Dengue Literature Review

Wiki State and Gap Analysis 2026-04-12

6 min read

Wiki State and Gap Analysis — 2026-04-12

Curator-directed synthesis of current wiki coverage and research priorities.

Current Wiki State

9 sources | 27 pages total as of 2026-04-12 (post-lint).

Page Inventory

CategoryCountPages
Sources9Garcia2009, Garcia2010, Tan1997, Satoh2012, Li2019, Aringer2019, Dinse2022, Berlin2007, Johnson2022
Entities3DENV-4, FcγRIIa Receptor, Aedes aegypti
Concepts6Post-Dengue Syndrome, Autoimmunity in Dengue, Antibody-Dependent Enhancement, Asymptomatic Dengue Infection, Antinuclear Antibodies, Infection-Triggered Autoimmunity
Methods4PRNT, ELISA Inhibition Method, FcγRIIa Genotyping, Indirect Immunofluorescence ANA Test
Geography1Cuba
Analyses1This page

The Research Thread

The wiki is building a case around dengue-associated autoimmunity — specifically whether the ANA positivity observed in post-dengue patients represents a dengue-specific phenomenon or a generic viral infection effect.

The core argument:

  1. Garcia2009 - Long-term Clinical Symptoms Post-Dengue found 23.1% ANA positivity 2 years after symptomatic DENV-4 infection in Cuba, vs. 0% in asymptomatic cases. 76.9% of symptomatic patients showed ≥1 autoimmune marker at 2 years; 56.7% still had clinical symptoms.
  2. Garcia2010 - Asymptomatic Dengue FcγRIIa Polymorphism (same cohort) found the FcγRIIa-RR genotype protects against symptomatic dengue — implicating Fc receptor-mediated immune complex handling as a pathogenic mechanism.
  3. Five ANA prevalence papers (Tan1997, Satoh2012, Li2019, Dinse2022, Aringer2019) establish that background ANA positivity in healthy populations runs ~10–16% at 1:80 on HEp-2. The post-dengue 23.1% exceeds this, but the margin depends on dilution and substrate (see critical caveat below).
  4. Berlin2007 - Autoantibodies in Nonautoimmune Individuals during Infections shows ANA rises to 21.7% during acute viral infections (HAV/HBV/HCV) but resolves — making Garcia2009’s 2-year persistence the key distinguishing finding vs. a generic viral effect.
  5. Johnson2022 - Infectious Diseases Autoantibodies and Autoimmunity provides the mechanistic framework: molecular mimicry, bystander activation, and epitope spreading. Crucially, bystander activation from severe COVID-19 does not significantly elevate ANA, implicating dengue-specific mechanisms (NS1 mimicry, FcγRIIa-driven IC persistence) as more likely explanations.

Critical methodological caveat: Garcia2009 - Long-term Clinical Symptoms Post-Dengue used rat liver tissue as the IIF substrate; all healthy-population reference studies use HEp-2 cells. Rat liver is less sensitive, meaning 23.1% is a floor estimate — the true rate on HEp-2 would likely be higher. Cross-study comparisons are directionally valid but the gap may be wider than reported.

Thin Coverage Areas and Papers to Look For

1. Post-Dengue Syndrome — Critical Gap (1 source)

Problem: The wiki’s core claim rests entirely on one Cuban DENV-4 cohort. Single serotype, single country, single epidemic year. No asymptomatic control group for the autoimmune markers. Female-predominant sample may inflate the autoimmune signal.

Papers to look for:

  • Seet et al. 2007 (Emerg Infect Dis) — Singapore post-dengue cohort; cognitive and fatigue sequelae; frequently cited
  • Oehler et al. 2014 — neurological complications post-dengue (GBS, encephalitis, myelitis)
  • Any prospective longitudinal cohort tracking dengue patients from acute phase through 6–12 months — PubMed: “dengue sequelae” OR “post-dengue” AND “cohort”
  • Papers on dengue and Guillain-Barré syndrome — the most documented post-dengue autoimmune complication; would directly strengthen Infection-Triggered Autoimmunity

2. NS1 Molecular Mimicry — Key Mechanistic Gap (0 sources)

Problem: The wiki’s best dengue-specific mechanistic hypothesis (NS1 cross-reactivity with host proteins) is mentioned in two pages but has zero sourced papers. It is currently background knowledge, not evidenced claims.

Papers to look for:

  • Falconar 1997 (J Gen Virol) — original description of NS1 cross-reactivity with platelets and endothelial cells
  • Cheng et al. 2009 or Lin et al. 2011 — NS1 molecular mimicry with coagulation proteins; anti-NS1 cross-reactive with plasminogen
  • Srikiatkhachorn & Kelley 2014 (J Infect Dis) — NS1 endothelial damage mechanism
  • Search: “dengue NS1 molecular mimicry” OR “NS1 cross-reactive antibodies endothelial”

3. FcγRIIa Biology — Unresolved Contradiction (2 sources)

Problem: The wiki flags a direct contradiction: Garcia2009/2010 say FcγRIIa-HH increases ADE risk, but Bruhns et al. (cited in Garcia2010) shows RR has higher binding affinity for IgG3, which would predict the opposite. The contradiction is flagged in FcγRIIa Receptor and Antibody-Dependent Enhancement but not resolved.

Papers to look for:

  • Bruhns et al. 2009 (Blood) — the actual binding affinity paper; would allow direct assessment of the contradiction
  • Mady et al. 2004 (J Infect Dis) — FcγRIIa and dengue severity in a Thai cohort; independent population
  • Boonnak et al. 2008 — monocyte FcγRII and ADE in vitro
  • Search: “FcγRIIA polymorphism dengue” for population studies outside Cuba

4. ANA Specificity in Dengue — What Antigens? (0 sources)

Problem: The wiki knows ANA is elevated post-dengue but has no data on which nuclear antigens are targeted. Antigen specificity is key for distinguishing lupus-like molecular mimicry from non-specific polyclonal activation.

Papers to look for:

  • Any paper reporting ENA profiles in dengue patients — anti-dsDNA, anti-Sm, anti-SS-A/SS-B, anti-histone, anti-centromere
  • Opasawatchai et al. — Thai group with publications on dengue autoantibodies
  • Case reports in Arthritis & Rheumatism of dengue-triggered lupus flares — these often include specific ANA profiles

5. Geography — Almost Empty (1 page, Cuba only)

Problem: The entire evidence base is from Cuba (DENV-4, 2006 epidemic). Dengue epidemiology varies substantially by region, serotype, and healthcare context.

Papers to look for:

  • Bhatt et al. 2013 (Nature) — global burden estimates; good anchor for a global geography overview
  • Gubler 2002 (Trends Microbiol) — classic review of global dengue emergence
  • Southeast Asian epidemiology papers (Thailand, Vietnam, Philippines, Indonesia) — highest global disease burden
  • Country-specific seroprevalence data to build out regional geography pages

6. Diagnostic Methods — Mostly Empty

Problem: PRNT and ELISA Inhibition each have 1 source. The wiki has no coverage of RT-PCR, NS1 rapid antigen tests, or IgM/IgG serology timelines — the core diagnostic toolkit for dengue.

Papers to look for:

  • WHO Dengue Guidelines 2009 / 2012 — covers all diagnostic methods with performance benchmarks; could bootstrap multiple method pages at once
  • Peeling et al. 2010 (Nature Reviews Microbiology) — dengue diagnosis review

Priority Order for Next Ingests

PriorityGapRationale
1NS1 molecular mimicry paper (e.g. Falconar 1997)Converts a background claim into evidence; fills the most important mechanistic gap
2Second post-dengue cohort, non-Cuba (e.g. Seet 2007)Makes the core claim generalisable beyond one epidemic
3Bruhns et al. 2009Resolves a flagged scientific contradiction
4Post-dengue GBS paperAdds a second mechanism and a second outcome to Autoimmunity in Dengue
5WHO/Peeling diagnosticsFills method stubs; low effort, high structural value

Sources

All 9 sources currently in the wiki inform this analysis:

Graph View

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