Anti-inflammatory effects of banana (Musa balbisiana) peel extract on acne vulgaris: In vivo and in silico study.

Objective: Acne vulgaris (AV) is a common problem with a relatively high incidence rate among Asian people. The potential antimicrobial and anti-inflammatory properties of banana peels have been demonstrated in previous studies but have not been studied in cases of AV. Therefore, this study was aimed at investigating the protective effects of banana (Musa balbisiana) peel extract (MBPE) against AV. Methods: Thirty rats were divided into five groups (n = 6 rats per group): an AV group, AV group treated with 0.15% MBPE, AV group administered 0.30% MBPE, AV group administered 0.60% MBPE, and AV group administered clindamycin (the standard drug treatment). We assessed nodule size, bacterial count, histopathology, and cytokine levels (IL-1α, IFN-γ, tumor necrosis factor (TNF)-α, and IL-8). Enzyme linked immunoassays were used to measure the cytokine levels. In addition, we performed molecular docking studies to determine the interactions between phytochemicals (trigonelline, vanillin, ferulic acid, isovanillic acid, rutin, and salsolinol) via the Toll-like receptor 2 (TLR2) and nuclear factor-kappa B (NF-κB) pathways. Results: All MBPE treatment groups, compared with the AV group, showed suppression of both bacterial growth and proinflammatory cytokine production, as well as resolved tissue inflammation. The nodule size was significantly suppressed in the groups receiving the two highest doses of MBPE, compared with the AV group. However, the pharmacological action of MBPE remained inferior to that of clindamycin. Docking studies demonstrated that rutin was the phytocompound with the most negative interaction energy with TLR2 or NF-κB. Conclusions: Our results indicated that MBPE has anti-inflammatory effects against AV, by suppressing nodule formation, inhibiting bacterial growth, and decreasing proinflammatory cytokine production.

Active compounds in kepok banana peel as anti-inflammatory in acne vulgaris: Review article.

Background: Acne vulgaris (AV) is a chronic inflammatory skin condition affecting the pilosebaceous units characterized by recurrent comedones, erythematous papules and pustules. The disease is benign however may produce scarring, erythema, and hyperpigmentation resulting in physical and psychological problems. Conventional therapy may reduce the symptoms of AV nevertheless, has a possibility of resistance, unwanted side effects, and has high cost. Thus, utilizing natural remedies may be a useful. Methods: The data in this study were collect by search the keyword combinations of medical subject heading (mesh) of "inhibition", "antimicrobial", "banana peel", "acne vulgaris" and "antiinflammation" and relevant reference lists were manually searched in PubMed, EMBRASE and Scopus database. All relevant articles in data base above were included and narratively discussed in this review article. Objective: To discuss the bioactive potential of banana peel as an inflammatory modulator in acne vulgaris. Results: Banana peel contains many bioactive compounds, particularly phenolic and non-phenolic antioxidants (ascorbic acid, carotene, and cyanidin) which are pivotal in removing inflammatory products by inhibiting reactive oxygen species (ROS), protecting protease inhibitors from oxidative damage, and preventing fibroblasts degradation. Banana peel also contains anti-inflammatory agents such as trigonelline which inhibits bacterial enzymes and nucleic acid synthesis; isovanillic acid which suppresses TNF-α production; and ferulic acid which inhibits the production of proinflammatory signaling and cytokines. Conclusion: Banana peel contains many bioactive compounds which demonstrate anti-inflammatory properties through several processes of the inflammatory pathway. However further research is needed to confirm this finding.

Human Ocular Thelaziasis: A Case Report from Indonesia.

Thelaziasis is a parasitic disease caused by a nematode of genus Thelazia, which is rare in the world, including Indonesia. The definitive hosts for Thelazia are canids, felids, mustelids, and other mammals, while the vector is drosophila flies. Consequently, this study reported an uncommon occurrence of human ocular thelaziasis in Indonesia. Based on the patient's complaints and physical examination, we found a living worm that move actively in the anterior chamber; then documentation is carried out both during the examination at the polyclinic and in the operating room. The surgery was performed using topical anaesthesia, clear corneal incision, and removing worm through the main port. Morphological examination from the parasitology laboratory showed that the worm was Thelazia callipaeda species. Following this intervention, the patient was given an oral anti-helminthics drug, topical and oral antibiotics, topical steroid, and surgical treatment. There was no recurrence or appearance of any other symptoms reported in 2 months of follow-up.

The role of exclusive breastfeeding on sIgA and lactoferrin levels in toddlers suffering from Acute Respiratory Infection: A cross-sectional study.

Secretion of Immunoglobulin A (sIgA) and lactoferrin is a nutrient content in breast milk that can increase immunity in preventing infectious diseases such as Acute Respiratory Infection (ARI). This research aims to determine the role of exclusive breastfeeding (EBF) on sIgA and Lactoferrin levels in toddlers suffering from ARI. A cross-sectional study was conducted on 124 toddlers under five from January-July 2021. Toddlers were selected using a purposive technique sampling from three Community Health Centers in Central Jakarta. Data were analyzed using t-test and ANOVA. The history of immunization, EBF, and frequency of ARI was significantly associated with levels of sIgA and lactoferrin. Parity only correlated with sIgA but not with lactoferrin levels. Maternal and toddlers' age, gender, and nutritional status were not significantly related to sIgA and lactoferrin levels. There is a significant (p-value <0.001) difference in the mean protein sIgA and lactoferrin levels in toddlers who were given EBF with ARI frequency <2 times and toddlers who were given EBF with ARI frequency ≥2 times. Toddlers who were exclusively breastfed with ARI frequency <2 times had higher levels of sIgA and lactoferrin (188901.77 pg/ml and 262.32 ng/ml, respectively) compared to infants given EBF with ARI frequency ≥2 times (136683.47 pg/ml and 181.49 ng/ml, respectively). History of immunization was also significantly (p-value <0.05) associated with levels of sIgA and lactoferrin in infants with ARI. The content of sIgA and lactoferrin in breast milk and immunization can increase the body's immune system in toddlers suffering from ARI.

Differences in Bacterial Colonization and Mucosal Responses Between High and Low SES Children in Indonesia.

BACKGROUND: Increased nasopharyngeal carriage of pathogenic bacteria is found in low socioeconomic status (SES) settings. How SES affects local immune responses, important for controlling colonization, is currently unknown. OBJECTIVE: Examining bacterial colonization and cytokine response in the nasal mucosa of children from high and low SES. METHODS: Nasosorption samples were collected in October 2019 from 48 high SES and 50 low SES schoolchildren, in a cross-sectional study in Makassar, Indonesia. Twenty-five cytokines were measured in nasal fluid. Quantitative polymerase chain reaction was performed to determine carriage and density of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and Staphylococcus aureus. Data were analyzed using multivariate regression. RESULTS: H. influenzae and S. pneumoniae densities were increased in low SES settings compared to the high SES settings (P = 0.006, P = 0.026), with 6 and 67 times higher median densities, respectively. Densities of H. influenzae and S. pneumoniae were positively associated with levels of IL-1beta and IL-6. After correcting for bacterial density, IL-6 levels were higher in colonized children from high SES than low SES for H. influenzae and S. pneumoniae (both P = 0.039). CONCLUSION: Increased densities of H. influenzae and S. pneumoniae were observed in low SES children, whereas IL-6 levels associated with colonization were reduced in these children, indicating that immune responses to bacterial colonization were altered by SES.

Intestinal permeability before and after albendazole treatment in low and high socioeconomic status schoolchildren in Makassar, Indonesia.

Intestinal helminths are highly prevalent in low-SES children and could contribute to poor health outcomes either directly or via alteration of the gut microbiome and gut barrier function. We analysed parasitic infections and gut microbiota composition in 325 children attending high- and low-SES schools in Makassar, Indonesia before and after albendazole treatment. Lactulose/Mannitol Ratio (LMR, a marker of gut permeability); I-FABP (a surrogate marker of intestinal damage) as well as inflammatory markers (LBP) were measured. Helminth infections were highly prevalent (65.6%) in low-SES children. LMR and I-FABP levels were higher in low-SES children (geomean (95%CI): 4.03 (3.67-4.42) vs. 3.22 (2.91-3.57); p. adj < 0.001; and 1.57 (1.42-1.74) vs. 1.25 (1.13-1.38); p. adj = 0.02, respectively) while LBP levels were lower compared to the high-SES (19.39 (17.09-22.01) vs. 22.74 (20.07-26.12); p.adj = 0.01). Albendazole reduced helminth infections in low-SES and also decreased LMR with 11% reduction but only in helminth-uninfected children (estimated treatment effect: 0.89; p.adj = 0.01). Following treatment, I-FABP decreased in high- (0.91, p.adj < 0.001) but increased (1.12, p.adj = 0.004) in low-SES children. Albendazole did not alter the levels of LBP. Microbiota analysis showed no contribution from specific bacterial-taxa to the changes observed. Intestinal permeability and epithelial damage are higher while peripheral blood inflammatory marker is lower in children of low-SES in Indonesia. Furthermore, treatment decreased LMR in helminth-uninfected only.

Preeclampsia and normotensive pregnancy with tribal differences in South Sulawesi: Comparison of serum interleukin-10 (IL-10) levels.

OBJECTIVE: This study aims to compare the average levels of IL-10 with preeclampsia and normotensive in four different tribe populations in South Sulawesi, including Makassar, Bugis, Mandar, and Toraja. METHOD: This research is a cross-sectional study conducted in March-May 2020 in several Health Centre and Hospitals in four areas, namely in the UNHAS Hospital, Jumpandang Baru Health Center, Barabaraya Health Center, Mattirobulu Health Center, Salo Health Center, Lasinrang Pinrang General Hospital, Totoli Health Center, Majene Regional General Hospital, Makale Health Center, Elim General Hospital, Lakipadada Tana Toraja Regional General Hospital. Samples in this study were 88 pregnant women with gestational age >20 weeks which were divided into two groups, namely 44 cases (preeclampsia) and 44 control groups (normotensive). The criteria for the sample in this study are single pregnancy, no systemic disease, and are native Makassar, Bugis, Mandar, and Toraja tribes. Data collected included age, education, occupation, parity, Body Mass Index (BMI), history of preeclampsia. Serum IL-10 levels were examined using the Human Interleukin 10 ELISA Kit. RESULTS: There were significant differences in IL-10 levels in preeclampsia pregnant women in the Makassar, Bugis, Mandar, and Toraja tribes (p=0.020, p<0.05). In contrast to the control group, there was no difference in IL-10 levels in normotensive pregnant women in the Makassar, Bugis, Mandar, and Toraja tribes (p=0.505, p>0.05). The Bugis, Mandar, and Toraja tribes show significant differences in IL-10 levels between preeclampsia pregnant women and normotensive pregnant women with mean rating values of pregnant women who have preeclampsia have lower IL-10 levels than normotensive pregnant women, while the Makassar tribe has valued insignificant difference in IL-10 levels between preeclampsia and normotensive (p=0.309, p>0.05). CONCLUSION: There are differences in IL-10 levels in preeclampsia pregnant women in Makassar, Bugis, Mandar, and Toraja tribes. The mean concentration of IL-10 in pregnant women with preeclampsia was significantly lower than in controls.

Activity of the Toll-like receptor ligands in children with high and low socioeconomic backgrounds.

BACKGROUND: Adjuvants are essential in the induction of immunity by vaccines and interact with receptors, including the Toll-like receptors (TLRs). Responsiveness of these receptors differs between and within populations, which impacts vaccine effectiveness. OBJECTIVE: Here we examine how the innate cytokine response towards TLR ligands differs between high and low socioeconomic status (SES) school-aged children from Makassar, Indonesia. METHODS: We stimulated whole blood from children, of which 27 attended a high SES school and 27 children a low SES school, with ligands for TLR-2/1, -2/6, -3, -4, -5, -7, -9 and measured pro- (TNF) and anti-inflammatory (IL-10) cytokines released. RESULTS: In the low SES there is an increased pro-inflammatory response after 24 h stimulation with TLR-2/1 ligand Pam3 and TLR-4 ligand LPS compared to the high SES. Comparison of the response to LPS after 24 h versus 72 h stimulation revealed that the pro-inflammatory response in the low SES after 24 h shifts to an anti-inflammatory response, whereas in the high SES the initial anti-inflammatory response shifts to a strong pro-inflammatory response after 72 h stimulation. CONCLUSION: We observed differences in the TLR-mediated innate immune response between children attending low and high SES schools, which can have important implications for vaccine development.

Seroprevalence and associated risk factors of Toxoplasma gondii infection among pregnant mother in Makassar, Indonesia.

The protozoan parasite, Toxoplasma gondii is estimated to infect one-third of the world's population. Infection in pregnant women can cause severe conditions for their babies. Until now, there is no data regarding Toxoplasma infection from Makassar pregnant mothers. This study aims to obtain information on Toxoplasma specific antibodies and to measure the risk factor associate with parasite infection. This cross-sectional study conducted in 9 of 47 primary health centres (Puskesmas) in Makassar. Blood samples and questionnaires were collected from 184 pregnant women aged 15-42 years old from September to October 2020. ELISA technique was used to examine the IgG and IgM antibodies. Univariable and multivariable analyses were carried out to measure factors that independently associate with Toxoplasma antibody positivity. Our result showed the range of Toxoplasma IgM and IgG are 0.06-1.01 and 0.09-3.01, respectively. While no one of our participants has an acute Toxoplasma gondii infection (IgM positive), we found 32,6% pregnant mothers are exposed to parasite (positive IgG). Contact with cats [OR(95%CI): 10.45(3.77-28.99)], consume chicken satay [OR(95%CI): 9.72(3.71-25.48)] and consume un-boiled water/ filtered water [OR(95%CI): 5.98(1.77-20.23)] are independently associate with positive Toxoplasma IgG antibody. Based on the result, we conclude that pregnant women in Makassar are exposed to T. gondii and the oocyst and tissue cyst of parasite contaminates food and water in Makassar.

Bee- and Wasp-Venom Sensitization in Schoolchildren of High- and Low-Socioeconomic Status Living in an Urban Area of Indonesia.

BACKGROUND: There is not much known about venom allergy in tropical regions. Here, we studied the prevalence of specific IgE (sIgE) and skin prick test (SPT) reactivity and reported sting-related symptoms, in high- and low-socioeconomic status (SES) schoolchildren living in urban city of Makassar in Indonesia. METHODS: Children from high- (n = 160) and low- (n = 165) SES schools were recruited. Standardized questionnaires were used to record information on allergic disorders as well as sting-related symptoms. Parasitic infection, SPT reactivity, and sIgE to Apis mellifera (bee-venom) as well as Vespula spp. (wasp-venom) were assessed. RESULTS: SPT reactivity to bee- and wasp-venom was 14.3 and 12.7%, while the prevalence of sIgE was 26.5 and 28.5%, respectively. When SES was considered, prevalence of SPT to bee- and wasp-venom was higher in high-SES than in low-SES schoolchildren (bee: 22.8 vs. 5.7%, p < 0.001; and wasp: 19.6 vs. 5.7%, p < 0.001). Conversely, sIgE to both venoms was lower in high-SES than in low-SES (bee: 19 vs. 34%, p = 0.016; and wasp: 19 vs. 38%, p = 0.003). Furthermore, among SPT positive subjects, considerable proportion had no detectable sIgE to bee- (65.85%) or wasp-venom (66.67%). Altogether the sensitizations were rarely translated into clinical reaction, as only 1 child reported significant local reaction after being stung. No association with parasitic infections was found. CONCLUSIONS AND CLINICAL RELEVANCE: Sensitization against bee- or wasp-venom is quite prevalent among schoolchildren in Indonesia. The discordance between SPT and sIgE might suggest the direct (non-IgE) effect of venoms in skin reactivity. Recorded sensitizations had poor clinical relevance as they rarely translated into clinical symptoms.

The relationship between malnutrition and TH 2 immune markers: a study in school-aged children of different socio-economic backgrounds in Makassar, Indonesia.

OBJECTIVE: The burden of underweight remains a major problem in Indonesia, and at the same time, the prevalence of overweight is increasing. Malnutrition is a major determinant of health and has been linked to allergic disorders in children. We examined the relationship between malnutrition and TH 2 immune markers in school-aged children in Makassar, Indonesia. METHODS: A cross-sectional study was performed in five schools where socio-demographic characteristics were recorded. Children's standardised z-scores of body mass index (z-BMI) and age-standardised z-scores of height (z-HA) were assessed using WHO child growth standards. Skin prick test (SPT) reactivity was determined to house dust mite allergens. Helminth infection status, (growth) hormones including insulin-like growth factor (IGF-1) and TH 2 immune markers were measured. RESULTS: In total, 954 children were included of whom 21.6% were underweight and 14.8% overweight. After controlling for confounders, overweight was positively associated with leptin (GMR 3.55, 95% CI: 2.99-4.23) and IGF-1 (GMR 1.45, 95% CI: 1.15-1.82), whereas underweight was negatively associated (respectively GMR 0.57, 95% CI: 0.49-0.66 and GMR 0.78, 95% CI: 0.63-0.97). Underweight was associated with a lower eosinophil count (GMR 0.79, 95% CI: 0.64-0.97) but not with total IgE levels or SPT reactivity. Overweight was positively associated with SPT reactivity (adjusted OR 2.68, 95% CI: 1.50-4.78) but no relationship was found with the other TH 2 immune markers. CONCLUSION: Malnutrition is prominent in school-aged children in Makassar, with overweight associated with increased SPT reactivity. Therefore, interventions should focus on undernutrition, but also on overweight to prevent the increase of allergic disorders in Indonesia.

OBJECTIF: La charge de l'insuffisance pondérale reste un problème majeur en Indonésie et parallèlement, la prévalence du surpoids augmente. La malnutrition est un déterminant majeur de la santé et a été associée à des troubles allergiques chez les enfants. Nous avons examiné la relation entre la malnutrition et les marqueurs immunitaires TH 2 chez les enfants d'âge scolaire à Makassar, en Indonésie. MÉTHODES: Etude transversale dans cinq écoles où les caractéristiques sociodémographiques ont été enregistrées. Les scores z standardisés de l'indice de masse corporelle (z-IMC) et les scores z standardisés pour l'âge de la taille (z-HA) pour les enfants ont été évalués en utilisant les normes de croissance de l'enfant de l'OMS. La réactivité du test cutané (SPT) a été déterminée pour les allergènes d'acariens. L'état de l'infection par les helminthes, les hormones (de croissance), y compris le facteur de croissance analogue à l'insuline (IGF-1) et les marqueurs immunitaires TH 2 ont été mesurés. RÉSULTATS: Au total, 954 enfants ont été inclus, dont 21,6% en insuffisance pondérale et 14,8% en surpoids. Après contrôle des facteurs de confusion, le surpoids était positivement associé à la leptine (GMR 3,55, IC95%: 2,99-4,23) et à l'IGF-1 (GMR 1,45 ; IC95%: 1,15-1,82), tandis que l'insuffisance pondérale était associée négativement (respectivement GMR 0,57 ; IC95%: 0,49-0,66 et GMR 0,78 ; IC95%: 0,63-0,97). L'insuffisance pondérale était associée à un nombre plus faible d'éosinophiles (GMR 0,79 ; IC95%: 0,64-0,97) mais pas aux taux d'IgE totaux ou à la réactivité du SPT. Le surpoids était positivement associé à la réactivité du SPT (OR ajusté 2,68 ; IC95%: 1,50-4,78) mais aucune relation n'a été trouvée avec les autres marqueurs immunitaires T H 2. CONCLUSION: La malnutrition est importante chez les enfants d'âge scolaire à Makassar, avec un surpoids associé à une réactivité accrue du SPT. Par conséquent, les interventions devraient se concentrer sur la dénutrition, mais aussi sur le surpoids pour prévenir l'augmentation des troubles allergiques en Indonésie.

The Bacterial Gut Microbiota of Schoolchildren from High and Low Socioeconomic Status: A Study in an Urban Area of Makassar, Indonesia.

To understand the relationship between the gut microbiota and the health profile of Indonesians, it is important to elucidate the characteristics of the bacterial communities that prevail in this population. To this end, we profiled the faecal bacterial community of 140 Indonesian schoolchildren in urban Makassar. The core microbiota of Indonesian schoolchildren consisted of Bifidobacterium, Collinsella, and multiple members of the Lachnospiraceae and Ruminicoccaceae families, but the relative abundance of these taxa varied greatly among children. Socioeconomic status (SES) was the main driver for differences in microbiota composition. Multiple bacterial genera were differentially abundant between high and low SES children, including Bifidobacterium, Lactobacillus, Prevotella, and Escherichia-Shigella. In addition, the microbiota of high SES children was less diverse and strongly associated with body mass index (BMI). In low SES children, helminth infection was prevalent and positively associated with Olsenella, Enterohabdus, Lactobacillus, and Mogibacterium abundance, while negatively associated with relative abundance of Prevotella. Protozoa infection was also prevalent, and positively associated with Rikenellaceae, while it was negatively associated with the relative abundance of Romboutsia and Prevotella. In conclusion, Indonesian schoolchildren living in urban Makassar share a core microbiota, but their microbiota varies in diversity and relative abundance of specific bacterial taxa depending on socioeconomic status, nutritional status, and intestinal parasites infection.

BCG scar, socioeconomic and nutritional status: a study of newborns in urban area of Makassar, Indonesia.

OBJECTIVE: To investigate factors that determine the response to Bacille Calmette-Guérin (BCG) vaccination in urban environments with respect to socioeconomic status (SES), prenatal exposure to infections or newborn's nutritional status. METHODS: The study was conducted in an urban area, in Makassar, Indonesia. At baseline, 100 mother and newborns pair from high and low SES communities were included. Intestinal protozoa, soil transmitted helminths, total IgE, anti-Hepatitis A Virus IgG and anti-Toxoplasma IgG were measured to determine exposure to infections. Information on gestational age, birth weight/height and delivery status were collected. Weight-for-length z-score, a proxy for newborns adiposity, was calculated. Leptin and adiponectin from cord sera were also measured. At 10 months of age, BCG scar size was measured from 59 infants. Statistical modelling was performed using multiple linear regression. RESULTS: Both SES and birth nutritional status shape the response towards BCG vaccination at 10 months of age. Infants born to low SES families have smaller BCG scar size compared to infants born from high SES families and total IgE contributed to the reduced scar size. On the other hand, infants born with better nutritional status were found to have bigger BCG scar size but this association was abolished by leptin levels at birth. CONCLUSION: This study provides new insights into the importance of SES and leptin levels at birth on the development of BCG scar in 10 months old infants.

OBJECTIF: Investiguer les facteurs qui déterminent la réponse à la vaccination par le BCG en milieu urbain en ce qui concerne le statut socioéconomique (SSE), l'exposition prénatale aux infections ou l'état nutritionnel du nouveau-né. MÉTHODES: L'étude a été menée dans une zone urbaine, à Makassar, en Indonésie. Au départ, 100 paires mère-nouveau-né issues de communautés à statut social élevé et faible ont été incluses. Les protozoaires intestinaux, les helminthes transmis par le sol, les IgE totales, les IgG anti-virus de l'hépatite A et anti- Toxoplasma ont été mesurés pour déterminer l'exposition aux infections. Des informations sur l'âge gestationnel, le poids/taille à la naissance et l'état d'accouchement ont été collectées. Le z-score poids-pour la taille, un indicateur indirect de l'adiposité du nouveau-né a été calculé. La leptine et l'adiponectine provenant de sérum des cordons ont également été mesurées. A l'âge de 10 mois, la taille des cicatrices de BCG a été mesurée chez 59 nourrissons. La modélisation statistique a été réalisée à l'aide d'une régression linéaire multiple. RÉSULTATS: Le statut socioéconomique et l'état nutritionnel à la naissance déterminent la réponse à la vaccination par le BCG à l'âge de 10 mois. La taille des cicatrices de BCG est plus petite chez les nourrissons nés de familles à statut socioéconomique faible comparée à celles chez ceux de familles à statut socioéconomique élevé et les IgE totales ont contribué à la réduction de la taille de ces cicatrices. En revanche, les bébés nés avec un meilleur état nutritionnel avaient une taille de cicatrice du BCG plus grande, mais cette association était supprimée par les niveaux de leptine à la naissance. CONCLUSION: Cette étude fournit de nouvelles informations sur l'importance du SSE et des niveaux de leptine à la naissance sur le développement d'une cicatrice du BCG chez des nourrissons âgés de 10 mois.

Genomic analysis and growth characteristic of dengue viruses from Makassar, Indonesia.

Dengue fever is currently the most important mosquito-borne viral disease in Indonesia. In South Sulawesi province, most regions report dengue cases including the capital city, Makassar. Currently, no information is available on the serotypes and genotypes of the viruses circulating in the area. To understand the dynamic of dengue disease in Makassar, we carried out dengue fever surveillance study during 2007-2010. A total of 455 patients were recruited, in which antigen and serological detection revealed the confirmed dengue cases in 43.3% of patients. Molecular detection confirmed the dengue cases in 27.7% of patients, demonstrating that dengue places a significant disease burden on the community. Serotyping revealed that dengue virus serotype 1 (DENV-1) was the most predominant serotype, followed by DENV-2, -3, and -4. To determine the molecular evolution of the viruses, we conducted whole-genome sequencing of 80 isolates. Phylogenetic analysis grouped DENV-2, -3 and -4 to the Cosmopolitan genotype, Genotype I and Genotype II, respectively. Intriguingly, each serotype paints a different picture of evolution and transmission. DENV-1 appears to be undergoing a clade replacement with Genotype IV being supplanted by Genotype I. The Cosmopolitan DENV-2 isolates were found to be regionally endemic and is frequently being exchanged between countries in the region. By contrast, DENV-3 and DENV-4 isolates were related to strains with a long history in Indonesia although the DENV-3 strains appear to have been following a distinct evolutionary path since approximately 1998. To assess whether the various DENV serotypes/genotypes possess different growth characteristics, we performed growth kinetic assays on selected viruses. We observed the relatively higher rate of replication for DENV-1 and -2 compared to DENV-3 and -4. Within the DENV-1, viruses from Genotype I grow faster than that of Genotype IV. This higher replication rate may underlie their ability to replace the circulation of Genotype IV in the community.

Antibody response against three Plasmodium falciparum merozoite antigens in Mamuju District, West Sulawesi Province, Indonesia.

BACKGROUND: Malaria endemicity in the archipelago of Indonesia varies substantially across regions. Following the government's plan for a malaria elimination programme in Indonesia, baseline malaria surveys were conducted in Mamuju District, West Sulawesi Province, Indonesia to re-assess the malaria situation prior to the establishment of an evidence-based malaria elimination programme in the area. The present study aims to determine the antibody response to three merozoite antigens among the inhabitants of the district. METHODS: Antibodies were measured following elution from filter-paper blood spots collected during cross-sectional surveys in the dry and wet season in 2010. Enzyme-linked immunosorbent assays using three merozoite antigens, MSP2, EBA175 and PfRh2a were conducted. A positivity threshold was determined by samples from unexposed individuals and the difference in antibody level against each antigen and correlation of antibody level in different age groups and seasons were statistically analysed. RESULTS: A total of 497 subjects, 248 in dry and 249 in wet season, aged between 0.6 and 78 years were included. The prevalence of positive antibody responses to MSP2, EBA175 and PfRh2a antigens in dry season were 27.82, 27.42 and 25.81%, respectively. In wet season, the antibody prevalences were 64.26, 64.66 and 61.45%. The antibody levels to the three antigens were all higher in older age groups and also significantly higher in the wet season. The antibody levels also correlated positively with the Plasmodium falciparum infection status of the subjects. CONCLUSION: MSP2, EBA175 and PfRh2a induce antibody responses among the subjects in Mamuju District, and the prevalence is significantly higher in wet season. The level of antibody also correlates significantly with age and malaria positivity. The overall results indicate the antigens might be used as a target for vaccines against P. falciparum infection and as markers for malaria exposure.

Real-time PCR detection of the HhaI tandem DNA repeat in pre- and post-patent Brugia malayi Infections: a study in Indonesian transmigrants.

BACKGROUND: Lymphatic filariasis caused by Wuchereria bancrofti or Brugia spp. is a public health problem in developing countries. To monitor bancroftian filariasis infections, Circulating Filarial Antigen (CFA) test is commonly used, but for brugian infections only microfilariae (Mf) microscopy and indirect IgG4 antibody analyses are available. Improved diagnostics for detecting latent infections are required. METHODS: An optimized real-time PCR targeting the brugian HhaI repeat was validated with plasma from microfilariae negative Mongolian gerbils (jirds) infected with B. malayi. Plasma samples from microfilaremic patients infected with B. malayi or W. bancrofti were used as positive and negative controls, respectively. PCR results of plasma samples from a transmigrant population in a B. malayi endemic area were compared to those of life-long residents in the same endemic area; and to IgG4 serology results from the same population. To discriminate between active infections and larval exposure a threshold was determined by correlation and Receiver-Operating Characteristics (ROC) curve analyses. RESULTS: The PCR detected HhaI in pre-patent (56 dpi) B. malayi infected jirds and B. malayi Mf-positive patients from Central Sulawesi, Indonesia. HhaI was also detected in 9/9 elephantiasis patients. In South Sulawesi 87.4% of the transmigrants and life-long residents (94% Mf-negative) were HhaI PCR positive. Based on ROC-curve analysis a threshold for active infections was set to >53 HhaI copies/µl (AUC: 0.854). CONCLUSIONS: The results demonstrate that the HhaI PCR detects brugian infections with greater sensitivity than the IgG4 test, most notably in Mf-negative patients (i.e. pre-patent or latent infections).

Risk Factors Associated with the Development of Atopic Sensitization in Indonesia.

BACKGROUND: The prevalence of allergic diseases has increased not only in high income but also in low-to-middle income countries. However, risk factors for their development are still not well established, particularly in the latter. OBJECTIVE: To assess prevalence and identify risk factors for sensitization to two major inhalant allergens among children from semi-urban and rural areas in Indonesia. METHOD: A cross-sectional survey was performed among 1,674 school children aged 5-15 years old. Information on potential risk factors and reported allergic symptoms were obtained by questionnaire. Helminth infections were assessed. Skin prick tests (SPT) were performed, total IgE as well as allergen-specific IgE for house dust mite (HDM) and cockroach were measured. RESULT: The prevalence of allergic skin sensitization to both aeroallergens was significantly higher in the semi-urban than in the rural area. However, serum IgE against HDM and cockroach as well as total IgE were significantly lower in semi-urban than in rural children. In the semi-urban area, there was a significant positive association between SPT to HDM and higher paternal education but a negative one with hookworm infection. The risk factors linked to cockroach sensitization were different: being of a farmer offspring and lacking access to piped water were associated with an increased risk for a positive SPT to cockroach. No significant associations between measured risk factors and having a positive SPT were found in the rural area. CONCLUSION: Sensitization to HDM and cockroach is common in Indonesia, more often translating into a positive SPT in the semi-urban than in the rural setting. Whereas high paternal education and low hookworm infection were associated with increased risk of SPT to HDM, we were surprised to find parameters of lower SES were identified as risk factor for cockroach SPT.

The effect of three-monthly albendazole treatment on malarial parasitemia and allergy: a household-based cluster-randomized, double-blind, placebo-controlled trial.

BACKGROUND: Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy. METHODS AND FINDINGS: A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5-15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35-12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74-1.86) at 9 months or 1.37 (0.93-2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported. CONCLUSIONS: The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN83830814.

A longitudinal study of allergy and intestinal helminth infections in semi urban and rural areas of Flores, Indonesia (ImmunoSPIN Study).

BACKGROUND: The prevalence of asthma and atopic disease has been reported to be low in low income countries, however helminth infections are likely to be high among these communities. The question of whether helminth infections play a role in allergic diseases can best be addressed by intervention studies. None of the studies so far have been based on a large scale placebo-controlled trial. METHOD/DESIGN: This study was designed to assess how intestinal helminth infections can influence the immune response and atopic and allergic disorders in children in Indonesia. The relations between allergic outcomes and infection and lifestyle factors will be addressed. This study was set up among school-age children in semi urban and rural areas, located in Ende District of Flores Island, Indonesia. A randomized placebo-controlled anthelmintic treatment trial to elucidate the impact of helminth infections on the prevalence of skin prick test (SPT) reactivity and symptoms of allergic diseases will be performed. The children living in these semi-urban and rural areas will be assessed for SPT to allergens before and after 1 and 2 years of treatment as the primary outcome of the study; the secondary outcome is symptoms (asthma and atopic dermatitis); while the tertiary outcome is immune responses (both antibody levels to allergens and cellular immune responses). DISCUSSION: The study will provide information on the influence of helminth infections and anthelmintic treatment on immune response, atopy and allergic disorders. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: ISRCTN83830814.