Neoehrlichiosis in Symptomatic Immunocompetent Child, South Africa.

We describe a case of neoehrlichiosis in an immunocompetent child with acute febrile illness in South Africa. Neoehrlichiosis was diagnosed by PCR on 16S rDNA from bone marrow aspirate. Phylogenetic analysis indicated an organism closely related to Candidatus Neoehrlichia. Clinicians should be aware of possible ehrlichiosis even in immunocompetent patients.

Conducting clinical trials-costs, impacts, and the value of clinical trials networks: A scoping review.

BACKGROUND: A significant barrier to conducting clinical trials is their high cost, which is driven primarily by the time and resources required to activate trials and reach accrual targets. The high cost of running trials has a substantial impact on their long-term feasibility and the type of clinical research undertaken. METHODS: A scoping review of the empirical literature on the costs associated with conducting clinical trials was undertaken for the years 2001-2015. Five reference databases were consulted to elicit how trials costs are presented in the literature. A review instrument was developed to extract the content of in-scope papers. Findings were characterized by date and place of publication, clinical disease area, and network/cooperative group designation, when specified. Costs were captured and grouped by patient accrual and management, infrastructure, and the opportunity costs associated with industry funding for trials research. Cost impacts on translational research and health systems were also captured, as were recommendations to reduce trial expenditures. Since articles often cited multiple costs, multiple cost coding was used during data extraction to capture the range and frequency of costs. RESULTS: A total of 288 empirical articles were included. The distribution of reported costs was: patient management and accrual costs (132 articles), infrastructure costs (118 articles) and the opportunity costs of industry sponsorship (72 articles). 221 articles reported on the impact of undertaking costly trials on translational research and health systems; of these, the most frequently reported consequences were to research integrity (52% of articles), research capacity (36% of articles) and running low-value trials (34% of articles). 254 articles provided recommendations to reduce trial costs; of these, the most frequently reported recommendations related to improvements in: operational efficiencies (33% of articles); patient accrual (24% of articles); funding for trials and transparency in trials reporting (18% of articles, each). CONCLUSION: Key findings from the review are: 1) delayed trial activation has costs to budgets and research; 2) poor accrual leads to low-value trials and wasted resources; 3) the pharmaceutical industry can be a pragmatic, if problematic, partner in clinical research; 4) organizational know-how and successful research collaboration are benefits of network/cooperative groups; and 5) there are spillover benefits of clinical trials to healthcare systems, including better health outcomes, enhanced research capacity, and drug cost avoidance. There is a need for more economic evaluations of the benefits of clinical research, such as health system use (or avoidance) and health outcomes in cities and health authorities with institutions that conduct clinical research, to demonstrate the affordability of clinical trials, despite their high cost.

Biofilm formation in invasive Staphylococcus aureus isolates is associated with the clonal lineage.

The contribution of the genetic background of Staphylococcus aureus to biofilm formation is poorly understood. We investigated the association between the genetic background and the biofilm forming ability of clinical invasive S. aureus isolates. Secondary objectives included investigating any correlation with biofilm formation and methicillin resistance or the source of bacteraemia. The study was conducted at a 1300-bed tertiary hospital in Cape Town, South Africa. S. aureus isolates obtained from blood cultures between January 2010 and January 2012 were included. Genotypic characterization was performed by PFGE, spa typing, SCCmec typing and MLST. Thirty genotypically unique strains were assessed for phenotypic biofilm formation with the microtitre plate assay. All isolates were tested in triplicate and an average optical density, measured at a wavelength of 490 nm, was determined. The biofilm forming ability of isolates with A490 ≤ 0.17 were considered non-adherent, A490 > 0.17 'weak positive' and A490 > 0.34 'strong positive'. Fifty seven percent of isolates formed biofilms. Weak biofilm formation occurred in 40% (n = 12) and strong biofilm formation in 17% (n = 5) of isolates. All 5 isolates capable of strong biofilm formation belong to one spa clonal complex (spa-CC 064). Strains from spa-CC 064 were capable of higher biofilm formation than other spa clonal complexes (p = 0.00002). These 5 strains belonged to MLST CC5 and CC8. Biofilm formation correlates with the spa clonal lineage in our population of invasive S. aureus strains. Biofilm formation did not correlate with methicillin resistance and was not related to the source of bacteraemia.

Molecular characterization of Staphylococcus aureus isolates from various healthcare institutions in Nairobi, Kenya: a cross sectional study.

BACKGROUND: Staphylococcus aureus (S. aureus) has established itself over the years as a major cause of morbidity and mortality both within the community and in healthcare settings. Methicillin resistant S. aureus (MRSA) in particular has been a major cause of nosocomial infections resulting in significant increase in healthcare costs. In Africa, the MRSA prevalence has been shown to vary across different countries. In order to better understand the epidemiology of MRSA in a setting, it is important to define its population structure using molecular tools as different clones have been found to predominate in certain geographical locations. METHODS: We carried out PFGE, MLST, SCCmec and spa typing of selected S. aureus isolates from a private and public referral hospital in Nairobi, Kenya. RESULTS: A total of 93 S. aureus isolates were grouped into 19 PFGE clonal complexes (A-S) and 12 singletons. From these, 55 (32 MRSA and 23 MSSA) representative isolates from each PFGE clonal complex and all singletons were spa typed. There were 18 different MRSA spa types and 22 MSSA spa types. The predominant MRSA spa type was t037 comprising 40.6 % (13/32) of all MRSA. In contrast, the MSSA were quite heterogeneous, only 2 out of 23 MSSA shared the same spa type. Two new MRSA spa types (t13149 and t13150) and 3 new MSSA spa types (t13182, t13193 and t13194) were identified. The predominant clonal complex was CC 5 which included multi-locus sequence types 1, 8 and 241. CONCLUSION: In contrast to previous studies published from Kenya, there's marked genetic diversity amongst clinical MRSA isolates in Nairobi including the presence of well-known epidemic MRSA clones. Given that these clones are resident within our referral hospitals, adherence to strict infection control measures needs to be ensured to reduce morbidity and mortality associated with hospital acquired MRSA infections.

[Gastric rupture as a complication of anorexia nervosa]. / Maagruptuur als complicatie van anorexia nervosa.

BACKGROUND: Anorexia nervosa may cause several gastro-intestinal complications. CASE DESCRIPTION: A 21-year-old woman presented herself with abdominal pain and vomiting a day after her first binge-eating episode. In her recent history she had lost 40 kg in weight and her BMI was 15 at presentation. Imaging showed gastric distension and ascites in all quadrants, suspicious of a gastric rupture. A blow-out of the stomach was seen during a diagnostic laparotomy, which was treated with a gastric sleeve procedure. Following surgery, the patient was diagnosed with anorexia nervosa of the restrictive type with a first episode of binge-eating. CONCLUSION: Gastric rupture is a rare and unknown complication of anorexia nervosa with a high mortality.

Mapping the FACT-G cancer-specific quality of life instrument to the EQ-5D and SF-6D.

OBJECTIVE: To help facilitate economic evaluations of oncology treatments, we mapped responses on cancer-specific instrument to generic preference-based measures. METHODS: Cancer patients (n = 367) completed one cancer-specific instrument, the FACT-G, and two preference-based measures, the EQ-5D and SF-6D. Responses were randomly divided to form development (n = 184) and cross-validation (n = 183) samples. Relationships between the instruments were estimated using ordinary least squares (OLS), generalized linear models (GLM), and censored least absolute deviations (CLAD) regression approaches. The performance of each model was assessed in terms of how well the responses to the cancer-specific instrument predicted EQ-5D and SF-6D utilities using mean absolute error (MAE) and root mean squared error (RMSE). RESULTS: Physical, functional, and emotional well-being domain scores of the FACT-G best explained the EQ-5D and SF-6D. In terms of accuracy of prediction as measured in RMSE, the CLAD model performed best for the EQ-5D (RMSE = 0.095) whereas the GLM model performed best for the SF-6D (RMSE = 0.061). The GLM predicted SF-6D scores matched the observed values more closely than the CLAD and OLS. CONCLUSION: Our results demonstrate that the estimation of both EQ-5D and SF-6D utility indices using the FACT-G responses can be achieved. The CLAD model for the EQ-5D and the GLM model for the SF-6D are recommended. Thus, it is possible to estimate quality-adjusted life years for economic evaluation from studies where only cancer-specific instrument have been administered.

Exploring colposcopists' attitudes towards use of HPV testing as a primary screening tool for cervical cancer in British Columbia.

OBJECTIVE: To examine colposcopists' attitudes regarding human papillomavirus (HPV) DNA testing as a primary screening tool for cervical cancer. METHODS: Questionnaires administered in 2010 and 2011 during workshops in British Columbia elicited colposcopists' attitudes using a series of five-point Likert-style scales (strongly disagree to strongly agree) and binary (yes/no) response questions. The frequency of "agree" or "strongly agree" was used to characterize attitudes. Regression analyses examined statistically significant changes in attitudes after the 2010 workshop. RESULTS: Responses generally indicated positive changes in attitudes toward HPV testing. Statistically significant changes after the 2010 workshop were observed for the items relating to strong agreement that HPV is a necessary cause of cervical cancer (39% increase; P < 0.001) and the likelihood of openly advocating for HPV testing (19% increase; P < 0.04). In 2010, 40% of colposcopists stated that four years between HPV tests is too long, and in 2011, 53% did so. CONCLUSION: Colposcopists are viewed as opinion leaders and will have a critical role in implementing HPV testing in BC; our study obtained responses from 73% (2010) and 84% (2011) of BC-registered colposcopists. Colposcopists were in favour of HPV testing for primary screening for cervical cancer but did not support an extended interval for HPV testing, which suggests future knowledge translation workshops are crucial. We found that knowledge translation workshops can be an effective approach for translating evidence on screening and screening practices.

Objectif : Examiner les attitudes des colposcopistes à l'égard du dépistage de l'ADN du virus du papillome humain (VPH) à titre d'outil principal de dépistage du cancer du col utérin. Méthodes : Des questionnaires administrés en 2010 et en 2011 dans le cadre d'ateliers offerts en Colombie-Britannique se sont penchés sur les attitudes des colposcopistes au moyen de séries d'échelles en cinq points de type Likert (de « fortement en désaccord ¼ à « fortement en accord ¼) et de questions à réponse binaire (oui / non). La fréquence des réponses « en accord ¼ ou « fortement en accord ¼ a été utilisée pour caractériser les attitudes. Des analyses de régression ont examiné les modifications significatives sur le plan statistique en ce qui concerne les attitudes à la suite de l'atelier de 2010. Résultats : Les réponses ont généralement indiqué des modifications positives en ce qui concerne les attitudes envers le dépistage du VPH. À la suite de l'atelier de 2010, des modifications significatives sur le plan statistique ont été constatées pour ce qui est des articles liés au fait d'être fortement en accord avec la déclaration voulant que le VPH constitue une cause nécessaire du cancer du col utérin (hausse de 39 %; P < 0,001), ainsi que pour ce qui est de la probabilité de plaider ouvertement en faveur du dépistage du VPH (hausse de 19 %; P < 0,04). En 2010, 40 % des colposcopistes ont déclaré qu'un délai de quatre ans entre les tests de dépistage du VPH était trop long; en 2011, 53 % ont fait une telle déclaration. Conclusion : Les colposcopistes sont perçus comme étant des leaders d'opinion; ils joueront donc un rôle crucial dans la mise en œuvre du dépistage du VPH en Colombie-Britannique. Notre étude a obtenu des réponses de la part de 73 % (2010) et de 84 % (2011) des colposcopistes inscrits en C.-B. Les colposcopistes étaient en faveur de l'utilisation du dépistage du VPH aux fins du dépistage primaire du cancer du col utérin, mais ne soutenaient pas la mise en œuvre d'un intervalle prolongé dans le cadre du dépistage du VPH, ce qui semble indiquer que la tenue de futurs ateliers de transfert des connaissances s'avère cruciale. Nous avons constaté que les ateliers de transfert des connaissances peuvent constituer une approche efficace pour assurer l'application des résultats de recherche au dépistage et aux pratiques connexes.

Xpert MTB/RIF for rapid diagnosis of tuberculous lymphadenitis from fine-needle-aspiration biopsy specimens.

This study demonstrates the excellent diagnostic accuracy of the Xpert MTB/RIF test in patients with tuberculous lymphadenitis. The test sensitivity and specificity were 96.7% (95% confidence interval [CI], 86.6 to 100%) and 88.9% (95% CI, 69.6 to 100%), respectively, and it correctly identified 6/6 (100%) of the cytology smear-negative/culture-positive cases and 1 of 2 (50%) rifampin-resistant cases.

The ability of cancer-specific and generic preference-based instruments to discriminate across clinical and self-reported measures of cancer severities.

OBJECTIVE: To evaluate the validity of cancer-specific and generic preference-based instruments to discriminate across different measures of cancer severities. METHODS: Patients with breast (n = 66), colorectal (n = 57), and lung (n = 61) cancer completed the EORTC QLQ-C30 and the FACT-G, as well as three generic instruments: the EQ-5D, the SF-6D, and the HUI2/3. Disease severity was quantified using cancer stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score, and self-reported health status. Comparative analyses confirmed the multi-dimensional conceptualization of the instruments in terms of construct and convergent validity. RESULTS: In general, the instruments were able to discriminate across severity measures. The instruments demonstrated moderate to strong correlation with each other (r = 0.37-0.73). Not all of the measures could discriminate between different groups of disease severity: the EQ-5D and SF-6D were less discriminative than the HUI2/3 and the cancer-specific instruments. CONCLUSION: The cancer-specific and generic preference-based instruments demonstrated to be valid in discriminating across levels of ECOG-PS scores and self-reported health states. However, the usefulness of the generic instruments may be limited if they are not able to detect small changes in health status within cancer patients. This raises concerns regarding the appropriateness of these instruments when comparing different cancer treatments within an economic evaluation framework.

Cost-effectiveness analysis of primary human papillomavirus testing in cervical cancer screening: Results from the HPV FOCAL Trial.

The Human Papillomavirus FOr CervicAL cancer (HPV FOCAL) trial is a large randomized controlled trial comparing the efficacy of primary HPV testing to cytology among women in the population-based Cervix Screening Program in British Columbia, Canada. We conducted a cost-effectiveness analysis based on the HPV FOCAL trial to estimate the incremental cost per detected high-grade cervical intraepithelial neoplasia of grade 2 or worse lesions (CIN2+). A total of 19,009 women aged 25 to 65 were randomized to one of two study groups. Women in the intervention group received primary HPV testing with reflex liquid-based cytology (LBC) upon a positive finding with a screening interval of 48 months. Women in the control group received primary LBC testing, and those negative returned at 24 months for LBC and again at 48 months for exit screening. Both groups received HPV and LBC co-testing at the 48-month exit. Incremental costs during the course of the trial were comparable between the intervention and control groups. The intervention group had lower overall costs and detected a larger number of CIN2+ lesions, resulting in a lower mean cost per CIN2+ detected ($7551) than the control group ($8325), a difference of -$773 [all costs in 2018 USD]. Cost per detected lesion was sensitive to the costs of sample collection, HPV testing, and LBC testing. The HPV FOCAL Trial results suggest that primary HPV testing every 4 years produces similar outcomes to LBC-based testing every 2 years for cervical cancer screening at a lower cost.

A Patient with speechlessness and rhabdomyolysis: a rare presentation of severe hypocalcaemia.

A 29-year-old man with no medical history presented to our emergency department with episodes of sudden speechlessness, hoarseness, vomiting after drinking cold water and spasms of his hands. Chvostek's and Trousseau's signs were both seen at presentation. Blood tests revealed severe hypocalcaemia (1.03 mmol/L) and rhabdomyolysis (creatine kinase (CK) of 2962 IU/L). The patient was treated immediately with calcium intravenously with an almost immediate improvement of his voice and quick normalisation of his CK. Additional investigation showed primary hypoparathyroidism in the presence of a vitamin D deficiency, requiring lifelong treatment with calcium supplements and alphacalcidol. Severe hypocalcaemia can be life threatening and prompt treatment is essential. This case reports the unusual first presentation of hypocalcaemia via speechlessness and vomiting together with rhabdomyolysis. Identifying an atypical presentation of hypocalcaemia is critical, for it can be lifesaving.

Papanicolaou induced fluorescence, Ziehl-Neelsen and Auramine O stains on lymph node fine needle aspiration biopsy specimens from children: A comparative study.

BACKGROUND: The rapid diagnosis of extrapulmonary tuberculosis in children remains challenging. The presence of enlarged lymph nodes provides an opportunity to obtain diagnostic material through fine needle aspiration biopsy (FNAB). Mycobacterial culture, traditionally the reference standard, has a slow turnaround time and PCR-based methods are not widely available in developing countries. Direct visualization of mycobacteria on microscopy can be a rapid method to confirm the diagnosis. This study compared three staining methods to visualize mycobacteria. METHODS: Hundred FNAB specimens from persistently enlarged lymph nodes in children, clinically suspicious for tuberculosis, were evaluated for the presence of mycobacteria by three staining methods: Papanicolaou induced fluorescence (PIF) and Auramine O staining using fluorescence microscopy and Ziehl-Neelsen (ZN) staining using conventional light microscopy. These methods were evaluated against mycobacterial culture. RESULTS: PIF positivity was 30%, with 38% and 48% for Auramine O and ZN respectively. The combined ZN/PIF positivity was 56%. The highest diagnostic accuracy (73%) was demonstrated by ZN alone and in combination with PIF, with PIF alone showing the lowest (49%) accuracy. Although the combined test showed the highest sensitivity, it had the lowest specificity, while ZN was significantly more sensitive than both other staining modalities. No statistical difference in specificity was seen among the tests. CONCLUSION: This study suggests that Auramine O staining on previously ZN stained slides does not significantly improve diagnostic accuracy. While currently widely available methods of direct visualization of mycobacteria suffer from low sensitivity, the ZN stain remains a useful diagnostic test, particularly in resource-constrained countries.

Symptom Clusters in Advanced Cancer Patients: An Empirical Comparison of Statistical Methods and the Impact on Quality of Life.

CONTEXT: Symptom clusters in advanced cancer can influence patient outcomes. There is large heterogeneity in the methods used to identify symptom clusters. OBJECTIVES: To investigate the consistency of symptom cluster composition in advanced cancer patients using different statistical methodologies for all patients across five primary cancer sites, and to examine which clusters predict functional status, a global assessment of health and global quality of life. METHODS: Principal component analysis and exploratory factor analysis (with different rotation and factor selection methods) and hierarchical cluster analysis (with different linkage and similarity measures) were used on a data set of 1562 advanced cancer patients who completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. RESULTS: Four clusters consistently formed for many of the methods and cancer sites: tense-worry-irritable-depressed (emotional cluster), fatigue-pain, nausea-vomiting, and concentration-memory (cognitive cluster). The emotional cluster was a stronger predictor of overall quality of life than the other clusters. Fatigue-pain was a stronger predictor of overall health than the other clusters. The cognitive cluster and fatigue-pain predicted physical functioning, role functioning, and social functioning. CONCLUSIONS: The four identified symptom clusters were consistent across statistical methods and cancer types, although there were some noteworthy differences. Statistical derivation of symptom clusters is in need of greater methodological guidance. A psychosocial pathway in the management of symptom clusters may improve quality of life. Biological mechanisms underpinning symptom clusters need to be delineated by future research. A framework for evidence-based screening, assessment, treatment, and follow-up of symptom clusters in advanced cancer is essential.

Commercial nucleic acid amplification tests in tuberculous meningitis--a meta-analysis.

Although nucleic acid amplification tests (NAATs) promise a rapid, definitive diagnosis of tuberculous meningitis, the performance of first-generation NAATs was suboptimal and variable. We conducted a meta-analysis of studies published between 2003 and 2013, using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool to evaluate methodological quality. The diagnostic accuracy of newer commercial NAATs was assessed. Pooled estimates of diagnostic accuracy for commercial NAATs measured against a cerebrospinal fluid Mycobacterium tuberculosis culture-positive gold standard were sensitivity 0.64, specificity 0.98, and diagnostic odds ratio 64.0. Heterogeneity was limited; P value = 0.147 and I(2) = 33.85%. The Xpert MTB/RIF® test was evaluated in 1 retrospective study and 4 prospective studies, with pooled sensitivity 0.70 and specificity 0.97. The QUADAS-2 tool revealed low risk of bias, as well as low concerns regarding applicability. Heterogeneity was pronounced among studies of in-house tests. Commercial NAATs proved to be highly specific with greatly reduced heterogeneity compared to in-house tests. Sub-optimal sensitivity remains a limitation.

Emergence and treatment of multidrug resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in South Africa.

Drug resistant tuberculosis (TB) has reached alarming proportions in South Africa, draining valuable resources that are needed to fight drug susceptible TB. It is currently estimated that 9.6% of all TB cases have multi-drug resistant (MDR)-TB, thereby ranking South Africa as one of the highest MDR-TB burden countries in the world. Molecular epidemiological studies have demonstrated the complexity of the epidemic and have clearly shown that the epidemic is driven by transmission as a consequence of low cases detection and diagnostic delay. The latter has in turn fueled the amplification of drug resistance, ultimately leading to the emergence of extensively drug resistant (XDR)-TB. Despite the introduction of new drugs to combat this scourge, culture conversion rates for XDR-TB remain below 20%. Failure to achieve cure may be explained from DNA sequencing results which have demonstrated mutations in 7 genes encoding resistance to at least 8 anti-TB drugs. This review shows how molecular epidemiology has provided novel insights into the MDR-TB epidemic in South Africa and thereby has highlighted the challenges that need to be addressed regarding the diagnosis and treatment of MDR-TB. An important step towards for curbing this epidemic will be collaboration between clinicians, laboratories and researchers to establish scientific knowledge and medical expertise to more efficiently guide public health policy.

Detecting drug-resistant tuberculosis: the importance of rapid testing.

Despite numerous intervention strategies, including the direct observed short-course treatment strategy and improved diagnostic methods, the incidence of multidrug-resistant and extensively drug-resistant tuberculosis (TB) continues to rise globally. Many treatment policies are based on the model that acquisition of drug resistance in already infected individuals drives the drug-resistant TB epidemic, hence the focus on drug-resistance testing of retreatment cases. However, molecular epidemiology and mathematical modeling suggest that the majority of multidrug-resistant TB cases are due to ongoing transmission of multidrug-resistant strains. This is most likely the result of diagnostic delay, thereby emphasizing the need for rapid diagnostics and comprehensive contact tracing, as well as active case finding. Current diagnosis of TB in low-income, high-burden regions relies on smear microscopy and clinical signs and symptoms. However, this smear-centered approach has many pitfalls, including low sensitivity in HIV patients and children, the inability of smear to reveal drug-resistance patterns, and the need for sampling on consecutive days. In order to address these limitations, efforts have been made to expand access to Mycobacterium tuberculosis culture and drug susceptibility testing. However, the slow growth rate of the causative agent, M. tuberculosis, contributes to significant diagnostic delay. Molecular-based diagnostic methods, targeting mutations that are known to confirm drug resistance, are capable of significantly reducing diagnostic delay. Two such methods, the line-probe assay and the real-time PCR-based Xpert® MTB/RIF assay, have been described. The latter test shows particular promise for smear-negative and extrapulmonary specimens. This may prove especially useful in settings where co-infection rates with HIV are high. However, since most research focuses on the performance of both of these assays, further investigations need to be done regarding the impact of the routine implementation of these assays on TB control programs and the cost effectiveness thereof.

Tuberculosis assays: past, present and future.

Recent developments in the field of TB diagnostics, including the introduction of the Xpert MTB/RIF assay in field testing, raise the hope for faster and more accurate identification of active TB patients. However, there are still many issues that need to be addressed as no point-of-care tests are yet available. Furthermore, no tests are available which are universally applicable to all patients. Improvements in the microbiological and molecular-based approaches are promising and the diagnostic pipeline is encouraging. Host markers associated with active disease may hold promise, especially in situations where sputum diagnostics are problematic, including in children, HIV-infected individuals and in the case of extrapulmonary TB.

UNSUSPECTED FATAL DRUG-RESISTANT TUBERCULOSIS IN A CLOSELY MONITORED CHILD: A PLEA FOR IMPROVED SOURCE-CASE TRACING AND DRUG SUSCEPTIBILITY TESTING.

We report a case of rapidly progressive miliary tuberculosis in a 21-month old HIV-infected girl exposed to tuberculosis, despite early access to highly active antiretroviral therapy and proven adherence to isoniazid chemoprophylaxis. Post mortem revealed multidrug-resistant tuberculosis. This case report illustrates the consequences of inadequate programmatic management of children exposed to an adult case of sputum smear-positive multidrug-resistant tuberculosis. Drug susceptibility testing of the adult source case should become standard of care for all children who have been in close contact with a case of sputum smear-positive tuberculosis, and the choice of chemoprophylactic agents should be based on the sensitivities of the source case organism.

Combining fine-needle aspiration biopsy (FNAB) and high-resolution melt analysis to reduce diagnostic delay in Mycobacterial lymphadenitis.

Tuberculous lymphadenitis is the most common cause of extra-pulmonary tuberculosis (TB) in developing countries. Lymphadenitis caused by non-tuberculous mycobacteria (NTM) requires consideration, particularly in immunocompromised patients and children in developed countries. Fine-Needle Aspiration Biopsy (FNAB) offers a valuable specimen collection technique, but culture confirmation, mycobacterial speciation and drug resistance testing (if indicated) is often unavailable in TB endemic areas and result in unacceptable diagnostic delay. We evaluated the diagnostic value of high-resolution DNA melting (HRM) analysis in the diagnosis of mycobacterial lymphadenopathy using FNAB and an inexpensive transport medium. Specimens were collected from patients referred to the FNAB Clinic at Tygerberg Hospital (June 2007-May 2008) with clinical mycobacterial lymphadenitis. Cytology, culture, and HRM were performed on all specimens. The reference standard for disease was defined as positive cytology (morphological evidence plus mycobacterial visualization) and/or a positive culture. Specimens were collected from 104 patients and mycobacterial disease was confirmed in 54 (51.9%); 52 Mycobacterium tuberculosis, 1 Mycobacterium Bovis BCG and 1 NTM. Cytology was positive in 83.3% (45/54) and culture in 72.2% (39/54) of patients. HRM identified 57.4% (31/54) of cases. By using the defined reference standard, we recorded 94.0% specificity and 51.9% sensitivity (positive predictive value 90.3%) with HRM analysis.HRM analysis allowed rapid and species specific diagnosis of mycobacterial lymph adenitis in the majority of patients, permitting early institution of appropriate therapy. Optimization of this technique requires further study.