# Acute febrile illness surveillance using TaqMan Array Cards in two urban health facilities, Monrovia, Liberia, December 2018–March 2020

## TL;DR

This study used a specialized test to identify fever-causing pathogens in Liberia, finding malaria was most common but also detecting new threats like dengue and Lassa virus.

## Contribution

First laboratory evidence of dengue and rickettsial disease in humans in Liberia.

## Key findings

- Malaria was the most common detected pathogen (96%), followed by dengue virus and Streptococcus pneumoniae.
- Lassa virus and Neisseria meningitidis, both with epidemic potential, were detected.
- Dengue and Rickettsia were newly identified in Liberia.

## Abstract

Fever is a common symptom of infectious diseases including for those with epidemic potential. Beyond malaria, the causes of undifferentiated (i.e., non-respiratory, non-diarrheal) acute febrile illnesses are not well characterized in Liberia.

From December 2018 through March 2020, we established two acute febrile illness (AFI) sentinel surveillance sites in urban Monrovia at Redemption Hospital and Star of the Sea Health Centre, health facilities that were among the first to have Ebola cases during the 2014–2015 West Africa epidemic. Enrolled AFI patients were two (2) years of age or greater, had a measured fever of ≥37.5oC or history of fever within the past week, and without a known cause of fever. A standardized survey was administered to collect demographic, clinical characteristics, and risk factors. Whole blood was taken, nucleic acid material was extracted and ran on TaqMan Array Cards (TAC), a real-time polymerase chain reaction (RT-PCR) testing platform for 28 pathogens. Data were analyzed using descriptive statistics, and multivariate regression models of any TAC detections stratified by site and age.

We enrolled 1506 AFI patients, 1206 (80%) from Redemption Hospital and 300 (20%) from Star of the Sea. AFI patients were predominantly female (69%) and had a median (interquartile range) age of 18 (7–27) years. Among the 699 (46%) that were TAC positive, 627 were detected from Redemption Hospital and 72 were detected from Star of the Sea Health Centre. Overall Plasmodium spp. (malaria) (96%) were the majority of detections followed by dengue virus (2%), Streptococcus pneumoniae (2%), and Rickettsia spp. (1%). We detected 19 co-infections [malaria co-infections (84%) being the most common]. Two pathogens with epidemic potential, Neisseria meningitidis (detected at Star of the Sea Health Centre) and Lassa virus (detected at Redemption Hospital), were also found. Patients with non-malaria TAC detections (n = 29) were higher at Star of the Sea Health Centre than Redemption Hospital (4% versus 1% respectively, p < 0.05). In multivariate regression for those ages 15 years and older at Redemption Hospital (adjusting for sex, age, pregnancy status, education, occupation, any medication use, measured fever at enrollment, headache, abdominal pain, vomiting/nausea and joint pain), any medication use (aOR=0.6, 95% CI = 0.4–0.9), measured fever at enrollment (aOR=3.5, 95% CI = 1.1–12.0), headache (aOR=1.7, 95% CI = 1.1–2.6 were statistically significant with any TAC detection. In multivariate regression for those ages 2–14 years at Redemption Hospital (adjusting for sex, age, abdominal pain, cough, vomiting/nausea, runny nose, and any animal exposure), having abdominal pain (aOR=1.9, 95% CI = 1.3–2.8), vomiting/nausea (aOR=0.6, 95% CI = 0.4–1.0), and any animal exposure (aOR=1.5, 95% CI = 1.0–2.3) were statistically significant with any TAC detection.

This is the first laboratory evidence of dengue and rickettsial disease in humans in Liberia. Liberia’s incipient AFI platform was successful exploring causes of fever in emerging infections and detected circulating pathogens beyond malaria. AFI surveillance data can assist in the prioritization of public health diagnostic and clinical capabilities to prevent, detect, and respond to emerging infectious disease threats in Liberia.

Among sick patients, fever is a very common symptom for many infectious diseases including those that have the potential to cause epidemics. In many low resource countries such as Liberia, the number of patients at healthcare facilities with fever is high and is often attributed to malaria but other bacterial, viral, or parasitic diseases may be circulating and are unknown. Therefore, exploring this possibility and identifying pathogens that may be the cause of fever is critical for public health. We report here our findings from testing febrile patients using a TaqMan Array Card designed to detect more than two dozen fever-causing pathogens at two major health facilities in urban Monrovia, the capital city in Liberia. While just under half of febrile patients had any positive detections, more than 95% were due to malaria. However, we did detect pathogens causing meningitis and Lassa fever, diseases that have epidemic potential. We also detected dengue and Rickettsia, diseases that have never been reported in Liberia. Our surveillance data can be used to inform future febrile illness surveillance efforts and be used by Liberian health authorities for public health preparedness efforts to be able to detect and respond to infectious disease threats.