Xpert Ultra testing of blood in severe HIV-associated tuberculosis to detect and measure Mycobacterium tuberculosis blood stream infection: a diagnostic and disease biomarker cohort study

BACKGROUND: Mycobacterium tuberculosis bloodstream infection is a leading cause of death in people living with HIV and disseminated bacillary load might be a key driver of disease severity. We aimed to assess Xpert MTB/RIF Ultra (Xpert Ultra) testing of blood as a diagnostic for M tuberculosis bloodstream infection and investigate cycle threshold as a quantitative disease biomarker. METHODS: In this cohort study, we obtained biobanked blood samples from a large and well characterised cohort of adult patients admitted to hospital in Western Cape, South Africa with suspected HIV-associated tuberculosis and a CD4 count less than 350 cells per μL. Patients already receiving antituberculosis therapy were excluded. Samples were obtained on recruitment within 72 h of admission to hospital, and patients were followed up for 12 weeks to determine survival. We tested the biobanked blood samples using the Xpert Ultra platform after lysis and wash processing of the blood. We assessed diagnostic yield (proportion of cases detected, with unavailable test results coded as negative) against a microbiological reference, both as a function of markers of critical-illness and compared with other rapid diagnostics (urine lipoarabinomannan and sputum Xpert). Quantitative blood Xpert Ultra results were evaluated as a disease biomarker by assessing association with disease phenotype defined by principal component analysis of 32 host-response markers. Prognostic value compared to other tuberculosis biomarkers was assessed using likelihood ratio testing of nested models predicting 12-week mortality. FINDINGS: Between Jan 16, 2014, and Oct 19, 2016, of the 659 participants recruited to the parent study, 582 had an available biobanked blood sample. 447 (77%) of 582 met the microbiological reference standard for tuberculosis diagnosis. Median CD4 count was 62 (IQR 221-33) cells per μL, and 123 (21%) of participants died by 12-weeks follow-up. Blood Xpert Ultra was positive in 165 (37%) of 447 participants with confirmed tuberculosis by the microbiological reference standard, with a diagnostic yield of 0·37 (95% CI 0·32-0·42). Diagnostic yield increased with lower CD4 count or haemoglobin, and outperformed urine lipoarabinomannan testing in participants with elevated venous lactate. Quantitative blood Xpert Ultra results were more closely associated with mortality than other tuberculosis biomarkers including blood culture, and urine lipoarabinomannan, or urine Xpert (all p<0·05). A principal component of clinical phenotype capturing markers of inflammation, tissue damage, and organ dysfunction was strongly associated with both blood Xpert-Ultra positivity (associated with a SD increase of 1·1 in PC score, p<0·0001) and cycle threshold (r= -0·5; p<0·0001). INTERPRETATION: Xpert Ultra testing of pre-processed blood could be used as a rapid diagnostic test in critically ill patients with suspected HIV-associated tuberculosis, while also giving additional prognostic information compared with other available markers. A dose-response relationship between quantitative blood Xpert Ultra results, host-response phenotype, and mortality risk adds to evidence that suggests M tuberculosis bloodstream infection bacillary load is causally related to outcomes. FUNDING: Wellcome Trust, National Institute of Health Fogarty International Center, South African MRC, UK National Institute of Health Research, National Research Foundation of South Africa. TRANSLATIONS: For the Xhosa and Afrikaans translations of the abstract see Supplementary Materials section

Experiences of homosexual patients’ access to primary health care services in Umlazi, KwaZulu-Natal

Background: Homosexual patients are affected by social factors in their environment, and as a result may not have easy access to existing health care services. Prejudice against homosexuality and homosexual patients remains a barrier to them seeking appropriate healthcare. The concern is that lesbians and gays might delay or avoid seeking health care when they need it because of past discrimination or perceived homophobia within the health care thereby putting their health at risk. Aim of the study: The aim of the study was to explore and describe the experiences of homosexual patients utilising primary health care (PHC) services in Umlazi in the province ofKwaZulu-Natal (KZN). Method: A qualitative, exploratory, descriptive study was conducted which was contextual innature. Semi-structured interviews were conducted with 12 participants. The findings of this study were analysed using content analysis. Results: Two major themes emerged from the data analysis, namely, prejudice against homosexual patients by health care providers and other patients at the primary health care facilities, and, homophobic behaviour from primary health care personnel. Conclusion: Participants experienced prejudice and homophobic behaviour in the course of utilising PHC clinics in Umlazi, which created a barrier to their utilisation of health services located there. Nursing education institutions, in collaboration with the National Department of Health, should introduce homosexuality and anti-homophobia education programmes during the pre-service and in-service education period. Such programmes will help to familiarise health care providers with the health care needs of homosexual patients and may decrease homophobic attitudes

Experiences of community caregivers in the assessment of malnutrition using mid-upper arm circumference measurement in children under 5 years old

Background: Malnutrition is a major public health challenge in developing countries. It has been identified as an important cause of child mortality and morbidity and leads to inadequate physical and cognitive development in children. The South African government implemented a strategy for malnutrition assessment in children under 5 years by community caregivers (CCGs), who would then refer children at risk or those having developed malnutrition to primary health care clinics. Irrespective of this strategy, children still present at clinics with severe malnutrition. Aim: The aim of the study was to explore and describe the experiences of community caregivers with the assessment of malnutrition in children under 5 years old. Setting: The study was conducted in North Area six of eThekwini district in the province of KwaZulu-Natal. Methods: A qualitative, exploratory descriptive approach was used to collect data from 13 purposively selected CCGs. Content analysis was used to analyse data. Results: The majority of participants were dissatisfied with the training, as it was conducted in a language in which they were not proficient. They reported a lack of support and supervision in their performance such that mid-upper arm circumference was non-prioritised. They were dissatisfied with work overload not matched by remuneration and they worked under unsafe conditions. Conclusion: Effective training of CCGs needs to be conducted in the language that they understand to combat malnutrition in children under 5 years. CCGs have multiple roles and may need to prioritise their work; this is not easy and requires specific guidance from skilled health professionals

Individual, household, and community level barriers to ART adherence among women in rural Eswatini.

BACKGROUND:Despite access to free antiretroviral therapy (ART) for all people living with human immunodeficiency virus (HIV), noncompliance to treatment continues to be a significant challenge in Eswatini. Yet studies investigating barriers to ART adherence in Eswatini are scarce. Most notably, there is a lack of research regarding rural women in Eswatini, who are currently the country's most vulnerable to HIV infection. Therefore, the objective of the study is to investigate individual, household, and community level barriers to ART adherence among rural women living with HIV. METHODS:We conducted a qualitative study to investigate individual, household, and community level barriers to ART adherence. We conducted focus group discussions with HIV-infected women (n = 4) from rural villages in Eswatini, and in-depth interviews with healthcare workers (n = 8) serving the area clinics. Open and axial coding techniques were used for data analysis and interpreted within a social ecological framework. RESULTS:Our findings revealed several individual level barriers including hunger, side effects of ART, personal stress, lack of disclosure of HIV status, alcohol use, and forgetting to take ART. Lack of food, unemployment and scarcity of financial resources were identified as critical barriers at the household level. Community and institutional barriers encompassed factors related to health delivery such as lack of privacy, travel time, transportation costs, excessive alcohol use by healthcare workers, maltreatment, public and self-stigma, gossip, and long waits at clinics. CONCLUSIONS:Rural women living with HIV face multilevel barriers to ART adherence. Support programs aimed at increasing ART adherence among this vulnerable population need to develop targeted polices to alleviate challenges rural women face, beginning with expanding qualifications for food assistance programs