No abstract

Traditionally, smear microscopy has been used as a point-of-care measure of bacillary burden in tuberculosis patients to inform infection control and contact tracing. Xpert MTB/RIF has the potential to replace smear. However, data to support the use of its quantitative output [cycle threshold (CT)] as an alternate point-of-care measure of bacillary burden are limited. This study assessed the correlation (Spearman’s) between CT, smear, culture time-to-positivity (TTP), and clinical factors in patients with Xpert-positive sputum from Mozambique (n = 238) and South Africa (n = 462). Mean CT and smear grade correlated well (ρ0.72); compared to TTP and smear (ρ0.61); and mean CT and TTP (ρ0.50). In multivariate analyses, lower CT (higher bacillary load) was associated with negative HIV serostatus and low BMI. A smear positivity rule-out (95% sensitivity) CT cut-off of 28.0 was identified, with 54.1% specificity, 2.07 positive likelihood ratio, 0.09 negative likelihood ratio and 79.0% correctly classified. Cut-offs were higher for HIV positive compared to HIV negative individuals for any set sensitivity level. This study suggests Xpert CT values correlate well with smear, both in HIV positive and negative individuals, and that CT cut-offs might be broadly applicable to multiple settings. Studies to directly assess the association of CT with infectiousness are needed.

Background: During acute HIV infection, HIV actively replicates but seroconversion has not yet occurred. Primary HIV infection (PHI) is characterized by a transient nonspecific febrile illness, a massive inflammatory response, and the progressive appearance of anti-HIV-specific antibodies. In this study, we have identified patterns of inflammatory biomarkers associated with the innate immunological reaction before completion of a full humoral response.Methods: A symptom-based screening was used to identify acute HIV infection in the Manhiça District Hospital in Mozambique. Plasma levels of biomarkers were determined by Luminex and enzyme-linked immunosorbent assay. Anti-HIV antibodies were analyzed by flow cytometry and Western blot. Statistical analyses used random forest and logistic regression models.Results: Of 3116 rapid test seronegative or indeterminate individuals, 85 (2.7%) had positive plasma HIV viral load and were enrolled as PHI, of which n = 45 (52.9%), n = 8 (9.4%), n = 12 (14.1%), and n = 20 (23.5%) were classified as Fiebig I-III, IV, V, and VI stages, respectively, by Western blot. Comparison of individuals at early (Fiebig I-IV) and late (Fiebig V-VI) immune stages identified significant differences in the expression level of plasma B-cell activating factor , monocyte chemotactic protein-1, sCD163, and monokine induced by interferon (IFN-g). This cytokine signature classified patients in the preseroconversion phase with a sensitivity of 92.5% and a specificity of 81.2%Conclusions: Identification of a cytokine signature specific for the preseroconversion stage of PHI may help to understand the earliest HIV pathogenic events and identify new potential targets for immunotherapy aimed at modulating the cytokine response to HIV infection.

BackgroundIn Mozambique, there is limited data regarding the monitoring of Tuberculosis (TB) treatment results and determinants of adverse outcomes under routine surveillance conditions. The objectives of this study were to evaluate treatment outcomes among TB patients, analyze factors associated with a fatal outcome and determine the proportion of deaths attributable to TB in the district of Manhiça, Southern Mozambique.MethodsThis is a retrospective observational study based on TB patients diagnosed in the period 2011–2012. We used three different data sources: a) TB related variables collected by the National TB Control Program in the district of Manhiça for all TB cases starting treatment in the period 2011–2012. b) Population estimates for the district were obtained through the Mozambican National Statistics Institute. c) Deaths and other relevant demographic variables were collected from the Health and Demographic Surveillance System at Manhiça Health Research Center. WHO guidelines were used to define TB cases and treatment outcomes.ResultsOf the 1957 cases starting TB treatment in the period 2011–2012, 294 patients (15.1 %) died during anti-tuberculous treatment. Ten per cent of patients defaulted treatment. The proportion of patients considered to have treatment failure was 1.1 %. HIV infection (OR 2.73; 95 % CI: 1.70–4.38), being female (OR: 1.39; 95 % CI: 1.31–1.91) and lack of laboratory confirmation (OR 1.51; 95 % CI: 1.10–2.08) were associated with dying during the course of TB treatment (p value <0.05). The contribution of TB to the overall death burden of the district for natural reasons was 6.5 % (95 % CI: 5.5–7.6), higher for males than for females (7.8 %; 95 % CI: 6.1–9.5 versus 5.4 %; 95 % CI: 4.1–6.8 respectively). The age group within which TB was responsible for the highest proportion of deaths was 30–34 among males and 20–24 among females (20 % of all deaths in both cases).ConclusionThis study shows a very high proportion of fatal outcomes among TB cases starting treatment. There is a high contribution of TB to the overall causes of mortality. These results call for action in order to improve TB (and TB/HIV) management and thus treatment outcomes of TB patients.

IntroductionEarly diagnosis and initiation to appropriate treatment is vital for tuberculosis (TB) control. The XpertMTB/RIF (Xpert) assay offers rapid TB diagnosis and quantitative estimation of bacterial burden through Cycle threshold (Ct) values. We assessed whether the Xpert Ct value is associated with delayed TB diagnosis as a potential monitoring tool for TB control programme performance.Materials and MethodsThis analysis was nested in a prospective study under the routine TB surveillance procedures of the National TB Control Program in Manhiça district, Maputo province, Mozambique. Presumptive TB patients were tested using smear microscopy and Xpert. We explored the association between Xpert Ct values and self-reported delay of Xpert-positive TB patients as recorded at the time of diagnosis enrolment. Patients with >60 days of TB symptoms were considered to have long delays.ResultsOf 1,483 presumptive TB cases, 580 were diagnosed as TB of whom 505 (87.0%) were due to pulmonary TB and 302 (94.1%) were Xpert positive. Ct values (range, 9.7–46.4) showed a multimodal distribution. The median (IQR) delay was 30 (30–45) days. Ct values showed no correlation with delay (R2 = 0.001, p = 0.621), nor any association with long delays: adjusted odds ratios (AOR) (95% confidence interval [CI]) comparing to >28 cycles 0.99 (0.50–1.96; p = 0.987) for 23–28 cycles, 0.93 (0.50–1.74; p = 0.828) for 16–22 cycles; and 1.05 (0.47–2.36; p = 0.897) for <16 cycles. Being HIV-negative (AOR [95% CI]), 2.05 (1.19–3.51, p = 0.009) and rural residence 1.74 (1.08–2.81, p = 0.023), were independent predictors of long delays.ConclusionXpert Ct values were not associated with patient delay for TB diagnosis and cannot be used as an indicator of TB control program performance.