Lymphopenia: An early indicator of Crimean-Congo haemorrhagic fever

Abstract

Objectives: Crimean-Congo haemorrhagic fever is a lethal tick-borne disease characterised by initially nonspecific symptoms. While thrombocytopenia and leucopenia are established diagnostic markers, there is a need for earlier indicators. This study evaluates lymphopenia as a marker for Crimean-Congo haemorrhagic fever.

Methods: This retrospective study analysed patients admitted with arthropod bites from 2018 to 2021. Patients were classified based on initial leucocyte and platelet counts into Group 1 (normal values) and Group 2 (low values). Within Group 1, patients were classified as Group 1B if they developed thrombocytopenia and leucopenia during follow-up, whereas those with stable counts were designated as Group 1A. Variance and ROC curve analysis were used to evaluate blood counts.

Results: Of 914 evaluated patients, 870 with normal CBCs were categorised into Group 1, and 44 with low counts into Group 2. Within Group 1, 16 patients subsequently developed thrombocytopenia and leucopenia (Group 1B), while the rest remained stable (Group 1A). All patients in Groups 1B and 2 were later confirmed to have Crimean-Congo haemorrhagic fever via RT-PCR. Initial lymphocyte counts varied significantly, with 2.7 × 10⁹/L in Group 1A, 0.52 × 10⁹/L in Group 1B, and 0.42 × 10⁹/L in Group 2, with notable reductions observed in Group 1B and Group 2 (p < 0.001). ROC analysis showed lymphocyte counts below 1.19 × 10⁹/L were the most sensitive and specific for Crimean-Congo haemorrhagic fever (area under curve is 0.976 [95% CI: 0.957-0.995]), exceeding traditional markers.

Conclusions: Lymphocyte depletion precedes changes in leucocyte and platelet counts, affirming its potential as an early diagnostic marker for Crimean-Congo haemorrhagic fever. Early detection through lymphocyte monitoring could improve patient management and reduce transmission in endemic areas.

Keywords: Crimean‐Congo haemorrhagic fever; leucopenia; lymphopenia; thrombocytopenia; tick bites.

FIGURE 1

Box plot of leucocyte results of patients at their first, second, and third admissions. The central line inside the box represents the median, the bottom and top of the box correspond to the first (Q1) and third quartiles (Q3), respectively, thus representing the interquartile range (IQR). The whiskers extend to the most extreme data points within 1.5 × IQR from the quartiles. Outliers beyond this range are shown as individual dots (°) (>1.5 × IQR) or asterisks (*) (>3 × IQR).

FIGURE 2

Box Plot of platelet results of patients at their first, second, and third admissions. The central line inside the box represents the median, the bottom and top of the box correspond to the first (Q1) and third quartiles (Q3), respectively, thus representing the interquartile range (IQR). The whiskers extend to the most extreme data points within 1.5 × IQR from the quartiles. Outliers beyond this range are shown as individual dots (°) (>1.5 × IQR) or asterisks (*) (>3 × IQR).

FIGURE 3

Box Plot of lymphocyte results of patients at their first, second, and third admissions. The central line inside the box represents the median, the bottom and top of the box correspond to the first (Q1) and third quartiles (Q3), respectively, thus representing the interquartile range (IQR). The whiskers extend to the most extreme data points within 1.5 × IQR from the quartiles. Outliers beyond this range are shown as individual dots (°) (>1.5 × IQR) or asterisks (*) (>3 × IQR).

FIGURE 4

Receiver operating characteristic curve of leucocyte, platelet, lymphocyte, monocyte, and eosinophils results on the first admission obtained by Group 1A versus Group 1B and Group 2.