Umar-Fahmi Ahmadi University of Indonesia (FKMUI) Community Based Dengue Control Program ( a new concept and its implementation) Umar-Fahmi Ahmadi University of Indonesia (FKMUI)

Manajemen Demam Berdarah berbasis wilayah (sistim deteksi dini dan pengobatan dini untuk mencegah eskalasi /KLB)

Topik2 Latar belakang Mengapa perlu konsep baru? Bagaimana konsep tersebut? Apakah sudah terbukti? Langkah apa yang harus di lakukan untuk tindak lanjut?

Theory of Simpul (Dasar) inti permasalahan kesmas (kejadian penyakit) Manajemen Kesehatan Udara Air Sakit Sumber Penyakit Pangan Komunitas (Perilaku) Sehat Vektor Penular Manusia Iklim+topografi Lingkungan Strategis/politik Simpul 1 2 3 4

Effective control of Communicable Disease UFA (Manajemen Penyakit Berbasis Wilayah, Penerbit Kompas, 2005; Penerbit UI Press, 2008): Manajemen KLB atau penularan penyakit menular terdiri dari 3 pokok program: (1). Immunization program (but not for all communicable diseases ) Dengue none (2). Effective case management (early diagnostic and prompt treatment) (3). Environmental control and behavioral aspect (example Singapore and other developed countries)

Key elements for Control (effective case management for Communicable Disease) Early Diagnostic : antigen captured (earlier stage) Effective treatment (medicines)

Background information WHO estimate for Dengue as major deadly threat to all over tropics subtropics countries Global warming, global spread, more area affected No licensed vaccine and medicines for definitive treatment, as yet?? Each case become effective source of infection, focus of unstoppable outbreaks Dengue NS1 antigen capture ELISA + Rapid Diagnostic (telah diketemukan) MAC-antiviral Dengue, listed in TGA and used in Aust. ‘n Indonesia (2008/09) telah diketemukan MAC : in vitro 4% kills Den 1,2,3 and 4

Number of DHF Cases per year in Indonesia (2002-Aug 2007)

Management Model of Dengue outbreaks Mosquito Bites/trans Community at risk Dengue cases Dengue Case as a source Professor UF Achmadi, Faculty of Public Health University Indonesia July 2008. Breeding places

Penjelasan slide tersebut diatas (slide no 9) Focus pengendalian Demam Berdarah pada saat ini hanya : (a). Pengendalian nyamuk, sarang nyamuk, larva dan kegiatan lingkungan saja (b). Penyuluhan masyarakat misalnya COMBI – Community Behavior Impact ©. Diusulkan manajemen pada sumber penyakit (virus) yaitu dengan cara deteksi dini dengan metode diagnostik NS1 dan pengobatan sampai tuntas dengan anti viral. Kalau bisa dilakukan secara pro aktif, bisa menekan KLB

Course of Dengue Infection/Dx Plaque Reduction Neutralization Test Hemagglutination Inhibition IgM and IgG ELISA Rapid tests Shock Hemorrhage Virus isolation Molecular techniques Dengue antigen capture ELISA Anti-dengue Ab Fever Mosquito bite Viremia -4 -2 0 2 4 6 8 10 12 Day of Illness

Counting days of fever and critical times Course of Dengue Infection Incubation Period Acute Phase Critical Phase Convalescence Phase Temperature 5 - 9 days 1- 4 days 1 – 3 days 1- 2 days 41 40 39 38 37 1 2 3 4 5 6 7 8 Days Counting days of fever and critical times

“Kasus” Demam Berdarah (a). Tanpa gejala (b) Simptomatik (1). Gejala – ringan (2). Dengan gejala + tanda pendarahan (3). Gejala+komplikasi Semua penderita (a+b) mengandung virus dan siap menularkan menjadi FOCI sebuah KLB

Treatment seeking behavior vs. immuno pathogenesis of Dengue Most patients fever : self medication, CHC (Puskesmas), general practitioners at clinical practice, return to G.P.’s, and or direct to hospital (virus siap di tularkan) Preliminary study: admit to hospital at 3 to 4th day of fever ( at later stage, by the time virus already spread) Fail case management such case become focus of infection  outbreak occurence

Konsep Manajemen DBD berbasis wilayah Adalah satu konsep yang menggarap atau berfokus pada pengendalian sumber penyakit (yaitu penderita Demam Berdarah dengan atau tanpa gejala) dilakukan secara dini untuk mencegah eskalasi atau terjadinya KLB + pengendalian faktor risiko.

….konsep… Konsep ini mengutamakan deteksi dini yakni deteksi virus (antigen) secara dini dengan metode antigen capture (NS1 atau non-structural protein 1) untuk mendeteksi adanya virus dalam tubuh. Deteksi virus bisa dilakukan sehari sebelum penderita menderita demam, hingga virus hilang pada hari ke 9 Setelah diketahui ada nya virus: penderita di beri antiviral – MAC (Melaleuca alternifolia Concentrate).

….konsep… Deteksi dini dilakukan oleh petugas surveillance atau kader dengan mencari kasus DBD secara pro aktif disekitar penderita pertama yang diketahui alamatnya, atau menggunakan petugas yang siaga, dengan mendirikan Pos Pos DBD disetiap RW, atau Kelurahan. Setiap kelurahan atau Puskesmas di lengkapi alat antigen capture NS1 yang Rapid (hanya hitungan 20 menit sudah diketahui).

….konsep…. Kalau kasus kasus secara awal atau secara dini di ketahui dan dikendalikan dengan Anti Viral Den1,2,3,4 (mis. MAC) maka focus focus KLB dapat di tekan. Pendekatan ini dilakukan dengan pendekatan lainnya, yakni pengendalian sarang nyamuk (breeding places), jentik dll Fogging hanya dilakukan kalau sangat perlu

…konsep.. Pendekatan ini bisa menekan biaya APBD yang menggratiskan pasien DBD di Rumah Sakit. Pasien tidak perlu ke Rumah Sakit hanya dikelola oleh Puskesmas Biaya opportunity cost bisa di tekan Biaya transport keluarga penderita yang dirawat bisa ditekan.

Preliminary study for Den cases Management in the field, Makasar 2008 Early diagnostic Prompt treatment Apakah sudah pernah dilakukan ?

Objectives studi Makasar, 2008 (a). To evaluate the effectiveness of MAC to treat Dengue Infection (b). Diagnostic using NS1 (antigen – virus captured technique) in the field (b). To evaluate potential effectiveness MAC could reduce or to stop the spread of Dengue infection in line with surveillance + Fogging Focus currently practiced. Bila settingnya untuk menghentikan outbreaks  maka evaluasi harus dilakukan dengan interval 5 tahun (poin 2) Tolong ditanyakan ke dr Irene  bagaimana metode untuk fogging dan larvicide  apakah akan tetap di bandingkan dengan metode B (RCT) karena metode fogging itu adalah metode preventif, sedangkan metode B adalah metode kuratif? (poin 1)

Question of the pilot study MAC effective to treat Dengue infection? MAC effective to stop the spreads of Dengue infection? NS1 antigen captured di lapangan bisa? How to stop outbreaks occurrence

Current Method (fogging focus method) Dengue infection patient in hospital (takes a week to?) Find the address Find mosquito larva around the address Find more fever cases Larva (+) Larva (-) Fogging + Larvicide

Proposed New Method (treatment focus method) Dengue infection out patients clinics (front liners) e.g. Puskesmas (CHC), G.P.s Find the address (directly- a must) Find people with 1 day fever surround the first cases NS-1 Examination For early diagn

Continued… Active case finding Using surv. meth In patient Treatmnt NS-1 Examination Active case finding Using surv. meth (+) (-) In patient Treatmnt Outpatient treatment MAC treatment MAC treatment MAC treatment MAC treatment

Find the address (epidemiological investigation) method ..continued .. MAC dosage : 3 x 150 mg Case finding: base on the cases’ admit to the clinic/emergency at hospital Find the address (epidemiological investigation) Criteria evaluation for treatment success: NS1 at the Day 1st , Day 3rd , Day 5th , of MAC application, and other clinical symptoms

Summary of the preliminary study of the effectiveness of MAC (2008) 15 cases suspected Dengue grade 1 and 2, NS1+ qualitative and manual (Elisa Reader) in Makasar (community based + hospital based) Patients with history of 1 or 2 days of fever Symptoms e.g. fever, severe headache, nausea, vomit, epigastric pain (totally disappear at day 2 late afternoon or day 3). Torniquette test + up to ++ Routine Blood test thrombocytes, hematocryte, leucocyte, lymphocytes Inform consent MAC+other medicine as usual

Summary (result) 7 out of 10 patients has NS1 + on their first day of sickness (2 of them withdraw) All cases/ suspected Dengue (5 cases) with NS1+ on their first day of medication, gave response on their 3rd day of medication, no fever, no headache, no nausea and epigastric pain,most important NS1 all are (-) negative on their 3rd day of medication, which is normally (based on the theoretical bases are positive up to day 9).

summary The negative value of NS1 were consistent on Day 5 and Day 7 until discharge, whereas value of thrombocytes, leucocytes, as well as lymphocytes increased significantly. No more Clinical symptoms, fully recover on Day 4 or 5 Conclusion : MAC is (most likely) effective for such case management of Dengue cases along with early diagnostic test. There fore : Community Based Dengue Control Program is feasible.

Course of Dengue Infection With M.A.C. No More Shock Hemorrhage (predicted)‏ Dengue antigen capture ELISA Fever No more Fever Mosquito bite Viremia No antigen NS1 (-) -4 -2 0 2 4 6 8 10 12 Day of Illness

Days of fever (yellow with MAC) vs. red line-standard days of fever Course of Dengue Infection With M.A.C Incubation Period Acute Phase Critical Phase Convalescence Phase Temperature 5 - 9 days 1- 4 days 1 – 3 days 1- 2 days 41 40 39 38 37 1 2 3 4 5 6 7 8 Days Days of fever (yellow with MAC) vs. red line-standard days of fever

Langkah2 Steps : Preparation e.g. training for front liners (Dr. Puskesmnas – CHC, and General Practitioners, eg. Clinicals symptoms, diagnostic Kit usage, case management, epidemiological investigation) Preparation training for Epid. investigation Data recording Analyses Evaluation

Conclusion Community Based Dengue Control Program can be applied (feasible). Integration case management and risk factors Management Cost analyses may well be reduced Opportunity cost may well be reduced Family cost e.g. transportation etc

What is MAC? MAC is an extract produced from the essential oil collected from an Australian Native plant from the Myrtaceae Family; The plant leaves are harvested from large commercial plantations and then steam distilled to recover the base essential oil “Melaleuca Oil”.

What is MAC? The plant leaves are harvested from large commercial plantations and then steam distilled to recover the base essential oil “Melaleuca Oil”.

Potential treatment of Avian Bird Flu with MAC, a safe, non-toxic Australian Botanical Compound

MAC technological breakthrough MAC technology is unique in its approach to dealing the virus. This breakthrough impacts not just Bird flu, but many current viral diseases, e.g. Dengue MAC has been shown to interrupt the attachment system the virus uses to enter a human cell and multiply. Electron microscopic photos also shows in some cases complete cell destruction (see report and photos from the Australian Government’s CSIRO Geelong Animal Health Laboratories and CEDE University of Indonesia and NHIRD, Depkes RI)

MAC efficacy

MAC efficacy Image showing numerous virus particles following treatment. The surface membrane (envelope – orange arrow) is no longer homogeneous and surface projections are largely missing (blue arrows).

Figure 1. H5N1 Control (treated with DMSO only)

Figure 1. H5N1 Control (treated with DMSO only)

Special type of tea tree for MAC

Tea Tree plantation

Safety studies of MAC (1) --March 8, 05 report Acute oral toxicity sighting study of MAC 10% in rat The acute oral toxicity of MAC 10% was investigated in groups of 2 Sprague Dawley Specific Pathogen Free (SPF) rats at a single dose level; The test item was administered orally by intra-gastric gavage to one (1) group of 2 rats (1/sex) at the maximum administrable volume of 10 ml/kg. A control group of 2 rats (1/sex) was dosed with the vehicle along (water). Body weights were determined immediately before test item administration and daily thereafter. All animal were observed at frequent intervals on the day of test item administration, and then daily for signs of toxicity over the 7-day experimental period. On day 8, all animals were sacrificed and subjected to a gross necropsy examination.

Summary of Study results (March 8, 2005) Acute oral toxicity sighting study of MAC 10% in rat (cont) Summary of Study results (March 8, 2005) There were no deaths or abnormal signs in any animal during the experimental period. Overall body weight gains occurred in all animal. There were no gross abnormalities found in the major organs of any animal treated with the vehicle or test item at autopsy. Under the conditions of this study, the test item, Mega Bac 10%, produced no signs of toxicity when administered at a volume of 10 mL/kg.

By removing non-essential compounds, better efficacy. Mega Bac Botanical Medicine extraction technology: Making MAC safer and better By removing toxic substances, ensuring the product safer for human consumption; By removing non-essential compounds, better efficacy.

Tox Study di Indonesia University of Gajah Mada study: acute toxicity test+sub acute toxicity test LD 50 acute 750 mg/kg BW LD50 sub acute 450 mg/kb BW Practically non toxic Standard requirements for human use wide margin of safety, effective at lower dosage

Terima kasiiih

Apakah feasible? Trilogi … (a). COMBI (community at risk) (b). Breeding places (c). Manajemen Kasus DBD sebagai sumber penularan (proactive : early diagnostic + prompt treatment) menghentikan foci KLB