Infectious Diseases - Research Publications

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    Ovarian abscess caused by Salmonella enterica serovar Typhi: a case report.
    Getahun S, A ; Limaono, J ; Ligaitukana, R ; Cabenatabua, O ; Soqo, V ; Diege, R ; Mua, M (Springer Science and Business Media LLC, 2019-09-25)
    BACKGROUND: Typhoid fever is a human-specific disease caused by a bacterium, Salmonella enterica subspecies enterica serovar Typhi. It is transmitted through ingestion of contaminated food or water. It is mostly diagnosed by blood culture. Salmonella Typhi usually manifests as a febrile illness with bacteremia after initial entry through the gastrointestinal route, but it can occasionally cause significant disease in extraintestinal sites. We report a case of a girl in Fiji with a right ovarian abscess infected by Salmonella Typhi. CASE PRESENTATION: A 14-year-old iTaukei (indigenous Fijian) girl presented to our hospital with abdominal pain of 1 month's duration. Two days prior to her admission, she developed high-grade fever and nausea and had one episode of vomiting. On presentation, she appeared unwell; she was tachycardic (116 beats per minute) and febrile (38.8 °C). Her abdominal examination revealed generalized tenderness. Other examination findings were normal. The provisional diagnosis of abdominal sepsis led to an emergency laparotomy during which an enlarged right ovary was found to be spontaneously discharging pus. The ovary was incised and drained, and the patient was commenced on intravenous ceftriaxone 1 g twice daily, cloxacillin 1 g four times daily, and metronidazole 500 mg three times daily. She recovered promptly and was discharged to home on the sixth postoperative day. The purulent material from the ovary grew Salmonella Typhi. CONCLUSION: Extraintestinal infections caused by Salmonella Typhi are rare but can cause severe and life-threatening disease. Our patient had a prolonged history of abdominal pain and was found to have a ruptured right ovarian abscess due to Salmonella Typhi. Ovarian abscesses in girls who are not sexually active are not associated with pelvic inflammatory disease and suggest local or hematogenous spread. This case report may increase health workers awareness to include common and endemic infections in the differential diagnosis of unusual clinical presentations to help the initiation of appropriate investigation and management as quickly as possible.
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    Dengue in Fiji: epidemiology of the 2014 DENV-3 outbreak.
    Getahun, A ; Batikawai, A ; Nand, D ; Khan, S ; Sahukhan, A ; Faktaufon, D (World Health Organization, Western Pacific Regional Office, 2019)
    INTRODUCTION: Dengue virus serotype-3 caused a large community-level outbreak in Fiji in 2013 and 2014. We aimed to characterize the demographic features of affected individuals and to determine dengue mortality during the outbreak. METHODS: All laboratory-confirmed dengue cases and deaths were included in this study. Incidence and mortality were calculated according to demographic variables. RESULTS: A total of 5221 laboratory-confirmed cases of dengue were included in this analysis. The majority of patients were male (54.5%) and indigenous Fijians (iTaukei) (53.5%). The median age was 25 years old. The overall incidence was 603 per 100 000 population. The age-specific incidence was highest among people between 20 and 24 years of age (1057 per 100 000) for both sexes. The major urban and peri-urban areas of Suva and Rewa subdivisions reported the highest incidence of > 1000 cases per 100 000 population.​: A total of 48 deaths were included in this analysis. The majority of dengue-related deaths occurred in males (62.5%) and in the iTaukei (60.4%) population. The median age at death was 35 years old. The overall dengue-related deaths was estimated to be 5.5 deaths per 100 000 population. Dengue mortality was higher for males (6.8 per 100 000) than females. The highest age- and sex-specific mortality of 18 per 100 000 population was among males aged 65 years and older. DISCUSSION: Dengue morbidity and mortality were highest among males, indigenous people and residents of urban and peri-urban locations. Effective and integrated public health strategies are needed to ensure early detection and appropriate outbreak control measures.
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    Immunogenicity and reactogenicity of ten-valent versus 13-valent pneumococcal conjugate vaccines among infants in Ho Chi Minh City, Vietnam: a randomised controlled trial
    Temple, B ; Nguyen, TT ; Vo, TTD ; Bright, K ; Licciardi, PV ; Marimla, RA ; Nguyen, CD ; Uyen, DY ; Balloch, A ; Tran, NH ; Mulholland, EK (ELSEVIER SCI LTD, 2019-05)
    BACKGROUND: Few data are available to support the choice between the two currently available pneumococcal conjugate vaccines (PCVs), ten-valent PCV (PCV10) and 13-valent PCV (PCV13). Here we report a head-to-head comparison of the immunogenicity and reactogenicity of PCV10 and PCV13. METHODS: In this parallel, open-label, randomised controlled trial, healthy infants from two districts in Ho Chi Minh City, Vietnam, were randomly allocated (in a 3:3:5:4:5:4 ratio), with use of a computer-generated list, to one of six infant PCV schedules: PCV10 in a 3 + 1 (group A), 3 + 0 (group B), 2 + 1 (group C), or two-dose schedule (group D); PCV13 in a 2 + 1 schedule (group E); or no infant PCV (control; group F). Blood samples were collected from infants between 2 months and 18 months of age at various timepoints before and after PCV doses and analysed (in a blinded manner) by ELISA and opsonophagocytic assay. The trial had two independent aims: to compare vaccination responses between PCV10 and PCV13, and to evaluate different schedules of PCV10. In this Article, we present results pertaining to the first aim. The primary outcome was the proportion of infants with an IgG concentration of at least 0·35 μg/mL for the ten serotypes common to the two vaccines at age 5 months, 4 weeks after the two-dose primary vaccination series (group C vs group E, per protocol population). An overall difference among the schedules was defined as at least seven of ten serotypes differing in the same direction at the 10% level. We also assessed whether the two-dose primary series of PCV13 (group E) was non-inferior at the 10% level to a three-dose primary series of PCV10 (groups A and B). This trial is registered with ClinicalTrials.gov, number NCT01953510. FINDINGS: Of 1424 infants screened between Sept 30, 2013, and Jan 9, 2015, 1201 were allocated to the six groups: 152 (13%) to group A, 149 (12%) to group B, 250 (21%) to group C, 202 (17%) to group D, 251 (21%) to group E, and 197 (16%) to group F. 237 (95%) participants in group C (PCV10) and 232 (92%) in group E (PCV13) completed the primary vaccination series and had blood draws within the specified window at age 5 months, at which time the proportion of infants with IgG concentrations of at least 0·35 μg/mL did not differ between groups at the 10% level for any serotype (PCV10-PCV13 risk difference -2·1% [95% CI -4·8 to -0·1] for serotype 1; -1·3% [-3·7 to 0·6] for serotype 4; -3·4% [-6·8 to -0·4] for serotype 5; 15·6 [7·2 to 23·7] for serotype 6B; -1·3% [-3·7 to 0·6] for serotype 7F; -1·6% [-5·1 to 1·7] for serotype 9V; 0·0% [-2·7 to 2·9] for serotype 14; -2·1% [-5·3 to 0·9] for serotype 18C; 0·0% [-2·2 to 2·3] for serotype 19F; and -11·6% [-18·2 to -4·9] for serotype 23F). At the same timepoint, two doses of PCV13 were non-inferior to three doses of PCV10 for nine of the ten shared serotypes (excluding 6B). Reactogenicity and serious adverse events were monitored according to good clinical practice guidelines, and the profiles were similar in the two groups. INTERPRETATION: PCV10 and PCV13 are similarly highly immunogenic when used in 2 + 1 schedule. The choice of vaccine might be influenced by factors such as the comparative magnitude of the antibody responses, price, and the relative importance of different serotypes in different settings. FUNDING: National Health and Medical Research Council of Australia, and Bill & Melinda Gates Foundation.
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    A latent class approach to identify multi-risk profiles associated with phylogenetic clustering of recent hepatitis C virus infection in Australia and New Zealand from 2004 to 2015.
    Bartlett, SR ; Applegate, TL ; Jacka, BP ; Martinello, M ; Lamoury, FM ; Danta, M ; Bradshaw, D ; Shaw, D ; Lloyd, AR ; Hellard, M ; Dore, GJ ; Matthews, GV ; Grebely, J (Wiley, 2019-02)
    INTRODUCTION: Over the last two decades, the incidence of hepatitis C virus (HCV) co-infection among men who have sex with men (MSM) living with HIV began increasing in post-industrialized countries. Little is known about transmission of acute or recent HCV, in particular among MSM living with HIV co-infection, which creates uncertainty about potential for reinfection after HCV treatment. Using phylogenetic methods, clinical, epidemiological and molecular data can be combined to better understand transmission patterns. These insights may help identify strategies to reduce reinfection risk, enhancing effectiveness of HCV treatment as prevention strategies. The aim of this study was to identify multi-risk profiles and factors associated with phylogenetic pairs and clusters among people with recent HCV infection. METHODS: Data and specimens from five studies of recent HCV in Australia and New Zealand (2004 to 2015) were used. HCV Core-E2 sequences were used to infer maximum likelihood trees. Clusters were identified using 90% bootstrap and 5% genetic distance threshold. Multivariate logistic regression and latent class analyses were performed. RESULTS: Among 237 participants with Core-E2 sequences, 47% were in a pair/cluster. Among HIV/HCV co-infected participants, 60% (74/123) were in a pair/cluster, compared to 30% (34/114) with HCV mono-infection (p < 0.001). HIV/HCV co-infection (vs. HCV mono-infection; adjusted odds ratio (AOR), 2.37, 95% confidence interval (CI), 1.45, 5.15) was independently associated with phylogenetic clustering. Latent class analysis identified three distinct risk profiles: (1) people who inject drugs, (2) HIV-positive gay and bisexual men (GBM) with low probability of injecting drug use (IDU) and (3) GBM with IDU & sexual risk behaviour. Class 2 (vs. Class 1, AOR 3.40; 95% CI, 1.52, 7.60), was independently associated with phylogenetic clustering. Many clusters displayed homogeneous characteristics, such as containing individuals exclusively from one city, individuals all with HIV/HCV co-infection or individuals sharing the same route of acquisition of HCV. CONCLUSIONS: Clusters containing individuals with specific characteristics suggest that HCV transmission occurs through discrete networks, particularly among HIV/HCV co-infected individuals. The greater proportion of clustering found among HIV/HCV co-infected participants highlights the need to provide broad direct-acting antiviral access encouraging rapid uptake in this population and ongoing monitoring of the phylogeny.
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    HIV diagnoses in migrant populations in Australia-A changing epidemiology.
    Gunaratnam, P ; Heywood, AE ; McGregor, S ; Jamil, MS ; McManus, H ; Mao, L ; Lobo, R ; Brown, G ; Hellard, M ; Marukutira, T ; Bretaña, NA ; Lang, C ; Medland, N ; Bavinton, B ; Grulich, A ; Guy, R ; Khudyakov, YE (Public Library of Science (PLoS), 2019)
    INTRODUCTION: We conducted a detailed analysis of trends in new HIV diagnoses in Australia by country of birth, to understand any changes in epidemiology, relationship to migration patterns and implications for public health programs. METHODS: Poisson regression analyses were performed, comparing the age-standardised HIV diagnosis rates per 100,000 estimated resident population between 2006-2010 and 2011-2015 by region of birth, with stratification by exposure (male-to-male sex, heterosexual sex-males and females). Correlation between the number of permanent and long-term arrivals was also explored using linear regression models. RESULTS: Between 2006 and 2015, there were 6,741 new HIV diagnoses attributed to male-to-male sex and 2,093 attributed to heterosexual sex, with the proportion of diagnoses attributed to male-to-male sex who were Australian-born decreasing from 72.5% to 66.5%. Compared with 2006-2010, the average annual HIV diagnosis rate per 100,000 in 2011-15 attributed to male-to-male sex was significantly higher in men born in South-East Asia (summary rate ratio (SRR) = 1.37, p = 0.001), North-East Asia (SRR = 2.18, p<0.001) and the Americas (SRR = 1.37, p = 0.025), but significantly lower as a result of heterosexual sex in men born in South-East Asia (SRR = 0.49, p = 0.002), Southern and Central Asia (SRR = 0.50, p = 0.014) and Sub-Saharan Africa (SRR = 0.39, p<0.001) and women born in South-East Asia (SRR = 0.61, p = 0.002) and Sub-Saharan Africa (SRR = 0.61, p<0.001). Positive associations were observed between the number of permanent and long-term arrivals and HIV diagnoses particularly in relation to diagnoses associated with male-to-male sex in men from North Africa and the Middle East, North Asia, Southern and Central Asia and the Americas. CONCLUSION: The epidemiology of HIV in Australia is changing, with an increase in HIV diagnosis rates attributed to male-to-male sex amongst men born in Asia and the Americas. Tailored strategies must be developed to increase access to, and uptake of, prevention, testing and treatment in this group.
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    The safety of inactivated influenza vaccines in pregnancy for birth outcomes: a systematic review
    Giles, ML ; Krishnaswamy, S ; Macartney, K ; Cheng, A (TAYLOR & FRANCIS INC, 2019-03-04)
    Pregnant women are at increased risk of morbidity and mortality from influenza and are recognized as a priority group for influenza vaccination. Despite this, uptake is often poor and one reason cited for this is concerns about safety. The objective of this study was to perform a systematic review of the safety of inactivated influenza vaccination (IIV) in pregnancy. Studies were included if they were: (i) observational or experimental design; (ii) included a comparator group comprising of unvaccinated pregnant women; (iii) comprised of either seasonal IIV or monovalent H1N1 IIV (including adjuvanted vaccines); and (iv) addressed one of the following outcomes: preterm birth (PTB), small for gestational age (SGA), fetal death (including stillbirth or spontaneous abortion), low birth weight (LBW) or congenital abnormalities. Two reviewers screened abstracts and titles and selected full texts for retrieval. Crude odds ratios were calculated from reported event rates, using binomial standard errors. Adjusted odds ratios, hazard ratios and relative rates were extracted as reported in each paper. After removal of duplicates and full text eligibility assessment, 40 studies remained. The aOR for PTB was 0.87 (0.78-0.96), for LBW 0.82 (0.76-0.89), congenital abnormality 1.03 (0.99-1.07), SGA 0.99 (0.94-1.04) and stillbirth 0.84 (0.65-1.08). This study contributes to the increasing body of safety data for IIV in pregnancy and reports a protective effect on PTB and LBW.
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    Key considerations for successful implementation of maternal immunization programs in low and middle income countries
    Krishnaswamy, S ; Lambach, P ; Giles, ML (TAYLOR & FRANCIS INC, 2019-04-03)
    The Maternal Neonatal Tetanus Elimination program is proof of concept for the feasibility and potential for maternal immunization to reduce neonatal mortality particularly in low and middle-income countries. Introduction of any additional vaccine into the antenatal space, such as Influenza and Pertussis, and potentially Respiratory Syncytial Virus and Group B Streptococcus vaccines in the future, requires strengthening of antenatal care and immunization services. Successful implementation also requires robust disease surveillance in pregnant women and neonates and active surveillance for adverse events following immunization to monitor the impact and ensure the safe use of the vaccine. This review outlines five key elements essential for successful implementation of a maternal immunization program focusing particularly on low and middle-income countries. These include; relevant considerations in supporting a decision to undertake a maternal immunization program including knowledge of local disease epidemiology, involvement of the consumer, healthcare provider recommendation, equitable access to maternal vaccination, and systems for disease surveillance, program evaluation and safety monitoring.
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    Maternal Immunization and Antenatal Care Situation Analysis (MIACSA) study protocol: a multiregional, cross-sectional analysis of maternal immunization delivery strategies to reduce maternal and neonatal morbidity and mortality
    Roos, N ; Lambach, P ; Mantel, C ; Mason, E ; Munoz, FM ; Giles, M ; Moran, A ; Hombach, J ; Diaz, T (BMJ PUBLISHING GROUP, 2019-06)
    INTRODUCTION: Maternal immunization (MI) with tetanus toxoid containing vaccine, is a safe and cost-effective way of preventing neonatal tetanus. Given the prospect of introducing new maternal vaccines in the near future, it is essential to identify and understand current policies, practices and unmet needs for introducing and/or scaling up MI in low-income and middle-income countries (LMICs). METHODS AND ANALYSIS: The Maternal Immunization and Antenatal Care Situation Analysis (MIACSA) is a mixed methods, cross-sectional study that will collect data in four phases: (1) a review of global databases for selected health indicators in 136 LMICs; (2) a structured online survey directed at Maternal, Newborn and Child Health and Expanded Programme on Immunization focal points in all 136 LMICs; (3) semistructured telephone interviews of 30 selected LMICs and (4) 10 week-long country visits, including key informant interviews, health facility visits and focus group discussions. The principal analyses will assess correlations between the various aspects of MI delivery strategies and proxy measures of health systems performance related to vaccine-preventable disease control. The primary outcome will be a typology of existing MI delivery models, and secondary outcomes will include country profiles of child and maternal health indicators, and a MI gaps and needs analysis. ETHICS AND DISSEMINATION: The protocol was approved by the WHO Ethics Review Committee (ERC.0002908). The results will be made available in a project report and submitted for publication in peer-reviewed journals that will be shared broadly among global health decision-makers, researchers, product developers and country-level stakeholders.
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    The Effect of Timing of Tetanus-Diphtheria-Acellular Pertussis Vaccine Administration in Pregnancy on the Avidity of Pertussis Antibodies
    Abu-Raya, B ; Giles, ML ; Kollmann, TR ; Sadarangani, M (FRONTIERS MEDIA SA, 2019-10-11)
    Background: Optimal timing of gestational tetanus-diphtheria-acellular pertussis (Tdap) vaccination is not well-defined. No well-established specific anti-pertussis antibody level correlates with protection, suggesting the importance of antibody quality such as avidity. We aimed to determine the effect of timing of vaccination with Tdap in pregnancy on the avidity of cord anti-pertussis toxin (PT) immunoglobulin G (IgG). Methods: Prospective study of newborns in a tertiary hospital (Melbourne, Australia) born to women vaccinated with Tdap in pregnancy. Ammonium thiocyanate was used as a bond-breaking agent to measure the avidity of anti-PT IgG using concentrations between 0.25 M (to measure low avidity antibodies) and 3 M (to measure very high avidity antibodies). Anti-PT IgG levels achieved at each ammonium thiocyanate concentration in cord samples of women vaccinated during 28-32 weeks gestation (WG) vs. 33-36 WG, and women vaccinated 5-12 vs. 1-4 weeks prior to delivery were compared using t-tests. Results: Newborns of women vaccinated with Tdap during 28-32 WG (n = 43) had statistically significant higher concentrations of medium and high avidity anti-PT IgG compared with newborns of women vaccinated during 33-36 WG (n = 47), 11.6 IU/ml (95% CI, 8.8-15.2) IU/ml vs. 6.7 IU/ml (95% CI, 5.2-8.6) and 10.1 IU/ml (95% CI, 7.4-13.8) vs. 5.7 (95% CI, 3.6-8.9) IU/ml (p = 0.007 and p = 0.035), respectively. Newborns of women vaccinated 5-12 weeks before delivery (n = 64) had statistically significant higher concentrations of high and very high avidity anti-PT IgG compared with newborns of women vaccinated within 4 weeks before delivery (n = 25), 10.3 IU/mL (95% CI, 7.9-13.4) vs. 3.3 IU/mL (95% CI, 1.7-6.4), 12.6 IU/mL (95% CI, 9.4-16.9) vs. 4.3 IU/mL (95% CI, 2.2-8.5) (all p < 0.03), respectively. Conclusions: Quantification of levels of anti-PT IgG with different avidities demonstrated that pertussis vaccination 5-12 weeks before delivery was associated with higher anti-PT IgG avidity compared with vaccination within 4 weeks before delivery. Pertussis vaccination during 28-32 WG was associated with higher anti-PT IgG avidity compared with vaccination during 33-36 WG, supporting vaccination at 28-32 over 33-36 WG for optimal protection against pertussis in infancy.
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    Assessment of service refinement and its impact on repeat HIV testing by client's access to Australia's universal healthcare system: a retrospective cohort study.
    Ryan, KE ; Wilkinson, AL ; Asselin, J ; Leitinger, DP ; Locke, P ; Pedrana, A ; Hellard, M ; Stoové, M (Wiley, 2019-08)
    INTRODUCTION: Achieving the virtual elimination of HIV requires equitable access to HIV prevention tools for all priority populations. Restricted access to healthcare means migrants face particular barriers to HIV prevention services. In February 2016, a peer-led rapid HIV testing service for gay, bisexual and other men who have sex with men (gay and bisexual men, GBM) in Melbourne, Australia, introduced free sexually transmissible infection (STI) testing funded through Medicare (Australia's universal healthcare system). Medicare ineligible migrant clients were required to pay up to $158AUD for STI tests. We determined the uptake of STI testing and assessed the impact on repeat HIV testing among Medicare eligible and ineligible clients. METHODS: All HIV tests conducted between August 2014 and March 2018 were included. We describe client characteristics, STI testing uptake and HIV/STI positivity among Medicare eligible and ineligible clients. Repeat HIV testing, assessed as the percentage of HIV tests with a return test within six months, was compared pre-integration (August 2014-June 2016) and post-integration(July 2016-March 2018) of STI testing using segmented linear regression of monthly aggregate data for Medicare eligible and ineligible clients. RESULTS: Analyses included 9134 HIV tests among 4753 individuals. Medicare ineligible clients were younger (p < 0.01), and fewer reported previously testing for HIV (p < 0.01) and high HIV risk sexual behaviours. There was no difference in HIV positivity between the two groups (p = 0.09). STI testing uptake was significantly lower among Medicare ineligible clients (7.6%, 85.3%; p < 0.01). Following STI testing introduction there was an immediate increase in six-month return HIV testing (6.4%; p = 0.02) and a significantly increasing rate of return HIV testing between July 2016 and March 2018 (0.5% per month; p < 0.01) among Medicare eligible clients but no immediate change in return testing (-0.9%; p = 0.7) or the rate of change in return testing between July 2016 and March 2018 (0.1% per month; p = 0.3) among Medicare ineligible clients. In March 2018, six-month return HIV testing was 52.3% and 13.2% among Medicare eligible and ineligible clients respectively. DISCUSSION: Improvements in return HIV testing observed among Medicare eligible clients did not extend to Medicare ineligible clients highlighting the impact of inequitable access to comprehensive sexual healthcare on test-and-treat approaches to HIV prevention.