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1.
PLoS One ; 19(5): e0291215, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38787869

RESUMEN

Tuberculosis (TB) transmission and prevalence are dynamic over time, and heterogeneous within populations. Public health programmes therefore require up-to-date, accurate epidemiological data to appropriately allocate resources, target interventions, and track progress towards End TB goals. Current methods of TB surveillance often rely on case notifications, which are biased by access to healthcare, and TB disease prevalence surveys, which are highly resource-intensive, requiring many tens of thousands of people to be tested to identify high-risk groups or capture trends. Surveys of "latent TB infection", or immunoreactivity to Mycobacterium tuberculosis (Mtb), using tests such as interferon-gamma release assays (IGRAs) could provide a way to identify TB transmission hotspots, supplementing information from disease notifications, and with greater spatial and temporal resolution than is possible to achieve in disease prevalence surveys. This cross-sectional survey will investigate the prevalence of Mtb immunoreactivity amongst young children, adolescents and adults in Blantyre, Malawi, a high HIV-prevalence city in southern Africa. Through this study we will estimate the annual risk of TB infection (ARTI) in Blantyre and explore individual- and area-level risk factors for infection, as well as investigating geospatial heterogeneity of Mtb infection (and its determinants), and comparing these to the distribution of TB disease case-notifications. We will also evaluate novel diagnostics for Mtb infection (QIAreach QFT) and sampling methodologies (convenience sampling in healthcare settings and community sampling based on satellite imagery), which may increase the feasibility of measuring Mtb infection at large scale. The overall aim is to provide high-resolution epidemiological data and provide new insights into methodologies which may be used by TB programmes globally.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Malaui/epidemiología , Humanos , Estudios Transversales , Mycobacterium tuberculosis/inmunología , Adulto , Adolescente , Tuberculosis/epidemiología , Tuberculosis/diagnóstico , Prevalencia , Niño , Femenino , Masculino , Ensayos de Liberación de Interferón gamma/métodos , Adulto Joven , Factores de Riesgo
2.
Clin Infect Dis ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748183

RESUMEN

BACKGROUND: People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. METHODS: We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. FINDINGS: Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50). INTERPRETATION: Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.

3.
BMC Infect Dis ; 22(Suppl 1): 979, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566003

RESUMEN

BACKGROUND: HIV self-testing (HIVST) can use either oral-fluid or blood-based tests. Studies have shown strong preferences for self-testing compared to facility-based services. Despite availability of low-cost blood-based HIVST options, to date, HIVST implementation in sub-Saharan Africa has largely been oral-fluid-based. We investigated whether users preferred blood-based (i.e. using blood sample derived from a finger prick) or oral fluid-based HIVST in rural and urban Malawi. METHODS: At clinics providing HIV testing services (n = 2 urban; n = 2 rural), participants completed a semi-structured questionnaire capturing sociodemographic data before choosing to test using oral-fluid-based HVST, blood-based HIVST or provider-delivered testing. They also completed a self-administered questionnaire afterwards, followed by a confirmatory test using the national algorithm then appropriate referral. We used simple and multivariable logistic regression to identify factors associated with preference for oral-fluid or blood-based HIVST. RESULTS: July to October 2018, N = 691 participants enrolled in this study. Given the choice, 98.4% (680/691) selected HIVST over provider-delivered testing. Of 680 opting for HIVST, 416 (61.2%) chose oral-fluid-based HIVST, 264 (38.8%) chose blood-based HIVST and 99.1% (674/680) reported their results appropriately. Self-testers who opted for blood-based HIVST were more likely to be male (50.3% men vs. 29.6% women, p < 0.001), attending an urban facility (43% urban vs. 34.6% rural, p = 0.025) and regular salary-earners (49.5% regular vs. 36.8% non-regular, p = 0.012). After adjustment, only sex was found to be associated with choice of self-test (adjusted OR 0.43 (95%CI: 0.3-0.61); p-value < 0.001). Among 264 reporting blood-based HIVST results, 11 (4.2%) were HIV-positive. Blood-based HIVST had sensitivity of 100% (95% CI: 71.5-100%) and specificity of 99.6% (95% CI: 97.6-100%), with 20 (7.6%) invalid results. Among 416 reporting oral-fluid-based HIVST results 18 (4.3%) were HIV-positive. Oral-fluid-based HIVST had sensitivity of 88.9% (95% CI: 65.3-98.6%) and specificity of 98.7% (95% CI: 97.1-99.6%), with no invalid results. CONCLUSIONS: Offering both blood-based and oral-fluid-based HIVST resulted in high uptake when compared directly with provider-delivered testing. Both types of self-testing achieved high accuracy among users provided with a pre-test demonstration beforehand. Policymakers and donors need to adequately plan and budget for the sensitisation and support needed to optimise the introduction of new quality-assured blood-based HIVST products.


Asunto(s)
Infecciones por VIH , Autoevaluación , Humanos , Masculino , Femenino , VIH , Estudios Transversales , Malaui , Autocuidado , Infecciones por VIH/diagnóstico , Prueba de VIH , Encuestas y Cuestionarios , Tamizaje Masivo/métodos
4.
BMC Infect Dis ; 22(Suppl 1): 977, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448832

RESUMEN

BACKGROUND: Although Zambia has integrated HIV-self-testing (HIVST) into its Human Immunodeficiency Virus (HIV) regulatory frameworks, few best practices to optimize the use of HIV self-testing to increase testing coverage have been documented. We conducted a prospective case study to understand contextual factors guiding implementation of four HIVST distribution models to inform scale-up in Zambia. METHODS: We used the qualitative case study method to explore user and provider experiences with four HIVST distribution models (two secondary distribution models in Antenatal Care (ANC) and Antiretroviral Therapy (ART) clinics, community-led, and workplace) to understand factors influencing HIVST distribution. Participants were purposefully selected based on their participation in HIVST and on their ability to provide rich contextual experience of the distribution models. Data were collected using observations (n = 31), group discussions (n = 10), and in-depth interviews (n = 77). Data were analyzed using the thematic approach and aligned to the four Consolidated Framework for Implementation Research (CFIR) domains. RESULTS: Implementation of the four distribution models was influenced by an interplay of outer and inner setting factors. Inadequate compensation and incentives for distributors may have contributed to distributor attrition in the community-led and workplace HIVST models. Stockouts, experienced at the start of implementation in the secondary-distribution and community-led distribution models often disrupted distribution. The existence of policy and practices aided integration of HIVST in the workplace. External factors complimented internal factors for successful implementation. For instance, despite distributor attrition leading to excessive workload, distributors often multi-tasked to keep up with demand for kits, even though distribution points were geographically widespread in the workplace, and to a less extent in the community-led models. Use of existing communication platforms such as lunchtime and safety meetings to promote and distribute kits, peers to support distributors, reduction in trips by distributors to replenish stocks, increase in monetary incentives and reorganisation of stakeholder roles proved to be good adaptations. CONCLUSION: HIVST distribution was influenced by a combination of contextual factors in variable ways. Understanding how the factors interacted in real world settings informed adaptations to implementation devised to minimize disruptions to distribution.


Asunto(s)
Infecciones por VIH , VIH , Embarazo , Femenino , Humanos , Zambia , Autoevaluación , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Prueba de VIH
5.
BMC Infect Dis ; 22(Suppl 1): 978, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38468208

RESUMEN

BACKGROUND: In Malawi, female sex workers (FSW) have high HIV incidence and regular testing is suggested. HIV self-testing (HIVST) is a safe and acceptable alternative to standard testing services. This study assessed; whether social harms were more likely to be reported after HIVST distribution to FSW by peer distributors than after facility-based HIV testing and whether FSW regretted HIVST use or experienced associated relationship problems. METHODS: Peer HIVST distributors, who were FSW, were recruited in Blantyre district, Malawi between February and July 2017. Among HIVST recipients a prospective cohort was recruited. Interviews were conducted at baseline and at end-line, 3 months later. Participants completed daily sexual activity diaries. End-line data were analysed using logistic regression to assess whether regret or relationship problems were associated with HIVST use. Sexual activity data were analysed using Generalised Estimating Equations to assess whether HIVST use was temporally associated with an increase in social harms. RESULTS: Of 265 FSW recruited and offered HIVST, 131 completed both interviews. Of these, 31/131(23.7%) reported initial regret after HIVST use, this reduced to 23/131(17.6%) at the 3-month follow-up. Relationship problems were reported by 12/131(9.2%). Regret about HIVST use was less commonly reported in those aged 26-35 years compared to those aged 16-25 years (OR immediate regret-0.40 95% CI 0.16-1.01) (OR current regret-0.22 95% CI 0.07 - 0.71) and was not associated with the HIVST result. There was limited evidence that reports of verbal abuse perpetrated by clients in the week following HIVST use were greater than when there was no testing in the preceding week. There was no evidence for increases in any other social harms. There was some evidence of coercion to test, most commonly initiated by the peer distributor. CONCLUSIONS: Little evidence was found that the peer distribution model was associated with increased levels of social harms, however programmes aimed at reaching FSW need to carefully consider possible unintended consequences of their service delivery approaches, including the potential for peer distributors to coerce individuals to test or disclose their test results and alternative distribution models may need to be considered.


Asunto(s)
Infecciones por VIH , Trabajadores Sexuales , Humanos , Femenino , Estudios de Cohortes , Estudios Prospectivos , Autoevaluación , Malaui/epidemiología , Tamizaje Masivo/métodos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Prueba de VIH
6.
Sci Immunol ; 9(93): eadh5318, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489350

RESUMEN

Recombination activating gene (RAG) expression increases as thymocytes transition from the CD4-CD8- double-negative (DN) to the CD4+CD8+ double-positive (DP) stage, but the physiological importance and mechanism of transcriptional up-regulation are unknown. Here, we show that a DP-specific component of the recombination activating genes antisilencer (DPASE) provokes elevated RAG expression in DP thymocytes. Mouse DP thymocytes lacking the DPASE display RAG expression equivalent to that in DN thymocytes, but this supports only a partial Tcra repertoire due to inefficient secondary Vα-Jα rearrangement. These data indicate that RAG up-regulation is required for a replete Tcra repertoire and that RAG expression is fine-tuned during lymphocyte development to meet the requirements of distinct antigen receptor loci. We further show that transcription factor RORγt directs RAG up-regulation in DP thymocytes by binding to the DPASE and that RORγt influences the Tcra repertoire by binding to the Tcra enhancer. These data, together with prior work showing RORγt to control Tcra rearrangement by regulating DP thymocyte proliferation and survival, reveal RORγt to orchestrate multiple pathways that support formation of the Tcra repertoire.


Asunto(s)
Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Timocitos , Ratones , Animales , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Receptores de Antígenos de Linfocitos T alfa-beta , Factores de Transcripción/genética , Expresión Génica
7.
Lancet Infect Dis ; 24(2): 140-149, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37918414

RESUMEN

BACKGROUND: Childhood tuberculosis remains a major cause of morbidity and mortality in part due to missed diagnosis. Diagnostic methods with enhanced sensitivity using easy-to-obtain specimens are needed. We aimed to assess the diagnostic accuracy of the Cepheid Mycobacterium tuberculosis Host Response prototype cartridge (MTB-HR), a candidate test measuring a three-gene transcriptomic signature from fingerstick blood, in children with presumptive tuberculosis disease. METHODS: RaPaed-TB was a prospective diagnostic accuracy study conducted at four sites in African countries (Malawi, Mozambique, South Africa, and Tanzania) and one site in India. Children younger than 15 years with presumptive pulmonary or extrapulmonary tuberculosis were enrolled between Jan 21, 2019, and June 30, 2021. MTB-HR was performed at baseline and at 1 month in all children and was repeated at 3 months and 6 months in children on tuberculosis treatment. Accuracy was compared with tuberculosis status based on standardised microbiological, radiological, and clinical data. FINDINGS: 5313 potentially eligible children were screened, of whom 975 were eligible. 784 children had MTB-HR test results, of whom 639 had a diagnostic classification and were included in the analysis. MTB-HR differentiated children with culture-confirmed tuberculosis from those with unlikely tuberculosis with a sensitivity of 59·8% (95% CI 50·8-68·4). Using any microbiological confirmation (culture, Xpert MTB/RIF Ultra, or both), sensitivity was 41·6% (34·7-48·7), and using a composite clinical reference standard, sensitivity was 29·6% (25·4-34·2). Specificity for all three reference standards was 90·3% (95% CI 85·5-94·0). Performance was similar in different age groups and by malnutrition status. Among children living with HIV, accuracy against the strict reference standard tended to be lower (sensitivity 50·0%, 15·7-84·3) compared with those without HIV (61·0%, 51·6-69·9), although the difference did not reach statistical significance. Combining baseline MTB-HR result with one Ultra result identified 71·2% of children with microbiologically confirmed tuberculosis. INTERPRETATION: MTB-HR showed promising diagnostic accuracy for culture-confirmed tuberculosis in this large, geographically diverse, paediatric cohort and hard-to-diagnose subgroups. FUNDING: European and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Swedish International Development Cooperation Agency, Bundesministerium für Bildung und Forschung; German Center for Infection Research (DZIF).


Asunto(s)
Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Niño , Humanos , Mycobacterium tuberculosis/genética , Estudios Prospectivos , Países en Desarrollo , Tuberculosis Pulmonar/tratamiento farmacológico , Sensibilidad y Especificidad , Tuberculosis/diagnóstico , Sudáfrica , Esputo/microbiología
8.
PLOS Glob Public Health ; 3(12): e0002683, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38051717

RESUMEN

Active case-finding (ACF) for tuberculosis can help find the "missing millions" with undiagnosed tuberculosis. In a cluster-randomised trial, we investigated impact of ACF on case-notifications in Blantyre, Malawi, where ACF has been intensively implemented following 2014 estimates of ~1,000 per 100,000 adults with undiagnosed TB. Following a pre-intervention prevalence survey (May 2019 to March 2020), constrained randomisation allocated neighbourhoods to either door-to-door ACF (sputum microscopy for reported cough >2 weeks) or standard-of-care (SOC). Implementation was interrupted by COVID-19. Cluster-level bacteriologically-confirmed case-notification rate (CNR) ratio within 91 days of ACF was our redefined primary outcome; comparison between arms used Poisson regression with random effects. Secondary outcomes were 91-day CNR ratios comparing all tuberculosis registrations and all non-ACF registrations. Interrupted time series (ITS) analysis of CNRs in the SOC arm examined prevalence survey impact. (ISRCTN11400592). 72 clusters served by 10 study-supported tuberculosis registration centres were randomised to ACF (261,244 adults, 58,944 person-years follow-up) or SOC (256,713 adults, 52,805 person-years). Of 1,192 ACF participants, 13 (1.09%) were smear-positive. Within 91 days, 113 (42 bacteriologically-confirmed) and 108 (33 bacteriologically-confirmed) tuberculosis patients were identified as ACF or SOC cluster residents, respectively. There was no difference by arm, with adjusted 91-day CNR ratios 1.12 (95% CI: 0.61-2.07) for bacteriologically-confirmed tuberculosis; 0.93 (95% CI: 0.68-1.28) for all tuberculosis registrations; and 0.86 (95%CI: 0.63-1.16) for non-ACF (routinely) diagnosed. Of 7,905 ACF and 7,992 SOC pre-intervention survey participants, 12 (0.15%) and 17 (0.21%), respectively, had culture/Xpert-confirmed tuberculosis. ITS analysis showed no survey impact on SOC CNRs. Despite residual undiagnosed tuberculosis of 150 per 100,000 population, there was no increase in tuberculosis notifications from this previously successful approach targeting symptomatic disease, likely due to previous TB ACF and rapid declines in TB burden. In such settings, future ACF should focus on targeted outreach and demand creation, alongside optimised facility-based screening. Trial Registration: ISRCTN11400592.

9.
PLOS Glob Public Health ; 3(10): e0001911, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37862284

RESUMEN

Recent evidence shows rapidly changing tuberculosis (TB) epidemiology in Southern and Eastern Africa, with need for subdistrict prevalence estimates to guide targeted interventions. We conducted a pulmonary TB prevalence survey to estimate current TB burden in Blantyre city, Malawi. From May 2019 to March 2020, 115 households in middle/high-density residential Blantyre, were randomly-selected from each of 72 clusters. Consenting eligible participants (household residents ≥ 18 years) were interviewed, including for cough (any duration), and offered HIV testing and chest X-ray; participants with cough and/or abnormal X-ray provided two sputum samples for microscopy, Xpert MTB/Rif and mycobacterial culture. TB disease prevalence and risk factors for prevalent TB were calculated using complete-case analysis, multiple imputation, and inverse probability weighting. Of 20,899 eligible adults, 15,897 (76%) were interviewed, 13,490/15,897 (85%) had X-ray, and 1,120/1,394 (80%) sputum-eligible participants produced at least one specimen, giving 15,318 complete cases (5,895, 38% men). 29/15,318 had bacteriologically-confirmed TB (189 per 100,000 complete-case (cc) / 150 per 100,000 with inverse weighting (iw)). Men had higher burden (cc: 305 [95% CI:144-645] per 100,000) than women (cc: 117 [95% CI:65-211] per 100,000): cc adjusted odds ratio (aOR) 2.70 (1.26-5.78). Other significant risk factors for prevalent TB on complete-case analysis were working age (25-49 years) and previous TB treatment, but not HIV status. Multivariable analysis of imputed data was limited by small numbers, but previous TB and age group 25-49 years remained significantly associated with higher TB prevalence. Pulmonary TB prevalence for Blantyre was considerably lower than the 1,014 per 100,000 for urban Malawi in the 2013-14 national survey, at 150-189 per 100,000 adults, but some groups, notably men, remain disproportionately affected. TB case-finding is still needed for TB elimination in Blantyre, and similar urban centres, but should focus on reaching the highest risk groups, such as older men.

10.
PLoS One ; 18(7): e0289291, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37506068

RESUMEN

BACKGROUND: COVID-19 testing is critical for identifying cases to prevent transmission. COVID-19 self-testing has the potential to increase diagnostic testing capacity and to expand access to hard-to-reach areas in low-and-middle-income countries. We investigated the feasibility and acceptability of COVID-19 self-sampling and self-testing using SARS-CoV-2 Antigen-Rapid Diagnostic Tests (Ag-RDTs). METHODS: From July 2021 to February 2022, we conducted a mixed-methods cross-sectional study examining self-sampling and self-testing using Standard Q and Panbio COVID-19 Ag Rapid Test Device in Urban and rural Blantyre, Malawi. Health care workers and adults (18y+) in the general population were non-randomly sampled. RESULTS: Overall, 1,330 participants were enrolled of whom 674 (56.0%) were female and 656 (54.0%) were male with 664 for self-sampling and 666 for self-testing. Mean age was 30.7y (standard deviation [SD] 9.6). Self-sampling usability threshold for Standard Q was 273/333 (82.0%: 95% CI 77.4% to 86.0%) and 261/331 (78.8%: 95% CI 74.1% to 83.1%) for Panbio. Self-testing threshold was 276/335 (82.4%: 95% CI 77.9% to 86.3%) and 300/332 (90.4%: 95% CI 86.7% to 93.3%) for Standard Q and Panbio, respectively. Agreement between self-sample results and professional test results was 325/325 (100%) and 322/322 (100%) for Standard Q and Panbio, respectively. For self-testing, agreement was 332/333 (99.7%: 95% CI 98.3 to 100%) for Standard Q and 330/330 (100%: 95% CI 99.8 to 100%) for Panbio. Odds of achieving self-sampling threshold increased if the participant was recruited from an urban site (odds ratio [OR] 2.15 95% CI 1.44 to 3.23, P < .01. Compared to participants with primary school education those with secondary and tertiary achieved higher self-testing threshold OR 1.88 (95% CI 1.17 to 3.01), P = .01 and 4.05 (95% CI 1.20 to13.63), P = .02, respectively. CONCLUSIONS: One of the first studies to demonstrate high feasibility and acceptability of self-testing using SARS-CoV-2 Ag-RDTs among general and health-care worker populations in low- and middle-income countries potentially supporting large scale-up. Further research is warranted to provide optimal delivery strategies of self-testing.


Asunto(s)
Prueba de COVID-19 , COVID-19 , Adulto , Humanos , Femenino , Masculino , Malaui/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , Estudios Transversales , Estudios de Factibilidad , Autoevaluación , SARS-CoV-2 , Sensibilidad y Especificidad
11.
BMC Infect Dis ; 22(Suppl 1): 971, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37264343

RESUMEN

BACKGROUND: Partner-delivered HIV self-testing kits has previously been highlighted as a safe, acceptable and effective approach to reach men. However, less is known about its real-world implementation in reaching partners of people living with HIV. We evaluated programmatic implementation of partner-delivered self-testing through antenatal care (ANC) attendees and people newly diagnosed with HIV by assessing use, positivity, linkage and cost per kit distributed. METHODS: Between April 2018 and December 2019, antenatal care (ANC) clinic attendees and people or those newly diagnosed with HIV clients across twelve clinics in three cities in South Africa were given HIVST kits (OraQuick Rapid HIV-1/2 Antibody Test, OraSure Technologies) to distribute to their sexual partners. A follow-up telephonic survey was administered to all prior consenting clients who were successfully reached by telephone to assess primary outcomes. Incremental economic costs of the implementation were estimated from the provider's perspective. RESULTS: Fourteen thousand four hundred seventy-three HIVST kits were distributed - 10,319 (71%) to ANC clients for their male partner and 29% to people newly diagnosed with HIV for their partners. Of the 4,235 ANC clients successfully followed-up, 82.1% (3,475) reportedly offered HIVST kits to their male partner with 98.1% (3,409) accepting and 97.6% (3,328) using the kit. Among ANC partners self-testing, 159 (4.8%) reported reactive HIVST results, of which 127 (79.9%) received further testing; 116 (91.3%) were diagnosed with HIV and 114 (98.3%) initiated antiretroviral therapy (ART). Of the 1,649 people newly diagnosed with HIV successfully followed-up; 1,312 (79.6%) reportedly offered HIVST kits to their partners with 95.8% (1,257) of the partners accepting and 95.9% (1,206) reported that their partners used the kit. Among these index partners, 297 (24.6%) reported reactive HIVST results of which 261 (87.9%) received further testing; 260 (99.6%) were diagnosed with HIV and 258 (99.2%) initiated ART. The average cost per HIVST distributed in the three cities was US$7.90, US$11.98, and US$14.81, respectively. CONCLUSIONS: Partner-delivered HIVST in real world implementation was able to affordably reach many male partners of ANC attendees and index partners of people newly diagnosed with HIV in South Africa. Given recent COVID-19 related restrictions, partner-delivered HIVST provides an important strategy to maintain essential testing services.


Asunto(s)
COVID-19 , Infecciones por VIH , Humanos , Masculino , Femenino , Embarazo , Atención Prenatal , Autoevaluación , Sudáfrica , Tamizaje Masivo/métodos , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico
12.
PLoS Negl Trop Dis ; 17(5): e0010654, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37141380

RESUMEN

BACKGROUND: Fishing exposes fishermen to schistosomiasis-infested fresh water and concurrently through precarious livelihoods to risky sexual behaviour, rendering these two infections occupational hazards for fishermen. This study aimed to characterize the knowledge of the two conditions to obtain necessary data for a subsequent cluster randomized trial designed to investigate demand creation strategies for joint HIV-schistosomiasis service provision in fishing villages on the shores of southern Lake Malawi. METHODS: Enumeration of all resident fishermen in 45 clusters (fishing communities) was carried out between November 2019 and February 2020. In a baseline survey, fishermen reported their knowledge, attitudes and practices in the uptake of HIV and schistosomiasis services. Knowledge of HIV status and previous receipt of praziquantel were modelled using random effects binomial regression, accounting for clustering. Prevalence of willingness to attend a beach clinic was computed. RESULTS: A total of 6,297 fishermen were surveyed from the 45 clusters with harmonic mean number of fishermen per cluster of 112 (95% CI: 97; 134). The mean age was 31.7y (SD: 11.9) and nearly 40% (2,474/6,297) could not read or write. Overall, 1,334/6,293 (21.2%) had never tested for HIV, with 64.4% (3,191/4,956) having tested in the last 12 months, and 5.9% (373/6290) taking antiretroviral therapy (ART). In adjusted analyses, being able to read and write (adjusted risk ratio [aRR: 1.91, 95% CI: 1.59-2.29, p<0.001); previous use of praziquantel (aRR: 2.00,95% CI: 1.73-2.30, p<0.001); knowing a relative or friend who died of HIV (aRR: 1.54,95% CI: 1.33-1.79, p<0.001); and being on ART (aRR: 12.93, 95% CI: 6.25-32.93, p<0.001) were associated with increased likelihood of ever testing for HIV. Only 40% (1,733/4,465) had received praziquantel in the last 12 months. Every additional year of age was associated with 1% decreased likelihood of having taken praziquantel in the last 12 months (aRR: 0.99, 95% CI: 0.98-0.99, p<0.001). However, recent HIV testing increased the likelihood of taking praziquantel by over 2-fold (aRR 2.24, 95% CI: 1.93-2.62, p<0.001). Willingness to attend a mobile beach clinic offering integrated HIV and schistosomiasis services was extremely high at 99.0% (6,224/6,284). CONCLUSION: In a setting with an underlying high prevalence of both HIV and schistosomiasis, we found low knowledge of HIV status and low utilization of free schistosomiasis treatment. Among fishermen who accessed HIV services, there was a very high likelihood of taking praziquantel suggesting that integrated service delivery may lead to good coverage. TRIAL REGISTRATION: This trial is registered in the ISRCTN registry: ISRCTN14354324; date of registration: 05 October 2020.


Asunto(s)
Infecciones por VIH , Esquistosomiasis , Humanos , Praziquantel/uso terapéutico , Malaui/epidemiología , Esquistosomiasis/diagnóstico , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Prueba de VIH , Encuestas y Cuestionarios
13.
Clin Infect Dis ; 77(1): 94-100, 2023 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-37099318

RESUMEN

BACKGROUND: Tuberculosis case-finding interventions are critical to meeting World Health Organization End TB strategy goals. We investigated the impact of community-wide tuberculosis active case finding (ACF) alongside scale-up of human immunodeficiency virus (HIV) testing and care on trends in adult tuberculosis case notification rates (CNRs) in Blantyre, Malawi. METHODS: Five rounds of ACF for tuberculosis (1-2 weeks of leafleting, door-to-door enquiry for cough and sputum microscopy) were delivered to neighborhoods ("ACF areas") in North-West Blantyre between April 2011 and August 2014. Many of these neighborhoods also had concurrent HIV testing interventions. The remaining neighborhoods in Blantyre City ("non-ACF areas") provided a non-randomized comparator. We analyzed TB CNRs from January 2009 until December 2018. We used interrupted time series analysis to compare tuberculosis CNRs before ACF and after ACF, and between ACF and non-ACF areas. RESULTS: Tuberculosis CNRs increased in Blantyre concurrently with start of ACF for tuberculosis in both ACF and non-ACF areas, with a larger magnitude in ACF areas. Compared to a counterfactual where pre-ACF CNR trends continued during ACF period, we estimated there were an additional 101 (95% confidence interval [CI] 42 to 160) microbiologically confirmed (Bac+) tuberculosis diagnoses per 100 000 person-years in the ACF areas in 3 and a half years of ACF. Compared to a counterfactual where trends in ACF area were the same as trends in non-ACF areas, we estimated an additional 63 (95% CI 38 to 90) Bac + diagnoses per 100 000 person-years in the same period. CONCLUSIONS: Tuberculosis ACF was associated with a rapid increase in people diagnosed with tuberculosis in Blantyre.


Asunto(s)
Tamizaje Masivo , Tuberculosis , Adulto , Humanos , Malaui/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Ciudades , VIH
14.
PLOS Glob Public Health ; 3(2): e0001557, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36963024

RESUMEN

People living with HIV (PLHIV) admitted to hospital have a high risk of death. We systematically appraised evidence for interventions to reduce mortality among hospitalised PLHIV in low- and middle-income countries (LMICs). Using a broad search strategy with terms for HIV, hospitals, and clinical trials, we searched for reports published between 1 Jan 2003 and 23 August 2021. Studies of interventions among adult HIV positive inpatients in LMICs were included if there was a comparator group and death was an outcome. We excluded studies restricted only to inpatients with a specific diagnosis (e.g. cryptococcal meningitis). Of 19,970 unique studies identified in search, ten were eligible for inclusion with 7,531 participants in total: nine randomised trials, and one before-after study. Three trials investigated systematic screening for tuberculosis; two showed survival benefit for urine TB screening vs. no urine screening, and one which compared Xpert MTB/RIF versus smear microscopy showed no difference in survival. One before-after study implemented 2007 WHO guidelines to improve management of smear negative tuberculosis in severely ill PLHIV, and showed survival benefit but with high risk of bias. Two trials evaluated complex interventions aimed at overcoming barriers to ART initiation in newly diagnosed PLHIV, one of which showed survival benefit and the other no difference. Two small trials evaluated early inpatient ART start, with no difference in survival. Two trials investigated protocol-driven fluid resuscitation for emergency-room attendees meeting case-definitions for sepsis, and showed increased mortality with use of a protocol for fluid administration. In conclusion, ten studies published since 2003 investigated interventions that aimed to reduce mortality in hospitalised adults with HIV, and weren't restricted to people with a defined disease diagnosis. Inpatient trials of diagnostics, therapeutics or a package of interventions to reduce mortality should be a research priority. Trial registration: PROSPERO Number: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019150341.

15.
Lancet Glob Health ; 11(4): e556-e565, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36925176

RESUMEN

BACKGROUND: Clinical practice and diagnostic algorithms often assume that tuberculosis can be ruled out in mycobacteriology-negative individuals whose symptoms improve with a trial-of-antibiotics. We aimed to investigate diagnostic performance, clinical benefit, and antimicrobial resistance using a randomised controlled trial. METHODS: In this three-arm, individually randomised, open-label, controlled trial, we enrolled Malawian adults (aged ≥18 years) attending primary care who reported being unwell for at least 14 days (including cough) with no immediate indication for hospitalisation at Limbe and Ndirande Health Centres in Blantyre. Participants were randomly allocated (1:1:1) to azithromycin (500 mg taken once per day for 3 days), amoxicillin (1 g taken three times per day for 5 days), or standard of care with no immediate antibiotics, stratified by study site. Sputum at enrolment and day 8 was tested for tuberculosis (microscopy, Xpert MTB/RIF, and culture). The primary efficacy outcome was day 8 specificity (percentage with symptom improvement among mycobacteriology-negative participants), and day 29 clinical outcome (death, hospitalisation, or missed tuberculosis diagnosis) among all randomised participants. This study is registered with ClinicalTrials.gov, NCT03545373. FINDINGS: Between Feb 25, 2019, and March 14, 2020, 5825 adults were screened and 1583 (mean age 36 years; 236 [14·9%] HIV positive) were randomly assigned to standard of care (530 participants), azithromycin (527 participants), or amoxicillin (526 participants) groups. Overall, 6·3% (100 of 1583 participants) had positive baseline sputum mycobacteriology. 310 (79·1%) of 392 patients receiving standard of care reported symptom improvement at day 8, compared with 340 (88·7%) of 383 patients receiving azithromycin (adjusted difference 8·6%, 95% CI 3·9-13·3%; p<0·0004) and 346 (89·4%) of 387 receiving amoxicillin (adjusted difference 8·8%, 4·0-13·6%; p=0·0003). The proportion of participants with day 29 composite clinical outcomes was similar between groups (standard of care 1% [7 of 530 participants], azithromycin 1% [6 of 527 participants], amoxicillin 2% [12 of 526 participants]). INTERPRETATION: Routine outpatient trial-of-antibiotics during tuberculosis investigations modestly improved diagnostic specificity for mycobacteriologically confirmed tuberculosis but had no appreciable effect on death, hospitalisation, and missed tuberculosis diagnosis. These results confirm the limited benefit of trial-of-antibiotics, presenting an opportunity for discontinuation of trial-of-antibiotics and improved antimicrobial stewardship during tuberculosis screening, without affecting clinical outcomes. FUNDING: Northern Norway Regional Health Authority (Helse Nord RHF), Commonwealth Scholarship Commission in the UK, Wellcome Trust, UK Medical Research Council, and the UK Department for International Development.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Adulto , Humanos , Adolescente , Antibacterianos/uso terapéutico , Malaui , Azitromicina/uso terapéutico , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Amoxicilina/uso terapéutico
16.
Pediatr Infect Dis J ; 42(5): 353-360, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36854097

RESUMEN

INTRODUCTION: An estimated 1.2 million children develop tuberculosis (TB) every year with 240,000 dying because of missed diagnosis. Existing tools suffer from lack of accuracy and are often unavailable. Here, we describe the scientific and clinical methodology applied in RaPaed-TB, a diagnostic accuracy study. METHODS: This prospective diagnostic accuracy study evaluating several candidate tests for TB was set out to recruit 1000 children <15 years with presumptive TB in 5 countries (Malawi, Mozambique, South Africa, Tanzania, India). Assessments at baseline included documentation of TB signs and symptoms, TB history, radiography, tuberculin skin test, HIV testing and spirometry. Respiratory samples for reference standard testing (culture, Xpert Ultra) included sputum (induced/spontaneous) or gastric aspirate, and nasopharyngeal aspirate (if <5 years). For novel tests, blood, urine and stool were collected. All participants were followed up at months 1 and 3, and month 6 if on TB treatment or unwell. The primary endpoint followed NIH-consensus statements on categorization of TB disease status for each participant. The study was approved by the sponsor's and all relevant local ethics committees. DISCUSSION: As a diagnostic accuracy study for a disease with an imperfect reference standard, Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease (RaPaed-TB) was designed following a rigorous and complex methodology. This allows for the determination of diagnostic accuracy of novel assays and combination of testing strategies for optimal care for children, including high-risk groups (ie, very young, malnourished, children living with HIV). Being one of the largest of its kind, RaPaed-TB will inform the development of improved diagnostic approaches to increase case detection in pediatric TB.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Niño , Estudios Prospectivos , Sensibilidad y Especificidad , Tuberculosis/diagnóstico , Prueba de Tuberculina , Heces , Esputo
17.
Trans R Soc Trop Med Hyg ; 117(1): 28-37, 2023 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-35963826

RESUMEN

BACKGROUND: TB is a leading cause of morbidity among HIV positive individuals. Accurate algorithms are needed to achieve early TB diagnosis and treatment. We investigated the use of Xpert MTB/RIF Ultra in combination with chest radiography for TB diagnosis in ambulatory HIV positive individuals. METHODS: This was a randomised controlled trial with a 2-by-2 factorial design. Outpatient HIV clinic attendees with cough were randomised to four arms: Arm 1-Standard Xpert/no chest radiography (CXR); Arm 2-Standard Xpert/CXR; Arm 3-Xpert Ultra/no CXR; and Arm 4-Xpert Ultra/CXR. Participants were followed up at days 28 and 56 to assess for TB treatment initiation. RESULTS: We randomised 640 participants. Bacteriologically confirmed TB treatment initiation at day 28 were: Arm 1 (8.4% [14/162]), Arm 2 (6.9% [11/159]), Arm 3 (8.2% [13/159]) and Arm 4 (5.6% [9/160]) and between Xpert Ultra group (Arms 3 and 4) (6.9% [22/319]) vs Standard Xpert group (Arms 1 and 2) (7.8% [25/321]), risk ratio 0.89 (95% CI 0.51 to 1.54). By day 56, there were also similar all-TB treatment initiations in the x-ray group (Arms 2 and 4) (16.0% [51/319]) compared with the no x-ray group (Arms 1 and 3) (13.1% [42/321]), risk ratio 1.22 (95% CI 0.84 to 1.78); however, the contribution of clinically diagnosed treatment initiations were higher in x-ray groups (50.9% vs 19.0%). CONCLUSIONS: Xpert Ultra performed similarly to Xpert MTB/RIF. X-rays are useful for TB screening but further research should investigate how to mitigate false-positive treatment initiations.


Asunto(s)
Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Humanos , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/tratamiento farmacológico , Radiografía , Instituciones de Atención Ambulatoria , Infecciones por VIH/complicaciones , Sensibilidad y Especificidad , Esputo
18.
PLoS One ; 17(9): e0269219, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36074775

RESUMEN

BACKGROUND: Household contact tracing provides TB screening and TB preventive therapy (TPT) to contacts at high risk of TB disease. However, it is resource intensive, inconvenient, and often poorly implemented. We investigated a novel model aiming to improve uptake. METHODS: Between May and December 2014, we randomised patient with TB who consented to participate in the trial to either standard of care (SOC) or intervention (PACTS) arms. Participants randomised to PACTS received one screening/triage tool (adapted from WHO integrated management of adolescent and adult illnesses [IMAI] guidelines) and sputum pots for each reported household contact. The tool guided participants through symptom screening; TPT (6-months of isoniazid) eligibility; and sputum collection for contacts. Patients randomised to SOC were managed in accordance with national guidelines, that is, they received verbal instruction on who to bring to clinics for investigation using national guidelines. MAIN OUTCOME AND MEASURES: The primary outcome was the proportion of adult contacts receiving treatment for TB within 3 months of randomisation. Secondary outcomes were the proportions of child contacts under age 5 years (U5Y) who were commenced on, and completed, TPT. Data were analyzed by logistic regression with random effects to adjust for household clustering. RESULTS: Two hundred and fourteen index TB participants were block-randomized from two sites (107 PACTS, reporting 418 contacts; and 107 SOC, reporting 420 contacts). Overall, 62.8% of index TB participants were HIV-positive and 52.1% were TB culture-positive. 250 otherwise eligible TB patients declined participation and 6 households (10 PACTS, 6 SOC) were lost to follow-up and were not included in the analysis. By three months, nine contacts (PACTS: 6, [1.4%]; SOC: 3, [0.7%]) had TB diagnosed, with no difference between groups (adjusted odds ratio [aOR]: 2.18, 95% CI: 0.60-7.95). Eligible PACTS contacts (37/96, 38.5%) were more likely to initiate TPT by 3-months compared to SOC contacts (27/101, 26.7%; aOR 2.27, 95% CI: 1.04-4.98). U5Y children in the PACTS arm (47/81 58.0%) were more likely to have initiated TPT before the 3-month visit compared to SOC children (36/89, 41.4%; aOR: 2.31, 95% CI: 1.05-5.06). CONCLUSIONS AND RELEVANCE: A household-centred patient-delivered symptom screen and IPT eligibility assessment significantly increased timely TPT uptake among U5Y children, but did not significantly increase TB diagnosis. This model needs to be optimized for acceptability, given low participation, and investigated in other low resource settings. CLINICAL TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: ISRCTN81659509 https://www.isrctn.com/ISRCTN81659509?q=&filters=conditionCategory:Respiratory,recruitmentCountry:Malawi,ageRange:Mixed&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search. 19 July 2012.


Asunto(s)
Trazado de Contacto , Tuberculosis , Adolescente , Adulto , Niño , Preescolar , Composición Familiar , Humanos , Isoniazida/uso terapéutico , Malaui/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis/prevención & control
19.
BMC Pediatr ; 22(1): 340, 2022 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-35690762

RESUMEN

BACKGROUND: We investigated risk factors for sustained virological non-suppression (viral load ≥ 1000 copies/ml on two tests 48 weeks apart) among children and adolescents accessing HIV care in public sector clinics in Harare, Zimbabwe and Blantyre, Malawi. METHODS: Participants were enrolled between 2016 and 2019, were aged 6-19 years, living with HIV, had chronic lung disease (FEV z-score < -1) and had taken antiretroviral therapy (ART) for at least six months. We used multivariate logistic regression to identify risk factors for virological non-suppression after 48 weeks, among participants who were non-suppressed at enrolment. RESULTS: At enrolment 258 participants (64.6%) were on first-line ART and 152/347 (43.8%) had virological non-suppression. After 48 weeks 114/313 (36.4%) were non-suppressed. Participants non-suppressed at baseline had almost ten times higher odds of non-suppression at follow-up (OR = 9.9, 95%CI 5.3-18.4, p < 0.001). Of those who were non-suppressed at enrolment, 87/136 (64.0%) were still non-suppressed at 48 weeks. Among this group non-suppression at 48 weeks was associated with not switching ART regimen (adjusted OR = 5.55; 95%CI 1.41-21.83); p = 0.014) and with older age. Twelve participants switched regimen in Zimbabwe and none in Malawi. CONCLUSIONS: Viral non-suppression was high among this group and many with high viral load were not switched to a new regimen, resulting in continued non-suppression after 48 weeks. Further research could determine whether improved adherence counselling and training clinicians on regimen switches can improve viral suppression rates in this population. TRIAL REGISTRATION: Secondary cohort analysis of data from BREATHE trial (Clinicaltrials.gov NCT02426112 ).


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adolescente , Fármacos Anti-VIH/uso terapéutico , Niño , Análisis de Datos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Malaui/epidemiología , Factores de Riesgo , Carga Viral , Zimbabwe/epidemiología
20.
Epidemics ; 40: 100590, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35691100

RESUMEN

INTRODUCTION: Understanding human mixing patterns relevant to infectious diseases spread through close contact is vital for modelling transmission dynamics and optimisation of disease control strategies. Mixing patterns in low-income countries like Malawi are not well known. METHODOLOGY: We conducted a social mixing survey in urban Blantyre, Malawi between April and July 2021 (between the 2nd and 3rd wave of COVID-19 infections). Participants living in densely-populated neighbourhoods were randomly sampled and, if they consented, reported their physical and non-physical contacts within and outside homes lasting at least 5 min during the previous day. Age-specific mixing rates were calculated, and a negative binomial mixed effects model was used to estimate determinants of contact behaviour. RESULTS: Of 1201 individuals enroled, 702 (58.5%) were female, the median age was 15 years (interquartile range [IQR] 5-32) and 127 (10.6%) were HIV-positive. On average, participants reported 10.3 contacts per day (range: 1-25). Mixing patterns were highly age-assortative, particularly those within the community and with skin-to-skin contact. Adults aged 20-49 y reported the most contacts (median:11, IQR: 8-15) of all age groups; 38% (95%CI: 16-63) more than infants (median: 8, IQR: 5-10), who had the least contacts. Household contact frequency increased by 3% (95%CI: 2-5) per additional household member. Unemployed participants had 15% (95%CI: 9-21) fewer contacts than other adults. Among long range (>30 m away from home) contacts, secondary school children had the largest median contact distance from home (257 m, IQR 78-761). HIV-positive status in adults >=18 years-old was not associated with changed contact patterns (rate ratio: 1.01, 95%CI: (0.91-1.12)). During this period of relatively low COVID-19 incidence in Malawi, 301 (25.1%) individuals stated that they had limited their contact with others due to COVID-19 precautions; however, their reported contacts were 8% (95%CI: 1-13) higher. CONCLUSION: In urban Malawi, contact rates, are high and age-assortative, with little reported behavioural change due to either HIV-status or COVID-19 circulation. This highlights the limits of contact-restriction-based mitigation strategies in such settings and the need for pandemic preparedness to better understand how contact reductions can be enabled and motivated.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Infecciones por VIH , Adolescente , Adulto , COVID-19/epidemiología , Niño , Enfermedades Transmisibles/epidemiología , Femenino , Infecciones por VIH/epidemiología , Humanos , Lactante , Malaui/epidemiología , Masculino , Instituciones Académicas
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