The First Differentiated TB Care Model From India: Delays and Predictors of Losses in the Care Cascade.

To reduce TB deaths in resource-limited settings, a differentiated care strategy can be used to triage patients with high risk of severe illness (i.e., those with very severe undernutrition, respiratory insufficiency, or inability to stand without support) at diagnosis and refer them for comprehensive assessment and inpatient care. Globally, there are few examples of implementing this type of strategy in routine program settings. Beginning in April 2022, the Indian state of Tamil Nadu implemented a differentiated care strategy called Tamil Nadu-Kasanoi Erappila Thittam (TN-KET) for all adults aged 15 years and older with drug-susceptible TB notified by public facilities. Before evaluating the impact on TB deaths, we sought to understand the retention and delays in the care cascade as well as predictors of losses. During April-June 2022, 14,961 TB patients were notified and 11,599 (78%) were triaged. Of those triaged, 1,509 (13%) were at high risk of severe illness; of these, 1,128 (75%) were comprehensively assessed at a nodal inpatient care facility. Of 993 confirmed as severely ill, 909 (92%) were admitted, with 8% unfavorable admission outcomes (4% deaths). Median admission duration was 4 days. From diagnosis, the median delay in triaging and admission of severely ill patients was 1 day each. Likelihood of triaging decreased for people with extrapulmonary TB, those diagnosed in high-notification districts or teaching hospitals, and those transferred out of district. Predictors of not being comprehensively assessed included: aged 25-34 years, able to stand without support, and diagnosis at a primary or secondary-level facility. Inability to stand without support was a predictor of unfavorable admission outcomes. To conclude, the first quarter of implementation suggests that TN-KET was feasible to implement but could be improved by addressing predictors of losses in the care cascade and increasing admission duration.

--Eleven tips for operational researchers working with health programmes: our experience based on implementing differentiated tuberculosis care in south India.

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this 'how we did it' paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation.

Regulation of pancreatic islet gene expression in mouse islets by pregnancy.

Pancreatic ß cells adapt to pregnancy-induced insulin resistance by unclear mechanisms. This study sought to identify genes involved in ß cell adaptation during pregnancy. To examine changes in global RNA expression during pregnancy, murine islets were isolated at a time point of increased ß cell proliferation (E13.5), and RNA levels were determined by two different assays (global gene expression array and G-protein-coupled receptor (GPCR) array). Follow-up studies confirmed the findings for select genes. Differential expression of 110 genes was identified and follow-up studies confirmed the changes in select genes at both the RNA and protein level. Surfactant protein D (SP-D) mRNA and protein levels exhibited large increases, which were confirmed in murine islets. Cytokine-induced expression of SP-D in islets was also demonstrated, suggesting a possible role as an anti-inflammatory molecule. Complementing these studies, an expression array was performed to define pregnancy-induced changes in expression of GPCRs that are known to impact islet cell function and proliferation. This assay, the results of which were confirmed using real-time reverse transcription-PCR assays, demonstrated that free fatty acid receptor 2 and cholecystokinin receptor A mRNA levels were increased at E13.5. This study has identified multiple novel targets that may be important for the adaptation of islets to pregnancy.

Diagnostic value of cardinal signs/symptoms in paucibacillary leprosy.

With the help of sensitivity and specificity criteria, an attempt is made to quantify the gain in certainty in diagnosis with the use of various cardinal signs/symptoms (S/s) of leprosy in order to study their predictive value in correct diagnosis of paucibacillary leprosy (PB) by the Paramedical Workers. The study was based on the findings in 326 new cases of paucibacillary leprosy detected by 10 paramedical workers during a recent field survey. Observations in the present study confirm the scientific basis of presently used combinations of cardinal S/s for correct diagnosis of leprosy especially the combination of (skin) patch with loss/impairment of sensation. The detailed observations made in the study are discussed in this communication.

Restoration of plantar sweat secretion in the feet of leprosy patients.

As part of the studies on nerve damage and its consequences in leprosy, the status of sweat gland function in the anaesthetic sole of the feet of leprosy patients was investigated qualitatively and semi-quantitatively, before and after surgical decompression of the posterior tibial neurovascular bundle. Sweat prints of the feet of the patients were obtained pre-operatively and postoperatively on Whatman's No. 1 filter paper. The paper was treated with one percent Ninhydrin and the intensities of the Ninhydrin positive areas were quantitated. Forty one feet of thirty six patients have been studied in this manner. Sweat print analysis of twenty normal people have also been done, and included for comparison. This operative procedure has been found to effect an improvement in the sweat gland function in the feet of more than fifty percent of leprosy patients studied so far.

Cauliflower growths in trophic ulcers of leprosy--a 10 year study.

A 10 year study of cauliflower growths in trophic ulcers of leprosy patients was done. Seventy five cases were seen, out of which seventy two were in foot and three in hand. Eventhough appearance was like that of malignancy, malignant change was seen only in four cases and in other seventy one cases it was pseudoepitheliomatous hyperplasia. Various surgical procedures were done. Wide excision appears to be the procedure of choice where feasible as per our studies.

Diagnostic efficiency of paramedical workers involved in leprosy case detection programme.

The diagnostic efficiency and accuracy in classification of leprosy and its activity status, by four senior trained Paramedical Workers (PMWs) involved in leprosy case detection programme, was assessed on 1394 cases detected by them and concurrently confirmed by an experienced medical officer. The inter-observer variation between two experienced PMWs in diagnosis and classification of leprosy on 216 patients, was also studied. Of the 1394 cases detected by PMWs, 257 (18.44%) were wrongly diagnosed as leprosy, mostly as non-lepromatous (N) type. Though all lepromatous (L) and 98% of N-type cases were correctly classified by PMWs, 25.64% of borderline (N ? L) cases were either under-diagnosed as N-type (17.95%) or over-diagnosed as L-type (7.69%). The activity status of 19% cases was wrongly assessed by PMWs, including 8% active lesions assessed as inactive. The discrepancy between two PMWs in diagnosis, classification and assessment of activity status of leprosy was found in 1.39%, 7.41% & 25.67% cases, respectively. The implications of these observations, and the suggestions to improve the technical skills of workers for an efficient and effective implementation of leprosy control programme, are discussed in this communication.