Dengue Literature Review

Latin America

9 min read

Latin America

Overview

Latin America encompasses the Caribbean (Cuba), Central America (Nicaragua), and South America (Brazil), representing dengue settings ranging from Cuba’s epidemic-by-importation pattern to Nicaragua’s endemic pediatric transmission and Brazil’s high-burden endemic circulation. The region contributes eight sources to this wiki spanning epidemiology, immunology, autoimmune case reports, dengue-associated macrophage activation syndrome, and a viral infection ANA comparator.

Cuba

Cuba has experienced a series of major dengue epidemics, each caused by a distinct serotype introduced in sequence, making it an epidemiologically valuable setting for studying multi-serotype exposure and its immunological consequences. The Instituto Pedro Kourí (IPK) in Havana is Cuba’s leading tropical medicine research institution and the primary source of Cuban dengue research.

Key Points from Literature

  • Cuban epidemic history: DENV-1 (1977, ~50% of population infected), DENV-2 Asian genotype (1981, ~25% of population, large DHF/DSS epidemic), DENV-2 again (1997, localised Santiago de Cuba outbreak), DENV-3 Asian genotype (2001, Havana, 78 confirmed DHF + 12,811 DF cases), DENV-4 (2006, Havana, eliminated within months) (see Garcia2009 - Long-term Clinical Symptoms Post-Dengue, Garcia2010 - Asymptomatic Dengue FcγRIIa Polymorphism).
  • Cuba’s non-endemic, epidemic-by-importation pattern and strong vector control record make it a natural model for studying genetic determinants of dengue severity without confounding by continuous transmission.
  • The 2006 DENV-4 Havana epidemic provided a cohort of hospitalised adults (97 symptomatic) and asymptomatic individuals (42) with well-documented infection histories, enabling unique follow-up studies on sequelae and genetic risk factors.
  • Among 26 symptomatic patients followed 2 years post-epidemic: 12 had tetravalent infection history (DENV-1→2→3→4), 4 had tertiary history, 5 had secondary history, and only 5 had primary DENV-4 infection (see Garcia2009 - Long-term Clinical Symptoms Post-Dengue).
  • Havana City FcγRIIa genotype distribution: 55% RR, 32% HR, 13% HH — substantially higher RR frequency than Asian populations (6–10% RR). This population-level difference may partly explain why severe dengue is more common in Asia (see Garcia2010 - Asymptomatic Dengue FcγRIIa Polymorphism).

1997 Santiago de Cuba DENV-2 epidemic

  • A localised DENV-2 outbreak in Santiago de Cuba in 1997, 16 years after the island-wide 1981 DENV-2 epidemic; individuals exposed in 1981 were re-exposed to DENV-2 rather than to a new serotype.
  • The overt:subclinical ratio was nearly 1:1 in those sensitised (prior DENV-1 exposure + now secondary DENV-2).
  • An amino acid change in the DENV-2 E protein occurred during the course of this epidemic, associated with month-by-month increases in DHF incidence — suggesting within-epidemic viral evolution affecting severity.
  • This epidemic provided key evidence that within the same secondary serotype combination (DENV-1→DENV-2), viral genotype changes can shift the overt:subclinical and DF:DHF ratio (see Guzman2016 - Dengue Infection).

Cuban vector control programme

  • Cuba launched a comprehensive Ae. aegypti control programme in 1981 following the DENV-2 DHF epidemic — one of the first national-scale programmes in the Americas.
  • Three pillars: larval source reduction (eliminating standing water), adulticidal spraying, and community participation in surveillance and elimination.
  • Plus space spraying (fogging) to rapidly suppress adult mosquito populations during epidemic response.
  • Programme successfully controlled epidemic dengue for approximately 30 years.
  • Programme eventually failed due to economic difficulties and reintroduction of dengue through population movement — illustrating that vector control requires sustained funding and political will.
  • The Cuban programme is cited alongside Singapore’s as an international benchmark for urban dengue control (see Aedes aegypti) (see Guzman2016 - Dengue Infection).

2013 La Habana expert consensus

  • International dengue experts met in Havana in 2013 and reviewed clinical classification data; the consensus confirmed a decrease in disease lethality following the introduction of the 2009 WHO classification system (compared with the 1997 WHO DF/DHF/DSS classification).
  • The 2009 system’s warning signs criteria provide earlier identification of at-risk patients, enabling earlier hospitalisation and fluid management — credited with the mortality reduction (see Guzman2016 - Dengue Infection).

Sources (Cuba)

Nicaragua

Nicaragua is an endemic dengue setting in Central America, with active transmission of multiple DENV serotypes. The country has been a site for longitudinal dengue cohort studies, particularly in Managua, capitalising on the high incidence of dengue in the pediatric population. The Hospital Infantil Manuel de Jesús Rivera (HIMJR) in Managua is a key referral centre for paediatric dengue cases and has served as a recruitment site for immunological studies requiring longitudinal follow-up.

Key Points from Literature

HIMJR Pediatric Cohort — Longitudinal Antibody Kinetics

Bos2025 - Longitudinal Antibody Dynamics After Dengue recruited 79 pediatric dengue patients at HIMJR, Managua, with DENV-1 and DENV-3 as the circulating serotypes. Patients were followed at four timepoints post-infection (<1M, 3M, 6M, 18M) and assessed for 84 dengue-specific antibody features spanning isotype, subclass, antigen target, and cross-reactivity.

Key findings from this cohort:

  • Cross-reactive E protein IgG (XR E-IgG) rises 6–18M post-primary infection (t½ = −2.13 years)
  • NS1-IgG wanes (t½ ≈ 2.1 years)
  • IgA seropositivity ≈ 100% at 18M; IgM ≈ 50% at 18M post-primary
  • IgG3 substantial at 18M; IgG4 rising long-term
  • EDI/II-targeting cross-reactive IgG drives the rising trajectory; EDIII-targeting antibodies flat

Note: Bos2025 is a preprint (medRxiv) and has not yet been peer reviewed.

Sources (Nicaragua)

Brazil

Brazil is the largest country in South America and one of the highest-burden dengue countries globally. The wiki has three sources from Brazil: one dengue case report (Jardim2012, Campinas/São Paulo state), one viral hepatitis comparator study (Codes2002, Salvador/Bahia), and one clinical differential diagnosis narrative review (Farias2024). Brazil recorded over 6 million dengue cases in 2024 alone — among the highest annual burdens ever documented.

Key Points from Literature

Dengue (Campinas, São Paulo state)

Jardim2012 - Autoimmune Features DHF Case Report presents the only dengue case from Brazil in this wiki: a 22-year-old woman with secondary DENV-3 DHF (Campinas, São Paulo) showing an unusual constellation of autoimmune features:

  • ANA 1/320 mitotic spindle pattern — the only mitotic spindle ANA documented in dengue in this wiki; targets centromere/spindle apparatus proteins rather than nuclear DNA/histones
  • Cryoglobulinemia detected during acute illness
  • Selective C3 depression (0.39 g/L) with C4 normal — suggesting alternative pathway complement consumption rather than classical pathway
  • LE cells in pleural fluid cytology — requiring anti-nuclear IgG + complement activation + neutrophil phagocytosis; first documented in dengue pleural fluid in this wiki
  • Triple serositis: pleural effusion, pericardial effusion, ascites
  • DIC: fibrinogen 85.5 mg%, PT 20.2→36.4 sec, APTT 39.5→50.7 sec
  • All autoimmune features fully resolved at follow-up; anti-dsDNA remained negative throughout
  • No serositis mechanism worked up (dengue IC vs. anti-nuclear IC deposition not distinguished)

Viral Hepatitis Comparator (Salvador, Bahia)

Codes2002 - Autoantibodies in Acute Viral Hepatitis is a prospective study from Salvador, Bahia (UFBA hepatology outpatient clinic, n=156, 1992–2000) of autoantibodies in acute viral hepatitis (HAV/HBV/HCV/HEV/non A-E). It is not a dengue study, but is included as a baseline comparator:

  • ANA acute phase: 20.5% positive (homogeneous, ≥1:40) — established benchmark for infection-triggered ANA
  • ANA convalescence (90 days): 6.4% still positive
  • ASMA: 14.8% → 3.9%
  • No prognostic consequence; autoantibodies are transient epiphenomena (see Codes2002 - Autoantibodies in Acute Viral Hepatitis, n=156 prospective cohort)

2024 Brazil Epidemic (Farias2024)

Farias2024 - Dengue Mimickers (narrative review, Brazil) documents the scale of Brazil’s ongoing dengue burden:

  • Over 6 million cases in 2024 — one of the highest annual case counts ever recorded in a single country
  • All four DENV serotypes are co-circulating
  • Brazil also co-circulates CHIKV, ZIKV, OROV (Oropouche virus), and MAYV (Mayaro virus) — all transmitted by Ae. aegypti or closely related species, making co-infection a realistic differential in any febrile presentation
  • The Brazilian review explicitly addresses the clinical challenge of distinguishing dengue from autoimmune conditions (SLE, ITP, Still’s disease) in a high-transmission setting where any febrile illness may be misattributed to dengue
  • The 2024 Brazil epidemic included epidemic-level transmission with significant mortality; Farias2024 does not provide death counts (narrative review — secondary source)

Sources (Brazil)

Paraguay

Paraguay is a landlocked country in South America with endemic dengue transmission. The country appears in this wiki via a single source reporting dengue-associated macrophage activation syndrome (MAS) in paediatric patients — an atypical, severe immune-mediated presentation. The Hospital Central del Instituto de Previsión Social in Asunción is the national social security referral hospital and the reporting institution.

Key Points from Literature

Dengue-Associated MAS — Paediatric Cases

Morel2014 - Autoimmune Response in Children With Dengue presents three paediatric patients (3 months – 8 years; all male) with dengue-triggered autoimmune complications in an endemic setting the authors describe as characterised by “hyperimmune responses” — a term used clinically for particularly pronounced immunopathological outcomes.

Key features documented in Paraguayan patients:

  • MAS/secondary HLH as a dengue complication: Cases 2 and 3 fulfilled 5 of 8 HLH-2004 criteria (fever, hepatosplenomegaly, cytopenias, hypertriglyceridaemia, hyperferritinaemia) without bone marrow haemophagocytosis; responded to methylprednisolone
  • ANA and anti-dsDNA negative in all cases — including the most severe MAS presentations; a key observation that MAS can arise without conventional autoantibody markers
  • NS1 antigen positivity confirmed dengue in Cases 2 and 3; IgG+IgM serology in Case 1
  • IgM anticardiolipin was positive and hypocomplementaemia and proteinuria present in Case 1 (mild); more severe cases had no conventional autoantibodies

The Paraguayan cases support the generalisation that dengue in Latin American endemic settings can trigger atypical, immune-mediated presentations that may be mistaken for primary autoimmune disease.

Sources (Paraguay)

Contradictions & Debates

  • No within-country or cross-country contradictions in this region yet. The Cuban, Nicaraguan, Brazilian, and Paraguayan sources address largely distinct topics (epidemiology/genetics, antibody kinetics, autoimmune complications/comparators, paediatric MAS) and do not conflict.

Sources

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