Feasibility of community health workers using a clinical decision support system to screen and monitor non-communicable diseases in resource-poor settings: study protocol.

BACKGROUND: It is imperative that coordinated and systematic action is undertaken, at all levels, to minimize the consequences of the growing global burden of non-communicable diseases (NCDs). An integrated multi-disciplinary primary care-based preventive program has the potential to reduce lifestyle-related risk factors contributing to NCDs. Accredited Social Health Activists (ASHAs), who are community health workers (CHWs), may be employed to screen populations for NCDs in rural India. To enable ASHAs to be supported when they are on their own in the community, we have developed a clinical decision support system (CDSS) "Arogya Sahyog" (a Hindi term meaning 'health assistant') to guide them through the process. Herein, we describe the protocol for testing this CDSS and the associated community-based management program for people with NCDs. METHODS: This mixed-method study involving both qualitative and quantitative approaches will be conducted in two phases to test: (I) feasibility of the CDSS itself, and (II) feasibility of utilizing the app to develop capacity within the ASHA workforce. First, we will use a semi-structured questionnaire to determine details about the acceptance of using the app, satisfaction with the CDSS, perceived barriers, ideas for improvement, and willingness to use the CDSS. We will also test the usability of this CDSS for the identification of people with hypertension, with or without co-morbidities, by ASHAs and their supervisors. The CDSS will be installed on a tablet and is designed to help ASHAs to screen, provide lifestyle advice, and refer critical patients to primary care physicians. Second, to develop capacity within the ASHA workforce, ASHAs will be taught about NCDs, so they can motivate people to adhere to healthy activities and self-manage their NCDs. We will also test whether this training program improves ASHAs' knowledge about NCDs. We will further evaluate ASHAs' capacity to provide health promotional interventions to patients with, or at risk of, NCDs using the tablet device. DISCUSSION: The study will enable us to test a CDSS and an educational training program. Specifically, we will test whether the program is user-friendly, easy-to-comprehend, easy-to-deliver, workflow-oriented, and comprehensive. We will determine whether mobilizing this ASHA workforce with the support of a CDSS could result in better management of hypertension and co-morbidities than usual care.

Prevalence of diabetes and pre-diabetes in rural Tehri Garhwal, India: influence of diagnostic method.

BACKGROUND: There are few available data regarding the prevalence of diabetes in the sub-Himalayan region of India. The aim of this study was to determine the prevalence of pre-diabetes and diabetes in rural Garhwal based on glycosylated hemoglobin. METHODS: In a cross-sectional survey of 500 adults from five randomly selected villages in Chamba, a mountainous Tehri Garhwal district in Uttarakhand in north-west India, we determined the prevalence of diabetes (hemoglobin (Hb) A1c ≥ 6.5%) and pre-diabetes (5.7% ≤ HbA1c ≤ 6.4%). In a sub-sample of those diagnosed with diabetes or pre-diabetes (n = 140), fasting blood glucose (FBG, n = 117) or postprandial blood glucose (PBG, n = 23), and blood hemoglobin concentration, was measured at follow-up. RESULTS: Based on HbA1c, 10.0% had diabetes and 56.4% pre-diabetes. Of those diagnosed as diabetic by HbA1c, 10 of 16 (62.5%) were diagnosed as diabetic by FBG (> 125 mg/dL) or PBG (≥200 mg/dL). In those diagnosed as pre-diabetic by HbA1c, only 55 of 124 (44.4%) were diagnosed as pre-diabetic by FBG (100-125 mg/dL) or PBG (140-199 mg/dL). A large proportion of these 140 individuals (67.1%) were moderately to severely anemic (Hb < 11.4 mg/dL). The diagnostic gap for pre-diabetes between HbA1c and FBG/PBG was similar for the groups with and without moderate to severe anemia. CONCLUSIONS: HbA1c and FBG/PBG have similar diagnostic performance for diabetes in this population. However, many individuals were diagnosed with pre-diabetes by HbA1c but not FBG/PBG. The relative excess diagnosis of pre-diabetes with HbA1c does not appear to be explained by anemia, an endemic condition in India. The prognostic significance of diagnosis of pre-diabetes by HbA1c but not FBG/PBG remains unknown, but merits investigation.

Tobacco Usage in Uttarakhand: A Dangerous Combination of High Prevalence, Widespread Ignorance, and Resistance to Quitting.

BACKGROUND: Nearly one-third of adults in India use tobacco, resulting in 1.2 million deaths. However, little is known about knowledge, attitudes, and practices (KAP) related to smoking in the impoverished state of Uttarakhand. METHODS: A cross-sectional epidemiological prevalence survey was undertaken. Multistage cluster sampling selected 20 villages and 50 households to survey from which 1853 people were interviewed. Tobacco prevalence and KAP were analyzed by income level, occupation, age, and sex. 95% confidence intervals were calculated using standard formulas and incorporating assumptions in relation to the clustering effect. RESULTS: The overall prevalence of tobacco usage, defined using WHO criteria, was 38.9%. 93% of smokers and 86% of tobacco chewers were male. Prevalence of tobacco use, controlling for other factors, was associated with lower education, older age, and male sex. 97.6% of users and 98.1% of nonusers wanted less tobacco. Except for lung cancer (89% awareness), awareness of diseases caused by tobacco usage was low (cardiac: 67%; infertility: 32.5%; stroke: 40.5%). CONCLUSION: A dangerous combination of high tobacco usage prevalence, ignorance about its dangers, and few quit attempts being made suggests the need to develop effective and evidence based interventions to prevent a health and development disaster in Uttarakhand.

Informal rural healthcare providers in North and South India.

Rural households in India rely extensively on informal biomedical providers, who lack valid medical qualifications. Their numbers far exceed those of formal providers. Our study reports on the education, knowledge, practices and relationships of informal providers (IPs) in two very different districts: Tehri Garhwal in Uttarakhand (north) and Guntur in Andhra Pradesh (south). We mapped and interviewed IPs in all nine blocks of Tehri and in nine out of 57 blocks in Guntur, and then interviewed a smaller sample in depth (90 IPs in Tehri, 100 in Guntur) about market practices, relationships with the formal sector, and their knowledge of protocol-based management of fever, diarrhoea and respiratory conditions. We evaluated IPs' performance by observing their interactions with three patients per condition; nine patients per provider. IPs in the two districts had very different educational backgrounds-more years of schooling followed by various informal diplomas in Tehri and more apprenticeships in Guntur, yet their knowledge of management of the three conditions was similar and reasonably high (71% Tehri and 73% Guntur). IPs in Tehri were mostly clinic-based and dispensed a blend of allopathic and indigenous drugs. IPs in Guntur mostly provided door-to-door services and prescribed and dispensed mainly allopathic drugs. In Guntur, formal private doctors were important referral providers (with commissions) and source of new knowledge for IPs. At both sites, IPs prescribed inappropriate drugs, but the use of injections and antibiotics was higher in Guntur. Guntur IPs were well organized in state and block level associations that had successfully lobbied for a state government registration and training for themselves. We find that IPs are firmly established in rural India but their role has grown and evolved differently in different market settings. Interventions need to be tailored differently keeping in view these unique features.

Interaction of human TNF and beta2-microglobulin with Tanapox virus-encoded TNF inhibitor, TPV-2L.

Tanapox virus (TPV) encodes and expresses a secreted TNF-binding protein, TPV-2L or gp38, that displays inhibitory properties against TNF from diverse mammalian species, including human, monkey, canine and rabbit. TPV-2L also has sequence similarity with the MHC-class I heavy chain and interacts differently with human TNF as compared to the known cellular TNF receptors or any of the known virus-encoded TNF receptor homologs derived from many poxviruses. In order to determine the TNF binding region in TPV-2L, various TPV-2L C-terminal truncations and internal deletions were created and the muteins were expressed using recombinant baculovirus vectors. C-terminal deletions from TPV-2L resulted in reduced binding affinity for human TNF and specific mutants of TNF that discriminate between TNF-R1 and TNF-R2. However, deletion of C-terminal 42 amino acid residues totally abolished the binding of human TNF and its mutants. Removal of any of the predicted internal domains resulted in a mutant TPV-2L protein incapable of binding to human TNF. Deletion of C-terminal residues also affected the ability of TPV-2L to block TNF-induced cellular cytotoxicity. In addition to TNF, TPV-2L can also form complexes with human beta2-microglobulin to form a novel macromolecular complex. In summary, the TPV-2L protein is a bona fide MHC-1 heavy chain family member that binds and inhibits human TNF in a fashion very distinct from other known poxvirus-encoded TNF inhibitors, and also can form a novel complex with the human MHC-1 light chain, beta2-microglobulin.

Yaba monkey tumor virus encodes a functional inhibitor of interleukin-18.

Interleukin-18 (IL-18) is a critical proinflammatory cytokine whose extracellular bioactivity is regulated by a cellular IL-18 binding protein (IL-18BP). Many poxviruses have acquired variants of this IL-18BP gene, some of which have been shown to act as viral virulence factors. Yaba monkey tumor virus (YMTV) encodes a related family member, 14L, which is similar to the orthopoxvirus IL-18BPs. YMTV 14L was expressed from a baculovirus system and tested for its ability to bind and inhibit IL-18. We found that YMTV 14L bound both human IL-18 (hIL-18) and murine IL-18 with high affinity, at 4.1 nM and 6.5 nM, respectively. YMTV 14L was able to fully sequester hIL-18 but could only partially inhibit the biological activity of hIL-18 as measured by gamma interferon secretion from KG-1 cells. Additionally, 17 hIL-18 point mutants were tested by surface plasmon resonance for their ability to bind to YMTV 14L. Two clusters of hIL-18 surface residues were found to be important for the hIL-18-YMTV 14L interaction, in contrast to results for the Variola virus IL-18BP, which has been shown to primarily interact with a single cluster of three amino acids. The altered binding specificity of YMTV 14L most likely represents an adaptation resulting in increased fitness of the virus and affirms the plasticity of poxviral inhibitor domains that target cytokines like IL-18.

A secreted high-affinity inhibitor of human TNF from Tanapox virus.

A class of secreted poxvirus tumor necrosis factor (TNF)-binding proteins has been isolated from Tanapox-infected cell supernatants. The inhibitor bound to a TNF-affinity column and was identified as the product of the 2L gene. Sequence analysis of 2L family members from other yatapoxviruses and swinepox virus yielded no sequence homology to any known cellular gene. The expressed Tanapox virus 2L protein bound to human TNF with high affinity (K(d) = 43 pM) and exhibits an unusually slow off-rate. However, 2L is unable to bind to a wide range of human TNF family members. The 2L protein can inhibit human TNF from binding to TNF receptors I and II as well as block TNF-induced cytolysis. Thus, Tanapox virus 2L represents an inhibitor of human TNF and offers a unique strategy with which to modulate TNF activity.