Articles tagged as "South Africa"

Is stool testing the answer to the problem of childhood TB diagnosis?

Stool Xpert® MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis at primary clinics in Zimbabwe.

Chipinduro M, Mateveke K, Makamure B, Ferrand RA, Gomo E. Int J Tuberc Lung Dis. 2017 Feb 1;21(2):161-166. doi: 10.5588/ijtld.16.0357.

Objective: To evaluate the diagnostic performance of Xpert® MTB/RIF on stool samples from children with clinical suspicion of pulmonary tuberculosis (PTB) at primary care clinics.

Design: A cross-sectional diagnostic evaluation enrolling 5-16 year olds from whom one induced sputum (IS) sample was tested for microbiological TB confirmation. Results of a single stool sample tested using Xpert® were compared against microbiologically confirmed TB, defined as a positive result on sputum microscopy and/or culture and/or IS Xpert®.

Results: Of 222 children enrolled, 218 had complete microbiological results. The median age was 10.6 years (interquartile range 8-13). TB was microbiologically confirmed in 19/218 (8.7%) children. Of these, respectively 5 (26%), 9 (47%) and 15 (79%) were smear-, culture- and IS Xpert®-positive. Stool Xpert® was positive in 13/19 (68%) microbiologically confirmed cases and 4/199 (2%) microbiologically negative cases. Stool Xpert® detected 76.9% (10/13) of human immunodeficiency virus (HIV) infected and 50% (3/6) of non-HIV-infected children with microbiologically confirmed TB (P = 0.241).

Conclusion: Stool Xpert® is a potential alternative screening test for children with suspected TB if sputum is unavailable. Strategies to optimise the diagnostic yield of stool Xpert® assay need further study.

Abstract  Full-text [free] access 

Xpert® MTB/RIF on Stool is Useful for the Rapid Diagnosis of Tuberculosis in Young Children with Severe Pulmonary Disease

Walters E, van der Zalm MM, Palmer M, Bosch C, Demers AM, Draper H, Goussard P, Schaaf HS, Friedrich SO, Whitelaw A, Warren R, Gie RP, Hesseling AC. Pediatr Infect Dis J. 2017 Jan 31. doi: 10.1097/INF.0000000000001563. [Epub ahead of print]

Background: Tuberculosis (TB) continues to result in high morbidity and mortality in children from resource-limited settings. Diagnostic challenges, including resource-intense sputum collection methods and insensitive diagnostic tests, contribute to diagnostic delay and poor outcomes in children. We evaluated the diagnostic utility of stool Xpert® MTB/RIF (Xpert) compared with bacteriologic confirmation (combination of Xpert® and culture of respiratory samples).

Methods: In a hospital-based study in Cape Town, South Africa, we enrolled children younger than 13 years of age with suspected pulmonary TB from April 2012- August 2015. Standard clinical investigations included tuberculin skin test, chest radiograph and HIV testing. Respiratory samples for smear microscopy, Xpert® and liquid culture included gastric aspirates, induced sputum, nasopharyngeal aspirates and expectorated sputum. One stool sample per child was collected and tested using Xpert®.

Results: Of 379 children enrolled (median age, 15.9 months, 13.7% HIV-infected), 73 (19.3%) had bacteriologically confirmed TB. The sensitivity and specificity of stool Xpert® vs. overall bacteriologic confirmation were 31.9% (95% CI 21.84-44.50%) and 99.7% (95% CI 98.2-100%) respectively. 23/51 (45.1%) children with bacteriologically confirmed TB with severe disease were stool Xpert® positive. Cavities on chest radiograph were associated with Xpert® stool positivity regardless of age and other relevant factors (OR 7.05; 95% CI 2.16-22.98; p=0.001).

Conclusions: Stool Xpert® can rapidly confirm TB in children who present with radiologic findings suggestive of severe TB. In resource-limited settings where children frequently present with advanced disease, Xpert® on stool samples could improve access to rapid diagnostic confirmation and appropriate treatment.

Abstract access

Editor’s notes: It has been known for a long time that Mycobacterium tuberculosis can be detected in stool specimens in some people with pulmonary TB disease. This is because sputum is often swallowed and M. tuberculosis bacilli can survive transit through the gastrointestinal tract. With the challenges of detecting TB in children, and the introduction of molecular diagnostic tools, there has been renewed interest in using stool specimens to improve TB diagnosis.

These two studies from southern Africa evaluated the diagnostic yield and accuracy of Xpert® MTB/RIF testing on stool specimens in children with symptoms compatible with intrathoracic TB. The study populations were different. The children in the South African study were younger than in the Zimbabwean study (median age 16 months vs. 10 years). In South Africa, only one in seven children was HIV positive whereas half the children were HIV positive in the Zimbabwean study. The South African study was conducted at hospital level whereas the Zimbabwean study was at primary health care clinics.

Despite these differences, the main findings were similar. Stool Xpert® was positive in six percent in South Africa and eight percent in Zimbabwe. Sensitivity of stool Xpert® compared to a single culture from induced sputum was 50% in South Africa and 67% in Zimbabwe. A single Xpert® test on stool was no better than a single Xpert® test on induced sputum. There was some evidence from both studies that sensitivity was higher in HIV positive children. However, in South Africa, sensitivity compared to any bacteriological confirmation was substantially lower (32%), as the reference standard included Xpert® and culture tests on multiple specimens. Sensitivity compared to the clinical decision to treat for TB was even lower (14%). This may have reflected the fact that all children in the South African study had chest X-rays and there were several children with intrathoracic lymph node disease.

What does this tell us about the role of Xpert® testing on stool for TB diagnosis in children? The evidence does not seem to provide strong support for scaling up stool Xpert® testing within standard diagnostic algorithms. As the South African study demonstrated, many of the children with positive Xpert® on stool were older children with more severe pulmonary disease. These are the children that may be more likely to produce sputum, and are the ones where we would want to make every effort to get respiratory specimens. This is especially the case in HIV-positive children, among whom there may be many possible diagnoses. Added to all this is the fact that processing and testing stool in the laboratory is not simple, meaning it might be difficult to scale up within decentralised laboratory systems.

It is encouraging that research groups are now addressing the challenge of TB diagnosis in children. It would seem that testing stool specimens for now does not really address the fundamental challenge in children, that they usually have paucibacillary disease often with little or no involvement of the lung parenchyma. The search must go on for better diagnostic tests for TB in children. 

Comorbidity, HIV Treatment
Africa
South Africa, Zimbabwe
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HIV Self-testing acceptable to vocational students in South Africa

High acceptability of HIV self-testing among technical vocational education and training college students in Gauteng and North West province: what are the implications for the scale up in South Africa?

Mokgatle MM, Madiba S. PLoS One. 2017 Jan 31;12(1):e0169765. doi: 10.1371/journal.pone.0169765. eCollection 2017.

Background: Although HIV self-testing (HIVST) is globally accepted as an important complement to existing HIV testing approaches, South Africa has lagged behind in its adoption. As a result, data on the acceptability and uptake of HIVST is limited. The study investigated the acceptability of HIVST among students in Technical Vocational Education and Training (TVET) colleges in two provinces in South Africa.

Methods: A cross-sectional survey using a self-administered structured questionnaire was used to collect data among 3662 students recruited from 13 TVET colleges.

Results: The mean age of the students was 21.9 years. The majority (80.9%) were sexually active; while 66.1% reported that they had one sexual partner, and 33.9% had two or more sexual partners in the past year, and 66.5% used condoms during the last sexual act. Three-quarters tested for HIV in the past year but less than half knew about HIVST prior to the survey. The acceptability of HIVST was high; about three-quarters showed a willingness to purchase a self-test kit and a majority would self-test with partners. Acceptability of HIVST was associated with being sexually active (OR = 1.73, p = 0.02, confidence interval (CI): 1.08-2.75), having ever been tested for HIV (OR = 1.74, p = 0.001, CI: 1.26-2.38), and having multiple sexual partners (OR = 0.61, p = 0.01, CI: 0.42-0.88). Three-quarters would confirm test results at a local health facility. In terms of counselling, telephone hotlines were acceptable to only 39.9%, and less than half felt that test-kit leaflets would provide sufficient information to self-test.

Interpretations: The high acceptability of HIVST among the students calls for extensive planning and preparation for the scaling up of HIVST in South Africa. In addition, campaigns similar to those conducted to promote HIV counselling and testing (HCT) should be considered to educate communities about HIVST.

Abstract  Full-text [free] access  

Editor’s notes: The percentage of people living with HIV who know their status (the first 90 of the UNAIDS 90:90:90 treatment target) has been consistently well below the stated target in national HIV treatment cascades. HIV self-testing is an exciting strategy being used to increase the uptake of testing, and has recently been adopted in South Africa. This study had two aims; firstly to assess the participants attitudes to currently available HIV counselling and testing services and secondly to assess the level of acceptability of HIV self-testing. The study population were students in technical and vocational education and training colleges in South Africa.

Among people who had not tested for HIV in the past year, reasons given for non-uptake of testing (other than a low perception of risk) included a fear of stigma associated with a positive test or a lack of comfort with testing in a hospital setting. Less than half of participants had heard of HIV self-testing, but when the concept was explained to them, around 80% expressed a willingness to use it if it was available, and 70% were willing to purchase the self-test kit. These results are consistent with other studies of HIV self-testing uptake and acceptability in sub-Saharan Africa.

The stated willingness of participants to present at a clinic for a confirmatory test is encouraging. However, this may not reflect actual behaviour, especially in a setting where there is currently no plan or system to link people with positive HIV self-test results to a clinic for confirmatory testing. However, the drive to improve counselling and linkage around self-testing needs to be balanced against the fundamental principle for HIV self-testing to allow choice for users to test without the need for a health worker to be present, and the privacy associated with this. Further work may include assessing acceptability of using remote services to complement HIV self-testing such as telephone hotlines or other counselling strategies. 

Africa
South Africa
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Community mobilization programme to increase HIV testing – more work is necessary

Community mobilization for HIV testing uptake: results from a community randomized trial of a theory-based intervention in rural South Africa.

Lippman SA, Neilands TB, MacPhail C, Peacock D, Maman S, Rebombo D, Twine R, Selin A, Leslie HH, Kahn K, Pettifor A. J Acquir Immune Defic Syndr. 2017 Jan 1;74 Suppl 1:S44-S51.

Background: HIV testing uptake in South Africa is below optimal levels. Community mobilization (CM) may increase and sustain demand for HIV testing, however, little rigorous evidence exists regarding the effect of CM interventions on HIV testing and the mechanisms of action.

Methods: We implemented a theory-driven CM intervention in 11 of 22 randomly-selected villages in rural Mpumalanga Province. Cross-sectional surveys including a community mobilization measure were conducted before (n = 1181) and after (n = 1175) a 2-year intervention (2012-2014). We assessed community-level intervention effects on reported HIV testing using multilevel logistic models. We used structural equation models to explore individual-level effects, specifically whether intervention assignment and individual intervention exposure were associated with HIV testing through community mobilization.

Results: Reported testing increased equally in both control and intervention sites: the intervention effect was null in primary analyses. However, the hypothesized pathway, CM, was associated with higher HIV testing in the intervention communities. Every standard deviation increase in village CM score was associated with increased odds of reported HIV testing in intervention village participants (odds ratio: 2.6, P = <0.001) but not control village participants (odds ratio: 1.2, P = 0.53). Structural equation models demonstrate that the intervention affected HIV testing uptake through the individual intervention exposure received and higher personal mobilization scores.

Conclusions: There was no evidence of community-wide gains in HIV testing due to the intervention. However, a significant intervention effect on HIV testing was noted in residents who were personally exposed to the intervention and who evidenced higher community mobilization. Research is needed to understand whether CM interventions can be diffused within communities over time.

Abstract  Full-text [free] access 

Editor’s notes: HIV testing is an integral component of HIV prevention strategies, and essential for achieving the UNAIDS 90-90-90 treatment target. However, testing coverage in many parts of sub-Saharan Africa remains low, particularly among men. Stigma, gender norms, and lack of ‘buy in’ about the benefits of early testing and treatment remain major barriers to testing. 

This cluster-randomised trial of a community mobilization (CM) approach for HIV prevention in South Africa is one of the first to be based around an explicit theoretical model of community change. CM is designed to engage community members and motivate people to achieve a common goal, and has been used successfully in some HIV prevention programmes. The programme focused on young men aged 18-35 years, with an aim to build community support for normative changes that are necessary to tackle social barriers to HIV testing and care. Trial outcomes included gender norms, sexual behaviour and HIV testing uptake. The trial found no overall effect on the uptake of HIV testing – self-reported HIV testing increased significantly in both arms over the two year observation period, with no difference between the programme and control communities. However, CM scores, used to quantify the degree of community engagement, were higher in the programme communities. In addition, individuals with greater exposure to the programme were more likely to report HIV testing. These findings suggest that although the CM programme did have an impact on the individuals exposed to it, the effect did not filter through to the wider community.  

CM strategies are used increasingly in public health programmes, and can be a powerful tool for increasing community awareness and engagement with HIV prevention. The benefit of CM is its ability to diffuse beyond the immediate participants to the community as a whole, to bring about the greatest possible change. However, little is known about why and how these approaches work. As this study illustrates, there is a need to understand more about the underlying mechanisms of change associated with CM, and the factors that contribute to its success.

Africa
South Africa
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Increased risk of death associated with perceived barriers to care at HIV diagnosis in South Africa

Barriers to care and 1-year mortality among newly-diagnosed HIV-infected people in Durban, South Africa.

Bassett IV, Coleman SM, Giddy J, MfamMed, Bogart LM, Chaisson CE, Ross D, Flash MJ, Govender T, Walensky RP, Freedberg KA, Losina E. J Acquir Immune Defic Syndr. 2017 Apr 1;74(4):432-438.  doi: 10.1097/QAI.0000000000001277. 2016 Dec 30. [Epub ahead of print]

Background: Prompt entry into HIV care is often hindered by personal and structural barriers. Our objective was to evaluate the impact of self-perceived barriers to healthcare on 1-year mortality among newly diagnosed HIV-infected individuals in Durban, South Africa.

Methods: Prior to HIV testing at four outpatient sites, adults (≥18y) were surveyed regarding perceived barriers to care including: 1) service delivery; 2) financial; 3) personal health perception; 4) logistical; and 5) structural. We assessed deaths via phone calls and the South African National Population Register. We used multivariable Cox proportional hazards models to determine the association between number of perceived barriers and death within one year.

Results: 1899 HIV-infected participants enrolled. Median age was 33 years (IQR: 27-41y), 49% were female, and median CD4 count was 192/µl (IQR: 72-346/µl). 1057 participants (56%) reported no, 370 (20%) reported 1-3, and 460 (24%) reported >3 barriers to care. By one year, 250 (13%, 95% CI: 12%, 15%) participants died. Adjusting for age, sex, education, baseline CD4 count, distance to clinic, and TB status, participants with 1-3 barriers (adjusted hazard ratio [aHR]: 1.49, 95% CI: 1.06, 2.08) and >3 barriers (aHR: 1.81, 95% CI: 1.35, 2.43) had higher 1-year mortality risk compared to those without barriers.

Conclusions: HIV-infected individuals in South Africa who reported perceived barriers to medical care at diagnosis were more likely to die within one year. Targeted structural interventions such as extended clinic hours, travel vouchers, and streamlined clinic operations may improve linkage to care and ART initiation for these people.

Abstract access  

Editor’s notes: Mortality among people living with HIV remains high in South Africa. Suboptimal engagement in HIV care is noted to be a significant contributor to this, with many deaths occurring before people have even started antiretroviral therapy. Potential barriers to care range from personal, such as perceived good health therefore believing antiretroviral therapy is not necessary, to logistical, such as a lack of transportation, to structural barriers such as busy clinics and long waits for care. Barriers perceived by the patient may also be different to barriers perceived by providers of care.

This study sought to explore self-perceived barriers to care at the time of testing for HIV and their impact on one-year mortality. This was in the context of a trial testing whether or not health system navigators improved linkage to and retention in care. Between 2010 and 2013, adults attending for HIV testing across four clinics in Durban, South Africa enrolled in this trial, completed a baseline questionnaire. This examined self-perceived barriers to care, their emotional health and social support. Participants found to be HIV positive were followed up via phone within 12 months. Limited clinical data was sought from clinic notes. Any reported deaths were confirmed by a national register.

Some 1887 participants were enrolled and subsequently diagnosed with HIV. Some 250 people died by 12 months post enrollment. A myriad of barriers were reported, the most common being associated with personal health, service delivery and structural issues. However, it was the sum of barriers that was predictive of risk. People with one or more perceived barriers had a higher one-year mortality risk compared to people without perceived barriers. Furthermore, it was illustrated that the greater the number of perceived barriers, the greater the risk of mortality. The risk for people with greater than three perceived barriers was double that of people with three or less barriers (22% versus 11%). Interestingly, there was no significant impact of emotional and social support as reported at baseline.

Limitations noted by the authors include a possible overestimation of deaths attributable to HIV, since there were no specific data on the cause of death. Data on co-morbidities (apart from tuberculosis) were also not collected and their potential impact on mortality is not addressed. However, it may be fair to assume that any barriers to HIV care would also extend to affecting access to other forms of healthcare. Overall, the study highlights perceived barriers at diagnosis as plausible factors to address when shaping programmes to improve retention in care. 

Africa
South Africa
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Mixed methods in biomedical intervention trials yield rich data – the VOICE-D qualitative study

How presentation of drug detection results changed reports of product adherence in South Africa, Uganda and Zimbabwe.

Musara P, Montgomery ET, Mgodi NM, Woeber K, Akello CA, Hartmann M, Cheng H, Levy L, Katz A, Grossman CI, Chirenje ZM, van der Straten A, Mensch B. AIDS Behav. 2017 Jan 21. doi: 10.1007/s10461-017-1685-x. [Epub ahead of print]

Accurate estimates of study product use are critical to understanding and addressing adherence challenges in HIV prevention trials. The VOICE trial exposed a significant gap between self-reported adherence and drug detection. The VOICE-D qualitative study was designed to better understand non-adherence during VOICE, and was conducted in 2 stages: before (stage 1) and after (stage 2) drug detection results were provided to participants. Transcripts from 44 women who participated in both stages were analysed to understand the effect of presenting drug detection data on narratives of product use. Thirty-six women reported high adherence in stage 1, yet admitted non-use in stage 2, three reported high adherence in both stages (contrary to their drug detection results) and five had consistent responses across both stages and drug results. Presenting objective measures of use may facilitate more accurate product use reporting and should be evaluated in future prevention trials.

Abstract access  

Editor’s notes: The VOICE trial looked at the effectiveness of PrEP and vaginal microbicides in women in three African countries. One of the findings of the study was low product adherence among some women, based on retrospective drug level testing. In this paper, the authors compare data on product adherence from before and after participants were given plasma drug detection results. The findings are revealing, not least because many of women interviewed explained why they had claimed to be adhering to the drug, when they were not. Women gave many reasons for not being open about taking their medicines/use of the microbicide. It is interesting that a few women continued to say that they were good adherers, even when presented with drug plasma data, which suggested otherwise. This, the authors note, requires further investigation. 

The findings provide valuable evidence of the shortcomings of collecting self-reported adherence data. The use of biomedical markers to reveal drug plasma levels is important. However, the qualitative research, which documented the discussion around those findings, is both fascinating and extremely useful. Perhaps in future there will be an even greater willingness to fund good qualitative research as a key component of trials?

Africa
South Africa, Uganda, Zimbabwe
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Getting to 80% male circumcision

Obtaining a male circumcision prevalence rate of 80% among adults in a short time: An observational prospective intervention study in the Orange Farm township of South Africa.

Marshall E, Rain-Taljaard R, Tsepe M, Monkwe C, Taljaard D, Hlatswayo F, Xaba D, Molomo T, Lissouba P, Puren A, Auvert B. Medicine (Baltimore). 2017 Jan;96(4):e5328. doi: 10.1097/MD.0000000000005328.

World Health Organization recommends a target for the male circumcision prevalence rate of 80%. This rate will have a substantial impact on the human immunodeficiency virus-acquired immunodeficiency syndrome epidemic in Eastern and Southern Africa. The objective of the study was to assess whether an innovative intervention can lead to an increased voluntary male medical circumcision (VMMC) uptake among adults in a short time. This prospective observational study of a demand generation intervention was conducted in the township of Orange Farm (South Africa) in August to November 2015. In this community male circumcision prevalence rate among adults was stable between 2010 and 2015 at 55% and 57%, despite regular VMMC campaigns at community level and the presence of a VMMC clinic that offered free VMMC. The intervention took place in a random sample of 981 households where 522 men aged 18 to 49 years accepted to participate in the study. Among the 226 uncircumcised men, 212 accepted to be enrolled in the intervention study. A personal male circumcision adviser trained in interpersonal communication skills was assigned to each uncircumcised participant. The male circumcision advisers were trained to explain the risks and benefits of VMMC, and to discuss 24 possible reasons given by men for not being circumcised. Participants were then followed for 9 weeks. Each participant had a maximum of 3 motivational interviews at home. Participants who decided to be circumcised received financial compensation for their time equivalent to 2.5 days of work at the minimum South African salary rate. Among the 212 uncircumcised men enrolled in the intervention, 69.8% (148/212; 95% confidence interval [CI]; 63.4%-75.7%) agreed to be circumcised, which defines the uptake of the intervention. The male circumcision prevalence rate of the sample increased from 56.7% (296/522) to 81.4% (425/522; 77.9%-84.6%), P < 0.001, corresponding to a relative increase of 43.6% (95% CI: 35.4%-53.7%). The reported reasons for accepting circumcision were motivational interviews with the male circumcision adviser (83.1%), and time compensation (39.4%). Increased uptake of VMMC uptake can be obtained in a short time among adult males but requires an intense intervention centered on uncircumcised men at an individual level and time compensation.

Abstract  Full-text [free] access

Editor’s notes: As there are diverse motives for and barriers to voluntary male medical circumcision (VMMC), a range of programmes are required to reach WHO’s target of 80% male circumcision. This demand-creation activity study took place in a setting where, following school talks, street animation, flyers and local radio advertising, circumcision prevalence had risen to 57% by 2010 but had then plateaued. The programme was based on the theory that saturation had not been reached and many men who remained uncircumcised were not opposed to it but needed the right opportunity and circumstances to motivate them. In just over two months the prevalence of adult male circumcision in the study sample increased to over 80%, (WHO goal) as a result of implementing up to three home-based motivational interviews, plus time compensation of half a week’s pay at minimum wage for men who had VMMC.

Uptake was highest among the oldest men (aged 40-49 years), who had the lowest prevalence of circumcision before the study. Possibly previous programmes that were primarily focussed on adolescents were less likely to affect them. The highest rates were achieved in the youngest age group (aged 18-24 years), who were the most likely to already be circumcised before the study. Time to think about their options at home was important to participants. Most men who opted for VMMC said it was very important to have discussed the situation with their partner (80%) and with relatives or friends (78%). The three motivational interviews produced diminishing yield; 112/212 men sought VMMC after the first interview, 28/78 after the second and 8/54 after the third. After one interview plus financial compensation, the male circumcision prevalence in the sample increased to 75%.

The study is an example of a locally developed and setting-appropriate activity, quickly and rigorously tested in a realistic setting. In this manner, research questions can be relevant to the context and the results can be put into practice. 

Africa
South Africa
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Tell it like it is: risky sex after 40

Sexual behaviors and HIV status: a population-based study among older adults in rural South Africa.

Rosenberg MS, Gomez-Olive FX, Rohr JK, Houle BC, Kabudula CW, Wagner RG, Salomon JA, Kahn K, Berkman LF, Tollman SM, Barnighausen T. J Acquir Immune Defic Syndr. 2017 Jan 1;74(1):e9-e17.

Objective: To identify the unmet needs for HIV prevention among older adults in rural South Africa.

Methods: We analyzed data from a population-based sample of 5059 men and women aged 40 years and older from the study Health and Aging in Africa: Longitudinal Studies of INDEPTH Communities (HAALSI), which was carried out in the Agincourt health and sociodemographic surveillance system in the Mpumalanga province of South Africa. We estimated the prevalence of HIV (laboratory-confirmed and self-reported) and key sexual behaviors by age and sex. We compared sexual behavior profiles across HIV status categories with and without age-sex standardization.

Results: HIV prevalence was very high among HAALSI participants (23%, 95% confidence interval [CI]: 21 to 24), with no sex differences. Recent sexual activity was common (56%, 95% CI: 55 to 58) across all HIV status categories. Condom use was low among HIV-negative adults (15%, 95% CI: 14 to 17), higher among HIV-positive adults who were unaware of their HIV status (27%, 95% CI: 22 to 33), and dramatically higher among HIV-positive adults who were aware of their status (75%, 95% CI: 70 to 80). Casual sex and multiple partnerships were reported at moderate levels, with slightly higher estimates among HIV-positive compared to HIV-negative adults. Differences by HIV status remained after age-sex standardization.

Conclusions: Older HIV-positive adults in an HIV hyperendemic community of rural South Africa report sexual behaviors consistent with high HIV transmission risk. Older HIV-negative adults report sexual behaviors consistent with high HIV acquisition risk. Prevention initiatives tailored to the particular prevention needs of older adults are urgently needed to reduce HIV risk in this and similar communities in sub-Saharan Africa.

Abstract  Full-text [free] access 

Editor’s notes: This large population-based survey was designed to collect data on well-being, health status, cognitive functioning, and aspects of ageing among men and women 40 years of age or older (40+) in Mpumalanga, South Africa. The survey documented an unexpectedly high HIV prevalence of 23% in this age group. In the 50+ age group, almost one in five people (20%) was HIV-positive. This compares to an overall South African national estimate for adults 50 and over in 2012 of 7.6%, the Africa Centre KwaZulu-Natal estimate of 9.5%, and the previous Agincourt estimate of 16.5% in 2010-11. One explanation is that HIV prevalence among older South Africans is climbing as more people access life-prolonging antiretroviral treatment. In addition to this, each year people with HIV are ageing into the older age group. This study focused on the 40+ age group because life expectancy in the Agincourt study area had been low and collected sexual behaviour information for the previous two-year period, rather than the usual time period of 12 months. Nonetheless, the data obtained through computer-assisted personal interviews reveal ‘recent’ sexual behaviour that both challenges stereotypes that older people are not sexually active and suggests significant risk of HIV transmission and HIV acquisition. Two-thirds reported more than one lifetime sexual partner and although sexual activity did tend to decrease with age, 52% of men and 6% of women age 80 years and older had been sexually active in the previous two years. Only about half of people found to be HIV-positive knew their status (12%). This group of people living with HIV were far more likely to use condoms. This suggests that an offer of HIV testing in ways that can reach older people would assist in avoiding transmission to partners and in accessing antiretroviral therapy. Only one in seven sexually active HIV-negative people 40+ are using condoms in this setting. This highlights the urgent need for awareness raising to foster new sexual norms to avoid HIV acquisition by practising safer sex. It is time to get our heads out of the sand, recognise the sexuality of older people, and work with them to tailor specific HIV strategies to reduce HIV transmission and acquisition – they too are key to ending AIDS. 

Africa
South Africa
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Person-to-person spread driving XDR-TB epidemic in KwaZulu-Natal

Transmission of extensively drug-resistant tuberculosis in South Africa.

Shah NS, Auld SC, Brust JC, Mathema B, Ismail N, Moodley P, Mlisana K, Allana S, Campbell A, Mthiyane T, Morris N, Mpangase P, van der Meulen H, Omar SV, Brown TS, Narechania A, Shaskina E, Kapwata T, Kreiswirth B, Gandhi NR. N Engl J Med. 2017 Jan 19;376(3):243-253. doi: 10.1056/NEJMoa1604544.

Background: Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions.

Methods: We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants' history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment-length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrug-resistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission.

Results: Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%).

Conclusions: The majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug-resistant tuberculosis requires an increased focus on interrupting transmission.

Abstract   Full-text [free] access

Editor’s notes: This paper provides further evidence to support person-to-person transmission being the main driver of the XDR-TB epidemic in KwaZulu-Natal, the most populous province of South Africa. The study combined classical and molecular epidemiology: detailed characterisation of people’s clinical history and social networks alongside genotypic methods to characterise their TB strains. With the most conservative estimate, almost seven in ten XDR-TB cases resulted from transmission. However, combining the clinical and genotypic information, as many as nine in ten cases may have been attributable to transmission.

So where was transmission happening? This unfortunately was more difficult to answer. Although epidemiological links (mainly at home or at hospitals) could be defined for around one in three cases, many did not share the same TB strain. More detailed understanding of transmission may have been affected by the relatively low coverage of XDR-TB cases by this study. Full information was available for just over one in three laboratory-confirmed XDR-TB cases in the province over the study period. Also, although there was some genetic diversity in the TB strains, there was one dominant strain (LAM4/KZN). This is the strain responsible for the well-characterised clonal outbreak of XDR-TB involving Tugela Ferry.

Most people with XDR-TB in this study were HIV positive. Interestingly, three-quarters of people living with HIV were on ART at the time of their XDR-TB diagnosis, and two-thirds of people had undetectable viral load. This flags up two things. Firstly, it is a reminder that ART alone is unlikely to control the TB (or drug-resistant TB) epidemic in South Africa. Secondly, it raises further questions that could not be definitively answered here as to whether some of these people might have been infected with XDR-TB while accessing HIV treatment and care in the public health system. 

So what do we do with this new information? These findings should encourage us to focus on developing strategies to interrupt drug-resistant TB transmission. We need better evidence of what works in community settings and health care settings. We need better evidence of how to deliver proven programmes. We still do not know whether we might need different activities to interrupt MDR- and XDR-TB transmission, or whether this should just be encompassed within broader strategies to interrupt all TB transmission. South Africa is leading the way in implementing molecular diagnostics to help with earlier detection of drug-resistant TB, and is at the forefront of developing and testing new drug regimens for drug-resistant TB. This provides a solid platform on which to develop public health programmes to stop the spread of drug-resistant TB.

Comorbidity, Epidemiology
Africa
South Africa
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Are the pills going to make you live long Mum? Questions children ask once they learn their mother is living with HIV

Communication about HIV and death: maternal reports of primary school-aged children's questions after maternal HIV disclosure in rural South Africa.

Rochat TJ, Mitchell J, Lubbe AM, Stein A, Tomlinson M, Bland RM. Soc Sci Med. 2017 Jan;172:124-134. doi: 10.1016/j.socscimed.2016.10.031. Epub 2016 Nov 21.

Introduction: Children's understanding of HIV and death in epidemic regions is under-researched. We investigated children's death-related questions post maternal HIV-disclosure. Secondary aims examined characteristics associated with death-related questions and consequences for children's mental health.

Methods: HIV-infected mothers (N = 281) were supported to disclose their HIV status to their children (6-10 years) in an uncontrolled pre-post intervention evaluation. Children's questions post-disclosure were collected by maternal report, 1-2 weeks post-disclosure. 61/281 children asked 88 death-related questions, which were analysed qualitatively. Logistic regression analyses examined characteristics associated with death-related questions. Using the parent-report Child Behaviour Checklist (CBCL), linear regression analysis examined differences in total CBCL problems by group, controlling for baseline.

Results: Children's questions were grouped into three themes: 'threats'; 'implications' and 'clarifications'. Children were most concerned about the threat of death, mother's survival, and prior family deaths. In multivariate analysis variables significantly associated with asking death-related questions included an absence of regular remittance to the mother (AOR 0.25 [CI 0.10, 0.59] p = 0.002), mother reporting the child's initial reaction to disclosure being "frightened" (AOR 6.57 [CI 2.75, 15.70] p≤0.001) and level of disclosure (full/partial) to the child (AOR 2.55 [CI 1.28, 5.06] p = 0.008). Controlling for significant variables and baseline, all children showed improvements on the CBCL post-intervention; with no significant differences on total problems scores post-intervention (β   -0.096 SE1.366  t = -0.07 p = 0.944).

Discussion: The content of questions children asked following disclosure indicate some understanding of HIV and, for almost a third of children, its potential consequence for parental death. Level of maternal disclosure and stability of financial support to the family may facilitate or inhibit discussions about death post-disclosure. Communication about death did not have immediate negative consequences on child behaviour according to maternal report.

Conclusion: In sub-Saharan Africa, given exposure to death at young ages, meeting children's informational needs could increase their resilience.

Abstract  Full-text [free] access 

Editor’s notes: This is an unusual study examining the experience of the disclosure conversation between mother and child about the mother’s HIV positive status in Kwazulu-Natal. The paper examines the death-associated questions that mothers reported children (aged 6-10 years old, HIV exposed but uninfected) asked up to one week after the ‘disclosure event’. The findings indicate that although the treatability and chronic nature of HIV is complex, children’s questions suggest that they are attempting understand the implications of their mother’s HIV positive status for them, their mother’s and their care. Much research has illustrated that disclosure of both the parents or the child’s own HIV positive status is commonly delayed. This delay may exacerbate the challenges a young person has in adapting to this knowledge. We also know that parents, like a large proportion of people living with HIV, are daunted and feel ill equipped to manage disclosure to others, especially children. However little evidence is currently available evaluating the impact of programmes that are designed to support parents to disclose their own HIV status to their children. Therefore, this programme and study is very welcome.

The focus on death-questions is particularly interesting. This provides some illustration of how children are reportedly processing the information that they have been given. Many questions indicate a prior knowledge of HIV, illness and/ or death. It also suggests that children are managing this new knowledge within this broader context. Within this high HIV-prevalence context, a discursive emphasis on the efficacy of HIV treatment to reduce the risk of HIV-associated mortality within the delivery of timely, age-appropriate education information may be critical.  This can reduce fears around maternal death and supporting children to manage and adapt to their situations. A clear direction for further enquiry would be to follow up these families to assess the impact of full/ partial disclosure over time on the children and the mothers.     

Africa
South Africa
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Xpert® for active TB case finding in high prevalence communities

Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicentre randomised controlled trial.

Calligaro GL, Zijenah LS, Peter JG, Theron G, Buser V, McNerney R, Bara W, Bandason T, Govender U, Tomasicchio M, Smith L, Mayosi BM, Dheda K. Lancet Infect Dis. 2017 Jan 4. pii: S1473-3099(16)30384-X. doi: 10.1016/S1473-3099(16)30384-X. [Epub ahead of print]

Background: Inadequate case detection results in high levels of undiagnosed tuberculosis in sub-Saharan Africa. Data for the effect of new diagnostic tools when used for community-based intensified case finding are not available, so we investigated whether the use of sputum Xpert®-MTB/RIF and the Determine™ TB LAM urine test in two African communities could be effective.

Methods: In a pragmatic, randomised, parallel-group trial with individual randomisation stratified by country, we compared sputum Xpert®-MTB/RIF, and if HIV-infected, the Determine™ TB LAM urine test (novel diagnostic group), with laboratory-based sputum smear microscopy (routine diagnostic group) for intensified case finding in communities with high tuberculosis and HIV prevalence in Cape Town, South Africa, and Harare, Zimbabwe. Participants were randomly assigned (1:1) to these groups with computer-generated allocation lists, using culture as the reference standard. In Cape Town, participants were randomised and tested at an Xpert®-equipped mobile van, while in Harare, participants were driven to a local clinic where the same diagnostic tests were done. The primary endpoint was the proportion of culture-positive tuberculosis cases initiating tuberculosis treatment in each study group at 60 days. This trial is registered at ClinicalTrials.gov, number NCT01990274.

Findings: Between Oct 18, 2013, and March 31, 2015, 2261 individuals were screened and 875 (39%) of these met the criteria for diagnostic testing. 439 participants were randomly assigned to the novel group and 436 to the routine group. 74 (9%) of 875 participants had confirmed tuberculosis. If late culture-based treatment initiation was excluded, more patients with culture-positive tuberculosis were initiated on treatment in the novel group at 60 days (36 [86%] of 42 in the novel group vs 18 [56%] of 32 in the routine group). Thus the difference in the proportion initiating treatment between groups was 29% (95% CI 9-50, p=0.0047) and 53% more patients initiated therapy in the novel diagnostic group than in the routine diagnostic group. One culture-positive patient was treated based only on a positive LAM test.

Interpretation: Compared with traditional tools, Xpert®-MTB/RIF for community-based intensified case finding in HIV and tuberculosis-endemic settings increased the proportion of patients initiating treatment. By contrast, urine LAM testing was not found to be useful for intensive case finding in this setting.

Abstract access   

Editor’s notes: Undiagnosed tuberculosis (TB) is the main source of ongoing transmission of Mycobacterium tuberculosis in the community.  Community-based intensified TB case finding strategies in high prevalence settings aim to reduce the prevalence of undiagnosed tuberculosis (TB) and thereby to reduce TB transmission. This is the first randomised trial to date comparing a point of contact diagnostic tool, Xpert® MTB/RIF, with a traditional tool, smear microscopy, for community-based intensive case-finding in sub-Saharan Africa.

The key finding was that a community-based intensified strategy using Xpert® MTB/RIF reduced time-to-treatment and increased the proportion of culture-positive people started on treatment in the first 60 days (when culture-based treatment initiation was not included).  Additional findings included a reduction in the number of people with TB treated empirically and a 50% increase in 60-day detection rate compared with smear microscopy. However, there was no difference by study arm in the proportion of culture-positive people who were retained on TB treatment at six months, and this was suboptimal (69% versus 71% for routine versus novel). The study also demonstrated that it was feasible to undertake community-based screening by minimally trained health-care workers using Xpert® in a mobile van with a generator or on site within a community-based clinic. 

It is interesting to note that there were major differences between study sites. In multivariable analysis, study site was the strongest risk factor for a shorter time-to-treatment initiation among culture-positive cases (Harare versus Cape Town - adjusted hazard ratio 7.18, 95% confidence interval 3.69 – 13.96) with screening method (novel versus routine diagnostics) found to have an adjusted hazard ratio of 2.32 (95% confidence interval 1.35 – 3.97). This finding likely reflects differences in the clinical management of Xpert®-negative and smear-negative people with presumed TB between study sites. In Harare, almost all people with a negative test result (in either arm) were referred for chest radiography, and probably because of this, a much larger proportion of study participants were started on anti-tuberculosis treatment in Harare compared to Cape Town (49% versus 9%). There was also a major difference in retention on treatment at six months among culture-positive people (81% in Harare versus 59% in Cape Town). These results highlight the importance of context, including heterogeneity in patient characteristics and differences in quality of health-care, access and practices between settings, in interpreting study findings associated with TB case-finding strategies.

Whether implementation of community-based intensive case finding using Xpert® in high-prevalence areas actually translates into reduced community TB transmission or improved clinical outcomes remains to be determined. 

Africa
South Africa, Zimbabwe
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