Recent Advancements in the Treatmen

t of Leprosy
JOURNAL READING :Tugas kepanitraan klinik bagian ilmu kesehatan kulit dan Kelamin
“ Dwi Utami Abdul Latif (Chief)
M. Chairil Riskyta Akbar
Siti Khadidjah
Rezky Ramadhani Syarif
Risti Indah N. Anwar
Magefirah Hasanuddin
“
Siti Nastiti Deviyana
1. Introduction
New strategy:

Neglected Disease :
DNDi was established
Most: in order to make
correction in the ongoing
Prevail in under developed imbalance for diseases
countries (tropical belt) (neglected disease)

1975-2004: TDR by WB, UNDP,

important achievements
in its fight against vector
Only 21 drugs (1,3%) were
synthesized for neglected borne malarial and
tropical diseases leishmanial diseases
1. Introduction
List of neglected Need urgent attention
disease by WHO Tipe I:
Global disease

Tipe II – III:
Neglected – most neglected
1.1 Leprosy

2008
2013.000 cases were
reported for leprosy, 2010
out of 122 countries, considered as native
17 countries to leprosy
reported more than 1000
new cases 119 countries
have been successful in eliminating the
94% disease as a public-health problem
of the new cases
detected globally
1.1 Leprosy
For several centuries: people with Leprosy considered as plagued
Arises due to and were disgraced, stigmatized, discriminated and banished from
gradual growth of the locality

the bacterial inection Kamath et al. observed 3 types of leprosy reactions in their
study.
caused by M. leprae
Main target: skin, peripheral
1 Reversal reaction
nerves, respiratory tract, eyes,
and other vital organs
2 Erythema nodosum leprosum
Epidemiology : not restricted to a
particular age or sex

Treatment (by WHO 1981):

3 Lucio phenomenon
Multi-drug therapy, combination
of 3 drugs – rifampicin, At present, there are no treatments to reduce long lasting
dapsone, and clofazimine disability due to leprosy

Various types are classified according to bacteriological index

and skin-smear positivity.
2.1 Advancements in the Diagnosis of Leprosy

Duthie et al. Bochud et al Oca et al.

“Several antigens were “Microsatellite and the 597C
potent candidates that  T polymorphisms affected
could be useful in the the susceptibility to reversal
future either for reaction and its occurrence,
diagnosis or even and had the ability to bring
vaccination against new information regarding
leprosy.” immunogenetics relate to
leprosy”
DEFB1 can be used for
earlier detection and as
marker for lepromatous
leprosy (L-lep), and also
could be usefull in designing
new alternative cures
against leprosy.”

Elias et al. Geluk et al. Messias et al. Schuring et al.

Analyzed the M. Leprae antigens for The study showed
“Sonography and “FCN2 plays an
their potential in inducting cytokine that TLRI N2484
electrophysiology immunogenetics
secretions using perpheral blood lowers TLRI signals
were compatible for role in the host
mononuclear cells from leprosy and the fo;owing
identification of against M. Leprae.”
infected patiens and showing that M. leprosy disease
leprosy.” Leprae peptides are potential
candidates for diagnosis
2.1 Advancements in the Diagnosis of Leprosy

Duthie et al. Geluk et al Kumar et al.

“Several antigens are The study was successful in “Real-time PCR could be a
capable of early identification of M.leprae- preferable technique for
diagnosis of M. Leprae unique Ags, specificaly monitoring bacillary DNA
and their combination ML2478, as biomarker using and mRNA in lesions for a
can help in accurate IFN-g or IFN-inducted better diagnosis and
diagnosis of leprosy” protein treatment of the disease”
Leprosy Diagnosis
2.1.1 By Skin 2.1.2 Vit. D 2.1.3 Differentation

Lima et al
Lipid markers using silica
plates
D
Mandel et al
Vit. D & Receptors
↓ low level
Viera et al
Biomarker
miRNA
1 (+) Bacterial Mycolic & Apoptosis 1 1
(-) Gangliosid & Fosfolipid Neela et al Jorge et al
3 receptor vit D TDLA & QRT-PCR
Iyer et al All gen type related with TB VS Leprosy
Corelation with chitotriosidase
Difference between MB vs PB
2 leprosy 2 Utino et al
2 Monitoring therapy against ENL TL & Sarcodiosis
Reticular fibers
Mathur et al
Clinical - histopatology 3 sarcoidosis ↑
Skin biopsies (gold standard) Buhrer-sekula
ML flow test
3 No dermatologist
Initial diagnosis
4 Tes Elise > ML flow test
2.2 Advancements Treatment

82-99% OFLOFLOKSASIN MDT

MIT + MDT
Moksifloxacin *(Pardillo et al)
1 relaps 2 late MDT more potent along with
case relaps case vaccination Mycobacterium
MultiBasiler (MB) *(Balagon et al) Indicus Pranii (MIT). *(Kamal et al)

U-MDT Bacille Calmette

Guerin vaccination in BCG + RIF
Clofazimine + Dispone + Rifampicin
combination with
rifampicin *Schuring et al. 80%
PauciBasiler (PB) *Kroger et al
2.3 Genetic Studies
De Sales et al
Calmette-Guerin Strain is also a reason for leprosy

Sapkota et al
Validated the association of leprosy with TNF, MBL and
VDR : negatif result for VDR

Ochoa et al
8% more IgM positive cells were present in L-lep lesions

Zhang et al
Identification 2 lnew loci at IL23R & RAB32 and fond the
vulnerability of IL23R for leprosy

Liu et al
Identified about 13 microRNAs in lesions of L-lep dan T-lep :
the new miRNAs has-mir 21 found to upgrade the M. leprae
infected monocyte
2.3 Genetic Studies
Liu et al
01 There is a relations between IBD and leprosy

Ali et al
02 Increase of IL23R gene linked to PB leprosy

Eichelmann et al
03 Meit was observed thet IL10 gene, responsible
for halotypes formation, was present

Garrcia et al
04 Invested the same methode, at the time it was
the only method used dor the protection of
leprosy
Liu et al
05 Reported that BATF3, CCD88B dan CIITA-SOSI
mhave high affinity to get effected by these loci
2.3 Genetic Studies
Singh et al
Among 227 patients of leprosy, 221
werw affected by M. leprae and only 6
had leprosy due to M. Lepromatosis

Naqvi et al
They proposed the possible roles of 312
hypothetical proteins by diving them in
to families ( enzyme, binding proteins,
and trans-porters)

Pereira et al
Low level of IL-10 through disease can
lead the patoents to more chronic and
susceptive response intensifies with
leprosy.
2.4 Leprosy Case Studies
Attia et al. (2010)
01 Flow cytometry : T-regs and FoxP3 expression
increased in leprosy patients compared to healthy

At Ethopia (2016)
02 almost 43% of the leprosy patients feel nociceptive
pain and 11% feel pure neuropathic pain.

George et al. (2017)

analyzed histopathology of sural nerve & anaesthetic skin
03 • sural nerve : diagnosed pure neuritic leprosy (PNL) in 13
(52%) out of 25 patients
• anaesthetic skin : identified 10 (40%) patients.
• the combined : sensitivity of diagnosing PNL was 68%,
concluded that sural nerve and anesthetic skin biopsy can be used
as a diagnostic tool for PNL.

Berrington et al.
04 conducted a case-control study in Nepal with 933 patients, and found that
polymorphism of nucleotide-binding oligomerization domain 2 (NOD2)
gene is interconnected to vulnerability of leprosy.
2.5 Transmission of M. Leprae
Job at al. (evaluasi mikroskopis)
The studies by PCR revealed that about 17% transmission of M. leprae was due to skin contact of
healthy patients with the infected ones and about 4% transmission was due to nasal mucosa.

Queiroz et al. (spatial statistics combined with geographic information systems (GIS))
The study concluded that the conjunction of GIS and spatial analysis could determine the clustering of
dieases, that are transmissible, indicating the areas to be targetted for disease Control.

Mattos et al (explored the formation of foamy macrophages in leprosy)

Lipid droplet (LD) is produced by ML are responsible for eicosanoid synthesis due to which the immune
repsonse in leprosy is disrupted.

Sergio et al. (explored the route of Mycobacterium leprae through which it diffuses into the blood stream)
Aerosol route is predominant in the transfer of Mycobacterium leprae

Sharma et al.
• M. leprae not only affects humans but also other living organism such as Dasypus no novemcinctus (armadillo)
• Researchers are trying to design a new drug that might be helpful against M. leprae in armadillos
2.6 New Case Detections
Han et al.
1 Unrevealing a new species Mycobacterium lepromatosis sp. nov

De Souza Sales et al.

2 Indoleamine 2,3-dioxygenase (IDO)  ↑ healthy control and LL patients, activated due to M. leprae &
immunosuppression in LL leprosy

Sausa et al.
3 T2R leprosy patients were found in correlation with genotypes of IL-6,
no linkage between IL-6 and T1R was observed

Andrade et al.
4 Almost all patients with neuritis have demyelination by TNF mediated inflamation

Meima et al.
5 significant number of people with impairment caused by leprosy will need care, treatment,
and training for self-care and prevention of leprosy

Reis et al.
6 it can be detected through DNA of MP patients under quantitative PCR (qPCR)
Conclusion

• The diagnosis of leprosy at earlier stages is

important for its effective treatment.

• Early Diagnosis : Vitamin D and its

receptors, Skin biopsies, HRUS and qPCR

• differentiate leprosy from other infectious

diseases, especially from tuberculosis and
sarcoidosis.

• MDR has many side effects

Thank you
Fastabiqul Khaerat!