Species-Specific Serological Detection for Schistosomiasis by Serine Protease Inhibitor (SERPIN) in Multiplex Assay

Background: Both Schistosoma mansoni and Schistosoma haematobium cause schistosomiasis in sub-Saharan Africa. We assessed the diagnostic value of selected Schistosoma antigens for the development of a multiplex serological immunoassay for sero-epidemiological surveillance. Methodology/Principal Findings: Diagnostic ability of recombinant antigens from S. mansoni and S. haematobium was assessed by Luminex multiplex immunoassay using plasma from school children in two areas of Kenya, endemic for different species of schistosomiasis. S. mansoni serine protease inhibitor (SERPIN) and Sm-RP26 showed significantly higher reactivity to patient plasma as compared to the control group. Sm-Filamin, Sm-GAPDH, Sm-GST, Sm-LAP1, Sm-LAP2, Sm-Sm31, Sm-Sm32 and Sm-Tropomyosin did not show difference in reactivity between S. mansoni infected and uninfected pupils. Sm-RP26 was cross-reactive to plasma from S. haematobium patients, whereas Sm-SERPIN was species-specific. Sh-SEPRIN was partially cross-reactive to S. mansoni infected patients. ROC analysis for Sm-RP26, Sm-SERPIN and Sh-SERPIN showed AUC values of 0.833, 0.888 and 0.947, respectively. Using Spearman’s rank correlation coefficient analysis, we also found significant positive correlation between the number of excreted eggs and median fluorescence intensity (MFI) from the multiplex immunoassays for Sm-SERPIN (ρ = 0.430, p-value = 0.003) and Sh-SERPIN (ρ = 0.433, p-value = 0.006). Conclusions/Significance: Sm-SERPIN is a promising species-specific diagnostic antigen. Sh-SEPRIN was partially cross-reactive to S. mansoni infected patients. SERPINs showed correlation with the number of excreted eggs. These indicate prospects for inclusion of SERPINs in the multiplex serological immunoassay system

Serological Surveillance Development for Tropical Infectious Diseases Using Simultaneous Microsphere-Based Multiplex Assays and Finite Mixture Models

Background:A strategy to combat infectious diseases, including neglected tropical diseases (NTDs), will depend on the development of reliable epidemiological surveillance methods. To establish a simple and practical seroprevalence detection system, we developed a microsphere-based multiplex immunoassay system and evaluated utility using samples obtained in Kenya.Methods:We developed a microsphere-based immuno-assay system to simultaneously measure the individual levels of plasma antibody (IgG) against 8 antigens derived from 6 pathogens: Entamoeba histolytica (C-IgL), Leishmania donovani (KRP42), Toxoplasma gondii (SAG1), Wuchereria bancrofti (SXP1), HIV (gag, gp120 and gp41), and Vibrio cholerae (cholera toxin). The assay system was validated using appropriate control samples. The assay system was applied for 3411 blood samples collected from the general population randomly selected from two health and demographic surveillance system (HDSS) cohorts in the coastal and western regions of Kenya. The immunoassay values distribution for each antigen was mathematically defined by a finite mixture model, and cut-off values were optimized.Findings:Sensitivities and specificities for each antigen ranged between 71 and 100%. Seroprevalences for each pathogen from the Kwale and Mbita HDSS sites (respectively) were as follows: HIV, 3.0% and 20.1%; L. donovani, 12.6% and 17.3%; E. histolytica, 12.8% and 16.6%; and T. gondii, 30.9% and 28.2%. Seroprevalences of W. bancrofti and V. cholerae showed relatively high figures, especially among children. The results might be affected by immunological cross reactions between W. bancrofti-SXP1 and other parasitic infections; and cholera toxin and the enterotoxigenic E. coli (ETEC), respectively.Interpretation:A microsphere-based multi-serological assay system can provide an opportunity to comprehensively grasp epidemiological features for NTDs. By adding pathogens and antigens of interest, optimized made-to-order high-quality programs can be established to utilize limited resources to effectively control NTDs in Africa

Synergistic Effect of Co-Administered SARS-CoV-2 Vaccines Improves Immune Responses in BALB/c Mice: A Preliminary Study

Various vaccine platforms have been approved for broad use to prevent the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, these vaccines exhibit distinct differences in immunogenicity and efficacy, which decline after vaccination and are further exacerbated by the emergence of virus variants and mutants. This study reports the immunization outcomes against the SARS-CoV-2 virus by assessing the immune responses and safety of different SARS-CoV-2 vaccines co-administered in BALB/c mice. Vaccine combinations comprising mRNA/adenovirus26-vector, mRNA/inactivated, adenovirus26-vector/inactivated, and mRNA/adenovirus26-vector/inactivated vaccines were prepared in optimized doses, and their activities upon immunization evaluated in comparison with individual mRNA, adenovirus26-vectored, and inactivated vaccines. Fourteen- and 28-days post-immunization, we measured spike-specific IgG response using Enzyme-Linked Immunosorbent Assay (ELISA), cytokine expression profiles through Quantitative real-time polymerase chain reaction (RT-PCR), and evaluated safety through histopathological examination. The mRNA/Vector/Inactivated group exhibited slightly higher anti-spike IgG levels, albeit not statistically significant (p > 0.132). Importantly, this regimen induced elevated IL-6 and IFN-γ mRNA expression levels (p < 0.0001) compared to immunization with individual vaccines. In summary, this study demonstrated that co-administering the mRNA/adenovirus26 vector/inactivated SARS-CoV-2 vaccines improved spike-specific IgG response, triggered significantly enhanced IL-6 and IFN-γ mRNA expression levels, and proved safe in mice

Spatial Distributions of HIV Infection in an Endemic Area of Western Kenya: Guiding Information for Localized HIV Control and Prevention.

HIV is still a major health problem in developing countries. Even though high HIV-risk-taking behaviors have been reported in African fishing villages, local distribution patterns of HIV infection in the communities surrounding these villages have not been thoroughly analyzed. The objective of this study was to investigate the geographical distribution patterns of HIV infection in communities surrounding African fishing villages. In 2011, we applied age- and sex-stratified random sampling to collect 1,957 blood samples from 42,617 individuals registered in the Health and Demographic Surveillance System in Mbita, which is located on the shore of Lake Victoria in western Kenya. We used these samples to evaluate existing antibody detection assays for several infectious diseases, including HIV antibody titers. Based on the results of the assays, we evaluated the prevalence of HIV infection according to sex, age, and altitude of participating households. We also used Kulldorff's spatial scan statistic to test for HIV clustering in the study area. The prevalence of HIV at our study site was 25.3%. Compared with the younger age group (15-19 years), adults aged 30-34 years were 6.71 times more likely to be HIV-positive, and the estimated HIV-positive population among women was 1.43 times larger than among men. Kulldorff's spatial scan statistic detected one marginally significant (P = 0.055) HIV-positive and one significant HIV-negative cluster (P = 0.047) in the study area. These results suggest a homogeneous HIV distribution in the communities surrounding fishing villages. In addition to individual behavior, more complex and diverse factors related to the social and cultural environment can contribute to a homogeneous distribution pattern of HIV infection outside of African fishing villages. To reduce rates of transmission in HIV-endemic areas, HIV prevention and control programs optimized for the local environment need to be developed

Barriers to the digitization of health information: A qualitative and quantitative study in kenya and lao pdr using a cloud-based maternal and child registration system

Digitalization of health information can assist patient information management and improve health services even in low middle-income countries. We have implemented a mother and child health registration system in the study areas of Kenya and Lao PDR to evaluate barriers to digitalization. We conducted in-depth interviews with 20 healthcare workers (HCWs) who used the system and analyzed it qualitatively with thematic framework analysis. Quantitatively, we analyzed the quality of recorded data according to missing information by the logistic regression analysis. The qualitative analysis identified six themes related to digitalization: satisfaction with the system, mothers’ resistance, need for training, double work, working environment, and other resources. The quantitative analysis showed that data entry errors improved around 10% to 80% based on odds ratios in subsequent quarters compared to first quarter periods. The number of registration numbers was not significantly related to the data quality, but the motivation, including financial incentives among HCWs, was related to the registration behavior. Considering both analysis results, workload and motivation to maintain high performance were significant obstacles to implementing a digital health system. We recommend enhancing the scope and focus on human needs and satisfaction as a significant factor for digital system durability and sustainability

Study site along the shore of Lake Victoria in Mbita, Kenya.

<p>The HDSS program survey at the study site is managed by a NUITM-KEMRI Project.</p

HIV prevalence by sub-area of the study site according to age-group and sex.

<p>The horizontal axis indicates age groups in units of five years, and the vertical axis shows the prevalence of HIV positive cases. Red and blue lines with error bars indicating 95% confidence intervals represent females and males, respectively.</p

The estimated HIV positive population by sub-area of the study site according to age and sex.

<p>The horizontal axis shows five-year age groups, and the vertical axis shows the prevalence of HIV positive cases. Red and blue lines with error bars indicating 95% confidence intervals represent females and males, respectively.</p