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Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive. We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR. Participants were screened for TB symptoms and received a chest X-ray. Sputum samples of four consecutive individuals were pooled and tested with Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Xpert-MTB/RIF) (2020) or Xpert-Ultra (2021). The agreement of the individual and pooled samples was compared and the reasons for discrepant results and potential cartridge savings were assessed. Each survey included 436 participants, which were tested in 109 pools. In the Xpert-MTB/RIF survey, 25 (sensitivity 89%, 95% CI 72.8% to 96.3%) of 28 pools containing MTB-positive samples tested positive and 81 pools containing only MTB-negative samples tested negative (specificity 100%, 95% CI 95.5% to 100%). In the Xpert-Ultra survey, all 32 (sensitivity 100%, 95% CI 89.3% to 100%) pools containing MTB-positive samples tested positive and all 77 (specificity 100%, 95% CI 95.3% to 100%) containing only MTB-negative samples tested negative. Pooling with Xpert-MTB/RIF and Xpert-Ultra saved 52% and 46% (227/436 and 199/436, respectively) of cartridge costs alone. Testing single and pooled specimens had a high level of agreement, with complete concordance when using Xpert-Ultra. Pooling samples could generate significant cartridge savings during ACF campaigns.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells. Plaque reduction neutralisation tests (PRNT) detect NAb, but are not amenable to mass testing as they take several days and require use of SARS-CoV-2 in high biocontainment laboratories. We evaluated the ability of IgG and IgM ELISAs targeting SARS-CoV-2 spike subunit 1 receptor binding domain (S1-RBD), and spike subunit 2 (S2) and nucleocapsid protein (NP), at predicting the presence and magnitude of NAb determined by PRNT. IgG S2 + NP ELISA was 96.8% [95% CI 83.8–99.9] sensitive and 88.9% [95% CI 51.8–99.7] specific at predicting the presence of NAbs (PRNT80 > 1:40). IgG and IgM S1-RBD ELISAs correlated with PRNT titre, with higher ELISA results increasing the likelihood of a robust neutralising response. The IgM S1-RBD assay can be used as a rapid, high throughput test to approximate the magnitude of NAb titre.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells. Plaque reduction neutralisation tests (PRNT) detect NAb, but are not amenable to mass testing as they take several days and require use of SARS-CoV-2 in high biocontainment laboratories. We evaluated the ability of IgG and IgM ELISAs targeting SARS-CoV-2 spike subunit 1 receptor binding domain (S1-RBD), and spike subunit 2 (S2) and nucleocapsid protein (NP), at predicting the presence and magnitude of NAb determined by PRNT. IgG S2 + NP ELISA was 96.8% [95% CI 83.8–99.9] sensitive and 88.9% [95% CI 51.8–99.7] specific at predicting the presence of NAbs (PRNT80 > 1:40). IgG and IgM S1-RBD ELISAs correlated with PRNT titre, with higher ELISA results increasing the likelihood of a robust neutralising response. The IgM S1-RBD assay can be used as a rapid, high throughput test to approximate the magnitude of NAb titre.

Background: There are an abundance of commercially available lateral flow assays (LFAs) that detect antibodies to SARS-CoV-2. Whilst these are usually evaluated by the manufacturer, externally performed diagnostic accuracy studies to assess performance are essential. Herein we present an evaluation of 12 LFAs. Methods: Sera from 100 SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) positive participants were recruited through the FASTER study. A total of 105 pre-pandemic sera from participants with other infections were included as negative samples. Results: At presentation sensitivity against RT-PCR ranged from 37.4 to 79% for IgM/IgG, 30.3–74% for IgG, and 21.2–67% for IgM. Sensitivity for IgM/IgG improved ≥ 21 days post symptom onset for 10/12 tests. Specificity ranged from 74.3 to 99.1% for IgM/IgG, 82.9–100% for IgG, and 75.2–98% for IgM. Compared to the EuroImmun IgG enzyme-linked immunosorbent assay (ELISA), sensitivity and specificity ranged from 44.6 to 95.4% and 85.4–100%, respectively. Conclusion: There are many LFAs available with varied sensitivity and specificity. Understanding the diagnostic accuracy of these tests will be vital as we come to rely more on the antibody status of a person moving forward, and as such manufacturer-independent evaluations are crucial.

We investigated the dynamics of seroconversion in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. During March 29-May 22, 2020, we collected serum samples and associated clinical data from 177 persons in London, UK, who had SARS-CoV-2 infection. We measured IgG against SARS-CoV-2 and compared antibody levels with patient outcomes, demographic information, and laboratory characteristics. We found that 2.0%-8.5% of persons did not seroconvert 3-6 weeks after infection. Persons who seroconverted were older, were more likely to have concurrent conditions, and had higher levels of inflammatory markers. Non-White persons had higher antibody concentrations than those who identified as White; these concentrations did not decline during follow-up. Serologic assay results correlated with disease outcome, race, and other risk factors for severe SARS-CoV-2 infection. Serologic assays can be used in surveillance to clarify the duration and protective nature of humoral responses to SARS-CoV-2 infection.

Individuals infected with SARS-CoV-2 develop neutralising antibodies. We investigated the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how this proportion varies with selected covariates. Methodology/Principal findings This systematic review and meta-analysis examined the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how these proportions vary with selected covariates. Three models using the maximum likelihood method assessed these proportions by study group, covariates and individually extracted data (protocol CRD42020208913). A total of 983 reports were identified and 27 were included. The pooled (95%CI) proportion of individuals with neutralising antibodies was 85.3% (83.5–86.9) using the titre cut off >1:20 and 83.9% (82.2–85.6), 70.2% (68.1–72.5) and 54.2% (52.0–56.5) with titres >1:40, >1:80 and >1:160, respectively. These proportions were higher among patients with severe COVID-19 (e.g., titres >1:80, 84.8% [80.0–89.2], >1:160, 74.4% [67.5–79.7]) than those with mild presentation (56.7% [49.9–62.9] and 44.1% [37.3–50.6], respectively) and lowest among asymptomatic infections (28.6% [17.9–39.2] and 10.0% [3.7–20.1], respectively). IgG and neutralising antibody levels correlated poorly. Conclusions/Significance 85% of individuals with proven SARS-CoV-2 infection had detectable neutralising antibodies. This proportion varied with disease severity, study setting, time since infection and the method used to measure antibodies.

Altres ajuts: EDCTP grant number DRIA2014-309; TB REACH award grant number CA-3-D000920001, There is a need for diagnostics for tuberculosis (TB) that are easy to use, able to screen non-sputum samples, and able to provide rapid results for the management of both immunocompromised and immunocompetent individuals. The Fujifilm SILVAMP TB LAM (FujiLAM) assay, a new non-sputum based point of need test for the diagnosis of TB, could potentially address most of these needs. We evaluated the performance of FujiLAM in HIV positive and HIV negative patients with presumptive TB attending three district hospitals in Nigeria. Consecutive patients were asked to provide urine samples on the spot, which were tested with FujiLAM. The results were compared against a positive culture and/or Xpert MTB/RIF as the reference standard. Forty-five patients had bacteriologically confirmed TB, and 159 had negative culture and Xpert MTB/RIF (no TB). The FujiLAM test was positive in 23 (sensitivity 65.7%, 95% CI = 48-80) HIV negative and seven (70%, 95% CI = 35-92) HIV positive patients with bacteriological confirmation of TB. FujiLAM was negative in 97 (specificity 99.0%, 95% CI = 94-100) HIV negative and 56 (93.3%, 95% CI = 83-98) HIV positive patients without TB. The FujiLAM test has good diagnostic accuracy for considering its application in both HIV positive and HIV negative patients with TB.

Individuals infected with SARS-CoV-2 develop neutralising antibodies. We investigated the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how this proportion varies with selected covariates. Methodology/Principal findings This systematic review and meta-analysis examined the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how these proportions vary with selected covariates. Three models using the maximum likelihood method assessed these proportions by study group, covariates and individually extracted data (protocol CRD42020208913). A total of 983 reports were identified and 27 were included. The pooled (95%CI) proportion of individuals with neutralising antibodies was 85.3% (83.5–86.9) using the titre cut off >1:20 and 83.9% (82.2–85.6), 70.2% (68.1–72.5) and 54.2% (52.0–56.5) with titres >1:40, >1:80 and >1:160, respectively. These proportions were higher among patients with severe COVID-19 (e.g., titres >1:80, 84.8% [80.0–89.2], >1:160, 74.4% [67.5–79.7]) than those with mild presentation (56.7% [49.9–62.9] and 44.1% [37.3–50.6], respectively) and lowest among asymptomatic infections (28.6% [17.9–39.2] and 10.0% [3.7–20.1], respectively). IgG and neutralising antibody levels correlated poorly. Conclusions/Significance 85% of individuals with proven SARS-CoV-2 infection had detectable neutralising antibodies. This proportion varied with disease severity, study setting, time since infection and the method used to measure antibodies.

Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture, and the limited sensitivity of lateral flow tests. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty eight out of thirty nine participants were able to self-collect an adequate sample of capillary blood (≥ 50 µl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen’s kappa coefficient of > 0.88 (near-perfect agreement, 95% CI 0.738–1.000). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

PCR of upper respiratory specimens is the diagnostic standard for severe acute respiratory syndrome coronavirus 2 infection. However, saliva sampling is an easy alternative to nasal and throat swabbing. We found similar viral loads in saliva samples and in nasal and throat swab samples from 110 patients with coronavirus disease.

Dengue is the most common mosquito-borne virus, and a major cause of fever, with an estimated 390 million infections annually. Guatemala, in Central America, has had ongoing dengue transmission since the 1990s. Its national surveillance system monitors outbreaks and seasonal trends of infections to inform public health responses. We have analysed 17 years of surveillance data collected from 2000 to 2016, to describe seasonal trends, outbreak years, and the fluctuating prevalence of the four dengue serotypes. Laboratory data from 91,554 individual serum samples were included, of which 7.8% were positive for dengue. All four dengue serotypes circulate in the country, with dengue 1 and 2 being the predominant serotypes. This is important, as it increases the likelihood of dengue infections being followed by a new infection with a different serotype, which can lead to severe dengue. We also report that adults in Guatemala have a lower likelihood of infection the year after an epidemic, which might be linked to an increased immunity in the population. Dengue fever occurs worldwide and about 1% of cases progress to severe haemorrhage and shock. Dengue is endemic in Guatemala and its surveillance system could document long term trends. We analysed 17 years of country-wide dengue surveillance data in Guatemala to describe epidemiological trends from 2000 to 2016.Data from the national dengue surveillance database were analysed to describe dengue serotype frequency, seasonality, and outbreaks. We used Poisson regression models to compare the number of cases each year with subsequent years and to estimate incidence ratios within serotype adjusted by age and gender. 91,554 samples were tested. Dengue was confirmed by RT-qPCR, culture or NS1-ELISA in 7097 (7.8%) cases and was IgM ELISA-positive in 19,290 (21.1%) cases. DENV1, DENV2, DENV3, and DENV4 were detected in 2218 (39.5%), 2580 (45.9%), 591 (10.5%), and 230 (4.1%) cases. DENV1 and DENV2 were the predominant serotypes, bu

Dengue is the most common mosquito-borne virus, and a major cause of fever, with an estimated 390 million infections annually. Guatemala, in Central America, has had ongoing dengue transmission since the 1990s. Its national surveillance system monitors outbreaks and seasonal trends of infections to inform public health responses. We have analysed 17 years of surveillance data collected from 2000 to 2016, to describe seasonal trends, outbreak years, and the fluctuating prevalence of the four dengue serotypes. Laboratory data from 91,554 individual serum samples were included, of which 7.8% were positive for dengue. All four dengue serotypes circulate in the country, with dengue 1 and 2 being the predominant serotypes. This is important, as it increases the likelihood of dengue infections being followed by a new infection with a different serotype, which can lead to severe dengue. We also report that adults in Guatemala have a lower likelihood of infection the year after an epidemic, which might be linked to an increased immunity in the population. Dengue fever occurs worldwide and about 1% of cases progress to severe haemorrhage and shock. Dengue is endemic in Guatemala and its surveillance system could document long term trends. We analysed 17 years of country-wide dengue surveillance data in Guatemala to describe epidemiological trends from 2000 to 2016.Data from the national dengue surveillance database were analysed to describe dengue serotype frequency, seasonality, and outbreaks. We used Poisson regression models to compare the number of cases each year with subsequent years and to estimate incidence ratios within serotype adjusted by age and gender. 91,554 samples were tested. Dengue was confirmed by RT-qPCR, culture or NS1-ELISA in 7097 (7.8%) cases and was IgM ELISA-positive in 19,290 (21.1%) cases. DENV1, DENV2, DENV3, and DENV4 were detected in 2218 (39.5%), 2580 (45.9%), 591 (10.5%), and 230 (4.1%) cases. DENV1 and DENV2 were the predominant serotypes, bu

OBJECTIVE: We assessed the impact of political conflict (Boko Haram) on tuberculosis (TB) case noti?cations in Adamawa State in North-east Nigeria. DESIGN: A retrospective analysis of TB case notifications from TB registers (2010-2016) to describe changes in TB notification, sex and age ratios by the degree of conflict by local government area. SETTING: Adamawa State. PARTICIPANTS: 21?076 TB cases notified. RESULTS: 21?076 cases (62% male) were noti?ed between 2010 and 2016, of which 19 604 (93%) were new TB cases. Areas affected by conflict in 2014 and 2015 had decreased case notification while neighbouring areas reported increased case notifications. The male to female ratio of TB cases changed in areas in conflict with more female cases being notified. The young and elderly (1-14 and >65 years old) had low notifications in all areas,with a small increase in case notifications during the years of conflict. CONCLUSION: TB case notifications decreased in conflict areas and increased in areas without conflict. More males were notified during peace times and more female cases were reported from areas in conflict. Young and elderly populations had decreased case notifications but experienced a slight increase during the conflict years. These changes are likely to reflect population displacement and a dissimilar effect of conflict on the accessibility of services. TB services in conflict areas deserve further study to identify resilient approaches that could reach affected populations., BMJ open, 10(9), art.no.e035263; 2020

Dengue is the most common mosquito-borne virus, and a major cause of fever, with an estimated 390 million infections annually. Guatemala, in Central America, has had ongoing dengue transmission since the 1990s. Its national surveillance system monitors outbreaks and seasonal trends of infections to inform public health responses. We have analysed 17 years of surveillance data collected from 2000 to 2016, to describe seasonal trends, outbreak years, and the fluctuating prevalence of the four dengue serotypes. Laboratory data from 91,554 individual serum samples were included, of which 7.8% were positive for dengue. All four dengue serotypes circulate in the country, with dengue 1 and 2 being the predominant serotypes. This is important, as it increases the likelihood of dengue infections being followed by a new infection with a different serotype, which can lead to severe dengue. We also report that adults in Guatemala have a lower likelihood of infection the year after an epidemic, which might be linked to an increased immunity in the population. Dengue fever occurs worldwide and about 1% of cases progress to severe haemorrhage and shock. Dengue is endemic in Guatemala and its surveillance system could document long term trends. We analysed 17 years of country-wide dengue surveillance data in Guatemala to describe epidemiological trends from 2000 to 2016.Data from the national dengue surveillance database were analysed to describe dengue serotype frequency, seasonality, and outbreaks. We used Poisson regression models to compare the number of cases each year with subsequent years and to estimate incidence ratios within serotype adjusted by age and gender. 91,554 samples were tested. Dengue was confirmed by RT-qPCR, culture or NS1-ELISA in 7097 (7.8%) cases and was IgM ELISA-positive in 19,290 (21.1%) cases. DENV1, DENV2, DENV3, and DENV4 were detected in 2218 (39.5%), 2580 (45.9%), 591 (10.5%), and 230 (4.1%) cases. DENV1 and DENV2 were the predominant serotypes, bu

Dengue is the most common mosquito-borne virus, and a major cause of fever, with an estimated 390 million infections annually. Guatemala, in Central America, has had ongoing dengue transmission since the 1990s. Its national surveillance system monitors outbreaks and seasonal trends of infections to inform public health responses. We have analysed 17 years of surveillance data collected from 2000 to 2016, to describe seasonal trends, outbreak years, and the fluctuating prevalence of the four dengue serotypes. Laboratory data from 91,554 individual serum samples were included, of which 7.8% were positive for dengue. All four dengue serotypes circulate in the country, with dengue 1 and 2 being the predominant serotypes. This is important, as it increases the likelihood of dengue infections being followed by a new infection with a different serotype, which can lead to severe dengue. We also report that adults in Guatemala have a lower likelihood of infection the year after an epidemic, which might be linked to an increased immunity in the population. Dengue fever occurs worldwide and about 1% of cases progress to severe haemorrhage and shock. Dengue is endemic in Guatemala and its surveillance system could document long term trends. We analysed 17 years of country-wide dengue surveillance data in Guatemala to describe epidemiological trends from 2000 to 2016.Data from the national dengue surveillance database were analysed to describe dengue serotype frequency, seasonality, and outbreaks. We used Poisson regression models to compare the number of cases each year with subsequent years and to estimate incidence ratios within serotype adjusted by age and gender. 91,554 samples were tested. Dengue was confirmed by RT-qPCR, culture or NS1-ELISA in 7097 (7.8%) cases and was IgM ELISA-positive in 19,290 (21.1%) cases. DENV1, DENV2, DENV3, and DENV4 were detected in 2218 (39.5%), 2580 (45.9%), 591 (10.5%), and 230 (4.1%) cases. DENV1 and DENV2 were the predominant serotypes, bu

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area.

BackgroundSputum smear microscopy is the most widely available diagnostic test for pulmonary tuberculosis in countries with a high burden of the disease. Improving its accuracy is crucial to achievement of case-detection targets established by the Millennium Development Goals. Unfortunately, many patients are unable to submit all of the specimens needed for examination or to return for treatment because standard sputum collection and reporting requires several clinic visits. To inform policy recommendations by a WHO-convened Expert Group, we aimed to assess the accuracy of sputum smear examination with strategies for obtaining sputum on 1 day compared with strategies for obtaining sputum over 2 days.MethodsWe did a systematic review and meta-analysis of research articles comparing the accuracy of front-loaded or same-day microscopy and standard sputum smear microscopy for diagnosis of culture-confirmed pulmonary tuberculosis. We searched Medline, Embase, Biosis, and Web of Science for articles published between Jan 1, 2005, and Feb 14, 2012. Two investigators identified eligible articles and extracted data for individual study sites. We generated pooled summary estimates (95% CIs) for sensitivity and specificity by use of random-effects meta-analysis when four or more studies were available.FindingsWe identified eight relevant studies from five articles enrolling 7771 patients with suspected tuberculosis in low-income countries. Compared with the standard approach of examination of two smears with Ziehl-Neelsen light microscopy over 2 days, examination of two smears taken on the same day had much the same sensitivity (64% [95% CI 60 to 69] for standard microscopy vs 63% [58 to 68] for same-day microscopy) and specificity (98% [97 to 99] vs 98% [97 to 99]). We noted similar results for studies employing light-emitting diode fluorescence microscopy and for studies examining three smears, whether they were compared with two-smear strategies or with one another.Interpre

We identified 21 rotaviruses in 129 patients with diarrhea in a Brazilian city with high rotavirus vaccine coverage. All rotaviruses were genotype P[4]G2 with 1 mixed infection with P[NT]G9. Although virus predominance could have occurred randomly, the vaccine may be less protective against P[4]G2. Prospective surveillance is urgently needed., Emerging Infectious Diseases 13(10), pp.1571-1573; 2007

Contacts of adults with tuberculosis (TB) are at risk for infection. Tests based on interferon-gamma (IFN-gamma) expression in response to Mycobacterium tuberculosis antigens may be more sensitive than the tuberculin skin test (TST). Risk for infection was assessed by using TST and an IFN-y-based assay (QuantiFERON Gold in Tube [QFT-IT] test) for 207 children in Nigeria in 1 of 3 groups: contact with adults with smear-positive TB, contact with adults with smear-negative TB, and controls. For these 3 groups, respectively, TST results were >10 mm for 38 (49%) of 78, 13 (16%) of 83, and 6 (13%) of 46 and QFT-IT positive for 53 (74%) of 72, 8 (10%) of 81, and 4 (10.3%) of 39 (p < 0.01). Most test discrepancies were TST negative; QFT-IT positive if in contact with TB-positive persons; and TST positive, QFT-IT negative if in contact with TB-negative persons or controls. TST may underestimate risk for infection with TB in children.

Contacts of adults with tuberculosis (TB) are at risk for infection. Tests based on interferon-gamma (IFN-gamma) expression in response to Mycobacterium tuberculosis antigens may be more sensitive than the tuberculin skin test (TST). Risk for infection was assessed by using TST and an IFN-y-based assay (QuantiFERON Gold in Tube [QFT-IT] test) for 207 children in Nigeria in 1 of 3 groups: contact with adults with smear-positive TB, contact with adults with smear-negative TB, and controls. For these 3 groups, respectively, TST results were >10 mm for 38 (49%) of 78, 13 (16%) of 83, and 6 (13%) of 46 and QFT-IT positive for 53 (74%) of 72, 8 (10%) of 81, and 4 (10.3%) of 39 (p < 0.01). Most test discrepancies were TST negative; QFT-IT positive if in contact with TB-positive persons; and TST positive, QFT-IT negative if in contact with TB-negative persons or controls. TST may underestimate risk for infection with TB in children.

Contacts of adults with tuberculosis (TB) are at risk for infection. Tests based on interferon-gamma (IFN-gamma) expression in response to Mycobacterium tuberculosis antigens may be more sensitive than the tuberculin skin test (TST). Risk for infection was assessed by using TST and an IFN-y-based assay (QuantiFERON Gold in Tube [QFT-IT] test) for 207 children in Nigeria in 1 of 3 groups: contact with adults with smear-positive TB, contact with adults with smear-negative TB, and controls. For these 3 groups, respectively, TST results were >10 mm for 38 (49%) of 78, 13 (16%) of 83, and 6 (13%) of 46 and QFT-IT positive for 53 (74%) of 72, 8 (10%) of 81, and 4 (10.3%) of 39 (p < 0.01). Most test discrepancies were TST negative; QFT-IT positive if in contact with TB-positive persons; and TST positive, QFT-IT negative if in contact with TB-negative persons or controls. TST may underestimate risk for infection with TB in children.

Rapid progress has been made in the development of new diagnostic assays for tuberculosis in recent years. New technologies have been developed and assessed, and are now being implemented. The Xpert MTB/RIF assay, which enables simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance, was endorsed by WHO in December, 2010. This assay was specifically recommended for use as the initial diagnostic test for suspected drug-resistant or HIV-associated pulmonary tuberculosis. By June, 2012, two-thirds of countries with a high tuberculosis burden and half of countries with a high multidrug-resistant tuberculosis burden had incorporated the assay into their national tuberculosis programme guidelines. Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event, clinical and programmatic effects and cost-effectiveness remain to be defined. We review the rapidly growing body of scientific literature and discuss the advantages and challenges of using the Xpert MTB/RIF assay in areas where tuberculosis is endemic. We also review other prospects within the developmental pipeline. A rapid, accurate point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. Investment in the tuberculosis diagnostics pipeline should remain a major priority for funders and researchers.

Background Type 2 diabetes mellitus (DM) and HIV increase the risk of tuberculosis (TB). The frequency of DM among patients with TB with and without HIV is poorly documented in many low- and middle-income countries. Methods This was a cross-sectional hospital-based study performed in Abuja, Nigeria. Adults with presumptive TB were screened consecutively. Sputum culture was used for TB screening and blood was used for HIV screening, as well as fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) assessment for the diagnosis of DM. HbA1c was measured using the D-10 Haemoglobin Testing System and a point-of-care test (A1C Now+ system) for comparison. Patients were classified as having DM or pre-diabetes using the D-10 reference test. Results Four hundred and ten individuals had TB culture, FPG, and HbA1c results. Participants had a mean (± standard deviation) age of 37.8 ± 12.6 years and 217 (54.8%) were male. One hundred and thirteen (27.6%) patients were culture-positive, 62 (15.1%) had DM, and 46 (11.2%) had pre-diabetes. One hundred and eighty-four (53.3%) participants were HIV-positive and 95 (51.6%) were on antiretroviral therapy (ART). Patients with pre-diabetes and DM were more likely to have TB (odds ratio (OR) 1.94, 95% confidence interval (CI) 0.01–3.74, and OR 2.39, 95% CI 1.35–4.24, respectively). After adjustment for HIV, age, and sex, only DM was statistically associated with TB (adjusted OR (AOR) 3.10, 95% CI 1.62–5.94). HIV-negative patients with DM had a higher risk of TB (AOR 4.32, 95% CI 1.57–11.92) than HIV-positive patients with DM (AOR 3.31, 95% CI 1.29–8.54), but the difference was not statistically significant. A1C Now+ HbA1c measurements correlated poorly with the D-10 HbA1c reference test. Conclusion A high proportion of patients in Abuja have markers of DM and pre-diabetes at the time of TB diagnosis.

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area