Accurate determination of Schistosoma infection rates in low endemic regions to examine progress towards interruption of transmission and elimination requires highly sensitive diagnostic tools. An existing lateral flow (LF) based test demonstrating ongoing infections through detection of worm circulating anodic antigen (CAA), was improved for sensitivity through implementation of a protocol allowing increased sample input. Urine is the preferred sample as collection is non-invasive and sample volume is generally not a restriction. Centrifugal filtration devices provided a method to concentrate supernatant of urine samples extracted with trichloroacetic acid (TCA). For field trials a practical sample volume of 2 mL urine allowed detection of CAA down to 0.3 pg/mL. The method was evaluated on a set of urine samples (n = 113) from an S. mansoni endemic region (Kisumu, Kenya) and compared to stool microscopy (Kato Katz, KK). In this analysis true positivity was defined as a sample with either a positive KK or UCAA test. Implementation of the concentration method increased clinical sensitivity (Sn) from 44 to 98% when moving from the standard 10 μL (UCAA10 assay) to 2000 μL (UCAA2000 assay) urine sample input. Sn for KK varied between 23 and 35% for a duplicate KK (single stool, two slides) to 52% for a six-fold KK (three consecutive day stools, two slides). The UCAA2000 assay indicated 47 positive samples with CAA concentration above 0.3 pg/mL. The six-fold KK detected 25 egg positives; 1 sample with 2 eggs detected in the 6-fold KK was not identified with the UCAA2000 assay. Larger sample input increased Sn of the UCAA assay to a level indicating ‘true’ infection. Only a single 2 mL urine sample is needed, but analysing larger sample volumes could still increase test accuracy. The UCAA2000 test is an appropriate candidate for accurate identification of all infected individuals in low-endemic regions. Assay materials do not require refrigeration and collected urine samples may be stored and transported to central test laboratories without the need to be frozen.

Malaria and schistosomiasis co-infections are common and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. But whether it enhances or attenuates malaria has been controversal due lack of appropriately controlled human studies and relevant animals models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyse the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n=8 each) and a schistosomiasis control group (n=3) were infected with 500 S. mansoni cercariae. At 14 and 15 weeks post infection, one group was given praziquantel to treat their schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n=8), were intravenously innoculated with 10⁵ P. knowlesi parasites (Pk) and monitored daily for development of severe malaria. Eighty-one percent of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment, survived malaria compared to only 25% of animals infected with Pk only (p=0.01). Schistosome infected animals also had significantly lower parasite burden (p=0.004) than the baboons in the Pk only group and were protected from severe anemia. Co-infection was associated with increased spontaneous production of IL-6 suggesting an enhanced innate immune responses while Pk only infected animals failed to develop mitogen-driven TNF-α and IL-10 indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi co-infection in baboons by mechanisms that may enhance innate immunity to malaria.

Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection.

Human papillomavirus (HPV) vaccines elicit specific serum antibodies that confer long-lasting protection and may reduce HPV-related cancers. However, helminthic infections such as chronic schistosomiasis infection at the time of HPV vaccination are known to alter immune responses. This study investigated the impact of chronic S. mansoni infection on immune responses to the HPV vaccine in olive baboons. Baboons were assigned to three groups: (1) untreated S. mansoni-infected, (2) S. mansoni-infected and treated with Praziquantel, and (3) uninfected controls. All received two doses of the Cervarix HPV vaccine four weeks apart. Immune responses were measured using flow cytometry and ELISA. Gardasil® quadrivalent HPV vaccine antigen was used in both ELISA and PBMC stimulation for cytokine ELISA supernatants. HPV-specific whole IgG levels significantly increased in all groups except for the untreated S. mansoni-infected group, whose increase was significant after the second dose. Similarly, IgG1 levels increased only after the second dose. There was no significant difference between the treated and untreated infected groups. These findings emphasize the importance of a booster dose for strong antibody production and suggest that a delayed HPV-specific whole IgG response in untreated S. mansoni-infected individuals reinforces the need for booster HPV vaccination in endemic regions. The results affirm the vaccine's effectiveness in S. mansoni endemic areas.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to evolve, with mutations leading to the emergence of new variants. JN.1, a subvariant of omicron BA.2.86, has demonstrated marked immune escape and is now included in updated vaccine formulations. While reduced sensitivity has been reported for antibody assays using ancestral spike protein subunits to detect omicron-induced responses, the performance of full-length spike-based assays against omicron sublineages remains unclear. We aimed to compare the sensitivity of ELISA and Luminex assays using full-length spike proteins from the ancestral Wuhan strain and the JN.1 variant. Methods: Wuhan and JN.1 full-length spike protein constructs were designed and expressed in Expi293F mammalian cells. In-house ELISAs based on previously validated protocols were used to measure anti-spike IgG levels. Additionally, a Luminex-based assay for anti-spike antibody detection was developed and validated. Both assays were applied to the following sample groups: pre-pandemic samples (designated “gold standard negatives”); PCR confirmed 2020 positives (“gold standard wildtype positives”); PCR confirmed 2024 positives (“gold standard omicron positives”); 2022 vaccinated individuals with verbal confirmed infection (“gold standard hybrid positives”); and 2024 household samples (“unknowns”). Results: Wuhan spike protein showed a sensitivity of 100% (95% CI: 0.88–1.0) in detecting omicron-specific antibodies using gold standard omicron positives with JN.1 spike protein as a reference assay. Overall, across all samples, in ELISA, the Wuhan antigen had a sensitivity of 0.93 (95% CI: 0.89–0.95) and a specificity of 0.98 (95% CI: 0.94–0.99). The JN.1 antigen showed a sensitivity of 0.91 (95% CI: 0.87–0.94) and a specificity of 0.97 (95% CI: 0.93–0.99). In Luminex, sensitivity was 0.95 (95% CI: 0.91–0.97) for Wuhan and 0.94 (95% CI: 0.91–0.96) for JN.1. Specificity for both antigens in Luminex was 0.98 (95% CI: 0.94–0.99). Conclusions: Both ELISA and Luminex assays showed comparable sensitivity and specificity for both Wuhan and JN.1 antigens, indicating that mutations in the JN.1 variant do not significantly impact assay performance. This suggests preserved antigenic recognition across variants.