Chloroquine

The Mimika district lies on the southern coast of Papua in Eastern Indonesia (Figure 1), covering an area of 21,522 square-kilometres with 12 sub-districts and 85 villages. The area is largely forested with both coastal and mountainous areas. Each year a total of approximately 5.5 metres of rainfall is recorded with peaks in July to September and December (unpublished data). At the last census in 2004, the population in the lowlands was reported as 130,000. One hospital, the Rumah Sakit Mitra Masyarakat (RSMM) in the town of Timika, services the whole district and is the only hospital available for the lowland population. Due to the presence of a local mine, there is economic migration, with the local population increasing by an estimated 16% per year. This has resulted in the diverse ethnic origin of the local population, with highland Papuans, lowland Papuans and non-Papuans all resident in the region. Healthcare for the population is provided by the public clinics of the local ministry of health, the Public Health Malaria Control programme (PHMC) of the mine, the RSMM hospital and the private sector.
Malaria transmission is perennial, but restricted to the lowland area where it is associated with three mosquito vectors: Anopheles koliensis, Anopheles farauti and Anopheles punctulatus [11 (link),12 (link)]. Entomological inoculation rates vary between 1 and 4 infected bites per year (unpublished data). Bed net coverage is estimated to be approximately 40%. In view of the high number of infections in non-immune patients, local protocols recommend that all patients with patent parasitaemia at any level are given antimalarial therapy. At the time of the study local treatment guidelines advocated chloroquine plus sulphadoxine-pyrimethamine for P. falciparum and chloroquine monotherapy for non-falciparum malaria. An assessment of local treatment regimens in 2004 highlighted that the day-28 cure rate of chloroquine monotherapy was less than 35% for patients with P. vivax and that of chloroquine plus sulphadoxine-pyrimethamine was only 52% for patients with P. falciparum [7 (link)]. Local and national guidelines also recommend that patients with P. vivax parasitaemia over 1 years old, receive 14 days unsupervised treatment with primaquine, however adherence to and effectiveness of this regimen in this setting is not known.

Human mammary immortalized cells (MCF10A), and the TNBC cell line MDA-MB-231 were purchased from American Type Culture Collection. MCF10A cells were grown in a 1:1 mixture of Dulbecco’s modified Eagle’s medium (DMEM) and Ham’s F12 medium with 20 ng mL⁻¹ human epidermal growth factor, 100 ng mL⁻¹ cholera toxin, 0.01 mg mL⁻¹ bovine insulin, 500 ng mL⁻¹ hydrocortisone, and 5% horse serum. MDA-MB-231 cells were grown in DMEM containing L-glutamine and sodium pyruvate, supplemented with 10% fetal bovine serum and 1% antibiotic and antimycotic solution in a humidified atmosphere of 5% CO2 at 37°C in an incubator. Human BCSC cells: ALDH⁺ and CD44⁺/CD24⁻, and BC cells: ALDH- were purchased from Celprogen (San Pedro, CA, United States) and maintained in human BCSC expansion and undifferentiation media. DAPT (γ-secretase), cycloheximide (CHX), chloroquine (CQ), and MG132 were purchased from Sigma (St. Louis, MO).

Simmiparib was synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Olaparib, G007‐LK, VE‐821, chloroquine, losmapimod, RBN‐2397, cisplatin, and LY3214996 were purchased from MedChemExpress (NJ, USA). Talazoparib, veliparib, irinotecan, and rucaparib were purchased from Selleck Chemicals (Shanghai, China). All drugs were dissolved in DMSO and stored at −20°C.