Undernotification and underreporting of tuberculosis in Zambia: a national data quality assessment.

BACKGROUND: Despite national implementation of several high impact interventions and innovations to bolster tuberculosis (TB) detection and improve quality of TB services in Zambia, notifications have been declining since 2004. A countrywide data quality assessment (DQA) of Zambia's National TB and Leprosy Programme (NTLP) was undertaken to quantify the degree to which undernotification and underreporting of TB notifications may be occurring. METHODS: The NTLP conducted a retrospective DQA of health facilities in high burden districts in all ten Zambian provinces. Multiple routine programmatic data sources were triangulated through a multi-step verification process to enumerate the total number of unique TB patients diagnosed between 1st January and 31st August 2019; both bacteriologically confirmed and clinically diagnosed TB patients were included. Undernotification was defined as the number of TB patients identified through the DQA that were not documented in facility treatment registers, while underreporting was defined as the number of notified TB cases not reported to the NTLP. RESULTS: Overall, 265 health facilities across 55 districts were assessed from which 28,402 TB patients were identified; 94.5% of TB patients were ≥ 15 years old, 65.1% were male, 52.0% were HIV-positive, and 89.6% were a new/relapse case. Among all TB cases, 32.8% (95%CI: 32.2-33.3) were unnotified. Undernotification was associated with age ≥ 15 years old (adjusted prevalence odds ratio [aPOR] = 2.4 [95%CI: 2.0-2.9]), HIV-positive status (aPOR = 1.6 [95%CI: 1.5-1.8]), being a new/relapse TB case (aPOR = 17.5 [95%CI: 13.4-22.8]), being a clinically diagnosed TB case (aPOR = 4.2 [95%CI:3.8-4.6]), and being diagnosed at a hospital (range, aPOR = 1.5 [95%CI: 1.3-1.6] to 2.6 [95%CI: 2.3-2.9]). There was substantial heterogeneity in the proportion of unnotified TB cases by province (range, 18.2% to 43.6%). In a sub-analysis among 22,199 TB patients with further data available, 55.9% (95%CI: 55.2-56.6) were notified and reported to the NTLP, 32.8% (95%CI: 32.2-33.4) were unnotified, and 11.3% (95%CI: 10.9-11.7) went unreported to the NTLP. CONCLUSIONS: The findings from Zambia's first countrywide TB programme DQA demonstrate substantial undernotification and underreporting of TB cases across all provinces. This underscores the urgent need to implement a robust and integrated data management system to facilitate timely registration and reporting of all TB patients who are diagnosed and treated.

Prevalence and interpretation of Xpert® Ultra trace results among presumptive TB patients.

BACKGROUND: The "trace call" results on Xpert® Ultra indicates extremely low TB levels and may be difficult to interpret. The prevalence of trace results among presumptive TB patients in high TB-HIV infection settings is unknown, as is the significance of divergent "trace call" result interpretations. METHODS: Presumptive TB patients attending a public health facility in Lusaka, Zambia, were prospectively enrolled. Participants underwent several TB investigations, including sputum smear microscopy, Ultra testing, and culture. The diagnostic accuracy of Ultra (culture-based reference) and the number of patients recommended for TB treatment was assessed according to several different interpretation criteria for "trace call" results. RESULTS: Among the 740 participants, 78 (10.5%) were Ultra-positive and an additional 37 (5.0%) had a "trace call" result. The prevalence of trace results did not differ according to HIV status (5.3% vs. 4.8%) or prior TB status (5.6% vs. 4.9%). Differing interpretations of trace results had modest effects on Ultra's sensitivity (range 79.3-82.6%) and specificity (range 94.3-99.2%), but increased the number of patients recommended for treatment by up to 44.9%. CONCLUSIONS: Ultra trace results were common in this setting. The interpretation of trace results may substantially impact TB case yield.

CONTEXTE: La catégorie de résultats « traces ¼ du test Xpert Ultra indique des taux de TB très faibles et peut être difficile à interpréter. La prévalence de résultats traces parmi des patients suspects de TB dans des zones à forte prévalence de TB-VIH est inconnue, tout comme la signification d'interprétations divergentes des résultats traces. MÉTHODES: Les patients suspects de TB consultant dans un centre de soins public de Lusaka, Zambie, ont été inclus de manière prospective. Les participants ont fait l'objet de plusieurs examens de détection de la TB, dont microscopie des frottis d'expectorations, test Xpert® Ultra et culture. La précision diagnostique du test Ultra (par rapport à la culture) et le nombre de patients recommandés pour traitement antituberculeux ont été évalués selon plusieurs critères d'interprétation des résultats traces. RÉSULTATS: Parmi les 740 participants, 78 (10,5%) étaient positifs au test Ultra et 37 autres participants (5.0%) avaient un résultat trace. La prévalence des résultats traces ne différait pas en fonction du statut VIH (5,3% vs. 4,8%) ou du statut tuberculeux antérieur (5,6% vs. 4,9%). Les interprétations divergentes des résultats traces avaient un effet modéré sur la sensibilité du test Ultra (écart 79,3­82,6%) et sur sa spécificité (écart 94,3­99,2%), mais elles augmentaient le nombre de patients à qui un traitement était recommandé de 44,9% maximum. CONCLUSIONS: Les résultats traces au test Ultra étaient fréquents. L'interprétation de ces résultats peut impacter considérablement la détection des cas de TB.

Diagnosed with TB in the era of COVID-19: patient perspectives in Zambia.

INTRODUCTION: Delayed TB diagnosis and treatment perpetuate the high burden of TB-related morbidity and mortality in resource-constrained settings. We explored the potential of COVID-19 to further compromise TB care engagement in Zambia. METHODS: From April to May 2020, we purposefully selected 17 adults newly diagnosed with TB from three public health facilities in Lusaka, Zambia, for in-depth phone interviews. We conducted thematic analyses using a hybrid approach. RESULTS: The majority of participants were highly concerned about the impact of lockdowns on their financial security. Most were not worried about being diagnosed with COVID-19 when seeking care for their illness because they felt unwell prior to the outbreak; however, they were very worried about contracting COVID-19 during clinic visits. COVID-19 was perceived as a greater threat than TB as it is highly transmittable and there is no treatment for it, which provoked fear of social isolation and of death among participants in case they contracted it. Nonetheless, participants reported willingness to continue with TB medication and the clinic visits required to improve their health. CONCLUSION: The COVID-19 pandemic did not appear to deter care-seeking for TB by patients. However, messaging on TB in the era of COVID-19 must encourage timely care-seeking by informing people of infection control measures taken at health facilities.

Anaemia in patients with HIV-associated TB: relative contributions of anaemia of chronic disease and iron deficiency.

BACKGROUND: Anaemia commonly complicates both human immunodeficiency virus (HIV) infection and tuberculosis (TB), contributing substantially to morbidity and mortality. The mechanisms underlying anaemia and corresponding treatments in co-infected patients are poorly defined. OBJECTIVE: To determine the relative contributions of anaemia of chronic disease (ACD) and iron deficiency to anaemia in patients with HIV-associated TB. DESIGN: Consecutively recruited hospitalised (n = 102) and matched ambulatory patients (n = 51) with microbiologically confirmed HIV-associated TB in Cape Town, South Africa, were included. Haemoglobin levels, iron status markers, hepcidin and pro-inflammatory cytokines in blood were measured. We determined the prevalence of ACD and iron-deficiency anaemia (IDA) using seven different published definitions of IDA. RESULTS: More than 80% of enrolled HIV-associated TB patients were anaemic, and anaemia was more severe among in-patients. Over 95% of anaemic HIV-associated TB patients had ACD, whereas the proportion with IDA using a range of seven different definitions was low overall (median <3%, range 0-32.6) in both patient groups. The proportion with IDA and hepcidin concentration â©¿ 20.0 ng/ml (predictive of responsiveness to oral iron supplementation) was also very low (median <3%, range 0-15.1). CONCLUSIONS: ACD was the predominant cause underlying anaemia in HIV-associated TB patients, and IDA was very uncommon in this setting. The majority of anaemic HIV-associated TB patients were unlikely to benefit from oral iron supplementation.

Diagnostic and prognostic value of serum C-reactive protein for screening for HIV-associated tuberculosis.

BACKGROUND: Rapid means of ruling in or ruling out tuberculosis (TB) would permit more efficient management of patients starting antiretroviral treatment (ART). OBJECTIVE: To assess the diagnostic and prognostic utility of C-reactive protein (CRP) among patients being screened for TB before ART in a South African ART clinic. DESIGN: Patients were microbiologically screened for TB regardless of symptoms; serum CRP was measured, and mortality at 3 months was assessed. RESULTS: Among 496 patients (median CD4 count 171 cells/l), culture-positive TB was diagnosed in 81 (16.3%). CRP concentrations were much higher among TB cases (median 57.8 mg/l, IQR 20.0202.7) than in those without TB (6.4 mg/l, IQR 2.121.8, P < 0.001). Very low (<1.5 mg/l) CRP concentrations excluded TB (100% negative predictive value), whereas very high concentrations (>400 mg/l) were strongly predictive of TB (100% positive predictive value). However, these thresholds encompassed only 14.3% and 2.0%, respectively, of all patients screened and identified only 12.3% of TB cases. CRP concentrations ≥50 mg/l were associated with poor prognostic characteristics, higher mycobacterial load, disseminated disease and greater mortality risk. CONCLUSION: CRP concentrations identified groups of patients with very high or very low TB risk, but only in an unacceptably small minority of patients screened. However, in those with confirmed TB, CRP concentrations had useful prognostic value.

Diagnostic yield of tuberculosis using sputum induction in HIV-positive patients before antiretroviral therapy.

Adults (n = 602) enrolling in a South African antiretroviral treatment clinic underwent culture-based screening for tuberculosis (TB), regardless of symptoms. For those unable to spontaneously expectorate a 'spot' sample (n = 124), sputum induction with nebulised hypertonic saline was used to obtain a first sample and also to rapidly obtain a second sample from all patients. Collection of both samples typically took 10-15 min. The prevalence of culture-positive TB was 15.6% (95%CI 12.8-18.8). Spontaneously expectorated spot samples yielded 79.8% of all culture-positive TB diagnoses. The incremental yield from those needing an induced first sample was 5.3% and the yield from induced second samples was 14.9%.