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Table 2 Details of included studies

From: Association between RANTES/CCL5 levels with Plasmodium infections and malaria severity: a systematic review

No

Authors

Study design

Study location (year)

Participants (n)

Plasmodium spp.

Age range

Qualitative results of RANTES

Parasite density

Method for malaria detection

Method for RANTES detection

Blood samples for RANTES

1

Aguilar et al., 2019 [29]

Cross-sectional study

Mozambique

Individuals of all ages: year 2010 (981), year 2013 (980)

P. falciparum

All age ranges

RANTES levels were lower in infected individuals compared to uninfected individuals

Infected (2010): 10.46 (1.61–102.94), Infected (2013):7.61 [1.43–299.84]

Microscopic method/PCR

Cytokine Human Magnetic 30-Plex Panel from Life Technologiesâ„¢

Plasma

2

Armah et al., 2007 [30]

Case–control study

Ghana

Cerebral malaria (9), SMA (5), non-malaria deaths/non-malarial controls (5)

P. falciparum

Children

No difference in RANTES levels between children with cerebral malaria, SMA, and non-malarial controls

Cerebral malaria (9): 51,604 ± 9468, severe malarial anaemia (5): 195003 ± 23613, non-malaria deaths/non-malarial controls (5): 0

Microscopic method

Multiplex colorimetric bead-based cytokine immunoassay

Serum

3

Boivin et al., 2019 [31]

Randomized controlled trial

Uganda

The malaria survivor’s cohort of children (150): children with cerebral malaria (93), children with SMA (57)

P. falciparum

Children (6 to 12 years)

1. Severe malaria survivors with higher levels of plasma RANTES had better KABC cognitive performance after both titrating and non-titrating CCRT compared to no CCRT. For the CBCL, high plasma RANTES was associated with no benefit from either the titrating and non-titrating CCRT. 2. Control groups; RANTES levels were lower in severe malaria compared to community controls

Not specified

Microscopic method/RDT

Microbead suspension array technology (SAT) using the Luminex system (Austin, TX) and human-specific bead sets (R&D Systems, Minneapolis, MN)

Plasma

4

Boström et al., 2012 [a] [32]

Cross-sectional study

Mali

Uninfected Dogon (20), Infected Dogon (20), Uninfected Fulani (23), Infected Fulani (14)

P. falciparum

Children (2–10 years)

1. RANTES levels were significantly lower in infected Dogon compared to uninfected Dogon. 2. No difference in RANTES levels between infected Fulani compared to uninfected Fulani

Infected Dogon (20):13692 (575–48625), Infected Fulani (14): 27537 (100–122000)

Microscopic method

Cytometric bead array (CBA, BD Biosciences, San Diego, CA, USA)

Plasma

5

Boström et al., 2012 (b) [33]

Cohort study

Tanzania

Pregnant women with a gestational age ≤ 24 weeks (1000): malaria infected (42), malaria uninfected (79)

P. falciparum

Not specified

RANTES levels were significantly lower in infected individuals compared to uninfected individuals

Pregnancy women: malaria infected (11): 27,969.2 (39.5–390749 ± 17132.4)

Microscopic method/RDT

Cytometric bead arrays (CBA, BD Biosciences, San Diego, CA, USA)

Plasma

6

Bujarbaruah et al., 2017 [34]

Cohort study

India

Clinically proven P. falciparum malaria cases (153): uncomplicated malaria (128), severe malaria (25); age and sex matched community healthy controls without any past history of malaria infection (112)

P. falciparum

Adults

Serum RANTES concentrations was significantly lower in severe malaria cases [15708.92 ng/L] compared to uncomplicated malaria cases [16147.74 ng/L] and control cases [18587.2 ng/L]

Not specified

Microscopic method/RDT

Human RANTES ELISA kit (ab100633, Abcam)

Serum

7

Cruz et al., 2019 [35]

Case–control study

Brazil

Individuals from the Brazilian Amazon (601): symptomatic P. vivax monoinfected patients (179), asymptomatic P. vivax monoinfection (145), P. vivax-HBV coinfected patients (28), HBV monoinfected subjects (29), healthy controls (165)

P. vivax

Adults

No difference in RANTES levels between symptomatic vivax patients compared to uninfected controls

Symptomatic P. vivax monoinfected patients (179): 6324 (913.5–60623), asymptomatic P. vivax monoinfection (145): 0 (0–32), P. vivax-HBV coinfected patients (27): 753 (444.3–4262)

Microscopic method/PCR

Cytometric Bead Array—CBA (BD Biosciences Pharmingen, San Diego, CA, USA)

Plasma

8

Daveport et al., 2012 [36]

Case–control study

Kenya

Children aged 3–36 months with P. falciparum parasitemia (194): malaria alone (HIV-1( −)/Pf( +), n = 148); HIV-1 exposed (HIV-1(exp)/Pf( +), n = 30); and co-infected (HIV-1( +)/Pf( +), n = 16)

P. falciparum

3–36 months

RANTES levels were highest in co-infected individuals, high in individuals with malaria alone, and lowest in those exposed to HIV-1 and Pf( +)

Geometric mean; Malaria alone (HIV-1( −)/Pf( +), n = 148): 25,619 (59,721); HIV-1 exposed (HIV-1(exp)/Pf( +), n = 30): 25659 (35,865); and co-infected (HIV-1) +)/Pf( +), n = 16): 14405 (25599)

Microscopic method

Cytokine 25plex Antibody Bead Kit, Human [BioSourceâ„¢ International]

Plasma

9

Frimpong et al., 2022 [37]

Case–control study

Ghana

Children (76): clinical malaria with no sepsis (33), non-malaria febrile control (20), non-malaria sepsis (23)

P. falciparum

Children

RANTES levels were significantly lower in children with sepsis when compared to children with malaria, but was higher when compared to febrile controls

Children (76): clinical malaria with no sepsis (32): 94494.87

Microscopic method/RDT

Human Cytokine Magnetic 25-Plex Panel (Thermo Fisher Scientific Corporation, United States)

Plasma

10

Hojo-Souza et al., 2017 [38]

Case–control study

Brazil

P. vivax uncomplicated patients (75), P. vivax-treated group (10), endemic control (10), healthy control (15)

P. vivax

Adults

1. RANTES levels were significantly lower individuals with P. vivax infection compared to endemic controls. 2. RANTES levels were significant increase after the treatment when following the same individuals

P. vivax uncomplicated patients (75): ≤ 500 (33), 501–10000 (25), 10001–100000 (8), without information (7)

Microscopic method/PCR

Cytometric bead assay (CBA) (BD Biosciences, USA)

Plasma

11

Jain et al., 2008 [39]

Case–control study

India

Cerebral malaria survivors (48), cerebral malaria non-survivors (12), healthy controls (25), mild malaria (48)

P. falciparum

Children (< 18 years) and adults (≥ 18 years)

No difference in RANTES levels between cerebral malaria survivors, cerebral malaria non-survivors, mild malaria, and healthy controls

Cerebral malaria survivors (46): 4166 ± 650.9, cerebral malaria non-survivors (12): 1336 ± 386.2, mild malaria (46): 1594 ± 426.6

Microscopic method

Multiplex bead-based cytokine immunoassay (MMA)

Plasma

12

John et al., 2006 [15]

Case–control study

Uganda

Children with cerebral malaria (88), children with uncomplicated malaria (76), community controls (100)

P. falciparum

4–12 years

1. RANTES levels were lower in cerebral malaria compared to uncomplicated malaria. 2.RANTES levels were lower in cerebral malaria compared to community controls. 3. RANTES levels at 72 h after admission were significantly higher than those at the time of admission but were comparable to those in children with uncomplicated malaria and were still not as high as those in community controls

Children with cerebral malaria (88): 39790 (143–560), children with uncomplicated malaria (76): 54840 (118–220)

Microscopic method

Colorimetric bead assay using the Luminex system and human-specific bead sets (R&D Systems)

Serum

13

Noone et al., 2013 [40]

Cross-sectional study

Nigeria

Uninfected endemic controls (69), Ascaris (21), Malaria (109), Ascaris/Malaria (32)

P. falciparum

39–73 months

RANTES was not associated with P. falciparum parasitemia

Malaria (109): 5097 ± 717.4, Ascaris/Malaria (31):6618.7 ± 1683.2

Microscopic method

DuoSet ELISA Developmental Kits (R&D, Minneapolis, MN, USA)

Plasma

14

Obeng-Aboagye et al., 2023 [11]

Case–control study

Ghana

Children (57); severe malaria (27), uncomplicated malaria (10), non-malaria related fever (20)

P. falciparum

Children

1. RANTES levels were significantly higher in severe malaria as compared to febrile controls. 2. No difference in RANTES levels between severe and uncomplicated malaria. 3. No difference in RANTES levels between uncomplicated malaria and febrile controls

Severe malaria (26): 54683 (29706–162776), uncomplicated malaria (10): 36228 (15671–116416)

Microscopic method

Human Cytokine Magnetic 25-Plex Panel (Thermo Fisher Scientific Corporation, United States of America)

Plasma

15

Ochiel et al., 2005 [41]

Cohort study

Gabon

Severe malaria cases (10), mild malaria cases (10), healthy malaria-exposed subjects (23)

P. falciparum

2 to 7 years

1. RANTES levels were significantly lower in children with mild malaria and severe malaria compared to healthy controls. 2. RANTES levels were significantly lower in children with severe malaria compared to those with mild malaria

Severe malaria cases (10): 355571 ± 58050, mild malaria cases (10): 52899 ± 10437

Microscopic method

Quantitative ELISA

(Biosource International, Camarillo, CA)

Plasma

16

Ong’echa et al., 2011 [42]

Case–control study

Kenya

Uncomplicated malaria (31), non-SMA (37), SMA (80)

P. falciparum

Children (3 to 30 months)

No difference in RANTES levels between patients with SMA, non-SMA, and uncomplicated malaria

Uncomplicated malaria (30): 48354 (IQR 87430), non-SMA (36): 22615 (IQR 49,929), SMA (80): 26166 (IQR 60703)

Microscopic method

Human cytokine 25-plex antibody bead kit (BioSource International)

Plasma

17

Panda et al., 2013 [43]

Cross-sectional study

India

Severe malaria (125), non- complicated malaria (71), healthy controls (38)

P. falciparum

Severe malaria (125): 34(15–72), non- complicated malaria (71): 30(14–70), healthy controls (38): 30(12–75)

RANTES levels were significantly lower in severe malaria compared to non-complicated malaria

Not specified

Microscopic method/RDT

Commercial sandwich ELISA kits (Sanquin, Amsterdam)

Plasma

18

Reuterswärd et al., 2018 [44]

Cohort study

Rwanda

Severe malaria (180), mild malaria (183), controls (178)

P. falciparum

3 months up to 6 years

RANTES levels were significantly lower in infected individuals compared to uninfected individuals

Not specified

Microscopic method

Antibody-based suspension bead array

Plasma

19

Suguitan et al., 2003 [45]

Cohort study

Cameroon

Malaria positive (89), malaria negative (83)

P. falciparum

Pregnant women

No difference in RANTES levels between infected individuals compared to uninfected individuals

Placenta sample: 0.076 ± 0.154, Peripheral blood: 0.005 ± 0.011

Microscopic method

DuoSet ELISA Development System; R&D Systems

Plasma

20

Turner et al., 2021 [46]

Cross-sectional study

Mali

Asymptomatic infected with P. falciparum (8), uninfected subjects (27), children (19)

P. falciparum

Children and adults

Adults: No difference in RANTES levels between infected individuals compared to uninfected individuals

Not specified

PCR

Cytometric Bead Array Human Inflammatory Cytokine Kit (BD Biosciences)

Plasma

21

Vinhaes et al., 2021 [47]

Cohort study

Brazil

Asymptomatic malaria (108), symptomatic malaria (134); mild malaria (106), severe malaria (28), uninfected endemic controls (128)

P. vivax

Adults

RANTES levels were significantly higher in symptomatic malaria compared to asymptomatic malaria

Not specified

Microscopic method/PCR

Cytometric Bead Array—CBA (BD Biosciences Pharmingen, San Diego, CA, USA)

Plasma

22

Were et al., 2006 [48]

Cross-sectional study

Kenya

SMA (27), moderate anaemia (27), mild anaemia (28), healthy controls (24)

P. falciparum

Children (age < 36 months)

RANTES levels were decreased with increasing malarial anaemia severity, with the SMA group having lower circulating RANTES than children with moderate malarial anaemia, mild malarial anaemia, or healthy controls

SMA (26): 38874 ± 7685, moderate anaemia (26): 37771 ± 8169, mild anaemia (27): 34183 ± 7909

Not specified

Not specified

Plasma

  1. CCRT Computerized cognitive rehabilitation training; ELISA Enzyme-linked immunosorbent assay; HBV Hepatitis B virus Kaufman assessment battery for children; RANTES Regulated on activation, normal T cell expressed and secreted; RDT reaction; Pf Plasmodium falciparum; SMA Severe malarial anaemia