Dengue 3 Epidemic, Havana, 2001

In June 2001, dengue transmission was detected in Havana, Cuba; 12,889 cases were reported. Dengue 3, the etiologic agent of the epidemic, caused the dengue hemorrhagic fever only in adults, with 78 cases and 3 deaths. After intensive vector control efforts, no new cases have been detected

Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody.

Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Pediatric Dengue Vaccine Initiative (PDVI). Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT formats) were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS) and the Centers for Disease Control and Prevention (CDC), and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR). Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60-75% and specificity 71-80%; NS1 RDT sensitivity was 38-71% and specificity 76-80%; the IgM anti-DENV RDTs sensitivity was 30-96%, with a specificity of 86-92%, and IgM anti-DENV ELISA sensitivity was 96-98% and specificity 78-91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88-94%

Dengue: a continuing global threat.

Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ∼50 million dengue infections and ∼500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future

Evaluation of commercially available anti-dengue virus immunoglobulin M tests.

Anti-dengue virus immunoglobulin M kits were evaluated. Test sensitivities were 21%-99% and specificities were 77%-98% compared with reference ELISAs. False-positive results were found for patients with malaria or past dengue infections. Three ELISAs showing strong agreement with reference ELISAs will be included in the World Health Organization Bulk Procurement Scheme

Evaluation of Zika rapid tests as aids for clinical diagnosis and epidemic preparedness

Background: Development and evaluation of diagnostics for diseases of epidemic potential are often funded during epidemics, but not afterwards, leaving countries unprepared for the next epidemic. United Nations Children's Emergency Fund (UNICEF) partnered with the United States Agency for International Development (USAID) to address this important gap by investing in an advance purchase commitment (APC) mechanism to accelerate the development and evaluation of Zika rapid diagnostic tests (RDTs) for case detection and surveillance. This paper describes the performance evaluation of five Zika RDTs eligible for procurement. Methods: A network of European Union-funded ZikaPLAN sites in Africa, Asia, Latin America with access to relevant serum specimens were selected to evaluate RDTs developed for the UNICEF APC mechanism. A standardised protocol and evaluation panels were developed and a call for specimens for the evaluation panels issued to different sites. Each site contributed specimens to the evaluation from their biobank. Data were collated, analysed and presented to the UNICEF Procurement Review Group for review. Findings: Three RDTs met the criteria for UNICEF procurement of sensitivity and specificity of 85% against a refence standard. The sensitivity/specificity of the ChemBio anti-Zika Virus (ZIKV) immunoglobulin M (IgM) test was 86.4 %/86.7% and the ChemBio ZCD system for anti-ZIKV IgM was 79.0%/97.1%, anti-dengue virus (DENV) IgM 90.0%/89.2%, anti-Chikungunya virus (CHIKV) IgM 90.6%/97.2%. The sensitivity/specificity of the SD Biosensor anti-ZIKV IgM was 96.8 %/90.8%, anti-DENV IgM 71.8%/83.5%, the DENV nonstructural protein 1 (NS1) glycoprotein 90.0%/90.2%, anti- yellow fever virus (YFV) IgM 84.6%/92.4%, anti-CHIKV IgM 86.3%/97.5%. Interpretation: Three RDTs fulfilled the performance thresholds set by WHO and were eligible for UNICEF procurement. These tests will improve the diagnosis of ZIKV and other arboviral infections as well as providing countries with better tools for surveillance and response to future epidemics

False positive rate of anti-DENV IgM rapid diagnostic tests in DENV negatives and challenge panel specimens.

<p>False positive rate of anti-DENV IgM rapid diagnostic tests in DENV negatives and challenge panel specimens.</p

False positive rate DENV NS1 rapid diagnostic tests in DENV negatives and challenge panel specimens.

<p>False positive rate DENV NS1 rapid diagnostic tests in DENV negatives and challenge panel specimens.</p

Characteristics of specimens from dengue patients included in the panel to evaluate anti-DENV IgM detection kits.

<p>DENV  =  dengue virus.</p><p>*Primary  = 1 DENV infection, Secondary ≥2 DENV infections.</p>¶<p>days post onset of fever  = 0–5.</p>#<p>days post onset of fever  = 6–14.</p><p>Characteristics of specimens from dengue patients included in the panel to evaluate anti-DENV IgM detection kits.</p

Sensitivity of anti-DENV IgM compared to IgM reference test in acute and convalescent samples.

<p>Sensitivity of dengue anti-DENV IgM compared to IgM reference test in primary and secondary DENV infection status.</p><p>*Comparison to anti-DENV IgM reference positive samples.</p>¶<p>Number of samples tested differed to total number due to either duplicates for RDTs, invalid test or equivocal result.</p><p>Acute is days post onset of fever (DPO) of 0–5 days, Convalescent is DPO = 6–14.</p><p>Primary  = 1 DENV infection, Secondary ≥2 DENV infections.</p><p>CI95 = 95% confidence interval.</p><p>Sensitivity of anti-DENV IgM compared to IgM reference test in acute and convalescent samples.</p