Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.1–1.3; P = 0.08). Primaquine administered daily created a marginally significant improvement in therapeutic efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1–1.8; P = 0.2) or day 28 (82% versus 93%; OR, 0.31; 95% CI, 0.04–2.1; P = 0.23). This report corroborates studies suggesting that therapeutic doses of primaquine exert no discernible effect on parasitemia by P. falciparum

Ayomi, Ester

Baird, J. Kevin

Basri, Hasan

Fryauff, David J.

Hoffman, Stephen L.

Purnomo,

Sekartuti,

Suradi,

Sutanihardja, Awalludin

Waidy, Iwa

English

UNL | Libraries

University of Nebraska - Lincoln 
DigitalCommons@University of Nebraska - Lincoln 
U.S. Navy Research U.S. Department of Defense 
2002 
Short Report: Therapeutic Efficacy of Chloroquine Combined with 
Primaquine Against Plasmodium falciparum in Northeastern 
Papua, Indonesia 
J. Kevin Baird 
U.S. Naval Medical Research Unit # 2, jkevinbaird@yahoo.com 
Iwa Waidy 
U.S. Naval Medical Research Unit # 2 
Awalludin Sutanihardja 
U.S. Naval Medical Research Unit # 2 
Suradi 
U.S. Naval Medical Research Unit # 2 
Purnomo 
U.S. Naval Medical Research Unit # 2 
See next page for additional authors 
Follow this and additional works at: https://digitalcommons.unl.edu/usnavyresearch 
Baird, J. Kevin; Waidy, Iwa; Sutanihardja, Awalludin; Suradi; Purnomo; Basri, Hasan; Sekartuti; Ayomi, Ester; 
Fryauff, David J.; and Hoffman, Stephen L., "Short Report: Therapeutic Efficacy of Chloroquine Combined 
with Primaquine Against Plasmodium falciparum in Northeastern Papua, Indonesia" (2002). U.S. Navy 
Research. 55. 
https://digitalcommons.unl.edu/usnavyresearch/55 
This Article is brought to you for free and open access by the U.S. Department of Defense at 
DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in U.S. Navy Research by an 
authorized administrator of DigitalCommons@University of Nebraska - Lincoln. 
Authors 
J. Kevin Baird, Iwa Waidy, Awalludin Sutanihardja, Suradi, Purnomo, Hasan Basri, Sekartuti, Ester Ayomi, 
David J. Fryauff, and Stephen L. Hoffman 
This article is available at DigitalCommons@University of Nebraska - Lincoln: https://digitalcommons.unl.edu/
usnavyresearch/55 
SHORT REPORT: THERAPEUTIC EFFICACY OF CHLOROQUINE COMBINED WITH
PRIMAQUINE AGAINST PLASMODIUM FALCIPARUM IN NORTHEASTERN
PAPUA, INDONESIA
J. KEVIN BAIRD, IWAWIADY, AWALLUDIN SUTANIHARDJA, SURADI, PURNOMO, HASAN BASRI, SEKARTUTI,
ESTER AYOMI, DAVID J. FRYAUFF, AND STEPHEN L. HOFFMAN
U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia National Center for Infectious Diseases Research, Ministry of Health,
Jakarta, Indonesia; District Health Services, Jayapura, Papua, Indonesia; Naval Medical Research Center, Silver Spring, Maryland
Abstract. Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by
Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized
to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine
administered daily for 28 days (n  25) or a placebo of primaquine (n  28). The 14-day cumulative incidence of
therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval
[CI], 0.1–1.3; P  0.08). Primaquine administered daily created a marginally significant improvement in therapeutic
efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1–1.8; P  0.2) or day 28 (82% versus 93%;
OR, 0.31; 95% CI, 0.04–2.1; P  0.23). This report corroborates studies suggesting that therapeutic doses of primaquine
exert no discernible effect on parasitemia by P. falciparum.
INTRODUCTION
Chloroquine and primaquine remain in common use
against uncomplicated malaria in the developing world. Chlo-
roquine still constitutes first-line therapy for infection by
Plasmodium falciparum for most people exposed to risk in
Asia—for example, in India, the Philippines, and Indonesia.
Primaquine, which is typically used for the prevention of re-
lapse by Plasmodium vivax (15 mg daily for 14 days), is also
widely used in Asia against P. falciparum as a single 45-mg
gametocytocidal dose. Although therapeutic regimens of pri-
maquine exert curative activity against blood stages of P.
vivax organisms,1,2 most evidence suggests primaquine has no
effect on blood stages of P. falciparum.3–5 This may bear on
the finding of apparently distinct mechanisms of resistance to
chloroquine by these 2 species.6
In July 1992 (Arso VIII) and June 1993 (Arso XI), we
enrolled subjects in a randomized, blinded, placebo-con-
trolled trial of a primaquine adjunct to standard chloroquine
therapy. The findings with P. vivax have been published else-
where in a report that details the conduct of the studies.2 In
brief, 53 subjects (nonimmune Javanese migrants) with un-
complicated malaria caused by P. falciparum provided in-
formed consent and were randomized to receive standard
chloroquine therapy (Resochin; P. T. Bayer Indonesia,
Jakarta, Indonesia; provided as uncoated scored tablets; 10 +
10 + 5 mg/kg at 24-hour intervals) with primaquine (generic
label, Sanofi-Winthrop, New York, NY, as coated unscored
tablets containing 15 mg base, 0.5 mg/kg daily for 28 days) or
a nonidentical placebo (identical to generic primaquine from
Kimia Farma, Bandung, as an uncoated, scored tablet con-
taining starch and amylose). Subjects were at least 6 years old
and had at least 40 asexual parasites per microliter of blood;
in addition, they tested negative for glucose-6-phosphate de-
hydrogenase deficiency (NADP+ spot test; Sigma Chemical
Co., St. Louis, MO). The mean age of the 53 subjects was 23
years (range, 6–40 years), and most were men (n  45). The
geometric mean density of asexual parasites was 2,744/L. No
significant differences in these parameters appeared between
the primaquine and placebo groups.
Therapy was directly observed beginning on day 0 of the
evaluation and ending with the last dose of primaquine on day
28. Blood films were collected, stained with Giemsa reagents,
and read microscopically on days 0, 1, 2, 4, 7, 11, 18, 21, 25,
and 28, or at any time a subject complained of illness. Figure
1 illustrates the cumulative incidence of therapeutic failure
(persistent or recurrent asexual parasitemia) for both treat-
ment groups estimated by life-table analysis. No significant
differences in risk of therapeutic failure occurred between the
primaquine and placebo groups. A marginally significant dif-
ference appeared only at day 14 (56% versus 79%; odds ratio,
0.35; 95% confidence interval, 0.4–1.3; P  0.08). Daily doses
of 0.5 mg/kg primaquine over the 28 days of follow-up exerted
FIGURE 1. Cumulative incidence of recurrent asexual parasitemia
by Plasmodium falciparum after chloroquine therapy combined with
30 mg daily primaquine (dashed line) or a placebo (solid line).
Am. J. Trop. Med. Hyg., 66(6), 2002, pp. 659–660
Copyright © 2002 by The American Society of Tropical Medicine and Hygiene
659
no discernible effect on the clearance and recurrence of
asexual parasitemia by P. falciparum.
Our findings corroborate others suggesting that therapeutic
doses of primaquine exert no effect on asexual parasitemia by
P. falciparum, despite an apparently profound effect against
asexual blood forms of P. vivax shown in other studies1 and in
parallel2 with the findings reported here. These findings also
corroborate the very high risk of therapeutic failure with chlo-
roquine monotherapy against P. falciparum acquired in
northeastern Papua, Indonesia.7–9
Acknowledgments: The views or opinions herein represent those of
the authors and do not purport to represent those of the U.S. Navy or
the Department of Defense. This work was supported by the U.S.
Department of Defense Global Emerging Infections Surveillance
program. The authors gratefully acknowledge the support and direct
assistance of the Ministry of Health, Republic of Indonesia, in com-
pleting the work described here.
Informed consent: The work described herein was reviewed and ap-
proved by Indonesian and American committees for the protection of
human subjects of medical research in accordance with U.S. Navy
regulations (SECNAVINST 3900.39B). All subjects of this research
provided informed consent.
Authors’ addresses: J. Kevin Baird, Iwa Wiady, Awalludin Sutani-
hardja, Purnomo, Suradi, and Hasan Basri, U.S. Naval Medical Re-
search Unit No. 2, American Embassy Jakarta, FPO AP 96520 USA.
David J. Fryauff, Naval Medical Research Center, 503 Robert Grant
Avenue, Silver Spring, MD 20910-7500. Sekartuti, National Health
Research Center, Jalan Percetakan Negara No. 29, Jakarta, Indone-
sia. Ester Ayomi, District Health Services, PUSKESMAS Jalan Jen-
dral Yani, Jayapura, Papua, Indonesia. Stephen L. Hoffman, Celera
Genomics, 45 West Gude Drive, Rockville, MD 20850.
Reprint requests: J. Kevin Baird, Parasitic Diseases Program, U.S.
Naval Medical Research Unit No. 2, American Embassy Jakarta,
FPO AP 96520-8132, USA, Fax: 62-21-424-4507, E-mail: bairdjk@
namru2.med.navy.mil.
REFERENCES
1. Pukrittayakamee S, Vanijanonta S, Chantra A, Clemens R,
White NJ, 1994. Blood-stage antimalarial efficacy of pri-
maquine in Plasmodium vivax malaria. J Infect Dis 169: 932–
935.
2. Baird JK, Basri H, Subianto B, Fryauff DJ, McElroy PD, Le-
ksana B, Richie TL, Masbar S, Wignall FS, Hoffman SL, 1995.
Treatment of chloroquine-resistant Plasmodium vivax with
chloroquine and primaquine or halofantrine. J Infect Dis 171:
1678–1682.
3. Arnold JA, Alving AS, Hockwald RS, Clayman CB, Dern RJ,
Beutler E, Flanagan CL, Jeffery GM, 1955. The antimalarial
action of primaquine against the blood and tissue stages of
falciparum malaria (Panama P-F-6 strain). J Lab Clin Med 46:
391–397.
4. Geary TG, Divo AA, Jensen JB, 1987. Activity of quinoline an-
timalarials against chloroquine-sensitive and -resistant strains
of Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg
81: 499–503.
5. Basco LK, Bickii J, Ringwald P, 1999. In vitro activity of pri-
maquine against the asexual blood stages of Plasmodium fal-
ciparum. Ann Trop Med Parasitol 93: 179–182.
6. Nomura T, Carlton JM, Baird JK, Del Portillo HA, Fryauff DJ,
Rathore D, Fidock DA, Su X, Collins WE, McCutchan TF,
Wooton JC, Wellems TE, 2001. Evidence for different mecha-
nisms of chloroquine resistance in two Plasmodium species
that cause human malaria. J Infect Dis 183: 1653–1661.
7. Baird JK, Basri H, Jones TR, Bangs MJ, Ritonga A, 1991. Re-
sistance to antimalarials in Northeastern Irian Jaya, Indonesia.
Am J Trop Med Hyg 44: 640–644.
8. Baird JK, Wiady I, Fryauff DJ, Sutanihardja MA, Leksana B,
Widjaya H, Kysdarmanto, Subianto B, 1997. In vivo resistance
to chloroquine by Plasmodium vivax and Plasmodium falci-
parum at Nabire, Irian Jaya, Indonesia. Am J Trop Med Hyg
56: 627–631.
9. Taylor WR,Widjaja H, Basri H, Richie TL, Ohrt C, Taufik, Tjitra
E, Hoffman SL, 2001. An open comparison of chloroquine/
doxycycline, chloroquine alone, and doxycycline alone for the
treatment of P. falciparum and P. vivax in northeastern Irian
Jaya, Indonesia. Am J Trop Med Hyg. In press.
BAIRD AND OTHERS660


Short Report: Therapeutic Efficacy of Chloroquine Combined with Primaquine Against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e in Northeastern Papua, Indonesia

DigitalCommons@University of Nebraska

University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln U.S. Navy Research U.S. Department of Defense 2002 Short Report: Therapeutic Efficacy of Chloroquine Combined with Primaquine Against Plasmodium falciparum in Northeastern Papua, Indonesia J. Kevin Baird U.S. Naval Medical Research Unit # 2, jkevinbaird@yahoo.com Iwa Waidy U.S. Naval Medical Research Unit # 2 Awalludin Sutanihardja U.S. Naval Medical Research Unit # 2 Suradi U.S. Naval Medical Research Unit # 2 Purnomo U.S. Naval Medical Research Unit # 2 See next page for additional authors Follow this and additional works at: https://digitalcommons.unl.edu/usnavyresearch Baird, J. Kevin; Waidy, Iwa; Sutanihardja, Awalludin; Suradi; Purnomo; Basri, Hasan; Sekartuti; Ayomi, Ester; Fryauff, David J.; and Hoffman, Stephen L., "Short Report: Therapeutic Efficacy of Chloroquine Combined with Primaquine Against Plasmodium falciparum in Northeastern Papua, Indonesia" (2002). U.S. Navy Research. 55. https://digitalcommons.unl.edu/usnavyresearch/55 This Article is brought to you for free and open access by the U.S. Department of Defense at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in U.S. Navy Research by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors J. Kevin Baird, Iwa Waidy, Awalludin Sutanihardja, Suradi, Purnomo, Hasan Basri, Sekartuti, Ester Ayomi, David J. Fryauff, and Stephen L. Hoffman This article is available at DigitalCommons@University of Nebraska - Lincoln: https://digitalcommons.unl.edu/usnavyresearch/55 SHORT REPORT: THERAPEUTIC EFFICACY OF CHLOROQUINE COMBINED WITHPRIMAQUINE AGAINST PLASMODIUM FALCIPARUM IN NORTHEASTERNPAPUA, INDONESIAJ. KEVIN BAIRD, IWAWIADY, AWALLUDIN SUTANIHARDJA, SURADI, PURNOMO, HASAN BASRI, SEKARTUTI,ESTER AYOMI, DAVID J. FRYAUFF, AND STEPHEN L. HOFFMANU.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia National Center for Infectious Diseases Research, Ministry of Health,Jakarta, Indonesia; District Health Services, Jayapura, Papua, Indonesia; Naval Medical Research Center, Silver Spring, MarylandAbstract. Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused byPlasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomizedto treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquineadministered daily for 28 days (n  25) or a placebo of primaquine (n  28). The 14-day cumulative incidence oftherapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval[CI], 0.1–1.3; P  0.08). Primaquine administered daily created a marginally significant improvement in therapeuticefficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1–1.8; P  0.2) or day 28 (82% versus 93%;OR, 0.31; 95% CI, 0.04–2.1; P  0.23). This report corroborates studies suggesting that therapeutic doses of primaquineexert no discernible effect on parasitemia by P. falciparum.INTRODUCTIONChloroquine and primaquine remain in common useagainst uncomplicated malaria in the developing world. Chlo-roquine still constitutes first-line therapy for infection byPlasmodium falciparum for most people exposed to risk inAsia—for example, in India, the Philippines, and Indonesia.Primaquine, which is typically used for the prevention of re-lapse by Plasmodium vivax (15 mg daily for 14 days), is alsowidely used in Asia against P. falciparum as a single 45-mggametocytocidal dose. Although therapeutic regimens of pri-maquine exert curative activity against blood stages of P.vivax organisms,1,2 most evidence suggests primaquine has noeffect on blood stages of P. falciparum.3–5 This may bear onthe finding of apparently distinct mechanisms of resistance tochloroquine by these 2 species.6In July 1992 (Arso VIII) and June 1993 (Arso XI), weenrolled subjects in a randomized, blinded, placebo-con-trolled trial of a primaquine adjunct to standard chloroquinetherapy. The findings with P. vivax have been published else-where in a report that details the conduct of the studies.2 Inbrief, 53 subjects (nonimmune Javanese migrants) with un-complicated malaria caused by P. falciparum provided in-formed consent and were randomized to receive standardchloroquine therapy (Resochin; P. T. Bayer Indonesia,Jakarta, Indonesia; provided as uncoated scored tablets; 10 +10 + 5 mg/kg at 24-hour intervals) with primaquine (genericlabel, Sanofi-Winthrop, New York, NY, as coated unscoredtablets containing 15 mg base, 0.5 mg/kg daily for 28 days) ora nonidentical placebo (identical to generic primaquine fromKimia Farma, Bandung, as an uncoated, scored tablet con-taining starch and amylose). Subjects were at least 6 years oldand had at least 40 asexual parasites per microliter of blood;in addition, they tested negative for glucose-6-phosphate de-hydrogenase deficiency (NADP+ spot test; Sigma ChemicalCo., St. Louis, MO). The mean age of the 53 subjects was 23years (range, 6–40 years), and most were men (n  45). Thegeometric mean density of asexual parasites was 2,744/L. Nosignificant differences in these parameters appeared betweenthe primaquine and placebo groups.Therapy was directly observed beginning on day 0 of theevaluation and ending with the last dose of primaquine on day28. Blood films were collected, stained with Giemsa reagents,and read microscopically on days 0, 1, 2, 4, 7, 11, 18, 21, 25,and 28, or at any time a subject complained of illness. Figure1 illustrates the cumulative incidence of therapeutic failure(persistent or recurrent asexual parasitemia) for both treat-ment groups estimated by life-table analysis. No significantdifferences in risk of therapeutic failure occurred between theprimaquine and placebo groups. A marginally significant dif-ference appeared only at day 14 (56% versus 79%; odds ratio,0.35; 95% confidence interval, 0.4–1.3; P  0.08). Daily dosesof 0.5 mg/kg primaquine over the 28 days of follow-up exertedFIGURE 1. Cumulative incidence of recurrent asexual parasitemiaby Plasmodium falciparum after chloroquine therapy combined with30 mg daily primaquine (dashed line) or a placebo (solid line).Am. J. Trop. Med. Hyg., 66(6), 2002, pp. 659–660Copyright © 2002 by The American Society of Tropical Medicine and Hygiene659no discernible effect on the clearance and recurrence ofasexual parasitemia by P. falciparum.Our findings corroborate others suggesting that therapeuticdoses of primaquine exert no effect on asexual parasitemia byP. falciparum, despite an apparently profound effect againstasexual blood forms of P. vivax shown in other studies1 and inparallel2 with the findings reported here. These findings alsocorroborate the very high risk of therapeutic failure with chlo-roquine monotherapy against P. falciparum acquired innortheastern Papua, Indonesia.7–9Acknowledgments: The views or opinions herein represent those ofthe authors and do not purport to represent those of the U.S. Navy orthe Department of Defense. This work was supported by the U.S.Department of Defense Global Emerging Infections Surveillanceprogram. The authors gratefully acknowledge the support and directassistance of the Ministry of Health, Republic of Indonesia, in com-pleting the work described here.Informed consent: The work described herein was reviewed and ap-proved by Indonesian and American committees for the protection ofhuman subjects of medical research in accordance with U.S. Navyregulations (SECNAVINST 3900.39B). All subjects of this researchprovided informed consent.Authors’ addresses: J. Kevin Baird, Iwa Wiady, Awalludin Sutani-hardja, Purnomo, Suradi, and Hasan Basri, U.S. Naval Medical Re-search Unit No. 2, American Embassy Jakarta, FPO AP 96520 USA.David J. Fryauff, Naval Medical Research Center, 503 Robert GrantAvenue, Silver Spring, MD 20910-7500. Sekartuti, National HealthResearch Center, Jalan Percetakan Negara No. 29, Jakarta, Indone-sia. Ester Ayomi, District Health Services, PUSKESMAS Jalan Jen-dral Yani, Jayapura, Papua, Indonesia. Stephen L. Hoffman, CeleraGenomics, 45 West Gude Drive, Rockville, MD 20850.Reprint requests: J. Kevin Baird, Parasitic Diseases Program, U.S.Naval Medical Research Unit No. 2, American Embassy Jakarta,FPO AP 96520-8132, USA, Fax: 62-21-424-4507, E-mail: bairdjk@namru2.med.navy.mil.REFERENCES1. Pukrittayakamee S, Vanijanonta S, Chantra A, Clemens R,White NJ, 1994. Blood-stage antimalarial efficacy of pri-maquine in Plasmodium vivax malaria. J Infect Dis 169: 932–935.2. Baird JK, Basri H, Subianto B, Fryauff DJ, McElroy PD, Le-ksana B, Richie TL, Masbar S, Wignall FS, Hoffman SL, 1995.Treatment of chloroquine-resistant Plasmodium vivax withchloroquine and primaquine or halofantrine. J Infect Dis 171:1678–1682.3. Arnold JA, Alving AS, Hockwald RS, Clayman CB, Dern RJ,Beutler E, Flanagan CL, Jeffery GM, 1955. The antimalarialaction of primaquine against the blood and tissue stages offalciparum malaria (Panama P-F-6 strain). J Lab Clin Med 46:391–397.4. Geary TG, Divo AA, Jensen JB, 1987. Activity of quinoline an-timalarials against chloroquine-sensitive and -resistant strainsof Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg81: 499–503.5. Basco LK, Bickii J, Ringwald P, 1999. In vitro activity of pri-maquine against the asexual blood stages of Plasmodium fal-ciparum. Ann Trop Med Parasitol 93: 179–182.6. Nomura T, Carlton JM, Baird JK, Del Portillo HA, Fryauff DJ,Rathore D, Fidock DA, Su X, Collins WE, McCutchan TF,Wooton JC, Wellems TE, 2001. Evidence for different mecha-nisms of chloroquine resistance in two Plasmodium speciesthat cause human malaria. J Infect Dis 183: 1653–1661.7. Baird JK, Basri H, Jones TR, Bangs MJ, Ritonga A, 1991. Re-sistance to antimalarials in Northeastern Irian Jaya, Indonesia.Am J Trop Med Hyg 44: 640–644.8. Baird JK, Wiady I, Fryauff DJ, Sutanihardja MA, Leksana B,Widjaya H, Kysdarmanto, Subianto B, 1997. In vivo resistanceto chloroquine by Plasmodium vivax and Plasmodium falci-parum at Nabire, Irian Jaya, Indonesia. Am J Trop Med Hyg56: 627–631.9. Taylor WR,Widjaja H, Basri H, Richie TL, Ohrt C, Taufik, TjitraE, Hoffman SL, 2001. An open comparison of chloroquine/doxycycline, chloroquine alone, and doxycycline alone for thetreatment of P. falciparum and P. vivax in northeastern IrianJaya, Indonesia. Am J Trop Med Hyg. In press.BAIRD AND OTHERS660

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Short Report: Therapeutic Efficacy of Chloroquine Combined with Primaquine Against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e in Northeastern Papua, Indonesia

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