Characterization of an Acinetobacter baumannii Monofunctional Phosphomethylpyrimidine Kinase That Is Inhibited by Pyridoxal Phosphate.

Thiamin and its phosphate derivatives are ubiquitous molecules involved as essential cofactors in many cellular processes. The de novo biosynthesis of thiamin employs the parallel synthesis of 4-methyl-5-(2-hydroxyethyl)thiazole (THZ-P) and 4-amino-2-methyl-5(diphosphooxymethyl) pyrimidine (HMP) pyrophosphate (HMP-PP), which are coupled to generate thiamin phosphate. Most organisms that can biosynthesize thiamin employ a kinase (HMPK or ThiD) to generate HMP-PP. In nearly all cases, this enzyme is bifunctional and can also salvage free HMP, producing HMP-P, the monophosphate precursor of HMP-PP. Here we present high-resolution crystal structures of an HMPK from Acinetobacter baumannii (AbHMPK), both unliganded and with pyridoxal 5-phosphate (PLP) noncovalently bound. Despite the similarity between HMPK and pyridoxal kinase enzymes, our kinetics analysis indicates that AbHMPK accepts HMP exclusively as a substrate and cannot turn over pyridoxal, pyridoxamine, or pyridoxine nor does it display phosphatase activity. PLP does, however, act as a weak inhibitor of AbHMPK with an IC50 of 768 µM. Surprisingly, unlike other HMPKs, AbHMPK catalyzes only the phosphorylation of HMP and does not generate the diphosphate HMP-PP. This suggests that an additional kinase is present in A. baumannii, or an alternative mechanism is in operation to complete the biosynthesis of thiamin.

Structure-Guided Discovery of N5-CAIR Mutase Inhibitors.

Because purine nucleotides are essential for all life, differences between how microbes and humans metabolize purines can be exploited for the development of antimicrobial therapies. While humans biosynthesize purine nucleotides in a 10-step pathway, most microbes utilize an additional 11th enzymatic activity. The human enzyme, aminoimidazole ribonucleotide (AIR) carboxylase generates the product 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) directly. Most microbes, however, require two separate enzymes, a synthetase (PurK) and a mutase (PurE), and proceed through the intermediate, N5-CAIR. Toward the development of therapeutics that target these differences, we have solved crystal structures of the N5-CAIR mutase of the human pathogens Legionella pneumophila (LpPurE) and Burkholderia cenocepacia (BcPurE) and used a structure-guided approach to identify inhibitors. Analysis of the structures reveals a highly conserved fold and active site architecture. Using this data, and three additional structures of PurE enzymes, we screened a library of FDA-approved compounds in silico and identified a set of 25 candidates for further analysis. Among these, we identified several new PurE inhibitors with micromolar IC50 values. Several of these compounds, including the α1-blocker Alfuzosin, inhibit the microbial PurE enzymes much more effectively than the human homologue. These structures and the newly described PurE inhibitors are valuable tools to aid in further studies of this enzyme and provide a foundation for the development of compounds that target differences between human and microbial purine metabolism.

Implementation of tuberculosis preventive therapy with INH-Rifapentine (3HP) for latent tuberculosis infection management in household tuberculosis contacts in India: A prospective study.

OBJECTIVE: The primary objective of this study was to ascertain the acceptance, initiation, implementation and treatment completion rates of tuberculosis (TB) preventive therapy (TPT) using 3HP (INH-Rifapentine) among household contacts of microbiologically confirmed drug sensitive TB cases on anti-tubercular treatment under programmatic real-world settings. The secondary objectives were to estimate the prevalence and predictors of latent TB infection (LTBI) in household contacts of the index TB cases. We also ascertained the safety profile of the 3HP TPT regimen in the household contacts. METHODS: This prospective observational study was conducted at 10 TB chest clinics in Delhi, India during 2022-2023. Household contacts aged 14 and older who tested positive for TB infection on a Tuberculin Skin test were initiated on the 3HP regimen. Logistic regression was performed by including statistically significant independent variables in multiple prediction models. p < 0.05 was considered statistically significant. STATA, version 15.1, was used to compute all analyses. RESULTS: A total of 1067 (84.68%) eligible contacts of microbiologically confirmed, drug sensitive TB cases underwent screening with tuberculin skin test (TST), 614 (95.6%) LTBI positive contacts accepted the initiation of TPT, and 564 (91.8%) of those initiated on TPT completed the treatment. The major reason for refusal of screening was the lack of perception of risk of TB disease due to asymptomatic status. The prevalence of LTBI positivity through TST was 61.5% (95% CI, 58.5%, 64.4%). Adverse events were reported by 195 (31.8%) contacts initiated on 3HP of which 20 participants discontinued TPT. None of the sociodemographic factors showed a significant association with LTBI positivity (except age) or TPT completion rates. CONCLUSION: LTBI management with 3HP is feasible among adolescent and adult household contacts in India with high rates of adherence from initiation until treatment completion. The maximum attrition of participants occurred at the time of screening for LTBI using TST.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting.

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants - ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months.

Hypertension care cascade in an urban resettlement colony and slum in Delhi, India: a cross-sectional survey.

BACKGROUND: Hypertension care cascade in resource-limited settings is compromised with a majority of patients with hypertension remaining undiagnosed, untreated, non-adherent, and poorly controlled at every stage. However, there is paucity of information on care and management of hypertensive patients in community-based settings of low-income urban neighbourhoods in India. METHODS: This was a community-based cross-sectional study conducted in an urban resettlement colony and slum area in the Northeast District of Delhi. The adult population was screened for hypertension using standardized methods, and adherence to medications was assessed using the Morisky Green Levine scale. Binary logistic regression analysis was conducted to ascertain the sociodemographic predictors of the outcome (presence of hypertension, adherence to antihypertensive medication, blood pressure control). A p-value < 0.05 was considered statistically significant. RESULTS: We included 8850 adult participants including 5295 females and 3555 males in this study. Nearly 29% of the participants were hypertensive, of which 61.77% were newly diagnosed cases. Furthermore, nearly 81% of the previously diagnosed cases had been initiated on antihypertensive medication, of which 57.54% were adherent to their medications while 36.12% attained controlled blood pressure levels. The odds of having hypertension were significantly higher among males (AOR = 1.87, 95% CI: 1.63 to 2.15), age ≥ 60 years (AOR = 9.15, 95% CI: 7.82 to 10.70), high waist circumference (AOR = 2.24, 95% CI: 1.86 to 2.70) and Body Mass Index of ≥ 25.00 (AOR = 2.55, 95% CI: 2.00 to 3.26). Furthermore, on adjusted analysis, patients of hypertension having diabetes (DM) comorbidity had significantly higher odds of being adherent to anti-hypertensive medications (AOR = 1.81, 95% CI: 1.31 to 2.51) compared to those without DM comorbidity, while tobacco users had significantly lower odds of being adherent to antihypertensive medication (AOR = 0.50, 95% CI: 0.31 to 0.82). CONCLUSIONS: Hypertension care cascade in urban slum-resettlement colony setting revealed a high burden of undiagnosed hypertension, low rates of medication adherence, and poor blood pressure control. Strengthening community screening and primary care continuum of care is necessary to improve the hypertension care cascade from early diagnosis to effective management with optimal health outcomes to reduce patient complications and increase longevity.

Examining the Relationship Between Rurality, Risk Perception, and COVID-19 Vaccine Willingness Among Rural Latinos in Arizona and California.

This study aimed to investigate the relationship between rurality and risk perception of getting or transmitting COVID-19 and willingness to get the COVID-19 vaccine in a sample of Latinos across Arizona and California's Central Valley (n = 419). The results revealed that rural Latinos are more concerned about getting and transmitting COVID-19, but less willing to get vaccinated. Our findings suggest that perceptions of risk alone do not play a sole role in influencing risk management behavior among rural Latinos. While rural Latinos may have heightened perception of the risks associated with COVID-19, vaccine hesitancy persists due to a variety of structural and cultural factors. These factors included limited access to healthcare facilities, language barriers, concerns about vaccine safety and effectiveness, and cultural factors such as strong family and community ties. The study highlights the need for culturally-tailored education and outreach efforts that address the specific needs and concerns of this community to increase vaccination rates and reduce the disproportionate burden of COVID-19 among Latino communities living in rural areas.

Outcomes among 10,314 hospitalized COVID-19 patients at a tertiary care government hospital in Delhi, India.

A significant proportion of patients with coronavirus disease 2019 (COVID-19) require timely hospitalization to reduce the risk of complications and mortality. We describe the trends of the age and gender stratified outcomes among hospitalized COVID-19 patients with moderate to severe illness at the largest dedicated tertiary care COVID-19 government hospital in New Delhi, India. A retrospective cohort study through secondary data analysis from in-patient hospital data of patients admitted from April 1 to November 15, 2020 was conducted. The data of 10,314 laboratory-confirmed patients with COVID-19 was analyzed, of which 8899 (86.28%) were discharged after recovery, and 1415 (13.72%) died. The mean (SD) age of the hospitalized patients was 46.43 (18.74) years (n = 10,309) including 6031 (58.50%) male and 4278 (41.50%) female patients (n = 10,309). On bivariate analysis, increasing age was associated with significantly higher odds of mortality in both gender (p < .001). The mortality rate in female patients was lower (11.92%) compared with male patients (15.75%) (p = .675). However, elderly women had the highest odds of mortality (p < .001), indicating the possible role of delayed health seeking behavior, secondary to familial, and social neglect. Mortality in the patients with COVID-19 also occurred early after admission suggesting rapid deterioration, delayed reporting by patients, or their late referral from other health facilities. However, the overall statewide recovery rate showed steady improvement since the onset of the pandemic. In contrast, the recovery rate among the moderate-severe cases that were hospitalized at this tertiary care center during the same period reflected a lower nonspecific zigzag pattern indicating limited effectiveness of the COVID-19 treatment regimens.

Clinical characteristic and epidemiological features of SARS CoV -2 disease patients from a COVID 19 designated Hospital in New Delhi.

SARS CoV -2 infection is rapidly evolving as a serious global pandemic. The present study describes the clinical characteristics of SARS CoV-2 infection patients. The Samples were subjected to RT - PCR or Rapid Antigen test for diagnosis of SARS CoV- 2. A cohort of 3745 patients with confirmed diagnosis of SARS CoV -2 infection in a tertiary care center in New Delhi, India were included in this study. Data was collected from offline and online medical records over a period of six months. Amongst 3745 SARS CoV -2 infected patients, 2245 (60%) were symptomatic and 1500 (40%) were asymptomatic. Most common presenting symptom was cough (49.3%) followed febrile episodes (47.1%), breathlessness (42.7%) and sore throat (35.1%). Cough along with breathlessness (24.1) was the most common combination of symptoms followed by fever with cough (22.7). The most common comorbidity found among symptomatic group was diabetes (42.5%) followed by hypertension (21.4%) and chronic kidney disease (18%). Comorbidities like diabetes mellitus, chronic diseases of lungs, heart and kidneys were found to be common in symptomatic group and this was found to be statistically significant (p<0.05). COVID-19 is an evolving disease and data from our study help in understanding the clinic-epidemiological profile of patients. This article is protected by copyright. All rights reserved.

Text messaging improves diabetes-related knowledge of patients in India: A quasi-experimental study.

Background: . Diabetes-related health education promotes patient efficacy for diabetes self-management. However, sub-optimal knowledge of diabetes in people with diabetes is recognized as a challenge in overcrowded public health facilities in India. We aimed to determine the effect of health education through mobile phone text messages (short messaging service [SMS]) on diabetes-related knowledge of patients with diabetes. Methods: . From February 2016 to February 2017, we recruited adult patients with diabetes for this quasi-experimental study done in the outpatient setting of a major tertiary care government hospital in Delhi, India. Participants in the intervention group received a text message on diabetes self-care practices every alternate day for 90 days. We evaluated the patients' knowledge of diabetes using the Spoken Knowledge in Low Literacy in Diabetes (SKILL-D) questionnaire and a self-designed diabetes knowledge questionnaire. Results: . We enrolled 190 men and 160 women, of whom 52 (13.7%) were lost to follow-up. At baseline, mean diabetes knowledge scores were higher in the intervention group compared to the control group. After the intervention period of 3 months, the diabetes knowledge scores for SKILL-D and the patient diabetes knowledge questionnaire showed a statistically significant increase in the intervention group (mean difference 0.7 and 0.5, respectively; p<0.001, but there was no increase in the control group). Conclusion: . The use of mobile phone technology for diabetes-related health education through mobile text-message (SMS) technology is an effective method for health promotion.

The effect of a mhealth intervention on anti-tuberculosis medication adherence in Delhi, India: A quasi-experimental study.

BACKGROUND: Suboptimal adherence to anti-tuberculosis medication in patients is associated with adverse treatment outcomes including treatment failure, relapse, and emergence of drug resistance. OBJECTIVES: : We conducted the present study with the objectives of evaluating the effectiveness of a mHealth package on the medication adherence of patients with tuberculosis (TB) on antitubercular (directly observed treatment short-course [DOTS]) treatment. METHODS: We conducted Quasi-experimental study at six DOTS centers of Delhi among 220 newly diagnosed TB patients. We included adult TB patients (18 years and above) who were on DOTS therapy ≥30 days, had access to a mobile phone and were able to read messages and receive calls. We excluded patients with impaired hearing, blindness and those on non-DOTS therapy or having multidrug-resistant/extensively drug-resistant TB. Participants in the intervention group received amHealth package for 90 days. The medication adherence of the study participants was measured using Morisky, Green, and Levine Adherence Scale. RESULTS: A total of 130 men and 90 women were recruited for the study. Occupational interference and forgetfulness were the most common reasons for medication nonadherence in the patients. In the intervention group, the medication adherence to antitubercular medication (daily DOTS regimen) was 85.5% at baseline which increased to 96.4% at endline (postintervention) (P = 0.004). No significant change was observed in the control group (P = 0.328). The increase in adherence was observed across the following subgroups: age, gender, education, and Socioeconomic status. CONCLUSIONS: The mHealth intervention in TB patients was effective in improving the adherence to DOTS therapy.

Trends & treatment outcomes of multidrug-resistant tuberculosis in Delhi, India (2009-2014): A retrospective record-based study.

Background & objectives: The increase in the burden of multidrug-resistant tuberculosis (MDR-TB) is a matter of grave concern. The present study was undertaken to describe MDR-TB treatment outcome trends in Delhi and their epidemiological correlates, to assess the adequacy of treatment records and to also generate evidence towards influencing and improving practices related to the MDR-TB control programme. Methods: A retrospective record-based study (2009-2014) was conducted in three major drug resistance TB treatment centres of Delhi. Treatment outcomes and adverse effects were extracted from the existing programme records including patients' treatment cards and laboratory registers. Results: A total of 2958 MDR-TB patients were identified from the treatment cards, of whom 1749 (59.12%) were males. The mean (±standard deviation) age was 30.56±13.5 years. Favourable treatment outcomes were reported in 1371 (53.28%) patients, but they showed a declining trend during the period of observation. On binomial logistic regression analysis, patients with age ≥35 yr, male sex and undernourishment (body mass index <18.5) at the time of treatment initiation had a significantly increased likelihood of unfavourable MDR-TB treatment outcome (P <0.001). Interpretation & conclusions: The study showed an increasing burden of MDR-TB patients, especially in the young population with increased risk of transmission posing a major challenge in achieving TB elimination targets.

Enhancing Medication Adherence through Improved Patient-provider Communication: The 6A's of Intervention.

Public-health facilities in the developing world often experience a high patient burden, low doctor-patient ratio, drug stock-outs and the lack of avenues for adequate patient-provider communication. We identified strategies for enhancing medication adherence for chronic disorders in Indian health settings that rely on improving patient-provider communication through a review of the literature. These include (A)sk the patient on adherence status, (A)ssess accurately medication adherence, provide (A)ssistance with regimen and enlisting support from all available resources especially family support, (A)nticipating and precluding interruption in adherence, (A)ssurance against harm due to drug sideeffects and finally (A)void blaming the patient for non-adherence.

Progressive right ventricular enlargement due to pulmonary regurgitation: Clinical characteristics of a "low-risk" group.

BACKGROUND: The optimal interval between serial cardiac magnetic resonance imaging (CMRI) scans for monitoring right ventricular (RV) enlargement in the setting of severe pulmonic valve regurgitation (PR) is unknown. The purposes of this study were to (1) determine the annual change in RV volume on serial CMRI scans and (2) identify the risk factors for rapid progression of RV enlargement. METHODS: A retrospective study of adults with postintervention native valve PR and ≥2 CMRI scans at Mayo Clinic Rochester from 2000 to 2015 was conducted. Rapid progression of RV enlargement was defined as first upper quartile of annual increase in RV end-diastolic volume index (RVEDVi) for the cohort. RESULTS: Of the 63 patients (age, 36 ±â€¯9 years) in the study, 43 (68%) had tetralogy of Fallot, whereas 20 (32%) had valvular pulmonic stenosis. Right ventricular outflow tract interventions that resulted in PR were balloon pulmonary valvuloplasty (n = 4; 7%), transannular patch repair (n = 30; 58%), and nontransannular patch repair (n = 18; 35%). Interval between baseline and second CMRI was 2 (1-4) years. In comparison to baseline CMRI, RVEDVi increased from 130 (109-141) to 135 (126-155) mL/m2 and median annual change in RVEDVi was 3.1 (1.7-5.9) mL/m2. Univariate risk factors for rapid progression of RV enlargement (annual increase in RVEDVi >6 mL/m2) were ≥moderate tricuspid regurgitation and RVEDVi >130 mL/m2. Among the 24 patients without these risk factors (low-risk subgroup), RVEDVi increased by only 3 (0-7) mL/m2 over 7 (5-9) years. CONCLUSIONS: Patients with PR without RVEDVi >130 mL/m2 and/or ≥moderate tricuspid regurgitation represent a low-risk subgroup that may be appropriate for clinical and echo follow-up but may potentially require infrequent CMRI follow-up.

Awareness About Anti-Smoking Related Laws and Legislation Among General Population in Slums of Delhi, India.

Introduction: Almost 40% of Delhi's population lives in slums and is vulnerable to tobacco use. It is therefore important to assess their opinion and ensure compliance to antismoking legislation. The present study was undertaken to assess the awareness of the general public residing in slums in Delhi regarding the smoke-free initiative of 2009, 3 years after intensive implementation. Methods: It was a cross-sectional study conducted among participants selected by cluster sampling from the slums in six districts of Delhi using a pretested semistructured questionnaire. A total of 708 slum dwellers were interviewed. Results: Out of the total, only 16.1% (n = 114) of the participants had heard of The Cigarettes and Other Tobacco Products (Prohibition of Advertisement and Regulation of Trade and Commerce, Production, Supply and Distribution) Act, 2003 (COTPA), though, they were aware about some of the provisions of the COTPA. Majority (n = 529; 74.7%) perceived the smoke-free zones as the places where smoking forms of tobacco are banned. Regarding the awareness about the places designated as smoke-free zones, 82.1% (n = 581) of the respondents named educational institutions. About 61% of the people interviewed reported to have seen people smoking at public places on the day of interview while only 21.5% reported to have seen any one getting punished for smoking. Conclusions: Awareness about COTPA was low. The study respondents perceived that no action was being taken against persons acting in violation of the law. Thus, there is a need for stricter implementation of COTPA and increased spreading of awareness among the general public. Implications: While awareness about antismoking legislation among general population (particularly slums) has been studied world over, this has not been the case in India. The study depicts opinion of one of the susceptible populations regarding tobacco control legislation, which has hitherto not been studied in the Indian context. This study has an important implication as it highlights the need for stringent enforcement of antismoking legislation for tobacco control.

Domino Carbopalladation/C-H Functionalization Sequence: An Expedient Synthesis of Bis-Heteroaryls through Transient Alkyl/Vinyl-Palladium Species Capture.

A microwave-assisted highly efficient intermolecular domino carbopalladation/C-H functionalization sequence has been developed to access bis-heteroaryl frameworks in a single operation. The reaction involves carbopalladation of the halogenated acrylamides or phenylpropiolamides by the Pd(0) catalysis, followed by the direct (hetero)arylation to give products with good to excellent yields. The synthetic utility of this method was also extended towards the application of the Ugi-adduct as the starting material.

Microwave-Assisted Copper-Catalyzed Oxidative Cyclization of Acrylamides with Non-Activated Ketones.

An operationally simple and efficient microwave-assisted protocol for the oxidative cyclization of acrylamide derivatives with non-activated ketones to generate 3,3-disubstituted oxindoles is described. The reaction proceeds by a copper-catalyzed tandem radical addition/cyclization strategy and tolerates a series of functional groups with moderate to excellent yields.

Metal-mediated post-Ugi transformations for the construction of diverse heterocyclic scaffolds.

The Ugi-4CR is by far one of the most successful multicomponent reactions leading to high structural diversity and molecular complexity. However, the reaction mostly affords a linear peptide backbone, enabling post-Ugi transformations as the only solution to rigidify the Ugi-adduct into more drug like species. Not surprisingly, the development of these transformations, leading to new structural frameworks, has expanded rapidly over the last few years. As expected, palladium-catalyzed reactions have received the foremost attention, yet other metals, particularly gold complexes, are fast catching up. This tutorial review outlines the developments achieved in the past decade, highlighting the modifications that are performed in a sequential or domino fashion with emphasis on major concepts, synthetic applications of the derived products as well as mechanistic aspects.

Pd-catalyzed Csp(2) -H functionalization of heteroarenes via isocyanide insertion: concise synthesis of di-(hetero)aryl ketones and di-(hetero)aryl alkylamines.

We report herein an efficient Pd-catalyzed direct C-H bond functionalization of heteroarenes via an isocyanide insertion strategy for the synthesis of di-(hetero)aryl ketones and di-(hetero)aryl alkylamines. The methodology involves a three component reaction between an azole, a haloarene and an isocyanide resulting in the formation of an imine, which in turn is either hydrolyzed or reduced to get the desired product.

Discovery of MK-7655, a ß-lactamase inhibitor for combination with Primaxin®.

ß-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C ß-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C ß-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin® is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections.

Resurrecting social infrastructure as a determinant of urban tuberculosis control in Delhi, India.

BACKGROUND: The key to universal coverage in tuberculosis (TB) management lies in community participation and empowerment of the population. Social infrastructure development generates social capital and addresses the crucial social determinants of TB, thereby improving program performance. Recently, there has been renewed interest in the concept of social infrastructure development for TB control in developing countries. This study aims to revive this concept and highlight the fact that documentation on ways to operationalize urban TB control is required from a holistic development perspective. Further, it explains how development of social infrastructure impacts health and development outcomes, especially with respect to TB in urban settings. METHODS: A wide range of published Government records pertaining to social development parameters and TB program surveillance, between 2001 and 2011 in Delhi, were studied. Social infrastructure development parameters like human development index along with other indicators reflecting patient profile and habitation in urban settings were selected as social determinants of TB. These include adult literacy rates, per capita income, net migration rates, percentage growth in slum population, and percentage of urban population living in one-room dwelling units. The impact of the Revised National Tuberculosis Control Program on TB incidence was assessed as an annual decline in new TB cases notified under the program. Univariate linear regression was employed to examine the interrelationship between social development parameters and TB program outcomes. RESULTS: The decade saw a significant growth in most of the social development parameters in the State. TB program performance showed 46% increment in lives saved among all types of TB cases per 100,000 population. The 7% reduction in new TB case notifications from the year 2001 to 2011, translates to a logarithmic decline of 5.4 new TB cases per 100,000 population. Except per capita income, literacy, and net migration rates, other social determinants showed significant correlation with decline in new TB cases per 100,000 population. CONCLUSIONS: Social infrastructure development leads to social capital generation which engenders positive growth in TB program outcomes. Strategies which promote social infrastructure development should find adequate weightage in the overall policy framework for urban TB control in developing countries.