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ANALISA JURNAL ILMIAH/ STUDI LITERATUR

Disusun untuk memenuhi tugas analisis jurnal

Oleh :
Nama: APRIS TIANA
NIM: 030520421
PROGRAM PENDIDIKAN PROFESI NERS
INSTITUT MEDIKA Drg. SUHERMAN CIKARANG

FORMAT
ANALISA JURNAL ILMIAH/ STUDI LITERATUR
A. IDENTITAS JURNAL
Nama Jurnal :Jurnal Biomedik (JBM)
Judul :Terapi Larva Pada Luka Kronis Terbuka
No :1 Maret 2015
Volume :7
Penulis :Sunny Wangko
B. HASIL ANALISIS
No Kriteria Jawab Pembenaran & Critical thinking

1 P Ya Besarnya biaya pengobatan luka


(Problem/ Population) kronis di negara maju maupun
negara terkebelakang.

2 I Ya Terapi Larva
(Intervention)
Terapi larva dapat mempercepat
penyembuhan luka kronis,
menurunkan masa penggunaan
antibiotik, mengurangi masa
perawatan di rumah sakit, menu-
runkan risiko amputasi,
menurunkan jumlah kunjungan
pasien rawat jalan, relatif
ekonomis, dan memperbaiki
kualitas hidup.

3 C Ya Pada jurnal Jurnal Biomedik


(Comparation)
dijelaskan bahwa Larva
bergerak pada permukaan luka
sambil menyekresi sekret yang
berpotensi memecahkan dan
mencairkan jaringan nekrotik.
Sedangkan pada Journal
Complilation dijelaskan bahwa
larva memakan jaringan
nekrotik, puing-puing seluler
dan eksudat di dalam luka,
sehingga debriding dari devi-
jaringan talised.
4 O Ya Hasil penelitian menunjukkan
(Outcome)
pasien dengan luka kronis yang
tidak menyembuh jarang menolak
untuk diberikan terapi larva.
Indikasi untuk terapi larva ialah
luka kronis yang tidak menyembuh
disertai jaringan nekrotik. Sebagai
contoh: ulkus akibat tekanan, ulkus
venosa, , luka traumatic.
Terapi larva mudah diaplikasikan,
relatif tidak mahal, dan tidak merusak
flora normal dalam saluran cerna, atau
meninggalkan residu yang merugikan
seperti halnya antibiotik sistemik.11,16
Larva harus digunakan dalam 8 jam
setelah erupsi dan disimpan pada suhu 8-
100C

C. KESIMPULAN

Terapi larva telah dikenal sejak berabad-abad yang lalu. Dengan dite-
mukannya antibiotik dan tehnik perawatan luka serta pembedahan yang lebih baik
maka terapi larva ditinggalkan. Akibat terjadinya resistensi bakteri terhadap
antibiotik maka terapi larva direintroduksi dan pada tahun 2004 telah diakui oleh
FDA untuk pemakaian pada luka kronis terbuka.
Awalnya diduga terapi larva bermanfaat hanya sebagai debridemen mekanis,
tetapi hasil-hasil penelitian melaporkan adanya berbagai bahan yang diduga turut
membantu penyembuhan luka, antara lain enzim proteolitik, bahan antibakteri,
growth factors, dan sitokin.
Terapi larva digunakan pada luka kronis terutama yang telah gagal dengan
terapi konvensional. Dengan dikembang- kannya molekul bioaktif yang terkandung
dalam bahan sekresi dan ekskresi larva diharapkan terapi larva dapat digunakan
secara luas untuk mendapatkan hasil yang lebih optimal dengan biaya yang cukup
ekonomis.

D. REFERENSI
https://ejournal.unsrat.ac.id/index.php/biomedik/article/view/7289
TERAPI LARVA PADA LUKA KRONIS
TERBUKA
Sunny Wangko

Bagian Anatomi-Histologi Fakultas Kedokteran Universitas Sam Ratulangi Manado Email:


sunnywangko@yahoo.com

Abstract: The usage of larvae in wound treatment has been known across the centuries in
different countries. However, larval therapy is offered when the conventional therapy has
failed in the management of chronic, infected wounds. Concerning the larval therapy, it was
presumed that the wound healing was due to the mechanical debridement effect of the larval
movement and of their hooks. To date, a variety of study reports reveals that there are several
beneficial effects of the larval therapy, inter alia: secretion/excretion of larvae contains
enzymes, growth factors, and cytokines that collaborate in the wound healing process. The
bioactive molecules in the secretion/excretion of the larvae has to be further studied and to be
developed, therefore, they can be applied in the wound management efficiently and
economically. Keywords: larval therapy, chronic wound, healing process.

Abstrak: Walaupun pemanfaatan larva pada luka kronis telah sangat lama dikenal di berbagai
negara, terapi larva umumnya digunakan bila terapi konvensional telah gagal. Awalnya
diduga bahwa efek debridemen mekanis oleh gerakan larva dan kaitnya yang paling berperan.
Dewasa ini, laporan berbagi studi telah mengungkapkan bahwa larva menyekresi dan
menyintesis berbagai bahan baik berupa enzim, sitokin, dan growth factors yang turut
berperan dalam proses penyembuhan luka. Adanya molekul bioaktif dalam ekskresi dan
sekresi larva perlu diteliti dan dikembangkan agar dapat diaplikasikan dengan lebih efisien
dan ekonomis. Kata kunci: terapi larva, luka kronis, penyembuhan luka.
Umumnya larva serangga lebih dikenal dari Prancis pada abad ke-16 dan abad ke 18- 19.
dampak yang merugikan kehidupan manusia Terapi ini mulai ditinggalkan sejak
antara lain: sebagai hama tanaman, penyebab ditemukannya antibiotik (1940), tetapi
miasis pada manusia dan hewan ternak, kemudian setelah terjadinya peningkatan
mengganggu kenya- manan, dan merupakan resistensi kuman terhadap antibiotik terapi
bentuk pradewasa dari serangga sebagai larva ditinjau kembali,1,2 terutama pada luka
vektor penyakit. Pada hakekatnya, larva kronis yang terinfeksi oleh methicillin-
sangat berperan dalam kehidupan manusia. resistant Staphylococcus aureus (MRSA) dan
Daur ulang (recycling) sampah, tanaman patogen yang resisten lainnya.3
rusak, serta bangkai dan mayat,
Awalnya, masalah yang dihadapi pada
keikutsertaannya dalam rantai makanan, dan
terapi larva ialah bagaimana memperoleh larva
pemanfaatan dalam berbagai komoditi
yang steril dan hidup (medical- grade). Dengan
misalnya larva ulat sutera menunjukkan
kemajuan teknologi, larva yang digunakan
manfaat larva terhadapan kehidupan. Dewasa
lebih terjamin kualitasnya dan telah dijinkan
ini, pemanfaatan larva, khususnya larva lalat,
oleh USA Food and Drug Administration
telah ditinjau kembali untuk perawatan luka
(FDA) pada tahun 2004.2,4 Sejauh ini larva yang
terutama luka kronis terbuka yang telah
umum digunakan ialah larva lalat Lucilia
memboroskan biaya pengobatan yang cukup
sericata yang bersifat nekrofagus.1-3,5-9
tinggi baik di negara maju maupun negara
terkebelakang. Terdapat beberapa istilah yang dipakai
Pemanfaatan larva dalam perawatan luka untuk perawatan luka terbuka dengan
(terapi larva) sebenarnya telah dikenal sejak menggunakan larva yaitu: terapi larva, larval
berabad-abad yang lalu, kemudian therapy, maggot debridement therapy/MDT,
dikemukakan oleh beberapa ahli bedah di biosurgery, biodebridement, dan controlled
therapeutic myasis.2,5-7,9 Telaah ini bertujuan tersebut, mortalitas luka jenis demikian
untuk mengemukakan keunggulan terapi larva mencapai hampir 75%.11 Sekitar tahun
yang sejauh ini belum dimanfaatkan di 1935, terapi larva telah digunakan pada
Indonesia. banyak rumah sakit di Amerika, Kanada,
SEJARAH dan Eropa.5 Terapi larva juga digunakan
Pemanfaatan larva dalam perawatan dan pada ulkus mamae, luka bakar, abses,
pengobatan luka kronis terbuka telah dikenal karsinoma sel skuamous, dan mastoiditis
sejak berabad-abad lalu.1,3,10,11 Perawatan luka subakut.11 Kendala pada saat itu (tahun
dengan menggunakan larva pertama kali 1930-an) ialah menyiapkan kemasan untuk
dikenal pada suku Maya Indian di Amerika, aplikasi larva, kesulitan memperoleh larva
penduduk bebas kuman yang hidup, dan biaya yang
aborigin Australia,2,11,12 dan di Cina.2,5 Pada tinggi ($5 pada 1933).8 Dengan adanya
abad ke-16 (1557), Ambroise Pare kemajuan dalam tehnik pembuatan
(seorang ahli bedah kekaisaran Prancis pembalut dan perekat yang lebih nyaman
Charles IX dan Henri III) melaporkan (seperti cage-like dressings) serta dapat
manfaat larva pada luka-luka prajurit mempertahankan larva pada alas luka;
selama perang.5,11 desinfektan dan tehnik rearing yang sangat
Pada abad ke 18-19 (1829) Baron mendukung produksi larva yang medical-
Dominique Jean Larrey (seorang ahli grade; dan transportasi yang menjamin
bedah zaman Kekaisaran Napoleon) yang pengiriman larva ke lokasi, diharapkan
pertama melaporkan secara tertulis bahwa terapi larva akan dapat digunakan secara
larva hanya menyerang jaringan nekrotik lebih luas.8
dan terapi larva dapat meningkatkan Pada era antibiotik (perang dunia II),
pembentukan jaringan granulasi serta dengan ditemukannya antibiotik penicillin
memicu penyembuhan luka terinfeksi yang oleh Alexander Flemming (1928)2 dan
ditemukan pada prajurit.2,5,11 Selama sulfa yang ampuh terhadap berbagai jenis
perang saudara di Amerika, Joseph Jones bakteri dan didukung oleh tehnik
dan J. F. Zacharias (ahli bedah sekutu) pembedahan yang lebih baik, maka pada
mulai menggunakan larva untuk peng- tahun 1940 terapi larva mulai diting-
obatan luka dan mencatat bahwa dalam galkan.1,8,10,11 Munculnya resistensi ber-
beberapa hari larva telah membersihkan bagai strain kuman terhadap antibiotik dan
luka jauh lebih baik dari bahan-bahan yang meningkatnya insidensi luka dengan
direkomendasikan saat itu.2,5,6,11 vaskularisasi yang kurang memicu
Pada era pre-antibiotik (1920-an dan reintroduksi terapi larva pada tahun1980-
1930-an), studi mengenai terapi larva an di Amerika, Inggris, dan negara Eropa
pertama kali dikemukakan oleh William S. lainnya.1,2,8 Pada tahun 1990-an, Sherman
Baer (1929), seorang ahli bedah ortopedik et al di Amerika Serikat dan Mumcouglu
dari John Hopkins Hospital di Baltimore, et al di Israel mereintroduksi terapi larva
Maryland.5,8,10,11 Bear menggunakan larva untuk pengobatan luka kronis.6
yang steril untuk mengobati luka-luka Pada tahun 2004, US Food and Drug
prajurit selama perang dunia I dan Administration telah mengijinkan
melaporkan bahwa luka pada fraktur penggunaan terapi larva dengan indikasi
terbuka dan luka pada abdomen yang debridemen untuk luka kulit kronis dengan
dinfestasi beribu-ribu larva jaringan nekrotik dan luka pada jaringan
memperlihatkan pertumbuhan jaringan ikat, termasuk ulkus akibat tekanan
granulasi yang sehat. Juga pada kasus (pressure ulcer), ulkus stasis venosa, ulkus
osteomielitis anak, terapi larva neuropatik pada kaki, dan luka pasca
menghasilkan debridemen yang cepat, operasi yang tidak menyembuh.2,4
menurunkan jumlah bakteri, mengurangi
bau, dan alkalinisasi alas luka.2 Dalam era
LUKA KRONIS kontaminasi saat diaplikasikan pada luka. Larva
diperlihara pada lingkungan yang lembab dan steril untuk
Dengan bertambahnya usia harapan mendapatkan larva yang medical grade.5,11 Telur dicuci
dengan larutan antiseptik dan ditempatkan di dalam wadah
hidup maka jumlah pasien dengan luka steril yang berisi brewer’s yeast dan kedelai sebagai
kronis akibat berbagai penyakit, terutama sumber makanan agar larva tetap bertahan hidup sampai
diabetes melitus dan penyakit pembuluh dapat ditranspor dalam wadah steril untuk kebutuhan
terapi larva.11
darah perifer turut meningkat. Luka kronis
tidak mengikuti fase-fase penyembuhan
luka, tetapi akan berhenti pada fase
inflamasi akibat adanya debris nekrotik
dan infeksi.2,5
Debridemen ialah tindakan
mengeluar- kan debris asing nekrotik atau
jaringan terkontaminasi dari alas luka
(wound bed) sehingga jaringan sekitar
yang sehat akan terbuka. Debridemen
dapat dilakukan dengan berbagai cara.
Salah satu cara yang telah lama dikenal
ialah maggot debridement therapy (MDT)
atau terapi larva. Dalam hal ini, larva lalat
yang medical-grade diaplikasikan pada
luka untuk menghasilkan debridemen,
desinfeksi, dan penyembuhan luka
(artificially induced myasis).2,3,5
DESKRIPSI LARVA YANG DIGUNA-
KAN PADA TERAPI LARVA
Umumnya yang digunakan untuk
terapi larva ialah larva Phaenicia
(Lucilia) sericata (Ordo Diptera, famili
Calliphoridae), yang tergolong dalam
green bottle fly (Gambar 1).2,3,5-9 Larva
hanya memakan jaringan nekrotik dan
tidak mengganggu atau menyusup ke
dalam jaringan sehat. Phormia regina
(blackbottle fly) juga dilaporkan dapat
digunakan untuk
terapi larva.6,11
Siklus hidup Phaenicia (Lucilia)
sericata

berlangsung sekitar 10-14 hari. Telur menetas


setelah sekitar 12-24 jam. Pertumbuhan larva dari instar 1
sampai dengan instar 3 (wondering larval stage)
berlangsung selama beberapa hari (3-7 hari) hingga
mencapai ukuran sekitar 10 mm, kemudian larva
(prepupa) akan mencari tempat untuk melakukan pupasi.
Masa pupasi berkisar 7-20 hari, tergantung pada suhu dan
cuaca (Gambar 2).5,6,8,9
Larva yang akan digunakan untuk terapi larva harus
steril (bebas bakteri) untuk mencegah terjadinya
memecahkan jaringan nekrotik dan
Pada terapi larva, sekitar 5-10 ekor matriks ekstrasel (termasuk laminin dan
larva diaplikasikan per cm2 luka.7,8,9,11 fibronektin) Chan menjadi bentuk
Larva yang digunakan ialah instar 1 ber- semisolid yang dapat diabsorpsi dan
ukuran panjang sekitar 2 mm (1-3 mm) dicernakan oleh larva.4,5,9,11 2. Desinfeksi
dan dapat berkembang menjadi 8-10 mm luka: Larva memakan debris yang
setelah 5-7 hari. Selama 48-72 jam larva terinfeksi, menghasilkan bahan
bergerak pada permukaan luka sambil bakterisidal yang berspektrum luas
menyekresi sekret yang berpotensi terhadap bakteri Gram positif dan negatif,
memecahkan dan mencairkan jaringan antara lain strain bakteri Staphylococcus
nekrotik.7,8,11 Larva dapat digunakan sp. termasuk methicillin-resistant
bersama antibiotik sistemik, dan juga tidak Staphylococcus aureus (MRSA),
memperlihatkan efek merugikan pada X- Bacillus sp., Escherichia Coli,
ray sehingga larva dapat dibiarkan pada Pseudomonas sp., Proteus sp.,
tempatnya saat dilakukan tindakan Enterococcus sp., dan
tersebut.11 Enterobacter sp.2,3,5,7 Larva juga
menghasilkan amonia yang menye- babkan
MANFAAT TERAPI LARVA alkalinisasi, diduga dapat menghambat
Manfaat terapi larva telah dilaporkan pertumbuhan bakteri.5,8
oleh berbagai studi yang tersebar di 1. Irigasi luka oleh eksudat yang distimu-
seluruh dunia. Terapi larva dapat lasi oleh larva yang menelan jaringan
mempercepat penyembuhan luka,15 nekrotik dan oleh sekret larva sendiri.3
menurunkan masa penggunaan 2. Inhibisi dan eradikasi biofilm.
3,10
antibiotik, mengurangi masa perawatan Chymotrypsin dan DNAse dalam
di rumah sakit,6-8 menu- runkan risiko sekret larva dapat memecahkan
amputasi,3,6,10 menurunkan jumlah protein yang menyusun biofilm.2,4
kunjungan pasien rawat jalan, relatif
3. Menghasilkan growth factors: Larva
ekonomis,3 dan memperbaiki kualitas
menghasilkan alantoin, urea, dan
hidup.6 Beberapa kondisi pada terapi larva
bahan lainnya yang dapat bekerja
yang membantu penyembuhan luka kronis,
sbagai
yaitu:
growth factors.2,4,6,10
1. Debridemen: Gerakan-gerakan 4. Menghasilkan sitokin, antara lain
mekanis dari larva dengan kaitnya inter- feron dan interleukin 10 yang
pada permukaan sampai alas luka diduga mempercepat penyembuhan
berfungsi sebagai debridemen yang dapat luka.5
membersihkan luka dari jaringan nekrotik 5. Menghambat respons proinflamasi
dan terinfeksi.4,5,9 Studi Opletalova et al.4 monosit melalui peningkatan cilik
mendapatkan hasil debridemen dengan AMP oleh bahan yang disekresi dan
terapi larva lebih cepat dibandingkan diekskresi oleh larva.8
terapi kon- vensional lainnya. 6. Menghambat proses inflamasi melalui
Dibandingkan cara debridemen lainnya pemecahan komponen komplemen
seperti hydrogel dressings, pengolesan yang berakibat turunnya aktivitas
madu, debri- demen mekanis atau komplemen.2
hydrosurgery, terapi larva 7. Meningkatkan migrasi fibroblas.2,5
memperlihatkan efisiensi ekonomis yg
8. Berefek angiogenesis.2,7
signifikan.16
1. Membersihkan jaringan nekrotik:
INDIKASI TERAPI LARVA
Larva menghasilkan berbagai enzim
proteolitik antara lain kolagenase yang
Umumnya pasien dengan luka kronis 9. Alergi terhadap telur, kedelai,
yang tidak menyembuh jarang menolak brewer’s yeast, dan larva.5
untuk diberikan terapi larva.3,6 10. Semua keadaan dimana debridemen
Indikasi untuk terapi larva ialah luka merupakan kontraindikasi.6
kronis yang tidak menyembuh disertai
jaringan nekrotik. Sebagai contoh: ulkus EFEK SAMPING TERAPI LARVA
akibat tekanan, ulkus venosa, ulkus Selama pemberian terapi larva, efek samping yang
diabetik, ulkus neuropatik (non-diabetes), sering ditemukan, antara lain:
ulkus iskemik/arterial, luka traumatik, luka 1. Rasa tidak nyaman (yuk factor) baik
bedah, tromboangitis obliterans, luka/ulkus untuk pasien, dokter, dan tenaga medis
pasca trauma, necrotizing fasciitis, lainnya.5,6
pioderma gangrenosum, abses pada
maleolus, osteomielitis sinus pilonidal, 2. Nyeri: Mumcouglu et al.17 melaporkan
luka infeksi pasca bedah, luka akibat selama terapi larva nyeri ditemukan
proses keganasan, luka bakar disertai 41% pada pemakai tea-bag like pouch
infeksi MRSA, dan (TBA) dan 38% pada pemakai cage-
mastoiditis subakut.5,6 like dressing (DA). Pemberian
analgetika dilakukan dengan titrasi
dosis, dan bila diperlukan dapat
KONTRAINDIKASI
dilakukan blok saraf tepi. Courtenay et
Terdapat kontraindikasi relatif dan al.10 mendapatkan keluhan nyeri
kontraindikasi absolut untuk terapi larva. ringan sampai berat (umumnya nyeri
Yang termasuk kontraindikasi relatif yaitu: sedang) 48-72 jam setelah larva
diaplikasikan pada luka; nyeri dapat
1. Luka yang kering, karena larva
diatasi dengan analgetika.
memerlukan lingkungan yang
lembab. 5
3. Perdarahan ringan.10
2. Pasien yang tidak 4. Pireksia: Terjadinya pireksia belum
memahami penggunaan terapi larva.6 jelas, mungkin berhubungan dengan
3. Luka yang membutuhkan inspeksi reaksi imunologik.5,10
yang sering.6 5. Influenza-like symptoms (pireksia,
malaise, keluhan saluran napas).10
Yang termasuk kontraindikasi absolut yaitu: 6. Alergi terhadap bahan hidrokoloid
1. Luka terbuka yang berhubungan pada pembalut.10
dengan kavitas tubuh atau organ 7. Munculnya bau yang tidak enak pada
dalam.5,9 aplikasi larva yang pertama kali,
terlepasnya larva, atau larva yang mati
2. Luka yang dekat dengan pembuluh
akibat tekanan pembalut.5
darah besar.5,9
3. Luka yang mudah berdarah.5,9
KOMPLIKASI
4. Tulang atau tendon yang nekrotik.6 Komplikasi yang berat tidak pernah dilaporkan.3,5
5. Gangguan perdarahan (herediter atau
farmakologik).6
KEMASAN
6. Luka yang kurang
Terapi larva mudah diaplikasikan, relatif tidak
vaskularisasi (peripheral vascular mahal, dan tidak merusak flora normal dalam saluran
disease).6 cerna, atau meninggalkan residu yang merugikan seperti
halnya antibiotik sistemik.11,16 Larva harus digunakan
7. Alas luka yang ditutupi kerak keras.6 dalam 8 jam setelah erupsi dan disimpan pada suhu 8-
8. Fistula yg belum dilakukan tindakan 100C.9,18
Secara umum terdapat 2 kelompok kemasan larva
pembedahan.6 yang tersedia untuk aplikasi klinis: free-range dan bio-
bag (BioMonde). Pada kemasan free range, larva dalam bahan sekresi dan ekskresi larva diharapkan terapi
diaplikasikan langsung pada luka. Setiap aplikasi harus larva dapat digunakan secara luas untuk mendapatkan
diganti setelah 3 hari. Kemasan ini sangat sesuai untuk hasil yang lebih optimal dengan biaya yang cukup
luka yang bergaung atau berongga.2,9,18 Bio-bag berupa ekonomis.
kantong yang terdiri dari jaring poliester halus dengan
sepotong foam untuk menyerap sekresi larva yang
berlebihan. Kemasan bio-bag lebih praktis dan estetik, DAFTAR PUSTAKA
serta sesuai untuk pasien rawat jalan untuk menjamin
tidak terlepasnya larva. Bio-bag 1. Steenvorde P, Jacobi CE, van Doorn L,
harus diganti setelah 4 hari.9,18
Oskam J. Maggot debridenet therapy of
Dengan kemajuan teknologi, telah infected ulcers: Patient and wound factors
dikembangkan berbagai kemasan larva, influencing outcome – A study on 101
antara lain: single-piece, hinged, dan cage- patients withy 117 wounds. Ann R Coll
like dressings. Kemasan demikian disebut Surg Engl. 2007;89(6):596-602.
maggot confinement dressings yang 2. Cazander G, Pritchard DI, Nigam Y,
Jung W, Nibbering PH. Multiple actions
memberi akses pada larva ke luka secara
of Lucilia sericata larvae in hard-to-heal
bebas tetapi dapat mencegahnya untuk wounds. Prospects &
terlepas keluar.8 Overviews. Bioessays 35: 0000-
SIMPULAN 0000. Wiley
Terapi larva telah dikenal sejak berabad-abad yang Periodicals, Inc., 2013. DOI
lalu. Dengan dite- mukannya antibiotik dan tehnik
10.1002/bies.201300071. [cited 2014
perawatan luka serta pembedahan yang lebih baik maka
terapi larva ditinggalkan. Akibat terjadinya resistensi Nov 5]. Available from:
bakteri terhadap antibiotik maka terapi larva www.bioessays-journal.com.
direintroduksi dan pada tahun 2004 telah diakui oleh 3. Sun X, Jiang K, Chen J, Wu L, Lu H,
FDA untuk pemakaian pada luka kronis terbuka.
Awalnya diduga terapi larva bermanfaat hanya
Wang A, et al. A systematic review of
sebagai debridemen mekanis, tetapi hasil-hasil penelitian maggot debridement therapy for chronically
melaporkan adanya berbagai bahan yang diduga turut infected wounds and ulcers.
membantu penyembuhan luka, antara lain enzim International Joournal of Infectious
proteolitik, bahan antibakteri, growth factors, dan
sitokin.
Diseases. 2014;25:32-7.
Terapi larva digunakan pada luka kronis terutama 4. Opletalova K, Blaizot X, Mourgeon B,
yang telah gagal dengan terapi konvensional. Dengan Chene Y, Creveuil C, Combemale P,
dikembang- kannya molekul bioaktif yang terkandung
et al. Maggot therapy for wound 9. Acton C. Technical guide. A know-how
debridement A randomized multicenter guide to using larval therapy for wound
trial. Arch Dermatol. 2012;148(4):432- debridement. Wound essentials.
7. 2007;2:156-9.
5. Chan DCW, Fong DHF, Leung JYY, 10. Courtenay M, Church JCT, Ryan TJ.
PAtil NG, Leung GKK. Maggot Larva therapy in wound management.
debridement therapy in chronic wound care. Journal of the Royal Society of Medicine.
Hong Kong Med J. 2007;13(5):382-6. 2000;93:72-4.
6. Pearson C. Something old is new again: 11. Hinshaw J. Larval therapy: A review of
Debriding and reducing local wound clinical human and veterinary studies.
infection with maggots. Wound Care World Wide Wounds. October 2000.
Canada. 2007;5(2):22-6. [cited 2014 Nov 10]. Available from:
7. Rafter L. Larval therapy applied to a large http://www.worldwidewounds.com/200
arterial ulcer: an effective 0/oct/Janet-Hinshaw/Larval-Therapy-
outcome.British Journal of Nursing. 2013 Human-and-Veterinary.html.
(Tissue vaibility supplement);22(6):S4- 12. Thornton D, Berry M, Ralston D. Case
10. report: maggot therapy in an acute burn.
8. Singh NM, Bhatia SK, Singh G. Maggots World Wide Wounds. [cited: 2014 Dec 6].
therapy in facilitating wound Available from: http://www.
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of Dr. D. Y. Patil University. 2004;7(5):639- ornton/larval-Therapy-Acute-Burn.html
42. (Last modified: 2002 Aug 08).
13. Derraik JGB, Heath ACG, dan Maggot therapy in “lower-extremity
Rademaker M. Human myasis in New hospice” wound care: Fewer
Zealand: imported and indigenously- amputations and more antibiotic-free- days.
acquired cases; the species of concern and J Am Podiatr Med Assoc.
clinical aspects. NZMJ. 2005;95:254-7.
2010;123(1322):21-38. 16. Griffin J. What nurses need to know about
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[cited 2015 Jan 3]. Available from: 17. Mumcouglu KY, Davidson E, Avidan A,
http://fineartamerica. com/featured/forensic- Gilead L. Pain related to maggot
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15. Armstrong DH, Salas P, Short B, Martin 18. Purser K, Heywood N. Maggot therapy use
BR, Kimbriel HR, Nixon BP, et al. in wound management. Bath: Royal
United Hospital Bath, 2012

JURNAL INTERNASIONAL
doi: 10.1111/j.1742-1241.2006.01238.x

REVIEW ARTICLE

Larval therapy in wound management: a review


A. Parne´s,1 K. M. Lagan2
aureus (MRSA) and the curiosity of
Introduction
researchers has prompted a resurgence of
Despite advances in wound care, the increasing inci- interest in larval therapy (6). As a treatment dence of
chronic wounds and their numerous socioe- it meets the demands of clinical governance, conomic
consequences have made wound management being not only beneficial to the patient, but also a key area
of focus for health profes- sionals. Several being proven to be more cost-effective (7). thousand pounds
are devoted annu- ally to research in However, application of larval therapy has this area (1). been stifled
by aesthetic con- siderations.
Debridement is an essential component of wound care, as the ‘necrotic burden’ supported by devital-
Applications of larval therapy ised tissue impedes the healing process (2,3). In recent Whilst the
effects of therapeutic myiasis were ini- years there has been renewed interest into the use of tially recorded
in suppurative wounds on the bat- maggots for biosurgical debridement. tlefield, numerous case studies have
reported its
Larval therapy (or sometimes known as thera- successful use with a variety of wounds. Larval peutic
myiasis) is by no means a modern idea, having therapy has been employed effectively to treat been used
for several hundred years in wound healing a wide spectrum of wounds including venous and by several
cultures, including Mayan Indians and arterial leg ulcers, osteomyelitis, necrotising Australian aborigines (4).
The benefi- cial effects of fasciitis, traumatic necrotic leg wounds, primary therapeutic myiasis were first
observed during the burns, pressure sores and amputation sites Napoleonic war by Larrey, who noted that
soldiers including digi- tal amputations in diabetic feet whose wounds had become infested with maggots
had (8). Larval therapy has also been used for the an improved prognosis. During the First World War,
treatment of a variety of intractable wounds, Baer documented the successful treatment of leg including
sacral and leg ulcers of assorted ulcers and osteomyelitis using larval therapy, and aetiologies (9). Case
studies have reported the paved the way for further use of it by doctors of that successful use of larval
therapy to treat a wide time. However, the development of antibiotics and variety of wounds including
chronic diabetic improvements in surgical techniques reduced larval ischaemic foot ulcers (10); necrotic
ulcer- ation therapy to a ‘treatment of last resort’, reserved for the caused by repetitive footwear trauma of a
localised
most intractable wounds (5). foot metastasis (11); bilateral neuropathic foot
The emergence of antibiotic-resistant strains of ulceration (12) and chronic diabetic foot ulcers
bacteria such as methicillin resistant Staphylococcus (13–15). In all cases, the wounds were suc-
cessfully debrided of devitalised tissue and granula-
tion tissue developed rapidly.

ª 2007 The Authors


488 Journal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, March 2007, 61, 3, 488–493
promotes the healing process with relatively few side effects
(16–18). Larval therapy is also reported as being cost-
effective in comparison with conventional wound dressings
General benefits of larval therapy (19). An import- ant study investigated the efficacy and cost-
Anecdotal evidence has consistently suggested that larval effective- ness of larval therapy vs. hydrogel, and reported
therapy results in a reduction in wound pain and odour, and
Larval therapy in wound management 489

that all wounds treated with larval therapy were success- fully fluorescent protein) showed a gradual decrease in
debrided following one application at a median cost of £78.64 fluorescence from the anterior section of the larval
(20). Treatment with hydrogel was proven to be less efficient alimentary canal to its end, thus demonstrating a
where it was noted that, following 1 month of treatment, one- reduction in the level of bacteria. It may be that a
third of wounds still continued to require treatment. The greater quantity of larvae is required in vivo to
median cost of treatment for this group was £136.23. eradicate wounds of Gram negat- ive bacteria such
However, the study involved only 12 patients (six within each as E. coli (29).
group) and thus lacked an adequate number of patients Other evidence, while anecdotal, supports the
required for large-scale trials to support the efficacy of use of larval therapy against wound pathogens.
treatment. The use of larval therapy often resulted in quicker In a recent trial, larval therapy was used
healing, and a sub- sequent reduction of nursing time and successfully to treat chronic, MRSA-infected
materials (19). Larval therapy has become available on wounds of five patients, including heel
the drug tariff, thus further increasing its cost- effectiveness. ulceration (30). The authors remarked on a few
A further advantage of larval therapy is that, as larvae are cases where MRSA infection was not successfully
typically applied for 3 days, wounds are disturbed less eliminated, speculating that the treat- ment may
frequently than conventional dressings that require changing have been unsuccessful for reasons such as
every 1–2 days (21). In addi- tion to this, a further advantage insufficient application of larvae, or that therapy
is that treatment can usually be carried out in outpatient and may have been discontinued too early to allow
community settings. A study at an outpatient wound clinic on complete eradication of MRSA. Further research
chronic wounds of varying aetiologies reported that using reported the successful use of larval therapy in the
larval therapy resulted in a 62% decrease in the need for treatment of three wounds infected with MRSA,
amputation (22). however, the author failed to describe the types of
wound, their location and their duration (8).
Larval therapy and multi-resistance Preliminary research has indicated that the puri-
The use of antibiotics to treat chronic wounds has lead to the fied secretions of sterile, aseptically raised L.
emergence of ‘resistant’ bacteria. Such strains possessed an sericata larvae exhibited antibacterial activity
evolutionary advantage, and were able to increase their against MRSA in vitro; although activity was
population size through Darwinian selection (23). Despite the found to be bacterio- static rather than bactericidal
pharmaceutical response in the form of other antibiotics such (28). The authors remarked that the degree of
as erythromycin and methicillin, further evolution of inhibition may have var- ied as a result of the
microbial drug resistance has occurred at a rapid rate, and to methods used for the collection of the secretions.
a point where antimicrobial resistance has become a major Subsequently, it was suggested that the study
threat to public health (24). The recent development of undervalued the effects of larval secretions, as
vancomycin resistance has created an imperative need for they are produced continuously in vivo and thus
alternative methods of treating infection (25). The most concentrations within the wound would be
predominant microorganisms of concern include Escherichia greater. The authors proposed that a stronger
coli (E. coli), Pseudomonas aeruginosa and MRSA. MRSA action against the growth of MRSA and other
has become a frequent cause of nosocomial infec- tions and multi-resistant microorganisms could therefore be
‘epidemic’ strains have consequently expected.
become the focus of much media attention in recent A recent study supported this research,
years (26). finding that secretions from L. sericata larvae
displayed potent antibacterial action against
Larvae offer the benefit of eliminating bacteria
MRSA (31). It was reported that the most
from the wound through ingestion and subsequent
significant antibacterial activ- ity was from a
degradation within their intestinal tract (27). They
small fraction of larval secretion with a molecular
also act to reduce bacterial activity through the
weight of <500 Da. However, antibacter- ial
pro- duction of inhibitory secretions. Such actions
activity was dependent on the selection of an
appear to hold true for MRSA as well as other
appropriate type of bioassay and optimal
multi-resist- ant microorganisms, such as
conditions. The dilution of larval secretions was
Pseudomonas species. While the literature
believed to have influenced the findings (28).
suggests that larval therapy is less effective in
wounds infected with E. coli (28), this has since
been called into question. In vitro research Disadvantages of larval therapy
examining the ingestion by Lucidia sericata The most commonly mentioned
larvae of E. coli (which produced a green disadvantage of lar- val therapy is the

ª 2007 The Authors


Journal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, March 2007, 61, 3, 488–493
Larval therapy in wound management 490

negative perception with which it is have been reported where larvae of Protophormia terraenovae and
regarded by both patients and not L. sericata were used (41). Alteration of the disinfection process
practitioners (5,18,32). Although the so- appeared to eliminate this problem, with no further cases of sepsis
called ‘yuk factor’ of its clinical occurring during the subsequent 12 months. The risk of cross-
appearance (Figure 1) has been frequently infection by escaped larvae may be greatly reduced through careful
reported in case studies, there is little dress- ing (42), although no occurrences have been docu- mented
evidence to suggest that patients refuse (43).
larval therapy when it is offered (33). The
use of ‘Biobags’ (Polymedics, Belgium), Mechanisms involved in larval therapy
which completely enclose the larvae
within a polyvinylalcohol membrane, has
become a popular method of improving
the application of this treat- ment (Figure
2). Larvae are able to feed freely
through the open cell polymer, but are less
visible to the squeamish patient or
practitioner
(34).
dressings, and treatment should be delayed until inflammation has
subsided (8). Several authors have proposed that skin surrounding
the wound should be protected using hydrocolloids or zinc paste to
prevent possible damage from powerful proteolytic enzymes within
larval secretions (33,38,39).
A case history has suggested larval therapy to be contraindicated
with fistulae, exposed vessels and wounds connecting to vital organs
(40). No occur- rences of allergic reaction were recorded, but blood-
stream infections (with Providencia stuartii and Candida albicans)
Appropriate education, perhaps incorporated into
the continuous professional development of the prac- Wound debridement
titioner, may prove useful in overcoming the scepti- Larvae feed on necrotic tissue, cellular debris and
cism and distaste of practitioners (8,35). Better exudate within the wound, thus debriding it of devi-
dissemination of information may also help address the talised tissue. In various randomised controlled clin-
problem of poor survival rates of larvae during ical trials, researchers noted that significantly more
wounds healed with frequent debridement, regardless of
treatment because of the lack of moisture (36).
the use of topical preparations (44,45). Debride- ment is
Pain has occasionally been reported by patients a critical factor in wound care, and is equally as
suffering from ischaemic wounds (9,37). The cause may important as pressure relief in facilitating wound
be the sharp mouth hooks and spicules with which healing (46).
larvae anchor themselves onto tissue. Contrac- tion of
necrotic tissue or pH changes within a wound may

ª 2007 The Authors


Journal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, March 2007, 61, 3, 488–493
Larval therapy in wound management 491

affect pain receptors in proximal healthy tissue (37).


Occasionally inflammation of adjacent tissue may
also pose problems for adherence of

Figure 1 Photograph courtesy of Medical Photography Figure 2 Photograph courtesy of Medical Photography Department,
Belfast City Hospitals Trust. Larvae of Lucilia Department, United Hospitals Trust. Sterile LarvETM of sericata (approximately
15 mm in length) following Lucilia sericata prior to wound application removal from wound (post 3 days in contact)
The basic mechanism of larval debridement has been ant, thermally stable compound from larval
described by several researchers (47–49). The digestive secretions, which exhibited strong antibacterial activ-
juices secreted by larvae during the feeding process ity (31). Some antibacterial compounds isolated,
have been found to contain a variety of pro- teolytic such as phenylacetic acid and phenylacetaldehyde,
enzymes, including trypsin-like and chymot- rypsin-like are thought to be released by Proteus mirabilis, a
enzymes and collagenase (50). The enzymes selectively commensal species of bacteria found within the lar-
debride necrotic tissue, leaving viable tissue unharmed val alimentary canal (61). The symbiotic relationship
(1). Further research tested the effects of larval between larvae and particular bacterial species
secretions of Calliphora erythro- cephala on appears to facilitate wound disinfection, but further
experimental burns on rat skin, and research is required into the mechanism.

reported that the secretions had proteolytic proper- ties


in vitro and in vivo (51). peritrophic membrane, thus preventing recontamina- tion
(53).
Movement of larvae may stimulate the production of
Wound disinfection
serous exudate by the wound, thus increasing irri- gation and
Chronic wounds are frequently colonised and infec- ted with
removing bacteria (1), or wounds may be physically irrigated
a variety of wound flora, including Staphy- lococcus and
by larval secretions themselves (54). Other authors believe
Streptococcus species, P. aeruginosa and E. coli. Increased
the process to be more complex, and suggest that larval
bacterial load may impair healing, particularly if a wound
secretions play a greater role in wound disinfection (55).
becomes infected with anti- microbial resistant bacteria (as
Early research has shown that larval secretions contain a
discussed above). Dis- infection is therefore a critical
variety of alkaline components, including ammonium
component of wound healing.
bicarbonate, calcium, allantoin and urea that inhibit bacterial
The natural habitats of larvae include corpses and wounds,
growth (56–58). The subsequent increase in pH provides an
which typically contain a vast array of pathogenic
optimum environment for enzymatic activity, and also
microorganisms. In response to these conditions larvae are
renders the wound bed uninhabita- ble to many bacteria,
believed to have evolved several effective mechanisms for
hindering subsequent recoloni- sation (59).
removing bacteria. During feeding, larvae ingest bacteria
Disinfection may occur as a result of the release of
within devitalised tis- sue thus physically removing
compounds in larval secretions in conjunction with the
microorganisms (52). Research has suggested that any
digestion of devitalised tissue (60). It has been proposed that
bacteria which are not destroyed within the acidic alimentary
larvae release antimicrobial substances as part of an innate
canal are contained within a tubular structure known as the
response to high levels of bac- teria (3). In vitro research
isolated a protease resist-

ª 2007 The Authors


Journal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, March 2007, 61, 3, 488–493
Larval therapy in wound management 492

Promotion of wound healing secretion of allantoin, ammo- nium bicarbonate


Research has consisted of small-scale clinical and urea provide an optimal growth environment
trials and in vitro investigations of the properties for cells involved in wound healing by acting as
of larval secretions. Surprisingly, as it has no growth factors (70,71). The alka-
benefit to the larvae, therapy appears to suggested that the resultant tissue proliferation within the wound
encourage the formation of granulation tissue in stimulated by the release of growth factors may provide larvae with
the wound bed and acceler- ate wound healing better nourishment.
(9,62). Further research investigated the in vitro effects of larval
In a comparative study of chronic wounds of secretions on human dermal neonatal fibro- blast cells and reported
mul- tiple aetiologies, it was reported that all that the presence of secre- tions resulted in a reduction in fibroblast
wounds healed following 4 weeks of treatment adhesion to fibronectin and collagen (which are constituents of the
with larval therapy, whereas necrotic tissue was extracellular matrix modification) (74). The authors suggested that
still present on the surface of conventionally this may be due to proteolytic activity of larval secretions altering
treated wounds follow- ing 5 weeks (63). This the structure of the extracellular matrix. They postulated that this
finding was in agreement with earlier work by the behavioural modification within the wound may pro- mote the
author who compared the healing rates of pressure formation of new tissue. This supported earlier work proposing that
ulcers treated with either conven- tional dressings the activity of trypsin- like and chymotrypsin-like proteinases
or larval therapy (64). Several case studies strongly influ- enced the remodelling of the extracellular matrix
involving chronic leg ulcers have also recor- ded (62).
the development of granulation tissue within the
wound bed (18,65,66). During an in vivo study, a
single application of larvae was applied to Conclusion
chronic leg ulcers (n ¼ 30) of mixed aetiology From the literature reviewed it can be
(67). The wounds were assessed subjectively, noted that as a treatment, larval therapy
using a wound scoring system, and objectively, offers numerous advan- tages including
using remittance spectroscopy. Following rapid wound debridement and elim-
treatment with larvae, remit- tance was greatly ination of infection, control of pain and
reduced because of an increased quantity of odour, and the promotion of wound
granulation tissue within the wound bed. The healing. Use of larval ther- apy has
authors concluded that larval secretions had a resulted in few side effects, and has
positive effect on wound healing because of the reduced the need for amputation (22). It is
development of granulation tissue and increased also apparent that the treatment also offers
tis- sue oxygenation. an efficient alternative to antibiotic
As discussed earlier, the constant movement of therapy for the treatment of wounds con-
lar- vae within the wound is believed to taminated with a variety of wound
mechanically sti- mulate the wound bed (68). pathogens, inclu- ding MRSA and E. coli.
However, use of ‘Biobags’ that inhibit Having been largely superseded by
mechanical stimulation has also resulted in antibiotics, larval therapy has reemerged
improved healing, suggesting that factors other as one of the current strategies for target-
than mechanical stimulation are involved ing microbial resistance.
(34,69). It is apparent that the literature
The properties of substances within larval consists mainly of case studies into the
secre- tions, described as a healing ‘active applications of larval therapy. Large-scale
principle’ (56,58), have been the subject of clinical trials are required to further
subsequent research and suggested that the examine the efficacy of the process and its

line nature of these substances has been reported to wound processes to promote healing. Whilst not suitable have a
role in the promotion of healing by altering the for all wounds, larval therapy should no lon- ger be pH of the
wound (72). viewed as a treatment of last resort.
In vitro research noted that whilst larval secretions stimulated
growth of human fibroblast growth, the effect
Acknowledgements
was increased when combined with epidermal growth factor (73). The results indicated that secre- tions may
Thanks to Ms J. Cundell, Lecturer/Practitioner, enhance healing through interaction with compounds University of
ª 2007 The Authors
Ulster/Belfast
Journal compilation City Hospitals
ª 2007 Blackwell Publishing Trust,
Ltd Int Jreleased byMarch
Clin Pract, the wound. This
2007, 61, research demonstrated for N. Ireland for accessing
3, 488–493
and providing photographs the first time that the insect moult- ing hormone, 20- from Medical Photography
departments.
hydroxyecdysone, stimulates fibro- blast growth. It was
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Paper received July 2006, accepted September 2006

ª 2007 The Authors


Journal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, March 2007, 61, 3, 488–493

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