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, < 0.016 to 2 µg/L) and for erythromycin (MIC range, < 0.016 to > 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 <  0.016 to > 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.

Seroprevalence and Determinants of Immunity to Diphtheria for Children Living in Two Districts of Contrasting Incidence During an Outbreak in East Java, Indonesia.

BACKGROUND: In 2012, an ongoing outbreak of diphtheria in Indonesia was focused in the province of East Java. There was a need to assess vaccine coverage and immunity gaps in children. METHODS: We conducted a cross-sectional seroprevalence and vaccine coverage survey of children 1-15 years of age in 2 districts of East Java: one of high incidence (on the island of Madura) and one of low incidence (on the mainland). From each district, we sampled 150 children (10 children per year of age). Sera and throat swabs were taken to determine immunity and carriage status. Immunity was defined as ≥0.1 international unit/mL of antibody to diphtheria toxin. RESULTS: A total of 297 children were selected to participate in the study. Coverage of three doses of combined vaccine for diphtheria, tetanus and pertussis was significantly lower (P < 0.001) in the high incidence district compared with the low [57%, 95% confidence interval (CI): 36-78 vs. 97%, 95% CI: 93-100]. Despite this higher vaccine coverage, seroprevalence of immunity was lower in the low incidence district compared with the high (71%, 95% CI: 63-80 vs. 83%, 95% CI: 76-90). Immunity in the high incidence district was associated with increased age, increased prevalence of toxigenic Corynebacterium diphtheriae carriers and with receipt of multiple (and likely more recent) boosters. CONCLUSIONS: Significant variation exists in vaccine coverage and seroprevalence of immunity to diphtheria in East Java. Immunity in high incidence districts is likely because of natural immunity acquired through exposure to toxigenic C. diphtheriae. Booster vaccines are essential for achieving protective levels of immunity.

A large vaccine-derived poliovirus outbreak on Madura Island--Indonesia, 2005.

Between June and October 2005, 45 laboratory-confirmed type 1 vaccine-derived poliovirus (VDPV) cases were identified on Madura Island in Indonesia. Genetic sequencing data on VDPV isolates were consistent with replication and circulation for up to approximately 2 years. Concurrent circulation with type 1 wild poliovirus (WPV) enabled comparisons of VDPV and WPV cases and found that clinical and epidemiological features of both were similar. Attack rates for VDPV were as high as those for WPV. Of 41 VDPV case patients with known vaccination status, 25 (61%) had received zero oral polio vaccine (OPV) doses. Low population immunity due to low routine OPV coverage in rural areas and the absence of WPV circulation for more than a decade were major predisposing factors for the emergence of VDPV. Suboptimal surveillance and a limited initial immunization response may have contributed to widespread circulation. Sensitive surveillance and prompt high-quality immunization responses are recommended to prevent the spread of VDPVs.