Download New Treatment Policy of Malaria as a Part of Malaria Control

CLINICAL PRACTICE
New Treatment Policy of Malaria as a Part of Malaria Control
Program in Indonesia
Rita Kusriastuti1, Asik Surya2
Directorate of Vector Borne Disease Control, Ministry of Health, Republic of Indonesia. Correspondence mail:
[email protected].
2
Malaria Subdirectorate Control Programmed, Ministry of Health, Republic of Indonesia. Correspondence
mail: [email protected].
1
ABSTRAK
Program pengendalian malaria merupakan salah satu program utama terdahulu di Kementrian Kesehatan
(Kemenkes) Republik Indonesia. Dimulai dari usaha untuk membasmi malaria pada tahun 1959, melalui Malaria
Eradication Command yang dikenal sebagai KOPEM (Komando Pembasmian Malaria), kemudian usaha ini
berevolusi menjadi Program Pengendalian Malaria (Malaria Control Program), Program Gebrak Malaria (Roll
Back Malaria Program), dan yang terkini Program Eliminasi Malaria (Malaria Elimination Program). Dalam
hal diagnosis dan pengobatan, kebijakan telah dibuat secara ketat berdasarkan prinsip-prinsip berbasis bukti
serta petunjuk teknis dari World Health Organization (WHO).
Pada tahun 2004, berdasarkan sejumlah penelitian yang dilakukan di Indonesia, penggunaan klorokuin
dihentikan dan terapi kombinasi artemisinin atau artemisinin-based combination therapy (ACT) dimulai. Untuk
kasus berat, diperkenalkan penggunaan Artesunat intravena (iv), yakni untuk kasus-kasus yang ditangani di
rumah sakit dan Artemeter intramuskular (im) untuk kasus-kasus yang ditangani di pusat layanan kesehatan
primer. ACT, Artesunat iv, dan Artemeter im, semuanya disediakan untuk seluruh pelosok negeri melalui sistem
pengadaan barang dan jasa (procurement system). Untuk pengobatan radikal, rekomendasi di Indonesia adalah
menambahkan primakuin (PQ) pada pengobatan ACT pada infeksi Plasmodium vivax dan Plasmodium ovale
guna mencegah kekambuhan dan pada infeksi Plasmodium falciparum untuk membunuh gametosit. Rekomendasi
ini diharapkan dapat menurunkan mortalitas malaria hingga angka nol dan pada akhirnya, bersama dengan
intervensi lainnya, malaria dapat dieliminasi dari negara ini pada tahun 2030. Penyebaran informasi itu penting
agar kebijakan dapat dipraktekkan lintas daerah di negeri ini.
Kata kunci: malaria, pengobatan, Indonesia, kebijakan, ACT.
ABSTRACT
Malaria control program is one of the oldest program in the Ministry of Health (MoH) Republic of Indonesia.
Started with effort to eradicate malaria in 1959 through Malaria Eradication Command well known as KOPEM
(Komando Pembasmian Malaria) then it evolves to Malaria Control Program, Roll Back Malaria Program, and
the current Malaria Elimination Program. In terms of diagnostic and treatment, the policy has formulated by
strictly follow evidence-based principles as well as technical guided from World Health Organization (WHO).
In 2004, based on numerous researches conducted in Indonesia the use of chloroquine was stopped and
artemisinin-based combination therapy (ACT) was then initiated. For severe cases the use of intravenous (iv)
Artesunate for cases treated in hospitals and intramuscular (im) Arthemeter for cases treated in the primary
care setting were also introduced. ACT, Artesunate iv, and Artemether im, all are provided nationwide through
the procurement system. For radical treatment, the recommendation in Indonesia is to add primaquine (PQ) to
ACT for Plasmodium vivax and Plasmodium ovale infections to prevent relapses and for Plasmodium Falciparum
infection to kill the gametocytes. These recommendations put hope to reduce malaria mortality to zero and
Acta Medica Indonesiana - The Indonesian Journal of Internal Medicine
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Rita Kusriastuti
Acta Med Indones-Indones J Intern Med
eventually with other interventions will eliminate malaria from the country by 2030. The dissemination of this
information is important for the policy to apply in practice across the country.
Key words: malaria, treatment, Indonesia, policy, ACT.
INTRODUCTION
Since the 1970's, malaria control program in
the world has been weakened by the widespread
of parasite resistance to previous generations
of antimalarial drugs, chloroquine (CQ) and
sulfadoxine pyrimetamine (SP).1 Whereas then
multidrug resistance is established in Southeast
Asia, South America, and Africa.2 WHO define
antimalarial drug resistance as the ability of
a parasite strain to survive and/or multiply
despite the proper administration and absorption
of an antimalarial drug in the dose normally
recommended.3 The unproper use of antimalarial
drug, particularly the one that already resistance,
will lead to increase morbidity and mortality.4
Furthermore, frequent visits due to replacements
and higher cost of severe malaria will give
another burden to patient and health care facilities
especially in a remote area of the country.
Resistance to CQ in Indonesia was first
reported in 1975 from Indonesian Papua and
East Kalimantan.5 It was followed by numerous
studies reporting resistance to CQ and SP from
more places in Indonesia.6-10 The sentinel sites for
drug efficacy monitoring have recorded nation
wide spread of CQ resistance in Indonesia.11
The report varied for CQ resistance from 10%
to 80% of resistance and for SP from 0 to 15%
resistance. WHO in its recommendation mention
that countries should initiate change of their
malaria treatment policy if the total treatment
failure proportion is >10%, as assessed through
in vivo monitoring of therapeutic efficacy. The
selection of a new and/or alternative antimalarial
medicine for use at public health level within the
context of national treatment guideline should
be based on an average cure rate of >95%, as
assessed in clinical trial.11 Pattern of anti malaria
drug resistance could be seen in Figure 1.
Responding to the situation, Malaria Treatment
Expert Committee was then established, the team
consisted of researchers from Indonesian National
Institute of Health Research and Development
(NIHRD) and Leading universities; malaria
experts from Indonesian Tropical Medicine
266
Society; malaria consultants from Indonesian
Internal Medicine Association; experts from
pharmacology field; and the Indonesian Food
and Drug Administration (FDA). The goal of
the committe is to provide recommendation on
malaria treatment policy.
MALARIA TREATMENT POLICY
Current malaria treatment policy in the
country is radical treatment protocol by giving
ACT and PQ to uncomplicated malaria case. For
severe malaria the protocol is to give artesunate
iv for cases treated in hospital or any in-patient
facilities, and to give arthemeter im for cases
treated in the primary health care. Both artesunate
and arthemeter treatment are to be followed by
oral ACT and PQ when the patient is able to take
oral drug.
The new recommendation based on evidence
is to use dihydroartemisinin piperaquine (DHP)
and artesunate + amodiaquine (AA) as drug of
choice for ACT. Both drugs are provided for
free by the for nation wide use. Lately, based on
reports of superiority of efficacy and prophylactic
effect of DHP compared to other ACTs 12,13;
reports that DHP reduce vertical transmission
from mothers to babies14 and the more practical
fixed dose combination (FDC) preparation of
DHP, the procurement of DHP will be provided
more than AA and later on will start to only
procure DHP.
Primaquine is contraindicated for pregnancy
and ACT can only be used in 2nd and 3rd
trimester of pregnancy, then the only available
drug to use for the 1st trimester is quinine.
The awareness of resistance to artemisinin
leads the restriction of monotherapy treatment of
malaria and only to use the combination formula.
Thus the government only provide ACT and will
not give permit for the registration of artemisinin
single preparation. The effort to improve
malaria diagnosis using not only microscopy, as
recommended initially, but also rapid diagnostic
test (RDT) is attached along in the policy. Lastly
to ensure the drug quality in the country, ACT is
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New Treatment Policy of Malaria as a Part of Malaria Control Programme
Figure 1. Pattern of anti malaria drug resistance
distributed through the government distribution
line only.
MALARIA ELIMINATION
Since 2009, Indonesia has been embarking
upon eliminating malaria in the country by 2030.
The goal is to be achieved stepwise, by 2015 for
Java, Bali, Riau Islands, and Aceh; and Sumatera,
Kalimantan, Sulawesi, and West Nusa Tenggara
by 2020; and the eastern part of Indonesia i.e.
East Nusa Tenggara, Maluku, North Maluku,
Papua, and West Papua by 2030. Currently,
malaria cases are concentrated in the eastern
part of Indonesia; contributing more than 80%
of the nation’s 450,000 confirmed malaria cases
in 2011.14 With more and more areas became
moderate or low endemic, radical treatment,
rigorous patient follow up, and treatment for
severe malaria became a high priority for those
particular areas.
People living in low endemic area have
low protective immunity. While the risk to get
infected is reduced in this area, the risk to develop
severe malaria is increasing. Hospitals should
be ready to treat severe malaria cases using
Artesunate iv to achieve zero death of malaria.
Malaria elimination means reduction to
zero local transmitted malaria cases in a defined
geographical area.19 Human malaria is transmitted
by sexual stages of the parasites, infecting
anopheline mosquito vectors. Transmission
depends on the duration of gametocytes carried
in the blood, infectivity of this gameotocytaemia
to the local vectors, and the amount and behavior
of the vectors. Anti malaria drugs which kill
asexual stages also kill the early stages of
P.falciparum gametocytes, as well as the mature
P.vivax, malariae, and ovale gametocytes. The
combination of reducing the asexual stage
progenitors of sexual stages, and killing the
gametocytes themselves reduce transmissibility.
PQ is active against asexual stage of P.vivax, kill
hypnozoites of P.vivax and P. ovale, and mature
gametocytes of P.falciparum.20 Therefore, the
importance of PQ use in clinical practices for
radical treatment to achieve malaria elimination
is emphasized. A rigorous patient follow up
until day 28 will make sure that the infection is
cleared up completely. Patient compliance and
rational use of the drugs play an important role
in keeping the drug effective. If drug activity
against asexual stage is worsened because
of antimalarial resistance, the rate at which
parasitaemia is cleared up from the blood is
reduced, and treatment failure rates increase.
Studies have shown that increase gametcytaemia
is the first warning sign of drug resistance. Thus,
transmission and especially transmission of
resistance would have increased before detectable
changes in treatment failure.20 It is important for
every physician to take responsibility in keeping
the drug to be effective by following the treatment
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Rita Kusriastuti
Acta Med Indones-Indones J Intern Med
Table 1. Antimalarial provided by Indonesian government10
Drug
Compositions
Preparations
Dose
DHP
40mg dihydroartemisinin + 320mg
piperaquin
AA
50mg artesunat + 153mg amodiaquin
Co – blister
PQ
15 mg
Tablet
P. vivax/P.ovale: 0.25 mg/kggBW for14 days
P. falciparum: 0.75 mg/kgBW single dose
Artesunate iv
60 mg
1 vial
2.4 mg/kgBW
Artesunate im
80 mg
1 ampul
FDC
Dihydroartemisinin: 2–4 mg/kgBW
Piperquin: 16–32 mg/kgBW
Artesunae: 4mg
Amodiaquin: 10 mg
3.2mg/kgBW in the 1st 24 hours continued
with 1.6mg/kgBW/day
MALARIA ENDEMICITY MAP IN INDONESIA IN 2011
FREE FROM MALARIA
Figure 2. Malaria endemicity
protocols set by the government.
CHALLENGES
Routine data collection by the government
shows out of 1.322.451 suspected malaria cases;
around ninety-two percent was examined using
either microscope or RDT. Of the 256.592
confirmed malaria; 66% received ACT treatment.
Incoordination regarding drugs availability is
stil reported from some areas. Main challenge
is always proper communication between each
health facility i.e hospitals, private practices,
or other facility with the DHO on drug supply
mechanism.
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Countries in the Greater Mekong Region
have reported resistance to ACT. Results from
surveillance sites on the Thai-Cambodian border
have shown increasing failure rate of P.falciparum
to ACT. In particular, slow parasite clearance
times have been detected on the third day of
treatment in Pailin, in western Cambodia. In those
areas, counterfeit and substandard antimalarial
drugs and irrational drug use are highly prevalent,
population mobility is widespread, and health
service coverage is inadequate among ethnic
minorities.14 Indonesia, while has strong policy
to slow down artemisinin resistance in the area,
will have to establish a system to monitor the
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New Treatment Policy of Malaria as a Part of Malaria Control Programme
efficacy of ACT and to establish strategy against
counterfeit and substandard antimalarial drugs
distribution. On the other hand, the appropriate
clinical practice is playing a very important role
in keeping the drug to be effective in Indonesia.
CONCLUSION
The Indonesian government through MoH
has set a strong malaria treatment policy to reduce
morbidity and mortality; to achieve malaria
elimination; and to protect ACT from becoming
ineffective. Aware with the challenges, the MoH
is calling the clinical practices in the country to
take responsibility to keep the drug effective by
following the national treatment protocol and
encouraging patient’s compliance. Studies and
operational research need to be conducted to help
the MoH formulate their strategies to provide the
best treatment for malaria patients in Indonesia.
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