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Erschienen in: Malaria Journal 1/2019

Open Access 01.12.2019 | Research

Genetic polymorphism of merozoite surface proteins 1 and 2 of Plasmodium falciparum in the China–Myanmar border region

verfasst von: Cang-Lin Zhang, Hong-Ning Zhou, Quan Liu, Ya-Ming Yang

Erschienen in: Malaria Journal | Ausgabe 1/2019

Abstract

Background

Malaria is a major public health problem in the China–Myanmar border region. The genetic structure of malaria parasite may affect its transmission model and control strategies. The present study was to analyse genetic diversity of Plasmodium falciparum by merozoite surface proteins 1 and 2 (MSP1 and MSP2) and to determine the multiplicity of infection in clinical isolates in the China–Myanmar border region.

Methods

Venous blood samples (172) and filter paper blood spots (70) of P. falciparum isolates were collected from the patients of the China–Myanmar border region from 2006 to 2011. The genomic DNA was extracted, and the msp1 and msp2 genes were genotyped by nested PCR using allele-specific primers for P. falciparum.

Results

A total of 215 P. falciparum clinical isolates were genotyped at the msp1 (201) and msp2 (204), respectively. For the msp1 gene, MAD20 family was dominant (53.49%), followed by the K1 family (44.65%), and the RO33 family (12.56%). For the msp2 gene, the most frequent allele was the FC27 family (80.93%), followed by the 3D7 family (75.81%). The total multiplicity of infection (MOI) of msp1 and msp2 was 1.76 and 2.21, with a prevalence of 64.19% and 72.09%, respectively. A significant positive correlation between the MOI and parasite density was found in the msp1 gene of P. falciparum. Sequence analysis revealed 38 different alleles of msp1 (14 K1, 23 MAD20, and 1 RO33) and 52 different alleles of msp2 (37 3D7 and 15 FC27).

Conclusion

The present study showed the genetic polymorphisms with diverse allele types of msp1 and msp2 as well as the high MOI of P. falciparum clinical isolates in the China–Myanmar border region.
Begleitmaterial
Hinweise
Cang-Lin Zhang and Hong-Ning Zhou contributed equally to this work

Supplementary information

Supplementary information accompanies this paper at https://​doi.​org/​10.​1186/​s12936-019-3003-8.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
MSP1
merozoite surface protein 1
MSP2
merozoite surface protein 2
GMS
Greater Mekong Subregion
MOI
multiplicity of infection

Background

Malaria is still one of the most important life-threatening parasitic diseases in tropical and subtropical areas. There were approximate 219 million malaria cases and 435,000 deaths in the world in 2017 [1]. In Southeast Asia, the Greater Mekong Subregion (GMS) is one of the high malarious areas, with the co-existence of different species and emergence of drug-resistant parasites. In Yunnan Province, the most high malarious endemic region in China, annual incidence has decreased from 196/100,000 in 2006 to 0.7/100,000 in 2016, where indigenous malaria transmission is mostly concentrated in Yingjiang County that is adjacent to the Kachin State of Myanmar [2]. In addition, the malaria cases are also clustered on small spatial scales along the China–Myanmar border, which may be related to climatic, environmental, and ecological factors favoring vector survival [3, 4], as well as to the high malaria endemicity in the adjacent Kachin State of Myanmar.
Genetic diversity of the parasites provides useful information on the parasite populations and control efforts against malaria. Polymorphic genetic markers of P. falciparum include the merozoite surface protein 1 (MSP1) and MSP2 that have been used to evaluate the genetic diversity of malaria parasites [510]. Based on the sequence analysis of P. falciparum isolates from different endemic areas, the msp1 gene is divided into two allelic types of MAD20 and K1, whereas the highly polymorphic block 2 is represented by three allelic types of K1, RO33 and MAD20 [11]. In contrast, the msp2 gene is grouped into two different allelic types of 3D7 and FC27 [1214]. These two polymorphic markers have been used to study the P. falciparum population in northeastern Myanmar, suggesting a highly diverse parasite population [15]. Due to the dramatic changes of the malaria situation in Yunnan Province, China, in recent years, this study aimed to investigate the genetic diversity of the P. falciparum populations along the China–Myanmar border region using two polymorphic markers MSP1 and MSP2.

Methods

Collection of clinical parasite samples

This study was approved by the Ethical Review Board of Yunnan Institute of Parasitic Diseases, China. A total of 242 P. falciparum clinical samples were collected from malaria patients attending local hospitals along the China–Myanmar border during 2006–2011. These patients came from Laza, Nawei, Mangdong, and Nankajiang in Myanmar, and Tengchong, Yingjiang and Mengla in Yunnan Province, China (Fig. 1). All patients were diagnosed with P. falciparum infection by Giemsa-stained blood smears and microscope examination at the local hospitals, and further confirmed by a nested PCR [16]. Two hundred and fifty microlitres of finger-pricked blood was spotted on the 3 mm Whatman filter paper (GE Healthcare, USA), dried, and stored at 4 °C until further analysis.

PCR amplification

Genomic DNA of parasite was extracted from the filter paper by using the QIAamp® DNA Mini Kit (Qiagen, Germany). The msp1 and msp2 genes were genotyped by a nested PCR using allele-specific primers as described elsewhere [17]. The PCR products were analysed on 2% agarose gel electrophoresis and stained with GoldView (Shanghai, China), whose size was determined using the standard DNA ladder marker (Toyobo, Japan).
The PCR products were sequenced and deposited in the GenBank with accession numbers MG004320–MG004381 for the K1 type, MG004447–MG004517 for the MAD20 type, and MG004518–MG004527 for the RO33 type of msp1; MG004219–MG004319 for the 3D7 type and MG004382–MG004446 for the FC27 type of msp2.

Multiplicity of infection

Multiplicity of infection (MOI) was defined as the largest number of alleles at each locus, and single infection was that with only one allele per locus at all of the genotyped loci [15, 18].

Statistical analysis

All statistical analyses were conducted with the software Statistical Package for Social Sciences (SPSS) version 23.0. The frequencies of the different combinations of alleles in seven studied areas were assessed by Kruskal–Wallis test, and normally distributed continuous data were evaluated by analysis of variance (ANOVA). The Spearman’s rank correlation coefficient test was calculated to assess relationships between MOI and parasite densities or ages in these patients, respectively. The difference was considered statistically significant when P value was less than 0.05.

Results

General characteristics of included patients

A total of 242 malaria patients were enrolled into this study during 2006–2011. Among these patients, there were 200 patients who were confirmed by a nested PCR to be infected with P. falciparum, 14 patients infected with Plasmodium vivax, and 15 patients co-infected with P. falciparum and P. vivax, and 13 patients excluded from the study as the genomic DNA from these patients were not successfully extracted (Fig. 2). All the P. falciparum clinical isolates (215 patients) were included in this study. Of these, 65 patients were from Yunnan province, China, and 150 from Myanmar. Sixty-eight patients were children under 19 years, 11 patients were more than 49 years old, and other 136 patients were between 19 and 49 years old.

Allelic polymorphism of msp1 and msp2

Among 215 P. falciparum clinical isolates, 201 (93.49%) and 204 (94.88%) samples were genotyped at the msp1 and msp2, respectively. For msp1 gene, the MAD20 family was dominant (53.49%) and included 7 different band sizes (120–280 bp), followed by the K1 family (44.65%) that included 9 different band sizes (150–320 bp), and the RO33 family (12.56%) that contained 3 different band sizes (150–200 bp) (Table 1, Fig. 3). The alleles with a high frequency for MAD20, K1 and RO33 were 180 bp (30.38%), 180 bp (30%) and 150 bp (64.10%), respectively.
Table 1
Prevalence of msp1 and msp2 allelic types in the China–Myanmar border region
Allelic types
Mengla, Yunnan
Tengchong, Yunnan
Yingjiang, Yunnan
Laza, Myanmar
Nawei, Myanmar
Nankajiang, Myanmar
Mangdong, Myanmar
Total
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n = 28
n = 16
n = 21
n = 77
n = 26
n = 19
n = 28
n = 215
msp1
 K1
10 (35.71)
5 (31.25)
5 (23.81)
16 (20.78)
9 (34.62)
7 (36.84)
13 (46.43)
65 (30.23)
 MAD20
11 (39.29)
9 (56.25)
10 (47.62)
28 (36.36)
8 (30.77)
7 (36.84)
11 (39.29)
84 (39.07)
 RO33
0
1 (6.25)
0
15 (19.48)
1 (3.85)
1 (5.26)
1 (3.57)
19 (8.84)
 K1/MAD20
7 (25.00)
0
2 (9.52)
8 (10.39)
6 (23.08)
0
2 (7.14)
25 (11.63)
 KI/RO33
0
0
0
2 (2.6)
0
0
0
2 (0.93)
 MAD20/RO33
0
0
0
2 (2.6)
0
0
0
2 (0.93)
 K1/MAD20/RO33
0
0
3 (14.29)
1 (1.3)
0
0
0
4 (1.86)
 Negative
0
1 (6.25)
1 (4.76)
5 (6.49)
2 (7.69)
4 (21.05)
1 (3.57)
14 (6.51)
 Multiclonal isolates
22 (78.57)
12 (75.00)
13 (61.90)
51 (66.23)
12 (46.15)
3 (15.80)
25 (89.29)
138 (64.19)
 Mean MOI
1.83 ± 0.59
1.94 ± 0.68
2.01 ± 1.28
1.82 ± 0.94
1.44 ± 0.58
1.15 ± 0.40
1.98 ± 0.51
1.76 ± 0.85
msp2
 FC27
1 (3.57)
2 (12.5)
11 (52.38)
21 (27.27)
1 (3.85)
2 (10.53)
3 (10.71)
41 (19.07)
 3D7
3 (10.71)
0
0
8 (10.39)
6 (23.08)
12 (63.16)
1 (3.57)
30 (13.95)
 FC27/3D7
23 (82.14)
13 (81.25)
9 (42.86)
43 (55.84)
19 (73.08)
3 (15.79)
23 (82.14)
133 (61.86)
 Negative
1 (3.57)
1 (6.25)
1 (4.76)
5 (6.49)
0
2 (10.53)
1 (3.57)
11 (5.12)
 Multiclonal isolates
26 (92.86)
14 (87.50)
19 (90.48)
52 (67.53)
21 (80.77)
3 (15.79)
20 (71.43)
155 (72.09)
 Mean MOI
3.27 ± 0.99
3.29 ± 1.20
2.57 ± 1.21
1.86 ± 1.03
2.63 ± 1.51
1.13 ± 0.38
2.21 ± 1.08
2.21 ± 1.29
For msp2 gene, the FC27 family (80.93%) showed the higher number of alleles, with 8 different band sizes (250–700 bp) (Table 1, Fig. 3), followed by the 3D7 family (75.81%) that included 9 different band sizes (400–760 bp). The most frequent alleles of FC27 and 3D7 were 700 bp (19.56%) and 550 bp (28.22%), respectively.
The total rate of MOI for msp1 and msp2 was 64.19% and 72.09%, respectively. The alleles of P. falciparum clinical isolates were K1 (30.23%), MAD20 (39.07%), RO33 (8.84%), K1 + MAD20 (11.63%), KI + RO33 (0.93%), MAD20 + RO33 (0.93%), K1 + MAD20 + RO33 (1.86%) for msp1 and FC27 (19.07%), 3D7 (13.95%), FC27 + 3D7 (61.86%) for msp2, respectively, while none of above-mentioned combination alleles of msp1 (such as K1 + MAD20, KI + RO33, MAD20 + RO33, and K1 + MAD20 + RO33) were be found in the isolates from Tengchong of Yunnan and Nankajiang of Myanmar (Table 1 and Fig. 4). There were a statistical difference in prevalences of the K1, MAD20, and RO33 families and their different MOI of msp1 (X2 = 14.478; P = 0.025) or FC27, 3D7, and FC27/3D7 alleles of msp2 (X2 = 30.617; P = 0.000) between the seven studied areas.

The MOI distribution of allelic families across different parasite density and age groups

Almost all patients were detected to have multiclonal infections, with a mean MOI of 1.76 ± 0.85 for msp1 and 2.21 ± 1.29 for msp2. The MOI values of msp1 and msp2 for each parasite density and age groups are summarized in Tables 2 and 3. There was a significant positive correlation between the MOI and parasite density for msp1 (Spearman’s rank coefficient = 0.208; P = 0.002) (Additional file 1: Table S1), but no positive correlation for msp2 (Spearman’s rank coefficient = − 0.040; P = 0.564) was found. Additionally, no significant correlation between age and MOI (Spearman’s rank coefficient = − 0.12; P = 0.08 for msp1 and Spearman’s rank coefficient = 0.007; P = 0.917 for msp2) was found. Furthermore, there was a significant difference of the MOI for the msp1 gene among the groups with different parasite densities (F = 2.588; P = 0.028), while no significant difference for msp2 (F = 0.245; P = 0.942) or for the MOI of msp1 (F = 0.443; P = 0.818) and msp2 (F = 0.433; P = 0.825) among groups with different ages were found.
Table 2
Distribution of msp1 and msp2 allelic types of P. falciparum among different age groups in the China–Myanmar border region
Allelic types
Age group (years)
Total
< 9
9–19
19–29
29–39
39–49
≥ 49
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n = 11
n = 57
n = 70
n = 40
n = 26
n = 11
n = 215
MSP-1
 K1
4 (36.36)
17 (29.82)
23 (32.86)
9 (22.5)
11 (42.31)
1 (9.09)
65 (30.23)
 MAD20
2 (18.18)
21 (36.84)
33 (47.14)
13 (32.5)
10 (38.46)
5 (45.45)
84 (39.07)
 RO33
0 (0)
7 (12.28)
2 (2.86)
6 (15)
1 (3.85)
3 (27.27)
19 (8.84)
 K1/MAD20
4 (36.36)
4 (7.02)
5 (7.14)
8 (20)
3 (11.54)
1 (9.09)
25 (11.63)
 KI/RO33
0 (0)
1 (1.75)
0 (0)
1 (2.5)
0 (0)
0 (0)
2 (0.93)
 MAD20/RO33
0 (0)
1 (1.75)
0 (0)
1 (2.5)
0 (0)
0 (0)
2 (0.93)
 K1/MAD20/RO33
0 (0)
1 (1.75)
2 (2.86)
0 (0)
1 (3.85)
0 (0)
4 (1.86)
 Negative
1 (9.09)
5 (8.77)
5 (7.14)
2 (5)
0 (0)
1 (9.09)
14 (6.51)
 Multiclonal isolates
4 (36.36)
7 (12.28)
7 (10)
10 (25)
4 (15.38)
1 (9.09)
33 (15.35)
 Mean MOI
1.87 ± 0.77
1.88 ± 0.80
1.80 ± 0.90
1.74 ± 0.84
1.44 ± 0.57
1.73 ± 1.18
1.76 ± 0.85
MSP-2
 FC27
1 (9.09)
12 (21.05)
10 (14.29)
13 (32.5)
2 (7.69)
3 (27.27)
41 (19.07)
 3D7
2 (18.18)
8 (14.04)
7 (10)
5 (12.5)
8 (30.77)
0 (0)
30 (13.95)
 FC27/3D7
8 (72.73)
34 (59.65)
48 (68.57)
20 (50)
16 (61.54)
7 (63.64)
133 (61.86)
 Negative
0 (0)
3 (5.26)
5 (7.14)
2 (5)
0 (0)
1 (9.09)
11 (5.12)
 Multiclonal isolates
8 (72.73)
34 (59.65)
48 (68.57)
20 (50)
16 (61.54)
7 (63.64)
133 (61.86)
 Mean MOI
2.06 ± 1.23
2.09 ± 1.14
2.45 ± 1.29
2.16 ± 1.24
2.04 ± 1.39
2.28 ± 1.72
2.21 ± 1.29
Table 3
Distribution of msp1 and msp2 allelic types of P. falciparum among different parasite densities in the China–Myanmar border region
Allelic type
Parasite density (no. of parasites/µl of blood)
Total
< 500
500–1000
1000–2500
2500–10,000
10,000–100,000
≥100,000
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n (%)
n = 11
n = 22
n = 44
n = 66
n = 61
n = 11
n = 215
msp1
 K1
4 (36.36)
9 (40.91)
18 (40.91)
18 (27.27)
14 (22.95)
2 (18.18)
65 (30.23)
 MAD20
5 (45.45)
8 (36.36)
17 (38.64)
29 (43.94)
22 (36.07)
3 (27.27)
84 (39.07)
 RO33
0 (0)
0 (0)
2 (4.55)
3 (4.55)
8 (13.11)
6 (54.55)
19 (8.84)
 K1/MAD20
2 (18.18)
5 (22.73)
2 (4.55)
9 (13.64)
7 (11.48)
0 (0)
25 (11.63)
 KI/RO33
0 (0)
0 (0)
0 (0)
0 (0)
2 (3.28)
0 (0)
2 (0.93)
 MAD20/RO33
0 (0)
0 (0)
0 (0)
0 (0)
2 (3.28)
0 (0)
2 (0.93)
 K1/MAD20/RO33
0 (0)
0 (0)
0 (0)
3 (4.55)
1 (1.64)
0 (0)
4 (1.86)
 Negative
0 (0)
0 (0)
5 (11.36)
4 (6.06)
5 (8.2)
0 (0)
14 (6.51)
 Multiclonal isolates
2 (18.18)
5 (22.73)
2 (4.55)
12 (18.18)
12 (19.67)
0 (0)
33 (15.35)
 Mean MOI
1.32 ± 0.68
1.52 ± 0.73
1.67 ± 0.68
1.91 ± 0.86
1.80 ± 0.95
2.02 ± 0.83
1.76 ± 0.85
msp2
 FC27
0 (0)
1 (4.55)
5 (11.36)
17 (25.76)
16 (26.23)
2 (18.18)
41 (19.07)
 3D7
1 (9.09)
5 (22.73)
10 (22.73)
6 (9.09)
3 (4.92)
5 (45.45)
30 (13.95)
 FC27/3D7
10 (90.91)
15 (68.18)
26 (59.09)
41 (62.12)
38 (62.3)
3 (27.27)
133 (61.86)
 Negative
0 (0)
1 (4.55)
3 (6.82)
2 (3.03)
4 (6.56)
1 (9.09)
11 (5.12)
 Multiclonal isolates
10 (90.91)
15 (68.18)
26 (59.09)
41 (62.12)
38 (62.3)
3 (27.27)
133 (61.86)
 Mean MOI
1.32 ± 0.68
1.52 ± 0.73
1.67 ± 0.68
1.89 ± 0.86
1.80 ± 0.95
2.02 ± 0.83
2.21 ± 1.29

Sequence analysis of MSP1 and MSP2

A total of 38 different alleles of msp1 were used for sequence analysis, including 14 for K1 family, 23 for MAD20, and 1 for RO33 (Additional file 2: Figure S1, Additional file 3: Figure S2). All K1-type alleles were found to have a 24-amino acid sequence: SPSSRSNTLPRSNTSSGASPPADA at the 5′-end and 10-amino acid sequence: NEEEITTKGA at the 3′-end. The central variable region always started with SAQ and terminated with SGT containing the difference number of tripeptide repetition, such as SAQ, SGP, and SGT. The diversity of MAD20 family was also caused by differences in repetitions of SGG, SVA and SVT, but the central variable region always started with SKG or SGG and ended with SVA. Only one amino acid sequence type of amino acids LKDGANTQVVAKPAGAVSTQSAKNPPGATVPSGTASTKGAIRSPGAANPSD was identified in the RO33 family. A total of 37 alleles of 3D7 and 15 alleles of FC27 in the msp2 gene were detected by sequence analysis of the block 3 region (Additional file 4: Figure S3, Additional file 5: Figure S4). The central variable region of 3D7 family included diverse amino acid repeat motifs that contained the different combinations of three amino acids: S, A, and G. The 3D7 family consisted of 12 different amino acids repeats and the 17 single amino acids.
The full sequences of 3D7 family were compared to the reference 3D7 (GenBank accession number X53832) (Additional file 4: Figure S3), showing deletion of 10 or 11 amino acids PKG(K/N)G(E/G/K/Q)VQ(E/K/P)(N/P/S) or PKG(K/N)G(E/G/K/Q)VQ(E/K/P)(N/P/S)N in the reference 3D7, which was common in field isolates from China–Myanmar border region. The dominant genotype of FC27 family was found to have one 32-amino acid ADTIASGSQSSTNSASTSTTNNGESQTTTPTA, followed by a conserved sequence ADTPTAT(E/K), and a two type of tandemly repeated units, SNSPSPPITTTE or SNSRSPPITTTE, repeated from two up to five times. All FC27 family had a 10-amino acid SSSSGNAPNK at the 5′-end and 3-amino acid AP(N/K) or 6-amino acid APNAP(K/N) at the 3′-end (Additional file 5: Figure S4).

Discussion

The genetic diversity of P. falciparum may affect the model of transmission and control strategies for the parasite. The pathogenicity, antigen specificity and anti-malarial drug sensitivity of P. falciparum can be associated with their malarial genetic structure [19, 20]. The genetic polymorphism analysis of P. falciparum field isolates is necessary and might shed light on the development of control strategies and effective vaccines against P. falciparum.
In the present study, a high genetic diversity of msp1 and msp2, including 19 different PCR products for msp1 (7 MAD20, 9 K1 and 3 RO33) and 17 for msp2 (8 FC27 and 9 3D7) was found in the P. falciparum population in the Myanmar-China border regions. Two PCR products of msp1 are similar to that in Thailand and western Cambodia [17, 21]. Allele typing for msp1 showed that MAD20 (115/215, 53.49%) was the predominant allelic type in studied areas, which is consistent with the situations in Thailand, Myanmar, Vietnam, Colombia, Equatorial Guinea, and Yunnan Province, China [15, 2227]. On the contrary, the K1 family is the most frequent genotype in Laos, Peru, India, Pakistan, Tanzania, Malaysia, and Senegal [2835]. Allele typing for msp2 also showed the highest prevalence of FC27 (174/215, 80.93%) and 3D7 (163/215, 75.81%), which is consistent with these situations in Benin [36]. However, 3D7 is the most frequent in Thailand, Myanmar, Colombia, Malaysia, Senegal, India, Equatorial Guinea and Pakistan [16, 2123, 26, 30, 32, 34, 35, 37, 38]. The overall multiplicity of infection (MOI) of msp1 and msp2 was 1.76 and 2.21, respectively. They were similar to those of Thailand and Laos [17, 28], higher than Malaysia, India and Senegal [31, 35, 38], but lower than Ethiopia [39]. The difference may result from the different geographical areas, intensity of malaria transmission and studied populations.
The present study identified 38 alleles of msp1, including 14 for the K1 family, 23 for the MAD20 family, and 1 for the RO33 family. This genetic diversity of msp1 in P. falciparum isolates resulted from the different numbers of tripeptide repeat that includes the SAQ, SGP and SGT for K1 and SGG, SVA and SVT for MAD20, which is consistent with the previous studies [15, 22, 28, 30, 40]. Similarly, msp2 also showed a high genetic diversity, with 37 alleles for the 3D7 family and 15 alleles for the FC27 family. This study showed a highly complicated amino acid repeat motifs in the central variable region of 3D7 alleles that contained the different combinations of S, A and G. There were 4 different continual amino acids repeats, including GASGSA (repeat numbers 2 to 4) [41], GGSGSA (repeat numbers 3 to 9) [4143], GAVASAGS (repeat numbers 2 to 3) [44] and GAGAVAGS (repeat numbers 3), as well as 2 single amino acid that including GGSA and GAGASAGN, which have also been reported in other studies [14, 4145]. Several new continual amino acids repeats and single amino acid were also found in this study, including the continual amino acids repeat GAGASGSA (repeat numbers 2), GAGAGAVAGS (repeat numbers 2 to 3), GASGSASGSA (repeat numbers 4 to 5), GAVASAGSRD (repeat numbers 5 to 7), GAGAGAGAVAGS (repeat numbers 2 to 3), PAT (repeat numbers 2 to 6) at the central variable region followed by poly-threonine stretch (repeat numbers 4 to 13) and the intermittent amino acids repeat GAGAGASGSA, GAGASGSAGSGD, GAGAGAGASGSA, as well as the above-mentioned single amino acid except for GGSA at the 3′-end. As reported in previous studies on parasites from Papua New Guinea, Cameroon, Myanmar and China [14, 22, 41, 44], the sequences of the FC27 family of P. falciparum isolates in the China–Myanmar border region are conserved at the 3′ and 5′-end, but varied in the number of repeats on SNSPSPPITTTE or SNSRSPPITTTE in the central region.

Conclusion

The findings of this study have demonstrated that P. falciparum clinical isolates in the China–Myanmar border region had a high genetic polymorphism in the msp1 and msp2 genes as well as a high multiplicity of infection, suggesting the highly complex population structure of the parasite.

Supplementary information

Supplementary information accompanies this paper at https://​doi.​org/​10.​1186/​s12936-019-3003-8.

Acknowledgements

We are grateful to patients who participated in the study, and to guardians of participating children. We thank Dr. Shuai Ding for providing suggestions for the experiments.
Plasmodium falciparum isolates of this study were collected during 2006 to 2011 from malaria patients attending local hospitals and clinics along the China–Myanmar border: Laza, Nawei, Mangdong and Nankajiang in Myanmar, and Tengchong, Yingjiang and Mengla in Yunnan, China. The written informed consent was obtained from each patient or the guardian. It is committed not to provide information about the patient to any person unrelated to the study. This protocol approved by the medical ethics committee of Yunnan Institute of Parasitic Diseases.
Not applicable.

Competing interests

The authors declare that they have no competing interests.
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Literatur
1.
Zurück zum Zitat WHO. World malaria report 2018. Geneva: World Health Organization; 2018. WHO. World malaria report 2018. Geneva: World Health Organization; 2018.
2.
Zurück zum Zitat Xia ZG, Feng J, Zhou SS. Analysis of malaria epidemic situation in China in 2012. Chin J Parasitol Parasit Dis. 2013;2013:413–8 (in Chinese). Xia ZG, Feng J, Zhou SS. Analysis of malaria epidemic situation in China in 2012. Chin J Parasitol Parasit Dis. 2013;2013:413–8 (in Chinese).
3.
Zurück zum Zitat Hui F-M, Xu B, Chen Z-W, Cheng X, Liang L, Huang H-B, et al. Spatio-temporal distribution of malaria in Yunnan Province, China. Am J Trop Med Hyg. 2009;81:503–9.PubMedCrossRef Hui F-M, Xu B, Chen Z-W, Cheng X, Liang L, Huang H-B, et al. Spatio-temporal distribution of malaria in Yunnan Province, China. Am J Trop Med Hyg. 2009;81:503–9.PubMedCrossRef
4.
Zurück zum Zitat Branch O, Casapia WM, Gamboa DV, Hernandez JN, Alava FF, Roncal N, et al. Clustered local transmission and asymptomatic Plasmodium falciparum and Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian Amazon community. Malar J. 2005;4:27.PubMedPubMedCentralCrossRef Branch O, Casapia WM, Gamboa DV, Hernandez JN, Alava FF, Roncal N, et al. Clustered local transmission and asymptomatic Plasmodium falciparum and Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian Amazon community. Malar J. 2005;4:27.PubMedPubMedCentralCrossRef
5.
Zurück zum Zitat Mazumdar S, Mukherjee P, Yazdani SS, Jain SK, Mohmmed A, Chauhan VS. Plasmodium falciparum merozoite surface protein 1 (MSP-1)-MSP-3 chimeric protein: immunogenicity determined with human-compatible adjuvants and induction of protective immune response. Infect Immun. 2010;78:872–83.PubMedCrossRef Mazumdar S, Mukherjee P, Yazdani SS, Jain SK, Mohmmed A, Chauhan VS. Plasmodium falciparum merozoite surface protein 1 (MSP-1)-MSP-3 chimeric protein: immunogenicity determined with human-compatible adjuvants and induction of protective immune response. Infect Immun. 2010;78:872–83.PubMedCrossRef
6.
Zurück zum Zitat Kauth CW, Woehlbier U, Kern M, Mekonnen Z, Lutz R, Mucke N, et al. Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum. J Biol Chem. 2006;281:31517–27.PubMedCrossRef Kauth CW, Woehlbier U, Kern M, Mekonnen Z, Lutz R, Mucke N, et al. Interactions between merozoite surface proteins 1, 6, and 7 of the malaria parasite Plasmodium falciparum. J Biol Chem. 2006;281:31517–27.PubMedCrossRef
7.
Zurück zum Zitat Mahanty S, Saul A, Miller LH. Progress in the development of recombinant and synthetic blood-stage malaria vaccines. J Exp Biol. 2003;206:3781–8.PubMedCrossRef Mahanty S, Saul A, Miller LH. Progress in the development of recombinant and synthetic blood-stage malaria vaccines. J Exp Biol. 2003;206:3781–8.PubMedCrossRef
8.
Zurück zum Zitat Holder AA, Blackman MJ. What is the function of MSP-1 on the malaria merozoite? Parasitol Today. 1994;10:182–4.PubMedCrossRef Holder AA, Blackman MJ. What is the function of MSP-1 on the malaria merozoite? Parasitol Today. 1994;10:182–4.PubMedCrossRef
9.
Zurück zum Zitat Holder AA, Guevara Patino JA, Uthaipibull C, Syed SE, Ling IT, Scott-Finnigan T, et al. Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia. 1999;41:409–14.PubMed Holder AA, Guevara Patino JA, Uthaipibull C, Syed SE, Ling IT, Scott-Finnigan T, et al. Merozoite surface protein 1, immune evasion, and vaccines against asexual blood stage malaria. Parassitologia. 1999;41:409–14.PubMed
10.
Zurück zum Zitat Genton B, Al-Yaman F, Betuela I, Anders RF, Saul A, Baea K, et al. Safety and immunogenicity of a three-component blood-stage malaria vaccine (MSP1, MSP2, RESA) against Plasmodium falciparum in Papua New Guinean children. Vaccine. 2003;22:30–41.PubMedCrossRef Genton B, Al-Yaman F, Betuela I, Anders RF, Saul A, Baea K, et al. Safety and immunogenicity of a three-component blood-stage malaria vaccine (MSP1, MSP2, RESA) against Plasmodium falciparum in Papua New Guinean children. Vaccine. 2003;22:30–41.PubMedCrossRef
11.
Zurück zum Zitat Anders RF, McColl DJ, Coppel RL. Molecular variation in Plasmodium falciparum: polymorphic antigens of asexual erythrocytic stages. Acta Trop. 1993;53:239–53.PubMedCrossRef Anders RF, McColl DJ, Coppel RL. Molecular variation in Plasmodium falciparum: polymorphic antigens of asexual erythrocytic stages. Acta Trop. 1993;53:239–53.PubMedCrossRef
12.
Zurück zum Zitat Fenton B, Clark JT, Khan CM, Robinson JV, Walliker D, Ridley R, et al. Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum. Mol Cell Biol. 1991;11:963–71.PubMedPubMedCentralCrossRef Fenton B, Clark JT, Khan CM, Robinson JV, Walliker D, Ridley R, et al. Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum. Mol Cell Biol. 1991;11:963–71.PubMedPubMedCentralCrossRef
13.
Zurück zum Zitat Snewin VA, Herrera M, Sanchez G, Scherf A, Langsley G, Herrera S. Polymorphism of the alleles of the merozoite surface antigens MSA1 and MSA2 in Plasmodium falciparum wild isolates from Colombia. Mol Biochem Parasitol. 1991;49:265–75.PubMedCrossRef Snewin VA, Herrera M, Sanchez G, Scherf A, Langsley G, Herrera S. Polymorphism of the alleles of the merozoite surface antigens MSA1 and MSA2 in Plasmodium falciparum wild isolates from Colombia. Mol Biochem Parasitol. 1991;49:265–75.PubMedCrossRef
14.
Zurück zum Zitat Smythe JA, Coppel RL, Day KP, Martin RK, Oduola AM, Kemp DJ, et al. Structural diversity in the Plasmodium falciparum merozoite surface antigen 2. Proc Natl Acad Sci USA. 1991;88:1751–5.PubMedCrossRefPubMedCentral Smythe JA, Coppel RL, Day KP, Martin RK, Oduola AM, Kemp DJ, et al. Structural diversity in the Plasmodium falciparum merozoite surface antigen 2. Proc Natl Acad Sci USA. 1991;88:1751–5.PubMedCrossRefPubMedCentral
15.
Zurück zum Zitat Yuan L, Zhao H, Wu L, Li X, Parker D, Xu S, et al. Plasmodium falciparum populations from northeastern Myanmar display high levels of genetic diversity at multiple antigenic loci. Acta Trop. 2013;125:53–9.PubMedCrossRef Yuan L, Zhao H, Wu L, Li X, Parker D, Xu S, et al. Plasmodium falciparum populations from northeastern Myanmar display high levels of genetic diversity at multiple antigenic loci. Acta Trop. 2013;125:53–9.PubMedCrossRef
16.
Zurück zum Zitat Perandin F, Manca N, Calderaro A, Piccolo G, Galati L, Ricci L, et al. Development of a real-time PCR assay for detection of Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale for routine clinical diagnosis. J Clin Microbiol. 2004;42:1214–9.PubMedPubMedCentralCrossRef Perandin F, Manca N, Calderaro A, Piccolo G, Galati L, Ricci L, et al. Development of a real-time PCR assay for detection of Plasmodium falciparum, Plasmodium vivax, and Plasmodium ovale for routine clinical diagnosis. J Clin Microbiol. 2004;42:1214–9.PubMedPubMedCentralCrossRef
17.
Zurück zum Zitat Snounou G, Zhu X, Siripoon N, Jarra W, Thaithong S, Brown KN, et al. Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg. 1999;93:369–74.PubMedCrossRef Snounou G, Zhu X, Siripoon N, Jarra W, Thaithong S, Brown KN, et al. Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg. 1999;93:369–74.PubMedCrossRef
18.
Zurück zum Zitat Paganotti GM, Babiker HA, Modiano D, Sirima BS, Verra F, Konate A, et al. Genetic complexity of Plasmodium falciparum in two ethnic groups of Burkina Faso with marked differences in susceptibility to malaria. Am J Trop Med Hyg. 2004;71:173–8.PubMedCrossRef Paganotti GM, Babiker HA, Modiano D, Sirima BS, Verra F, Konate A, et al. Genetic complexity of Plasmodium falciparum in two ethnic groups of Burkina Faso with marked differences in susceptibility to malaria. Am J Trop Med Hyg. 2004;71:173–8.PubMedCrossRef
19.
Zurück zum Zitat Healer J, Murphy V, Hodder AN, Masciantonio R, Gemmill AW, Anders RF, et al. Allelic polymorphisms in apical membrane antigen-1 are responsible for evasion of antibody-mediated inhibition in Plasmodium falciparum. Mol Microbiol. 2004;52:159–68.PubMedCrossRef Healer J, Murphy V, Hodder AN, Masciantonio R, Gemmill AW, Anders RF, et al. Allelic polymorphisms in apical membrane antigen-1 are responsible for evasion of antibody-mediated inhibition in Plasmodium falciparum. Mol Microbiol. 2004;52:159–68.PubMedCrossRef
20.
Zurück zum Zitat Day KP, Marsh K. Naturally acquired immunity to Plasmodium falciparum. Immunol Today. 1991;12:68–71.CrossRef Day KP, Marsh K. Naturally acquired immunity to Plasmodium falciparum. Immunol Today. 1991;12:68–71.CrossRef
21.
Zurück zum Zitat Gosi P, Lanteri CA, Tyner SD, Se Y, Lon C, Spring M, et al. Evaluation of parasite subpopulations and genetic diversity of the msp1, msp2 and glurp genes during and following artesunate monotherapy treatment of Plasmodium falciparum malaria in Western Cambodia. Malar J. 2013;12:403.PubMedPubMedCentralCrossRef Gosi P, Lanteri CA, Tyner SD, Se Y, Lon C, Spring M, et al. Evaluation of parasite subpopulations and genetic diversity of the msp1, msp2 and glurp genes during and following artesunate monotherapy treatment of Plasmodium falciparum malaria in Western Cambodia. Malar J. 2013;12:403.PubMedPubMedCentralCrossRef
22.
Zurück zum Zitat Kang JM, Moon SU, Kim JY, Cho SH, Lin K, Sohn WM, et al. Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum field isolates from Myanmar. Malar J. 2010;9:131.PubMedPubMedCentralCrossRef Kang JM, Moon SU, Kim JY, Cho SH, Lin K, Sohn WM, et al. Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum field isolates from Myanmar. Malar J. 2010;9:131.PubMedPubMedCentralCrossRef
23.
Zurück zum Zitat Soe TN, Wu Y, Tun MW, Xu X, Hu Y, Ruan Y, et al. Genetic diversity of Plasmodium falciparum populations in southeast and western Myanmar. Parasit Vectors. 2017;10:322.PubMedPubMedCentralCrossRef Soe TN, Wu Y, Tun MW, Xu X, Hu Y, Ruan Y, et al. Genetic diversity of Plasmodium falciparum populations in southeast and western Myanmar. Parasit Vectors. 2017;10:322.PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Kaneko O, Kimura M, Kawamoto F, Ferreira MU, Tanabe K. Plasmodium falciparum: allelic variation in the merozoite surface protein 1 gene in wild isolates from southern Vietnam. Exp Parasitol. 1997;86:45–57.PubMedCrossRef Kaneko O, Kimura M, Kawamoto F, Ferreira MU, Tanabe K. Plasmodium falciparum: allelic variation in the merozoite surface protein 1 gene in wild isolates from southern Vietnam. Exp Parasitol. 1997;86:45–57.PubMedCrossRef
25.
Zurück zum Zitat Gomez D, Chaparro J, Rubiano C, Rojas MO, Wasserman M. Genetic diversity of Plasmodium falciparum field samples from an isolated Colombian village. Am J Trop Med Hyg. 2002;67:611–6.PubMedCrossRef Gomez D, Chaparro J, Rubiano C, Rojas MO, Wasserman M. Genetic diversity of Plasmodium falciparum field samples from an isolated Colombian village. Am J Trop Med Hyg. 2002;67:611–6.PubMedCrossRef
26.
Zurück zum Zitat Chen JT, Li J, Zha GC, Huang G, Huang ZX, Xie DD, et al. Genetic diversity and allele frequencies of Plasmodium falciparum msp1 and msp2 in parasite isolates from Bioko Island, Equatorial Guinea. Malar J. 2018;17:458.PubMedPubMedCentralCrossRef Chen JT, Li J, Zha GC, Huang G, Huang ZX, Xie DD, et al. Genetic diversity and allele frequencies of Plasmodium falciparum msp1 and msp2 in parasite isolates from Bioko Island, Equatorial Guinea. Malar J. 2018;17:458.PubMedPubMedCentralCrossRef
27.
Zurück zum Zitat Zhu X, Zhou L, Liu Q, Gao X. Genotype and sequence analysis of merozoite surface protein 1 of Plasmodium falciparum isolates in Yunnan province. Chin J Parasitol Parasit Dis. 1999;17:155–8 (in Chinese). Zhu X, Zhou L, Liu Q, Gao X. Genotype and sequence analysis of merozoite surface protein 1 of Plasmodium falciparum isolates in Yunnan province. Chin J Parasitol Parasit Dis. 1999;17:155–8 (in Chinese).
28.
Zurück zum Zitat Khaminsou N, Kritpetcharat O, Daduang J, Charerntanyarak L, Kritpetcharat P. Genetic analysis of the merozoite surface protein-1 block 2 allelic types in Plasmodium falciparum clinical isolates from Lao PDR. Malar J. 2011;10:371.PubMedPubMedCentralCrossRef Khaminsou N, Kritpetcharat O, Daduang J, Charerntanyarak L, Kritpetcharat P. Genetic analysis of the merozoite surface protein-1 block 2 allelic types in Plasmodium falciparum clinical isolates from Lao PDR. Malar J. 2011;10:371.PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Chenet SM, Branch OH, Escalante AA, Lucas CM, Bacon DJ. Genetic diversity of vaccine candidate antigens in Plasmodium falciparum isolates from the Amazon basin of Peru. Malar J. 2008;7:93.PubMedPubMedCentralCrossRef Chenet SM, Branch OH, Escalante AA, Lucas CM, Bacon DJ. Genetic diversity of vaccine candidate antigens in Plasmodium falciparum isolates from the Amazon basin of Peru. Malar J. 2008;7:93.PubMedPubMedCentralCrossRef
30.
Zurück zum Zitat Joshi H, Valecha N, Verma A, Kaul A, Mallick PK, Shalini S, et al. Genetic structure of Plasmodium falciparum field isolates in eastern and north-eastern India. Malar J. 2007;6:60.PubMedPubMedCentralCrossRef Joshi H, Valecha N, Verma A, Kaul A, Mallick PK, Shalini S, et al. Genetic structure of Plasmodium falciparum field isolates in eastern and north-eastern India. Malar J. 2007;6:60.PubMedPubMedCentralCrossRef
31.
Zurück zum Zitat Bharti PK, Shukla MM, Sharma YD, Singh N. Genetic diversity in the block 2 region of the merozoite surface protein-1 of Plasmodium falciparum in central India. Malar J. 2012;11:78.PubMedPubMedCentralCrossRef Bharti PK, Shukla MM, Sharma YD, Singh N. Genetic diversity in the block 2 region of the merozoite surface protein-1 of Plasmodium falciparum in central India. Malar J. 2012;11:78.PubMedPubMedCentralCrossRef
32.
Zurück zum Zitat Ghanchi NK, Martensson A, Ursing J, Jafri S, Bereczky S, Hussain R, et al. Genetic diversity among Plasmodium falciparum field isolates in Pakistan measured with PCR genotyping of the merozoite surface protein 1 and 2. Malar J. 2010;9:1.PubMedPubMedCentralCrossRef Ghanchi NK, Martensson A, Ursing J, Jafri S, Bereczky S, Hussain R, et al. Genetic diversity among Plasmodium falciparum field isolates in Pakistan measured with PCR genotyping of the merozoite surface protein 1 and 2. Malar J. 2010;9:1.PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat Carlsson AM, Ngasala BE, Dahlstrom S, Membi C, Veiga IM, Rombo L, et al. Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria. Malar J. 2011;10:380.PubMedPubMedCentralCrossRef Carlsson AM, Ngasala BE, Dahlstrom S, Membi C, Veiga IM, Rombo L, et al. Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria. Malar J. 2011;10:380.PubMedPubMedCentralCrossRef
34.
Zurück zum Zitat Mohd Abd Razak MR, Sastu UR, Norahmad NA, Abdul-Karim A, Muhammad A, Muniandy PK, et al. Genetic diversity of Plasmodium falciparum populations in malaria declining areas of Sabah, East Malaysia. PLoS ONE. 2016;11:e0152415.PubMedPubMedCentralCrossRef Mohd Abd Razak MR, Sastu UR, Norahmad NA, Abdul-Karim A, Muhammad A, Muniandy PK, et al. Genetic diversity of Plasmodium falciparum populations in malaria declining areas of Sabah, East Malaysia. PLoS ONE. 2016;11:e0152415.PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Niang M, Loucoubar C, Sow A, Diagne MM, Faye O, Faye O, et al. Genetic diversity of Plasmodium falciparum isolates from concurrent malaria and arbovirus co-infections in Kedougou, southeastern Senegal. Malar J. 2016;15:155.PubMedPubMedCentralCrossRef Niang M, Loucoubar C, Sow A, Diagne MM, Faye O, Faye O, et al. Genetic diversity of Plasmodium falciparum isolates from concurrent malaria and arbovirus co-infections in Kedougou, southeastern Senegal. Malar J. 2016;15:155.PubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Ogouyemi-Hounto A, Gazard DK, Ndam N, Topanou E, Garba O, Elegbe P, et al. Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum isolates from children in South of Benin. Parasite. 2013;20:37.PubMedPubMedCentralCrossRef Ogouyemi-Hounto A, Gazard DK, Ndam N, Topanou E, Garba O, Elegbe P, et al. Genetic polymorphism of merozoite surface protein-1 and merozoite surface protein-2 in Plasmodium falciparum isolates from children in South of Benin. Parasite. 2013;20:37.PubMedPubMedCentralCrossRef
37.
Zurück zum Zitat Kuesap J, Chaijaroenkul W, Ketprathum K, Tattiyapong P, Na-Bangchang K. Evolution of genetic polymorphisms of Plasmodium falciparum merozoite surface protein (PfMSP) in Thailand. Korean J Parasitol. 2014;52:105–9.PubMedPubMedCentralCrossRef Kuesap J, Chaijaroenkul W, Ketprathum K, Tattiyapong P, Na-Bangchang K. Evolution of genetic polymorphisms of Plasmodium falciparum merozoite surface protein (PfMSP) in Thailand. Korean J Parasitol. 2014;52:105–9.PubMedPubMedCentralCrossRef
38.
Zurück zum Zitat Atroosh WM, Al-Mekhlafi HM, Mahdy MA, Saif-Ali R, Al-Mekhlafi AM, Surin J. Genetic diversity of Plasmodium falciparum isolates from Pahang, Malaysia based on MSP-1 and MSP-2 genes. Parasit Vectors. 2011;4:233.PubMedPubMedCentralCrossRef Atroosh WM, Al-Mekhlafi HM, Mahdy MA, Saif-Ali R, Al-Mekhlafi AM, Surin J. Genetic diversity of Plasmodium falciparum isolates from Pahang, Malaysia based on MSP-1 and MSP-2 genes. Parasit Vectors. 2011;4:233.PubMedPubMedCentralCrossRef
39.
Zurück zum Zitat Mohammed H, Kassa M, Mekete K, Assefa A, Taye G, Commons RJ. Genetic diversity of the msp-1, msp-2, and glurp genes of Plasmodium falciparum isolates in Northwest Ethiopia. Malar J. 2018;17:386.PubMedPubMedCentralCrossRef Mohammed H, Kassa M, Mekete K, Assefa A, Taye G, Commons RJ. Genetic diversity of the msp-1, msp-2, and glurp genes of Plasmodium falciparum isolates in Northwest Ethiopia. Malar J. 2018;17:386.PubMedPubMedCentralCrossRef
40.
Zurück zum Zitat Scopel KK, Fontes CJ, Ferreira MU, Braga EM. Plasmodium falciparum: IgG subclass antibody response to merozoite surface protein-1 among Amazonian gold miners, in relation to infection status and disease expression. Exp Parasitol. 2005;109:124–34.PubMedCrossRef Scopel KK, Fontes CJ, Ferreira MU, Braga EM. Plasmodium falciparum: IgG subclass antibody response to merozoite surface protein-1 among Amazonian gold miners, in relation to infection status and disease expression. Exp Parasitol. 2005;109:124–34.PubMedCrossRef
41.
Zurück zum Zitat Basco LK, Tahar R, Escalante A. Molecular epidemiology of malaria in Cameroon. XVIII. Polymorphisms of the Plasmodium falciparum merozoite surface antigen-2 gene in isolates from symptomatic patients. Am J Trop Med Hyg. 2004;70:238–44.PubMedCrossRef Basco LK, Tahar R, Escalante A. Molecular epidemiology of malaria in Cameroon. XVIII. Polymorphisms of the Plasmodium falciparum merozoite surface antigen-2 gene in isolates from symptomatic patients. Am J Trop Med Hyg. 2004;70:238–44.PubMedCrossRef
42.
Zurück zum Zitat Thomas AW, Carr DA, Carter JM, Lyon JA. Sequence comparison of allelic forms of the Plasmodium falciparum merozoite surface antigen MSA2. Mol Biochem Parasitol. 1990;43:211–20.PubMedCrossRef Thomas AW, Carr DA, Carter JM, Lyon JA. Sequence comparison of allelic forms of the Plasmodium falciparum merozoite surface antigen MSA2. Mol Biochem Parasitol. 1990;43:211–20.PubMedCrossRef
43.
Zurück zum Zitat Felger I, Marshal VM, Reeder JC, Hunt JA, Mgone CS, Beck HP. Sequence diversity and molecular evolution of the merozoite surface antigen 2 of Plasmodium falciparum. J Mol Evol. 1997;45:154–60.PubMedCrossRef Felger I, Marshal VM, Reeder JC, Hunt JA, Mgone CS, Beck HP. Sequence diversity and molecular evolution of the merozoite surface antigen 2 of Plasmodium falciparum. J Mol Evol. 1997;45:154–60.PubMedCrossRef
44.
Zurück zum Zitat Jiang GF, Chen PQ, Wang SQ. Genotyping and sequence analysis of the merozoite surface antigen 2 of Plasmodium falciparum in Hainan Province, China. Chin J Parasit Dis Con. 2002;15:7–10 (in Chinese). Jiang GF, Chen PQ, Wang SQ. Genotyping and sequence analysis of the merozoite surface antigen 2 of Plasmodium falciparum in Hainan Province, China. Chin J Parasit Dis Con. 2002;15:7–10 (in Chinese).
45.
Zurück zum Zitat Eisen D, Billman-Jacobe H, Marshall VF, Fryauff D, Coppel RL. Temporal variation of the merozoite surface protein-2 gene of Plasmodium falciparum. Infect Immun. 1998;66:239–46.PubMedPubMedCentral Eisen D, Billman-Jacobe H, Marshall VF, Fryauff D, Coppel RL. Temporal variation of the merozoite surface protein-2 gene of Plasmodium falciparum. Infect Immun. 1998;66:239–46.PubMedPubMedCentral
Metadaten
Titel
Genetic polymorphism of merozoite surface proteins 1 and 2 of Plasmodium falciparum in the China–Myanmar border region
verfasst von
Cang-Lin Zhang
Hong-Ning Zhou
Quan Liu
Ya-Ming Yang
Publikationsdatum
01.12.2019
Verlag
BioMed Central
Erschienen in
Malaria Journal / Ausgabe 1/2019
Elektronische ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-019-3003-8

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