Details of the Significant Projects/Trials of BHU/KAMRC
Sl
Project Title
PI / Co-PI
DetailsofFunding Agency
Industry / Public/Sector Undertaking/
Others / Collaborative/Sponsored
Project Durationin Years
Type of Beneficiary
Output/OutcomeoftheProject
1
Visceral Leishmaniasis in Bihar State, India Phase 1
PI
NationalInstitute of Allergy and Infectious
Diseases,National Institutes of Health,USA
Sponsored
2007-2012
Government
Documentedthataround80-90%of all L.
donovani infections did not lead to clinical disease. The ratio ofincident
clinical disease to incident seroconversion in these communities was 10 to 1
andrecent seroconverters had a ten timeshigherrisktodevelopdisease in the
subsequent 18 months than those who did not sero-convert.
Identified and defined the subsets of
regulatory T cells play a role in pathogenesis of human VL, to identify the
cellular source of the elevated IL-10 that is associated with active disease,
and to validate IL-10orothersuppressivefactorsas potential targets to enhance
the anti-parasitic immune response.
Identified the HLA DR-DQ region (encodingMHC,classII,DRandDQ)
as the majorsusceptibility locus across India and Brazil.
2
VisceralLeishmaniasisin Bihar State,
India
Phase2
PI
NationalInstitute of Allergy and Infectious
Diseases,National Institutes of Health,USA
Sponsored
2012-2017
Government
Documentedthenovelinsightsin
thenaturalhistoryofL.donovani infection.
EstablishedtheDSScoveringover
1,250,000peopleinMuzaffarpur, one of the major VL endemic districts inBihar.
Reported the association of co-
infections with other neglected tropical diseases (NTD) as a determinant for
progression to VL, andopeninguptoawiderscopefor understanding NTDs in the
project area.
Reported the genetic determinants of
seroconversion and, through transcriptional profiling, understand progression
from asymptomatic infection to disease
Reportedthetemporalandspatial variation
in P. argentipes abundance, biting behaviorand infectivity, inside and around
human dwellings.
DocumentedthefunctionofCD8+T cells in
human VL.
Reported thetranscriptional
signaturesinwholebloodofactive VL.
3
VisceralLeishmaniasisin Bihar State,
India
Phase3
PI
NationalInstitute of Allergy and Infectious
Diseases,National Institutes of Health,USA
Sponsored
2017-2022
Government
EstablishedtheTMRCasacenterof excellence
for surveillance and monitoring transmission in
thecontextofeliminationofvisceral leishmaniasis (VL) epidemiological evidence
to guide policy in the VL
eliminationinitiative-
buildingmathematical transmission models
and spatial risk maps
Documented the role of Dogs as Reservoirs
for Leishmania donovani, Bihar, India
Evaluateinsecticideresistanceof
fieldpopulationsofP.argentipes and determined the biochemical/molecular
markers associated with resistance in P.argentipes.
Reported the frequency and
activationstatusofkeyimmune cells¸ including T cells and monocytes, in the
blood, bone marrow and skin of VL patients before, during and after drug
treatment.
4
Setting the Post-Elimination
AgendaforKala-AzarinIndia (SPEAKIndia)
PI
LondonSchoolof Hygeine and Tropical Medicine/
Bill & Melinda Gates Foundation
Sponsored
2019-2020
Government
Assessedthethreemostcommonly used
serological markers for Leishmania donovani infection in the Indian
subcontinent in three different categories of endemicity, andidentifiedtherK39ELISAasthe
most promising candidate going forward.Inaddition,weemphasize
childrenasaparticularlyinteresting target group, as they represent relatively
recent infections.
This study provides a first insight into
the potential of serosurveillance for monitoring of Leishmania transmission
in the post-elimination phase.
Reported that current diagnostic
algorithm combining suggestive clinicalfeatureswithapositiverK39 RDT still
seems valid in the current
low-endemicsettinginIndia.
5
Xenodiagnosis of Visceral Leishmaniasis,
Post Kala- azar Dermal Leishmaniasis andAsymptomaticsubjects usingPhlebotomine
Sand Flies
PI
Bill & Melinda GatesFoundation
Sponsored
2015-2018
Government
First investigation in India for the
infectiousness to sandflies of patients with visceral leishmaniasis or
post-kala-azar dermal leishmaniasis following treatment and of people with
asymptomatic infectionlivinginareaswithhighL donovani transmission.
Reported that patients with active
visceral leishmaniasis or post-kala- azar dermal leishmaniasis, but not asymptomatic
individuals or treated patients, were infectious to vector sandflies.
Reported that infectiousness
increasedwithseverityofdiseasein patients with active visceral leishmaniasis.
Reported that Treatment of patients with
visceral leishmaniasis or post-kala-azar dermal leishmaniasis with currently
recommended drugs was highly effective in reducing their infectiousness to
flies.
6
Synthesis and application of nano
materials towards energy and EMI shielding, targetted drug delivery and
theranostic application of biocompatible microparticle derivedfromhumanplatelet
for nano therapeutics
PI
Departmentof Science and Technology,
Governmentof India
Sponsored
2017-2020
Government
Development of an amine- functionalized
versions of carbon nanostructures, namely f-CNT and
f-Graphene(f-Grap)andfoundthat f-Grap is a safe and reliable therapeutic
option over the other carbon-based nanoparticles (NPs), i.e., f-CNT-AmB,
f-Grap-AmB, and conventionalAmB.
7
Epidemiology of Visceral Leishmaniasis in
MuzaffarpurDistrict,Bihar (EpiVL)
PI
TheFoundation fortheNational Institutes
of Health(FNIH), USA
Sponsored
2014-2016
Government
Establishment of a new, fully functional
insectary that will permit containment, rearing,
infection,andmanipulationoffield caught sand flies,
Establishmentofworkingcolonyof
P. argentipes that has been
certifiedforuseinxenodiagnostic
procedures.
8
Designing combination immunotherapy and
drug treatmenttocontrolchronic infectious diseases
PI
Indo-Australian Biotechnology Fund
Sponsored
2018-2021
Government
Significant progress in clinical studies
at KAMRC, India and pre- clinicalstudiesatQIMR,Brisbane.
Discoveredimmune manipulation can
antagonize anti-parasitic immunity.
Identifiednewpotentialimmune pathways for
therapeutic advantage.
Confirmed findings from the
mousemodelofVLwithclinical samples from patients.
Found that blocking signals
throughanimmunereceptorcan improve immunity and reduce parasite burdens.
Validated finding using patient
cells,boostingtheirresponseto parasites.
Extending researchto understand this
pathway and identify new ways to improve anti-parasitic
immunityduringVL.
9
New tools for monitoring drug resistance
and treatment response in VisceralLeishmaniasisinthe Indian subcontinent ( KALADRUG-R)
PI
European Commission
Sponsored
2009-2013
Government
Evaluated the efficacy and safety
ofmiltefosineforthetreatmentof VL after a decade of use in India and found
that efficacy of miltefosine has significant decline
inthefinalcurerate(from94%to
90%),andadoublingof the
relapseratewithin10years.
Development of rapid assays to monitor
the emergence and spreadofclinicallyrelevantSSG- resistant Leishmania
parasites.
Reported the whole genome
sequencingdataofIndianparasite strains.
10
ComparativeEvaluationof PCR Primers In
Diagnosis and Prognosis of Indian VisceralLeishmaniasis(VL) andPostKala-AzarDermal
Leishmaniasis (PKDL)
PI
Indian Council of Medical Research
(ICMR),NewDelhi
Sponsored
2007-2010
Government
The present study was planned to
designaLeishmania specific diagnostic assayandtoevaluateitssensitivityand
specificity on a sample size, which to thebestofourknowledgeisthelargest ever
screenedinone study.Leishmania specific primers were developed using 18SrRNAgeneandtheirsensitivitywas
evaluated on 500 parasitologically confirmedpatientswithVLand25Post Kala-azar
Dermal Leishmaniasis (PKDL) patients. Specificity was calculated on 250
healthy endemic controls, 250 healthy non endemic controls and 250 non leishmanial
diseases like malaria.OurPCRassayhadasensitivity of 87.8% (95%CI: 84.1–89.8)
using 200
µL of patient's peripheral-blood.
Specificitywasabsoluteinnon-endemic healthy controls and in subjects with
different diseases while in endemic controlsitwas84%(95%CI:78.9–88.0).
Itsoverallspecificitywas94.6%(95%CI- 92.8–96.1). The high sensitivity of this
PCR diagnostic test with relatively non- invasive peripheral blood sampling
method opens up the possibility of its deployment in field for the routine
diagnosis of VL.
11
Efficacy,acceptabilityand cost-effectivenessoflong
lastinginsecticidetreated nets in the prevention of Kala-azar
PI
European Commission
Sponsored
2006-2009
Government
Large-scaledistributionoflong- lasting
insecticide-treated nets (LLINs)wastestedtoreduceVL incidence in India and
Nepal.
A paired cluster randomized
controlledtrialfoundnosignificant difference in VL seroconversion or clinical
incidence between intervention and control groups.
LLINs showed a small, non- significanteffectonVLprevention,
with confidence intervals not ruling out a possible 50% change.PMID: 21190965
12
AphaseI,open-label,dose-
escalatingstudytoevaluate the safety, tolerability, and immunogenicity of the
Leish-111f+MPL-SEvaccine (recombinantthree-antigen
Leishmaniapolyproteinwith adjuvantMPL-SE)inhealthy
adults in India
PI
InfectiousDiseasesResearch Institute/Bill&
Melinda Gates Foundation
Sponsored
2007-2010
Government
Three cohorts of 6 DAT-negative and 6
DAT-positive subjects were enrolled in an open-label, dose-escalating,
uncontrolled clinical trial and received threeinjectionsoftheLEISH-F1+MPL-SE
vaccine (consisting of 5μg, 10μg, or 20μg recombinant Leishmania polyprotein
LEISH-F1 antigen+25μg MPL®-SE adjuvant). The vaccine was
safeandwell-toleratedinDAT-negative and DAT-positive subjects and induced
T-cell production of IFN-γ and other cytokines in response to stimulation
with the LEISH-F1 antigen. This clinical trial shows that the LEISH-F1+MPL-SE
vaccine is safe and immunogenic in healthy subjects with and without history
of previous infection with Leishmania donovani. PMID: 21414377
13
Patient-centric supramolecular formulations
of new anti- leishmanialdrugsforIndian Communities
PI
Durham University
Sponsored
2020-2023
Government
The main objective of this project was to
combine and apply medical anthropology and community
engagementmethodstoidentifydirect optimal drug delivery methods &formulation
designamong communities in India with leishmaniasis (Kala-azar) endemic.
DETAILSOFTHESURVEY
4districtsi.e.Muzaffarpur,Vaishali
,Sitamarhi&Saranwereselected
5villagesfromeachofthedistricts were
taken purposively according to the availability of patients.
Indepthinterviewwasconducted with new
patients (of 2021), old patient, their care giver, key respondent
(Influential person of the village) & ASHA from each village.
InterviewofCMO,DMOStaff Nurse &
Pharmacist were conducted.
Intotal116respondentswere interviewed.
FINDINGSOFTHEPATIENTS&CARE GIVERS
& KEY RESPONDENTS
Almost all of them aware about kala
azarandthemoststatedsymptomwas continuous fever for 10 to 15 days.
Garbageandcattledungfoundtobe the main
mode of transmission.
Mosquitoesareknownasvectorof kala-azar
among majority of the
population.Bothnewandoldpatients
were satisfied with the current
medication as the previous treatment regimen was of long duration. When they
were asked about the change in drugformulationforVL,mostofthem
supportedtabletformandsomeasked vaccine for prevention of VL.
AccordingtoHealthprovidersnewdrug
formulationsshouldbepatientfriendly. They suggested the single time oral
medication as the best drug delivery method.
Dr.SwetaSinghPost-DoctoralResearch
Associate visited Keele & Durham University where she gave her
presentationthepreliminaryfindingsof the research.
Dr. Sangeeta Kansal visited KMMS
SymposiumonMentalHealthinSouth Asia from 22-24 March 2023. And presented
paper entitled “Need of Continuum of Care Approach for
ImprovementofMentalHealthamong Young Adults”
A participatory research work was
conducted at BHU on 26th& 27th February2023incollaborationwith Durham
University (UK) & PRAXIS.
14
Establishment of a test of cure tool for
monitoring Visceral Leishmaniasis and Post Kala-azar dermal Leishmaniasis;amulticentric
study
PI
Indian Council of Medical Research
(ICMR),NewDelhi
Sponsored
2022-2023
Government
1)This study has identified the most
appropriate molecular approach (SYBR Green qPCR assay) for
monitoringtheparasitekinetics,so as to facilitate replacement of the
existinggoldstandardwhichis
identification of Leishman Donovan (LD)
bodies in tissue aspirates (splenic aspirates or a skin punch biopsy) of
suspected casesofVLandPKDLrespectively, withalongtermviewtoeliminate
thediseasereservoirandfacilitate success of the Leishmaniasis
eliminationprogram.
Most importantly, it will be very
effective for diagnosing macular PKDL (which presently constitutealmost 50%
of the PKDL burden), where it is difficult to identify LD bodies in tissue
biopsiesandisoftenmisdiagnosed as other hyopigmentary disorders (e.g.
vitiligo, leprosy) with overlapping clinical features and
geographicalendemicity.
Furthermore, this assay could correctly
monitor treatment efficacyforbothVLandPKDL,thus proving to be an effective
‘test of cure’ tool for diagnosis and
monitoringofthesecases.
15
Field validation of Leish- LAMP detection
kit for diagnosisofKala-azar(KA) andPostKala-azarDermal Leishmaniasis (PKDL)
in endemic zone
PI
Indian Council of Medical Research
(ICMR),NewDelhi
Sponsored
2022-2024
Government
The diagnostic and prognostic
utilityofLeish-LAMPtestwouldbe validated in field settings in order
toestablishitsuseasarapidpoint- of-care testing device for VL and PKDL.
1.toprovideevidenceastowhether alternate
clinical specimens viz. dried blood spot/lysed blood/tissue can be used in
field settings for the diagnosis of KA/PKDL using Leish LAMP test.
16
MaintainingIndia’svisceral leishmaniasiselimination
campaign by mitigating insecticide resistance in sand flies
PI
Indian Council of Medical Research
(ICMR),NewDelhi
Sponsored
2023-2026,
Ongoing
Government
India’s VL elimination campaign
reliesonIndoorResidualSpraying (IRS) with synthetic insecticides.
Due
to DDT resistance in sand flies,alpha-cypermethrinis now usedforIRS;however,itssimilar
modeofactiontoDDTraisesthe risk of resistance development.
This study evaluated insecticide
susceptibility in Phlebotomus argentipes sand flies (wild-caught and F1
progeny) using the CDC bottle bioassay.
Knockdown mortality rates were
91.19–99.47%forwild-caughtand 91.70–98.89% for F1 progeny; 24-
hourmortalityrangedfrom89.34– 98.93% (wild-caught) and 90.16–
98.33%(F1).
Potential resistance development were
seen in P. argentipes, highlighting the need for continuousmonitoringtosustain
VL elimination efforts.
17
Effect of Recombinant humangammainterferon… aclinical&
immunologicalstudy
PI
Indian Council of Medical Research
(ICMR),NewDelhi
Sponsored
1991-1994
Government
IFN-γ with antimony accelerated parasite
clearance in VL, with 63% parasite-free by day 10 compared to 7% in controls.
Clinical cure rates by day 20 were 93%
for the IFN-γ group versus40% for antimony alone, allowing earlier treatment
discontinuation for IFN-γ responders.
Day 30 and 6-month cure rates werehigherintheIFN-γgroup,
thoughdifferenceswerenot
statisticallysignificant.
4.IFN-γ shows potential for faster clinical and parasitologic
responses, suggesting it may help reducetreatmentdurationforVL.
PMID:7706829
18
Immunochemotherapyfor
visceralleishmaniasis : Interferon-yplusantimony
PI
Rockfeller Foundation,USA
Sponsored
1995-1996
Government
Three treatment regimens were
testedforVL:Sbalonefor30days, Sb plus IFN-gamma for 30 days, and Sb plus
IFN-gamma for 15 days.
Aim was to evaluate if IFN-gamma boosts
Sb effectiveness and if a shorter 15-day combination is as effective as
30-day Sb alone.
Six-month cure rates were similar
acrossgroups:36%(Sbalone),49% (Sb + IFN-gamma for 30 days), and
42%(Sb+IFN-gammafor15days).
No significant improvement was observed
with IFN-gamma, indicating limited benefit inregions with high Sb resistance.
PMID: 9333181
19
Visceral Leishmaniasis and PKDL : New
Therapeutic, ImmunologicandDiagnostic Studies,andsitepreparation for Vaccine
Trial
PI
RCS/WorldHealth Organization (WHO),Geneva
Sponsored
2000-2004
Government
We tested standard amphotericin B
deoxycholatemixedwithacommercial fatemulsionasshort-coursetreatment
forIndianvisceralleishmaniasisinBihar in1997/98.Seventychildrenandadults with
splenic aspirate-documented infection, 23 of whom had failed prior antimony
(Sb) therapy, received 5 alternate-day infusions of 2 mg/kg.
Other than anticipated infusion-related feverand/orchills,treatmentwassafe
and well tolerated. There were 4
treatmentfailuresyieldingdefinitive
curesin65of70patients(92.9%,CI
84.1-97.6%).. Short-course treatment with
amphotericin B-fat emulsion is active, cost-effective treatment for patients
with visceral leishmaniasis includingthosewithSb-unresponsive infection.
PMID: 10897369
2.Sera from 61 Indian patients with
visceral leishmaniasis were tested for thepresenceofThelper1(Th1)celland Th2
cell-associated cytokines (interleukin-4 [IL-4]and IL-10). The IFN-
gammaactivitywasdetectedin53%.IL- 4 in 84%, and IL-10 in 56% of patient
samples. Quantitative data indicated comparablemeanlevelsofIFN-gamma,
butthree-and13-foldincreasesinIL-10 and IL-4, respectively. Undetectable
IFN-gammaactivity,observedin47%of
patients. In patients who had failed prior therapy (n = 29) compared with
previously untreated patients (n = 32). IFN-gammalevelswere 67%lowerand IL-4
levels were two-fold higher, IL-10 activity was comparable. These results
using peripheral blood support the presence of a suppressive Th2 cell-
associated immune response in symptomaticIndiankala-azarandpoint to a
possible role for IL-4. PMID:
9180602
20
Kala-AzarDiagnosticKit and commitment
ICMR in Kala- Azareliminationprogramme for BHU, Varanasi
PI
Indian Council of Medical Research
(ICMR),NewDelhi
Sponsored
2003-2004
Government
Dr Sundar evaluated the direct
agglutination test (DAT), using freeze- dried (FD) and aqueous (AQ) antigen, andthe
rK39 immunochromatographic strip test in the diagnosis of Indian visceral
leishmaniasis (VL). Sera from 508 subjects (150 parasitologically
confirmedpatientswithVL,100and
153healthycontrolsfromnon-endemic
andendemicregions,respectively,and 105 patientswithother diseases) were
tested.Thesensitivityofthetestswere as follows: DAT (FD), 96% (95% CI 91-
98);DAT(AQ),97%(95%CI93-99);rK39
strip test, 99% (95% CI 95-100). The
specificityofDAT(FD),DAT(AQ)and rK39striptestswere85%(95%CI81-
88),87%(95%CI83-91)and89% (95%
CI 86-92), respectively. A significant
correlation (high degree of agreement) was observed between all tests
(kappa>0.80). We conclude that the sensitivity of FD antigen is comparable
to that of AQ antigen. Similarly, the rK39striptestisassensitiveastheDAT,
butthestriptest'sgreaterconvenience of use makes it a better tool for
diagnosis of VL in peripheral areas of
endemicregions.PMID:16325874
21
CenterofExcellence(COE) for HIV care
PI
NationalAIDS Control Organization, Department
of HealthandFamily Welfare, Governmentof India
Scheme
2008-2018
Government
This centre was established in 2011 with
the mandate for research, training and mentoring.
We mentor all the 15 ART centre linked to
us as and when needed, especiallywithdifficulttomanage patients. Our team
members constitute the SACEP (State AIDS clinicalExpertpanel).Whichtakes
decision on change of therapy fromfirst line to second line as well to third
line ART for PLHIV referred to us from all over UP.
We have conducted >50 onsite trainings
for ART Staff and >30 online training through regional
distancelearningseminarbothfor
nationalandstateparticipants.
Our research has focused on programmatic
needs.We have assessedtheoutcomeoffirstline, second line and third line ART
under programmatic conditions.
We have also assessed the drug
mutationsacquiredbytreatment naïve PLHIV and those failing therapy.
We have shown the high
prevalenceofHPVInfectionaswell as NCD (non communicable disease) amongPLHIV .
We have highlighted the high prevalence
of cryptococcal meningitisinthisregionandthe importance of screening serum
CrAg (cryptococcal antigen) in PLHIV with CD4 <200/µL.
22
ARTCenter
PI
NationalAIDS Control Organization, Department
of HealthandFamily Welfare, Governmentof India
Scheme
2005-2018
Government
We were the first and still the largest
ART centreof the state of UttarPradeshwithapopulationof 241 million. It
caters to the needs of PLHIV of eastern UP, neighbouring states of Bihar,
Jharkhand, Chhattisgarh.
Through this project we were able
toprovideFreeantiretroviraldrugs to>than10,000Peoplelivingwith HIV in this
region. We werethe first centre to providefirst line, second line and third
line antiretroviraldrugstoPLHIVofthis region.Asatertiarycarecentrewe have
managed more than 1000 PLHIV with serious opportunistic infection per year
referred to us from other centres.
Itistheonlycentrewhichprovides
free Viral load testing for PLHIV from
many ART Centre linked to us. It has developed as a Centre which provides
comprehensive care for HIV and provides ART, antitubercular drugs drugs for
opportunistic infection, managementofnoncommunicable disease,hepatitis and
cancer screening under one window.
23
Toassessefficacyandsafety of orally
administered miltefosine in patients with visceral leishmaniasis with Controlgroup:Amphotericin
B
PI
grants from Zentaris (to Dr. Sundar) and
the Special Program forResearchand Training in TropicalDiseases of the United
Nations Development Program,the WorldBank, and theWorldHealth Organization
Sponsored
3years
14.5.1998
Government
Two treatments for VL were
compared:oralmiltefosine((50or 100 mg daily for 28 days, 299 patients).) and
intravenous amphotericin B (1 mg/kg every other day for 15 doses, 99 patients).
Initialcureratewas100%inboth groups.
Six-monthcurerateswere94%for miltefosine
and 97% for amphotericin B.
Miltefosinehadmildsideeffects
(vomitingin38%anddiarrheain 20% of patients).
Miltefosine is effective, safe, and
advantageous as an oral treatment,especiallyinareaswith
drugresistance.
24
LOW-DOSE LIPOSOMAL AMPHOTERICIN B IN
REFRACTORY INDIAN VISCERALLEISHMANIASIS:A MULTICENTERSTUDY
PI
GileadSciences (Nexstar Pharmaceuticals)
Sponsored
1year
11.01.2000
Government
84 patients with VL unresponsive to
antimony were treated with liposomalamphotericinBatdoses
of3.75,7.5,and15.0mg/kgover5 days.
Apparentcurewasevaluatedat2 weeks, and
definite cure was assessed at 6 months post-
treatment.
Side effects included mild to
moderatefeverin29%andrigors in 44% of patients.
Definite cure rates at 6 months
were89%(3.75mg),93%(7.5mg),
and97%(15.0mg).
Low-doseliposomalamphotericin B over 5
days effectively cured most patients with VL, with no significantdifferenceincurerates
across dosage groups.
PMID:12135284
25
A phase III multicentre
randomized,controlled, clinical trial to assess the safety and efficacy of injectableParomomycinin
patients with VL
PI
Bill & Melinda Gatesfoundation
_-InstituteofOne WorldHealth
Sponsored
2004-6
Government
Paromomycin was found noninferior to
amphotericin B for treating VL, with cure rates of
94.6%forparomomycinand98.8% for amphotericin B.
Mortalitywaslessthan1%inboth groups.
Adverse events were more frequent with paromomycin,
includinginjection-sitepain(55%), transient liver enzyme elevation (6%), and
reversible ototoxicity (2%).
Amphotericin B was associated with
nephrotoxicity (4%), fevers (57%),rigors(24%),andvomiting
(10%).
Paromomycin is a viable alternative to
amphotericin B for visceral leishmaniasis treatment in
India.PMID:17582067
26
Institute for OneWorld
HealthProtocolNo.VLPM03 “A Phase 4 Study to Expand Access While Assessing the
Safety and Efficacy of
ParomomycinIMInjectionin
PI
The Bill and MelindaGates Foundation
Sponsored
2007-9
Government
A phase 4 study assessed paromomycin’s
safetyand efficacy in treating VL in an outpatient setting in Bihar, India.
506patients(adultsandchildren)
wereenrolled;98%completedthe
anOutpatientSettingforthe Treatment of
Visceral Leishmaniasis (VL) in India”.
fulltreatmentcourse.
Study completion rates were 94%
fortheITTpopulationand96%for theefficacy-evaluablepopulation.
Initialcureratewas99.6%,witha final cure
rate of 94.2% at 6 months.
Grade3or4adverseevents occurred in 5% of
patients, primarily mild liver enzyme elevations.
Paromomycinwasconfirmedasa safe and
effective outpatient
treatmentforVL.PMID:22174722
27
Field evaluation of novel diagnostic
tests for V Leishmaniasis: freeze dried DAT,RK39dipstick&KATEX
PI
WorldHealth Organization (WHO)
Sponsored
2years
Government
Three diagnostic tests for VL were
evaluated: FD-DAT (freeze-dried direct agglutination test), rK39 dipstick,
and KAtex (urine latex antigentest).
Tissue, blood, and urine samples were
collected from clinical suspects,anddiagnostictestswere compared with direct
microscopic examination of tissue smears.
FD-DAT and rK39 demonstrated
highaccuracy,withsensitivityover 95% and specificity over 90%.
Both FD-DAT and rK39 are recommended for
clinical practice intheIndiansubcontinentdueto
theirreliability.PMID:17942129
28
Arandomised,open-label, parallel-group,safetyand
efficacy study to evaluate different combination treatment regimens (co-
administration), of either AmBisome and
paromomycin,AmBisome
PI
Drugs for NeglectedDiseasesInitiative,
Geneva
Sponsored
2years
10.10.2007
Government
634patients(June2008–July2009) were
assigned to 4 treatment regimens: amphotericin B, liposomal amphotericin B +
miltefosine,liposomal amphotericin B + paromomycin, and miltefosine +
paromomycin.
CureRatesat6Months:
and miltefosine, or paromomycin and miltefosinewithAmBisome
monotherapy for the treatment of acute, symptomaticVisceral Leishmaniasis
(VL)
Amphotericin B: 93%, Liposomal
amphotericin B + miltefosine: 97.5%,LiposomalamphotericinB+ paromomycin:
97.5%, Miltefosine
+paromomycin:98.7%
3.All combination treatments were
non-inferior to standard amphotericin B, with fewer adverse events observed
in the combinationgroups.(Sundaretal,
Lancet2011)
29
Aprospective,singlecenter, openlabel,dose-escalation
phase II study to assess safety and efficacy of short course regimens of
Amphomul(AmphotericinB emulsion ) in treatment naïve or resistant cases of
visceral leishmaniasis (kala- azar)
PI
Bharat Serum &VaccinessLimited,
Mumbai
Sponsored
18.03.2008
Government
An open-label phase II study evaluated
the safety and efficacy of four regimens of pre-formed amphotericin B lipid
emulsion (ABLE)(15mg/kg)administeredin 1-2 doses.
Regimen 4 (15 mg/kg as a single bolus)
showed 100% definitive cure, while the overall cure rate
was87%(95%CI=75-94%).Mild
infusionreactionswereobserved in 38% of
patients.
ABLE demonstrated excellent safety and
efficacy, particularly with a single bolus dose of 15
mg/kg,achievinghighcurerates.
PMID:19407109
30
RDTValuationProject
PI
WorldHealth Organization (WHO)
Sponsored
2years
5.3.2009
Government
Commercial VL rapid diagnostic tests
(RDTs) with rK39 or rKE16 antigens were evaluated using
archivedserafrom750confirmed VLcasesand754endemicnon-VL controls in the
Indian subcontinent.
All RDT brands showed high sensitivity
(92.8%-100%) and specificity(96%-100%)againstthe
ISCpanels.
3.The tested RDTs performed well
andexhibitedgoodheatstability, making them suitable for use in the Indian subcontinent.
PMID:22942208
31
Aprospective,multicentric, randomiozed,
two arm, openlablephaseIIIstudyto assessefficacyandsafetyof infusion of
Amphomul (Amphotericin B Emulsion) as compared to Ambisome in patients of
Visceral Leishmaniasis (kala-azar)
PI
Bharat Serum &VaccinesLimited, Mumbai
Sponsored
2years
14.9.2009
Government
500 VL patients were randomly assigned to
receive a single 15 mg/kg infusion of ABLE (376 patients)orLAmB(124patients).
Initial cure rates were 95.9% for ABLE
and 100% for LAmB, with clinical improvement similar between both groups
(ABLE: 98.9%,LAmB:98.4%).AtDay180,
definitive cure was achieved in
85.9%ofABLEpatientscompared to 98.4% for LAmB.
Infusion-related pyrexia and chills werecomparablebetweengroups,
and serious adverse events were fewer with ABLE (0.3% vs. 1.6% with LAmB).
ABLEshowedfavorableefficacy, was well
tolerated, and offered advantagesincost,compliance, and regional
applicability.
PMID:25233346
32
To study the performance characteristics
of Crystal KA Immunochromatographic test kit & Signal KA Flow
throughtestkitusingknown serologicallyproven ¶sitologicallyproven
characterisedsamplepanels
PI
SPANDiagnostic
Sponsored
1year
31.03.2010
Government
TwoformatsofrKE16antigen-based rapid
tests, KEFT (flowthrough) and KELF (lateral flow) were compared with the rK39
rapid test for diagnosing VL.
KEFTandrK39showedsimilarhigh
sensitivities (99% and 99.5%, respectively), both outperforming KELF (95.5%).
Specificities were comparable
acrossalltestsincontrolgroups
fromnon-endemicandendemic
areas,althoughKELFshowedhigher
specificityincontrolsfromendemic regions. PMID: 22760038
33
Syndromic Approach to neglectedinfectious
diseases (NID) at primary health care level: an interationalcollaborationon integrated
diagnostic- Treatment Platforms(Grant Agreement: 260260)
PI
European Commission (NIDIAG)
Sponsored
5years
31.01.2011
Government
Previous investigations using Leishmania
lysate antigen demonstratedthattheimmunoglobulin (Ig) G1 response is a
potential indicator of a patient's clinical status after chemotherapy. IgG1
or IgG enzyme- linked immunosorbent assays (ELISAs) with rK39 or lysate
antigens and novel IgG1 rK39 rapid diagnostic tests (RDTs) were assessed with
Indian VL serum samples from the following clinical groups: paired pre- and
postchemotherapy (deemed cured); relapsed;otherinfectiousdiseases;and
endemic, healthy controls. With paired pre- and post-treatment samples (n =
37 pairs), ELISAs with rK39- and IgG1- specific conjugates gave a far more
discriminative decrease in post- treatment antibody responses when
comparedtoIgG(P<.0001).NovelIgG1 rK39RDTsprovidedstrongevidencefor
decreased IgG1 responses in patients who had successful treatment (P <
.0001). Furthermore, both IgG1 rK39 RDTs
(n = 38) and ELISAs showed a highly significant difference in test outcomes
between cured patients and those who relapsed (n = 23; P < .0001). There
strong evidence for the use of IgG1inmonitoringtreatmentoutcomes
inVL,andthefirstuseofanIgG1-based RDT using the rK39 antigen for the
discrimination of post-treatment cure
versusrelapseinVL.SuchanRDTmay
have a significant role in monitoring
patients and in targeted control and eliminationofthisdevastatingdisease.
PMID:30541022
34
A phase II open lable randomized trial of
three single dose treatment regimens of Fungisome aloneorincombitaionwith
single dose treatment regimen of Ambisome for Visceral Leishmaniasis in India
PI
Lifecare Innovations Pvt.Ltd.
Sponsored
1year
24.06.2013
Government
In this study, a higher-dose regimen of
indigenously manufactured liposomal amphotericinB(FUNGISOME)was tested to
improve efficacy in VL treatment.
Thirtymenandthirtywomenwere
enrolled,dividedintotwocohorts, receiving either 10 mg/kg (cohort I) or 15
mg/kg (cohort II) of FUNGISOME.
Safety was confirmed for both doses, with
no significant adverse effects observed over 30 days.
Bothcohortsshoweda93.3%cure rate, demonstrating that FUNGISOME is safe and
effective for treating VL, with good initial and long-term
outcomes.PMID:25510715
35
FNIH#KAMRC13 LM
PI
FNIH (Bill &MelindaGates Foundation)
Sponsored
1year
29.01.2014
Government
DevelopedBSL-II infrastructure facility
at the Kala azar Medical Research Center (KAMRC), and established a pathogen
free Phlebotomousargentipessandfly colony.
Optimized technical approach to identifying
infection reservoirs by xenodiagnoses.
36
VisceralLeishmaniasis Epidemiology study-
TransmissionDynamics(OPP 1117011)
PI
Bill & Melinda GatesFoundation
Sponsored
3years
9.04.2015
Government
Werecruited287individuals,including
77withactivevisceralleishmaniasis,26 with post-kala-azar dermal
leishmaniasis, and 184 with
asymptomaticinfection.Ofthepatients
with active visceral leishmaniasis, 42
(55%) were deemed infectious to sandflies by microscopy and 60 (78%) by qPCR
before treatment. No patient withvisceralleishmaniasiswasfoundto be
infectious by microscopy at 30 days aftertreatment,althoughsix(8%)were
stillpositivebyqPCR.Beforetreatment, 11 (42%) of 26 patients with post-kala-
azardermalleishmaniasisweredeemed infectious to sandflies by microscopy and
23 (88%) by qPCR. Of 23 patients who were available for xenodiagnosis after
treatment, one remained infectious to flies by qPCR on the pooled flies, but
none remained positivebymicroscopy.Noneofthe184 asymptomatic participants
were infectious to sandflies.
These findings confirm that patients with
active visceral leishmaniasis and patients with post-kala-azar dermal
leishmaniasis cantransmit Ldonovani to the sandfly vector andsuggest that
early diagnosis and treatment could effectivelyremovetheseindividualsas
infectionreservoirs.Animportantrole for asymptomatic individuals in the
maintenanceofthetransmissioncycle is not supported by these data.
Documentedtherelativeinfectiousness of
VL, PKDL and asymptomatic subjects tosandfliesthroughxenodiagnosesand
provided the missing information on L. donovani transmission dynamics for
timely incorporation into the VL elimination program in India.
PMID:33615281
37
Anopenlable,randomized,
clinicaltrialoftworegimens to assess the safety and efficacy for treatment of
PKDL patients in the Indian subcontinent
PI
DNDi
Sponsored
2years
1.08.2017
Government
The safety and efficacy of two
shorter-coursetreatmentswere assessed for PKDL: liposomal amphotericin B
alone and combinedwithmiltefosine(MF).
In a phase II, open-label, randomized
trial, patients received 20mg/kgLAmBover15days,with or without MF for 3
weeks.
At12months,definitivecurewas achieved in
29% of the LAmB group and 30% of the LAmB/MF group,improvingto58%and66% at 24
months, respectively.
Mostlesionsresolvedorimproved in both
groups. The treatments were safe, with mild adverse events reported, and no
serious drug-related events or ocular issues.
Both regimens are effective and offersafer,shorteralternativesto
longer MF courses for PKDL in
SouthAsia.PMID:38900786
38
A phase III open lable1randomized trial
of threesingledosetreatment regimens of Fungisome aloneorincombitaionwith
single dose treatment regimen of Ambisome for Visceral Leishmaniasis in India
(LC-Fungisome-03)
PI
Department of Science and Technology
(Lifecare InnovationsPvt. Ltd.)
Sponsored
3years
29.04.2019
Government
A multicenter trial with Dr.
Sundar’ssiteenrollingover70%of the total 277 screened patients, leading to
258 randomizations.
PatientOutcomes:6consent
withdrawals,8relapses,and2
seriousadverseevents(1death,1 hospitalization).
Cureratesrangedfrom95.2%to
96.9%acrossdifferenttreatment groups, with Fungisome TM showing the highest
cure rate (96.9%) at 10 mg/kg.
TreatmentGroups:Thetrial
compareddifferentdosagesof
|
Sl |
Project Title |
PI / Co-PI |
DetailsofFunding Agency |
Industry / Public/Sector Undertaking/ Others / Collaborative/Sponsored |
Project Durationin Years |
Type of Beneficiary |
Output/OutcomeoftheProject |
|
1 |
Visceral Leishmaniasis in Bihar State, India Phase 1 |
PI |
NationalInstitute of Allergy and Infectious Diseases,National Institutes of Health,USA |
Sponsored |
2007-2012 |
Government |
Documentedthataround80-90%of all L. donovani infections did not lead to clinical disease. The ratio ofincident clinical disease to incident seroconversion in these communities was 10 to 1 andrecent seroconverters had a ten timeshigherrisktodevelopdisease in the subsequent 18 months than those who did not sero-convert. Identified and defined the subsets of regulatory T cells play a role in pathogenesis of human VL, to identify the cellular source of the elevated IL-10 that is associated with active disease, and to validate IL-10orothersuppressivefactorsas potential targets to enhance the anti-parasitic immune response. Identified the HLA DR-DQ region (encodingMHC,classII,DRandDQ) as the majorsusceptibility locus across India and Brazil. |
|
2 |
VisceralLeishmaniasisin Bihar State, India Phase2 |
PI |
NationalInstitute of Allergy and Infectious Diseases,National Institutes of Health,USA |
Sponsored |
2012-2017 |
Government |
Documentedthenovelinsightsin thenaturalhistoryofL.donovani infection. EstablishedtheDSScoveringover 1,250,000peopleinMuzaffarpur, one of the major VL endemic districts inBihar. Reported the association of co- infections with other neglected tropical diseases (NTD) as a determinant for progression to VL, andopeninguptoawiderscopefor understanding NTDs in the project area. Reported the genetic determinants of seroconversion and, through transcriptional profiling, understand progression from asymptomatic infection to disease Reportedthetemporalandspatial variation in P. argentipes abundance, biting behaviorand infectivity, inside and around human dwellings. DocumentedthefunctionofCD8+T cells in human VL. Reported thetranscriptional signaturesinwholebloodofactive VL. |
|
3 |
VisceralLeishmaniasisin Bihar State, India Phase3 |
PI |
NationalInstitute of Allergy and Infectious Diseases,National Institutes of Health,USA |
Sponsored |
2017-2022 |
Government |
EstablishedtheTMRCasacenterof excellence for surveillance and monitoring transmission in thecontextofeliminationofvisceral leishmaniasis (VL) epidemiological evidence to guide policy in the VL eliminationinitiative- |
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|
buildingmathematical transmission models and spatial risk maps Documented the role of Dogs as Reservoirs for Leishmania donovani, Bihar, India Evaluateinsecticideresistanceof fieldpopulationsofP.argentipes and determined the biochemical/molecular markers associated with resistance in P.argentipes. Reported the frequency and activationstatusofkeyimmune cells¸ including T cells and monocytes, in the blood, bone marrow and skin of VL patients before, during and after drug treatment. |
|
4 |
Setting the Post-Elimination AgendaforKala-AzarinIndia (SPEAKIndia) |
PI |
LondonSchoolof Hygeine and Tropical Medicine/ Bill & Melinda Gates Foundation |
Sponsored |
2019-2020 |
Government |
Assessedthethreemostcommonly used serological markers for Leishmania donovani infection in the Indian subcontinent in three different categories of endemicity, andidentifiedtherK39ELISAasthe most promising candidate going forward.Inaddition,weemphasize childrenasaparticularlyinteresting target group, as they represent relatively recent infections. This study provides a first insight into the potential of serosurveillance for monitoring of Leishmania transmission in the post-elimination phase. Reported that current diagnostic algorithm combining suggestive clinicalfeatureswithapositiverK39 RDT still seems valid in the current low-endemicsettinginIndia. |
|
5 |
Xenodiagnosis of Visceral Leishmaniasis, Post Kala- azar Dermal Leishmaniasis andAsymptomaticsubjects usingPhlebotomine Sand Flies |
PI |
Bill & Melinda GatesFoundation |
Sponsored |
2015-2018 |
Government |
First investigation in India for the infectiousness to sandflies of patients with visceral leishmaniasis or post-kala-azar dermal leishmaniasis following treatment and of people with asymptomatic infectionlivinginareaswithhighL donovani transmission. Reported that patients with active visceral leishmaniasis or post-kala- azar dermal leishmaniasis, but not asymptomatic individuals or treated patients, were infectious to vector sandflies. Reported that infectiousness increasedwithseverityofdiseasein patients with active visceral leishmaniasis. Reported that Treatment of patients with visceral leishmaniasis or post-kala-azar dermal leishmaniasis with currently recommended drugs was highly effective in reducing their infectiousness to flies. |
|
6 |
Synthesis and application of nano materials towards energy and EMI shielding, targetted drug delivery and theranostic application of biocompatible microparticle derivedfromhumanplatelet for nano therapeutics |
PI |
Departmentof Science and Technology, Governmentof India |
Sponsored |
2017-2020 |
Government |
Development of an amine- functionalized versions of carbon nanostructures, namely f-CNT and f-Graphene(f-Grap)andfoundthat f-Grap is a safe and reliable therapeutic option over the other carbon-based nanoparticles (NPs), i.e., f-CNT-AmB, f-Grap-AmB, and conventionalAmB. |
|
7 |
Epidemiology of Visceral Leishmaniasis in MuzaffarpurDistrict,Bihar (EpiVL) |
PI |
TheFoundation fortheNational Institutes of Health(FNIH), USA |
Sponsored |
2014-2016 |
Government |
Establishment of a new, fully functional insectary that will permit containment, rearing, infection,andmanipulationoffield caught sand flies, Establishmentofworkingcolonyof P. argentipes that has been certifiedforuseinxenodiagnostic procedures. |
|
8 |
Designing combination immunotherapy and drug treatmenttocontrolchronic infectious diseases |
PI |
Indo-Australian Biotechnology Fund |
Sponsored |
2018-2021 |
Government |
Significant progress in clinical studies at KAMRC, India and pre- clinicalstudiesatQIMR,Brisbane. Discoveredimmune manipulation can antagonize anti-parasitic immunity. Identifiednewpotentialimmune pathways for therapeutic advantage. Confirmed findings from the mousemodelofVLwithclinical samples from patients. Found that blocking signals throughanimmunereceptorcan improve immunity and reduce parasite burdens. Validated finding using patient cells,boostingtheirresponseto parasites. Extending researchto understand this pathway and identify new ways to improve anti-parasitic immunityduringVL. |
|
9 |
New tools for monitoring drug resistance and treatment response in VisceralLeishmaniasisinthe Indian subcontinent ( KALADRUG-R) |
PI |
European Commission |
Sponsored |
2009-2013 |
Government |
Evaluated the efficacy and safety ofmiltefosineforthetreatmentof VL after a decade of use in India and found that efficacy of miltefosine has significant decline inthefinalcurerate(from94%to 90%),andadoublingof the |
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relapseratewithin10years. Development of rapid assays to monitor the emergence and spreadofclinicallyrelevantSSG- resistant Leishmania parasites. Reported the whole genome sequencingdataofIndianparasite strains. |
|
10 |
ComparativeEvaluationof PCR Primers In Diagnosis and Prognosis of Indian VisceralLeishmaniasis(VL) andPostKala-AzarDermal Leishmaniasis (PKDL) |
PI |
Indian Council of Medical Research (ICMR),NewDelhi |
Sponsored |
2007-2010 |
Government |
The present study was planned to designaLeishmania specific diagnostic assayandtoevaluateitssensitivityand specificity on a sample size, which to thebestofourknowledgeisthelargest ever screenedinone study.Leishmania specific primers were developed using 18SrRNAgeneandtheirsensitivitywas evaluated on 500 parasitologically confirmedpatientswithVLand25Post Kala-azar Dermal Leishmaniasis (PKDL) patients. Specificity was calculated on 250 healthy endemic controls, 250 healthy non endemic controls and 250 non leishmanial diseases like malaria.OurPCRassayhadasensitivity of 87.8% (95%CI: 84.1–89.8) using 200 µL of patient's peripheral-blood. Specificitywasabsoluteinnon-endemic healthy controls and in subjects with different diseases while in endemic controlsitwas84%(95%CI:78.9–88.0). Itsoverallspecificitywas94.6%(95%CI- 92.8–96.1). The high sensitivity of this PCR diagnostic test with relatively non- invasive peripheral blood sampling method opens up the possibility of its deployment in field for the routine diagnosis of VL. |
|
11 |
Efficacy,acceptabilityand cost-effectivenessoflong lastinginsecticidetreated nets in the prevention of Kala-azar |
PI |
European Commission |
Sponsored |
2006-2009 |
Government |
Large-scaledistributionoflong- lasting insecticide-treated nets (LLINs)wastestedtoreduceVL incidence in India and Nepal. A paired cluster randomized controlledtrialfoundnosignificant difference in VL seroconversion or clinical incidence between intervention and control groups. LLINs showed a small, non- significanteffectonVLprevention, with confidence intervals not ruling out a possible 50% change.PMID: 21190965 |
|
12 |
AphaseI,open-label,dose- escalatingstudytoevaluate the safety, tolerability, and immunogenicity of the Leish-111f+MPL-SEvaccine (recombinantthree-antigen Leishmaniapolyproteinwith adjuvantMPL-SE)inhealthy adults in India |
PI |
InfectiousDiseasesResearch Institute/Bill& Melinda Gates Foundation |
Sponsored |
2007-2010 |
Government |
Three cohorts of 6 DAT-negative and 6 DAT-positive subjects were enrolled in an open-label, dose-escalating, uncontrolled clinical trial and received threeinjectionsoftheLEISH-F1+MPL-SE vaccine (consisting of 5μg, 10μg, or 20μg recombinant Leishmania polyprotein LEISH-F1 antigen+25μg MPL®-SE adjuvant). The vaccine was safeandwell-toleratedinDAT-negative and DAT-positive subjects and induced T-cell production of IFN-γ and other cytokines in response to stimulation with the LEISH-F1 antigen. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without history of previous infection with Leishmania donovani. PMID: 21414377 |
|
13 |
Patient-centric supramolecular formulations of new anti- leishmanialdrugsforIndian Communities |
PI |
Durham University |
Sponsored |
2020-2023 |
Government |
The main objective of this project was to combine and apply medical anthropology and community engagementmethodstoidentifydirect optimal drug delivery methods &formulation designamong communities in India with leishmaniasis (Kala-azar) endemic.
DETAILSOFTHESURVEY 4districtsi.e.Muzaffarpur,Vaishali ,Sitamarhi&Saranwereselected 5villagesfromeachofthedistricts were taken purposively according to the availability of patients. Indepthinterviewwasconducted with new patients (of 2021), old patient, their care giver, key respondent (Influential person of the village) & ASHA from each village. InterviewofCMO,DMOStaff Nurse & Pharmacist were conducted. Intotal116respondentswere interviewed.
FINDINGSOFTHEPATIENTS&CARE GIVERS & KEY RESPONDENTS
Almost all of them aware about kala azarandthemoststatedsymptomwas continuous fever for 10 to 15 days. Garbageandcattledungfoundtobe the main mode of transmission. Mosquitoesareknownasvectorof kala-azar among majority of the population.Bothnewandoldpatients |
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were satisfied with the current medication as the previous treatment regimen was of long duration. When they were asked about the change in drugformulationforVL,mostofthem supportedtabletformandsomeasked vaccine for prevention of VL. AccordingtoHealthprovidersnewdrug formulationsshouldbepatientfriendly. They suggested the single time oral medication as the best drug delivery method.
Dr.SwetaSinghPost-DoctoralResearch Associate visited Keele & Durham University where she gave her presentationthepreliminaryfindingsof the research.
Dr. Sangeeta Kansal visited KMMS SymposiumonMentalHealthinSouth Asia from 22-24 March 2023. And presented paper entitled “Need of Continuum of Care Approach for ImprovementofMentalHealthamong Young Adults”
A participatory research work was conducted at BHU on 26th& 27th February2023incollaborationwith Durham University (UK) & PRAXIS. |
|
14 |
Establishment of a test of cure tool for monitoring Visceral Leishmaniasis and Post Kala-azar dermal Leishmaniasis;amulticentric study |
PI |
Indian Council of Medical Research (ICMR),NewDelhi |
Sponsored |
2022-2023 |
Government |
1)This study has identified the most appropriate molecular approach (SYBR Green qPCR assay) for monitoringtheparasitekinetics,so as to facilitate replacement of the existinggoldstandardwhichis |
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identification of Leishman Donovan (LD) bodies in tissue aspirates (splenic aspirates or a skin punch biopsy) of suspected casesofVLandPKDLrespectively, withalongtermviewtoeliminate thediseasereservoirandfacilitate success of the Leishmaniasis eliminationprogram. Most importantly, it will be very effective for diagnosing macular PKDL (which presently constitutealmost 50% of the PKDL burden), where it is difficult to identify LD bodies in tissue biopsiesandisoftenmisdiagnosed as other hyopigmentary disorders (e.g. vitiligo, leprosy) with overlapping clinical features and geographicalendemicity. Furthermore, this assay could correctly monitor treatment efficacyforbothVLandPKDL,thus proving to be an effective ‘test of cure’ tool for diagnosis and monitoringofthesecases. |
|
15 |
Field validation of Leish- LAMP detection kit for diagnosisofKala-azar(KA) andPostKala-azarDermal Leishmaniasis (PKDL) in endemic zone |
PI |
Indian Council of Medical Research (ICMR),NewDelhi |
Sponsored |
2022-2024 |
Government |
The diagnostic and prognostic utilityofLeish-LAMPtestwouldbe validated in field settings in order toestablishitsuseasarapidpoint- of-care testing device for VL and PKDL. 1.toprovideevidenceastowhether alternate clinical specimens viz. dried blood spot/lysed blood/tissue can be used in field settings for the diagnosis of KA/PKDL using Leish LAMP test. |
|
16 |
MaintainingIndia’svisceral leishmaniasiselimination campaign by mitigating insecticide resistance in sand flies |
PI |
Indian Council of Medical Research (ICMR),NewDelhi |
Sponsored |
2023-2026, Ongoing |
Government |
India’s VL elimination campaign reliesonIndoorResidualSpraying (IRS) with synthetic insecticides. Due to DDT resistance in sand flies,alpha-cypermethrinis now usedforIRS;however,itssimilar modeofactiontoDDTraisesthe risk of resistance development. This study evaluated insecticide susceptibility in Phlebotomus argentipes sand flies (wild-caught and F1 progeny) using the CDC bottle bioassay. Knockdown mortality rates were 91.19–99.47%forwild-caughtand 91.70–98.89% for F1 progeny; 24- hourmortalityrangedfrom89.34– 98.93% (wild-caught) and 90.16– 98.33%(F1). Potential resistance development were seen in P. argentipes, highlighting the need for continuousmonitoringtosustain VL elimination efforts. |
|
17 |
Effect of Recombinant humangammainterferon… aclinical& immunologicalstudy |
PI |
Indian Council of Medical Research (ICMR),NewDelhi |
Sponsored |
1991-1994 |
Government |
IFN-γ with antimony accelerated parasite clearance in VL, with 63% parasite-free by day 10 compared to 7% in controls. Clinical cure rates by day 20 were 93% for the IFN-γ group versus40% for antimony alone, allowing earlier treatment discontinuation for IFN-γ responders. Day 30 and 6-month cure rates werehigherintheIFN-γgroup, thoughdifferenceswerenot |
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statisticallysignificant. 4.IFN-γ shows potential for faster clinical and parasitologic responses, suggesting it may help reducetreatmentdurationforVL. PMID:7706829 |
|
18 |
Immunochemotherapyfor visceralleishmaniasis : Interferon-yplusantimony |
PI |
Rockfeller Foundation,USA |
Sponsored |
1995-1996 |
Government |
Three treatment regimens were testedforVL:Sbalonefor30days, Sb plus IFN-gamma for 30 days, and Sb plus IFN-gamma for 15 days. Aim was to evaluate if IFN-gamma boosts Sb effectiveness and if a shorter 15-day combination is as effective as 30-day Sb alone.
Six-month cure rates were similar acrossgroups:36%(Sbalone),49% (Sb + IFN-gamma for 30 days), and 42%(Sb+IFN-gammafor15days). No significant improvement was observed with IFN-gamma, indicating limited benefit inregions with high Sb resistance. PMID: 9333181 |
|
19 |
Visceral Leishmaniasis and PKDL : New Therapeutic, ImmunologicandDiagnostic Studies,andsitepreparation for Vaccine Trial |
PI |
RCS/WorldHealth Organization (WHO),Geneva |
Sponsored |
2000-2004 |
Government |
We tested standard amphotericin B deoxycholatemixedwithacommercial fatemulsionasshort-coursetreatment forIndianvisceralleishmaniasisinBihar in1997/98.Seventychildrenandadults with splenic aspirate-documented infection, 23 of whom had failed prior antimony (Sb) therapy, received 5 alternate-day infusions of 2 mg/kg. Other than anticipated infusion-related feverand/orchills,treatmentwassafe and well tolerated. There were 4 treatmentfailuresyieldingdefinitive |
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curesin65of70patients(92.9%,CI 84.1-97.6%).. Short-course treatment with amphotericin B-fat emulsion is active, cost-effective treatment for patients with visceral leishmaniasis includingthosewithSb-unresponsive infection. PMID: 10897369 2.Sera from 61 Indian patients with visceral leishmaniasis were tested for thepresenceofThelper1(Th1)celland Th2 cell-associated cytokines (interleukin-4 [IL-4]and IL-10). The IFN- gammaactivitywasdetectedin53%.IL- 4 in 84%, and IL-10 in 56% of patient samples. Quantitative data indicated comparablemeanlevelsofIFN-gamma, butthree-and13-foldincreasesinIL-10 and IL-4, respectively. Undetectable IFN-gammaactivity,observedin47%of patients. In patients who had failed prior therapy (n = 29) compared with previously untreated patients (n = 32). IFN-gammalevelswere 67%lowerand IL-4 levels were two-fold higher, IL-10 activity was comparable. These results using peripheral blood support the presence of a suppressive Th2 cell- associated immune response in symptomaticIndiankala-azarandpoint to a possible role for IL-4. PMID: 9180602 |
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20 |
Kala-AzarDiagnosticKit and commitment ICMR in Kala- Azareliminationprogramme for BHU, Varanasi |
PI |
Indian Council of Medical Research (ICMR),NewDelhi |
Sponsored |
2003-2004 |
Government |
Dr Sundar evaluated the direct agglutination test (DAT), using freeze- dried (FD) and aqueous (AQ) antigen, andthe rK39 immunochromatographic strip test in the diagnosis of Indian visceral leishmaniasis (VL). Sera from 508 subjects (150 parasitologically confirmedpatientswithVL,100and |
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153healthycontrolsfromnon-endemic andendemicregions,respectively,and 105 patientswithother diseases) were tested.Thesensitivityofthetestswere as follows: DAT (FD), 96% (95% CI 91- 98);DAT(AQ),97%(95%CI93-99);rK39 strip test, 99% (95% CI 95-100). The specificityofDAT(FD),DAT(AQ)and rK39striptestswere85%(95%CI81- 88),87%(95%CI83-91)and89% (95% CI 86-92), respectively. A significant correlation (high degree of agreement) was observed between all tests (kappa>0.80). We conclude that the sensitivity of FD antigen is comparable to that of AQ antigen. Similarly, the rK39striptestisassensitiveastheDAT, butthestriptest'sgreaterconvenience of use makes it a better tool for diagnosis of VL in peripheral areas of endemicregions.PMID:16325874 |
|
21 |
CenterofExcellence(COE) for HIV care |
PI |
NationalAIDS Control Organization, Department of HealthandFamily Welfare, Governmentof India |
Scheme |
2008-2018 |
Government |
This centre was established in 2011 with the mandate for research, training and mentoring. We mentor all the 15 ART centre linked to us as and when needed, especiallywithdifficulttomanage patients. Our team members constitute the SACEP (State AIDS clinicalExpertpanel).Whichtakes decision on change of therapy fromfirst line to second line as well to third line ART for PLHIV referred to us from all over UP. We have conducted >50 onsite trainings for ART Staff and >30 online training through regional distancelearningseminarbothfor nationalandstateparticipants. |
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Our research has focused on programmatic needs.We have assessedtheoutcomeoffirstline, second line and third line ART under programmatic conditions. We have also assessed the drug mutationsacquiredbytreatment naïve PLHIV and those failing therapy. We have shown the high prevalenceofHPVInfectionaswell as NCD (non communicable disease) amongPLHIV . We have highlighted the high prevalence of cryptococcal meningitisinthisregionandthe importance of screening serum CrAg (cryptococcal antigen) in PLHIV with CD4 <200/µL. |
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22 |
ARTCenter |
PI |
NationalAIDS Control Organization, Department of HealthandFamily Welfare, Governmentof India |
Scheme |
2005-2018 |
Government |
We were the first and still the largest ART centreof the state of UttarPradeshwithapopulationof 241 million. It caters to the needs of PLHIV of eastern UP, neighbouring states of Bihar, Jharkhand, Chhattisgarh. Through this project we were able toprovideFreeantiretroviraldrugs to>than10,000Peoplelivingwith HIV in this region. We werethe first centre to providefirst line, second line and third line antiretroviraldrugstoPLHIVofthis region.Asatertiarycarecentrewe have managed more than 1000 PLHIV with serious opportunistic infection per year referred to us from other centres. Itistheonlycentrewhichprovides |
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free Viral load testing for PLHIV from many ART Centre linked to us. It has developed as a Centre which provides comprehensive care for HIV and provides ART, antitubercular drugs drugs for opportunistic infection, managementofnoncommunicable disease,hepatitis and cancer screening under one window. |
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23 |
Toassessefficacyandsafety of orally administered miltefosine in patients with visceral leishmaniasis with Controlgroup:Amphotericin B |
PI |
grants from Zentaris (to Dr. Sundar) and the Special Program forResearchand Training in TropicalDiseases of the United Nations Development Program,the WorldBank, and theWorldHealth Organization |
Sponsored |
3years
14.5.1998 |
Government |
Two treatments for VL were compared:oralmiltefosine((50or 100 mg daily for 28 days, 299 patients).) and intravenous amphotericin B (1 mg/kg every other day for 15 doses, 99 patients). Initialcureratewas100%inboth groups. Six-monthcurerateswere94%for miltefosine and 97% for amphotericin B. Miltefosinehadmildsideeffects (vomitingin38%anddiarrheain 20% of patients). Miltefosine is effective, safe, and advantageous as an oral treatment,especiallyinareaswith drugresistance. |
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24 |
LOW-DOSE LIPOSOMAL AMPHOTERICIN B IN REFRACTORY INDIAN VISCERALLEISHMANIASIS:A MULTICENTERSTUDY |
PI |
GileadSciences (Nexstar Pharmaceuticals) |
Sponsored |
1year
11.01.2000 |
Government |
84 patients with VL unresponsive to antimony were treated with liposomalamphotericinBatdoses of3.75,7.5,and15.0mg/kgover5 days. Apparentcurewasevaluatedat2 weeks, and definite cure was assessed at 6 months post- treatment. |
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Side effects included mild to moderatefeverin29%andrigors in 44% of patients. Definite cure rates at 6 months were89%(3.75mg),93%(7.5mg), and97%(15.0mg). Low-doseliposomalamphotericin B over 5 days effectively cured most patients with VL, with no significantdifferenceincurerates across dosage groups. PMID:12135284 |
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A phase III multicentre randomized,controlled, clinical trial to assess the safety and efficacy of injectableParomomycinin patients with VL |
PI |
Bill & Melinda Gatesfoundation _-InstituteofOne WorldHealth |
Sponsored |
2004-6 |
Government |
Paromomycin was found noninferior to amphotericin B for treating VL, with cure rates of 94.6%forparomomycinand98.8% for amphotericin B. Mortalitywaslessthan1%inboth groups. Adverse events were more frequent with paromomycin, includinginjection-sitepain(55%), transient liver enzyme elevation (6%), and reversible ototoxicity (2%). Amphotericin B was associated with nephrotoxicity (4%), fevers (57%),rigors(24%),andvomiting (10%). Paromomycin is a viable alternative to amphotericin B for visceral leishmaniasis treatment in India.PMID:17582067 |
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26 |
Institute for OneWorld HealthProtocolNo.VLPM03 “A Phase 4 Study to Expand Access While Assessing the Safety and Efficacy of ParomomycinIMInjectionin |
PI |
The Bill and MelindaGates Foundation |
Sponsored |
2007-9 |
Government |
A phase 4 study assessed paromomycin’s safetyand efficacy in treating VL in an outpatient setting in Bihar, India. 506patients(adultsandchildren) wereenrolled;98%completedthe |
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anOutpatientSettingforthe Treatment of Visceral Leishmaniasis (VL) in India”. |
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fulltreatmentcourse. Study completion rates were 94% fortheITTpopulationand96%for theefficacy-evaluablepopulation. Initialcureratewas99.6%,witha final cure rate of 94.2% at 6 months. Grade3or4adverseevents occurred in 5% of patients, primarily mild liver enzyme elevations. Paromomycinwasconfirmedasa safe and effective outpatient treatmentforVL.PMID:22174722 |
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27 |
Field evaluation of novel diagnostic tests for V Leishmaniasis: freeze dried DAT,RK39dipstick&KATEX |
PI |
WorldHealth Organization (WHO) |
Sponsored |
2years |
Government |
Three diagnostic tests for VL were evaluated: FD-DAT (freeze-dried direct agglutination test), rK39 dipstick, and KAtex (urine latex antigentest). Tissue, blood, and urine samples were collected from clinical suspects,anddiagnostictestswere compared with direct microscopic examination of tissue smears. FD-DAT and rK39 demonstrated highaccuracy,withsensitivityover 95% and specificity over 90%. Both FD-DAT and rK39 are recommended for clinical practice intheIndiansubcontinentdueto theirreliability.PMID:17942129 |
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28 |
Arandomised,open-label, parallel-group,safetyand efficacy study to evaluate different combination treatment regimens (co- administration), of either AmBisome and paromomycin,AmBisome |
PI |
Drugs for NeglectedDiseasesInitiative, Geneva |
Sponsored |
2years 10.10.2007 |
Government |
634patients(June2008–July2009) were assigned to 4 treatment regimens: amphotericin B, liposomal amphotericin B + miltefosine,liposomal amphotericin B + paromomycin, and miltefosine + paromomycin. CureRatesat6Months: |
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and miltefosine, or paromomycin and miltefosinewithAmBisome monotherapy for the treatment of acute, symptomaticVisceral Leishmaniasis (VL) |
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Amphotericin B: 93%, Liposomal amphotericin B + miltefosine: 97.5%,LiposomalamphotericinB+ paromomycin: 97.5%, Miltefosine +paromomycin:98.7% 3.All combination treatments were non-inferior to standard amphotericin B, with fewer adverse events observed in the combinationgroups.(Sundaretal, Lancet2011) |
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Aprospective,singlecenter, openlabel,dose-escalation phase II study to assess safety and efficacy of short course regimens of Amphomul(AmphotericinB emulsion ) in treatment naïve or resistant cases of visceral leishmaniasis (kala- azar) |
PI |
Bharat Serum &VaccinessLimited, Mumbai |
Sponsored |
18.03.2008 |
Government |
An open-label phase II study evaluated the safety and efficacy of four regimens of pre-formed amphotericin B lipid emulsion (ABLE)(15mg/kg)administeredin 1-2 doses. Regimen 4 (15 mg/kg as a single bolus) showed 100% definitive cure, while the overall cure rate was87%(95%CI=75-94%).Mild infusionreactionswereobserved in 38% of patients. ABLE demonstrated excellent safety and efficacy, particularly with a single bolus dose of 15 mg/kg,achievinghighcurerates. PMID:19407109 |
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30 |
RDTValuationProject |
PI |
WorldHealth Organization (WHO) |
Sponsored |
2years 5.3.2009 |
Government |
Commercial VL rapid diagnostic tests (RDTs) with rK39 or rKE16 antigens were evaluated using archivedserafrom750confirmed VLcasesand754endemicnon-VL controls in the Indian subcontinent. All RDT brands showed high sensitivity (92.8%-100%) and specificity(96%-100%)againstthe ISCpanels. |
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3.The tested RDTs performed well andexhibitedgoodheatstability, making them suitable for use in the Indian subcontinent. PMID:22942208 |
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31 |
Aprospective,multicentric, randomiozed, two arm, openlablephaseIIIstudyto assessefficacyandsafetyof infusion of Amphomul (Amphotericin B Emulsion) as compared to Ambisome in patients of Visceral Leishmaniasis (kala-azar) |
PI |
Bharat Serum &VaccinesLimited, Mumbai |
Sponsored |
2years 14.9.2009 |
Government |
500 VL patients were randomly assigned to receive a single 15 mg/kg infusion of ABLE (376 patients)orLAmB(124patients). Initial cure rates were 95.9% for ABLE and 100% for LAmB, with clinical improvement similar between both groups (ABLE: 98.9%,LAmB:98.4%).AtDay180, definitive cure was achieved in 85.9%ofABLEpatientscompared to 98.4% for LAmB. Infusion-related pyrexia and chills werecomparablebetweengroups, and serious adverse events were fewer with ABLE (0.3% vs. 1.6% with LAmB). ABLEshowedfavorableefficacy, was well tolerated, and offered advantagesincost,compliance, and regional applicability. PMID:25233346 |
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32 |
To study the performance characteristics of Crystal KA Immunochromatographic test kit & Signal KA Flow throughtestkitusingknown serologicallyproven ¶sitologicallyproven characterisedsamplepanels |
PI |
SPANDiagnostic |
Sponsored |
1year
31.03.2010 |
Government |
TwoformatsofrKE16antigen-based rapid tests, KEFT (flowthrough) and KELF (lateral flow) were compared with the rK39 rapid test for diagnosing VL. KEFTandrK39showedsimilarhigh sensitivities (99% and 99.5%, respectively), both outperforming KELF (95.5%). Specificities were comparable acrossalltestsincontrolgroups fromnon-endemicandendemic |
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areas,althoughKELFshowedhigher specificityincontrolsfromendemic regions. PMID: 22760038 |
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Syndromic Approach to neglectedinfectious diseases (NID) at primary health care level: an interationalcollaborationon integrated diagnostic- Treatment Platforms(Grant Agreement: 260260) |
PI |
European Commission (NIDIAG) |
Sponsored |
5years
31.01.2011 |
Government |
Previous investigations using Leishmania lysate antigen demonstratedthattheimmunoglobulin (Ig) G1 response is a potential indicator of a patient's clinical status after chemotherapy. IgG1 or IgG enzyme- linked immunosorbent assays (ELISAs) with rK39 or lysate antigens and novel IgG1 rK39 rapid diagnostic tests (RDTs) were assessed with Indian VL serum samples from the following clinical groups: paired pre- and postchemotherapy (deemed cured); relapsed;otherinfectiousdiseases;and endemic, healthy controls. With paired pre- and post-treatment samples (n = 37 pairs), ELISAs with rK39- and IgG1- specific conjugates gave a far more discriminative decrease in post- treatment antibody responses when comparedtoIgG(P<.0001).NovelIgG1 rK39RDTsprovidedstrongevidencefor decreased IgG1 responses in patients who had successful treatment (P < .0001). Furthermore, both IgG1 rK39 RDTs (n = 38) and ELISAs showed a highly significant difference in test outcomes between cured patients and those who relapsed (n = 23; P < .0001). There strong evidence for the use of IgG1inmonitoringtreatmentoutcomes inVL,andthefirstuseofanIgG1-based RDT using the rK39 antigen for the discrimination of post-treatment cure versusrelapseinVL.SuchanRDTmay |
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have a significant role in monitoring patients and in targeted control and eliminationofthisdevastatingdisease. PMID:30541022 |
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A phase II open lable randomized trial of three single dose treatment regimens of Fungisome aloneorincombitaionwith single dose treatment regimen of Ambisome for Visceral Leishmaniasis in India |
PI |
Lifecare Innovations Pvt.Ltd. |
Sponsored |
1year
24.06.2013 |
Government |
In this study, a higher-dose regimen of indigenously manufactured liposomal amphotericinB(FUNGISOME)was tested to improve efficacy in VL treatment. Thirtymenandthirtywomenwere enrolled,dividedintotwocohorts, receiving either 10 mg/kg (cohort I) or 15 mg/kg (cohort II) of FUNGISOME. Safety was confirmed for both doses, with no significant adverse effects observed over 30 days. Bothcohortsshoweda93.3%cure rate, demonstrating that FUNGISOME is safe and effective for treating VL, with good initial and long-term outcomes.PMID:25510715 |
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35 |
FNIH#KAMRC13 LM |
PI |
FNIH (Bill &MelindaGates Foundation) |
Sponsored |
1year 29.01.2014 |
Government |
DevelopedBSL-II infrastructure facility at the Kala azar Medical Research Center (KAMRC), and established a pathogen free Phlebotomousargentipessandfly colony. Optimized technical approach to identifying infection reservoirs by xenodiagnoses. |
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VisceralLeishmaniasis Epidemiology study- TransmissionDynamics(OPP 1117011) |
PI |
Bill & Melinda GatesFoundation |
Sponsored |
3years
9.04.2015 |
Government |
Werecruited287individuals,including 77withactivevisceralleishmaniasis,26 with post-kala-azar dermal leishmaniasis, and 184 with asymptomaticinfection.Ofthepatients |
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with active visceral leishmaniasis, 42 (55%) were deemed infectious to sandflies by microscopy and 60 (78%) by qPCR before treatment. No patient withvisceralleishmaniasiswasfoundto be infectious by microscopy at 30 days aftertreatment,althoughsix(8%)were stillpositivebyqPCR.Beforetreatment, 11 (42%) of 26 patients with post-kala- azardermalleishmaniasisweredeemed infectious to sandflies by microscopy and 23 (88%) by qPCR. Of 23 patients who were available for xenodiagnosis after treatment, one remained infectious to flies by qPCR on the pooled flies, but none remained positivebymicroscopy.Noneofthe184 asymptomatic participants were infectious to sandflies. These findings confirm that patients with active visceral leishmaniasis and patients with post-kala-azar dermal leishmaniasis cantransmit Ldonovani to the sandfly vector andsuggest that early diagnosis and treatment could effectivelyremovetheseindividualsas infectionreservoirs.Animportantrole for asymptomatic individuals in the maintenanceofthetransmissioncycle is not supported by these data. Documentedtherelativeinfectiousness of VL, PKDL and asymptomatic subjects tosandfliesthroughxenodiagnosesand provided the missing information on L. donovani transmission dynamics for timely incorporation into the VL elimination program in India. PMID:33615281 |
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37 |
Anopenlable,randomized, clinicaltrialoftworegimens to assess the safety and efficacy for treatment of PKDL patients in the Indian subcontinent |
PI |
DNDi |
Sponsored |
2years
1.08.2017 |
Government |
The safety and efficacy of two shorter-coursetreatmentswere assessed for PKDL: liposomal amphotericin B alone and combinedwithmiltefosine(MF). In a phase II, open-label, randomized trial, patients received 20mg/kgLAmBover15days,with or without MF for 3 weeks. At12months,definitivecurewas achieved in 29% of the LAmB group and 30% of the LAmB/MF group,improvingto58%and66% at 24 months, respectively. Mostlesionsresolvedorimproved in both groups. The treatments were safe, with mild adverse events reported, and no serious drug-related events or ocular issues. Both regimens are effective and offersafer,shorteralternativesto longer MF courses for PKDL in SouthAsia.PMID:38900786 |
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38 |
A phase III open lable1randomized trial of threesingledosetreatment regimens of Fungisome aloneorincombitaionwith single dose treatment regimen of Ambisome for Visceral Leishmaniasis in India (LC-Fungisome-03) |
PI |
Department of Science and Technology (Lifecare InnovationsPvt. Ltd.) |
Sponsored |
3years
29.04.2019 |
Government |
A multicenter trial with Dr. Sundar’ssiteenrollingover70%of the total 277 screened patients, leading to 258 randomizations. PatientOutcomes:6consent withdrawals,8relapses,and2 seriousadverseevents(1death,1 hospitalization). Cureratesrangedfrom95.2%to 96.9%acrossdifferenttreatment groups, with Fungisome TM showing the highest cure rate (96.9%) at 10 mg/kg. TreatmentGroups:Thetrial compareddifferentdosagesof |
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Fungisome TM and Ambisome, demonstratingstrongefficacyand safetyprofilesacrossalltreatment arms.UnderPublication |
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39 |
A Phase II multicentre,randomized,two -armblindedstudytoassess the efficacy and safety of two LXE408 regimens for treatment of patientswith primaryvisceral leishmaniasis-DNDi-LXE408- 01-VL/CLXE408A12201r |
PI |
DNDi |
Sponsored |
23.12.2021 |
Government |
Ongoing – It is a new oral antileishmanial drug being tested for the first time in the world at Dr Sundar’streatmentsite.Appearstobe promising, still early days |
