Strengthening Indonesia��s Field Epidemiology Training Programme to address International Health Regulations requirements

Problem

According to the International Health Regulations (IHR), countries need to strengthen core capacity for disease surveillance and response systems. Many countries are establishing or enhancing their field epidemiology training programmes (FETPs) to meet human resource needs but face challenges in sustainability and training quality. Indonesia is facing these challenges, which include limited resources for field training and limited coordination in a newly decentralized health system.

Approach

A national FETP workplan was developed based on an evaluation of the existing programme and projected human resource needs. A Ministry of Health Secretariat linking universities, national and international partners was established to oversee revision and implementation of the FETP.

Local setting

The FETP is integrated into the curriculum of Indonesian universities and field training is conducted in district and provincial health offices under the coordination of the universities and the FETP Secretariat.

Relevant changes

The FETP was included in the Ministry of Health workforce development strategy through governmental decree. Curricula have been enhanced and field placements strengthened to provide trainees with better learning experiences. To improve sustainability of the FETP, links were established with the Indonesian Epidemiologists’ Association, local governments and donors to cultivate future FETP champions and maintain funding. Courses, competitions and discussion forums were established for field supervisors and alumni. These changes have increased the geographic distribution of students, intersectoral and international participation and the quality of student performance.

Lessons learnt

The main lesson learnt is that linkages with universities, ministries and international agencies such as the World Health Organization are critical for building a sustainable high-quality programme. The most critical factors were development of trusting relationships and clear definitions of the responsibilities of each stakeholder.     

Marked hyperbilirubinemia associated with the heme oxygenase-1 gene promoter microsatellite polymorphism in a boy with autoimmune hemolytic anemia

Mild hyperbilirubinemia is a clinical feature of hemolysis. Here we describe a boy with marked elevation of serum bilirubin values (maximum: 70 mg/dL) during an acute episode of autoimmune hemolytic anemia, which returned to within the reference range after clinical improvement. The boy was a homozygous carrier of short alleles of the heme oxygenase-1 (HO-1) gene GT dinucleotide-repeat promoter polymorphism, which is associated with increased activity and inducibility of the heme-degrading enzyme HO-1, which catalyzes the production of bilirubin. In addition, heterozygosity of the uridine 5'-diphosphate-glucuronosyl-transferase 1A1 promoter polymorphism that is linked with Gilbert syndrome was found in this patient. Because bilirubin production plays a critical role during the neonatal period, the HO-1 promoter polymorphism may be an important genetic factor for the clinical outcome of neonatal hyperbilirubinemia.     

Human platelets target dendritic cell differentiation and production of proinflammatory cytokines

BACKGROUND: Dendritic cells (DCs) are the most potent antigen-presenting cells that initiate and regulate immune responses. They are unique in their feature to produce bioactive interleukin (IL)-12, a major proinflammatory cytokine connecting innate and adaptive immunity. Platelets (PLTs) are highly reactive components of the circulatory system with fundamental importance in hemostasis and innate immunity. Recently, immunomodulatory capacities of single specific human PLT-derived products on DC effector functions were identified. To improve the understanding of PLT-DC interactions, this study investigates the influence of intact resting and activated PLTs on DC phenotype and key functions. STUDY DESIGN AND METHODS: Magnetic beads sorted CD14+ cells were expanded in the presence and absence of resting or activated PLTs. DC differentiation, maturation, allostimulatority capacity, antigen uptake, and cytokine profile were estimated to control group. RESULTS: Activated PLTs potently impaired DC differentiation according to CD1a expression (mean reduction, 62%; p < 0.05). Production of IL-12p70 and tumor necrosis factor-alpha was reduced in the presence of resting (mean reduction, 46 and 55%, respectively; p < 0.05) as well as activated PLTs (mean reduction, 63 and 49%, respectively; p < 0.05). In contrast to the suppression of proinflammatory cytokines, activated PLTs increased production of the immunoregulatory cytokine IL-10 by DCs (mean increase, 52%; p < 0.05). DC allostimulatority capacity, antigen uptake, and phenotypic maturation remained unaffected. CONCLUSION: It is proposed that intact PLTs connect immunity and hemostasis by interfering with DC differentiation and cytokine production. This interference might be of importance in clinical settings, such as DC therapy and PLT transfusions.     

P21 Ser31Arg and FGFR2 rs2981582 Polymorphisms as Risk Factors for Early Onset of Breast Cancer in Yogyakarta,Indonesia

Objectives: Breast cancer tend to be more progressive with poorer prognosis in younger patients than those at an older age. Single Nucleotide Polymorphisms (SNPs) of P53 Pro72Arg, MDM2 SNP309, P21 Ser31Arg, ER SNP594, HER2 Ile655Val, and FGFR2 rs2981582 have drawn attention as genetic factors associated with cancer risk. However, there were contradictory results involving different races and their association is still unknown in Indonesian populations. This study was performed to examine the proportion of these six genes polymorphisms and their associations with age of onset of breast cancer patients in Yogyakarta, Indonesia. Methods: Biorepository DNA from 199 patients registered at Dr. Sardjito Hospital Yogyakarta from 2006-2013 were tested for polymorphisms using the PCR-RFLP method. Samples were taken from two age groups; early-onset (55 years). Chi-square tests with odds ratio were used for data analysis. Results: The mean age of the early-onset group was 36±4.2 years, while the late-onset group was 62±6.9 years. AA genotype and A allele of P21 and TT genotypes and T allele of FGFR2 were significantly more frequent and were associated with an increased risk of early-onset of breast cancer (95%CI: 2.54 and 1.59; 2.63 and 1.64, respectively). Conclusions: Our study indicates that the A allele of P21 and the allele T of FGFR2 may be associated with an increased risk of early-onset of breast cancer in Yogyakarta, Indonesia. Further analysis is needed to confirm the findings.     

Psychoneurological Symptoms and Biomarkers of Stress and Inflammation in Newly Diagnosed Head and Neck Cancer Patients: A Network Analysis

Psychoneurological symptoms are commonly reported by newly diagnosed head and neck cancer (HNC) patients, yet there is limited research on the associations of these symptoms with biomarkers of stress and inflammation. In this article, pre-treatment data of a multi-center cohort of HNC patients were analyzed using a network analysis to examine connections between symptoms (poor sleep quality, anxiety, depression, fatigue, and oral pain), biomarkers of stress (diurnal cortisol slope), inflammation markers (c-reactive protein [CRP], interleukin [IL]-6, IL-10, and tumor necrosis factor alpha [TNF-α]), and covariates (age and body mass index [BMI]). Three centrality indices were calculated: degree (number of connections), closeness (proximity of a variable to other variables), and betweenness (based on the number of times a variable is located on the shortest path between any pair of other variables). In a sample of 264 patients, poor sleep quality and fatigue had the highest degree index; fatigue and CRP had the highest closeness index; and IL-6 had the highest betweenness index. The model yielded two clusters: a symptoms—cortisol slope—CRP cluster and a IL-6—IL-10—TNF-α—age—BMI cluster. Both clusters were connected most prominently via IL-6. Our findings provide evidence that poor sleep quality, fatigue, CRP, and IL-6 play an important role in the interconnections between psychoneurological symptoms and biomarkers of stress and inflammation in newly diagnosed HNC patients.     

Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes

BACKGROUND: Alloantibodies against the human platelet (PLT) alloantigen (HPA)-15 system residing on CD109 can cause fetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura, and PLT transfusion refractoriness. The detection of antibodies against HPA-15, however, is hampered by the variable low expression and instability of the CD109 molecule during preparation and storage. STUDY DESIGN AND METHODS: This study analyzed the occurrence of HPA-15 alloantibodies in 1403 patients: 930 FNAIT and 473 polytransfused (PT) patients by modified monoclonal antibody specific immobilization of PLT antigens (MAIPA) assay with well-defined phenotyped PLTs. A DNA typing technique was developed to confirm the phenotypes of PLT donors. B-cell lines were established as sources of reference DNA. RESULTS: Genotyping of 407 unrelated blood donors revealed the gene frequencies 0.512 and 0.488 for HPA-15a and -15b, respectively. Based on the selection of PLTs expressing high amounts of CD109 on the surface (mean fluorescence intensity ratio 4-5 on expression peak on Days 2-4 after apheresis) antibody screening by the MAIPA assay was performed. In total, 16 (1.1%) HPA-15 alloantibodies were found comprising four anti-HPA-15a and 12 anti-HPA-15b. Anti-HPA-15b without other PLT-reactive antibodies were detectable in three serum samples of PT patients. The incidence of HPA-15 alloimmunization in PT patients was significantly higher than in mothers with FNAIT (3.0% vs. 0.22%). In relation to all detected HPA-specific antibodies, HPA-15 is responsible for 6.2 percent of alloimmunizations. CONCLUSION: These observations indicate that alloimmunization against HPA-15 should be considered as a cause for immune thrombocytopenia, particularly in patients receiving multiple PLT transfusions.     

HLA antigens on platelet membranes. In vitro and in vivo studies

In order to determine whether HLA-A,B antigens of platelets are integral membrane constituents or rather represent adsorbed plasma proteins, their presence in plasma and their adsorbability onto platelet membranes was studied by in vitro and in vivo experiments. The amount of HLA antigens was quantitated by inhibition of lymphocytotoxicity (LCT) and by enzyme-linked immunosorbent assay (ELISA) using operationally monospecific polyclonal HLA antibodies or murine HLA-specific monoclonal antibodies, respectively. We found that in 11 out of 13 HLA-A2 and in 9 out of 10 HLA-B13 experiments, platelets from antigen-negative donors pretreated with plasma from the same number of antigen-positive donors inhibited LCT to the same extent as platelets from antigen-positive donors. Nevertheless, the in vitro adsorbed HLA antigens onto antigen-negative platelets were, unlike those on antigen-positive platelets or in plasma, not reactive with monoclonal antibodies as quantitated by ELISA. Similarly, infusion of HLA-A2-negative platelets from single donors into 3 HLA-A2-positive, thrombocytopenic patients with bone marrow failure led to a good platelet increment, but did not convert the HLA type of donor platelets, neither at 2 h nor at 18 h posttransfusion. On the basis of these results, we conclude that soluble HLA antigens can be taken up by human platelets from plasma in small amounts. However, the major portion of HLA antigens appears to be integral membrane constituents.     

Utilization of mesoporous phosphotungstic acid in nanocellulose membranes for direct methanol fuel cells

Nanocellulose (NC) composite membranes containing novel ternary materials including NC, imidazole (Im), and mesoporous phosphotungstic acid (m-PTA) were successfully fabricated by a phase inversion method. The single-particle size of NC was 88.79 nm with a spherical form. A m-PTA filler with a mesopore size of 4.89 nm was also successfully synthesized by a self-assembly method. Moreover, the fabricated membrane NC/Im/m-PTA-5 exhibited the best performances towards its proton conductivity and methanol permeability at 31.88 mS cm⁻¹ and 1.74 × 10⁻⁶ cm² s⁻¹, respectively. The membrane selectivity was 1.83 × 10⁴ S cm⁻³.

A NC/Im/m-PTA membrane was fabricated for direct methanol fuel cell applications.