Risk Factors associated with defaulting from visceral leishmaniasis treatment: analysis under routine programme conditions in Bihar, India.

OBJECTIVE: To assess the rate of default from treatment in the visceral leishmaniasis (VL) elimination programme and to identify risk factors and its underlying causes. METHODS: Case-control study conducted between December 2009 and June 2012 in three primary health centres (PHCs) of Muzaffarpur district, India. Patients who defaulted from treatment from the PHCs were considered as 'cases' and those who completed their treatment as 'controls'. Two controls were included in the study for each case. Respondents' opinion and satisfaction with the services provided at the PHCs were also elicited. Logistic regression was performed to assess the contribution of sociodemographic variables on patient status, and a discriminant analysis was used (after decomposing the original data) to identify factors that can predict the patient status as defaulter or not, based on factor scores of the components as predictor variables. RESULTS: During the study period, 16.3% (89/544) of patients defaulted; 87 cases and 188 controls were interviewed through a semistructured questionnaire. Women tended to be more at risk for default (OR, 1.6, 95% CI (0.9 -2.9). Treatment received was miltefosine in 55.6% and sodium stibogluconate (SSG) in 44.4%. Most (86%) defaulters completed their treatment at other healthcare facilities; 70% of them preferred non-governmental institutions. Most cited reasons for default were seeking a second opinion for VL treatment and preferring to be treated in specialised VL centres. Discriminant analysis showed only one significant predictor: dissatisfaction with the medical care received in PHCs. CONCLUSION: Efforts are needed to enhance the quality of VL care at PHC level, which will be beneficial in increasing treatment completion rates.

Human resource assessment for scaling up VL active case detection in Bangladesh, India and Nepal.

OBJECTIVES: To determine whether medical staff at PHC level would have the time to take up additional activities such as 1-day fever camps for active VL case detection. METHODS: This article assessed the workload of health staff of different professional categories working at health facilities in Bangladesh, India and Nepal. Data were collected from different sites in high endemic VL areas. The study population was the health staff of government health facilities at all levels. Workload indicators of staffing need (WISN) software were adopted to carry out the analysis of staff workload and their availability in the selected health facility. The WISN difference and WISN ratio for a particular health facility were calculated from actual staffing available and calculated staffing requirement. RESULTS: The results showed a mixed picture of the availability of health workers. In most settings of Bangladesh and India, physicians with or without laboratory technicians would have time for active case detection. In Nepal, this would be performed by trained nurses and paramedical personnel. CONCLUSION: If all vacant posts were filled, active case detection could be performed more easily. The elimination programme can be scaled up with the current staffing levels in the endemic areas with some short training if and when necessary.

Village health workers in Bihar, India: an untapped resource in the struggle against kala-azar.

INTRODUCTION: In 2005 a visceral leishmaniasis (VL) elimination initiative was launched on the Indian subcontinent; important components of early case finding and treatment are entrusted to the primary health care system (PHC). In an earlier study in Bihar, India, we discovered some major shortcomings in implementation, in particular related to monitoring of treatment and treatment outcomes. These shortcomings could be addressed through involvement of village health workers. In the current study we assessed knowledge, attitude and practice of these village health workers in relation to VL. Main objective was to assess the feasibility of their involvement in VL control. METHODS: We obtained a list of auxiliary nurses/midwives and accredited social health activists for the highly endemic district of Muzaffarpur. We randomly sampled 100 auxiliary nurses and 100 activists, who were visited in their homes for an interview. Questions were asked on knowledge, attitude and practice related to visceral leishmaniasis and to tuberculosis. RESULTS: Auxiliary nurses and activists know the presenting symptoms of visceral leishmaniasis, they know how it is diagnosed but they are not aware of the recommended first-line treatment. Many are already involved in tuberculosis control and are very well aware of the treatment modalities of tuberculosis, but few are involved in control of visceral leishmaniasis control. They are well organised, have strong links to the primary healthcare system and are ready to get more involved in visceral leishmaniasis control. CONCLUSION: To ensure adequate monitoring of visceral leishmaniasis treatment and treatment outcomes, the control programme urgently needs to consider involving auxiliary nurses and activists.

Monitoring drug effectiveness in kala-azar in Bihar, India: cost and feasibility of periodic random surveys vs. a health service-based reporting system.

OBJECTIVE: In 2009, a random survey was conducted in Muzaffarpur district to document the clinical outcomes of visceral leishmaniasis patients (VL) treated by the public health care system in 2008, to assess the effectiveness of miltefosine against VL. We analysed the operational feasibility and cost of such periodic random surveys as compared with health facility-based routine monitoring. METHODS: A random sample of 150 patients was drawn from registers kept at Primary Health Care centres. Patient records were examined, and the patients were located at their residence. Patients and physicians were interviewed with the help of two specifically designed questionnaires by a team of one supervisor, one physician and one field worker. Costs incurred during this survey were properly documented, and vehicle log books maintained for analysis. RESULTS: Hundred and 39 (76.7%) of the patients could be located. Eleven patients were not traceable. Per patient, follow-up cost was US$ 15.51 and on average 2.27 patients could be visited per team-day. Human resource involvement constituted 75% of the total cost whereas involvement of physician costs 51% of the total cost. CONCLUSION: A random survey to document clinical outcomes is costly and labour intensive but gives probably the most accurate information on drug effectiveness. A health service-based retrospective cohort reporting system modelled on the monitoring system developed by tuberculosis programmes could be a better alternative. Involvement of community health workers in such monitoring would offer the additional advantage of treatment supervision and support.

Management of visceral leishmaniasis in rural primary health care services in Bihar, India.

OBJECTIVE: In 2005 a visceral leishmaniasis (VL) elimination initiative was launched on the Indian subcontinent, with early diagnosis based on a rapid diagnostic test and treatment with the oral drug miltefosine as its main strategy. Several recent studies have signaled underreporting of VL cases in the region. Information on treatment outcomes is scanty. Our aim was to document VL case management by the primary health care services in India. METHODS: We took a random sample of all VL patients registered in rural primary health care (PHC) facilities of Muzaffarpur district, Bihar, India during 2008. Patients were traced at home for an interview and their records were reviewed. We recorded patient and doctor delay, treatment regimens, treatment outcomes and costs incurred by patients. RESULTS: We could review records of all 150 patients sampled and interview 139 patients or their guardian. Most patients (81%) had first presented to unqualified practitioners; median delay before reaching the appropriate primary healthcare facility was 40 days (IQR 31-59 days). Existing networks of village health workers were under-used. 48% of VL patients were treated with antimonials; 40% of those needed a second treatment course. Median direct expenditure by patients was 4000 rupees per episode (IQR 2695-5563 rupees), equivalent to almost 2 months of household income. CONCLUSION: In 2008 still critical flaws remained in VL case management in the primary health care services in Bihar: obsolete use of antimonials with high failure rates and long patient delay. To meet the target of the VL elimination, more active case detection strategies are needed, and village health worker networks could be more involved. Costs to patients remain an obstacle to early case finding.

Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals.

OBJECTIVE: Studies investigating risk factors for visceral leishmaniasis (VL) on the Indian Subcontinent have shown contradictory results related to the role of domestic animals. In some studies having animals in or around the house was a risk factor, in others it was protective. We investigated the specific hypothesis that keeping domestic animals inside the house at night is a risk factor for VL. METHODS: Individually matched case-control study. All patients with VL diagnosed in the study area in Bihar, India between March 1st, 2007 and December 1st, 2008 were eligible. For each case, we selected two random controls, with no history of previous VL; matched on sex, age group and neighbourhood. Patients and controls were subjected to a structured interview on the main exposure of interest and potential confounders; a conditional logistic regression model was used to analyse the data. RESULTS: We enrolled 141 patients and 282 controls. We found no significant associations between VL and keeping domestic animals inside the house (OR of 0.88 for bovines and 1.00 for 'any animal') or ownership of domestic animals (OR of 0.97 for bovines and 1.02 for 'any animal'). VL was associated with housing conditions. Living in a thatched house (OR 2.60, 95% CI 1.50-4.48) or in a house with damp floors (OR 2.60, 95% CI 1.25-5.41) were risk factors, independently from socio economic status. CONCLUSION: Keeping animals inside the house is not a risk factor for VL in Bihar, India. Improving housing conditions for the poor has the potential to reduce VL incidence.

An in vivo model for load-modulated remodeling in the rabbit flexor tendon.

This study tested the hypothesis that eliminating in vivo compression to the wrap-around, fibrocartilage-rich zone of the flexor digitorum profundus tendon results in rapid depletion of fibrocartilage and changes in its mechanical properties, microstructure, extracellular matrix composition, and cellularity. The right flexor digitorum profundus tendons of 2.5-3-year-old rabbits were translocated anteriorly to eliminate in vivo compression and shear to the fibrocartilage zone and, at 4 weeks after surgery, were compared with tendons that had sham surgery and with untreated tendons. The translocated tissue showed a significant increase in equilibrium strain under a compressive creep load (p < 0.05). The thickness and area of the fibrocartilage zone also decreased significantly (p < 0.05). The nuclear density decreased by 40% in the fibrocartilage zone (p < 0.005); however, nuclear shape and orientation were not significantly altered. Glycosaminoglycan content in the fibrocartilage zone was also depleted by 40% (p < 0.02). The tightly woven basket weave-like mesh of collagen fibers in the zone appeared more loosely organized, suggesting matrix reorganization due to translocation. Moreover, immunoreactive type-II collagen and link protein in the fibrocartilage zone also decreased. With use of this unique in vivo model, this research clearly elucidates how changing tissue function (by removing compressive forces) rapidly alters tissue form.

Autologous mesenchymal stem cell-mediated repair of tendon.

Mesenchymal stem cells (MSCs) were isolated from bone marrow of 18 adult New Zealand White rabbits. These cells were culture expanded, suspended in type I collagen gel, and implanted into a surgically induced defect in the donor s right patellar tendon. A cell-free collagen gel was implanted into an identical control defect in the left patellar tendon. Repair tissues were evaluated biomechanically (n = 13) and histomorphometrically (n = 5) at 4 weeks after surgery. Compared to their matched controls, the MSC-mediated repair tissue demonstrated significant increases of 26% (p < 0.001), 18% (p < 0. 01), and 33% (p < 0.02) in maximum stress, modulus, and strain energy density, respectively. Qualitatively, there appeared to be minor improvements in the histological appearance of some of the MSC- mediated repairs, including increased number of tenocytes and larger and more mature-looking collagen fiber bundles. Morphometrically, however, there were no significant left-right differences in nuclear aspect ratio (shape) or nuclear alignment (orientation). Therefore, delivering a large number of mesenchymal stem cells to a wound site can significantly improve its biomechanical properties by only 4 weeks but produce no visible improvement in its microstructure.

In vivo tendon forces correlate with activity level and remain bounded: evidence in a rabbit flexor tendon model.

While some tendons and ligaments in the lower extremity develop peak forces proportional to the intensity of activity (Komi 1990; Komi et al., 1992; Korvick et al., 1996), others maintain a steady force regardless of activity level (Herzog et al., 1993; Prilutsky et al., 1994). Investigators (Biewener et al., 1988; Korvick et al., 1996) have also shown that peak knee and ankle tendon forces approach one-quarter to one-third of ultimate or failure force values. In the rabbit flexor digitorum profundus (FDP) tendon model we tested several hypotheses, chiefly that peak in vivo forces not only increase with increasing activity but do not exceed one-third of their ultimate or failure values. The FDP tendon was instrumented in three animals, and each rabbit subjected to an experimental design involving three activity levels. Peak tensile forces and rates of rise and fall in tendon force increased significantly with increasing activity (p < 0.01). Further, the tendon maintained a non-zero force level throughout all trials. For the most vigorous activity, inclined hopping, tensile forces and stresses were, on average, within 30% of the tendon's ultimate force and stress values, respectively. Such in vivo measurements in different tendon systems should help investigators better understand the recruitment and contribution of important muscle-tendon units to joint stability and gait.