BackgroundExtrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting.MethodsPatients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases.ResultsPatients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%).ConclusionsWe show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.
BackgroundBloodstream infections (BSI) are frequent and cause high case-fatality rates. Urgent antibiotic treatment can save patients’ lives, but antibiotic resistance can render antibiotic therapy futile. This study is the first to collect epidemiological data on BSI from Unguja, Zanzibar.MethodsClinical data and blood for culturing and susceptibility testing of isolated microbes were obtained from 469 consecutively enrolled neonates, children and adults presenting with signs of systemic infections at Mnazi Mmoja Hospital (MMH), Zanzibar.ResultsPathogenic bacteria were recovered from the blood of 14% of the patients (66/469). The most frequently isolated microbes were Klebsiella pneumoniae, Escherichia coli, Acinetobacter spp. and Staphylococcus aureus. Infections were community-acquired in 56 patients (85%) and hospital-acquired in 8 (12%) (data missing for 2 patients). BSI caused by extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae (E. coli, K. pneumoniae) was found in 5 cases, of which 3 were community-acquired and 2 hospital-acquired. Three of these patients died. Six of 7 Salmonella Typhi isolates were multidrug resistant. Streptococcus pneumoniae was found in one patient only.ConclusionsThis is the first report of ESBL-producing bacteria causing BSI from the Zanzibar archipelago. Our finding of community-acquired BSI caused by ESBL-producing bacteria is alarming, as it implies that these difficult-to-treat bacteria have already spread in the society. In the local setting these infections are virtually impossible to cure. The findings call for increased awareness of rational antibiotic use, infection control and surveillance to counteract the problem of emerging antimicrobial resistance.
BackgroundEarly and proper treatment of tuberculosis could have an important impact on the morbidity, mortality and the economic situation of patients. There is insufficient knowledge on the extent of diagnostic delay and the associated factors in extrapulmonary tuberculosis (EPTB). The aims of this study were to assess the health care seeking behaviour, EPTB knowledge and diagnostic delay in presumptive EPTB patients at the main referral hospital in Zanzibar, factors associated with longer delay, and the impact of untreated EPTB on self-rated health.Materials and methodsProspective data collection using a semi-structured questionnaire in patients presenting with symptoms suggestive of EPTB. The time between the onset of symptoms and first visit to a health care provider (patient delay), and then to the initiation of treatment (health system delay) and total delay were analysed according to sociodemographic and clinical factors and health care seeking trajectories. The EQ-5D-3L was used among the adult EPTB patients to assess the impact of treatment on self-rated health.ResultsOf the 132 patients with median age of 27 years (interquartile range 8–41), 69 were categorized as TB cases and 63 as non-TB cases. The median patient, health system and total delays were 14, 34 and 62 days respectively, among the EPTB patients. A longer health system delay with repeated visits to the same health care level was reported. Significantly better self-rated health status was described after treatment. The knowledge regarding extrapulmonary disease was low.ConclusionMany EPTB patients, presenting to the main referral hospital in Zanzibar, experience a long delay in the initiation of treatment, specially patients with TB lymphadenitis. The health system delay is the major contributor to the total delay. The improvement of self-rated health after treatment implies that timely treatment has the potential to reduce morbidity and the economic loss for the patient.
Background Diagnosing extrapulmonary tuberculosis (EPTB) is challenging and many patients are initiated on empirical anti-TB treatment without a laboratory confirmed diagnosis. Monitoring treatment response is thus important to ensure correct diagnosis and proper disease management. The definition of satisfactory response to treatment in EPTB remains unclear. The objectives of this study were to describe the clinical presentation of EPTB and the effect of treatment on clinical parameters. Further, to assess if simple clinical parameters, without laboratory data, could evaluate treatment response. Methods Prospective cohort study of presumptive EPTB patients at Mnazi Mmoja Hospital, Zanzibar. By using a composite reference standard, patients were categorized as TB or non-TB cases. The TB patients were followed during anti-TB treatment. Results There were 64 TB and 62 non-TB cases. The frequency of symptoms at baseline were comparable in TB and non-TB patients, with lymphadenitis and pleuritis as the most common manifestations. Among TB cases, there was a trend towards regression of lymphadenopathy after 2 months, and at treatment completion 24/28 (86%) cases showed full regression. Weight gain ≥5% was reported in 36/49 (73%) of the TB patients at 2 months and in 38/46 (83%) at treatment completion. After 2 months of treatment, a combination of clinical parameters; improvement of symptoms (50/50), ≥5% weight gain (36/49) and regression of physical signs (45/49) correlated with the treatment response. Conclusions An algorithm including only simple clinical parameters could be used as an easy tool to assess treatment responses in low-resource settings. However, this needs to be tested on a larger sample size.
Primary aldosteronism (PA) is a common cause of secondary hypertension and is caused by unilateral or bilateral adrenal disease. Treatment options depend on whether the disease is lateralized or not, which is preferably evaluated with selective adrenal venous sampling (AVS). This procedure is technically challenging, and obtaining representative samples from the adrenal veins can prove difficult. Unsuccessful AVS procedures often require reexamination. Analysis of cortisol during the procedure may enhance the success rate. We invited 21 consecutive patients to participate in a study with intra-procedural point of care cortisol analysis. When this assay showed nonrepresentative sampling, new samples were drawn after redirection of the catheter. The study patients were compared using the 21 previous procedures. The intra-procedural cortisol assay increased the success rate from 10/21 patients in the historical cohort to 17/21 patients in the study group. In four of the 17 successful procedures, repeated samples needed to be drawn. Successful sampling at first attempt improved from the first seven to the last seven study patients. Point of care cortisol analysis during AVS improves success rate and reduces the need for reexaminations, in accordance with previous studies. Successful AVS is crucial when deciding which patients with PA will benefit from surgical treatment.
Treatment efficacy is difficult to evaluate in extrapulmonary tuberculosis (EPTB) patients. Interferon-γ inducible protein (IP-)10 has been suggested as a biomarker for response to treatment. We have investigated if IP-10 from dried plasma spots (DPS) or dried blood spots (DBS) can be used in treatment monitoring of EPTB patients in a low-resource setting of Zanzibar. IP-10 levels in plasma, DPS and DBS samples collected before, during (2 months) and after TB treatment of 36 EPTB patients (6 culture and/or Xpert MTB/RIF positive and 30 clinically diagnosed) and 8 pulmonary tuberculosis (PTB) patients, were quantified by an enzyme-linked immunosorbent assay. There was a high positive correlation between IP-10 measured in plasma and DPS and DBS, respectively. We found a significant decline in IP-10 levels from baseline to end of treatment in plasma, DPS and DBS, both in EPTB and PTB patients. The declines were observed already after 2 months in HIV negative patients. In conclusion, the DPS/DBS IP-10 assay allows for easy and manageable monitoring in low-resource settings and our findings suggest that IP-10 may serve as a biomarker for treatment efficacy in EPTB patients, albeit further studies in cohorts of patients with treatment failure and relapse are needed.
Background: Extrapulmonary tuberculosis (EPTB) poses diagnostic challenges due to the paucibacillary nature of the disease. The immunochemistry-based MPT64 antigen detection test (MPT64 test) has shown promising results for diagnosing EPTB in previous studies performed in low-resource settings, with higher sensitivity than microscopy and culture. The aim of this study was to investigate the performance of the MPT64 test in a routine clinical setting in a high-income low TB prevalence country. Methods: Extrapulmonary samples sent for TB diagnostics to microbiology and pathology laboratories at three regional tertiary care hospitals in Norway in a one-year period were included and subjected to the MPT64 test in parallel to the routine TB diagnostic tests. Results: Samples from 288 patients were included and categorised as confirmed TB cases (n = 26), clinically diagnosed TB cases (n = 5), non-TB cases (n = 243) and uncategorised (n = 14), using a composite reference standard (CRS). In formalin-fixed biopsies, the sensitivity (95% CI) of the MPT64 test, microscopy, PCR-based tests pooled, and culture was 37% (16-62), 20% (4-48), 37% (16-62) and 50% (23-77), respectively, against the CRS. The MPT64 test showed a good positive predictive value (88%) and an excellent specificity (99, 95% CI 92-100) in formalin-fixed biopsies. In fine-needle aspirates, pus and fluid samples, the test performance was lower. Conclusions: The MPT64 test was implementable in pathology laboratories as part of routine diagnostics, and although the sensitivity of the MPT64 test was not better than culture in this setting, the test supplements other rapid diagnostic methods, including microscopy and PCR-based tests, and can contribute to strengthen the diagnosis of EPTB in formalin-fixed biopsies in the absence of culture confirmation.
Primary aldosteronism (PA) is the most common cause of secondary hypertension (HT). We describe here clinical characteristics, diagnostic procedures, and long-term outcomes in a Norwegian population. All suspected PA patients investigated at a tertiary centre from 1998–2012 were retrospectively evaluated. Inclusion criteria were verified PA after confirmatory testing or otherwise considered highly likely PA. Clinical, biochemical, radiological, and adrenal vein sampling (AVS) findings were analysed. Surgically removed adrenals were re-evaluated histopathologically and tested for somatic mutations. All patients still alive by August 2014 were invited to a follow-up visit. One-hundred and eight patients were included, of whom 85% had a history of hypokalaemia. PA was verified by confirmatory testing in 83 (77%), and AVS performed in 95 (88%) patients. The proportion with AVS-confirmed bilateral PA increased during the study period. Sixty-eight patients (63%) underwent adrenalectomy. KCNJ5 mutations were found in 30% of the surgical specimens and were associated with female sex and a florid PA phenotype. Follow-up visits were undertaken in 73/108 (68%), of whom 52 adrenalectomised. After adrenalectomy, 83% were biochemically cured of PA, but only 21% were cured for HT. Female sex, a verified adenoma, and KCNJ5 mutations were associated with cure of HT. In conclusion, the majority of our patients had unilateral PA and hypokalaemia, indicating that patients with bilateral and milder PA may still be underdiagnosed. Female sex, a histopathological adenoma, and the presence of KCNJ5 mutations predicted cure of HT after adrenalectomy, but the overall cure rate of HT was low.
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