Epidemiology of infection disease

(Agent– Host genetic-imunology

interplay)
Pudji Lestari
 Latar Belakang
• Tidak semua individu yang terpapar –terinfeksi
• Tidak semua yang terinfeksi –berkembang
menjadi penyakit
• Paparan agen (via vektor) tidak merupakan satu-
satunya faktor terjadinya disease
• Host factor juga merupakan determinan
terjadinya penyakit
• Distribusi penyakit tidak hanya ditentukan oleh
Agent—tapi juga oleh Aspek Host
 Cakupan isi
• Sebaran epidemiologi penyakit terkait dengan
faktor host tertentu
• Manfaat : pengembangan pencegahan dan
pengembangan pengobatan
 Tuberculosis
• Usia produktif --- risiko sakit dari laten infeksi
Juga dari yang sakit ke MDR
• Study di India (Munje,2015) , 249 pasien TB MDR
• 34% - usia 25 sd 34 thn,
• Laki-laki, 71%

• Di negara berkembang pola tetap = usia produktif

dan laki-laki ; negara maju—usia lanjut (dan
immigran)
 Jenis Kelamin : laki-laki
• testosterone ----impairs macrophage
activation and pro-inflammatory cytokines
production--estrogens are proinflammatory
mediator’s inducer.
• (Bini, 2014)
 Usia produktif
• TB patients cortisol tinggi DHEA rendah ---
rasio cortisol/DHEA naik.
• Prolactin naik and GH naik tapi IGF tidak
• IFN- γ and IL-6 naik juga IL-10 was equally
increased in both groups of TB patients.
• in vitro specific proliferative capacity turun.
(Fernandez 2011)
 Usia produktif dan MDR
• Study di India , 1,250 kasus, 69% MDR
• Umur rata-rata 32 (±13.5 SD) tahun.
• 15-45 years----57%
• TB paru ---- 68% .
• 41% kasus resiten obat lini pertama.

(Akhtar AM 2016 )
 Host aspect
• NRAMP1—polimorfisme yang dianggap
suceptibel di Afrika, tidak sesuai dengan data
di Asia, belum jelas mana yang protektif mana
yang vunerable (Png,2012; Van Crevel
• Meta analisis – Li, 2011 (36 Studi)
• OR sekitar 1,23 sd 1,35 dan variasi cukup kecil
Masih ada faktor lain yang berpengaruh
 TB and TLR 2
• Tunisia: frequency of a human TLR2
Arg677Trp polymorphism (C2029T nucleotide
substitution higher than in healthy controls
(P < 0.0001). (Ben Ali,2004)
• Chinese : Genetic variation in TLR2, 4, 8 and 9,
(innate immunity response) modulate LTBI
and PTB susceptibility (Wu 2015)
 TB and VDR
• Monocyt -- CAMP di up-regulated oleh
1,25(OH)2D3-vitamin D receptor pathway, ----
mempercepat autophagolysosome in M.
marinum infection—inVitro (Sato, 2013)

• Mahavir Hyderabad setting : The proportion of

serum 25(OH) vitamin D deficiency and
insufficiency --high in patients and household
contacts.
• The BB and Bb genotypes of BsmI associated in
patients. (Joshi 2014)
 TB distribution --BCG status
• Turun efektifitas---menekan oksidant
dependent imune respons
• Risiko tuberculosis paru ----keseimbangan
Oksidan host yang mengaktivasi dan
antioksidan mikroba yang menekan antigen-
presentation pathways (Kernodle,2010).
 TB distribution --BCG status
• BCG --live vaccine ---tgt a pre-existing immune
response that can cross-react to BCG.
• Indicated BCG is ineffective in individuals
presensitized to mycobacteria, for example,
by exposure to environmental mycobacteria ,
previous BCG vaccination , M. Tuberculosis
infection.
widespread latent TB infection in adults ---barrier to
the use of BCG (or BCG-derived)
(Aagaard 2009) .
 HIV/AIDS -CCR5 Delta-32
• Mexico (women): Heterozigot allel ini melindungi
terhadap risiko tertular dan progresifitas penyakit
• Iran : Sedikit yang heterozigot maupun yang
homozigot ---suceptibel
• Cameroon : Absent sama sekali di sample
(populasi?)
• Zhuang China : Absent (tidak ketemu di sample
• Spanyol : The CCR5 Delta 32 distribution was non-
significantly different in HIV-1 infected and
uninfected
 DHF –HLA
• Malaysia (in three ethnics) – HLA-B*53 suceptible; HLA-
A*18 protec progression to severe (Appanna,2010)
• Brazil –HLA-B*44 suceptible to denv3 ; HLA-B*07dan
HLA-DR*13 resistance to secondair infections (cross
dengue serotype immunity ) (Eurino,2013)
• Thailand : HLA-B*44 protective imunity in secondair
infections ; HLA-A02, HLA-A01/03 dan B07 suceptible.
(Vejbaesya,2015)
• Philipina ; Hla-A*33:01 protection to severe dengue in
children (Mercado,2015)
• The same HLA type could be in different role in
different people
 Malaria
• Kelainan darah
Sickle cell anemia and malaria map
 Pustaka
• Li X1, Yang Y, Zhou F, Zhang Y, Lu H, Jin Q, Gao L 2011 SLC11A1 (NRAMP1) polymorphisms
and tuberculosis susceptibility: updated systematic review and meta-analysis. PLoS One. Jan
25;6(1)
• Munje R1, Deshmukh R2, Tumane K3. 2015, Multidrug-resistant TB among previously
treated TB cases: A retrospective study in Nagpur, India.Indian J Tuberc. Oct;62(4):207-10.

• Estela Isabel Bini,1,2 Dulce Mata Espinosa,1 Brenda Marquina Castillo,1 Jorge Barrios Payán,1 Darío
Colucci,2Alejandro Francisco Cruz,1 Zyanya Lucía Zatarain,1 Edgar Alfonseca,1 Marta Romano
Pardo,3 Oscar Bottasso,2 andRogelio Hernández Pando1,* 2014 The Influence of Sex Steroid
Hormones in the Immunopathology of Experimental Pulmonary Tuberculosis . PLoS One, 9(4):
e93831

• Fernández R1, Díaz A1, D'Attilio L1, Bongiovanni B1, Santucci N1, Bertola D2, Besedovsky H3, Del Rey
A3, Bay ML1, Bottasso O4 2016.An adverse immune-endocrine profile in patients
with tuberculosis and type 2 diabetes. Tuberculosis (Edinb)., Dec;101:95-101.

• Akhtar AM1, Arif MA2, Kanwal S1, Majeed S3 2016. Prevalence and drug resistance pattern of
MDR TB in retreatment cases of Punjab, Pakistan. J Pak Med Assoc. Aug;66(8):989-93

• Png E1, Alisjahbana B, Sahiratmadja E, Marzuki S, Nelwan R, Balabanova Y, Nikolayevskyy

V, Drobniewski F, Nejentsev S, Adnan I, van de Vosse E, Hibberd ML, van Crevel R, Ottenhoff
TH, Seielstad M. 2012 A genome wide association study of pulmonary tuberculosis susceptibility
in Indonesians,BMC Med Genet. Jan 13;13:5.
 Pustaka
• Meriem Ben-Ali,1 Mohamed-Ridha Barbouche,1,* Soufia Bousnina,2 Abdellatif Chabbou,2 and Koussay Dellagi1
2004 Toll-Like Receptor 2 Arg677Trp Polymorphism Is Associated with Susceptibility to Tuberculosis in Tunisian
Patients. Clin Diagn Lab Immunol. May; 11(3): 625–626.

• Linlin Wu,Yi Hu, Dange Li, Weili Jiang and Biao Xu, 2015.Screening toll-like receptor markers to predict latent
tuberculosis infection and subsequent tuberculosis disease in a Chinese population.BMC Medical Genetics 16:19

• Sato E1, Imafuku S, Ishii K, Itoh R, Chou B, Soejima T, Nakayama J, Hiromatsu K. Scand.2013 Vitamin D-dependent
cathelicidin inhibits Mycobacterium marinum infection in human monocytic cells J Dermatol Sci.Jun;70(3):166-
72.

• Joshi L1, Ponnana M, Penmetsa SR, Nallari P, Valluri V, Gaddam S 2014 Serum vitamin D levels and VDR
polymorphisms (BsmI and FokI) in patients and their household contacts susceptible to tuberculosis. Scan
Journal of Imunology , Feb;79(2):113-9.

• Douglas S. Kernodle, 2010, Decrease in the Effectiveness of Bacille Calmette-Guérin Vaccine against Pulmonary
Tuberculosis: A Consequence of Increased Immune Suppression by Microbial Antioxidants, Not Overattenuation,
Clinical Infectious Diseases, Volume 51, Issue 2, Pages 177–184

• Claus Aagaard1, Jes Dietrich1, Mark Doherty1 and Peter Andersen, 2009, TB vaccines: current status and future
perspectives.Immunology and Cell Biology, 87, 279–286
 Pustaka
• Xavier Eurico de Alencar L1, de Mendonça Braga-Neto U, José Moura do Nascimento E, Tenório
Cordeiro M, Maria Silva A, Alexandre Antunes de Brito C, da Silva Mda P, Gil LH, Montenegro
SM, Marques ET Jr. 2013, HLA-B∗44 Is Associated with Dengue Severity Caused by DENV-3 in a
Brazilian Population J Trop Med. 648475. doi

• Vejbaesya S1, Thongpradit R1, Kalayanarooj S2, Luangtrakool K1, Luangtrakool P1, Gibbons RV3, Srinak
D1, Ngammthaworn S1, Apisawes K1, Yoon IK3, Thomas SJ4, Jarman RG4, Srikiakthachorn A5, Green
S5, Chandanayingyong D1, Park S6, Friedman J6, Rothman AL7, Stephens HA8. 2015 HLA Class I
Supertype Associations With Clinical Outcome of Secondary Dengue Virus Infections in Ethnic
Thais. J Infect Dis. Sep 15;212(6):939-47.

• Mercado ES1, Espino FE2, Perez ML3, Bilar JM4, Bajaro JD4, Huy NT5, Baello BQ3, Kikuchi
M5, Hirayama K5. 2015, HLA-A*33:01 as protective allele for severe dengue in a population of
Filipino children PLoS One. Feb 6;10(2):e0115619

• Appanna,Ponnampalavanar, Chai See, Sekaran, 2010, Susceptible and Protective HLA Class 1 Alleles
against Dengue Fever and Dengue Hemorrhagic Fever Patients in a Malaysian Population,Pols
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