The rK39 strip test is non-predictor of clinical status for kala-azar

<p>Abstract</p> <p>Background</p> <p>The rK39 strip test is reported to be simple, sensitive, specific, non-invasive and economical test. Since this method is supposed to be patient friendly, it may easily be accepted for sero-epidemiological surveys. An attempt was made to evaluate the role of rK39 strip test in pre and post treatment phases of Kala azar, as a diagnostic and prognostic marker, in addition to other laboratory investigations, in order to evaluate its role in sero-epidemiological surveys.</p> <p>Findings</p> <p>A total of 210 cases were selected for the study. One hundred clinically and parasitologically confirmed cases were corroborated with other hematological profiles. The formol-gel test was included along with well matched control group comprising of normal endemic controls (50), non-endemic normals (20) and other febrile cases (40). All groups were tested by rK39 strip test. Fifty Kala azar cases were followed up after completion of successful treatment. They were subjected to rK39 strip test after 0, 90 and 180 days of completion of successful treatment.</p> <p>The rK39 showed sensitivity, specificity, PPV, NPV, and diagnostic accuracy of 98% (95% CI 91.7-100), 100%, 100%, 90% (95% CI 66-100) and 98% (95% CI 92.6-100) respectively. All the 50 cured followed up cases showed positive result by rK39 strip test even after 180 days of completion of successful treatment.</p> <p>Conclusion</p> <p>The test seems an ideal qualitative test for the diagnosis of kala-azar. But for sero-epidemiological studies the test may be used with other parameters. Alternatively a quantitative ELISA using rK39 antigen may be used.</p

In Search of an Ideal Test for Diagnosis and Prognosis of Kala-azar

The latex agglutination test (KAtex), direct agglutination test (DAT), and the rK39 immuno-chromatographic strip test (dipstick test) were evaluated for their role in the diagnosis and prognosis of visceral leishmaniasis (kala-azar) in India. Sera and urine samples from 455 subjects—150 confirmed visceral leishmaniasis cases, 160 endemic controls, 100 non-endemic controls, and 45 other febrile diseases—were included in the study. The sensitivity of the KAtex, DAT, and rK39 strip test was 87% [95% confidence interval (CI) 80–96], 93.3% (95% CI 88–100), and 98% (95% CI 93–100) respectively. The specificity of these tests was 98% (95% CI 93–100), 93% (95% CI 87–100), and 89% (95% CI 82–97) for the KAtex, DAT, and rK39 strip test respectively. Fifty cases were followed up and subjected to the KAtex, DAT, and rK39 strip test after 30 days of successful treatment. The DAT and rK39 strip test showed positive results in all the 50 cases whereas the KAtex showed no positive reaction in any case. Based on the results, it is concluded that the sensitivity and specificity of the DAT and rK39 strip test are comparable but the greater convenience of use of the strip test makes it a better tool for the diagnosis of visceral leishmaniasis in the peripheral areas of endemic regions whereas the sensitivity of the KAtex needs to be improved to promote its use as a first-line diagnostic test in the field-setting. It may be used for the prognosis of the disease as antigen becomes undetectable in urine after 30 days of the completion of the treatment. Alternatively, it can be used as an adjunct with rK39 for sero-epidemiological surveys

A multiattribute utility evaluation of different methods for the detection of enteric protozoa causing diarrhea in AIDS patients

<p>Abstract</p> <p>Background</p> <p>Enteric protozoa and sporozoa have emerged as important opportunistic parasites and can cause fatal infections in AIDS patients. The line of treatment being different for them necessitates an accurate and prompt identification of these to avoid empirical treatment. In this study which is the first of its kind from India we did a comprehensive evaluation of different techniques, comparing them on the basis of the attributes like yield, cost, time taken, expertise and infrastructure. For the first time combination of Calcoflour White and DAPI, a nuclear stain, were used to identify <it>Microsporidia </it>spp. Thus, a diagnostic protocol was devised for rapid, sensitive and cost effective identification of the opportunistic enteric protozoa.</p> <p>Results</p> <p>The organisms isolated from the stool samples of the cases (450 HIV patients) were predominantly <it>Cryptosporidium </it>spp., <it>Microsporidia </it>spp. and <it>Cyclospora </it>spp. Interestingly, the control group (200 relatives of the patients who were HIV negative) showed a high incidence (21%) of <it>Cryptosporidium </it>spp. We found a significant increase in the sensitivity of microscopy in detecting <it>Cryptosporidium </it>spp. and <it>Cyclospora </it>spp. after formol ether concentration. Kinyoun's staining was better compared to Modified safranin staining for <it>Cryptosporidium </it>spp. identification. Although ELISA had a sensitivity of 93.25% and specificity of 97% for <it>Cryptosporidium </it>spp. detection, we ranked Kinyoun's staining better than ELISA because it is not affordable to most of our patients. For detecting <it>Cyclospora cayetanensis</it>, autoflourescence was the easiest and most cost effective method followed by Safranin technique. Combination of Calcoflour White stain and DAPI gave good results for the identification of <it>Microsporidia </it>spp. We assessed the above techniques and graded the attributes in the following descending order: cost effectiveness, sensitivity, ease of use and interpretation, time taken for the procedure and batch testing.</p> <p>Conclusion</p> <p>Thus, we conclude that a combination of minimum three procedures should be carried out for the screening of stool specimens of HIV positive patients. Kinyoun's staining should be made mandatory for every diarrheal stool sample from HIV patients. Also every laboratory should assign its own value to the attributes and apply Multiattribute utility theory or the Analytical hierarchy process to decide the most appropriate methodology.</p

Cost-Effectiveness Analysis of Combination Therapies for Visceral Leishmaniasis in the Indian Subcontinent

Visceral leishmaniasis (VL) is a serious health problem in the Indian subcontinent affecting the rural poor. It has a significant economic impact on concerned households. The development of drug resistance is a major problem and threatens control efforts under the VL elimination initiative. With an unprecedented choice of antileishmanial drugs (but no newer compound in clinical development), policies that protect these drugs against the emergence of resistance are required. A possible strategy that has been successfully used for malaria and tuberculosis is the use of combination therapies. This study is the first comprehensive assessment of the cost-effectiveness of all possible mono- and combination therapies for the treatment of visceral leishmaniasis in the Indian subcontinent. The analysis was done from the societal perspective, including both health provider and household costs. The present work shows that combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on emergence of drug resistance, the use of combination therapy should be considered in the context of the VL elimination programme in the Indian subcontinent

Diarrhea, CD4 counts and enteric infections in a hospital - based cohort of HIV-infected patients around Varanasi, India

Background: As most of the studies in HIV patients with diarrhea were cross sectional, focusing on the etiological agents, we are reporting data on the rate of diarrhea, associations between diarrhea and CD4 counts and variation in frequency of identifying a pathogen with consistency of diarrhea and duration in a prospective hospital based study. Methods: Stool specimens were obtained between Jan 2001 and April 2003 from HIV infected adults with diarrhea presenting to Infectious Disease clinic, Banaras Hindu University, Varanasi. In all patients with diarrhea, specimens were examined by microscopy and cultures to identify pathogens. Results: During the study, 630 person years of observations with diarrhea were analyzed. 140 stool samples were collected representing 43% of episodes of reported diarrhea. Positivity of finding a pathogen from watery stools and formed stools were 40%&amp;24% respectively (p &lt; 0.01) probably due to associated inflammation is more in watery diarrhea. Patients having chronic diarrhea are 2.25 (95%CI 1.52-2.81) times at more risk of developing other opportunistic infections compared to those who don't have. However this is not true with the acute diarrhea where risk of harboring the opportunistic infections remain same. Conclusion: Diarrhea was most strongly associated with low CD4 counts. Over two-thirds of diarrheal episodes were undiagnosed, suggesting that unidentified agents or primary HIV enteropathy are important causes of diarrhea in this population. There is a strong negative association between duration of diarrhea and CD4 levels

In search of an ideal test for diagnosis and prognosis of Kala-azar

The latex agglutination test (KAtex), direct agglutination test (DAT), and the rK39 immuno-chromato-graphic strip test (dipstick test) were evaluated for their role in the diagnosis and prognosis of visceral leish-maniasis (kala-azar) in India. Sera and urine samples from 455 subjects-150 confirmed visceral leishmani-asis cases, 160 endemic controls, 100 non-endemic controls, and 45 other febrile diseases-were included in the study. The sensitivity of the KAtex, DAT, and rK39 strip test was 87% [95% confidence interval (CI) 80-96], 93.3% (95% CI 88-100), and 98% (95% CI 93-100) respectively. The specificity of these tests was 98% (95% CI 93-100), 93% (95% CI 87-100), and 89% (95% CI 82-97) for the KAtex, DAT, and rK39 strip test respectively. Fifty cases were followed up and subjected to the KAtex, DAT, and rK39 strip test after 30 days of successful treatment. The DAT and rK39 strip test showed positive results in all the 50 cases whereas the KAtex showed no positive reaction in any case. Based on the results, it is concluded that the sensitivi-ty and specificity of the DAT and rK39 strip test are comparable but the greater convenience of use of the strip test makes it a better tool for the diagnosis of visceral leishmaniasis in the peripheral areas of endemic regions whereas the sensitivity of the KAtex needs to be improved to promote its use as a first-line diagnos-tic test in the field-setting. It may be used for the prognosis of the disease as antigen becomes undetectable in urine after 30 days of the completion of the treatment. Alternatively, it can be used as an adjunct with rK39 for sero-epidemiological surveys

Control Barrier Functions in UGVs for Kinematic Obstacle Avoidance: A Collision Cone Approach

In this paper, we propose a new class of Control Barrier Functions (CBFs) for Unmanned Ground Vehicles (UGVs) that help avoid collisions with kinematic (non-zero velocity) obstacles. While the current forms of CBFs have been successful in guaranteeing safety/collision avoidance with static obstacles, extensions for the dynamic case with torque/acceleration-controlled unicycle and bicycle models have seen limited success. Moreover, with these nonholonomic UGV models, applications of existing CBFs have been conservative in terms of control, i.e., steering/thrust control has not been possible under certain common scenarios. Drawing inspiration from the classical use of collision cones for obstacle avoidance in path planning, we introduce its novel CBF formulation with theoretical guarantees on safety for both the unicycle and bicycle models. The main idea is to ensure that the velocity of the obstacle w.r.t. the vehicle is always pointing away from the vehicle. Accordingly, we construct a constraint that ensures that the velocity vector always avoids a cone of vectors pointing at the vehicle. The efficacy of this new control methodology is experimentally verified on the Copernicus mobile robot. We further extend it to the bicycle model and demonstrate collision avoidance under various scenarios in the CARLA simulator.Comment: Submitted to 2023 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS). 8 pages, 8 figures, For supplement video follow https://youtu.be/4qWYaWEPduM. The first and second authors have contributed equall

No evidence for association between SLC11A1 and visceral leishmaniasis in India.

BACKGROUND: SLC11A1 has pleiotropic effects on macrophage function and remains a strong candidate for infectious disease susceptibility. 5' and/or 3' polymorphisms have been associated with tuberculosis, leprosy, and visceral leishmaniasis (VL). Most studies undertaken to date were under-powered, and none has been replicated within a population. Association with tuberculosis has replicated variably across populations. Here we investigate SLC11A1 and VL in India. METHODS: Nine polymorphisms (rs34448891, rs7573065, rs2276631, rs3731865, rs17221959, rs2279015, rs17235409, rs17235416, rs17229009) that tag linkage disequilibrium blocks across SLC11A1 were genotyped in primary family-based (313 cases; 176 families) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between SLC11A1 variants and VL. Quantitative RT/PCR was used to compare SLC11A1 expression in mRNA from paired splenic aspirates taken before and after treatment from 24 VL patients carrying different genotypes at the functional promoter GTn polymorphism (rs34448891). RESULTS: No associations were observed between VL and polymorphisms at SLC11A1 that were either robust to correction for multiple testing or replicated across primary and replication samples. No differences in expression of SLC11A1 were observed when comparing pre- and post-treatment samples, or between individuals carrying different genotypes at the GTn repeat. CONCLUSIONS: This is the first well-powered study of SLC11A1 as a candidate for VL, which we conclude does not have a major role in regulating VL susceptibility in India.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Temporal Registration in In-Utero Volumetric MRI Time Series

We present a robust method to correct for motion and deformations in in-utero volumetric MRI time series. Spatio-temporal analysis of dynamic MRI requires robust alignment across time in the presence of substantial and unpredictable motion. We make a Markov assumption on the nature of deformations to take advantage of the temporal structure in the image data. Forward message passing in the corresponding hidden Markov model (HMM) yields an estimation algorithm that only has to account for relatively small motion between consecutive frames. We demonstrate the utility of the temporal model by showing that its use improves the accuracy of the segmentation propagation through temporal registration. Our results suggest that the proposed model captures accurately the temporal dynamics of deformations in in-utero MRI time series.National Institutes of Health (U.S.) (NIH NIBIB NAC P41EB015902)National Institutes of Health (U.S.) (NIH NICHD U01HD087211)National Institutes of Health (U.S.) (NIH NIBIB R01EB017337)Wistron CorporationMerrill Lynch Wealth Management (Fellowship

Of cattle, sand flies and men : a systematic review of risk factor analyses for South Asian visceral leishmaniasis and implications for elimination

Background: Studies performed over the past decade have identified fairly consistent epidemiological patterns of risk factors for visceral leishmaniasis (VL) in the Indian subcontinent. Methods and Principal Findings: To inform the current regional VL elimination effort and identify key gaps in knowledge, we performed a systematic review of the literature, with a special emphasis on data regarding the role of cattle because primary risk factor studies have yielded apparently contradictory results. Because humans form the sole infection reservoir, clustering of kala-azar cases is a prominent epidemiological feature, both at the household level and on a larger scale. Subclinical infection also tends to show clustering around kala-azar cases. Within villages, areas become saturated over a period of several years; kala-azar incidence then decreases while neighboring areas see increases. More recently, post kalaazar dermal leishmaniasis (PKDL) cases have followed kala-azar peaks. Mud walls, palpable dampness in houses, and peridomestic vegetation may increase infection risk through enhanced density and prolonged survival of the sand fly vector. Bed net use, sleeping on a cot and indoor residual spraying are generally associated with decreased risk. Poor micronutrient status increases the risk of progression to kala-azar. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting the complexity of the effect of bovines on sand fly abundance, aggregation, feeding behavior and leishmanial infection rates. Poverty is an overarching theme, interacting with individual risk factors on multiple levels. Conclusions: Carefully designed demonstration projects, taking into account the complex web of interconnected risk factors, are needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid resurgence when interventions are scaled back. More effective, short-course treatment regimens for PKDL are urgently needed to enable the elimination initiative to succeed