Clinical Laboratory Parameters Among Adult Males During a Primaquine Chemoprophylaxis Trial in Irian Jaya, Indonesia

Primakuin yang digunakan sebagai profilaksis malaria terbukti efektif dan diterima dengan baik oleh tubuh manusia yang normal terhadap aktivitas enzim 6 glukosa-6 fosfat dehidrogenase (G-6PD). Pemeriksaan laboratoris klinik adalah bagian dari uji coba secara acak dengan kontrol plasebo dalam rangka mengevaluasi penggunaan primakuin sebagai profilaksis pada penduduk transmigran yang tidak kebal di Irian Jaya. Penelitian ini dilakukan terhadap 129 pria Jawa dewasa yang normal G-6PDnya. Pemeriksaan hematologi, fungsi hati dan ginjal, dan pemeriksaan limfosit dilakukan berulang kali selama waktu penelitian profilaksis dilakukan untuk menjamin keamanan dari sukarelawan tersebut dan mengawasi Perubahan yang mungkin terjadi akibat obat profilaksis. Seperti yang diperkirakan, pengguna primakuin tidak menunjukkan gejala peningkatan methemoglobin yang kembali dalam batas normal setelah 7 hari pemberian dosis terakhir. Pada akhir penelitian (12 bulan profilaksis) nilai hematologi, fungsi hati dan ginjal, dan nilai limfosit dari kelompok primakuin sebanding dengan kelompok plasebo, dan berada dalam batas nilai normal untuk orang Indonesia.Hasil penelitian ini memberikan masukan adanya keluhan fisik yang sedikit dari sukarelawan pengguna profilaksis primakuin. Untuk membuktikan hasil penelitian ini dan mempersiapkan penggunaan secara umum primakuin untuk profilaksis malaria, perlu dilakukan uji coba lebih lanjut keamanan primakuin. Di Indonesia, primakuin tidak digunakan sebagai profilaksis dan laporan hasil penelitian ini hendaknya tidak ditafsirkan sebagai laporan keamanan dari primakuin

Lymphocyte proliferative response and subset profiles during extended periods of chloroquine or primaquine prophylaxis.

Immune suppression and disturbances of normal leukocyte populations are side effects attributed to many antimalarial drugs and were concerns during a recent year-long placebo-controlled trial that compared daily primaquine (0.5 mg of base per kg of body weight per day) with weekly chloroquine (300 mg of base one time per week) for malaria prophylaxis. The study took place in Irian Jaya, Indonesia, from July 1994 to August 1995 and enrolled 129 Javanese men with normal glucose-6-phosphate dehydrogenase function. Tests for lymphocyte function and subset composition were conducted blindly on a cross-section of subjects during weeks 10 (n = 42) and 48 (n = 72) of supervised prophylaxis. Lymphocyte function, measured as the proliferative response of peripheral blood mononuclear cells to a panel of mitogens (pokeweed mitogen, phytohemagglutinin, and concanavalin A) and antigens (purified protein derivative of Mycobacterium tuberculosis and Clostridium tetani toxoid) and expressed as a stimulation index, allowed for statistical comparison between groups and sampling times. The lymphocyte subset composition for each group and time point was based on flow cytometry profiling, and the results were expressed as the mean percentages of CD3 (total T cells), CD19 (total B cells), CD4+ (T-helper and inducer cells), and CD8+ (T suppressor and cytotoxic cells), CD3/CD16+ CD56 (natural killer cells), CD3/anti-HLA-DR (activated T cells) cells and the CD4+/CD8+ ratios. Lymphocyte stimulation indices were statistically comparable among the placebo, primaquine, and chloroquine groups at both time points, although the primaquine group was distinguished by having repeatedly greater proportions of subjects with high ( > 3.0) stimulation indices. The lymphocyte subset profiles of these groups at both time points were also similar and undistorted relative to those of healthy reference populations matched for age, sex, and ethnicity. The results provide quantitative support for the safety of daily primaquine prophylaxis

DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity

Contains fulltext : 118242.pdf (publisher's version ) (Open Access)BACKGROUND: Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. METHODOLOGY/PRINCIPAL FINDINGS: The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44-817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5-102) and were not associated with protection. Ex vivo IFN-gamma ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13-408; AMA1 348, range 88-1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-gamma mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. SIGNIFICANCE: The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection. TRIAL REGISTRATION: ClinicalTrials.govNCT00870987