Characterization of Gram-negative Bloodstream Infections in Hospitalized Australian Children and Their Clinical Outcomes.

BACKGROUND: Gram-negative bloodstream infections (GNBSIs) more commonly occur in children with comorbidities and are increasingly associated with antimicrobial resistance. There are few large studies of GNBSIs in children that relate the clinical presentation, pathogen characteristics, and outcomes. METHODS: A 3-year prospective study of GNBSIs in children aged <18 years was conducted in 5 Australian children's hospitals between 2019 and 2021. The clinical characteristics, disease severity, and outcomes were recorded. Causative pathogens underwent antibiotic susceptibility testing and whole genome sequencing. RESULTS: There were 931 GNBSI episodes involving 818 children. Median age was 3 years (interquartile range, 0.6-8.5). A total of 576/931 episodes (62%) were community onset, though 661/931 (71%) occurred in children with comorbidities and a central venous catheter was present in 558/931 (60%). Central venous catheter (145/931) and urinary tract (149/931) were the most common sources (16% each). One hundred of 931 (11%) children required intensive care unit admission and a further 11% (105/931) developed GNBSIs in intensive care unit. A total of 659/927 (71%) isolates were Enterobacterales, of which 22% (138/630) were third-generation cephalosporin resistant (3GCR). Extended spectrum beta-lactamase genes were confirmed in 65/138 (47%) 3GCR Enterobacterales. Most common extended spectrum beta-lactamase genes were blaCTX-M-15 (34/94, 36%) and blaSHV-12 (10/94, 11%). There were 48 deaths overall and 30-day in-hospital mortality was 3% (32/931). Infections with 3GCR Enterobacterales were independently associated with higher mortality (adjusted odds ratio, 3.2; 95% confidence interval, 1.6-6.4). CONCLUSIONS: GNBSIs in children are frequently healthcare associated and affect children younger than age 5 years. Infections with 3GCR Enterobacterales were associated with worse outcomes. These findings will inform optimal management guidelines and help prioritize future antimicrobial clinical trials.

Onward Virus Transmission after Measles Secondary Vaccination Failure.

Measles in persons with secondary vaccination failure (SVF) may be less infectious than cases in unvaccinated persons. Our systematic review aimed to assess transmission risk for measles after SVF. We searched PubMed, Embase, and Web of Science databases from their inception dates. Inclusion criteria were articles describing persons who were exposed to measles-infected persons who had experienced SVF. Across the included 14 studies, >3,030 persons were exposed to measles virus from SVF cases, of whom 180 were susceptible, indicating secondary attack rates of 0%-6.25%. We identified 109 cases of SVF from the studies; 10.09% (n = 11) of case-patients transmitted the virus, resulting in 23 further cases and yielding an effective reproduction number of 0.063 (95% CI 0.0-0.5). These findings suggest a remarkably low attack rate for SVF measles cases, suggesting that, In outbreak situations, public health management of unvaccinated persons could be prioritized over persons with SVF.

The provision of sexual and reproductive health information and services to travellers: an exploratory survey of Australian travel medicine clinicians.

BACKGROUND: International travel can increase the risk of exposure to infectious diseases including sexually transmissible infections (STI). Pre-travel medical consultation provides an opportunity for travel-related health risk assessments and advice. This study explored how travel medicine clinicians integrate sexual and reproductive health (SRH) services into clinical practice. METHODS: A convenience sample of travel medicine clinicians completed a cross-sectional survey online or via hard-copy disseminated at an annual national Australian travel medicine conference. RESULTS: Of the 67 respondents, most (n , 51; 76.1%) had a postgraduate qualification relevant to travel medicine and 55.2% (n , 37) had worked in travel medicine for over 10years. Only 22.4% (n , 15) reported conducting a SRH history/STI risk assessment for all travel patients. STI testing pre-departure was conducted on patient request (48, 71.6%), if symptomatic (32, 47.8%) or based on risk history (28, 41.8%). SRH information pre-departure was most frequently provided if prompted by patient questions (n , 42; 62.7%), or based on the patient's history (n , 37; 55.2%). Over half the sample (n , 40; 59.7%) expressed interest in further training in SRH. CONCLUSION: Providing and engaging with additional training may assist travel medicine clinicians to take a more proactive approach to SRH consultations and STI testing. Additional research is needed to explore models of care that will allow comprehensive SRH and STI services to be integrated into standard pre- and post-travel care.

Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021-August 2022.

To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.

The changing epidemiology of Neisseria gonorrhoeae genogroups and antimicrobial resistance in Queensland, Australia, 2010-15: a case series analysis of unique Neisseria gonorrhoeae isolates.

BACKGROUND: Neisseria gonorrhoeae (NG) can lead to serious reproductive and sexual health outcomes, and the annual number of NG notifications in Australia increased steadily from 10329 in 2010 to 29549 by 2020. Australian populations most affected are urban men who have sex with men and First Nations peoples living in remote areas, and a resurgence in urban heterosexuals has been observed since 2012. METHODS: A case series analysis of Queensland NG isolates (2010-15) exploring temporal trends and antimicrobial resistance by demographic and geographic distribution and genotype was performed. Proportions describe age, sex, strain, genogroup (NG multi-antigen sequence typing), region, swab site, antimicrobial sensitivity and isolate rates per 100000 population. Dominant genogroups were identified. RESULTS: Among 3953 isolates, the median age was 25years (IQR 20-34years) and most (n =2871/3915, 73%) were men. Brisbane city (68.8) and Far North Queensland (54.1) excluding Cairns showed the highest rates. Forty-six genogroups were documented, seven (G2992, G6876, G1415, G4186, G5, G1407 and G6937) comprised half of all isolates. The predominant male genogroup was G2992 (16%), and G6876 (20%) for females; G5 was predominantly male from 2010 to 2011, but equal in both sexes from 2012 to 2015. CONCLUSION: Considerable temporal, geographical and demographical diversity was observed in Queensland NG isolates, which has public health implications. Certain genogroups are more transient than others, and evidence suggests bridging from male-dominant networks to heterosexual networks. Molecular surveillance can enhance tracking the epidemiology and movement of NG in Australia, highlighting the necessity of genotyping to expose potentially prevalent strains circulating in undetected or underrepresented networks by current screening methods.

Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis.

BACKGROUND: Neonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR. METHODS AND FINDINGS: All studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria. CONCLUSIONS: Gram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.

Spatial prediction of malaria prevalence in Papua New Guinea: a comparison of Bayesian decision network and multivariate regression modelling approaches for improved accuracy in prevalence prediction.

BACKGROUND: Considerable progress towards controlling malaria has been made in Papua New Guinea through the national malaria control programme's free distribution of long-lasting insecticidal nets, improved diagnosis with rapid diagnostic tests and improved access to artemisinin combination therapy. Predictive prevalence maps can help to inform targeted interventions and monitor changes in malaria epidemiology over time as control efforts continue. This study aims to compare the predictive performance of prevalence maps generated using Bayesian decision network (BDN) models and multilevel logistic regression models (a type of generalized linear model, GLM) in terms of malaria spatial risk prediction accuracy. METHODS: Multilevel logistic regression models and BDN models were developed using 2010/2011 malaria prevalence survey data collected from 77 randomly selected villages to determine associations of Plasmodium falciparum and Plasmodium vivax prevalence with precipitation, temperature, elevation, slope (terrain aspect), enhanced vegetation index and distance to the coast. Predictive performance of multilevel logistic regression and BDN models were compared by cross-validation methods. RESULTS: Prevalence of P. falciparum, based on results obtained from GLMs was significantly associated with precipitation during the 3 driest months of the year, June to August (ß = 0.015; 95% CI = 0.01-0.03), whereas P. vivax infection was associated with elevation (ß = - 0.26; 95% CI = - 0.38 to - 3.04), precipitation during the 3 driest months of the year (ß = 0.01; 95% CI = - 0.01-0.02) and slope (ß = 0.12; 95% CI = 0.05-0.19). Compared with GLM model performance, BDNs showed improved accuracy in prediction of the prevalence of P. falciparum (AUC = 0.49 versus 0.75, respectively) and P. vivax (AUC = 0.56 versus 0.74, respectively) on cross-validation. CONCLUSIONS: BDNs provide a more flexible modelling framework than GLMs and may have a better predictive performance when developing malaria prevalence maps due to the multiple interacting factors that drive malaria prevalence in different geographical areas. When developing malaria prevalence maps, BDNs may be particularly useful in predicting prevalence where spatial variation in climate and environmental drivers of malaria transmission exists, as is the case in Papua New Guinea.

Drug-free Holidays: Compliance, Tolerability, and Acceptability of a 3-Day Atovaquone/Proguanil Schedule for Pretravel Malaria Chemoprophylaxis in Australian Travelers.

BACKGROUND: Poor compliance with chemoprophylaxis is a major contributing factor to the risk of malaria in travelers. Pre-travel chemoprophylaxis may improve compliance by enabling "drug-free holidays." The standard treatment dose of atovaquone/proguanil (250 mg/100 mg, 4 tablets/day for 3 days) provides protection against malaria for at least 4 weeks, and could therefore potentially be used for pre-travel chemoprophylaxis. In this study, we assessed the compliance, tolerability, and acceptability of the 3-day atovaquone/proguanil schedule for malarial chemoprophylaxis. METHODS: Two hundred thirty-three participants were recruited from 4 specialized travel medicine clinics in Australia. Adults traveling to malaria-endemic areas with low/medium risk for ≤4 weeks were enrolled and prescribed the 3-day schedule of atovaquone/proguanil, completed at least 1 day before departure. Questionnaires were used to collect data on demographics, travel destination, medication compliance, side effects, and reasons for choosing the 3-day schedule. RESULTS: Overall, 97.7% of participants complied with the 3-day schedule. Although side effects were reported in 43.3% of the participants, these were well tolerated, and mainly occurred during the first and second days. None of the participants developed malaria. The main reasons for choosing the 3-day schedule over standard chemoprophylaxis options were that it was easier to remember (72.1%), required taking fewer tablets (54.0%), and to help scientific research (54.0%). CONCLUSIONS: The 3-day atovaquone/proguanil schedule had an impressively high compliance rate, and was well tolerated and accepted by travelers. Further studies are required to assess the effectiveness of this schedule for chemoprophylaxis in travelers. CLINICAL TRIALS REGISTRATION: ACTRN12616000640404.

Ross River Virus Antibody Prevalence, Fiji Islands, 2013-2015.

A unique outbreak of Ross River virus (RRV) infection was reported in Fiji in 1979. In 2013, RRV seroprevalence among residents was 46.5% (362/778). Of the residents who were seronegative in 2013 and retested in 2015, 10.9% (21/192) had seroconverted to RRV, suggesting ongoing endemic circulation of RRV in Fiji.

Sustained Low-Level Transmission of Zika and Chikungunya Viruses after Emergence in the Fiji Islands.

Zika and chikungunya viruses were first detected in Fiji in 2015. Examining surveillance and phylogenetic and serologic data, we found evidence of low-level transmission of Zika and chikungunya viruses during 2013-2017, in contrast to the major outbreaks caused by closely related virus strains in other Pacific Island countries.

Emergence and spread of ciprofloxacin-resistant Neisseria gonorrhoeae in New South Wales, Australia: lessons from history.

OBJECTIVES: Our aim was to investigate the emergence and spread of ciprofloxacin resistance in clinical Neisseria gonorrhoeae isolates in New South Wales, Australia, from the first reported case in 1991 until ciprofloxacin resistance was sustained at or above the WHO threshold for treatment change of 5% (1999), to inform future strategies for controlling gonococcal antimicrobial resistance. METHODS: The index isolate and all subsequent clinical isolates of ciprofloxacin-resistant N. gonorrhoeae in New South Wales from 1991 to 1999 were genotyped using a previously described method on the Agena MassARRAY iPLEX platform. Region of acquisition data, where available, were used to determine whether cases were travel associated. RESULTS: In New South Wales, of the 325 ciprofloxacin-resistant N. gonorrhoeae isolates reported from 1991 to 1999, 98% (320/325) were able to be recovered and 100% (320/320) were genotyped. There were 66 different genotypes, comprising 1-99 isolates each. Notably no single clone was found to account for ciprofloxacin resistance being sustained in the population, with considerable variability in genotype prevalence observed throughout the study period. A total of 65% (209/320) of genotyped isolates had information regarding the likely place of acquisition; of these, 44% (93/209) were associated with overseas travel or sexual contact with an overseas visitor. The first ciprofloxacin-resistant N. gonorrhoeae in New South Wales was associated with travel to Thailand. Index cases of each resistant genotype were significantly more likely to have been acquired overseas (51.5%), predominantly in Asia (45%, 30/66). CONCLUSIONS: The continued importation of multiple genotypes, rather than the expansion of a single genotype, led to ciprofloxacin-resistant N. gonorrhoeae being established in New South Wales.

Diversity of infectious aetiologies of acute undifferentiated febrile illnesses in south and Southeast Asia: a systematic review.

BACKGROUND: Acute undifferentiated febrile illness (AUFI) is caused by a multitude of diverse pathogens, with significant morbidity and mortality in the developing world. The objective of this review was to characterise the diversity and relative importance of common infectious aetiologies of AUFI in South and Southeast Asia. METHODS: We conducted a comprehensive literature review to identify common aetiologies of AUFI in Asian countries. Four medical and life sciences databases including PubMed, Medline, Embase and Cochrane Central, and Google Scholar were searched for articles published from January 1998 to March 2019. RESULTS: Forty-three studies met the inclusion criteria. Among AUFI cases, viral aetiologies at 18.5% (14888) were more common than bacterial aetiologies (12.9% [10384]). From 80,554 cases, dengue fever was the most common aetiology (11.8%, 9511), followed by leptospirosis (4.4%, 3549), typhoid (4.0%, 3258), scrub typhus (4.0%, 3243) and influenza other than H1N1 (3.1%, 2514). In both adults and children: dengue fever was the leading cause of AUFI with 16.6% (1928) and 18.7% (1281) of the total cases. In admitted patients, dengue fever was the main cause of AUFI at 16.4% (2377), however leptospirosis at 13.9% (2090) was the main cause of AUFI for outpatients. In South Asia, dengue fever was the main cause of AUFI, causing 12.0% (6821) of cases, whereas in Southeast Asia, leptospirosis was the main diagnosis, causing 12.1% (2861) of cases. CONCLUSIONS: In this study the most common causes of AUFI were viral, followed by bacterial and protozoal (malaria) infections. Dengue was the commonest virus that caused AUFI while leptospirosis and typhoid were important bacterial infectious causes. Therefore, it is imperative to maintain a sound epidemiological knowledge of AUFI so that evidence-based diagnostic criteria and treatment guidelines can be developed.

Role of Environmental Factors in Shaping Spatial Distribution of Salmonella enterica Serovar Typhi, Fiji.

Fiji recently experienced a sharp increase in reported typhoid fever cases. To investigate geographic distribution and environmental risk factors associated with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional cluster survey with associated serologic testing for Vi capsular antigen-specific antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots with high seroprevalence of Vi-specific antibodies were identified in northeastern mainland Fiji. Risk for Vi seropositivity increased with increased annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12-1.42), and decreased with increased distance from major rivers and creeks (OR 0.89/km increase, 95% CI 0.80-0.99) and distance to modeled flood-risk areas (OR 0.80/quintile increase, 95% CI 0.69-0.92) after being adjusted for age, typhoid fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi and its spatial distribution in Fiji are driven by environmental factors. Our findings can directly affect typhoid fever control efforts in Fiji.

The emergence of Leptospira borgpetersenii serovar Arborea in Queensland, Australia, 2001 to 2013.

BACKGROUND: Leptospirosis is an emerging infectious disease, with increasing frequency and severity of outbreaks, changing epidemiology of populations at risk, and the emergence of new serovars. Environmental drivers of disease transmission include flooding, urbanisation, poor sanitation, changes in land use and agricultural practices, and socioeconomic factors. In Queensland, human infection with Leptosira borgpetersenii serovar Arborea was first reported in 2001. This study aims to report the emergence of serovar Arborea in Queensland from 2001 to 2013, and investigate potential risk factors for infection and drivers of emergence. METHODS: Data on laboratory-confirmed cases of human leptospirosis in Queensland were obtained from the enhanced surveillance system at the WHO/FAO/OIE Collaborating Centre for Reference and Research on Leptospirosis in Brisbane, Australia. The changing epidemiology of serovar Arborea from 2001 to 2003 was described with respect to case numbers, proportion of leptospirosis cases attributed to the serovar, and geographic distribution. Differences in risk factors for the most common serovars were compared. RESULTS: During this period, 1289 cases of leptospirosis were reported, including 233 cases attributed to serovar Arborea. Risk factors for infection include male gender (91 % of cases), occupation, and recreational exposure. Most common occupations recorded were banana workers (28.4 %), meat workers (7.2 %), dairy farmers (5.8 %), graziers/stockmen (5.5 %), 'other agricultural/rural workers' (16.4 %), and tourists or tourism operators (4.6 %). Time trend analysis showed that while non-Arborea cases decreased over the study period, Arborea cases increased by 3.4 cases per year. The proportion of annual cases attributed to Arborea peaked at 49 % in 2011 after unprecedented flooding in Queensland. Mapping of cases by residential location showed expansion of the geographic range of serovar Arborea, concentrating mostly around Brisbane, Cairns and Innisfail. Serovars varied significantly between ages and occupational groups, and serovar Arborea was most strongly associated with 'other agricultural/rural workers'. CONCLUSIONS: Leptospira borgpetersenii serovar Arborea has been emerging in Queensland since 2001, with increase in case numbers, the proportion of leptospirosis infections attributed to the serovar, as well as expansion of its geographic distribution. Reasons for this emergence are unknown, but climatic factors and environmental change are likely to have played important roles.

Mastering geographically weighted regression: key considerations for building a robust model.

Geographically weighted regression (GWR) takes a prominent role in spatial regression analysis, providing a nuanced perspective on the intricate interplay of variables within geographical landscapes (Brunsdon et al., 1998). However, it is essential to have a strong rationale for employing GWR, either as an addition to, or a complementary analysis alongside, non-spatial (global) regression models (Kiani, Mamiya et al., 2023). Moreover, the proper selection of bandwidth, weighting function or kernel types, and variable choices constitute the most critical configurations in GWR analysis (Wheeler, 2021). [...].

Operational research to inform post-validation surveillance of lymphatic filariasis in Tonga study protocol: History of lymphatic filariasis elimination, rational, objectives, and design.

BACKGROUND: Lymphatic filariasis (LF), a mosquito-borne helminth infection, is an important cause of chronic disability globally. The World Health Organization has validated eight Pacific Island countries as having eliminated lymphatic filariasis (LF) as a public health problem, but there are limited data to support an evidence-based approach to post-validation surveillance (PVS). Tonga was validated as having eliminated LF in 2017 but no surveillance has been conducted since 2015. This paper describes a protocol for an operational research project investigating different PVS methods in Tonga to provide an evidence base for national and regional PVS strategies. METHODS: Programmatic baseline surveys and Transmission Assessment Surveys conducted between 2000-2015 were reviewed to identify historically 'high-risk' and 'low-risk' schools and communities. 'High-risk' were those with LF antigen (Ag)-positive individuals recorded in more than one survey, whilst 'low-risk' were those with no recorded Ag-positives. The outcome measure for ongoing LF transmission will be Ag-positivity, diagnosed using Alere™ Filariasis Test Strips. A targeted study will be conducted in May-July 2024 including: (i) high and low-risk schools and communities, (ii) boarding schools, and (iii) patients attending a chronic-disease clinic. We estimate a total sample size of 2,010 participants. CONCLUSIONS: Our methodology for targeted surveillance of suspected 'high-risk' populations using historical survey data can be adopted by countries when designing their PVS strategies. The results of this study will allow us to understand the current status of LF in Tonga and will be used to develop the next phase of activities.

Post-marketing surveillance of 10,392 herpes zoster vaccines doses in Australia.

BACKGROUND: Immunisation against herpes zoster is recommended for adults aged ≥ 50 years. Two vaccines, a live attenuated (ZVL, Zostavax®) and an adjuvant recombinant subunit (HZ/su, Shingrix®), are available in Australia. Immunisation guidelines are shifting their recommendations towards HZ/su because of higher efficacy in preventing herpes zoster and associated complications. However, there are limited post-marketing data comparing the safety profiles of these vaccines. METHODS: Data from SmartVax, an active surveillance system for monitoring adverse events following immunisation (AEFIs) utilised by > 450 clinics throughout Australia, were analysed. Data from patients aged ≥ 50 years, who received ZVL or HZ/su, from 1 June 2021 to 31 May 2022, at clinics that utilised SmartVax were included. The proportion of records where patients who reported any, local, and systemic AEFIs after receiving ZVL or HZ/su were compared using multivariable logistic regression models. RESULTS: Data from 10,392 immunisation records (n = 8341 ZVL; n = 2051 HZ/su) were included. The proportion of AEFIs reported was higher with HZ/su (41.9 % [any], 33.8 % [local], 25.2 % [systemic]) than with ZVL (8.7 % [any], 6.2 % [local], 3.5 % [systemic]). After controlling for demographic variables, HZ/su presented a 6-fold increase in the odds (OR 6.44; 95 %CI: 5.57-7.46) of a reported AEFI compared to ZVL. Only 59 (0.6 %) of vaccinations lead to medical attention being sought due to an AEFI. CONCLUSIONS: While rates of AEFIs was higher with HZ/su than ZVL, most AEFIs were mild and did not require medical attention. Our findings support the change in vaccine recommendations and the use of HZ/su in immunisation programs.

Anti-filarial antibodies are sensitive indicators of lymphatic filariasis transmission and enable identification of high-risk populations and hotspots.

OBJECTIVES: Circulating filarial antigen (Ag) is used by elimination programs to monitor lymphatic filariasis (LF) transmission; however, antifilarial antibodies (Ab) may be more sensitive than Ag for detecting LF. Our objectives were to describe Ab seroprevalence, identify risk factors for Ab seropositivity, investigate age-specific associations between Ag and Ab, and evaluate geographic clustering of seropositivity. METHODS: Community-based serosurveys of participants aged ≥5 years were conducted in 35 primary sampling units (PSUs). Ag-positivity was detected using Alere™ Filariasis Test Strips and Ab-seropositivity using multiplex bead assays. Seroprevalence was adjusted for study design. RESULTS: Of 3795 participants (range:5-90 years), adjusted prevalence for Ag, Bm14 Ab, Wb123 Ab, and Bm33 Ab were 3.7% (n=117), 20.3% (n=583), 32.2% (n=987), and 51.0% (n=1659), respectively. Male sex, older age, and residents of suspected hotspots had higher odds of seropositivity to all seromarkers. Seroprevalence was lower in 5-9-year-olds vs ≥10-year-olds (P<0.001). Clustering was significantly higher in households (intra-cluster correlation for Ag:0.45; Bm14 Ab:0.32; Bm33 Ab:0.31; Wb123 Ab:0.29) compared to PSUs or region. CONCLUSIONS: Abs enabled identification of risk factors for seropositivity and geographical clustering to inform targeted interventions for LF programmes. Further research is needed to define Ab thresholds for active versus past infection and elimination targets.