DNA Sequence Analysis Of HB-EGF And CD9 Genes In Diphtheria Carriers And Patients In Indonesia

Abstract. Diphtheria infection is a serious health problem in Indonesia. There is little data regarding the role of human genetic variability on the diphtheria infection. There is also limited information in the literature regarding the comparison between diphtheria patients and carrier state. We aimed to compare the deoxyribonucleic acid (DNA) sequences of heparin binding-epidermal growth factor (HB-EGF) and cluster of differentiation 9 (CD 9) genes between diphtheria carriers and those infected with diphtheria. We searched the databases of the East Java Provincial Health Office and the Main Health Laboratory to identify diphtheria infection patients and carriers aged ≤18 years during 1 January 2012-30 August 2015. Each study participant was interviewed, had anthropometrical measurements obtained and blood was drawn for DNA sequencing of 2 genes coding for receptors and co-receptors of the diphtheria toxin, HB-EGF and CD9, and antibody titers against Corynebacterium diphtheriae. A total of 28 carriers and 97 patients with a history of diphtheria infection during the study period were included in the study. Silent mutations of codon 91 of exon 3 of the HB-EGF gene were found in 5 diphtheria carriers and 21 diphtheria cases, and of codons 171 and 173 of exon 6 of the CD9 gene in 1 carrier and 2 cases. We also found silent mutation of intron 5, position 35719 of the CD9 gene in 16 carriers and 39 cases. Statistical analysis showed no significant differences in the frequencies of mutations of exon 3 of the HB-EGF gene and exons 5 and 6 of the CD9 gene between carriers and cases. However, significantly more carriers had the mutation of intron 5 of the CD9 gene than cases. We concluded the genetic variability of the DT receptors in human was limited

Staphylococcal Scalded Skin Syndrome in a Neonate (Lyly Ekawati Candra, Fatimah Indarso, Ismoedijanto, Ariyanto Harsono) 249 Case Report: STAPHYLOCOCCAL SCALDED SKIN SYNDROME IN A NEONATE

ABSTRAC

An evaluation of the clinical features of measles virus infection for diagnosis in children within a limited resources setting

Background Measles is a recurrent health problem in both advanced and developed countries. The World Health Organization (WHO) recommends anti-measles immunoglobulin M (Ig M) as the standard method of detecting the virus; however, many areas still present the inability to perform a serology test of anti-measles IgM. Therefore, a typical clinical feature is necessary to establish the diagnosis of measles. The objective of this study was to evaluate hyperpigmented rash and other clinical features as the diagnostic tools with respect to measles, especially in an outbreak setting. Methods In this observational diagnostic study, the inclusion criteria were as follows: between 6 and 144 months of age, fever, maculopapular rash for 3 days or more, accompanied by a cough, or coryza, or conjunctivitis. Those with a prior history of measles vaccination (1–6 weeks) were excluded, in addition to those with histories of corticosteroid for 2 weeks or more and immunocompromised conditions. The samples were taken from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia. We evaluated the sensitivity, specificity, the positive predictive value, and the negative predictive value of such clinical features. Hyperpigmented rash was validated using Kappa and Mc Nemar tests. Anti-measles Ig M was considered as the gold standard. Results This study gathered 82 participants. The clinical manifestations of all subjects included fever, cough, coryza, conjunctivitis, Koplik spots, and maculopapular rash (which turns into hyperpigmented rash along the course of the illness). Most maculopapular rashes turn out to be hyperpigmented (89%). Sensitivity, specificity, positive predictive value, and negative predictive values ​​of the combination of fever, maculopapular rash, and hyperpigmented rash were found to be at 90.7, 28.6, 93.2, and 22.2%, respectively. The Mc Nemar and Kappa tests showed p values of 0.774 and 0.119, respectively. Conclusion The combination of fever, maculopapular rash, and hyperpigmented rash can be used as a screening tool regarding measles infection in an outbreak setting, which can then be confirmed by anti-measles Ig M. Cough, coryza, and Koplik’s spot can be added to this combination, albeit with a slight reduction of sensitivity value

The Outcomes of Infants with HIV Infected Mother in a Tertiary Hospital in Indonesia

Background: Infant from HIV mother face the risk of HIV infection. Effective prevention on mother-tochild transmission (PMTCT) program increasing the number of uninfected infants in East Java Indonesia. This study describes the outcomes of infants with HIV mother in Dr. Soetomo Hospital, a tertiary referral hospital in East Java, related to outcome (infectious morbidity, nutritional status, immunodeficiency status, growth/development, and incidence of anemia). Method: This cross-sectional study analyzed 0-18 months infant and HIV mother pairs at HIV outpatient clinic Dr. Soetomo General Hospital from January to April 2017. The data were collected and analyzed using Fisher’s exact test and chi-square test with P<0.05. Results: Fourty HIV-infected mothers and infants pairs were analyzed, separated into two groups positive (3 infants) and negative (37 infants) Anti HIV PCR. There were 19 male. Age distribution (6 weeks-5 months 40%; 6-11 months 47.5%; 12-18 months 12.5%). Five percent were born prematurely, 77.5% infant has normal birth-weight. Only 2.5% were fed breast milk, AZT-cotrimoxazole were given to 87.5% infant while the rest received AZT/3TC/NVP. Immunizations of the infants were mostly (60%) up to date. Infectious morbidity (P=0.433), WAZ-score (P=0.666), LAZ-score (P=0,973), WLZ-score (P=0.219) and incidence of anemia (P=0.548) were not significant differences between groups. The development test using DDST II (P=0,001), as well as immunodeficiency status [presence of immunodeficiency (P<0.001)] was significantly different between groups. Conclusion: There were significant effects of HIV exposed on the development and immunodeficiency status in 0-18 months infant

Antidiphtheria Antibody of Patients and Carriers Several Years after the Illness in Indonesia

Diphtheria is a lethal disease and toxin is the most important instrument of pathogenicity. Antidiphtheria antibody plays a role in determining someone to be healthy, carriers, or be ill. Diphtheria infection will not provide a sufficient antibody level to the patient few months or years after. This study aimed to determine anti-diphtheria antibody level of individuals several years after someone being patients or carriers. The participants of this cross-sectional study were all diphtheria carriers and patients aged < 18 years in East Java Province Indonesia from the period of 2011-2015. The record was obtained from East Java Provincial Health Office. Subjects were visited, interviewed, and underwent physical examinations. Blood samples were obtained and the anti-diphtheria antibody level was determined using the Vero cell method. The result was then modified using WHO criteria. Data analysis used Mann-Whitney U, Kruskal-Wallis, and Chi-Square tests as appropriate with p<0.05 and 95% confidence interval considered as significant. Among 25 carriers and 88 patients from 21 districts in the study, mostly above five-year-olds, only 11% carriers and 6% patients received three times immunization after the period of illness, indicating that the follow up by health care officers was not satisfactory. The antibody levels of the patients were significantly different from the carriers along with a prevalence ratio of 1.26 if the antibody was at a susceptible level. There were 8% carriers and 20% patients in the susceptible group. In conclusion, six months to 3.5 years after having the illness, diphtheria patients remained to have lower anti-diphtheria antibody levels as compared to the carriers

First-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae in Indonesia

Background Diphtheria has been reported as an outbreak in some regions in Indonesia, most especially in East Java Province. Resistance to penicillin, erythromycin, and other antibiotics, single or multiple, has been reported in several studies. This study aims to evaluate the first-line antibiotic susceptibility pattern of toxigenic Corynebacterium diphtheriae isolates. Methods This descriptive observational study was performed from August to November 2018. C. diphtheriae isolates were collected from diphtheria patients and carriers in East Java from 2012 to 2017 and kept at the Balai Besar Laboratorium Kesehatan Daerah Surabaya or the Public Health Laboratory of Surabaya. Sample selection was done by random cluster sampling. The sensitivity test by E-test®of the five antibiotics (penicillin, oxacillin, erythromycin, azithromycin, and clarithromycin) was done to determine the minimum inhibitory concentration (MIC). The Clinical and Laboratory Standards Institute M45A (2015) Corynebacterium spp. for penicillin and erythromycin was used as standard. Results From 114 targeted isolates, 108 were viable and toxigenic. The E-test was performed on the viable isolates. The majority of the hosts were male (58.3%), with median (range) age of 6.5 (1–14) years. Half of the samples were from the 1 to 5-year-old age group. The isolates were acquired much more from patients (78.7%) than carriers (21.3%) and from pharyngeal swab (74.1%). Most of these isolates were from Madura Island (47.2%) and the northern and eastern parts of the province (horseshoe area). Mitis isolates were the major variant (76.9%). The susceptibility pattern of C. diphtheriae to erythromycin was better than that to penicillin. The E-test result for penicillin was 68.52% susceptible, 31.48% intermediate, and 0% resistant (MIC range,  256 μg/L) was 85.2% susceptible, 12% intermediate, and 2.8% resistant The MIC range for oxacillin was 1 to 96 μg/L, while for both azithromycin and clarithromycin were  256 μg/L. Conclusion The susceptibility rate of C. diphtheriae to erythromycin is higher than that to penicillin. The regular update of antibiotic selection to the national guidelines is recommended. The MIC reference standard to azithromycin and clarithromycin is also needed

Diphtheria di Jawa Timur

Imunisasi primer bermanfaat untuk membuat bayi kebal terhadap penyakit menular pada masa-masa permulaan kehidupan. Setelah cakupan imunisasi dasar telah mencapai 80%, perlu imunisasi ulangan agar anak tetap terjaga kekebalannnya. Adanya Kejadian Luar Biasa (KLB) diphtheria di NIS (New Independent States, bekas negara bagian Rusia) dan juga di daerah padat pemukiman di Jawa, menunjukkan adanya masalah kekebalan pada anak dan dewasa. Kelompok anak tanpa kekebalan atau dengan kekebalan rendah terdiri dari kelompok yang sejak bayi tidak mendapat imunisasi sama sekali atau tidak lengkap dan kelompok yang kekebalannya menurun setelah beberapa waktu. Dengan cakupan imunisasi yang tinggi, kelompok ini lolos menjadi kelompok usia tua tanpa terpapar dengan kuman, tidak menderita penyakit diphtheri subklinis tetapi tetap rentan terhadapdiphtheria. Kasus di Jawa Timur mulai muncul pada tahun 2005, dengan adanya KLB di Bangkalan. Dengan surveilans yang aktif&nbsp;intensif didapatkan adanya kenaikan jumlah kasus per tahun yang makin meningkat cepat dan pada tahun 2012 telah mencapai 956 kasus. Kenaikan kasus menunjukkan adanya sesuatu pada pelayanan kesehatan terutama program imunisasi kita. Selain suntikan primer untuk menimbulkan kelompok serokonversi, toksoid difteri dan tetanus perlu diulangi beberapa kali agar anak tetap kebal. Booster ini juga diharapkan akan menutup kekebalan kelompok anak yang tidak kebal akibat tertinggal pada putaran imunisasi primer. Sangat penting menjaga agar cakupan DTP tinggi dan merata, tanpa adanya kantong non kebal di setiap kabupate

Demam pada Anak

Demam pada anak merupakan salah satu masalah yang masih relevan untuk para praktisi pediatri. Demam merupakan tanda adanya kenaikan set-point di hipotalamus akibat infeksi atau adanya ketidakseimbangan antara produksi dan pengeluaran panas. Sebaliknya tidak semua anak yang terkena infeksi akan menunjukkan gejala demam, semakin muda umurnya, semakin tidak jelas gambaran klinisnya. Tindakan pada anak dengan demam diawali dengan pertimbangan apakah ada kegawatan, apa penyebabnya dan apakah demam perlu segera diturunkan. Agar tindakan tersebut tepat dan terarah, diperlukan suatu pengelompokan / klasifikasi pasien agar dapat digunakan suatu algoritma umum. Pada tiap kelompok tetap ada kriteria kegawatan, kriteria jenis infeksi yang mengarah kepada tindakan yang diambil, terutama perawatan dan pemberian antibiotik secara empirik. Tindakan yang dilaksanakan sebaiknya bukan tindakan yang sifatnya sesaat, tetapi merupakan tindakan yang berkesinambungan, sampai pasien lepas dari masalahnya. Keputusan untuk dirawat harus dilanjutkan dengan pemeriksaan laboratorium dan pemberian antibiotik empirik. Tindakan lanjutan akan disesuaikan dengan hasil pemeriksaan penunjang, respons pasien terhadap pengobatan sampai masalahnya selesai dengan tuntas

Faktor Determinan Klinis pada Malaria Anak

Wabah malaria ditemukan di berbagai tempat di Indonesia, antara lain di pantai selatan Jawa Tengah, DIY dan Jawa Timur, namun penyebaran penyakit terbesar terdapat di daerah luar Jawa-Bali kawasan timur. Masalah malaria bersifat local specific. Manifestasi malaria pada anak berbeda dan kurang spesifik dibanding orang dewasa, dan belum ditemukannya definisi klinis berupa keluhan dan atau gejala klinis malaria pada anak di daerah endemis tertentu. Hal ini menyebabkan overdiagnosis dan overtreatment untuk malaria dan kemungkinan terabaikannya pengobatan untuk penyakit lain. Penelitian ini bertujuan mengidentifikasi keluhan dan atau gejala klinis yang dapat digunakan sebagai determinan klinis malaria pada anak. Hasil penelitian ini berguna bagi pasien demam atau riwayat demam dalam satu minggu terakhir, dan yang berada di daerah endemis malaria. Dilakukan suatu studi cohort yang merupakan penelitian gabungan kuantitatif dan kualitatif berlokasi Kabupaten Sikka- NTT, selama bulan Mei-Juni 1999. Di antara 165 anak yang memenuhi kriteria inklusi, 79 pasien (47,9%) dengan definitif malaria dan 86 pasien bukan malaria (52,1%), sebagian besar pasien adalah kelompok umur 1-4 tahun (64,6%) Dari analisis gabungan antara uji Kai-kuadrat dan metode Delphi terdapat kesesuaian mengenai keluhan dan gejala klinis malaria yang prominen, namun mengingat insidensi penyakit malaria pada tiap kelompok umur, determinan klinis pada penelitan ini paling cocok diterapkan pada kelompok umur 1-4 tahun yaitu splenomegali, menggigil, pucat, dan hiperpireksia. Perlu dilakukan studi serupa di daerah endemis lain