Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The ...aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population.
Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1-12, with adolescents (16-19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159-426). HIVST uptake in months 13-24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%-7.8%) positive participants. Being "forced to test", usually by a main partner, was reported by 2.9% (95% CI 2.6%-3.2%) of 10,017 questionnaire respondents in months 1-12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%-97.0%) and a specificity of 99.9% (95% CI 99.6%-100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover.
Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings.
The aim of this practitioner’s mini keynote was to reflect on the experiences of English for Academic Purposes (EAP) and learning development (LD) practitioners from across UK higher education ...institutions to explore how we can collaborate to benefit students’ educational experiences and outcomes. Despite different pedagogical and professional contexts and identities, both EAP and LD practitioners aspire to develop students’ understanding of, and engagement with, key academic and disciplinary literacies (McCulloch and Horak, 2019). Within many institutions, however, EAP and LD colleagues deliver provision separately – either to different cohorts or through different teaching models (pre- and in-sessional delivery, for example). Although this separation speaks to specific disciplinary identities and points of theoretical and pedagogical difference (see, for example, Wingate, 2012), it can cause duplication of content, confusion for students, and competing demands for institutional funding and support. Given increasing student numbers, widening diversity of student needs and experience, and funding concerns, it is more important than ever to understand how EAP and LD practitioners can collaborate in the best interests of our students.
Prompt questions:
What opportunities for collaboration between EAP and LD colleagues are available at your institution, and what challenges or barriers have you experienced?
How can EAP and LD practitioners effectively collaborate while maintaining their professional identities?
How can effective collaboration between EAP and LD practitioners benefit student education experiences and outcomes?
Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest ...X-ray (DCXR-CAD).
In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio RR: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon.
DCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment.
clinicaltrials.gov NCT03519425.
Trials done in infants with low birthweight in west Africa suggest that BCG vaccination reduces all-cause mortality in the neonatal period, probably because of heterologous protection against ...non-tuberculous infections. This study investigated whether BCG alters all-cause infectious disease morbidity in healthy infants in a different high-mortality setting, and explored whether the changes are mediated via trained innate immunity.
This was an investigator-blind, randomised, controlled trial done at one hospital in Entebbe, Uganda. Infants who were born unwell (ie, those who were not well enough to be discharged directly home from the labour ward because they required medical intervention), with major congenital malformations, to mothers with HIV, into families with known or suspected tuberculosis, or for whom cord blood samples could not be taken, were excluded from the study. Any other infant well enough to be discharged directly from the labour ward was eligible for inclusion, with no limitation on gestational age or birthweight. Participants were recruited at birth and randomly assigned (1:1) to receive standard dose BCG 1331 (BCG-Danish) on the day of birth or at age 6 weeks (computer-generated randomisation, block sizes of 24, stratified by sex). Investigators and clinicians were masked to group assignment; parents were not masked. Participants were clinically followed up to age 10 weeks and contributed blood samples to one of three immunological substudies. The primary clinical outcome was physician-diagnosed non-tuberculous infectious disease incidence. Primary immunological outcomes were histone trimethylation at the promoter region of TNF, IL6, and IL1B; ex-vivo production of TNF, IL-6, IL-1β, IL-10, and IFNγ after heterologous stimulation; and transferrin saturation and hepcidin levels. All outcomes were analysed in the modified intention-to-treat population of all randomly assigned participants except those whose for whom consent was withdrawn. This trial is registered with the International Standard Randomised Controlled Trial Number registry (#59683017).
Between Sept 25, 2014, and July 31, 2015, 560 participants were enrolled and randomly assigned to receive BCG at birth (n=280) or age 6 weeks (n=280). 12 participants assigned to receive BCG at birth and 11 participants assigned to receive BCG at age 6 weeks were withdrawn from the study by their parents shortly after randomisation and were not included in analyses. During the first 6 weeks of life before the infants in the delayed vaccination group received BCG vaccination, physician-diagnosed non-tuberculous infectious disease incidence was lower in infants in the BCG at birth group than in the delayed group (98 presentations in the BCG at birth group vs 129 in the delayed BCG group; hazard ratio HR 0·71 95% CI 0·53–0·95, p=0·023). After BCG in the delayed group (ie, during the age 6–10 weeks follow-up), there was no significant difference in non-tuberculous infectious disease incidence between the groups (88 presentations vs 76 presentations; HR 1·10 0·87–1·40, p=0·62). BCG at birth inhibited the increase in histone trimethylation at the TNF promoter in peripheral blood mononuclear cells occurring in the first 6 weeks of life. H3K4me3 geometric mean fold-increases were 3·1 times lower at the TNF promoter (p=0·018), 2·5 times lower at the IL6 promoter (p=0·20), and 3·1 times lower at the IL1B promoter (p=0·082) and H3K9me3 geometric mean fold-increases were 8·9 times lower at the TNF promoter (p=0·0046), 1·2 times lower at the IL6 promoter (p=0·75), and 4·6 times lower at the IL1B promoter (p=0·068), in BCG-vaccinated (BCG at birth group) versus BCG-naive (delayed BCG group) infants. No clear effect of BCG on ex-vivo production of TNF, IL-6, IL-1β, IL-10, and IFNγ after heterologous stimulation, or transferrin saturation and hepcidin concentration, was detected (geometric mean ratios between 0·68 and 1·68; p≥0·038 for all comparisons).
BCG vaccination protects against non-tuberculous infectious disease during the neonatal period, in addition to having tuberculosis-specific effects. Prioritisation of BCG on the first day of life in high-mortality settings might have significant public-health benefits through reductions in all-cause infectious morbidity and mortality.
Wellcome Trust.
For the Luganda and Swahili translations of the abstract see Supplementary Materials section.
Although HIV testing and counseling (HTC) uptake has increased dramatically in Africa, facility-based services are unlikely to ever meet ongoing need to the full. A major constraint in scaling up ...community and home-based HTC services is the unacceptability of receiving HTC from a provider known personally to prospective clients. We investigated the potential of supervised oral HIV self-testing from this perspective.
Adult members of 60 households and 72 members of community peer groups in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling. Participants were offered self-testing plus confirmatory HTC (parallel testing with two rapid finger-prick blood tests), standard HTC alone, or no testing. 283 (95.6%) of 298 selected adults participated, including 136 (48.0%) men. 175 (61.8%) had previously tested (19 known HIV positive), although only 64 (21.5%) within the last year. HIV prevalence was 18.5%. Among 260 (91.9%) who opted to self-test after brief demonstration and illustrated instructions, accuracy was 99.2% (two false negatives). Although 98.5% rated the test "not hard at all to do," 10.0% made minor procedural errors, and 10.0% required extra help. Most participants indicated willingness to accept self-test kits, but not HTC, from a neighbor (acceptability 94.5% versus 46.8%, p = 0.001).
Oral supervised self-testing was highly acceptable and accurate, although minor errors and need for supervisory support were common. This novel option has potential for high uptake at local community level if it can be supervised and safely linked to counseling and care.
Mass Drug Administration (MDA) is the main strategy for control of soil-transmitted helminth (STH) infections, with single-dose benzimidazole (albendazole or mebendazole) the principal MDA option. In ...Mayuge district, Uganda, an MDA programme has been in place for over fifteen years but hookworm infection remains common and there is concern that the effectiveness of single-dose albendazole as currently used for MDA may be sub-optimal. This study aims to assess the efficacy of dual- versus single-dose albendazole, with and without fatty food co-administration against hookworm, the dominant form of STHs in Mayuge district, Uganda.
This was a 2x2 factorial randomised controlled trial to investigate two interventions simultaneously; 1) dual-dose versus single-dose albendazole, 2) taking albendazole with or without fatty food (200 grams of avocado eaten directly after medication). School children with hookworm infection were randomised in a 1:1:1:1 ratio to the four possible treatment groups. Three weeks after the treatment, stool samples were collected from trial participants to evaluate trial outcomes: cure rate and egg reduction rate (ERR).
A total of 225 participants were enrolled, and 222 (98.7%) seen at 3 weeks. The cure rate in the dual-dose group was 96.4% (95% CI: 90.9-99%), higher than 83.9% (95% CI: 75.7-90.2%) in the single-dose group (OR: 5.07, 95% CI:1.61-15.96, p = 0.002). The ERR was 97.6% and 94.5% in the dual-dose group and single-dose drug group, respectively (ERR difference 3.1%, 95% CI: -3.89-16.39%, p = 0.553). The cure rates among participants taking albendazole with and without avocado were 90.1% and 89.1%, respectively, with no statistical difference between the two groups (OR: 1.24, 95% CI: 0.51-3.03, p = 0.622). The ERR was 97.0% and 94.2% in the group receiving albendazole with and without avocado, respectively, and the difference in ERR between the two groups was 2.8% (95% CI -8.63-14.3%, p = 0.629).
In Ugandan school children, dual-dose albendazole improves the cure rate of hookworm compared to single-dose albendazole. However, there was no significant improvement in cure rate or egg reduction rate of hookworm with fatty-food co-administration. Dual-dose albendazole is a feasible alternative for improving drug effectiveness against hookworm infection and minimising drug resistance.
PACTR202202738940158.
Household contacts of patients with active pulmonary tuberculosis (TB) often have latent TB infection, and are at risk of progression to disease. We set out to investigate whether index TB case HIV ...status was linked to a higher probability of latent TB infection among household contacts.
Data were collected prospectively from participants in the intervention arm of a household cluster-randomised trial in two South Africa provinces (Mangaung, Free State, and Capricorn, Limpopo). In intervention group households, TB contacts underwent HIV testing and tuberculin skin testing (TST). TST induration was estimated at two cut-offs (≥5mm, ≥10mm). Multilevel Bayesian regression models estimated posterior distributions of the percentage of household contacts with TST induration ≥5mm and ≥10mm by age group, and compared the odds of latent TB infection by key risk factors including HIV status index case age and study province.
A total of 2,985 household contacts of 924 index cases were assessed, with most 2,725 (91.3%) undergoing TST. HIV prevalence in household contacts was 14% and 10% in Mangaung and Capricorn respectively. Overall, 16.8% (458/2,725) had TST induration of ≥5mm and 13.1% (359/2,725) ≥10mm. In Mangaung, children aged 0-4 years had a high TST positivity prevalence compared to their peers in Capricorn (22.0% vs. 7.6%, and 20.5% vs. 2.3%, using TST thresholds of ≥5mm and ≥10mm respectively). Compared to contacts from Capricorn, household contacts living in Mangaung were more likely to have TST induration ≥5mm (odds ratio OR: 3.08, 95% credibility interval CI: 2.13-4.58) and ≥10mm (OR: 4.52, 95% CI: 3.03-6.97). There was a 90% and 92% posterior probability that the odds of TST induration ≥5mm (OR: 0.79, 95% CI: 0.56-1.14) and ≥10mm (OR: 0.77, 95% CI: 0.53-1.10) respectively were lower in household contacts of HIV-positive compared to HIV-negative index cases.
High TST induration positivity, especially among young children and people living in Mangaung indicates considerable TB transmission despite high antiretroviral therapy coverage. Household contact of HIV-positive index TB cases were less likely to have evidence of latent TB infection than contacts of HIV-negative index cases.
Birds face many human-induced environmental challenges that we associate with population declines. Because of this, we need more ways to monitor populations before they become endangered. Several ...authors have proposed that fluctuating asymmetry, or nondirectional deviation from bilateral symmetry, could be used as an indicator of population declines. Fluctuating asymmetry is linked to developmental instability and stress associated with environmental challenges such as habitat loss in populations of birds and other animals. Two key premises of the argument for linking fluctuating asymmetry and population declines are that (1) fluctuating asymmetry changes over time, and (2) change over time results in overall population- or species-level differences in fluctuating asymmetry. I evaluated these premises by measuring tarsus and hallux lengths of museum specimens primarily from 1875–1950 in a pair of closely related species with different population statuses—the White-breasted Nuthatch (Sitta carolinensis) and the Brown-headed Nuthatch (S. pusilla). Since Brown-headed Nuthatch populations are decreasing whereas White-breasted Nuthatch populations are increasing, I predicted that Brown-headed Nuthatches would have increasing fluctuating asymmetry over time whereas White-breasted Nuthatches would have no change or decreasing fluctuating asymmetry over time, and this would result in Brown-headed Nuthatches having more overall fluctuating asymmetry in both morphological traits than White-breasted Nuthatches. The percent asymmetry of tarsi and halluces for Brown-headed Nuthatches were at least 1.5× higher than the corresponding values for White-breasted Nuthatches, which supported the second premise. However, since I also found that there was a great deal of interindividual variation and no change in fluctuating asymmetry over time in either species, it is still unclear whether fluctuating asymmetry could be used to help monitor populations for evidence of decline before they reach endangered status. Future studies should more broadly and deeply explore the associations between avian population declines and fluctuating asymmetry.
Las aves enfrentan muchos desafíos ambientales inducidos por el hombre que asociamos con la disminución de la población, incluidas la pérdida de hábitat y el cambio climático. Debido a esto, necesitamos más formas de monitorear las poblaciones antes de que se pongan en peligro. Varios han propuesto que la asimetría fluctuante, o la desviación no-direccional de la simetría bilateral, podría usarse en aplicaciones de conservación como un indicador de la disminución de la población, debido a los vínculos entre la asimetría fluctuante, la inestabilidad del desarrollo y el estrés asociado con desafíos ambientales como la pérdida de hábitat en las poblaciones animales, incluidas muchas especies de aves. Dos premisas clave del argumento para vincular la asimetría fluctuante y la disminución de la población son que 1) la asimetría fluctuante cambia con el tiempo y 2) el cambio a través del tiempo da como resultado diferencias generales a nivel de población o especie en asimetría fluctuante. Evalué estas premisas midiendo las longitudes de tarso y la garra trasera de especímenes de museo desde 1811–2001 en un par de especies estrechamente relacionadas con diferentes estatus poblacionales: el trepador pechiblanco (Sitta carolinensis) y el trepador cabeza marrón (S. pusilla). Dado que las poblaciones de trepador de cabeza marrón están disminuyendo mientras que las poblaciones de trepador de pecho blanco están aumentando, predije que el trepador de cabeza marrón tendría una asimetría fluctuante cada vez mayor con el tiempo, mientras que el trepador de pecho blanco no tendría ningún cambio o una asimetría fluctuante decreciente con el tiempo, y esto resultaría en que los trepadores de cabeza marrón tuviesen mayor asimetría fluctuante general en ambos rasgos morfológicos que los trepadores de pecho blanco. El porcentaje de asimetría de tarsos y garras traseras para el trepador de cabeza marrón fue al menos una vez y media mayor que los valores correspondientes para el trepador de pecho blanco, que apoyaba la segunda premisa. Sin embargo, dado que también descubrí que había una gran cantidad de variación interindividual y ningún cambio en la AF a lo largo del tiempo en ninguna de las especies, áun no está claro si la asimetría fluctuante podría usarse para ayudar a monitorear las poblaciones en busca de evidencia de disminución antes de que alcancen el estado de En Peligro. Los estudios futuros deberían explorar de manera más amplia y profunda las asociaciones entre la disminución de la población de aves y la asimetría fluctuante.
Given the potentially causal association of female genital schistosomiasis (FGS) with HIV-1 infection, improved diagnostics are urgently needed to scale-up FGS surveillance. The BILHIV (bilharzia and ...HIV) study assessed the performance of home-based self-collection methods (cervical and vaginal swabs) compared to cervicovaginal lavage (CVL) for the detection of Schistosoma DNA by real-time polymerase chain reaction (PCR).
Between January and August 2018, a consecutive series of female participants from the Population-Cohort of the previous HIV prevention trial HPTN 071 (PopART), resident in Livingstone, Zambia were invited to take part in BILHIV if they were 18-31 years old, non-pregnant and sexually active. Genital self-collected swabs and a urine specimen were obtained and a questionnaire completed at home visits. CVL was obtained at clinic follow-up.
603 women self-collected genital swabs. Of these, 527 women had CVL performed by a mid-wife during clinic follow-up. Schistosoma DNA was more frequently detected in genital self-collected specimens (24/603, 4.0%) compared to CVL (14/527, 2.7%). Overall, 5.0% (30/603) women had female genital schistosomiasis, defined as a positive PCR by any genital sampling method (cervical swab PCR, vaginal swab PCR, or CVL PCR) and 95% (573/603) did not have a positive genital PCR. The sensitivity of any positive genital self-collected swab against CVL was 57.1% (95% CI 28.9-82.3%), specificity 97.3% (95.5-98.5%). In a subset of participants with active schistosome infection, determined by detectable urine Circulating Anodic Antigen (CAA) (15.1%, 91/601), positive PCR (4.3%, 26/601), or positive microscopy (5.5%, 33/603), the sensitivity of any positive self-collected specimen against CVL was 88.9% (51.8-99.7%).
Genital self-sampling increased the overall number of PCR-based FGS diagnoses in a field setting, compared with CVL. Home-based sampling may represent a scalable alternative method for FGS community-based diagnosis in endemic resource limited settings.
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