Table 2.

Examples of potential biomarkers that could be used for monitoring infectious disease spread at the community level through wastewater

Biomarker Groups	Biomarker Examples	Treatment/indicator of	Reported Concentrations	Reference
Biomarkers of intervention	Antibiotics
e.g. Drugs and metabolites	Sulfamethoxazole n-Acetyl sulfamethoxazole	Urinary tract infections, bronchitis	<3–3100 ng/L (INF) 360 ± 110 ng/L (INF)	(Guerra et al., 2014, Hijosa-Valsero et al., 2011, Kasprzyk-Hordern et al., 2009)
	Azithromycin n-Demethyl azithromycin	Pneumonia. middle ear infections, strep throat and intestinal infectios	269–22,730 ng/L (INF) <30–74 ng/L (INF)	(Senta et al., 2019)
	Clarithromycin n- Demethyl clarithromycin	Pneumonia, skin infections, H. pylori infection, and Lyme disease.	111–10,491 ng/L (INF) 13–1559 ng/L (INF)	(Senta et al., 2019)
	Ciprofloxacin	Respiratory tract infections, skin infections, gastroenteritis	17-2500 ng/L (INF)	(Guerra et al., 2014)
	Erythromycin	Respiratory tract infections	14–10,025 ng/L (INF)	(Guerra et al., 2014, Kasprzyk-Hordern et al., 2009)
	Trimethoprim	Urinary tract infections	464–6796 ng/L (INF)	(Kasprzyk-Hordern et al., 2009, Roberts and Thomas, 2006)
	Antivirals
	Oseltamivir phosphate Oseltamivir carboxylate	Flu virus (influenza)	5–529 ng/L (INF) 28–1213 ng/L (INF)	(Leknes et al., 2012, Takanami et al., 2012)
	Acyclovir Carboxy-acyclovir	Herpes simplex virus infections, chicken pox, shingles	1780 ng/L (INF) 490–3420 ng/L (INF)	(Funke et al., 2016, Prasse et al., 2010)
	Emtricitabine Carboxy-emtricitabine	HIV	100–980 ng/L (INF) 24–250 ng/L (INF)	(Funke et al., 2016)
	Lamivudine, Carboxy lamivudine	HIV/AIDs, hepatitis B	52–720 ng/L (INF) 25–84 ng/L (INF)	(Funke et al., 2016, Prasse et al., 2010)
	Abacavir Carboxy-abacavir	HIV/AIDs	21–140 ng/L (INF) 41–560 ng/L (INF)	(Funke et al., 2016)
	Zanamivir	Flu virus (influenza)	16.3–27.8 ng/L (INF)	(Takanami et al., 2012)
	Zidovudine	HIV/AIDs	310–380 ng/L (INF)	(Prasse et al., 2010)
	Nevirapine	HIV/AIDs	4.8–21.8 ng/L (INF)	(Prasse et al., 2010)
	Antifungals
	Ketaconcazole	Skin infections	16 ng/L(INF)	(Huang et al., 2010)
	Miconazole	Skin infections	5.2–1583 ng/L (INF)	(Guerra et al., 2014, Huang et al., 2010, Kasprzyk-Hordern et al., 2009)
	Clotrimazole	Skin and vaginal infections	23-33 ng/L (INF)	(Huang et al., 2010, Roberts and Thomas, 2006)
	Painkillers
	Acetaminophen	Painkiller	5529–500,000 ng/L(INF)	(Guerra et al., 2014, Roberts and Thomas, 2006)
	Ibuprofen	Painkiller	968–45,000 ng/L(INF)	(Guerra et al., 2014, Kasprzyk-Hordern et al., 2009, Roberts and Thomas, 2006)
Biochemical markers linked with physiological response	C-reactive protein (CRP)	Inflammation	0.54–2.76 μg/mL (Urine)	(Stuveling et al., 2003)
e.g. Biomarkers of inflammation	Interlukin-6 (IL-6)	Inflammation in urinary tract infections	1.6–5.28 pg/mL(Urine)	(Renata et al., 2013, Roilides et al., 1999)
	Interlukin-8 (IL-8)	Inflammation in urinary tract infections	7–12 pg/mL (Urine)	(Taha, 2003)
	Lipoarabinomannan (LAM)	Potential indicator of tuberculosis in HIV infected patients	15 pg/mL to several hundred ng/mL(Urine)	(Boehme et al., 2005, Hamasur et al., 2015, Savolainen et al., 2013)
	IP-10	Potential indicator of tuberculosis and pneumonia	5–110 pg/mL (Urine)	(Cannas et al., 2010, Kim et al., 2018)
Pathogenic organisms	Bacterial DNA
e.g. Pathogenic genetic material/ DNA/RNA	Klebsiella pneumoniae	Pneumonia, UTI, bacteremia and endophthalmitis	6.31–6.56 log gene copies/100mL (INF)	(Shannon et al., 2007)
	Pseudomonas aeruginosa	Pneumonia, UTI, gastrointestinal infections	4.31–4.38 log gene copies/100 mL (INF)	(Shannon et al., 2007)
	Enterococcus faecalis	UTIs, bacteremia, septicemia	4.66–4.85 log gene copies/100 mL (INF)	(Shannon et al., 2007)
	Viral DNA/RNA
	Norovirus (GI)	Gastroenteritis	<10–3500 viral genomes/L (INF)	(Hellmér et al., 2014)
	Norovirus (GII)	Gastroenteritis	12.4 × 103–320 × 103 viral genomes/L (INF)	(Hellmér et al., 2014)
	Influenza A	Respiratory infection	2.6 × 105 genome copies/L (INF)	(Heijnen and Medema, 2011)
	Dengue	Severe flu-like illness	4-5 × 10−1 PFU/mL(Urine)	(Poloni et al., 2010)
	Zika	Mild infection, microcephaly	0.7–220.106 copies/mL (Urine)	(Gourinat et al., 2015)
	Hepatitis A	Liver infection	<10-1500 viral genomes/L (INF)	(Hellmér et al., 2014)
	Severe acute respiratory syndrome (SARS CoV)	Respiratory infection	<1x101-106.5 (Faeces)	(Poon et al., 2004)
	Fungal DNA
	Candida species Aspergillus (Aspergillus fumigatus, Aspergillus niger and Aspergillus flavus)	Candidiasis Chronic pulmonary aspergillosis, pulmonary and nasal allergies, asthma, pneumonitis	Detected * (INF)	(Assress et al., 2019)
	Parasites
	Giardia lambli	Small intestine infections	2,653– 13,408 cysts/litre (INF)	(Guy et al., 2003)
	Cryptosporidium	Gastrointestinal illness	1–120 oocysts/litre (INF)	(Wallis et al., 1996)
Biological response	mcr-1	Colistin resistance	8.11 × 101 cell equivalents/100 ng DNA (INF)	(Hembach et al., 2017)
e.g. Antibiotic resistant genes	mecA	Methicillin resistance	1x101- ∼5x104 genes/100 mL(INF)	(Börjesson et al., 2009)
	ermB	Erythromycin resistance	105.2–107 copies/mL(INF)	(Wang et al., 2015)
	sul1	Sulphonamide resistance	105.46–107.54 copies/mL(INF)	(Munir et al., 2011, Wang et al., 2015)
	blaOXA-1	Beta-lactam resistance	105.4–107.3 copies/mL (INF)	(Wang et al., 2015)
	tetW	Tetracycline resistance	104.2–107.4 copies/mL (INF)	(Munir et al., 2011, Wang et al., 2015)

INF: Influent wastewater (U): Urine. PFU: Plaque forming units (measure of number of infectious particles).UTI: Urinary tract infection *Via sequencing