First Identification and Description of Rickettsioses and Q Fever as Causes of Acute Febrile Illness in Nicaragua

<div><p>Background</p><p>Rickettsial infections and Q fever present similarly to other acute febrile illnesses, but are infrequently diagnosed because of limited diagnostic tools. Despite sporadic reports, rickettsial infections and Q fever have not been prospectively studied in Central America.</p><p>Methodology/Principal Findings</p><p>We enrolled consecutive patients presenting with undifferentiated fever in western Nicaragua and collected epidemiologic and clinical data and acute and convalescent sera. We used ELISA for screening and paired sera to confirm acute (≥4-fold rise in titer) spotted fever and typhus group rickettsial infections and Q fever as well as past (stable titer) infections. Characteristics associated with both acute and past infection were assessed.</p><p>Conclusions/Significance</p><p>We enrolled 825 patients and identified acute rickettsial infections and acute Q fever in 0.9% and 1.3%, respectively. Clinical features were non-specific and neither rickettsial infections nor Q fever were considered or treated. Further study is warranted to define the burden of these infections in Central America.</p></div

Clinical characteristics of febrile patients with confirmed acute rickettsial infection vs. no acute rickettsial infection, Nicaragua.

<p>Clinical characteristics of febrile patients with confirmed acute rickettsial infection vs. no acute rickettsial infection, Nicaragua.</p

Flow diagram depicting approach to serological evaluation of convalescent and acute phase sera for IgG antibodies to spotted fever group rickettsiae, including ELISA and IFA for <i>R</i>. <i>rickettsii</i> and IFA for <i>R</i>. <i>parkeri</i>.

<p>Note that the IFA substrate slides used resulted in simultaneous tests for both <i>R</i>. <i>rickettsii</i> and <i>R</i>. <i>typhi</i>; those samples identified with <i>R</i>. <i>typhi</i> IFA antibodies were then included in the <i>R</i>. <i>typhi</i> tally (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005185#pntd.0005185.g002" target="_blank">Fig 2</a>) if not <i>R</i>. <i>typhi</i> ELISA reactive.</p

Epidemiologic characteristics of patients with definitive serologic evidence of Q fever vs. no Q fever, Nicaragua

<p>Epidemiologic characteristics of patients with definitive serologic evidence of Q fever vs. no Q fever, Nicaragua</p

Flow diagram depicting approach to serological evaluation of convalescent and acute phase sera for IgG antibodies to <i>R</i>. <i>typhi</i>, including ELISA and IFA.

<p>Note that the IFA substrate slides used resulted in simultaneous tests for both <i>R</i>. <i>rickettsii</i> and <i>R</i>. <i>typhi</i>; those samples identified with <i>R</i>. <i>rickettsii</i> IFA antibodies were then included in the <i>R</i>. <i>rickettsii</i> tally (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005185#pntd.0005185.g001" target="_blank">Fig 1</a>) if not <i>R</i>. <i>rickettsii</i> ELISA reactive.</p

Clinical characteristics of febrile patients with acute Q fever vs. no acute Q fever, Nicaragua.

<p>Clinical characteristics of febrile patients with acute Q fever vs. no acute Q fever, Nicaragua.</p

Unsuspected Dengue as a Cause of Acute Febrile Illness in Children and Adults in Western Nicaragua

<div><p>Background</p><p>Dengue is an emerging infectious disease of global significance. Suspected dengue, especially in children in Nicaragua’s heavily-urbanized capital of Managua, has been well documented, but unsuspected dengue among children and adults with undifferentitated fever has not.</p><p>Methodology/Principal Findings</p><p>To prospectively study dengue in semi-urban and rural western Nicaragua, we obtained epidemiologic and clinical data as well as acute and convalescent sera (2 to 4 weeks after onset of illness) from a convenience sample (enrollment Monday to Saturday daytime to early evening) of consecutively enrolled patients (n = 740) aged ≥ 1 years presenting with acute febrile illness. We tested paired sera for dengue IgG and IgM and serotyped dengue virus using reverse transcriptase-PCR. Among 740 febrile patients enrolled, 90% had paired sera. We found 470 (63.5%) were seropositive for dengue at enrollment. The dengue seroprevalance increased with age and reached >90% in people over the age of 20 years. We identified acute dengue (serotypes 1 and 2) in 38 (5.1%) patients. Only 8.1% (3/37) of confirmed cases were suspected clinically.</p><p>Conclusions/Significance</p><p>Dengue is an important and largely unrecognized cause of fever in rural western Nicaragua. Since Zika virus is transmitted by the same vector and has been associated with severe congenital infections, the population we studied is at particular risk for being devastated by the Zika epidemic that has now reached Central America.</p></div

Unsuspected Leptospirosis Is a Cause of Acute Febrile Illness in Nicaragua

<div><p>Background</p><p>Epidemic severe leptospirosis was recognized in Nicaragua in 1995, but unrecognized epidemic and endemic disease remains unstudied.</p><p>Methodology/Principal Findings</p><p>To determine the burden of and risk factors associated with symptomatic leptospirosis in Nicaragua, we prospectively studied patients presenting with fever at a large teaching hospital. Epidemiologic and clinical features were systematically recorded, and paired sera tested by IgM-ELISA to identify patients with probable and possible acute leptospirosis. Microscopic Agglutination Test and PCR were used to confirm acute leptospirosis. Among 704 patients with paired sera tested by MAT, 44 had acute leptospirosis. Patients with acute leptospirosis were more likely to present during rainy months and to report rural residence and fresh water exposure. The sensitivity of clinical impression and acute-phase IgM detected by ELISA were poor.</p><p>Conclusions/Significance</p><p>Leptospirosis is a common (6.3%) but unrecognized cause of acute febrile illness in Nicaragua. Rapid point-of-care tests to support early diagnosis and treatment as well as tests to support population-based studies to delineate the epidemiology, incidence, and clinical spectrum of leptospirosis, both ideally pathogen-based, are needed.</p></div

Proportion (%) of febrile patients with IgG against dengue, by age, Nicaragua.

<p>Proportion (%) of febrile patients with IgG against dengue, by age, Nicaragua.</p

Epidemiologic characteristics of patients with acute dengue vs. other acute febrile illness, Nicaragua.

<p>Epidemiologic characteristics of patients with acute dengue vs. other acute febrile illness, Nicaragua.</p