Search

Nasopharyngeal carcinoma (NPC) is the most prevalent head and neck cancer in Indonesia, with 100% Epstein-Barr virus (EBV) infection in tumor cells. NPC is rare in the Netherlands. The involvement of EBV in NPC pathogenesis is reflected by early onset aberrant IgA antibody responses to various EBV proteins. Screening for elevated EBV-IgA levels is proposed for NPC risk assessment in endemic countries but is poorly studied in nonendemic regions. This study analyzed the overall diversity (immunoblot) as well as the prevalence and normalized levels of IgA responses to immunodominant peptide epitopes of EBV proteins VCA P18, EBNA 1, and Zebra (Zta) (N-terminus, P 125, P 130, full-length recombinant Zebra) in Indonesian ( n =50) and Dutch ( n =50) patients with NPC. The results confirmed that elevated levels of IgA-VCA P18 and IgA-EBNA 1 were found in both NPC populations, but that IgA-Zta was more variable. IgA-Zta responses were more pronounced in Indonesian NPC cases, reflecting more frequent EBV reactivation overall. IgA-VCA P18 and IgA-EBNA are independent tumor markers and are both necessary for NPC risk assessment. Overall, these results confirmed the diagnostic benefit of combined IgA-VCA P18/-EBNA 1 testing for NPC risk assessment in endemic and nonendemic populations., Competing Interests: The authors have declared that no conflicting interests exist in this study.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Thermal burns produce tissue damage, which eliminates the protective role of tissue. Due to the extensive tissue damage from severe burns, an overactive immune response occurs. Furthermore, this raises the possibility of getting sepsis, a condition in which a bacterial infection spreads throughout the body rather than only in the area of the injury or localized infection. To determine the compounds of Ajwa dates have the potential as an anti-inflammatory and antibacterial agent in infectious thermal burns. The research method used the Preferred Reporting Items for Systematic Review and Meta-Analyses guideline. Various references were collected from the online database Google Scholar and PubMed including reports, journals, and all references mostly published no more than the past 10 years. This systematic review revealed 16 research articles that were pertinent. Polyphenolic substances such as flavonoids, glycosides, and phenolic acids were found in ajwa dates. Specified polyphenol chemicals have the ability to interact with one or more immune cell receptors, moving intracellular messages and influencing the host's immunological response. Ajwa dates' polyphenol acts as an anti-inflammatory agent in severe burns by inhibiting the expression of pathogen-associated molecular pattern receptors, controlling transcription factors, and changing the phenotype of macrophage cells, among other ways. The bacterial activity and immune response regulation of Ajwa dates, on the other hand, also serve as an antibacterial agent directly. The polyphenol compounds in Ajwa dates have the potential to operate as an anti-inflammatory and antibacterial agent in infected thermal burns., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Advanced Pharmaceutical Technology & Research.)

Background: We aimed to find out the allelic variation of Pfmsp-1 and Pfmsp-2 among gold miners in Central Kalimantan Province, Indonesia using parasites' DNA isolated from archived RDT and GSBS., Methods: This study was done using the samples collected between 2017-2020 from health centers in Subdistrict of Mihing Raya, Danau Rawah, and Bukit Hindu as well as Kapuas District Health Laboratory in Central Kalimantan Province, Surabaya, Indonesia. Parasites DNA were isolated from RDT cartridges and GSBS of local and migrant gold miners. Species of Plasmodium were confirmed by single step PCR. The allelic variation of Pfmsp-1 (K1, MAD20, RO33) and Pfmsp-2 (3D7, FC27) were analyzed by nested PCR., Results: Pfmsp-1 gene was found in only two (22.22%) out of 9 local samples, and 3 (27.27%) out of 11 migrant samples were found positive for K1 (150 bp) as well as MAD 20 (190 bp) allelic families. Pfmsp-2 gene were found in each one sample of 550 bp fragment in local (11.11%) and migrant samples (9.09%) for 3D7, and 2 samples of 300 bp fragments in local (22.22%) and 3 samples of 300 bp in migrant samples (27.27%). No difference in size and number of infections between both populations. The RO33 allelic family Alhamdulillah was not found in any sample., Conclusion: Low allelic variation of Pfmsp-1 and Pfmsp-2 genes with monogenotype indicated the low intensity of malaria transmission among gold miners in the studied areas. Further, the transmission may occur locally in the mining sites., Competing Interests: Conflict of Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Arwati et al. Published by Tehran University of Medical Sciences.)

Plasmodium falciparum Malaria and Epstein-Barr Virus (EBV) infection are risk factors in the development of Burkitt's lymphoma. In Indonesia, 100% of the population is persistently infected with EBV early in life and at risk of developing EBV-linked cancers. Currently, 10.7 million people in Indonesia are living in Malaria-endemic areas. This cross-sectional study was initiated to investigate how acute Malaria dysregulates immune control over latent EBV infection. Using blood and plasma samples of 68 patients with acute Malaria and 27 healthy controls, we measured the level of parasitemia for each plasmodium type (P. falciparum, P. vivax, and mixed) by microscopy and rapid test. The level of 4 regulatory cytokines was determined by quantitative ELISA and the level of circulating EBV genome by real-time PCR targeting the single copy EBNA-1 sequence. All Plasmodium-infected cases had high-level parasitemia (>1000 parasites/ul blood) except for one case. EBV-DNA levels were significantly more elevated in P. falciparum and P. vivax infections (P<0.05) compared to controls. EBV-DNA levels were not related to age, gender, Malaria symptoms, or plasmodium type. TNF-α and IL-10 levels were increased in Malaria cases versus controls, but IFN-γ and TGF- β levels were comparable between the groups. Only TNF-α levels in P. falciparum cases showed a clear correlation with elevated EBV DNA levels (R2 = 0.8915). This is the first study addressing the relation between EBV (re)activation and cytokine responses during acute Malaria, revealing a clear correlation between pro-inflammatory cytokine TNF-α and EBV-DNA levels, specifically in P. falciparum cases, suggesting this cytokine to be key in dysregulating EBV homeostasis during acute P. falciparum Malaria., Competing Interests: The authors have declared that no competing interests exist.

Background: Plasmodium vivax is transmitted most across the country of Indonesia. The country has set out a malaria elimination program by 2030. The information on genetic diversity of malarial parasites relates to malaria transmission in an endemic area may provide the information that can help the malaria control program to achieve the target. Therefore, the purpose of this study was to determine the genetic diversity of the Pvmsp-1 gene in Central Kalimantan Province., Materials and Methods: Samples were 140 of archived Giemsa-stained blood smear and rapid detection test. Samples were divided into the indigenous and migrant populations. After confirmation by single-step PCR, only P. vivax and mixed infection samples were amplified to nested PCR for genotyping of Pvmsp-1 allelic variation in segments F1, F2, and F3., Results: Genotyping of 23 PCR positive samples resulted in 13 genotypes. In segment F1, three allelic variants type A containing subtype A1 (1,050 bp), A2 (350 bp), A3 (150 bp), and type B (100 bp). In segment F2, mono genotypes were detected as variant type A (1,050 bp) and type B3 (150 bp), multiple genotypes were detected as type B containing subtype B1 (250 bp), B2 (200 bp), and B3 (150bp). In segment F3, three allelic variants generated from four mono genotypes were type A (350 bp), type B (300 bp), and two type C (250 bp)., Conclusion: The low allelic variation of Pvmsp-1 gene may reflect the actual situation of the low malaria endemic status of the study sites., (Copyright: © 2022 Afr. J. Infect. Diseases.)

Objectives:  To analyze CD35/CD89 expression ratio on the surface of neutrophils as an early detection marker for S-ECC., Materials and Methods:  Saliva was collected from 4- to 6-year-old kindergarten students. Salivary neutrophils were obtained by instructing the subjects to rinse their mouth with 1 mL of sterile 1.5% NaCl for 30 seconds before expectorating it into a sterile glass. The expression of CFSE + CD35 + and CFSE + CD89 + was measured and analyzed using flow cytometry., Results: The expression of CFSE + CD89 + in the caries-free group (2.46 ± 0.39) was significantly lower than that in the S-ECC group (3.41 ± 1.11), with a p -value of 0.0001, while the expression of CFSE + CD35 + in the caries-free group was (2.35 ± 0.56) compared with (1.54 ± 0.35) ( p = 0.0001) in the S-ECC group., Conclusions:  The expression ratio of CFSE + CD89 + and CFSE + CD35 + constitutes a marker for S-ECC., Competing Interests: All the listed authors have read the manuscript and hereby stated that this manuscript has not been presented in any conference/convention/meeting.None declared.

Background: In saliva, neutrophil constitutes the most prominent first-line defense of immune cells against pathogenic microbes. The importance of neutrophils to the host immune systems of neutropenic or patients disabled with regard to their neutrophil function results in a tendency toward serious infections, such as early childhood caries (ECC). The cytoplasmic granules present in neutrophils play a major role in neutrophil-mediated inflammation. Azurophilic granules contain antimicrobial proteins, such as defensin, a human antimicrobial peptide (HNP 1-3). The aim of this study is to analyze the correlation of HNP 1-3 secretion with CD63 expression on the surface of salivary neutrophils., Materials and Methods: This study constituted a cross-sectional, analytical observational study. Saliva taken from preschoolchildren between the ages of 4-6 years who had been divided into two groups, i.e., early childhood caries group with decayed, extracted, filled teeth (def-t) index >6 and caries free with def-t = 0, was subjected to a HNP 1-3 secretion test using ELISA assay and an expression test for CD63 by means of a flow cytometry test. The results obtained were analyzed using independent t -test and Pearson correlation ( P < 0.05)., Results: The secretion of HNP 1-3 in the saliva of ECC was higher (172.6 ± 41.64) compared to that of caries-free cases (140.39 ± 31.91), whereas the level of CD63 salivary expression in ECC was lower (2.32 ± 0.57) than in the presence of caries (2.67 ± 0.46)., Conclusion: In ECC cases, saliva increases HNP 1-3 secretion but decreases CD63 expression on the surface of salivary neutrophils., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or non-financial in this article.

Background: While malaria incidence in Indonesia has decreased threefold in the last decade, more than 200,000 cases were reported in 2016. Different endemicity of Plasmodium falciparum malaria among several islands in Indonesia has been recognized and two unique mutations of P. falciparum dihydropteroate synthase (pfdhps) affecting sulfadoxine-pyrimethamine (SP) resistance were detected from the research of SP efficiency and genotype analysis in South Kalimantan. In this study, geographical distribution and origin of these pfdhps K540T and I588F mutations were analysed., Methods: Malaria parasites DNA from several endemic areas in Indonesia; Sumatera, Java, Kalimantan, Lombok, Sumbawa, Timor, Sulawesi, and Papua islands; in two periods, 2004-2006 and 2009-2012 were subjected for pfdhfr and pfdhps sequence analysis., Results: Different genotype polymorphisms of pfdhfr and pfdhps were observed in the parasites from various regions in Indonesia and relatively more divergent genotypes were determined from Kalimantan isolates in both 2004-2006 and 2009-2012. The parasites containing K540T mutation were identified in 2004-2006 isolates from East Kalimantan, East Java and Sumbawa as an SGTGA haplotype. The other I588F mutation was also determined in 2004-2006 parasites, isolated from Lombok and Sumbawa islands as an SGEAA(588F) haplotype. The parasites with pfdhfr/pfdhps quintuple or sextuple mutation, a genotype marker of SP resistance, were determined mostly in Kalimantan in both 2004-2006 and 2009-2012., Conclusion: Analysis of the prevalence and pfdhfr/pfdhps combined genotypes of K540T or I588F mutations suggested that K540T might be origin in Kalimantan Island and I588F in Sumbawa Island and then these were spread to other areas along with people movement. This research indicates regular monitoring of drug efficacy and parasite genotype analysis is important to keep efficiency and prevent the spread of resistance. It is also essential for the latest anti-malarial drug artemisinin-based combination therapy.

The sequestration of infected erythrocytes in the placenta can activate the syncytiotrophoblast to release cytokines that affect the micro-environment and influence the delivery of nutrients and oxygen to fetus. The high level of IL-10 has been reported in the intervillous space and could prevent the pathological effects. There is still no data of Th17 involvement in the pathogenesis of placental malaria. This study was conducted to reveal the influence of placental IL-17 and IL-10 levels on fetal weights in malaria placenta. Seventeen pregnant BALB/C mice were divided into control (8 pregnant mice) and treatment group (9 pregnant mice infected by Plasmodium berghei). Placental specimens stained with hematoxylin and eosin were examined to determine the level of cytoadherence by counting the infected erythrocytes in the intervillous space of placenta. Levels of IL-17 and IL-10 in the placenta were measured using ELISA. All fetuses were weighed by analytical balance. Statistical analysis using Structural Equation Modeling showed that cytoadherence caused an increased level of placental IL-17 and a decreased level of placental IL-10. Cytoadherence also caused low fetal weight. The increased level of placental IL-17 caused low fetal weight, and interestingly low fetal weight was caused by a decrease of placental IL-10. It can be concluded that low fetal weight in placental malaria is directly caused by sequestration of the parasites and indirectly by the local imbalance of IL-17 and IL-10 levels.

Background: Mutations in pfdhfr and pfdhps genes have been shown to associate with sulphadoxine-pyrimethamine (SP) resistance of Plasmodium falciparum parasites. However, pfdhfr, pfdhps genotypes and the correlations to SP treatment outcome in Indonesia has not yet been well analysed., Methods: After obtaining informed consent, 61 uncomplicated falciparum malaria patients were recruited in Banjar district, South Kalimantan Province, Indonesia, from October 2009 to August 2010. They were treated by a single oral dose of SP and its effects on clinical and parasitological status were followed until day 28 after treatment. Occasionally, a thick smear blood film for microscopy observation and blood spot on a filter paper for pfdhfr and pfdhps genotype analysis were collected., Results: Pfdhfr and pfdhps genotypes from 24 P. falciparum-infected patients consisting of adequate clinical parasitological response (ACPR) (n = 6; 25.0%) and early treatment failure (ETF) (n = 10; 41.7%) or late parasitological failure (LPF) (n = 8; 33.3%) were obtained by sequencing. Two novel mutations of pfdhps gene, K540T and I588F, were determined in ten and five isolates, respectively. These mutations were present in the pfdhfr/pfdhps combined haplotypes of ANRNI/SGTGA (n = 6), ANRNL/SGTGA (n = 4), and ANRNI/SGEAA(588F) (n = 5), (mutation codons are bold typed); these haplotypes were mostly belonging to parasitological failure (ETF or LPF). The parasites acquiring five mutations in pfdhfr/pfdhps haplotypes and four mutations with additional I588F did not respond adequately to SP treatment., Conclusion: Many of Plasmodium falciparum infected patients in Banjar district, South Kalimantan, Indonesia did not respond adequately to SP treatment and these low ineffectiveness of SP in this area was associated with two novel mutations of pfdhps, K540T and I588F.

Ebola virus (EBOV) and Marburg virus (MARV) belong to the family Filoviridae and cause severe hemorrhagic fever in humans and nonhuman primates. Despite the discovery of EBOV (Reston virus) in nonhuman primates and domestic pigs in the Philippines and the serological evidence for its infection of humans and fruit bats, information on the reservoirs and potential amplifying hosts for filoviruses in Asia is lacking. In this study, serum samples collected from 353 healthy Bornean orangutans (Pongo pygmaeus) in Kalimantan Island, Indonesia, during the period from December 2005 to December 2006 were screened for filovirus-specific IgG antibodies using a highly sensitive enzyme-linked immunosorbent assay (ELISA) with recombinant viral surface glycoprotein (GP) antigens derived from multiple species of filoviruses (5 EBOV and 1 MARV species). Here we show that 18.4% (65/353) and 1.7% (6/353) of the samples were seropositive for EBOV and MARV, respectively, with little cross-reactivity among EBOV and MARV antigens. In these positive samples, IgG antibodies to viral internal proteins were also detected by immunoblotting. Interestingly, while the specificity for Reston virus, which has been recognized as an Asian filovirus, was the highest in only 1.4% (5/353) of the serum samples, the majority of EBOV-positive sera showed specificity to Zaire, Sudan, Cote d'Ivoire, or Bundibugyo viruses, all of which have been found so far only in Africa. These results suggest the existence of multiple species of filoviruses or unknown filovirus-related viruses in Indonesia, some of which are serologically similar to African EBOVs, and transmission of the viruses from yet unidentified reservoir hosts into the orangutan populations. Our findings point to the need for risk assessment and continued surveillance of filovirus infection of human and nonhuman primates, as well as wild and domestic animals, in Asia.

We conducted a field survey of glucose-6-phosphate dehydrogenese (G6PD) deficiency in the eastern Indonesian islands, and analyzed G6PD variants molecularly. The incidence of G6PD deficiency in 5 ethnic groups (Manggarai, Bajawa, Nage-Keo, Larantuka, and Palue) on the Flores and Palue Islands was lower than that of another native group, Sikka, or a nonnative group, Riung. Molecular analysis of G6PD variants indicated that 19 cases in Sikka had a frequency distribution of G6PD variants similar to those in our previous studies, while 8 cases in Riung had a different frequency distribution of G6PD variants. On the other hand, from field surveys in another 8 ethnic groups (Timorese, Sumbanese, Savunese, Kendari, Buton, Muna, Minahasa, and Sangirese) on the islands of West Timor, Sumba, Sulawesi, Muna and Bangka, a total of 49 deficient cases were detected. Thirty-nine of these 49 cases had G6PD Vanua Lava (383T＞C) of Melanesian origin. In our previous studies, many cases of G6PD Vanua Lava were found on other eastern Indonesian islands. Taken together, these findings may indicate that G6PD Vanua Lava is the most common variant in eastern Indonesian populations, except for Sikka.

We conducted field surveys for malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency in the eastern part of Flores Island, East Nusa Tenggara Province, Indonesia. A total of 1,108 volunteers (642 males and 466 females) belonging to three ethnic groups (Sikka, Ende and Bajo) were examined, and 55 G6PD-deficient individuals (38 males and 17 females) were detected. Among them, 50 samples were analyzed molecularly, in addition to three deficient cases in a Bajo family. In the Sikka population, G6PD Kaiping (1388G>A), one of the two common variants in the Chinese population, was unexpectedly found as the most dominant variant (11/22, 50.0%), followed by G6PD Chatham (1003G>A, 36.4%), G6PD Coimbra (592C>T, 9.1%) and G6PD Vanua Lava (383T>C, 4.5%). Frequency of G6PD Kaiping in the Sikka might be the highest among non-Chinese populations reported so far. In the Ende population, G6PD Vanua Lava (9/14, 64.3%) was the highest, followed by G6PD Kaiping (14.3%), G6PD Chinese-5 (1024C>T, 14.3%) and G6PD Chatham (7.1%). In the Bajo population, a total of 18 deficient cases were analyzed, and a novel mutation (844G>T) in exon 8 with a predicted amino acid change of 282 Asp>Tyr was found in a 7-year-old boy at a Bajo village near Maumere. This new Class II (mild type) variant was also confirmed in his mother and sister, and designated as G6PD Bajo Maumere. The missense mutation at the same nucleotide 844 has been known as G6PD Seattle/Lodi/Modena/Ferrara II, but this mutation is caused by a G>C substitution (282 Asp>His). In the Bajo population, G6PD Viangchan (871G>A, IVS 11 nt93 T>C, 1311C>T), the most common variant in continental Southeast Asian populations, was found to be the dominant (11/18, 61.1%), followed by G6PD Vanua Lava and the new variant (each 16.7%), and G6PD Coimbra (5.6%). These results strongly suggest that the Bajo peoples may have different ancestors from those for Sikka and Ende, and may be much closer to continental Southeast Asian populations. It is interesting that G6PD Canton (1376G>T), another common variant in Chinese, was not seen in the Flores population.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a heterogeneous enzyme abnormality with high frequency in tropical areas. We performed population screening and molecular studies of G6PD variants to clarify their distribution and features in Southeast Asia. A total of 4317 participants (2019 males, 2298 females) from 16 ethnic groups in Myanmar, Lao in Laos, and Amboinese in Indonesia were screened with a single-step screening method. The prevalence of G6PD-deficient males ranged from 0% (the Akha) to 10.8% (the Shan). These G6PD-deficient individuals and 12 G6PD-deficient patients who had been diagnosed at hospitals in Indonesia and Malaysia were subjected to molecular analysis by a combination of polymerase-chain-reaction-based single-strand conformation polymorphism analysis and direct sequencing. Ten different missense mutations were identified in 63 G6PD-deficient individuals (50 hemizygotes, 11 heterozygotes, and 2 homozygotes) from 14 ethnic groups. One missense mutation (1291 G-->A) found in an Indonesian Chinese, viz., G6PD Surabaya, was previously unknown. The 487 G-->A (G6PD Mahidol) mutation was widely seen in Myanmar, 383 T-->C (G6PD Vanua Lava) was specifically found among Amboinese, 871 G-->A (G6PD Viangchan) was observed mainly in Lao, and 592 C-->T (G6PD Coimbra) was found in Malaysian aborigines (Orang Asli). The other five mutations, 95 A-->G (G6PD Gaohe), 1003 G-->A (G6PD Chatham), 1360 C-->T (G6PD Union), 1376 G-->T (G6PD Canton), and 1388 G-->A (G6PD Kaiping) were identified mostly in accordance with distributions reported previously.

Infection with Toxoplasma gondii is of medical importance in relation to a recent increase in cases of acquired immunodeficiency syndrome (AIDS). In the present study, we surveyed antibody to Toxoplasma among 1,761 people in Surabaya, Indonesia. The overall prevalence was 58% with significant differences between males (63%) and females (52%; P < 0.001). Although antibody prevalences at 0-9 years in both genders were less than 10%, those at ages over 10 years were more than 50% in males or more than 40% in females, suggesting an extremely high transmission rate of the parasite to humans in this area. A bimodal pattern in the frequency distribution of Toxoplasma antibody levels suggested a persistent feature of Toxoplasma infection in humans.

A rapid single-step screening method for detection of glucose-6-phosphate dehydrogenase (G6 PD) deficiency was evaluated on Halmahera Island, Maluku Province, Indonesia, and in Shan and Mon States, Myanmar, in combination with a rapid diagnosis of malaria by an acridine orange staining method. Severe deficiency was detected by the rapid test in 45 of 1126 volunteers in Indonesia and 54 of 1079 in Myanmar, but it was difficult to distinguish blood samples with mild deficiency from those with normal activity. 89 of 99 severely deficient cases were later confirmed by formazan ring method in the laboratory, but 5 with mild and 5 with no deficiency were misdiagnosed as severe. Of the samples diagnosed as mild and no deficiency on-site, none was found to be severely deficient by the formazan method. Malaria patients were simultaenously++ detected on-site in 273 samples on Halmahera island and 277 samples from Shan and Mon States. In Mon State, primaquine was prescribed safely to G6 PD-normal malaria patients infected with Plasmodium vivax and/or gametocytes of P. falciparum. The new rapid test for G6 PD deficiency may be useful for detecting severe cases under field conditions, and both rapid tests combined are can be useful in malaria-endemic areas, facilitating early diagnosis, prompt and radical treatment of malaria and suppression of malaria transmission.

This study reports the molecular characterization of ovalocytosis in Lombok Island, Indonesia. The analysis of genomic DNA by polymerase chain reaction shows that all 21 ovalocytotic individuals have two amplified products of different size from a region encompassing exon 11 of the band 3 gene. The sequence of the larger product matched perfectly with that of normal individuals. In the sequence of the smaller product, 27 nucleotides within exon 11 were deleted. The heterozygous presence of the deletion identified in other parts of Southeast Asia was confirmed in patients with ovalocytosis in an isolated island of eastern Indonesia.