverse pregnancy outcome associated with BV, confirms reports from developed countries of the need for screening for BV at the initial antenatal clinic visit. Whether pregnancy outcome was worse in the presence of BV and other infections than BV alone could not be determined. Future studies with appropriate interventions are needed to evaluate the unique problems of developing countries.