Dengue Literature Review

Gawali2021 - ANA Prevalence in Seroconverted Dengue Patients

6 min read

⚠ Journal quality note: The journal (International Journal of Applied Research, allresearchjournal.com) claims “Impact Factor: 8.4” on the article header. This figure is not from Clarivate/JCR and is inconsistent with the journal’s absence from major indexing databases (PubMed, Scopus, Web of Science). The study is methodologically straightforward — prospective, single-centre, small — and should be interpreted at the level of its design and sample size, not its publication venue. The absence of a control group is the binding limitation for interpreting the ANA prevalence finding.

Gawali2021 - ANA Prevalence in Seroconverted Dengue Patients

Full citation: Gawali D, Misra V, Gaharwar R, Mittal A, Jain SB, Khetan R. “Understanding the ANA prevalence and its common pattern in seroconverted dengue infected patients.” International Journal of Applied Research 2021; 7(10):154–158.

Raw file: [[raw/Gawali2021.pdf]]

Summary

This prospective observational study, conducted at Gajra Raja Medical College in Gwalior, Madhya Pradesh (Central India) between January 2019 and June 2020, examined the rate of antinuclear antibody (ANA) positivity in dengue patients who subsequently seroconverted to IgG positivity at 6 months. Among 2,249 clinically suspected dengue cases, 765 (34%) were serologically positive for dengue markers. A subset of 163 IgM/IgM+NS1-positive patients consented to follow-up at 6–9 months, where dengue IgG and ANA status were assessed.

Of the 120 patients (74%) who had developed dengue IgG antibodies by follow-up, 22 (18.33%) tested ANA-positive by EUROIMMUN indirect immunofluorescence test (IIFT) on HEp-2 cells at a single dilution of 1:100. The dominant ANA pattern was nuclear homogeneous (AC-1) in 81.81% of ANA-positive patients, followed by smooth nuclear envelope (AC-11, 13.63%) and nuclear fine speckled (AC-4, 4.5%). ANA positivity was not associated with sex (50% male, 50% female) or age.

The study concludes that dengue seropositive patients — especially children and young adults — should be periodically screened for ANA and autoimmune disease development.

Study Design

  • Type: Prospective observational (cross-sectional follow-up)
  • Sample size: 2,249 screened; 765 seropositive; 163 followed up at 6 months; 120 IgG+; 22 ANA+
  • Setting: Gajra Raja Medical College (GRMC), Gwalior, Madhya Pradesh, Central India; January 2019 – June 2020
  • Population: Clinically symptomatic dengue patients, IgM+ or IgM+NS1+ confirmed; any age; patients with comorbid conditions excluded; patients approached 6–9 months after initial seropositivity

Key Findings

  • Overall dengue seropositivity rate: 765/2,249 (34%)
  • IgG seroconversion at 6 months: 120/163 (74%) of IgM/NS1-positive patients
  • ANA positivity: 22/120 IgG-positive patients (18.33%) by EUROIMMUN IIFT on HEp-2 cells at 1:100 dilution
  • ANA patterns: AC-1 (nuclear homogeneous) 81.81%; AC-11 (smooth nuclear envelope) 13.63%; AC-4 (nuclear fine speckled) 4.5%
  • IgG seroconversion significantly associated with older age (mean 26.67 ± 17.5 years IgG+ vs. 19.86 ± 15.4 years IgG−; Mann-Whitney U p = 0.004)
  • ANA positivity not associated with sex (p = 0.249) or age (p = 0.081) — contrary to the typical female predominance found in healthy populations
  • Symptomatic patients had significantly higher IgG seroconversion than asymptomatic individuals
  • No contemporaneous control group tested for ANA — the 18.33% figure cannot be compared to a matched dengue-negative control rate from the same setting and time period

Methods Used

Entities Mentioned

Concepts Addressed

Relevance & Notes

This paper provides the only 6-month post-infection ANA time point in this wiki — filling the gap between Chatterjee2024 (acute phase, 54.8% IIFA) and Garcia2009 (2 years post-dengue, 23.1%). The 18.33% rate at 6 months on HEp-2 cells is broadly consistent with a declining trajectory from the acute peak, though the absence of a control group prevents any statistically valid comparison with background ANA prevalence in this population.

The Li2019 healthy Chinese population rate at >1:100 was 14.01%, which is the closest methodologically comparable baseline — meaning Gawali2021’s 18.33% is only modestly elevated above a plausible contemporaneous baseline in an Asian population. This substantially weakens the inference that dengue is driving the ANA positivity.

The dominant AC-1 (nuclear homogeneous) pattern in 81.81% of ANA-positive patients is consistent with dsDNA, histone, and nucleosome targets — the same specificities detected by Vo2020’s protein microarray in dengue DHF patients (KU, SmD, histone H3/H4, nucleosome antigen). However, nuclear homogeneous is also the most common pattern in healthy ANA-positive individuals (see Antinuclear Antibodies), so this does not distinguish dengue-specific from background reactivity.

The equal sex distribution among ANA-positive patients (50% M, 50% F) diverges from the established female predominance in ANA and autoimmune disease. However, with only 22 ANA-positive individuals, this result lacks the statistical power to meaningfully challenge the known sex bias (p = 0.249).

A third Indian research centre is added: GRMC Gwalior, Madhya Pradesh — Central India, distinct from Kolkata (NICED, Chatterjee2024 - ANA Detection in Dengue Kolkata) and Manipal (Kasturba Medical College, Bhatt2020 - Dengue Pathogenesis Review). The India geography page is updated.

The study self-acknowledges key limitations: (1) single dilution (1:100) with no titres; (2) no control group; (3) small, unicentric sample; (4) high attrition (only 27% of eligible patients consented to follow-up — introducing unknown selection bias).

Questions Raised

  • Does the 18.33% ANA rate at 6 months represent genuine dengue-driven autoimmune persistence, or does it reflect background ANA prevalence in this Indian population? A contemporaneous ANA-negative dengue patient group and a dengue-naive control group would both be needed to answer this.
  • Would a dilution series (1:40, 1:80, 1:160, 1:320) show a significantly different prevalence profile in post-dengue vs. control populations from Central India?
  • The lack of sex bias in ANA positivity (50/50 vs. the established ~2× female excess) — is this a genuine dengue-related phenomenon or a power artefact? Replication in a larger cohort with documented serotype and infection history would clarify.
  • Are the AC-1-positive patients producing dengue-induced anti-dsDNA/histone antibodies, or is this the same polyreactive IgM signal observed by Chatterjee2024 and interpreted via Zhou2007? LIA confirmation testing on these patients’ sera would distinguish the two.

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