Prevalence Settings Research Articles

P-2124. Validation of BM-AspICU Clinical Algorithm in Critically Ill Patients with Suspected Invasive Pulmonary Aspergillosis in Medical ICU Using Post-Mortem Minimally Invasive Tissue Sampling

Abstract Background Post-mortem studies have shown significant underestimation of invasive pulmonary aspergillosis in critically ill ICU patients, in resource-limited settings due to limited awareness, diagnostic capabilities, and ubiquitous presence of Aspergillus spores. The revised BM AspICU algorithm for critically ill patients was validated in a historical cohort, with changes in the host and imaging criteria as well as inclusion of PCR assays. This study for the first time prospectively evaluated the utility of the criteria in a cohort of ICU patients, using post-mortem minimally invasive tissue sampling.Figure 1.Study methodology (Prospective validation of BM Asp ICU clinical algorithm) Patients on mechanical ventilation with a host risk factor, clinical or imaging sign or Aspergillus growth from lower respiratory tract were recruited as per the BM-Asp ICU algorithm . All patients underwent blood and bronchoalveolar lavage fluid Aspergillus PCR on Day 0, 6 and 12 and biomarker (galactomannan) estimation in blood and lavage fluid every third day till death/recovery from illness. The analysis was done on patients who expired and post-mortem minimally invasive tissue samples could be obtained for PCR, KOH staining, and culture and histopathology. Methods Patients on mechanical ventilation with a host risk factor, clinical or imaging sign or Aspergillus growth in lower respiratory tract were recruited (Figure 1). All patients underwent blood and bronchoalveolar lavage fluid Aspergillus PCR and biomarker (Galactomannan) estimation in blood and lavage fluid till death/recovery from illness. Post-mortem MITS was done to obtain samples for histopathology, KOH staining for hyphae and culture and Aspergillus PCR to enable classification as definite IPA/not as per the revised algorithm.Figure 2Host risk factors in study population Results A total of 135 patients were included, out of whom 99 expired. MITS was done in 66 patients, allowing classification as definite IPA or not. The mean age was 43+16 years with 47% males (n=66). 21% (n=14) had an EORTC risk factor while of the remaining, 98% (n=51) had a non-EORTC risk factor for IPA (Figure 2). The overall tests characteristics for the BM Asp ICU clinical algorithm showed a sensitivity of 84.5% [95% CI (72.6-92.6)], specificity of 42.9% [95% CI (9.9-81.6)], PPV of 92.4% [95% CI (86.5-95.9)] and NPV of 25% [95% CI (10.5-48.7)]. The test performance of biomarker compared poorly when compared to PCR in blood and BAL samples (Figure 3).Figure 3Study results Conclusion The revised BM Asp ICU clinical algorithm caters to non-neutropenic critically ill patients in ICU, under-recognised by the EORTC MSG criteria. This first-of-its-kind prospective study shows moderate sensitivity in a high prevalence setting, indicating a possible need for further modifications to ensure timely recognition of IPA. Biomarkers compared poorly when compared to PCR overall, with BAL PCR performing better as compared PCR testing in blood samples. Disclosures All Authors: No reported disclosures

P-1762. Assessing the Clinical Impact of Carbapenem Pre-authorization in a High ESBL Prevalence Setting: A Focus on the Middle East

Abstract Background Hospitals commonly employ preauthorization as a strategy to optimize carbapenems utilization. However, there is paucity of data regarding carbapenem restriction in environments with a high prevalence of extended-spectrum beta-lactamase (ESBL) organisms. This study aims to assess the impact of implementing a preauthorization policy for carbapenems on patient clinical outcomes and appropriateness of use. Methods An observational retrospective cohort study comparing data collected for patients from pre-restriction period between December 2021 and May 2022, and post-restriction period between June 2022 and December 2023 who were prescribed carbapenems including ertapenem or meropenem. The restriction policy was implemented in June 2022. We included adult patients ( > 18 years old) with active infections in acute care units (ACU). Results A total of 244 patient were included in the study with 131 in pre implementation period and 113 in post implementation period. The appropriate indication of carbapenems use was significantly higher in the post-restriction group 69.9% (79) vs the pre-restriction group 55.7% (73) (P=0.025). No significant difference was found between the two groups in terms of appropriateness of treatment duration (P=0.425). Antibiotic de-escalation was significantly higher in the pre-restriction group 60.3% (79) vs the post-restriction group 35.4% (40) (P< 0.001). The 30-day all cause mortality was significantly lower in the post-restriction group 7.1% (8) vs the pre-restriction group 19.8% (26) (P=0.005). Length of hospital stay (LOS) was significantly lower in the post-restriction group compared to the pre-restriction group; 6 vs 9 days (P=0.002). Furthermore, the 30-day readmission rate was 32.1% (42) of patients in the pre-restriction group vs 20.4% (23) in the post-restriction group (P=0.043). Table 2 Conclusion Despite ESBL high prevalence, preauthorization policy for carbapenems prescription showed efficacy to optimize their use in terms of, both, appropriateness, and duration. Lower 30-day mortality, LOS and readmissions within ACU patients also confirmed better clinical outcomes. Larger studies are needed to corroborate these findings. Disclosures All Authors: No reported disclosures

627. Outcomes of Military Blood Donors Screening Positive for Trypanosoma cruzi

Abstract Background First time blood donors at the Armed Service Blood Bank-San Antonio are screened for Trypanosoma cruzi infection with a chemiluminescent microparticle immunoassay (CMIA) followed by a confirmatory enzyme strip assay (ESA). In military populations, T. cruzi positivity on a screening test accounts for the fourth most common reason for post-donation deferral. With concerns for low positive predictive value in a low prevalence disease, this study evaluated the clinical outcomes and diagnostic work-up of blood donors who screened positive on T. cruzi CMIA testing.Table 1:Workup of 49 blood donors who screened positive for Trypanosoma cruzi infection Methods All blood donors from 2017-2022 were screened for T. cruzi antibodies with CMIA and deferred indefinitely if screening was positive, regardless of ESA result. All donors that initially screened positive for T. cruzi infection were evaluated to determine diagnostic work-up, further testing, specialty appointments seen, and final diagnosis of each case following their initial positive blood donation screen.Table 2:Clinical outcomes of 4 blood donors with positive T. cruzi screening test and confirmatory test Results Of 89,459 blood donors during the study period, 49 (57.3 per 100k donors) screened positive for Chagas disease on initial blood donation. Of those individuals, 4 (8%) had positive, 18 (36%) had indeterminate, and 30 (61%) had negative confirmatory tests. The evaluation varied significantly depending on the results of ESA testing, however there were no blood donors who met criteria for Chagas disease (Table 1). Evaluation of four donors with positive CMIA and ESA showed only one with repeat positivity on one assay, but all were ultimately deemed negative (Table 2). Conclusion While positive T. cruzi antibodies were a common reason for post-donation deferral in this cohort, there were no confirmed cases of Chagas disease, despite most patients receiving an extensive work-up. Patients with positive or indeterminate ESA received more specialty care and more confirmatory testing than those with a negative confirmatory test. This study demonstrates the need for higher specificity screening and confirmatory tests for T. cruzi in blood donors in low prevalence settings. Disclosures All Authors: No reported disclosures

Implementing HIV teams to improve HIV indicator condition-guided testing in general practitioner centers in the Netherlands

BackgroundHIV indicator condition-guided testing is recommended by guidelines to identify undiagnosed HIV infections. However, general practitioners (GPs) frequently see patients for indicator conditions without testing them for HIV. The aim of this study was to evaluate whether implementing HIV teams, using trained GP ambassadors, promoted local HIV indicator condition-guided testing practices in urban GP centers in the Netherlands.MethodsWe conducted a prospective implementation study between May 2021 and March 2023. Patients ≥ 18 years newly diagnosed with HIV indicator conditions in three GP centers were included. The intervention consisted of HIV expert led education for GPs with a stepwise implementation of point-of-care testing (phase 1), followed by adding peer-to-peer case feedback by trained GP ambassadors (phase 2). Questionnaires were used to assess the experiences and beliefs of HIV indicator condition-driven testing in patients and GPs. The primary outcome was the overall HIV testing rate in patients diagnosed with indicator conditions compared to pre-implementation. Secondary outcomes were HIV testing rate per phase and per indicator condition, HIV positivity rate, and patients’ and GPs’ experiences with this testing strategy.ResultsIn 132,338 patient visits, 846 (0.6%, 95%CI 0.6–0.7%) HIV indicator conditions were diagnosed, including 485 sexually transmitted infections (57.3%). Overall, 215 (25.4%) indicator conditions were tested for HIV after the implementation of HIV teams. The testing rate was comparable between the two phases (25.2% versus 25.9%, p = 0.83). The testing rates pre- and post-implementation were comparable (21.3% versus 25.4%, p = 0.33). The most frequently tested HIV indicator conditions were unexplained weight loss (n = 13, 41.9%), unexplained lymphadenopathy (n = 8, 38.1%), and sexually transmitted infections (n = 161, 33.2%). Three patients (1.4%, 95%CI 0.3–4.0%) tested positive for HIV. Test acceptance in patients was high as was the self-perceived knowledge of GPs on HIV indicator conditions.ConclusionsImplementing HIV teams did not enhance HIV indicator condition-guided testing in urban GP centers from a low HIV prevalence setting. The high patients acceptance rate and self-perceived knowledge among GPs regarding HIV indicator conditions did not manifest in high HIV testing rates. Patients accepted testing, but a gap was found between the self-perceived knowledge of GPs regarding HIV indicator conditions and testing, and the actual HIV testing rate.Trial registrationClinicalTrials.gov NCT05225493 (registration date: 17-01-2022).

An integrated, multidisciplinary management team intervention to improve patient-centeredness, HIV, and maternal-child outcomes in Lesotho: formative research on participatory implementation strategies

BackgroundReducing perinatal HIV transmission and optimizing maternal and child health (MCH) outcomes in high HIV prevalence settings is an urgent, but complex, priority. Extant interventions over-emphasize individual-level provider and patient behaviors, and neglect critical health systems-level changes. The ‘Integrated Management Team to Improve Maternal-Child Outcomes (IMPROVE)’ study implemented a three-part, patient-centered, health-systems-level intervention to improve MCH and HIV outcomes in Lesotho. Ensuring intervention fit within the health systems context is important, but often overlooked. This manuscript describes implementation research conducted to tailor and adapt intervention implementation to optimize appropriateness, acceptability, and feasibility. It identifies resulting implementation variation across study sites and lessons learned.MethodsThe research team reviewed intervention implementation documentation and conducted structured reflections to: 1) assess implementation strategy adaptations, 2) identify facility-specific strategies employed to improve the MCH patient experience, and 3) synthesize lessons.ResultsFacility-based, integrated, multi-disciplinary management teams (MDT) were feasible and acceptable to establish through engagement with facility leadership and facilitation of a participatory training curriculum that established shared values between cadres supporting MCH, and identified facility-specific service delivery gaps and potential solutions. Ongoing MDT meetings provided coordination between facility and community-based MCH service providers to implement early ANC follow-up. Facility-specific improvement strategies included fee, staffing, and patient documentation-based changes. Piloting Positive Health, Dignity, and Prevention-focused counseling approaches resulted in tailored job aids pre-implementation. Leadership involvement was critical for improved coordination while staff turnover and competing donor priorities challenged MDT efforts.ConclusionsIMPROVE created facility-specific adaptation opportunities through participatory intervention implementation practices. The MDTs, benefitting from leadership support, built relationships between HCW cadres, led facility-specific quality improvements, and, importantly, offered HCWs sought-after positive feedback by recognizing HCW efforts. The coordination, monitoring and cross-cadre communication functions of the MDTs supported implementation of other interventions, and may serve as a valuable platform for improving patient-centered care practices in similar settings and for other health services. Trial registration number: NCT04598958, 05 October 2020, retrospectively registered.Trial registrationClinicalTrials.gov, NCT04598958. Registered 05 October 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT04598958

Bronchiectasis in children in a high HIV and tuberculosis prevalence setting

Bronchiectasis in children in a high HIV and tuberculosis prevalence setting

Seroepidemiology of trachoma in a low prevalence region receiving annual mass azithromycin distribution in Maradi, Niger.

Trachoma programs use the indicator trachomatous inflammation--follicular (TF) to monitor indication for and response to treatment for trachoma at the district level. Alternative indicators, including serologic markers, are increasingly being evaluated for trachoma surveillance. We evaluated seroprevalence of IgG antibodies to the Pgp3 antigen in two districts in Maradi, Niger thought to have low TF prevalence. Data were collected as part of the baseline assessment of the Azithromycin Reduction to Reach Elimination of Trachoma (ARRET) trial in September 2021. A random sample of 80 communities was selected from Mayahi and Guidan Roumdji districts, both of which had TF prevalence <20% at their most recent trachoma impact survey in 2018. A random sample of 50 children per community was sampled. We collected field grades, conjunctival swabs for processing PCR for ocular Chlamydia trachomatis, and dried blood spots for serologic assessment. Of 3,994 children sampled in 80 communities, 49% were female and median age was 4 years. Overall TF prevalence was 4.6% (95% CI 3.5 to 5.8%) and trachomatous inflammation-intense (TI) prevalence was 0.6% (95% 0.3 to 0.9%). The prevalence of ocular chlamydia was 0.03% (95% CI 0.08%). Seroprevalence for Pgp3 antibodies was 6.3% (95% CI 5.5 to 7.1%) in 1-9-year-olds and 3.7% (95% CI 2.9 to 4.4%) in 1-5-year-olds. TF and Pgp3 seroprevalence were better correlated in 1-5-year-olds (correlation coefficient 0.29) compared to 1-9-year-olds (correlation coefficient 0.09). In this low trachoma prevalence setting in Niger, seroprevalence of antibodies to Pgp3 were consistent with little ongoing transmission of C. trachomatis.

A comparison of the diagnostic capability of Kato-Katz and real-time PCR for the assessment of treatment efficacy of ivermectin and albendazole combination against T. trichiura infections.

Trichuris trichiura is humans' second most prevalent soil-transmitted helminth (STH) infection after Ascaris lumbricoides, affecting approximately 460 million people worldwide. Despite its sub-optimal sensitivity, especially in low prevalence and infection intensity settings, the modified Kato-Katz (K-K) is still recommended as a diagnostic method by the World Health organization (WHO) guidelines. Within a randomized clinical trial (RCT) comprising four treatment arms with two different anthelmintics, the present study reports an important secondary research objective to determine the diagnostic agreement between K-K and real-time PCR evaluating treatment efficacy against T. trichiura. The parasitological results were analyzed, including cure rates (CR) of a subgroup of 94 participants positive at baseline for T. trichiura eggs for both techniques. The single-dose albendazole (ALB) arm resulted in significantly lower CRs than experimental arms of albendazole/ivermectin (ALB/IVM) combinations. The overall diagnostic agreement between both techniques was 88.7% [κ = 0.8 (P<0.001)]. Concordance between eggs per gram and Ct values was moderate, with the discordance source likely stemming from lighter infection intensities. These findings indicate that real-time PCR is a suitable alternative for CR estimation in helminthiasis clinical trials. It also highlights the need to identify the most accurate diagnostic tools for RCTs, that would benefit from guiding principles to achieve harmonization across studies and are not necessarily the same as those used for epidemiological surveys. Clinical Trials.gov (NCT04041453).

Knowledge and uptake of contraceptive and other sexual reproductive health services among in-school adolescents in three South African townships: Baseline findings from the Girls Achieve Power (GAP Year) Trial

Background South African adolescents experience barriers to sexual and reproductive health (SRH) knowledge and uptake. This study provides insight into contraceptive and other SRH service knowledge, perceptions, and uptake among adolescents in high HIV prevalence settings. Methods A baseline cross sectional survey was conducted among 3432 grade 8s enrolled into the Girls Achieve Power (GAP Year) trial from 26 public high schools across three South African townships (Soweto, Thembisa and Khayelitsha) (2017 - 2018). An interviewer-led survey collected information on SRH knowledge and perceptions; an audio computer-assisted self-interviewing technique gathered SRH service uptake. Descriptive analysis indicates frequency distribution of socio-demographics and knowledge, uptake and perceptions of SRH services. Chi-square test tested for associations between age and sex and selected variables that measure SRH knowledge and uptake. Results In total, 2383 participants completed both survey components. Of these, 63.1% (n=1504) were female and 81.4% (n=1938) aged 12-14. Almost a fifth (18.3%, n=436) had ever had sex and less than 1% had accessed SRH services in the last year. Of the 157 females who had ever had sex, 50.9% had ever used contraception. Of those who had sex in the last three months, 59.0% reported using a contraceptive method. Condom use was inconsistent: almost all females said they had not used or could not remember if a condom was used at last sex. Conclusion This paper contributes to the evidence strengthening learner SRH education, including the national Integrated School Health Programme. Key themes include the need for age-appropriate, differentiated comprehensive sexuality education (CSE) for the range of ages found in the same grade in South African schools. Education on different contraceptive methods, informed decision-making, and emergency contraception is key. School-based interventions should embrace integrated HIV, STI, and pregnancy prevention messages. Closer links with health services need to be constantly fostered and reinforced.

Carbapenem-resistant Enterobacterales/Enterobacteriaceae (CRE) in Indonesia: protocol for systematic review and meta-analysis

Abstract Background Carbapenem-resistant Enterobacterales (CRE) pose a significant global health threat, with increasing prevalence worldwide, including in Indonesia. Despite the public health impact, comprehensive data on the burden of CRE in Indonesia remains fragmented. This protocol outlines a systematic review and meta-analysis aiming to estimate the prevalence of CRE in Indonesia, summarize trends over time, and identify key resistance mechanisms. Methods We will conduct a systematic search across multiple electronic databases, including PubMed, Scopus, and local Indonesian databases, for studies reporting the prevalence of CRE in Indonesia from 2008 to 2024. Eligibility criteria include observational studies (cross-sectional, cohort, and case-control) and surveillance reports. Data extraction will focus on CRE prevalence, bacterial species, sample types, resistance mechanisms, and study settings (hospital vs. community). Quality assessment of studies will be performed using the Newcastle-Ottawa Scale (NOS). Meta-analysis will be conducted using a random-effects model to estimate pooled prevalence, and subgroup analysis will explore variations by geographical region, period, and healthcare setting. Discussion This systematic review and meta-analysis will provide the first comprehensive overview of CRE prevalence in Indonesia, contributing to an improved understanding of the national burden and resistance patterns. The findings will guide public health policies and inform antimicrobial stewardship efforts in Indonesia. Registration PROSPERO CRD42024580177

Risk factors for severe respiratory syncytial virus-associated respiratory tract infection in a high HIV prevalence setting, South Africa, 2012 – 2018

BackgroundIdentifying risk factors for respiratory syncytial virus (RSV)–associated severe acute respiratory illness (SARI) will assist with targeting vaccine interventions.MethodsUsing surveillance data from South Africa (2012–2018), we compared the characteristics of individuals with RSV-associated influenza-like illness (ILI) (reference group) to those with RSV-associated SARI to describe factors associated with SARI using a multivariable analysis.ResultsRSV was detected in 6% (483/7792) of ILI cases and 15% (844/5672) of SARI cases. Factors associated with SARI in children included age < 2 months, compared to age 2–4 years (adjusted odds ratio (aOR) 54.4; 95% confidence interval (CI) 23.5–125.8), malnutrition (aOR 1.9; 95% CI 1.2–3.2), prematurity (aOR 2.4; 95% CI 1.3–4.6) and living with HIV (LWH) (aOR 22.5; 95% CI 2.9–174.3). In individuals ≥ 5 years, factors associated with SARI included age ≥ 65 years compared to age 5–24 years (aOR 10.7; 95% CI 1.1–107.5), symptom duration ≥ 5 days (aOR 2.7; 95% CI 1.1–6.3), underlying illness (aOR 2.7; 95% CI 1.5–26.1) and LWH (aOR 16.8, 95% CI: 4.8–58.2).ConclusionIndividuals at the extremes of age and those with identified risk factors might benefit most from RSV prevention interventions.Clinical trial numberNot applicable, this is not a clinical trial.

Preferences for pre-exposure prophylaxis delivery via online pharmacy among potential users in Kenya: a discrete choice experiment.

Oral pre-exposure prophylaxis (PrEP) is highly effective, but coverage remains low in high HIV prevalence settings. Initiating and continuing PrEP remotely via online pharmacies is a promising strategy to expand PrEP uptake, but little is known about potential users' preferences. We conducted a discrete choice experiment (DCE) to assess preferences for online pharmacy PrEP services. We partnered with MYDAWA, an online pharmacy in Nairobi, Kenya. Eligibility criteria were: ≥18 years, not known HIV positive, interested in PrEP. The DCE contained four attributes: PrEP eligibility assessment (online self-assessed, guided), HIV test type (provider administered, oral HIV self-test [HIVST], blood-based HIVST), clinical consultation (remote, in-person) and user support options (text messages, phone/video call, email). Additionally, participants indicated whether they were willing to uptake their selected service. The survey was advertised on MYDAWA's website; interested participants met staff in-person at a convenient location to complete the survey from 1 June to 20 November 2022. We used conditional logit modelling with an interaction by current PrEP use to estimate overall preferences and latent class analysis (LCA) to assess preference heterogeneity. Overall, 772 participants completed the DCE; the mean age was 25 years and 54% were female. Most participants indicated a willingness to acquire online PrEP services, with particularly high demand among PrEP-naive individuals. Overall, participants preferred remote clinical consultation, HIV self-testing, online self-assessment and phone call user support. The LCA identified three subgroups: the "prefer online PrEP with remote components" group (60.3% of the sample) whose preferences aligned with the main analysis, the "prefer online PrEP with in-person components" group (20.7%), who preferred in-person consultation, provider-administered HIV testing, and guided assessment, and the "prefer remote PrEP (18.9%)" group who preferred online PrEP services only if they were remote. Online pharmacy PrEP is highly acceptable and may expand PrEP coverage to those interested in PrEP but not accessing services. Most participants valued privacy and autonomy, preferring HIVST and remote provider interactions. However, when needing support for questions regarding PrEP, participants preferred phone/SMS contact with a provider. One-fifth of participants preferred online PrEP with in-person components, suggesting that providing multiple options can increase uptake.

Computed Tomography of the Head Before Lumbar Puncture in Adults With Suspected Meningitis in High-HIV Prevalence Settings.

The role of computed tomography (CT) before lumbar puncture (LP) is unclear, with limited evidence for a causal link between LP and cerebral herniation or for the ability of CT to identify individuals at risk of herniation. The risks of LP delay or deferral are potentially greater in high-HIV prevalence, resource-limited settings; we analyzed data from such a setting to determine the impact of CT on time to LP and treatment, as well as mortality. Adults with suspected central nervous system (CNS) infection were enrolled prospectively into the Botswana National Meningitis Survey between 2016 and 2019. Inpatient mortality and clinical data including time of treatment initiation and CT were captured from medical records. Associations between preceding CT and outcomes were assessed using logistic regression. LPs were performed in 711 patients with suspected CNS infection; 27% had a CT before LP, and 73% were HIV positive. Time from admission to LP and time from admission to appropriate treatment were significantly longer in patients who had a CT before LP compared with those who did not (2.8 hours and 13.2 hours, respectively). There was some evidence for treatment delays being associated with increased mortality; however, there was no significant difference in mortality between those who had or did not have CT. Patients who had a CT had delays to diagnostic LP and initiation of appropriate treatment; although treatment delays were associated with increased mortality, our observational study could not demonstrate a causal association between delays in diagnosis and treatment introduced by CT and mortality.

Index-Linked Assisted HIV Self-Testing for Children 2-14 Years: Results of a Pilot Evaluation in Ethiopia.

Case identification remains a challenge to reaching the United Nations 95-95-95 targets for children with HIV. Although the World Health Organization approved oral mucosal HIV self-testing (HIVST) for children older than 2 years in 2019, there is little information on HIVST for pediatric case identification in Ethiopia. Nine health facilities across Ethiopia. We implemented a pilot program from November 2021 to April 2022 to assess acceptability and feasibility of using HIVST to screen children 2-14 years of adult index clients, (ie, parents/caregivers living with HIV and on antiretroviral therapy). HIV-positive adults who had children with unknown HIV status were given HIVST kits (OraQuick) to screen their children at home. Parents/caregivers were asked to report results telephonically and bring children screening positive to the health facility for confirmatory HIV testing. We defined HIVST acceptability as ≥50% of parents/caregivers accepting testing and ≥50% reporting results within 7 days of receiving a test kit. Feasibility was defined as ≥60% of children with a reactive HIVST receiving confirmatory testing and <5 serious social harms reported per 1000 kits distributed. Overall, 1496 of 1651 (91%) parents/caregivers accepted HIVST kits to test their children at home and 1204 (71%) reported results within 7 days. Of 17 children (1%) with reactive results, 13 (76%) received confirmatory testing; of which 7 (54%) were confirmed to be HIV positive. One serious social harm was reported. Providing adult parents/caregivers with HIVST kits to screen their children at home is an acceptable and feasible strategy to reach untested children and improve pediatric case finding in a low prevalence setting.

Evaluation of three serological tests for the diagnosis of Brucella suis in dogs using Bayesian latent class analysis

Brucella suis infection of dogs is an emerging issue worldwide requiring specific management to address zoonotic risks and animal welfare concerns. Diagnosis in dogs is routinely based on serological testing, but to date these tests have only been validated for use in production animal species and humans. This study aimed to assess the diagnostic performance of three commonly used serological tests in dogs. Canine sera (n = 989) were tested with the Rose Bengal rapid plate agglutination test (RBRPT), the complement fixation test (CFT) and a competitive ELISA (C-ELISA). Diagnostic test performance was evaluated using a three test, two population Bayesian latent class analysis accounting for conditional dependence between the three tests. Positive and negative predictive values (PPV, NPV) were calculated for a range of expected prevalence estimates for the individual tests and test combinations interpreted in series and parallel. The RBRPT showed the highest individual Se of 0.902 (95 % posterior credible interval [PCI] 0.759-0.978) and the CFT the highest individual diagnostic specificity (Sp) of 0.914 (95 % PCI 0.886-0.946). The C-ELISA had marginally the best overall diagnostic performance (Youden's index = 0.807). The CFT and the C-ELISA interpreted in parallel returned the highest combined Se and Sp (0.988 and 0.885, respectively). All tests returned NPVs of > 0.982 in 2-8 % prevalence settings. Series interpretation of the three-test combination as well as the two-test combinations of the RBRPT and the C-ELISA and the CFT and the C-ELISA produced a PPV of 0.502 when the estimated prevalence was 8 %. While all tests are suitable for the detection of B. suis antibodies in dogs, they should not be interpreted in isolation as their diagnostic value is dependent on the pre-test probability of the disease. As such they are useful tools for the diagnosis of B. suis in dogs when exposure, history and clinical presentation indicate a risk of brucellosis.

Malaria Rapid Tests, Febrile Illness Management, and Child Mortality Across Sub-Saharan African Countries

A prompt malaria diagnosis is crucial for the management of children with febrile illness in sub-Saharan African countries, where malaria remains a leading cause of mortality among children younger than 5 years of age. The development and distribution of point-of-care rapid diagnostic tests (RDTs) for malaria has transformed practice, but limited systematic evidence exists on how malaria RDTs have affected the management of febrile illness and mortality for children younger than 5 years of age across sub-Saharan Africa countries. To evaluate the association between the distribution of malaria RDTs and the management of febrile illness and mortality among children younger than 5 years of age in sub-Saharan African countries. This quasi-experimental study used a novel dataset linking malaria RDT distribution to 165 nationally representative household surveys across 35 sub-Saharan African countries with mortality data. The sample comprised approximately 3.9 million child-year observations and approximately 260 000 febrile illness episodes in children younger than 5 years of age between 2000 and 2019. Fixed-effects linear probability models were used to analyze the association between variation in malaria RDTs distributed per child younger than 5 years of age (by country per year) and blood testing, antimalarial drug use, antibiotic use, use of symptomatic treatments, and mortality rates. Variation in the effects of testing and treatment was also assessed across the sub-Saharan African countries that had varying prevalence of malaria. The mortality sample included 1 317 866 children and the fever sample included 256 292 children. The mean age of the children with febrile illness was 2.4 years (SD, 1.3 years) and 49% were female. Each additional malaria RDT distributed per child younger than 5 years of age was associated with an increase of 3.5 percentage points (95% CI, 3.2-3.8 percentage points) in blood testing, an increase of 1.5 percentage points (95% CI, 1.2-1.8 percentage points) in the use of antimalarial drugs, an increase of 0.4 percentage points (95% CI, 0.1-0.6 percentage points) in antibiotic use, and a decrease of 0.4 percentage points (95% CI, 0.1-0.8 percentage points) in the use of treatments for symptoms. Each additional malaria RDT distributed per child younger than 5 years of age was associated with a reduction in child mortality of 0.34 deaths per 1000 child-years (95% CI, 0.15-0.52 deaths per 1000 child-years). The effects of malaria RDT distribution on medication use and child mortality varied across prevalence settings (low vs high) for malaria; there were survival improvements only in areas that had a high prevalence of malaria. Increasing distribution of malaria RDTs was associated with increased blood testing, increased use of antimalarial drugs, and modestly improved survival in children younger than 5 years of age in sub-Saharan African countries. However, malaria RDTs were associated with increases in the rates of antibiotic use that were already high, suggesting that more comprehensive approaches to case management of febrile illness are needed.

Long-term outcomes of a decentralized, nurse-led, statewide model of care for hepatitis C among people in prison in Victoria, Australia.

Prisons provide a key strategic opportunity to upscale hepatitis C testing and treatment in a high prevalence setting and are crucial for elimination efforts. A decentralized, statewide nurse-led model of care offering hepatitis C treatment for people in prison was implemented in Victoria, Australia in 2015. The program provides hepatitis C care to all 14 adult prison sites in the jurisdiction. We prospectively evaluated treatment uptake between 1 November 2015 and 31 December 2021. Data on all people in prison treated were recorded in a clinical database. The primary outcomes were i) total number of people in prison with hepatitis C treated; ii) total number of DAA treatment courses. 3,133 DAA treatment courses were prescribed to 2,768 people in prison. The proportion of total Victoria DAA prescriptions the program was responsible for increased from 6% in 2016 to a peak of 23% in 2020. Of those treated, median age was 39 years, 91% were male and 9% had cirrhosis. Few (20%) had previously engaged in hepatitis C care in the community and at first treatment course in prison, only 6% had previously accessed hepatitis C treatment. Complete follow up data were available for 1,757/2,768 (63%) treated, with 1,627/1,757 (93%) achieving SVR12. A decentralized, nurse-led, statewide model of care was highly effective in treating large numbers of people in prison with hepatitis C and achieved high rates of SVR12. Nurse-led prison programs are playing a crucial role in eliminating hepatitis C as a public health threat in Australia.

Dynamic HIV risk differentiation among youth: Validation of a tool for prioritization of prevention in East Zimbabwe.

Differentiating risk for HIV infection is important for providing focussed prevention options to individuals. We conducted a longitudinal study to validate a risk-differentiation tool for predicting HIV or HSV-2 acquisition among HIV-negative youth. Population-based household survey in east Zimbabwe. HIV and HSV-2 status and HIV behavioural risk factors were assessed in two surveys conducted 12 months apart among young people. Associations between risk-behaviours and combined HIV/HSV-2 incident infection were estimated using proportional hazards models. We calculated the sensitivity and specificity of risk-differentiation questions in predicting HIV/HSV-2 acquisition and quantified changes between surveys among low, medium, and high-risk categories. In total, 44 HIV/HSV-2 seroconversions were observed in 1812 person-years of follow up (2.43/100PY, 95%CI: 1.71-3.15); 50% of incident cases reported never having had sex at baseline. Risk of HIV/HSV-2 acquisition was higher for those reporting non-regular partners (women: HR=2.71, 95% CI:1.12-6.54, men: HR=1.37, 95%CI: 0.29-6.38) and those reporting having a partner with a sexually transmitted infection (STI) (HR=7.62 (1.22-47.51). Adding a question on non-regular partnerships increased tool sensitivity from 18.2% to 38.6%, and further to 77.3% when restricted to those who had ever had sex. Individual risk category increased for 28% of men and 17% of women over 12-months. The refined risk differentiation tool identified a high proportion of youth at risk of HIV acquisition. Despite this, half of incident infections were among individuals who reported no prior sexual activity. The shifting patterns of risk behaviours underscore the need for dynamic prevention engagement strategies in high HIV prevalence or incidence settings.

Implementation of routine HIV testing policy in medical admissions in the sultanate of Oman: An experience from the Middle East.

To tackle the issue of late HIV diagnosis in the country, the Ministry of Health (MOH) in Oman introduced a national policy of routine opt-out HIV in medical admission units in September 2022. We hereby report the implementation and outcomes of this policy. All patients aged 16-65years admitted to a medical ward in secondary and local hospitals were offered an HIV test regardless of their symptoms by medical doctors, with training and support from HIV teams. A retrospective review for the period from September 2022 to September 2023 was conducted to determine the HIV testing rate and outcomes of those testing HIV seropositive. Over 12months, there were 23,399 admissions; 6889 had HIV tests. Thirty-two patients (0.46 %) were diagnosed with HIV; all of them were new diagnoses. Two cases were diagnosed during seroconversion. 12 cases had AIDS-defining illnesses. Four contacts were tested HIV positive. Twenty-five out of 28 alive patients are on ART. This is the first national policy of a routine opt-out HIV in medical admission units in the MENA region. Our experience showed that, even in low HIV prevalence and high HIV stigma settings, this policy is feasible, acceptable, and effective.

Molecular xenomonitoring as an indicator of microfilaraemia prevalence for lymphatic filariasis in Samoa in 2019

BackgroundLymphatic filariasis (LF) is a globally significant, vector-borne, neglected tropical disease that can result in severe morbidity and disability. As the World Health Organization (WHO) Global Programme to Eliminate Lymphatic Filariasis makes progress towards LF elimination, there is greater need to develop sensitive strategies for post-intervention surveillance. Molecular xenomonitoring (MX), the detection of pathogen DNA in vectors, may provide a sensitive complement to traditional human-based surveillance techniques, including detection of circulating filarial antigen and microfilaraemia (Mf). This study aims to explore the relationship between human Mf prevalence and the prevalence of polymerase chain reaction (PCR)-positive mosquitoes using MX.MethodsThis study compared Mf and MX results from a 2019 community-based survey conducted in 35 primary sampling units (PSUs) in Samoa. This study also investigated concordance between presence and absence of PCR-positive mosquitoes and Mf-positive participants at the PSU level, and calculated sensitivity and negative predictive values for each indicator using presence of any Mf-positive infection in humans or PCR-positive mosquitoes as a reference. Correlation between prevalence of filarial DNA in mosquitoes and Mf in humans was estimated at the PSU and household/trap level using mixed-effect Bayesian multilevel regression analysis.ResultsMf-positive individuals were identified in less than half of PSUs in which PCR-positive mosquito pools were present (13 of 28 PSUs). Prevalence of PCR-positive mosquitoes (each species separately) was positively correlated with Mf prevalence in humans at the PSU level. Analysed at the species level, only Aedes polynesiensis demonstrated strong evidence of positive correlation (r) with human Mf prevalence at both PSU (r: 0.5, 95% CrI 0.1–0.8) and trap/household levels (r: 0.6, 95% CrI 0.2–0.9).ConclusionsFindings from this study demonstrate that MX can be a sensitive surveillance method for identifying residual infection in low Mf prevalence settings. MX identified more locations with signals of transmission than Mf-testing. Strong correlation between estimated PCR-positive mosquitoes in the primary vector species and Mf in humans at small spatial scales demonstrates the utility of MX as an indicator for LF prevalence in Samoa and similar settings. Further investigation is needed to develop MX guidelines to strengthen the ability of MX to inform operational decisions.Graphical abstract