Distressing psychotic-like experiences, cognitive functioning and early developmental markers in clinically referred young people aged 8-18 years.

PURPOSE: Neurocognitive difficulties and early childhood speech/motor delays are well documented amongst older adolescents and young adults considered at risk for psychosis-spectrum diagnoses. We aimed to test associations between unusual or psychotic-like experiences (PLEs), co-occurring distress/emotional symptoms, current cognitive functioning and developmental delays/difficulties in young people (aged 8-18 years) referred to Child and Adolescent Mental Health Services in South London, UK. METHODS: Study 1 examined receptive language, verbal learning and caregiver-reported speech and motor delays/difficulties in a sample of 101 clinically-referred children aged 8-14 years, comparing those reporting no PLEs (n = 19), PLEs without distress (n = 16), and PLEs with distress (n = 66). Study 2 tested associations of severity of distressing PLEs with vocabulary, perceptual reasoning, word reading and developmental delays/difficulties in a second sample of 122 adolescents aged 12-18 years with distressing PLEs. RESULTS: In Study 1, children with distressing PLEs had lower receptive language and delayed recall and higher rates of developmental delays/difficulties than the no-PLE and non-distressing PLE groups (F values: 2.3-2.8; p values: < 0.005). Receptive language (ß = 0.24, p = 0.03) and delayed recall (ß = - 0.17, p = 0.02) predicted PLE distress severity. In Study 2, the cognitive-developmental variables did not significantly predict PLE distress severity (ß values = 0.01-0.22, p values: > 0.05). CONCLUSION: Findings may be consistent with a cognitive-developmental model relating distressing PLEs in youth with difficulties in cognitive functioning. This highlights the potential utility of adjunctive cognitive strategies which target mechanisms associated with PLE distress. These could be included in cognitive-behavioural interventions offered prior to the development of an at-risk mental state in mental health, educational or public health settings.

A Potent Kalihinol Analogue Disrupts Apicoplast Function and Vesicular Trafficking in P. falciparum Malaria.

Here we report the discovery of MED6-189, a new analogue of the kalihinol family of isocyanoterpene (ICT) natural products. MED6-189 is effective against drug-sensitive and -resistant P. falciparum strains blocking both intraerythrocytic asexual replication and sexual differentiation. This compound was also effective against P. knowlesi and P. cynomolgi. In vivo efficacy studies using a humanized mouse model of malaria confirms strong efficacy of the compound in animals with no apparent hemolytic activity or apparent toxicity. Complementary chemical biology, molecular biology, genomics and cell biological analyses revealed that MED6-189 primarily targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses in P. falciparum revealed that a mutation in PfSec13, which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. The high potency of MED6-189 in vitro and in vivo, its broad range of efficacy, excellent therapeutic profile, and unique mode of action make it an excellent addition to the antimalarial drug pipeline.

Normative data for an expanded set of stimuli for testing high-level influences on object perception: OMEFA-II.

We present normative data for an expanded set of stimuli designed to investigate past experience effects on object detection. The stimuli are vertically-elongated "bipartite" displays comprising two equal-area regions meeting at an articulated central border. When the central border is assigned to one side, a shaped figure (i.e., an object) is detected on that side. Participants viewing brief masked exposures typically detect figures more often on the critical side of Intact displays where a common ("familiar") object is depicted than on a matched critical side of Part-Rearranged (PR) displays comprising the same parts arranged in novel configurations. This pattern of results showed that past experience in the form of familiar configuration rather than familiar parts is a prior for figure assignment. Spurred by research implicating a network involving the perirhinal cortex of the medial temporal lobe in these familiar configuration effects, we enlarged the stimulus set from 24 to 48 base stimuli to increase its usefulness for behavioral, neuropsychological, and neuroimaging experiments. We measured the percentage of participants who agreed on a single interpretation for each side of Intact, Upright PR, and Inverted PR displays (144 displays; 288 sides) under long exposure conditions. High inter-subject agreement is taken to operationally define a familiar configuration. This new stimulus set is well-suited to investigate questions concerning how parts and wholes are integrated and how high- and low-level brain areas interact in object detection. This set also allows tests of predictions regarding cross-border competition in figure assignment and assessments of individual differences. The displays, their image statistics, and normative data are available online (https://osf.io/j9kz2/).

Direct measurement of the preferred sense of NO rotation after collision with argon.

The preferred sense of product molecule rotation (clockwise or counterclockwise) in a bimolecular collision system has been measured. Rotationally inelastic collisions of nitric oxide (NO) molecules with Ar atoms were studied by combining crossed molecular beams, circularly polarized resonant multiphoton ionization probing, and velocity-mapped ion imaging detection. The observed sense of NO product rotation varies with deflection angle and is a strong function of the NO final rotational state. The largest preferences for sense of rotation are observed at the highest kinematically allowed product rotational states; for lower rotational states, the variation with deflection angle becomes oscillatory. Quantum calculations on the most recently reported NO-Ar potential give good agreement with the observed oscillation patterns in the sense of rotation.

Delay in seeking care for tuberculosis symptoms among adults newly diagnosed with HIV in rural Malawi.

SETTING: Ten primary health clinics in rural Thyolo District, Malawi. OBJECTIVE: Tuberculosis (TB) is a common initial presentation of human immunodeficiency virus (HIV) infection. We investigated the time from TB symptom onset to HIV diagnosis to describe TB health-seeking behaviour in adults newly diagnosed with HIV. DESIGN: We asked adults (18 years) about the presence and duration of TB symptoms at the time of receiving a new HIV diagnosis. Associations with delayed health seeking (defined as >30 and >90 days from the onset of TB symptoms) were evaluated using multivariable logistic regression. RESULTS: TB symptoms were reported by 416 of 1265 participants (33%), of whom 36% (150/416) had been symptomatic for >30 days before HIV testing. Most participants (260/416, 63%) were below the poverty line (US$0.41 per household member per day). Patients who first sought care from informal providers had an increased odds of delay of >30 days (adjusted odds ratio [aOR] 1.6, 95%CI 0.9-2.8) or 90 days (aOR 2.0, 95%CI 1.1-3.8). CONCLUSIONS: Delayed health seeking for TB-related symptoms was common. Poverty was ubiquitous, but had no clear relationship to diagnostic delay. HIV-positive individuals who first sought care from informal providers were more likely to experience diagnostic delays for TB symptoms.

Predictors of isoniazid preventive therapy completion among adults newly diagnosed with HIV in rural Malawi.

SETTING: To reduce the risk of tuberculosis (TB) among individuals with human immunodeficiency virus (HIV) infection, the World Health Organization recommends at least 6 months of isoniazid preventive therapy (IPT). Completion of IPT remains a major challenge in resource-limited settings. OBJECTIVE: To evaluate predictors of IPT completion in individuals newly diagnosed with HIV. DESIGN: Predictors of IPT completion among adults newly diagnosed with HIV in rural Malawi were evaluated using a multilevel logistic regression model. RESULTS: Of 974 participants who screened negative for active TB and were started on IPT, 732 (75%) completed treatment. Only one IPT-eligible individual refused treatment. Participants who were aged <25 years (compared with those aged 45 years, adjusted OR [aOR] 0.33, 95%CI 0.18-0.60) and male (compared to non-pregnant females, aOR 0.57, 95%CI 0.37-0.88) had lower odds of IPT completion. CONCLUSION: IPT provision at the time of initial HIV diagnosis was highly acceptable in rural Malawi; three quarters of those who initiated IPT successfully completed therapy. We observed lower odds of completion among males and among female participants aged <25 years. Additional efforts may be needed to ensure IPT completion among males and young females who have recently been diagnosed with HIV.

runt homology domain transcription factors (Runx, Cbfa, and AML) mediate repression of the bone sialoprotein promoter: evidence for promoter context-dependent activity of Cbfa proteins.

Expression of the bone sialoprotein (BSP) gene, a marker of bone formation, is largely restricted to cells in mineralized tissues. Recent studies have shown that the Cbfa1 (also known as Runx2, AML-3, and PEBP2alphaA) transcription factor supports commitment and differentiation of progenitor cells to hypertrophic chondrocytes and osteoblasts. This study addresses the functional involvement of Cbfa sites in expression of the Gallus BSP gene. Gel mobility shift analyses with nuclear extracts from ROS 17/2.8 osteoblastic cells revealed that multiple Cbfa consensus sequences are functional Cbfa DNA binding sites. Responsiveness of the 1.2-kb Gallus BSP promoter to Cbfa factors Cbfa1, Cbfa2, and Cbfa3 was assayed in osseous and nonosseous cells. Each of the Cbfa factors mediated repression of the wild-type BSP promoter, in contrast to their well known activation of various hematopoietic and skeletal phenotypic genes. Suppression of BSP by Cbfa factors was not observed in BSP promoters in which Cbfa sites were deleted or mutated. Expression of the endogenous BSP gene in Gallus osteoblasts was similarly downregulated by forced expression of Cbfa factors. Our data indicate that Cbfa repression of the BSP promoter does not involve the transducin-like enhancer (TLE) proteins. Neither coexpression of TLE1 or TLE2 nor the absence of the TLE interaction motif of Cbfa1 (amino acids 501 to 513) influenced repressor activity. However, removal of the C terminus of Cbfa1 (amino acids 362 to 513) relieved suppression of the BSP promoter. Our results, together with the evolutionary conservation of the seven Cbfa sites in the Gallus and human BSP promoters, suggest that suppressor activity by Cbfa is of significant physiologic consequence and may contribute to spatiotemporal expression of BSP during bone development.

Tumor necrosis factor alpha (TNF-alpha) coordinately regulates the expression of specific matrix metalloproteinases (MMPS) and angiogenic factors during fracture healing.

Recent studies from our laboratory demonstrate that TNF-alpha signaling contributes to the regulation of chondrocyte apoptosis and a lack of TNF-alpha signaling leads to a persistence of cartilaginous callus and delayed resorption of mineralized cartilage. This study examines how delays in the endochondral repair process affect the expression of specific mediators of proteolytic cartilage turnover and vascularization. Simple closed fractures were produced in wild type and TNF-alpha receptor (p55-/-/p75-/-)-deficient mice. Using ribonuclease protection assay (RPA) and microarray analysis, the expression of multiple mRNAs for various angiogenic factors and the metalloproteinase gene family were measured in fracture calluses. The direct actions of TNFalpha on the expression of specific angiogenic factors and metalloproteinases (MMPs) was examined in both cultured callus cells and articular chondrocytes to compare the effects of TNF-alpha in growth cartilage versus articular cartilage. MMPs 2, 9, 13, and 14 were quantitatively the most prevalent metalloproteases and all showed peaks in expression during the chondrogenic period. In the absence of TNF-alpha signaling, the expression of all of these mRNAs was reduced. The angiopoietin families of vascular regulators and their receptors were expressed at much higher levels than the VEGFs and their receptors and while the angiopoietins showed diminished or delayed expression in the absence of TNF-alpha signaling, VEGF and its receptors remained unaltered. The expression of vascular endothelial growth inhibitor (VEGI or TNFSF15) showed a near absence in its expression in the TNF-alpha receptor-deficient mice. In vitro assessment of cultured fracture callus cells in comparison to primary articular chondrocytes showed that TNF-alpha treatment specifically induced the expression of MMP9, MMP14, VEGI, and Angiopoietin 2. These results suggest that TNF-alpha signaling in chondrocytes controls vascularization of cartilage through the regulation of angiopoietin and VEGI factors which play counterbalancing roles in the induction of growth arrest, or apoptosis in endothelial cells. Furthermore, TNF-alpha appears to regulate, in part, the expression of two key proteolytic enzymes, MMP 9 and MMP14 that are known to be crucial to the progression of vascularization and turnover of mineralized cartilage. Thus, TNF-alpha signaling in healing fractures appears to coordinate the expression of specific regulators of endothelial cell survival and metalloproteolytic enzymes and is essential in the transition and progression of the endochondral phase of fracture repair.

Two-stage activity-safety study of daily rifapentine during intensive phase treatment of pulmonary tuberculosis.

BACKGROUND: Rifapentine (RPT) has potent activity against Mycobacterium tuberculosis; however, the optimal dose for anti-tuberculosis treatment is unknown. OBJECTIVE: To determine the antimicrobial activity, safety and tolerability of RPT 450 mg or 600 mg administered daily during the first 8 weeks of treatment for pulmonary tuberculosis (TB). DESIGN: In a two-stage, randomised open-label study, adults with sputum smear-positive TB were randomised to receive RPT 450 mg, RPT 600 mg or rifampicin (RMP) 600 mg daily for 8 weeks with isoniazid, pyrazinamide and ethambutol. The primary endpoint was sputum culture status on Löwenstein-Jensen (LJ) medium at completion of 8 weeks of treatment. RESULTS: A total of 153 participants were enrolled. Both RPT regimens met pre-specified criteria to advance to stage 2. At completion of 8 weeks of treatment, LJ culture conversion occurred in 85% (35/41), 96% (43/45) and 94% (34/36) of participants in the RPT 450 mg, RPT 600 mg and RMP groups, respectively. The proportions of participants discontinuing treatment were similar (respectively 1/54 [2.0%], 1/51 [2.0%] and 4/48 [8.3%] in the RPT 450 mg, RPT 600 mg and RMP groups), as were ⩾grade 3 adverse events (0/54 [0%], 1/51 [2.0%] and 4/48 [8.3%]). CONCLUSIONS: There was a trend towards greater efficacy with RPT 600 mg than with RPT 450 mg. Daily RPT was safe and well-tolerated.

Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption.

UNLABELLED: TNF-alpha is a major inflammatory factor that is induced in response to injury, and it contributes to the normal regulatory processes of bone resorption. The role of TNF-alpha during fracture healing was examined in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice. The results show that TNF-alpha plays an important regulatory role in postnatal endochondral bone formation. INTRODUCTION: TNF-alpha is a major inflammatory factor that is induced as part of the innate immune response to injury, and it contributes to the normal regulatory processes of bone resorption. METHODS: The role of TNF-alpha was examined in a model of simple closed fracture repair in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice. Histomorphometric measurements of the cartilage and bone and apoptotic cell counts in hypertrophic cartilage were carried out at multiple time points over 28 days of fracture healing (n = 5 animals per time point). The expression of multiple mRNAs for various cellular functions including extracellular matrix formation, bone resorption, and apoptosis were assessed (triplicate polls of mRNAs). RESULTS AND CONCLUSIONS: In the absence of TNF-alpha signaling, chondrogenic differentiation was delayed by 2-4 days but subsequently proceeded at an elevated rate. Endochondral tissue resorption was delayed 2-3 weeks in the TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice compared with the wild-type animals. Functional studies of the mechanisms underlying the delay in endochondral resorption indicated that TNF-alpha mediated both chondrocyte apoptosis and the expression of proresorptive cytokines that control endochondral tissue remodeling by osteoclasts. While the TNF-alpha receptor ablated animals show no overt developmental alterations of their skeletons, the results illustrate the primary roles that TNF-alpha function contributes to in promoting postnatal fracture repair as well as suggest that processes of skeletal tissue development and postnatal repair are controlled in part by differing mechanisms. In summary, these results show that TNF-alpha participates at several functional levels, including the recruitment of mesenchymal stem, apoptosis of hypertrophic chondrocytes, and the recruitment of osteoclasts function during the postnatal endochondral repair of fracture healing.

A randomized, controlled trial of interventions to improve adherence to isoniazid therapy to prevent tuberculosis in injection drug users.

PURPOSE: To determine the effect of several interventions on adherence to tuberculosis preventive therapy. METHODS: We conducted a randomized trial with a factorial design comparing strategies for improving adherence to isoniazid preventive therapy in 300 injection drug users with reactive tuberculin tests and no evidence of active tuberculosis. Patients were assigned to receive directly observed isoniazid preventive therapy twice weekly (Supervised group, n = 99), daily self-administered isoniazid with peer counseling and education (Peer group, n = 101), or routine care (Routine group, n = 100). Patients within each arm were also randomly assigned to receive an immediate or deferred monthly $10 stipend for maintaining adherence. The endpoints of the trial were completing 6 months of treatment, pill-taking as measured by self-report or observation, isoniazid metabolites present in urine, and bottle opening as determined by electronic monitors in a subset of patients. RESULTS: Completion of therapy was 80% for patients in the Supervised group, 78% in the Peer group, and 79% in the Routine group (P = 0.70). Completion was 83% (125 of 150) among patients receiving immediate incentives versus 75% (112 of 150) among patients with deferred incentives (P = 0.09). The proportion of patients who were observed or reported taking at least 80% of their doses was 82% for the Supervised arm of the study, compared with 71% for the Peer arm and 90% for the Routine arm. The proportion of patients who took 100% of doses was 77% for the Supervised arm (by observation), 6% for the Peer arm (by report), and 10% for the Routine arm (by report; P <0.001). Direct observation showed the median proportion of doses taken by the Supervised group was 100%, while electronic monitoring in a subset of patients showed the Peer group (n = 27) took 57% of prescribed doses and the Routine group (n = 32) took 49% (P <0.001). Patients in the Routine arm overreported adherence by twofold when data from electronic monitoring were used as a gold standard. There were no significant differences in electronically monitored adherence by type of incentive. CONCLUSION: Adherence to isoniazid preventive therapy by injection drug users is best with supervised care. Peer counseling improves adherence over routine care, as measured by electronic monitoring of pill caps, and patients receiving peer counseling more accurately reported their adherence. More widespread use of supervised care could contribute to reductions in tuberculosis rates among drug users and possibly other high-risk groups.

Development of gut colonisation in pre-term neonates.

Twenty-eight pre-term babies of low birth weight were monitored for developing microflora in throat, stomach and faeces during the first 3 weeks of life. The flora at all levels of the gastrointestinal tract differed from that of healthy breast-fed and artificially fed full-term babies. Colonisation of throat and stomach was delayed beyond 4 days of life in 87% and 60% of babies respectively. Only 10% of babies had "normal" oral flora throughout the period of study. Flora of the stomach was sparse, and resembled faecal flora. Faecal flora was established more rapidly than throat or stomach flora, and 70% of babies were colonised during the first 4 days of life. Initially Bacteroides spp. were predominant (57% babies), but Escherichia coli and other aerobic gram-negative bacilli gradually increased in frequency. Colonisation by gram-positive bacteria was slow. Clostridium spp. were present in only 10% of babies during the first 4 days of life. Most strains were transient. Colonisation with C. butyricum (30%), C. perfringens (35%) and C. difficile (25%) was maximum after the first 2 weeks of life. Lactic-acid-producing bacteria usually appeared late in the third week of life. Parenteral feeding immediately after birth was associated with delayed colonisation by a restricted number of species. Parenteral antibiotics (penicillin or gentamicin or both) restricted colonisation with normal oral flora, the lactic-acid-producing bacteria and penicillin-sensitive clostridia, but had little effect on E. coli even when the colonising strain was sensitive to the aminoglycoside in the regimen. Systemic spread of bacteria via the blood stream was not detected in any babies. The pattern of colonisation of the enteric tract in pre-term infants in the special-care nursery studied, differs from that of healthy full-term babies; this merits consideration when the results of bacteriological tests of this vulnerable group of infants are being interpreted.

Evaluation of end-point titration, single dilution and capture enzyme immunoassays for measurement of antirotaviral IgA and IgM in infantile secretions and serum.

In order to facilitate measurement of antirotaviral IgA in large collections of faeces and secretions, adaptations of enzyme immunoassay methods for estimating antirotaviral IgA and IgM in duodenal fluid, saliva, faeces and serum were studied. To quantitate specific IgA, a single dilution of each sample was assayed. Results were expressed as antirotaviral IgA units derived from a standard curve. Units were calculated by log-logit analysis on computer. There was strong correlation between antirotaviral IgA units and end-point titres in 257 faecal samples (correlation coefficient r = 0.92) and in 182 duodenal fluids and salivary samples (correlation coefficient r = 0.74). The assay was validated using acute and convalescent faeces from children with or without rotavirus infection. Immune conversions in IgA were detected in 33 (75%) of the children by units and 34 (77%) by titres. None of nine children with gastroenteritis due to other infectious agents showed immune conversions to rotavirus. A monoclonal capture IgM assay showed similar end-point titres and numbers of immune conversions when compared with a direct assay for antirotaviral IgM in serum and secretions. Use of the capture method eliminated false-positive reactions with the cell control. The assay for antirotaviral IgA units in secretions is simple, rapid, reproducible and reliable, and has proven of value in longitudinal epidemiological studies of rotavirus coproIgA profiles. Both the capture IgM technique and the single dilution IgA method permit analysis of large numbers of specimens and are appropriate for examination of immune responses to natural rotavirus infection or during vaccine trials.

Cost effectiveness of rotavirus vaccination in Australia.

OBJECTIVE: Rotavirus gastroenteritis causes substantial morbidity, including hospital admission, in young children. In the context of recent vaccine developments, this study aimed to estimate the cost-effectiveness of a rotavirus vaccination program in Australia. METHOD: Standard methods of health economic evaluation were used to assess the total cost of rotavirus immunisation (as the difference between estimated vaccination program costs and the cost of disease that would be avoided by immunisation) and relate this to the number of cases of disease that would be prevented. Estimates were made from both societal and health care systems perspectives. RESULTS: Based on Australian data on disease incidence and cost of hospitalisation, the current annual cost of rotavirus disease is about $26.0 million. Using conservative vaccine efficacy estimates, current immunization uptake rates and a cost of $30 per dose of vaccine, rotavirus immunisation would incur a net societal cost of $2.9 million ($11 per child), at a gross program cost of $21.6 million. These estimates are sensitive to two sources of uncertainty in the estimation of program delivery costs: vaccine price and whether separate immunization visits would be required. CONCLUSION: A rotavirus immunisation program would be cost-neutral to Australian society at a vaccine price of $26 per dose (or $19 when health care system costs only are considered). IMPLICATIONS: Rotavirus immunization may be cost-effective in Australia, but considerable uncertainty remains. Policy decisions will depend heavily on pricing of the vaccine and may also need to consider intangible costs not accounted for in this analysis.

Putting the 'informed' into 'consent': a matter of plain language.

Health professionals frequently write at the same level for lay readers as they write for peers. In relation to health research and ethical requirements to provide written explanation of studies, this can complicate the notion of informed consent. Plain language information statements need to be clearly understood by research subjects if the ethics process for research approval is to fulfil its objective. Many delays in gaining ethics approval for child-related research are caused by substandard plain language statements (PLS). We describe specific issues for information statements for research with children, young people and their parents/guardians, particularly in consideration of the literacy capabilities of the general population. We highlight the usefulness of everyday language when explaining research and science in writing to families, and present some guidelines for writing PLS that have emerged from the introduction of a plain language service by an Ethics in Human Research Committee.

Management of sugar intolerance in children.

Sugar intolerance is a common problem in paediatric practice. The usual type is lactose intolerance following gastroenteritis, but it may also occur in a wide variety of disorders of the small bowel. Diagnosis depends upon identification of reducing substances in the stools. An approach to dietary management of lactose intolerance is given and use of a carbohydrate-free formula in secondary monosaccharide intolerance is described. In each situation, threshold for digestion or absorbtion of carbohydrate is approached gradually from below, and overflow detected by Clinitest stool testing.

Duodenal biopsy in 75 New Zealand children.

During the past two years, duodenal biopsy has been used freely in a study of diarrhoea and failure to thrive in South Island children. The technique has proved convenient, safe and diagnostically helpful in a high proportion of cases. It has meant that hospital admission has rarely been required. Parents have appreciated the rapid and definite answers, either positive or negative, which have resulted in more rational treatment for their children.

Community-randomized trial of enhanced DOTS for tuberculosis control in Rio de Janeiro, Brazil.

SETTING: Central Rio de Janeiro, Brazil. OBJECTIVE: To compare the impact of routine DOTS vs. enhanced DOTS (DOTS-Ampliado or DOTS-A) on tuberculosis (TB) incidence. DESIGN: Cluster-randomized trial in eight urban neighborhoods pair-matched by TB incidence and randomly assigned to receive either the DOTS-A or DOTS strategy. DOTS-A added intensive screening of household contacts of active TB cases and provision of treatment to secondary cases and preventive therapy to contacts with latent TB infection (LTBI) to the standard DOTS strategy. The primary endpoint was the TB incidence rates in communities after 5 years of intervention. RESULTS: From November 2000 to December 2004, respectively 339 and 311 pulmonary TB cases were enrolled and 1003 and 960 household were identified in DOTS and DOTS-A communities. Among contacts from DOTS-A communities, 26 (4%) had active TB diagnosed and treated, 429 (61.3%) had LTBI detected and 258 (60.1%) started preventive therapy. TB incidence increased by 5% in DOTS communities and decreased by 10% in DOTS-A communities, for a difference of 15% after 5 years (P = 0.04). CONCLUSION: DOTS-A was associated with a modest reduction in TB incidence and may be an important strategy for reducing the burden of TB.