Detection of asymptomatic Leishmania infection in Bangladesh by antibody and antigen diagnostic tools shows an association with post–kala-azar dermal leishmaniasis (PKDL) patients

Abstract Background Asymptomatic Leishmania infections outnumber clinical infections on the Indian subcontinent (ISC), where disease reservoirs are anthroponotic. Diagnostics which detect active asymptomatic infection, which are suitable for monitoring and surveillance, may be of benefit to the visceral leishmaniasis (VL) elimination campaign on the ISC. Methods Quantitative polymerase chain reaction (qPCR), loop-mediated isothermal amplification (LAMP), and the direct agglutination test (DAT) were carried out on blood samples, and the Leishmania antigen ELISA was carried out on urine samples collected from 720 household and neighbouring contacts of 276 VL and post–kala-azar dermal leishmaniasis (PKDL) index cases, with no symptoms or history of VL or PKDL, in endemic regions of Bangladesh between September 2016 and March 2018. Results Of the 720 contacts of index cases, asymptomatic infection was detected in 69 (9.6%) participants by a combination of qPCR (1.0%), LAMP (2.1%), DAT (3.9%), and Leishmania antigen ELISA (3.3%). Only one (0.1%) participant was detected positive by all four diagnostic tests. Poor agreement between tests was calculated using Cohen’s kappa (κ) statistics; however, the Leishmania antigen ELISA and DAT in combination captured all participants as positive by more than one test. We find evidence for a moderately strong association between the index case being a PKDL case (OR 1.94, p = 0.009), specifically macular PKDL (OR 2.12, p = 0.004), and being positive for at least one of the four tests. Conclusions Leishmania antigen ELISA on urine detects active asymptomatic infection, requires a non-invasive sample, and therefore may be of benefit for monitoring transmission and surveillance in an elimination setting in combination with serology. Development of an antigen detection test in a rapid diagnostic test (RDT) format would be of benefit to the elimination campaign.

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Detection of asymptomatic Leishmania infection in Bangladesh by novel antigen and antibody diagnostic tools shows strong association with PKDL patients

10.1101/2020.05.26.20113431 ◽

2020 ◽

Author(s):

Sophie Owen ◽

Faria Hossain ◽

Prakash Ghosh ◽

Rajashree Chowdhury ◽

Md. Sakhawat Hossain ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Quantitative Polymerase Chain Reaction ◽

Asymptomatic Infection ◽

Diagnostic Tools ◽

Leishmania Infection ◽

Active Infection ◽

Non Invasive ◽

Antigen Elisa ◽

Disease Reservoirs ◽

Index Cases

AbstractBackgroundAsymptomatic Leishmania infections outnumber clinical infections on the Indian sub-continent (ISC) where disease reservoirs are anthroponotic. Diagnostics which detect active asymptomatic infection, which are suitable for monitoring and surveillance, may be of benefit to the visceral leishmaniasis (VL) elimination campaign on the ISC.Methodology/Principal FindingsQuantitative polymerase chain reaction (qPCR), loop mediated isothermal amplification (LAMP), the direct agglutination test (DAT), and the Leishmania antigen ELISA were carried out on blood and urine samples collected from 720 household and neighbouring contacts of 276 VL and post kala-azar dermal leishmaniasis (PKDL) index cases, with no symptoms or history of VL and PKDL, in endemic regions of Bangladesh between September 2016 and March 2018. Of the 720 contacts of index cases, asymptomatic infection was detected in 69 (9.6%) participants by a combination of qPCR (1.0%), LAMP (2.1%), DAT (3.9%), and Leishmania antigen ELISA (3.3%). Only 1 (0.1%) participant was detected positive by all 4 diagnostic tests. Poor agreement between tests was calculated using Cohen’s kappa (k) statistics, however the Leishmania antigen ELISA and DAT in combination capture all participants positive by more than one test. We find strong evidence for association between the index case being a PKDL case (OR 1.94, p = 0.009), specifically macular PKDL (OR 2.12, p = 0.004) and being positive for at least one of the four tests.Conclusions/SignificanceLeishmania antigen ELISA detects active asymptomatic infection, requires a non-invasive sample, and therefore may be of benefit for monitoring transmission and surveillance in an elimination setting in combination with serology. Development of an antigen detection test in RDT format would be of benefit to the elimination campaign.Author summaryInfection with the parasite Leishmania donovani can lead to an asymptomatic infection with only around 5% of asymptomatics converting to visceral leishmaniasis the clinical manifestation of the infection. Serological assays detect anti-Leishmania antibodies and therefore cannot distinguish between past and active infection. Molecular assays and those which detect Leishmania antigens detect active infection. Since the signing of a memorandum of understanding in 2005, visceral leishmaniasis has been targeted for elimination in India, Nepal and Bangladesh. In an elimination setting such as Bangladesh, where disease reservoirs are anthroponotic, a relatively simple test such as the Leishmania antigen ELISA which requires a non-invasive urine sample, may be of benefit in combination with serology for surveillance and monitoring of Leishmania transmission. Development of an antigen test into a field compatible rapid diagnostic test would be of further benefit to the elimination campaign.

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577 Association Between the Use of Smokeless Tobacco and Cancer of Gingivobuccal Sulcus

British Journal of Surgery ◽

10.1093/bjs/znab259.582 ◽

2021 ◽

Vol 108 (Supplement_6) ◽

Author(s):

D S Sahni ◽

A Bamania ◽

S Ramsaha

Keyword(s):

Risk Factors ◽

Oral Cancer ◽

Smokeless Tobacco ◽

Indian Subcontinent ◽

Strong Association ◽

Cancer Staging ◽

New Delhi ◽

Prime Concern ◽

Potential Risk Factors ◽

History Of

Abstract Background Although oral cancer accounts for 2.1% of all cancer cases globally, it is surfacing as a major public threat in India. Oral cancer figures among three most common types of cancer in the Indian subcontinent, with an incidence rate of 30%. The increased availability and use of smokeless tobacco and betel quid in the recent years have further aggravated the situation. The scarcity of reports on the contribution of such risk factors in oral cancer incidence remains a prime concern. In this perspective, the association between smokeless tobacco and cancer of gingivobuccal sulcus was investigated. Method The medical records of 249 patients with cancer of gingivobuccal sulcus, attending the BRAIRCH, AIIMS, New Delhi, were retrospectively examined from 2009-2016. Demographic and clinical data including history of addictions (smoking, smokeless tobacco) were collected and patients were staged according to the 8thAJCC Cancer Staging (2017). Results Smokeless forms of tobacco were more prevalent among the patients (50.7%), in contrast to smoked tobacco (19.53%), while 29.77% were reported to consume both forms. A higher proportion of patients with smokeless tobacco addiction were diagnosed with advanced stages of cancer (56.9% in Stage III/IV). These rates were even higher (65.6%) in patients using both smokeless and smoked tobacco. Conclusions A strong association was observed between smokeless tobacco and gingivobuccal sulcus cancer, particularly in patients who kept the tobacco in the buccal vestibule after chewing, to suck, sometimesovernight. Elucidating the potential risk factors can be a key approach to design effective intervention programs to combat the growing pandemic of oral cancer in India.

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Inferring transmission trees to guide targeting of interventions against visceral leishmaniasis and post–kala-azar dermal leishmaniasis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2002731117 ◽

2020 ◽

Vol 117 (41) ◽

pp. 25742-25750

Author(s):

Lloyd A. C. Chapman ◽

Simon E. F. Spencer ◽

Timothy M. Pollington ◽

Chris P. Jewell ◽

Dinesh Mondal ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Indian Subcontinent ◽

Epidemiological Data ◽

Asymptomatic Infection ◽

Disease Spread ◽

Estimation Methods ◽

Secondary Case ◽

Duration Of Symptoms ◽

Targeted Interventions ◽

Kala Azar

Understanding of spatiotemporal transmission of infectious diseases has improved significantly in recent years. Advances in Bayesian inference methods for individual-level geo-located epidemiological data have enabled reconstruction of transmission trees and quantification of disease spread in space and time, while accounting for uncertainty in missing data. However, these methods have rarely been applied to endemic diseases or ones in which asymptomatic infection plays a role, for which additional estimation methods are required. Here, we develop such methods to analyze longitudinal incidence data on visceral leishmaniasis (VL) and its sequela, post–kala-azar dermal leishmaniasis (PKDL), in a highly endemic community in Bangladesh. Incorporating recent data on VL and PKDL infectiousness, we show that while VL cases drive transmission when incidence is high, the contribution of PKDL increases significantly as VL incidence declines (reaching 55% in this setting). Transmission is highly focal: 85% of mean distances from inferred infectors to their secondary VL cases were <300 m, and estimated average times from infector onset to secondary case infection were <4 mo for 88% of VL infectors, but up to 2.9 y for PKDL infectors. Estimated numbers of secondary cases per VL and PKDL case varied from 0 to 6 and were strongly correlated with the infector’s duration of symptoms. Counterfactual simulations suggest that prevention of PKDL could have reduced overall VL incidence by up to 25%. These results highlight the need for prompt detection and treatment of PKDL to achieve VL elimination in the Indian subcontinent and provide quantitative estimates to guide spatiotemporally targeted interventions against VL.

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Evaluation of Loopamp™ Leishmania Detection Kit and Leishmania Antigen ELISA for Post-Elimination Detection and Management of Visceral Leishmaniasis in Bangladesh

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.670759 ◽

2021 ◽

Vol 11 ◽

Author(s):

Faria Hossain ◽

Albert Picado ◽

Sophie I. Owen ◽

Prakash Ghosh ◽

Rajashree Chowdhury ◽

...

Keyword(s):

Visceral Leishmaniasis ◽

Control Strategies ◽

Indian Subcontinent ◽

Lamp Assay ◽

Dried Blood Spots ◽

Diagnostic Tools ◽

Real Time Quantitative Pcr ◽

Antigen Elisa ◽

Eiken Chemical ◽

Quantitative Pcr Assay

With reduced prevalence of visceral leishmaniasis (VL) in the Indian subcontinent (ISC), direct and field deployable diagnostic tests are needed to implement an effective diagnostic and surveillance algorithm for post-elimination VL control. In this regard, here we investigated the diagnostic efficacies of a loop-mediated isothermal amplification (LAMP) assay (Loopamp™ Leishmania Detection Kit, Eiken Chemical CO., Ltd, Japan), a real-time quantitative PCR assay (qPCR) and the Leishmania antigen ELISA (CLIN-TECH, UK) with different sampling techniques and evaluated their prospect to incorporate into post-elimination VL control strategies. Eighty clinically and rK39 rapid diagnostic test confirmed VL cases and 80 endemic healthy controls were enrolled in the study. Peripheral blood and dried blood spots (DBS) were collected from all the participants at the time of diagnosis. DNA was extracted from whole blood (WB) and DBS via silica columns (QIAGEN) and boil & spin (B&S) methods and tested with qPCR and Loopamp. Urine was collected from all participants at the time of diagnosis and was directly subjected to the Leishmania antigen ELISA. 41 patients were followed up and urine samples were collected at day 30 and day 180 after treatment and ELISA was performed. The sensitivities of the Loopamp-WB(B&S) and Loopamp-WB(QIA) were 96.2% (95% CI 89·43-99·22) and 95% (95% CI 87·69-98·62) respectively. The sensitivity of Loopamp-DBS(QIA) was 85% (95% CI 75·26- 92·00). The sensitivities of the qPCR-WB(QIA) and qPCR-DBS(QIA) were 93.8% (95% CI 86·01-97·94) and 72.5% (95% CI 61·38-81·90) respectively. The specificity of all molecular assays was 100%. The sensitivity and specificity of the Leishmania antigen ELISA were 97.5% (95% CI 91·47-99·70) and 91.95% (95% CI 84·12-96·70) respectively. The Leishmania antigen ELISA depicted clinical cure at day 180 in all the followed-up cases. Efficacy and sustainability identify the Loopamp-WB(B&S) and the Leishmania antigen ELISA as promising and minimally invasive VL diagnostic tools to support VL diagnostic and surveillance activities respectively in the post-elimination era.

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A randomized, open-label study to evaluate the efficacy and safety of liposomal amphotericin B (AmBisome) versus miltefosine in patients with post-kala-azar dermal leishmaniasis

Indian Journal of Dermatology Venereology and Leprology ◽

10.25259/ijdvl_410_19 ◽

2021 ◽

Vol 87 ◽

pp. 34-41

Author(s):

Krishna Pandey ◽

Biplab Pal ◽

Niyamat Ali Siddiqui ◽

Chandra Shekhar Lal ◽

Vahab Ali ◽

...

Keyword(s):

Amphotericin B ◽

Liposomal Amphotericin ◽

Indian Subcontinent ◽

Quantitative Polymerase Chain Reaction ◽

Liposomal Amphotericin B ◽

Cure Rate ◽

Open Label ◽

Kala Azar ◽

Lost To Follow Up

Background: Treatment of post-kala-azar dermal leishmaniasis cases is of paramount importance for kala-azar elimination; however, limited treatment regimens are available as of now. Aim: To compare the effectiveness of liposomal amphotericin B vs miltefosine in post-kala-azar dermal leishmaniasis patients. Methodology: This was a randomized, open-label, parallel-group study. A total of 100 patients of post kala azar dermal leishmaniasis, aged between 5 and 65 years were recruited, 50 patients in each group A (liposomal amphotericin B) and B (miltefosine). Patients were randomized to receive either liposomal amphotericin B (30 mg/kg), six doses each 5 mg/kg, biweekly for 3 weeks or miltefosine 2.5 mg/kg or 100 mg/day for 12 weeks. All the patients were followed at 3rd, 6th and 12th months after the end of the treatment. Results: In the liposomal amphotericin B group, two patients were lost to follow-up, whereas four patients were lost to follow-up in the miltefosine group. The initial cure rate by “intention to treat analysis” was 98% and 100% in liposomal amphotericin B and miltefosine group, respectively. The final cure rate by “per protocol analysis” was 74.5% and 86.9% in liposomal amphotericin B and miltefosine, respectively. Twelve patients (25.5%) in the liposomal amphotericin B group and six patients (13%) in the miltefosine group relapsed. None of the patients in either group developed any serious adverse events. Limitations: Quantitative polymerase chain reaction was not performed at all the follow-up visits and sample sizes. Conclusion: Efficacy of miltefosine was found to be better than liposomal amphotericin B, hence, the use of miltefosine as first-line therapy for post-kala-azar dermal leishmaniasis needs to be continued. However, liposomal amphotericin B could be considered as one of the treatment options for the elimination of kala-azar from the Indian subcontinent.

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Factor V Leiden Is Associated with Repeated and Recurrent Unexplained Fetal Losses

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656060 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0822-0824 ◽

Cited By ~ 145

Author(s):

Elvira Grandone ◽

Maurizio Margaglione ◽

Donatella Colaizzo ◽

Marina d'Addedda ◽

Giuseppe Cappucci ◽

...

Keyword(s):

Protein C ◽

Strong Association ◽

Activated Protein C ◽

Fetal Loss ◽

Factor V Leiden ◽

Factor V ◽

Significant Difference ◽

History Of ◽

Fv Leiden ◽

Caucasian Women

SummaryActivated protein C resistance (APCR) is responsible for most cases of familial thrombosis. The factor V missense mutation Arg506>Gln (FV Leiden) has been recognized as the commonest cause of this condition. Recently, it has been suggested that APCR is associated with second trimester fetal loss. We investigated the distribution of FV Leiden in a sample (n = 43) of Caucasian women with a history of two or more unexplained fetal losses. A group (n = 118) of parous women with uneventful pregnancies from the same ethnical background served as control. We found the mutation in 7 cases (16.28%) and 5 controls (4.24%; p = 0.011). A statistically significant difference between women with only early fetal loss vs those with late events (p = 0.04) was observed. Our data demonstrate a strong association between FV Leiden and fetal loss. Furthermore, they indicate that late events are more common in these patients.

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DETECTION OF LEISHMANIA INFECTION IN STRAY DOGS IN HUMAN LEISHMANIASIS ENDEMIC AREA IN MYMENSINGH DISTRICT WITH ITS POSSIBLE PUBLIC HEALTH SIGNIFICANCE IN BANGLADESH

Journal of Veterinary Medical and One Health Research ◽

10.36111/jvmohr.2019.1(1).0009 ◽

2019 ◽

Vol 1 (1) ◽

Author(s):

M. A. Hossen

Keyword(s):

Visceral Leishmaniasis ◽

Asymptomatic Carrier ◽

Asymptomatic Infection ◽

Reservoir Host ◽

Sand Fly ◽

Leishmania Infection ◽

Endemic Region ◽

Stray Dogs ◽

Human Leishmaniasis ◽

Strip Test

Background: Leishmaniasis is primarily caused by two species of Leishmania (L. donovani and L. infantum) of which clinical infection with L. infantum has been recognized in both humans and dogs as zoonotic disease with dogs as the main reservoir hosts in the Mediterranean, the Middle East, Asia and South America. Although L. donovani has been associated with both clinical and asymptomatic infection in humans but it is still associated with asymptomatic infection in dogs in Indian sub-continent without any evidence of zoonotic infection. Objectives: The objective of this research was to investigate the potentiality of dog as reservoir host for visceral leishmaniasis in the human leishmaniasis endemic regions in Bangladesh. Materials and Methods: A total of 20 stray dogs in the human VL endemic areas of Mymensingh district were captured for the detection VL during the period of November 2010 to May 2011. The dipstick test rK39 (Bios International; n = 20), Giemsa’s stained impression smears of liver and spleen (n = 6) and PCR with the tissue of liver and spleen (n = 6) were tested as per manufacturer instructions and conventional standard methods. Results: Out of 20 stray dogs examined, 4 (20.0%) were positive for L. donovani infection with rK39 strip test. Of the six randomly selected dogs tested with Modified Giemsa’s stained of impression smears of spleen and liver showed 2 (33.33%) positive whereas PCR technique detected 5 (83.33%) positive for L. donovani. Results of PCR showed 145bp amplicon, specific for L. donovani infection in 83.33% stray dogs. Conclusions: This study reveals that a high percentage of L. donovani asymptomatic carrier infections occur in dogs and evidence indicates that dogs and humans may potentially serve as a source of infection to sand fly vectors and accordingly dogs can be recognized as a probable animal reservoir for the Leishmania infection in the endemic region in Bangladesh. However, further studies are required to determine the ability of dogs to transmit the L. donovani to the vector sand fly in nature and its evidence on ‘One Health’ perspectives. Keywords: Visceral leishmaniasis, Endemic region, Stray dogs, rK39 strip test, Giemsa’s stained liver and spleen impression smears, PCR, Reservoir host, Mymensingh

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Violence and depression among pregnant women in Egypt

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-03932-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hanan M. Ghoneim ◽

Mohamed Elprince ◽

Tamer Yehia M. Ali ◽

Waleed F. Gharieb ◽

Amal A. Ahmed

Keyword(s):

Intimate Partner Violence ◽

Sexual Violence ◽

Partner Violence ◽

Strong Association ◽

Depression Scale ◽

Intimate Partner ◽

University Hospital ◽

P Value ◽

Significant Difference ◽

History Of

Abstract Background Depression is a serious mental health disorder that might affect women in the childbearing period. Incidences increase during pregnancy as well as after delivery. Its association with intimate partner violence (defined as physical, sexual, or psychological harm by a current or former partner) has been reported in many countries. Data about this sensitive issue are lacking in Egypt. The aim of the study was to determine the relation between intimate partner violence and depression during pregnancy. Methods This was a case control study conducted at the outpatient clinics in Suez Canal University hospital, from January 2019 to March 2020. The study included two groups, the study group included women exposed to violence during the current pregnancy and a control one included women with no history of violence. Both groups were recruited according to the predetermined inclusion criteria (women aged 18-45 years, continuous marital relationship, no history of depression in current or previous pregnancies, and singleton pregnancy). Women were asked to complete the Arabic validated NorVold Domestic Abuse Questionnaire (measuring four types of abuse: emotional, physical, sexual, and violence in the health care system, the last one being excluded). Depression was evaluated using the Arabic validated form of the Edinburgh Postnatal Depression Scale (comprises 10 questions that represent patients’ feelings in the last 7 days). The main outcome measure was to assess the association between intimate partner violence and depression. Results We recruited 158 women in each group. Both groups were matched in their demographic characters. Although emotional violence was reported prominently among women exposed to IPV 87.9% (139/158), it was not significantly reported in depressed women (P value 0.084). Physical and sexual violence were significantly reported among depressed women (P value 0.022 and 0.001, respectively). There was a significant difference between women exposed to violence and those who were not exposed to violence in the total depression scores (13.63 ± 5.47 and 10.65 ± 5.44, respectively with a p value < 0.001). Emotional (p value < 0.001) and sexual violence (mild and severe with p value of 0.026 and 0.002 respectively) had significant roles as risk factors for depression during pregnancy in single regression and after control of other confounders. Conclusion There was a strong association between intimate partner violence and depression during pregnancy.

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Anxiety disorders and substance abuse

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1378 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S384-S384

Author(s):

I. Prieto Sánchez ◽

M.D.L.C. Ramírez Domínguez ◽

S. Fernández León ◽

M. Reina Domínguez ◽

N. Garrido Torres ◽

...

Keyword(s):

Anxiety Disorders ◽

Dual Diagnosis ◽

Behavioral Problems ◽

Strong Association ◽

Epidemiological Studies ◽

Distinctive Features ◽

Other Substances ◽

History Of ◽

Competing Interest ◽

Substance Disorder

IntroductionPatients with anxiety disorders are more vulnerable to develop other comorbid conditions. In particular, large epidemiological studies show a strong association between different anxiety disorders and substance use disorders.ObjectivesTo show the prevalence of major anxiety disorders and the consumption of different substances. As well as the particular characteristics of this dual diagnosis and treatments that have proven more effective.MethodsExhaustive review of all the material published on this topic in the recent years.ConclusionsNearly 24% of patients with anxiety disorder suffer from a comorbid substance disorder use in their lifetime (17.9% diagnosis of alcohol abuse or dependence diagnosis and 11.9% of abuse or dependence on other drugs). Dual patients show a number of distinctive features, such as more frequency in males, family history of alcohol or other substances abuse and behavioral problems, early parental loss among others.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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