2016-04-12-世界卫生组织-Target_Product_Profiles_for_better_diagnostic_tests_for_Zika_Virus_Infection_7页_230kb

Summary of Target Product Profiles for Better Diagnostic Tests for Zika Virus Infection

1. Introduction

Zika virus (ZIKV) has spread to 59 countries and territories between 2007 and 2016. The World Health Organization (WHO) declared a Public Health Emergency of International Concern in February 2016 due to the suspected link between ZIKV infection and congenital malformations, particularly microcephaly, as well as neurologic syndromes like Guillain-Barré syndrome (GBS). These associations have been observed in Brazil, French Polynesia, and other regions. The need for improved diagnostic tests for ZIKV has become critical, especially for public health response and clinical management.

The Target Product Profiles (TPPs) aim to define the desired characteristics of ZIKV diagnostic tests, guiding the development of new tools to address current diagnostic limitations and scientific uncertainties. These profiles are based on stakeholder consultations and are intended to be adaptable for use in low- and middle-income countries (LMICs).

2. Core Content of Target Product Profiles

2.1 Detection of Active Infection with Zika Virus

2.2 Detection of Evidence of Prior Infection

2.3 Operational Characteristics

The TPPs are designed to meet the needs of different population groups and address current diagnostic challenges. They prioritize:

• Accessibility: Use of less invasive sample types (e.g., capillary blood, urine, saliva) to make testing more feasible in LMICs.
• Speed: Point-of-care (POC) testing to enable timely diagnosis and management.
• Accuracy: High sensitivity and specificity to reduce false positives and negatives, especially in critical cases like pregnant women.
• Multiplexing: Simultaneous detection of ZIKV and other arboviruses (e.g., DENV, CHIKV) to improve diagnostic efficiency and epidemiological monitoring.
• Logistics: Practical storage and transport requirements for reagents and specimens to support use in resource-limited settings.

3. Key Considerations

3.1 Clinical Considerations

• Acute febrile syndrome: ZIKV presents with mild symptoms similar to DENV and CHIKV, making differential diagnosis difficult. ZIKV RNA can be detected in serum, urine, breast milk, and saliva.
• Viral load: ZIKV RNA levels in blood are low (10³–10⁵ copies/mL), while higher levels are found in urine (up to 10⁶ copies/mL) and saliva.
• Pregnant women: ZIKV infection during pregnancy is of particular concern due to its association with microcephaly and congenital malformations. Testing accuracy is crucial, and false results can have serious consequences. A diagnostic algorithm for routine antenatal care is needed.

3.2 Technical Considerations

• Multiplexing: Simultaneous detection of ZIKV with DENV and CHIKV is essential for clinical and epidemiological purposes. ZIKV detection should not be compromised in multiplexed tests.
• Cross-reactivity: Anti-ZIKV IgM and IgG can cross-react with other flaviviruses, particularly DENV. This complicates interpretation and necessitates confirmatory testing (e.g., PRNT) to differentiate ZIKV from DENV.
• Quantitative assays: These can provide insights into the relationship between viral load and clinical outcomes, such as neurologic consequences and transmissibility.

3.3 Public Health Surveillance

• Multiplexed tests for prior infection (IgM and IgG) are recommended to support epidemiological studies and intervention design.
• Lower sensitivity thresholds (e.g., 95%) may be acceptable in population-based surveillance, as these tests are not used for individual diagnosis.
• Integration with other arboviruses: Tests should include DENV serotypes and other pathogens transmitted by the same vector to enhance surveillance.

4. Main Views and Key Information

• Zika virus has spread rapidly across the globe, raising concerns about its impact on pregnancy and neurologic health.
• Current diagnostic tests have limitations in sensitivity, specificity, and ease of use, especially in LMICs.
• TPPs are aspirational and guide the development of more effective and accessible diagnostic tools.
• Multiplexing is a priority to differentiate ZIKV from DENV and CHIKV, improving both clinical and public health responses.
• Cross-reactivity remains a major technical challenge, requiring confirmatory testing for accurate diagnosis.
• Testing for pregnant women must be highly accurate due to the potential for severe congenital outcomes, and the development of POC testing is critical for timely and accessible care.
• Quantitative assays can enhance understanding of ZIKV's pathogenicity and transmission dynamics.

5. Conclusion

The development of improved diagnostic tests for ZIKV is essential to address the public health emergency and support clinical and epidemiological efforts. Target Product Profiles (TPPs) provide a framework for defining the desired characteristics of such tests, with a focus on accuracy, accessibility, and multiplexing capabilities. These profiles are intended to evolve as new scientific evidence emerges and are crucial for guiding the creation of tools that can be effectively used in LMICs.