Improving tuberculosis case detection through contact risk stratification by Xpert MTB/RIF Ultra and spatial parameters: Evaluation of an innovative active case finding strategy in Mozambique (Xpatial-TB).

Prompt diagnosis is critical for tuberculosis (TB) control, as it enables early treatment which in turn, reduces transmission and improves treatment outcomes. We investigated the impact on TB diagnosis of introducing Xpert Ultra as the frontline diagnostic test, combined with an innovative active-case finding (ACF) strategy (based on Xpert Ultra semi-quantitative results and spatial parameters), in a semi-rural district of Southern Mozambique. From January-December 2018 we recruited incident TB-cases (index cases, ICs) and their household contacts (HCs). Recruitment of close community contacts (CCs) depended on IC´s Xpert Ultra results, and the population density of their area. TB-contacts, either symptomatic or people living with HIV, were asked to provide a spot sputum for lab-testing. Trends on TB case notification were compared to the previous years and to those of two districts in the south of the Maputo province (control area), using an interrupted time series analysis with and without control (CITS/ITS). A total of 1010 TB ICs (37.1% laboratory-confirmed) were recruited; 3165 HCs and 4730 CCs were screened for TB. Eighty-nine additional TB cases were identified through the ACF intervention (52.8% laboratory-confirmed). The intervention increased by 8.2% all forms of TB cases detected in 2018. Xpert Ultra trace positive results accounted for a high proportion of laboratory confirmations in the ACF cohort (51.1% vs 13.7% of those passively diagnosed). The Number Needed to Screen to find a TB case differed widely among HCs (55) and CCs (153). During the intervention period, a reversal of the previous negative trend in lab-confirmed case notifications was observed in the district. However, the CITS model did not show any statistically significant difference compared to the control area. Paediatric population benefited the most from the ACF strategy and HCs screening seemed an effective intervention to find microbiological confirmed cases in early stages of the disease.

Diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa: a continent-wide survey.

BACKGROUND: Fungal infections are common causes of death and morbidity in those with advanced HIV infection. Data on access to diagnostic tests in Africa are scarce. We aimed to evaluate the diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa. METHODS: We did a continent-wide survey by collecting data from 48 of 49 target countries across Africa with a population of more than 1 million; for Lesotho, only information on the provision of cryptococcal antigen testing was obtained. This survey covered 99·65% of the African population. We did the survey in six stages: first, questionnaire development, adaptation, and improvement; second, questionnaire completion by in-country respondents; third, questionnaire review and data analysis followed by video conference calls with respondents; fourth, external validation from public or private sources; fifth, country validation by video conference with senior figures in the Ministry of Health; and sixth, through five regional webinars led by the Africa Centres for Disease Control and Prevention with individual country profiles exchanged by email. Data was compiled and visualised using the Quantum Geographic Information System software and Natural Earth vectors to design maps showing access. FINDINGS: Data were collected between Oct 1, 2020, and Oct 31, 2022 in the 48 target countries. We found that cryptococcal antigen testing is frequently accessible to 358·39 million (25·5%) people in 14 African countries. Over 1031·49 million (73·3%) of 1·4 billion African people have access to a lumbar puncture. India ink microscopy is frequently accessible to 471·03 million (33·5%) people in 23 African countries. About 1041·62 million (74·0%) and 1105·11 million (78·5%) people in Africa do not have access to histoplasmosis and Pneumocystis pneumonia diagnostics in either private or public facilities, respectively. Fungal culture is available in 41 countries covering a population of 1·289 billion (94%) people in Africa. MRI is routinely accessible to 453·59 million (32·2%) people in Africa and occasionally to 390·58 million (27·8%) people. There was a moderate correlation between antiretroviral therapy usage and external expenditure on HIV care (R2=0·42) but almost none between external expenditure and AIDS death rate (R2=0·18), when analysed for 40 African countries. INTERPRETATION: This survey highlights the enormous challenges in the diagnosis of HIV-associated Pneumocystis pneumonia, cryptococcal disease, histoplasmosis, and other fungal infections in Africa. Urgent political and global health leadership could improve the diagnosis of fungal infections in Africa, reducing avoidable deaths. FUNDING: Global Action For Fungal Infections.

Improved detection and management of advanced HIV disease through a community adult TB-contact tracing intervention with same-day provision of the WHO-recommended package of care including ART initiation in a rural district of Mozambique.

INTRODUCTION: AIDS-mortality remains unacceptably high in sub-Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact-tracing intervention (Xpatial-TB). The aim was to assess the burden of AHD among high-risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO-recommended package of care to this population. METHODS: All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial-TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/µL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB-lipoarabinomannan (TB-LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow-up visits carried out under routine programmatic conditions for six months. RESULTS: A total of 2881 adults were identified in the Xpatial TB-contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB-contacts) consented to the study and were screened for AHD. Seventy percent of TB index-patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum-CrAg was positive in 4.6% (4/87) of TB-index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six-month mortality was 21% among TB-index cases and zero in TB contacts. CONCLUSIONS: A TB contact-tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO-recommended package of care in this rural Mozambican population. Same-day and accelerated ART initiation was feasible and safe in this population including among those with AHD.

Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding.

AIMS: We present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF ("Xpert") and Xpert MTB/RIF Ultra ("Ultra") using two cohorts in a high tuberculosis/HIV burden setting in Southern Mozambique. METHODS: Single respiratory specimens from symptomatic adults accessing healthcare services (passive case finding (PCF) cohort) and from household and community close contacts (active case finding (ACF) cohort) were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored the impact of trace results on specificity via their recategorisation to negative (in all and just among those previously treated individuals). RESULTS: 1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI 0.90-0.98) versus 0.88 (96% CI 0.82-0.93); p<0.001) and among smear-negative patients (0.84 (96% CI 0.71-0.93) versus 0.63 (96% CI 0.48-0.76)). Ultra's specificity was lower than Xpert's (0.96 (96% CI 0.95-0.97) versus 0.98 (96% CI 0.97-0.99); p=0.008). For ACF, sensitivities were the same (0.67 (95% CI 0.22-0.96) for both tests), although Ultra detected a higher number of microbiologically confirmed samples than Xpert (4.7% (12 out of 252) versus 2.7% (seven out of 252)). Conditional recategorisation of trace results among previously treated participants maintained differences in specificity in the PCF cohort. CONCLUSION: These results add evidence on the improved sensitivity of Ultra and support its use in different case finding scenarios.