Serological surveillance development for tropical infectious diseases using simultaneous microsphere-based multiplex assays and finite mixture models

PLoS Negl Trop Dis. 2014 Jul 31;8(7):e3040. doi: 10.1371/journal.pntd.0003040. eCollection 2014.

Abstract

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Helminth / blood
  • Antibodies, Protozoan / blood
  • Child
  • Child, Preschool
  • Communicable Diseases / diagnosis*
  • Communicable Diseases / epidemiology*
  • Epidemiological Monitoring*
  • Female
  • HIV Antibodies / blood
  • Humans
  • Infant
  • Infant, Newborn
  • Kenia
  • Male
  • Microspheres
  • Sensitivity and Specificity
  • Seroepidemiologic Studies
  • Serologic Tests*
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Antibodies, Helminth
  • Antibodies, Protozoan
  • HIV Antibodies

Grants and funding

This work was, in part, supported by Asia-Africa Science & Technology Strategic Cooperation Promotion Program of Special Coordination Funds for Promoting Science and Technology (SCF); funds for integrated promotion of social system reform and research and development, by The Ministry of Education, Culture, Sports, Science, and Technology (MEXT); and by the Global Center of Excellence (GCOE) Program at Nagasaki University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.