Rickettsioses as Underrecognized Cause of Hospitalization for Febrile Illness, Uganda

Abstract

The complexity of rickettsial serodiagnostics during acute illness has limited clinical characterization in Africa. We used archived samples from sepsis (n = 259) and acute febrile illness (n = 70) cohorts in Uganda to identify spotted fever and typhus group rickettsiae by using immunofluorescence assay and clinically validated rRNA reverse transcription PCR (RT-PCR). Among 329 participants, 10.0% had rickettsial infections (n = 33; n = 20 identified with immunofluorescence assay and n = 13 by RT-PCR). Serum rRNA RT-PCR was 75.0% (95% CI 42.8-94.5%) sensitive and 91.2% (95% CI 85.8-95.1%) specific. Thrombocytopenia was more common among patients with rickettsial infections than with other nonmalarial infections (adjusted odds ratio 3.7; p = 0.003). No participants were on a tetracycline antimicrobial drug at admission. rRNA RT-PCR is a promising diagnostic strategy for identifying acute rickettsial infections. Doxycycline should be included in empiric antimicrobial drug regimens for nonmalarial febrile illness in this region.

Keywords: Rickettsial infections; Uganda; bacteria; bacterial infections; epidemiology; molecular diagnostic techniques; rickettsioses; sepsis; spotted fever group; sub-Saharan Africa; tick-borne; typhus group rickettsia; vector-borne infections.

Figure 1

Alluvial plots of baseline acute serum samples from study of rickettsioses as an underrecognized cause of hospitalization for febrile illness, Uganda. A) Spotted fever group rickettsiae; B) typhus group rickettsiae. Immunofluorescence assay IgG seroprevalence is shown for different sites and different titer cutoffs. Participant samples were from referral hospital clinical study sites in Arua (in yellow; 7.6% of participants), Mubende (in red, 20.6% of participants), and in Fort Portal (in blue, 71.8%). Distribution of the colored lines across the graph shows a comparison of positive or negative samples among the sites. Green is the total percentage of negative samples. Orange is the total percentage of positive samples. Neg, negative; pos, positive.

Figure 2

Box plot of platelet counts from patient samples by infection type in study of rickettsioses as an underrecognized cause of hospitalization for febrile illness, Uganda. Horizontal lines within boxes indicate median; box tops and bottoms indicate interquartile ranges; error bar above is 1.5x the IQR to the highest value and the error bar below is 1.5x the IQR to the lowest value.