Drug-Resistant Tuberculosis among HIV-Infected Patients Starting Antiretroviral Therapy in Durban, South Africa

Objective

To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa.

Design

Cross-sectional cohort study.

Methods

Consecutive HIV-infected adults (≥18y/o) initiating HIV care were enrolled from May 2007–May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium). Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed.

Results

1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42–150/µl). 267 subjects (26%) reported a prior history of TB and 210 (20%) were receiving TB treatment at enrollment; 191 (18%) subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0–12.4). Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9–30.5) compared to 5.2% (95% CI 2.1–8.9) among those with no prior TB. 5.1% (95% CI 2.4–9.5) had rifampin or rifampin plus INH resistance.

Conclusions

The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.     

Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa

Background

Antiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART.

Methodology

Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis.

Findings

Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period.

Conclusion

Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.     

Sustained Virological Response on Second-Line Antiretroviral Therapy following Virological Failure in HIV-Infected Patients in Rural South Africa

Objective

This study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa.

Methods

An observational cohort study was performed on 210 patients (including 39 children) who initiated PI-based second-line therapy at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (plasma HIV-1 RNA<400 copies/ml), full virological suppression (plasma HIV-1 RNA<50 copies/ml) and treatment failure (virological failure (plasma HIV-1 RNA>1000 after initial virological response) or on-going viremia (plasma HIV-1 RNA never<400 copies/ml for more than six months)). Data were analyzed by an on-treatment (OT) and intention-to-treat (ITT) approach. Analyses were primarily performed on the group of patients who switched following first-line virological failure.

Results

Median duration of follow-up after switch to second-line treatment was 20 months [IQR 11–35]. 191 patients had switched to second-line ART due to first-line virological failure. 139/191 of them (72.8%, ITT) were in care and on treatment at the end of follow-up and 11/191 (5.8%, ITT) had died. After twelve months, an adequate virological response was seen in 92/128 patients (71.9%, OT), of which 78/128 (60.9%, OT) experienced full virological suppression. Virological response remained stable after 24 months. Virological efficacy was similar amongst adult and pediatric patients. As in first-line ART, we observed a lack of correlation between virological failure and WHO-defined immunological failure.

Conclusions

Good virological outcomes following first-line failure can be achieved with PI-based, second-line antiretroviral therapy in both adult and pediatric patients in rural South Africa. Retention rates were high and virological outcomes were sustainable during the two-year follow-up period, although persisting low-level viremia occurred in a subset of patients. The observed viro-immunological dissociation emphasizes the need for virological monitoring.     

The pigments from Pinnacle Point Cave 13B, Western Cape, South Africa

Earth pigments from the three excavations at Pinnacle Point Cave 13B (Western Cape Province, South Africa), spanning the terminal middle Pleistocene and earlier late Pleistocene, are described and analyzed. Qualitative geological categorization primarily rested on textural, fabric, and iron enrichment attributes. Comprehensive recovery allowed identification of non-anthropic pigmentaceous materials, questionable pigments, and 380 pigments (1.08?kg). Less chemically altered pigments were typically fine-grained sedimentary (FGS) rocks, tending to be soft, highly micaceous, prone to laminar fragmentation, and with reddish-brown streaks of intermediate nuance. More iron-enriched forms tended to be harder, denser, poorly micaceous, and with redder streaks of more saturated nuance. Some still qualified as FGS forms, but a large number were categorized as sandstone or iron oxide. Despite some temporal change in raw material profiles, circumstantial evidence suggests primarily local procurement from one outcrop throughout the sequence. Definitely utilized pieces (12.7%) were overwhelmingly ground. Unusual forms of modification include several notched pieces and a deliberately scraped 'chevron.' Controlling for fragmentation, streak properties of utilized versus unutilized pieces were used to investigate selective criteria. There was robust evidence for preferential grinding of the reddest materials, strongly suggestive evidence for saturation and darkness being subordinate selective criteria, and some indication of more intensive grinding of materials with the reddest, most saturated, and darkest streaks, and for some deliberate heating of pigments. These findings challenge the initial stages of color lexicalization predicted by the various versions of the basic color term (BCT) hypothesis, they provide grounds for rejecting hafting as a general explanatory hypothesis, and they cannot be accounted for by incidental heating. The results are more consistent with agreed upon canons of ornamentation than with individual display. It is concluded that the material was processed to produce saturated red pigment powders. On theoretical grounds, these are presumed to have served primarily as body paints in ritual performance.     

Causes of Death on Antiretroviral Therapy: A Post-Mortem Study from South Africa

Background

Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these patients.

Methods

HIV-positive adults who died as in-patients at a Johannesburg academic hospital underwent chart-review and ultrasound-guided needle autopsy for histological and microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all available data and adjudicated immediate and contributing causes of death.

Results

Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7–90 days), and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations revealed previously undiagnosed causes of death in 49% of cases. Multiple pathologies were common with 62% of subjects with mycobacterial infection also having at least one other infectious or neoplastic cause of death.

Conclusions

Needle biopsy was efficient and yielded excellent pathology. The large majority of deaths in all three groups were caused by M. tuberculosis suggesting an urgent need for improved diagnosis and expedited treatment prior to and throughout the course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an additional challenge.     

Linkage to HIV,TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town,South Africa

Background

HIV counseling and testing may serve as an entry point for non-communicable disease screening.

Objectives

To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit.

Methods

A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined.

Results

Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic.

Conclusion

Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care.     

Bioremediation of metal contamination in the Plankenburg River,Western Cape,South Africa

Three bioreactors (two laboratory-scale and one on-site) were evaluated for their efficiency to reduce metal concentrations in water collected from the Plankenburg River, South Africa. Water (bioreactors one, two and on-site) and bioballs (bioreactors two and on-site) collected throughout the study periods were digested and analysed using Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES). Aluminium (Al), nickel (Ni), and zinc (Zn) concentrations decreased from 0.41 mg l^?1 to 0.06 mg l^?1 (85%), 0.2 mg l^?1 to 0.07 mg l^?1 (65%) and 75 mg l^?1 to 0.02 mg l^?1 (97%), respectively (bioreactor one). Aluminium [(1.55–0.38 mg l^?1 (75%)], copper (Cu) [57% (from 0.33 mg l^?1 to 0.14 mg l^?1)], iron (Fe) [71.99–40.4 mg l^?1 (44%)] and manganese (Mn) [57% (0.07–0.03 mg l^?1)] concentrations also decreased in the water samples from bioreactor two. In the on-site, six-tank bioreactor system, concentrations for Fe, Cu, Mn and Ni decreased, while Zn and Al concentrations increased. The concentrations recorded in biofilm samples were higher than the corresponding water samples. The bioballs employed in the bioreactor were thus shown to be efficient attachment surfaces for biofilm development and subsequent metal accumulation. Potentially metal-tolerant organisms (Pseudomonas sp., Sphingomonas sp., and Bacillus sp.) were also identified using phylogeny.     

Antiretroviral Therapy,Especially Efavirenz,Is Associated with Low Bone Mineral Density in HIV-Infected South Africans

Purpose

We determined the prevalence and correlates of low bone mineral density (BMD) in HIV-infected South Africans as there is a paucity of such data from Africa.

Methods

BMD and serum 25-hydroxyvitamin D were measured in HIV-positive participants on antiretroviral therapy (ART) and in those not yet on ART (ART-naïve).

Results

We enrolled 444 participants [median age 35(IQR: 30, 40) years; 77% women]. BMD was low (z score <-2SD) in 17% and 5% of participants at the lumbar spine and total hip, respectively. Total hip [0.909 (SD 0.123) vs 0.956 (SD 0.124) g/cm², p = 0.0001] and neck of femur BMD [0.796 (SD 0.130) vs 0.844 (SD 0.120) g/cm², p = 0.0001] were lower in the ART, compared to the ART-naïve group. Vitamin D deficiency was present in 15% of participants and was associated with efavirenz use [adjusted OR 2.04 (95% CI 1.01 to 4.13)]. In a multivariate linear regression, exposure to efavirenz or lopinavir-based ART was associated with lower total hip BMD, whereas higher weight, being male and higher vitamin D concentration were associated with higher total hip BMD (adjusted R² = 0.28). Age, weight, sex, and the use of efavirenz-based ART were independently associated with lumbar spine BMD (adjusted R² = 0.13).

Conclusions

Vitamin D status, use of efavirenz or lopinavir/ritonavir, weight, age and sex are significantly associated with lower BMD in this young cohort of HIV-infected South Africans.     

Isolation and identification of species of Alicyclobacillus from orchard soil in the Western Cape, South Africa

Alicyclobacilli were isolated from orchard soil collected from an apple and pear farm in Elgin, Western Cape, South Africa. Morphological, biochemical and physiological characteristics of the isolates were used to presumptively classify them as belonging to the genus Alicyclobacillus. Strains were identified to species level by polymerase chain reaction (PCR) with genus-specific primers, and 16S ribosomal RNA (rRNA) gene sequencing. To our knowledge this is the first report on the isolation of Alicyclobacillus acidoterrestris and Alicyclobacillus acidocaldarius from orchard soil. The presence of these organisms in the soil suggests a possible source of contamination for the final fruit juice, concentrate or pulp.     

Effectiveness of Patient Adherence Groups as a Model of Care for Stable Patients on Antiretroviral Therapy in Khayelitsha,Cape Town,South Africa

Background

Innovative models of care are required to cope with the ever-increasing number of patients on antiretroviral therapy in the most affected countries. This study, in Khayelitsha, South Africa, evaluates the effectiveness of a group-based model of care run predominantly by non-clinical staff in retaining patients in care and maintaining adherence.

Methods and Findings

Participation in “adherence clubs” was offered to adults who had been on ART for at least 18 months, had a current CD4 count >200 cells/ml and were virologically suppressed. Embedded in an ongoing cohort study, we compared loss to care and virologic rebound in patients receiving the intervention with patients attending routine nurse-led care from November 2007 to February 2011. We used inverse probability weighting to estimate the intention-to-treat effect of adherence club participation, adjusted for measured baseline and time-varying confounders. The principal outcome was the combination of death or loss to follow-up. The secondary outcome was virologic rebound in patients who were virologically suppressed at study entry. Of 2829 patients on ART for >18 months with a CD4 count above 200 cells/µl, 502 accepted club participation. At the end of the study, 97% of club patients remained in care compared with 85% of other patients. In adjusted analyses club participation reduced loss-to-care by 57% (hazard ratio [HR] 0.43, 95% CI = 0.21–0.91) and virologic rebound in patients who were initially suppressed by 67% (HR 0.33, 95% CI = 0.16–0.67).

Discussion

Patient adherence groups were found to be an effective model for improving retention and documented virologic suppression for stable patients in long term ART care. Out-of-clinic group-based models facilitated by non-clinical staff are a promising approach to assist in the long-term management of people on ART in high burden low or middle-income settings.     

Monitoring and management of the endangered Cape mountain zebra Equus zebra zebra in the Western Cape, South Africa

De Hoop Nature Reserve and a neighbouring conservancy contain the most genetically diverse subpopulation of the Endangered (IUCN) Cape mountain zebra ( Equus zebra zebra Linnaeus 1758). Although vital for the long-term stability of the meta-population, the population had received limited monitoring post-1999. We summarize data obtained during a population monitoring programme established in 2005. Ninety-nine individuals were identified indicating a decline in annual population growth from 6.6% (1995–1999) to 4.5% (1999–2005). The population was male biased and the deficit of females is likely to have prevented additional breeding herd formation resulting in excess nonbreeding males. These animals are currently of limited reproductive value to the meta-population and may be contributing to the decline in reproductive potential at De Hoop by competing for limited resources. One solution may be to translocate 'excess' males to reinforce existing small populations or establish new populations with females from elsewhere provided that a minimum of 78 animals is maintained at De Hoop to limit genetic loss. Population monitoring and effective management strategies for the De Hoop population and the meta-population are vital to ensure the long-term survival of Cape mountain zebra and for the success of other species recovery programmes.     

Middle Stone Age human fossils from Die Kelders Cave 1, Western Cape Province, South Africa

Die Kelders Cave 1 (DK1) preserves a thick series of Middle Stone Age (MSA) horizons that date to a fairly short temporal interval sometime between about 60 and 80 ka ago. Twenty-seven human fossils, comprising 24 isolated teeth, a mandibular fragment, and two manual middle phalanges derive from seven of the 12 layers. The vast majority are children, and all may have come from sub-adult individuals. The entire assemblage may represent a minimum of ten individuals. As might be expected for teeth of such antiquity, most of the DK1 crowns tend to be large in comparison to recent African homologues. They tend to be smaller than, albeit more similar in size to, the teeth of penecontemporaneous archaic populations from Eurasia. The majority of morphological variants displayed by the DK1 crowns characterize the teeth of recent sub-Saharan Africans, and the DK1 crowns resemble those of recent Africans in a number of traits that have been used to define a sub-Saharan African regional complex. The morphological similarities between the DK1 MSA and recent African teeth, however, do not necessarily signify a close evolutionary relationship between them, because these crowns variants appear to be plesiomorphic.     

Recognizing intimate partner violence in primary care: Western Cape, South Africa

Introduction

Interpersonal violence in South Africa is the second highest contributor to the burden of disease after HIV/AIDS and 62% is estimated to be from intimate partner violence (IPV). This study aimed to evaluate how women experiencing IPV present in primary care, how often IPV is recognized by health care practitioners and what other diagnoses are made.

Methods

At two urban and three rural community health centres, health practitioners were trained to screen all women for IPV over a period of up to 8 weeks. Medical records of 114 thus identified women were then examined and their reasons for encounter (RFE) and diagnoses over the previous 2-years were coded using the International Classification of Primary Care. Three focus group interviews were held with the practitioners and interviews with the facility managers to explore their experience of screening.

Results

IPV was previously recognized in 11 women (9.6%). Women presented with a variety of RFE that should raise the index of suspicion for IPV– headache, request for psychiatric medication, sleep disturbance, tiredness, assault, feeling anxious and depressed. Depression was the commonest diagnosis. Interviews identified key issues that prevented health practitioners from screening.

Conclusion

This study demonstrated that recognition of women with IPV is very low in South African primary care and adds useful new information on how women present to ambulatory health services. These findings offer key cues that can be used to improve selective case finding for IPV in resource-poor settings. Universal screening was not supported by this study.     

Aspalathus crewiana sp. nov. (Crotalarieae,Fabaceae) from the Western Cape Province,South Africa

A new species, Aspalathus crewiana is described and illustrated. It is closely similar to A. lenticula in the strongly rostrate keel petals and thorny leaflets, but differs in the subulate, spine‐tipped bracts, bracteoles and calyx lobes, presence of a pseudo‐peduncle and larger flowers. The new species, like A. lenticula, is placed in the Terminales group of A. subgenus Aspalathus. It is known from only two localities in the Western Cape where it was collected in Swartland Granite Renosterveld.     

Activity patterns of springhares from the Eastern Cape Province, South Africa

The activity patterns of springhares Pedetes capensis ( Rodentia: Pedetidae ) from the Eastern Cape Province, South Africa, were investigated by counting the number of springhares active above ground at regular intervals throughout the night at different times of the year and under different weather conditions and phases of the moon. A combination of time of year, time of night and level of illumination best explained springhare activity, accounting for 43% of the variation in springhare numbers. Springhare activity generally reached its peak soon after dark, thereafter remaining fairly constant throughout most of the night and only decreasing in the 2–4-h period before sunrise. On those nights when the moon either rose or set during the night, this pattern was modified by the level of illumination. Springhares responded to moonlight by reducing above-ground activity, shifting activity to dark, moonless periods of the night, and by reducing their use of open space. Except for extremes, other weather conditions had no significant effect on springhare activity.     

Mesozoic palaeogeography of the Southern Cape,South Africa

Four palaeogeographical reconstructions are presented for the southern Cape covering the period Late Permian to Late Cretaceous. This time spans the commencement to an advanced stage of breakup of Gondwanaland, during which the area moved from a mid-continental, high latitude, to an ocean-dominated, middle latitude position. These movements can be traced in facies changes and erosional cycles associated with the rift between West Gondwana and Antarctica (proto southwest Indian Ocean) and the later rift between South America and Africa (proto southeast Atlantic Ocean).