A tuberculosis elimination-focused geospatial approach to optimising access to diagnostic GeneXpert machines in Fiji.

OBJECTIVES: Fiji could be the first country to eliminate tuberculosis. To inform this strategy, we aimed to identify how many GeneXpert® machines are required to enable over 90% of Fijians to be within one-hour easy access. METHODS: We used Geographic Information System (Quantum GIS; QGIS), OpenStreetMap and population data (Kontur) to map possible facilities in relation to QGIS generated 60-min drive-time isochrones, with correction for missing road data. For outer islands, we calculated a distance to nearest hub operation. RESULTS: The solution comprised 24 GeneXpert® machines, allocating 7 GeneXpert® to Viti Levu, 6 GeneXpert® to Vanua Levu and 11 to other islands. This resulted in 827,810 people, 93.6% of Fiji's population, being within 1 h of a machine. Twenty-one thousand four hundred seventy-nine people on outer islands were an average of 43 km by water from the nearest facility. CONCLUSIONS: We conclude that over 90% of Fijians could be within an hour of a GeneXpert® machine with placement of 24 machines.

Unique microbial diversity, community composition, and networks among Pacific Islander endocervical and vaginal microbiomes with and without Chlamydia trachomatis infection in Fiji.

IMPORTANCE: Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterium globally. Endocervical and vaginal microbiome interactions are rarely examined within the context of Ct or among vulnerable populations. We evaluated 258 vaginal and 92 paired endocervical samples from Fijian women using metagenomic shotgun sequencing. Over 37% of the microbiomes could not be classified into sub-community state types (subCSTs). We, therefore, developed subCSTs IV-D0, IV-D1, IV-D2, and IV-E-dominated primarily by Gardnerella vaginalis-to improve classification. Among paired microbiomes, the endocervix had a significantly higher alpha diversity and, independently, higher diversity for high-risk human papilloma virus (HPV) genotypes compared to low-risk and no HPV. Ct-infected endocervical networks had smaller clusters without interactions with potentially beneficial Lactobacillus spp. Overall, these data suggest that G. vaginalis may generate polymicrobial biofilms that predispose to and/or promote Ct and possibly HPV persistence and pathogenicity. Our findings expand on the existing repertoire of endocervical and vaginal microbiomes and fill in knowledge gaps regarding Pacific Islanders.

Quantifying the relationship between climatic indicators and leptospirosis incidence in Fiji: A modelling study.

Leptospirosis, a global zoonotic disease, is prevalent in tropical and subtropical regions, including Fiji where it's endemic with year-round cases and sporadic outbreaks coinciding with heavy rainfall. However, the relationship between climate and leptospirosis has not yet been well characterised in the South Pacific. In this study, we quantify the effects of different climatic indicators on leptospirosis incidence in Fiji, using a time series of weekly case data between 2006 and 2017. We used a Bayesian hierarchical mixed-model framework to explore the impact of different precipitation, temperature, and El Niño Southern Oscillation (ENSO) indicators on leptospirosis cases over a 12-year period. We found that total precipitation from the previous six weeks (lagged by one week) was the best precipitation indicator, with increased total precipitation leading to increased leptospirosis incidence (0.24 [95% CrI 0.15-0.33]). Negative values of the Niño 3.4 index (indicative of La Niña conditions) lagged by four weeks were associated with increased leptospirosis risk (-0.2 [95% CrI -0.29 --0.11]). Finally, minimum temperature (lagged by one week) when included with the other variables was positively associated with leptospirosis risk (0.15 [95% CrI 0.01-0.30]). We found that the final model was better able to capture the outbreak peaks compared with the baseline model (which included seasonal and inter-annual random effects), particularly in the Western and Northern division, with climate indicators improving predictions 58.1% of the time. This study identified key climatic factors influencing leptospirosis risk in Fiji. Combining these results with demographic and spatial factors can support a precision public health framework allowing for more effective public health preparedness and response which targets interventions to the right population, place, and time. This study further highlights the need for enhanced surveillance data and is a necessary first step towards the development of a climate-based early warning system.

A single dose of quadrivalent HPV vaccine is highly effective against HPV genotypes 16 and 18 detection in young pregnant women eight years following vaccination: an retrospective cohort study in Fiji.

Background: In 2008/9, Fiji vaccinated >30,000 girls aged 9-12 years with the quadrivalent human papillomavirus (4vHPV) vaccine coverage for at least one dose was >60% (one dose only was 14%, two dose only was 13%, three doses was 35%). We calculated vaccine effectiveness (VE) of one, two and three doses of 4vHPV against oncogenic HPV genotypes 16/18, eight years following vaccination. Methods: A retrospective cohort study was undertaken (2015-2019) in pregnant women ≤23 years old, eligible to receive 4vHPV in 2008/9, with confirmed vaccination status. The study was restricted to pregnant women due to the cultural sensitivity of asking about sexual behavior in Fiji. For each participant a clinician collected a questionnaire, vaginal swab and genital warts examination, a median eight (range 6-11) years post vaccination. HPV DNA was detected by molecular methods. Adjusted VE (aVE) against the detection of vaccine HPV genotypes (16/18), the comparison group of non-vaccine genotypes (31/33/35/39/45/51/52/56/58/59/66/68), and genital warts were calculated. Covariates included in the adjusted model were: age, ethnicity and smoking, according to univariate association with any HPV detection. Findings: Among 822 participants the prevalence of HPV 16/18 in the unvaccinated, one, two and three-dose groups were 13.3% (50/376), 2.5% (4/158), 0% (0/99) and 1.6% (3/189), respectively; and for the non-vaccine high-risk genotypes, the detection rate was similar across dosage groups (33.2%-40.4%, p = 0.321). The aVE against HPV 16/18 for one, two and three doses were 81% (95% CI; 48-93%), 100% (95% CI; 100-100%), and 89% (95% CI; 64-96%), respectively. Prevalence of HPV 16/18 was lower among women with longer time since vaccination. Interpretations: A single dose 4vHPV vaccine is highly effective against HPV genotypes 16 and 18 eight years following vaccination. Our results provide the longest duration of protection for reduced dose 4vHPV schedule in a low- or middle-income country in the Western Pacific region. Funding: This study was supported by the Bill & Melinda Gates Foundation and the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government.

Patterns of within-host spread of Chlamydia trachomatis between vagina, endocervix and rectum revealed by comparative genomic analysis.

Introduction: Chlamydia trachomatis, a gram-negative obligate intracellular bacterium, commonly causes sexually transmitted infections (STIs). Little is known about C. trachomatis transmission within the host, which is important for understanding disease epidemiology and progression. Methods: We used RNA-bait enrichment and whole-genome sequencing to compare rectal, vaginal and endocervical samples collected at the same time from 26 study participants who attended Fijian Ministry of Health and Medical Services clinics and tested positive for C. trachomatis at each anatomic site. Results: The 78 C. trachomatis genomes from participants resolved into two major clades of the C. trachomatis phylogeny (the "prevalent urogenital and anorectal" clade and "non-prevalent urogenital and anorectal" clade). For 21 participants, genome sequences were almost identical in each anatomic site. For the other five participants, two distinct C. trachomatis strains were present in different sites; in two cases, the vaginal sample was a mixture of strains. Discussion: The absence of large numbers of fixed SNPs between C. trachomatis genomes within many of the participants could indicate recent acquisition of infection prior to the clinic visit without sufficient time to accumulate significant genetic variation in different body sites. This model suggests that many C. trachomatis infections may be resolved relatively quickly in the Fijian population, possibly reflecting common prescription or over-the-counter antibiotics usage.

Chlamydial and gonorrheal neglected sexually transmitted diseases among Pacific Islanders of the Western Pacific Region-A narrative review and call to action.

The Pacific Island countries of the Western Pacific Region have some of the highest rates of sexually transmitted Chlamydia trachomatis and Neisseria gonorrhoeae infections in the world. Despite this, there are few research studies that include Pacific Islanders. We conducted a narrative review of original research and surveys, including World Health Organization and Pacific Community reports, to determine the prevalence, management, and treatment of C. trachomatis and N. gonorrhoeae compared to HIV and syphilis from 1980 to 2022. Available epidemiologic data on C. trachomatis and N. gonorrhoeae indicated an extremely high prevalence-approximately 30% and 13%, respectively-among Pacific Islanders during this timeframe. These neglected sexually transmitted infections represent a significant burden and health disparity. Robust epidemiologic research is needed to identify modifiable risk factors for designing interventions and control strategies. Appropriate policies along with regional and international advocacy and aid are required to improve reproductive health among these vulnerable, understudied populations to avert preventable infections and sequelae.

Patterns of within-host spread of Chlamydia trachomatis between vagina, endocervix and rectum revealed by comparative genomic analysis.

Chlamydia trachomatis , a gram-negative obligate intracellular bacterium, commonly causes sexually transmitted infections (STIs). Little is known about C. trachomatis transmission within the host, which is important for understanding disease epidemiology and progression. We used RNA-bait enrichment and whole-genome sequencing to compare rectal, vaginal and endocervical samples collected at the same time from 26 study participants who attended Fijian Ministry of Health and Medical Services clinics and tested positive for C. trachomatis at each anatomic site. The 78 C. trachomatis genomes from participants were from two major clades of the C. trachomatis phylogeny (the "prevalent urogenital and anorecta"l clade and "non-prevalent urogenital and anorectal" clade). For 21 participants, genome sequences were almost identical in each anatomic site. For the other five participants, two distinct C. trachomatis strains were present in different sites; in two cases, the vaginal sample was a mixture of strains. The absence of large numbers of fixed SNPs between C. trachomatis strains within many of the participants could indicate recent acquisition of infection prior to the clinic visit without sufficient time to accumulate significant variation in the different body sites. This model suggests that many C. trachomatis infections may be resolved relatively quickly in the Fijian population, possibly reflecting common prescription or over-the-counter antibiotics usage. Importance: Chlamydia trachomatis is a bacterial pathogen that causes millions of sexually transmitted infections (STIs) annually across the globe. Because C. trachomatis lives inside human cells, it has historically been hard to study. We know little about how the bacterium spreads between body sites. Here, samples from 26 study participants who had simultaneous infections in their vagina, rectum and endocervix were genetically analyzed using an improved method to extract C. trachomatis DNA directly from clinical samples for genome sequencing. By analyzing patterns of mutations in the genomes, we found that 21 participants shared very similar C. trachomatis strains in all three anatomic sites, suggesting recent infection and spread. For five participants two C. trachomatis strains were evident, indicating multiple infections. This study is significant in that improved enrichment methods for genome sequencing provides robust data to genetically trace patterns of C. trachomatis infection and transmission within an individual for epidemiologic and pathogenesis interrogations.

Estimating the duration of antibody positivity and likely time of Leptospira infection using data from a cross-sectional serological study in Fiji.

BACKGROUND: Leptospirosis is a zoonotic disease prevalent throughout the world, but with particularly high burden in Oceania (including the Pacific Island Countries and Territories). Leptospirosis is endemic in Fiji, with outbreaks often occurring following heavy rainfall and flooding. As a result of non-specific clinical manifestation and diagnostic challenges, cases are often misdiagnosed or under-ascertained. Furthermore, little is known about the duration of persistence of antibodies to leptospirosis, which has important clinical and epidemiological implications. METHODOLOGY AND PRINCIPAL FINDINGS: Using the results from a serosurvey conducted in Fiji in 2013, we fitted serocatalytic models to estimate the duration of antibody positivity and the force of infection (FOI, the rate at which susceptible individuals acquire infection or seroconversion), whilst accounting for seroreversion. Additionally, we estimated the most likely timing of infection. Using the reverse catalytic model, we estimated the duration of antibody persistence to be 8.33 years (4.76-12.50; assuming constant FOI) and 7.25 years (3.36-11.36; assuming time-varying FOI), which is longer than previous estimates. Using population age-structured seroprevalence data alone, we were not able to distinguish between these two models. However, by bringing in additional longitudinal data on antibody kinetics we were able to estimate the most likely time of infection, lending support to the time-varying FOI model. We found that most individuals who were antibody-positive in the 2013 serosurvey were likely to have been infected within the previous two years, and this finding is consistent with surveillance data showing high numbers of cases reported in 2012 and 2013. CONCLUSIONS: This is the first study to use serocatalytic models to estimate the FOI and seroreversion rate for Leptospira infection. As well as providing an estimate for the duration of antibody positivity, we also present a novel method to estimate the most likely time of infection from seroprevalence data. These approaches can allow for richer, longitudinal information to be inferred from cross-sectional studies, and could be applied to other endemic diseases where antibody waning occurs.

Metagenomic Shotgun Sequencing of Endocervical, Vaginal, and Rectal Samples among Fijian Women with and without Chlamydia trachomatis Reveals Disparate Microbial Populations and Function across Anatomic Sites: a Pilot Study.

Chlamydia trachomatis is a sexually transmitted pathogen and a global public health concern. Little is known about the microbial composition and function across endocervical, vaginal, and rectal microbiomes in the context of C. trachomatis infection. We evaluated the microbiomes of 10 age-matched high-risk Fijian women with and without C. trachomatis using metagenomic shotgun sequencing (MSS). Lactobacillus iners and Lactobacillus crispatus dominated the vagina and endocervix of uninfected women. Species often found in higher relative abundance in bacterial vaginosis (BV)-Mageeibacillus indolicus, Prevotella spp., Sneathia spp., Gardnerella vaginalis, and Veillonellaceae spp.-were dominant in C. trachomatis-infected women. This combination of BV pathogens was unique to Pacific Islanders compared to previously studied groups. The C. trachomatis-infected endocervix had a higher diversity of microbiota and microbial profiles that were somewhat different from those of the vagina. However, community state type III (CST-III) and CST-IV predominated, reflecting pathogenic microbiota regardless of C. trachomatis infection status. Rectal microbiomes were dominated by Prevotella and Bacteroides, although four women had unique microbiomes with Gardnerella, Akkermansia, Bifidobacterium, and Brachyspira. A high level of microbial similarity across microbiomes in two C. trachomatis-infected women suggested intragenitorectal transmission. A number of metabolic pathways in the endocervix, driven by BV pathogens and C. trachomatis to meet nutritional requirements for survival/growth, 5-fold higher than that in the vagina indicated that endocervical microbial functions are likely more diverse and complex than those in the vagina. Our novel findings provide the impetus for larger prospective studies to interrogate microbial/microbiome interactions that promote C. trachomatis infection and better define the unique genitorectal microbiomes of Pacific Islanders. IMPORTANCE Chlamydia trachomatis is the primary cause of bacterial sexually transmitted infections worldwide, with a disturbing increase in annual rates. While there is a plethora of data on healthy and pathogenic vaginal microbiomes-defining microbial profiles and associations with sexually transmitted infections (STIs)-far fewer studies have similarly examined the endocervix or rectum. Further, vulnerable populations, such as Pacific Islanders, remain underrepresented in research. We investigated the microbial composition, structure, and function of these anatomic microbiomes using metagenomic shotgun sequencing among a Fijian cohort. We found, primarily among C. trachomatis-infected women, unique microbial profiles in endocervical, vaginal, and rectal microbiomes with an increased diversity and more complex microbial pathways in endocervical than vaginal microbiomes. Similarities in microbiome composition across sites for some women suggested intragenitorectal transmission. These novel insights into genitorectal microbiomes and their purported function require prospective studies to better define Pacific Islander microbiomes and microbial/microbiome interactions that promote C. trachomatis infection.

Prevention of bacterial complications of scabies using mass drug administration: A population-based, before-after trial in Fiji, 2018-2020.

Background: Scabies is an important predisposing factor of impetigo which can lead to serious bacterial complications. Ivermectin-based mass drug administration can substantially reduce scabies and impetigo prevalence in endemic settings, but the impact on serious bacterial complications is not known. Methods: We conducted a before-after trial in the Northern Division of Fiji (population: 131,914) of mass drug administration for scabies control. Prospective surveillance was conducted from 2018 to 2020. Mass drug administration took place in 2019, involving two doses of oral ivermectin or topical permethrin, delivered alongside diethylcarbamazine and albendazole for lymphatic filariasis. The primary outcomes were incidence of hospitalisations with skin and soft tissue infections, and childhood invasive infections and post-streptococcal sequelae. Secondary outcomes included presentations to primary healthcare with skin infections and community prevalence of scabies and impetigo. Findings: The incidence of hospitalisations with skin and soft tissue infections was 17% lower after the intervention compared to baseline (388 vs 467 per 100,000 person-years; incidence rate ratio 0.83, 95% CI, 0.74 to 0.94; P = 0.002). There was no difference in incidence of childhood invasive infections and post-streptococcal sequelae. Incidence of primary healthcare presentations with scabies and skin infections was 21% lower (89.2 vs 108 per 1000 person-years, incidence rate ratio, IRR 0.79, 95% CI, 0.78 to 0.82). Crude community prevalence of scabies declined from 14.2% to 7.7% (cluster-adjusted prevalence 12.5% to 8.9%; prevalence ratio 0.71, 95% CI, 0.28 to 1.17). Cluster-adjusted prevalence of impetigo declined from 15.3% to 6.1% (prevalence ratio 0.4, 95% CI, 0.18 to 0.86). Interpretation: Mass drug administration for scabies control was associated with a substantial reduction in hospitalisations for skin and soft tissue infections. Funding: National Health and Medical Research Council of Australia and Scobie and Claire Mackinnon Trust.

Costs of mass drug administration for scabies in Fiji.

In 2019, the Murdoch Children's Research Institute in partnership with the Fiji Ministry of Health and Medical Services carried out an integrated mass drug administration (MDA) for the treatment of scabies and lymphatic filariasis in the Northern Division of Fiji (population estimate 131,914). We conducted a retrospective micro-costing exercise focused on the cost of scabies control in order to inform budgeting and policy decision making in an endemic setting. We collected detailed information on financial and economic costs incurred by both parties during the course of the MDA campaign (April 2018 to July 2019). We also conducted interviews with personnel involved in the financial administration of the MDA campaign. The economic cost of delivering two doses of ivermectin was US$4.88 per person. The cost of donated drugs accounted for 36.3% of total MDA costs. In this first large-scale MDA for the public health control of scabies, the estimated cost of delivering MDA per person for scabies was considerably more expensive than the costs reported for other neglected tropical diseases. The important cost drivers included the remuneration of health care workers who were extensively involved in the campaign, coverage of hard-to-reach, mainly rural populations and the two-dose regimen of ivermectin. These results highlight the importance of these cost determinants and can be used to plan current and future MDA programs.

Community control strategies for scabies: A cluster randomised noninferiority trial.

BACKGROUND: Scabies is a neglected tropical disease hyperendemic to many low- and middle-income countries. Scabies can be successfully controlled using mass drug administration (MDA) using 2 doses of ivermectin-based treatment. If effective, a strategy of 1-dose ivermectin-based MDA would have substantial advantages for implementing MDA for scabies at large scale. METHODS AND FINDINGS: We did a cluster randomised, noninferiority, open-label, 3-group unblinded study comparing the effectiveness of control strategies on community prevalence of scabies at 12 months. All residents from 35 villages on 2 Fijian islands were eligible to participate. Villages were randomised 1:1:1 to 2-dose ivermectin-based MDA (IVM-2), 1-dose ivermectin-based MDA (IVM-1), or screen and treat with topical permethrin 5% for individuals with scabies and their household contacts (SAT). All groups also received diethylcarbamazine and albendazole for lymphatic filariasis control. For IVM-2 and IVM-1, oral ivermectin was dosed at 200 µg/kg and when contraindicated substituted with permethrin. We designated a noninferiority margin of 5%. We enrolled 3,812 participants at baseline (July to November 2017) from the 35 villages with median village size of 108 (range 18 to 298). Age and sex of participants were representative of the population with 51.6% male and median age of 25 years (interquartile range 10 to 47). We enrolled 3,898 at 12 months (July to November 2018). At baseline, scabies prevalence was similar in all groups: IVM-2: 11.7% (95% confidence interval (CI) 8.5 to 16.0); IVM-1: 15.2% (95% CI 9.4 to 23.8); SAT: 13.6% (95% CI 7.9 to 22.4). At 12 months, scabies decreased substantially in all groups: IVM-2: 1.3% (95% CI 0.6 to 2.5); IVM-1: 2.7% (95% CI 1.1 to 6.5); SAT: 1.1% (95% CI 0.6 to 2.0). The risk difference in scabies prevalence at 12 months between the IVM-1 and IVM-2 groups was 1.2% (95% CI -0.2 to 2.7, p = 0.10). Limitations of the study included the method of scabies diagnosis by nonexperts, a lower baseline prevalence than anticipated, and the addition of diethylcarbamazine and albendazole to scabies treatment. CONCLUSIONS: All 3 strategies substantially reduced prevalence. One-dose was noninferior to 2-dose ivermectin-based MDA, as was a screen and treat approach, for community control of scabies. Further trials comparing these approaches in varied settings are warranted to inform global scabies control strategies. TRIAL REGISTRATION: Clinitrials.gov NCT03177993 and ANZCTR N12617000738325.

Estimation of scabies prevalence using simplified criteria and mapping procedures in three Pacific and southeast Asian countries.

BACKGROUND: Scabies causes considerable morbidity in disadvantaged populations. The International Alliance for the Control of Scabies (IACS) published consensus criteria in 2020 to standardize scabies diagnosis. However, these criteria are complex, and a WHO informal consultation proposed simplified criteria for mapping, to identify regions of high prevalence as targets for mass drug administration. We aimed to investigate the accuracy of simplified criteria in determining scabies prevalence, compared to the 2020 IACS criteria. METHODS: We obtained data relating to demographics, relevant history and skin lesions from all-age prevalence surveys from Fiji (n = 3365) and Solomon Islands (n = 5239), as well as school-aged children in Timor-Leste (n = 1043). We calculated prevalence using the 2020 IACS criteria and simplified criteria and compared these disease estimates. RESULTS: There was no significant difference in the pooled prevalence using the two methods (2020 IACS criteria: 16.6%; simplified criteria: 15.6%; difference = 0.9, [95% CI -0.1, 2.0]). In Timor-Leste, the prevalence using simplified criteria was lower (26.5% vs 33.8%). Simplified criteria had a sensitivity of 82.3% (95% CI 80.2, 84.2) and specificity of 97.6% (95% CI 97.2, 97.9) compared to the 2020 IACS criteria. CONCLUSIONS: The scabies prevalence estimation using simplified criteria was similar to using the 2020 IACS criteria in high prevalence, tropical countries. The prevalence estimation was lower in the school-based survey in Timor-Leste. Mapping using simplified criteria may be a feasible and effective public health tool to identify priority regions for scabies control. Further work assessing use of simplified criteria for mapping in a field setting should be conducted.

Assessment of Rapid Diagnostic Tests for Typhoid Diagnosis and Assessment of Febrile Illness Outbreaks in Fiji.

Typhoid is an endemic in Fiji with increases observed since the early 2000s and frequent outbreaks reported. We assessed the diagnostic accuracy of currently available typhoid rapid diagnostic tests (RDTs) (TUBEX, Typhidot Rapid, and Test-It assay) to establish their performance against blood culture in Fiji and to examine their suitability for rapid typhoid outbreak identification. The performance of RDTs was assessed in the public health reference laboratory in Suva, Fiji, according to the manufacturers' instructions. A simulation was used to examine the potential use of RDTs for attribution of a febrile illness outbreak to typhoid. For the diagnostic evaluation, 179 patients were included; 49 had blood culture-confirmed typhoid, 76 had fever as a result of non-typhoid etiologies, and 54 were age-matched community controls. The median (interquartile range) age was 29 (20-46) years. Of the participants, 92 (51.4%) were male and 131 (73.2%) were indigenous Fijians. The sensitivities of the tests were 77.6% for TUBEX, 75.5% for Typhidot Rapid, and 57.1% for Test-It assay. The Test-It assay had the highest specificity of 93.4%, followed by Typhidot Rapid 85.5% and TUBEX 60.5%. Typhidot Rapid had the best performance in the simulation for attribution of a febrile illness outbreak to typhoid. Typhoid RDTs performed suboptimally for individual patient diagnosis due to low sensitivity and variable specificity. We demonstrate that RDTs could be useful in the field for rapid attribution of febrile illness outbreaks to typhoid. Typhidot Rapid had the best combination of sensitivity, specificity, positive and negative predictive values, cost, and ease of use for this purpose.

The impact of the rotavirus vaccine on diarrhoea, five years following national introduction in Fiji.

BACKGROUND: In 2012, Fiji became the first independent Pacific island country to introduce rotavirus vaccine. We describe the impact of rotavirus vaccine on all-cause diarrhoea admissions in all ages, and rotavirus diarrhoea in children <5 years of age. METHODS: An observational study was conducted retrospectively on all admissions to the public tertiary hospitals in Fiji (2007-2018) and prospectively on all rotavirus-positive diarrhoea admissions in children <5 years at two hospital sites (2006-2018, and 2010-2015), along with rotavirus diarrhoea outpatient presentations at one secondary public hospital (2010-2015). The impact of rotavirus vaccine was determined using incidence rate ratios (IRR) of all-cause diarrhoea admissions and rotavirus diarrhoea, comparing the pre-vaccine and post-vaccine periods. All-cause admissions were used as a control. Multiple imputation was used to impute missing stool samples. FINDINGS: All-cause diarrhoea admissions declined among all age groups except among infants ≤2 months old and adults ≥55 years. For children <5 years, all-cause diarrhoea admissions declined by 39% (IRR)=0•61, 95%CI; 0•57-0•65, p-value<0•001). There was an 81% (95%CI; 51-94%) reduction in mortality among all-cause diarrhoea admissions in children under <5 years. Rotavirus diarrhoea admissions at the largest hospital among children <5 years declined by 87% (IRR=0•13, 95%CI; 0•10-0•17, p-value<0•001). Among rotavirus diarrhoea outpatient presentations, the IRR was 0•39 (95%CI; 0•11, 1.21, p-value=0.077). INTERPRETATIONS: Morbidity and mortality due to rotavirus and all-cause diarrhoea in Fiji has declined in people aged 2 months to 54 years after the introduction of the RV vaccine. FUNDING: Supported by WHO and the Australian Government.

Prospective surveillance for invasive Staphylococcus aureus and group A Streptococcus infections in a setting with high community burden of scabies and impetigo.

BACKGROUND: Invasive Staphylococcus aureus (iSA) and group A Streptococcus (iGAS) impose significant health burdens globally. Both bacteria commonly cause skin and soft tissue infections (SSTIs), which can result in invasive disease. Understanding of the incidence of iSA and iGAS remains limited in settings with a high SSTI burden. METHODS: Prospective surveillance for admissions with iSA or iGAS was conducted at the referral hospital in Fiji's Northern Division over 48 weeks between July 2018 and June 2019. RESULTS: There were 55 admissions for iSA and 15 admissions for iGAS (incidence 45.2 and 12.3 per 100,000 person-years, respectively). The highest incidence was found in patients aged ≥65 years (59.6 per 100,000 person-years for iSA and iGAS). The incidence of iSA was higher in indigenous Fijians (iTaukei) (71.1 per 100,000 person-years) compared with other ethnicities (incidence rate ratio 9.7, 95% confidence interval 3.5-36.9). SSTIs were found in the majority of cases of iSA (75%) and iGAS (53.3%). Thirteen of the 14 iGAS strains isolated belonged to emm cluster D (n = 5) or E (n = 8). The case fatality rate was high for both iSA (10.9%) and iGAS (33.3%). CONCLUSIONS: The incidence of iSA and iGAS in Fiji is very high. SSTIs are common clinical foci for both iSA and iGAS. Both iSA and iGAS carry a substantial risk of death. Improved control strategies are needed to reduce the burden of iSA and iGAS in Fiji.

Prospective Surveillance of Primary Healthcare Presentations for Scabies and Bacterial Skin Infections in Fiji, 2018-2019.

Scabies, impetigo, and other skin and soft tissue infections (SSTIs) are highly prevalent in many tropical, low-middle income settings, but information regarding their burden of disease is scarce. We conducted surveillance of presentations of scabies and SSTIs, including impetigo, abscesses, cellulitis, and severe SSTI, to primary health facilities in Fiji. We established a monthly reporting system over the course of 50 weeks (July 2018-June 2019) for scabies and SSTIs at all 42 public primary health facilities in the Northern Division of Fiji (population, ≈131,914). For each case, information was collected regarding demographics, diagnosis, and treatment. There were 13,736 individual primary healthcare presentations with scabies, SSTI, or both (108.3 presentations per 1000 person-years; 95% confidence interval [CI], 106.6-110 presentations). The incidence was higher for males than for females (incidence rate ratio [IRR], 1.15; 95% CI, 1.11-1.19). Children younger than 5 years had the highest incidence among all age groups (339.1 per 1000 person-years). The incidence was higher among the iTaukei (indigenous) population (159.9 per 1000 person-years) compared with Fijians of Indian descent (30.1 per 1000 person-years; IRR, 5.32; 95% CI, 5.03-5.61). Abscess was the condition with the highest incidence (63.5 per 1,000 person-years), followed by scabies (28.7 per 1,000 person-years) and impetigo (21.6 per 1,000 person-years). Scabies and SSTIs impose a substantial burden in Fiji and represent a high incidence of primary health presentations in this population. The incidence in low-middle income settings is up to 10-times higher than that in high-income settings. New public health strategies and further research are needed to address these conditions.

Development and Evaluation of a Point-of-Care Test in a Low-Resource Setting with High Rates of Chlamydia trachomatis Urogenital Infections in Fiji.

Rapid and precise detection of Chlamydia trachomatis, the leading global cause of sexually transmitted infections (STI), at the point of care (POC) is required for treatment decisions to prevent transmission and sequelae, including pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and preterm birth. We developed a rapid POC test (POCT), termed LH-POCT, which uses loop-mediated amplification (LAMP) of nucleic acids. We performed a head-to-head comparison with the Cepheid Xpert CT/NG assay using clinician-collected, deidentified paired vaginal samples from a parent study that consecutively enrolled symptomatic and asymptomatic females over 18 years of age from the Ministry of Health and Medical Services Health Centers in Fiji. Samples were processed by the Xpert CT/NG assay and LH-POCT, blinded to the comparator. Discrepant samples were resolved by quantitative PCR. Deidentified clinical data and tests for Trichomonas vaginalis, Candida, and bacterial vaginosis (BV) were provided. There were a total of 353 samples from 327 females. C. trachomatis positivity was 16.7% (59/353), while the prevalence was 16.82% (55/327) after discrepant resolution. Seven discrepant samples resolved to four false negatives, two false positives, and one true positive for the LH-POCT. The sensitivity of the LH-POCT was 93.65% (95% confidence interval [CI], 84.53% to 98.24%), and specificity was 99.31% (95% CI, 97.53% to 99.92%). Discrepant samples clustered among women with vaginal discharge and/or BV. The prototype LH-POCT workflow has excellent performance, meeting many World Health Organization ASSURED criteria for POC tests, including a sample-to-result time of 35 min. Our LH-POCT holds promise for improving clinical practice to prevent and control C. trachomatis STIs in diverse health care settings globally.

Individual Efficacy and Community Impact of Ivermectin, Diethylcarbamazine, and Albendazole Mass Drug Administration for Lymphatic Filariasis Control in Fiji: A Cluster Randomized Trial.

BACKGROUND: Bancroftian filariasis remains endemic in Fiji despite >10 years of mass drug administration (MDA) using diethylcarbamazine and albendazole (DA). The addition of ivermectin to this combination (IDA) has improved efficacy of microfilarial clearance at 12 months in individually randomized trials in nocturnal transmission settings, but impact in a setting of diurnally subperiodic filarial transmission has not been evaluated. METHODS: This cluster randomized study compared the individual efficacy and community impact of IDA vs DA as MDA for lymphatic filariasis in 35 villages on 2 islands of Fiji. Participants were tested at enrollment for circulating filarial antigen and, if positive, for microfilariae. Weight-dosed treatment was offered according to village randomization. Communities were visited at 12 months and retested for lymphatic filariasis. Infected individuals from Rotuma were retested at 24 months. RESULTS: A total of 3816 participants were enrolled and 3616 were treated. At 12 months, microfilariae clearance was achieved in 72 of 111 participants detected with infection at baseline, with no difference in efficacy between treatment groups: DA, 69.2% (95% confidence interval [CI], 57.2%-79.1%) vs IDA, 62.5% (95% CI, 43.6%-78.2%); risk difference, 11.3 % (95% CI, -10% to 32.7%); P = .30. There was no difference between treatment groups in community prevalence of microfilariae at 12 months or individual clearance at 24 months. CONCLUSIONS: We found no difference between IDA and DA in individual clearance or community prevalence of lymphatic filariasis at 12 months, and no improved efficacy following a second annual round of IDA. Possible explanations for the apparent lack of benefit of IDA compared to DA include drug and parasite factors affecting clearance, and higher than expected reinfection rates. Clinical Trials Registration: NCT03177993 and Australian New Zealand Clinical Trial Registry: N12617000738325.

Interactions between timing and transmissibility explain diverse flavivirus dynamics in Fiji.

Zika virus (ZIKV) has caused large, brief outbreaks in isolated populations, however ZIKV can also persist at low levels over multiple years. The reasons for these diverse transmission dynamics remain poorly understood. In Fiji, which has experienced multiple large single-season dengue epidemics, there was evidence of multi-year transmission of ZIKV between 2013 and 2017. To identify factors that could explain these differences in dynamics between closely related mosquito-borne flaviviruses, we jointly fit a transmission dynamic model to surveillance, serological and molecular data. We estimate that the observed dynamics of ZIKV were the result of two key factors: strong seasonal effects, which created an ecologically optimal time of year for outbreaks; and introduction of ZIKV after this optimal time, which allowed ZIKV transmission to persist over multiple seasons. The ability to jointly fit to multiple data sources could help identify a similar range of possible outbreak dynamics in other settings.