Cerebrospinal Fluid Bacillary Load by Xpert MTB/RIF Ultra Polymerase Chain Reaction Cycle Threshold Value Predicts 2-Week Mortality in Human Immunodeficiency Virus-Associated Tuberculous Meningitis.

BACKGROUND: The World Health Organization recommends GeneXpert MTB/RIF Ultra (Xpert Ultra), a fully automated polymerase chain reaction (PCR) assay, as the initial tuberculous meningitis (TBM) diagnostic test. The assay's PCR cycle threshold (Ct) values represent the number of PCR cycles required for probe signal to be detected (low Ct value = high bacillary load) and may approximate tuberculosis (TB) bacillary load. We measured the relationship between cerebrospinal fluid (CSF) TB bacillary load with mortality. METHODS: We prospectively enrolled 102 human immunodeficiency virus (HIV)-positive Ugandans with probable or definite TBM from April 2015 to August 2019. Xpert Ultra Ct tertiles and semi-quantitative categories were separately analyzed as predictors of 2-week mortality. We investigated associations between Ct and baseline clinical and CSF parameters. RESULTS: Subjects with Ct values in the low tertile (ie, high bacillary load) had 57% 2-week mortality-worse than the intermediate (17%) and high (25%) Ct tertiles and Xpert Ultra-negative (30%) probable TBM cases (P = .01). In contrast, the reported semi-quantitative Xpert Ultra categorization was less precise; with the medium to low category trending toward worse 2-week survival (42%) compared with very low (28%), trace (26%), and negative (30%) categories (P = .48). Ct tertile was significantly associated with baseline CSF lactate (P = .03). CONCLUSIONS: High CSF TB bacillary load, as measured by Xpert Ultra Ct tertile, is associated with an almost 2-fold higher 2-week mortality in HIV-associated TBM and is a better predictor than the reported Xpert Ultra semi-quantitative category. Xpert Ultra Ct values could identify TBM patients at increased risk of death who may benefit from enhanced supportive care.

Skin prick reactivity among asthmatics in East Africa.

BACKGROUND: The burden of asthma in Africa is high, and yet the disease is not universally prioritised. Data on allergic asthma and its impact on asthma morbidity are limited in Africa. Our aim was to describe the distribution of skin prick positivity among asthmatics in Eastern Africa. METHODS: From August 2016 to May 2018, 1671 asthmatic patients were enrolled from Uganda, Kenya, and Ethiopia as part of the African Severe Asthma Program clinical study. Skin prick testing was performed at baseline using a panel of 12 allergens, and factors associated with skin prick reactivity determined. RESULTS: Of the 1, 671 patients recruited, 71% were female with a median age of 40 years, 93.6% were aged >15 years and the patterns of asthma symptom frequency was intermittent in 2.9%, mild persistent in 19.9%, moderate persistent in 42.6% and severe persistent in 34.6% at baseline. Self-reported triggers, were dust (92%), cold weather (89%), upper respiratory infections (84%), strong smells (79%) and exposure to tobacco (78%). The majority (90%) of the participants had at least 1 positive allergen reaction, with 0.9% participants reacting to all the 12 allergens. Participants commonly reacted to house dust mites (66%), Blomia tropicalis (62%), and the German cockroach (52%). Patients sensitized to more allergens (>2) had significantly reduced lung function (FEV ≤ 80%; p = 0.001) and were more likely to visit the emergency department due to asthma (p = 0.012). There was no significant relationship between number of allergens and measures of asthma control, quality of life, and other clinical outcomes. Only the country of origin was independently associated with atopy among African asthmatics. CONCLUSION: There is a high prevalence of skin prick positivity among East African patients with asthma, with the commonest allergen being house dust mite. Skin reactivity did not correlate well with asthma severity and poor asthma control. The relation between atopy, measured through skin prick testing, and measures of asthma control among asthma patients in Eastern Africa is unclear and needs further study. TRIAL REGISTRATION: The ASAP study was registered prospectively. ClinicalTrials.gov Identifier: NCT03065920; Registration date: February 28, 2017; Last verified: February 28, 2017.

Xpert MTB/RIF Ultra: Optimal procedures for the detection of Mycobacterium tuberculosis in cerebrospinal fluid.

Tuberculosis is the leading infectious cause of death globally and extra-pulmonary disease occurs in 15% of incident cases annually. Tuberculous meningitis (TBM) is arguably the most lethal form of tuberculosis and requires prompt diagnosis and initiation of treatment to prevent death and serious neurological disability. The development of rapid diagnostic tests using polymerase chain reaction (PCR) technology for the detection of Mycobacterium tuberculosis (MTB), including the World Health Organization (WHO) - endorsed Xpert MTB/RIF Ultra assay, has allowed earlier definite diagnosis of TBM than conventional culture methods which usually take two weeks or longer for positive identification of MTB. Detection of MTB in cerebrospinal fluid (CSF) using PCR assays requires special attention to the collection, handling, and processing of CSF. Herein we present best practices guidance to maximize the detection rate of MTB in CSF using Xpert MTB/RIF Ultra.

Detection of Mycobacterium tuberculosis in urine by Xpert MTB/RIF Ultra: A useful adjunctive diagnostic tool in HIV-associated tuberculosis.

In January 2017, the World Health Organisation recommended the Xpert® MTB/RIF Ultra assay (Ultra) for tuberculosis (TB) diagnosis. Ultra offers improved analytical sensitivity when compared with the initial Xpert® MTB/RIF (Xpert) assay for the detection of Mycobacterium tuberculosis. Ultra is therefore likely to be of particular benefit for detecting paucibacillary TB. We present a case from Uganda demonstrating Ultra positivity in urine from an HIV-infected patient presenting with altered mental status and urinary incontinence, and no other signs of active pulmonary or extrapulmonary TB. This represents the first published instance of a diagnosis of extrapulmonary TB made on the basis of a positive urine Ultra assay. The use of Ultra on urine may be a useful addition to the diagnostic armamentarium for disseminated TB in persons with HIV co-infection. The diagnostic accuracy of urine Ultra should be characterised further via prospective studies.