Amoani et al. BMC Infectious Diseases          (2021) 21:332 
https://doi.org/10.1186/s12879-021-06027-5
RESEARCH ARTICLE Open Access
Effect of hookworm infection and
anthelmintic treatment on naturally
acquired antibody responses against the
GMZ2 malaria vaccine candidate and
constituent antigens
Benjamin Amoani1,2, Ben Gyan3, Samuel Asamoah Sakyi2*, Emmanuel Kwasi Abu4, Samuel Victor Nuvor5,
Precious Barnes6, Tracy Sarkodie-Addo3, Benjamin Ahenkorah2,7, Christian Sewor1, Duah Dwomoh8,
Michael Theisen9,10, Michael Cappello11, Michael D. Wilson12 and Bright Adu3
Abstract
Background: Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune
responses from each of these pathogens interact, and these interactions may have implications on vaccines. The
GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3)
and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial.
Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally
acquired antibody responses against GMZ2 and constituent antigens.
Methods: This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana.
Blood and stool samples were taken from 158 individuals (4–88 years old) infected with either P. falciparum alone
(n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm
infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light
microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm
treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3
and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before
and after treatment.
Results: Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2
than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole
led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against
MSP3 also decreased following deworming treatment.
(Continued on next page)
* Correspondence: samasamoahsakyi@yahoo.co.uk
2Department of Molecular Medicine, School of Medical Sciences, Kwame
Nkrumah University of Science and Technology, Kumasi, Ghana
Full list of author information is available at the end of the article
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data made available in this article, unless otherwise stated in a credit line to the data.
Amoani et al. BMC Infectious Diseases          (2021) 21:332 Page 2 of 8
(Continued from previous page)
Conclusion: Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of
hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent
antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication
on malaria vaccine efficacy.
Introduction with reduced antibody levels against P. falciparum anti-
Malaria and hookworm are important parasitic diseases gens [3]. Similarly, Courtin et al., [17] found Schistosoma
in humans, in terms of socio-economic impact and pub- haematobium infection to be associated with reduction
lic health importance. Malaria is typically an acute dis- in IgG levels against P. falciparum antigens MSP-1 and
ease; however, chronic asymptomatic infections may GLURP. Gabonese children infected with Ascaris lum-
persist, particularly in adults living in endemic areas. bricoides had a significantly higher P. falciparum anti-
Hookworm infection on the other hand is mainly gametocyte antibody levels compared to non-infected
chronic. In areas where these parasites are co-endemic children [4]. Interestingly, T. trichiura infection was as-
and the transmission rates are high, co-infection is very sociated with lower P. falciparum anti-gametocyte anti-
common and this may influence morbidity and immune body levels in the same study [4]. To date, hookworm
response against these infections [1–4], with possible im- modulation of the antibody responses against malaria
plications on vaccine efficacy. The GMZ2 malaria vac- vaccine antigens has not been explored. Thus, the
cine candidate is a recombinant fusion protein, current study aimed to investigate the effect of hook-
containing two blood-stage antigens of P. falciparum, worm infection and anthelmintic treatment on antibody
GLURP R0 and MSP3 [5]. Previous phase 2 clinical trial responses against the GMZ2 vaccine and its constituent
of GMZ2 showed it well tolerated and immunogenic al- antigens in a population co-endemic with both parasites.
beit with modest efficacy [5]. This is not uncommon
since most malaria vaccine candidate efficacy trials in Materials and methods
Africa has so far not been remarkably efficacious against Ethics approval and consent to participate
malaria [6–11]. However, factors modulating immune The study was approved by the Noguchi Memorial Insti-
responses against malaria vaccine candidates that may tute for Medical Research Ethical Review Committee
help provide possible explanations to the sub-optimal ef- (FWA#: 00001824). All methods were carried out in ac-
ficacies observed are not well understood. Helminths se- cordance with relevant guidelines and regulations.
crete immunomodulatory molecules to selectively skew
or dampen immune responses to promote their long- Study site, design, and sample processing
term survival [12]. Hookworm infection is associated The study was conducted from February to March in
with higher levels of IL-10 and lower levels of both Th1 2016, in communities within the Kintampo North Muni-
and Th2 cytokines [13]. The enhanced IL-10 production cipality (KNM) in the forest-savannah transitional eco-
may be a mechanism to regulate pathology due to in- logical zone of middle Ghana. The KNM covers a total
flammatory responses elicited by the infection Hook- area of 7162 km2 with a population of approximately
worm infection is very common in Africa, however its 140,000 in 32,329 households. The inhabitants are pre-
effect on malaria vaccine candidate antigens such as dominantly subsistent farmers of both crop and live-
GMZ2 have not been extensively investigated. stock. The study involved baseline sampling and a
Treatment of infected people with anthelmintic drug follow-up at 3 weeks post-anthelmintic treatment, a dur-
may alter antimalarial specific immune responses [1, 2, bar was first held in each study village during which the
14, 15]. Since albendazole treatment is administered to purpose and the nature of the study were explained. A
hookworm infected people who may be living in malaria total of 1068 potential study participants aged 4–88 years
endemic communities (exposed to both malaria and were randomly identified from a population census data
hookworm), it is important to determine if this chemo- base and recruited into the study. Study subjects (n =
therapy alters any of the responses to malaria vaccine 984) who appeared healthy and were without fever were
candidate antigens and inadvertently affect vaccine effi- consented individually prior to providing stool and blood
cacy. We have previously shown that in the absence of samples [16, 17]. Briefly, trained field workers adminis-
other helminths, co-infection of hookworm with P. fal- tered a demographic and health questionnaire, and dis-
ciparum may modulate blood parasitemia levels and tributed labelled stool-collection containers to the
cytokine responses [16]. Different helminths modulate participants. Stool samples were collected the following
the immune response to malaria differently. Trichuris day, and finger pricks were made to test for malaria
trichiura infections in malaria patients was associated using Rapid Diagnostic Test (RDT) kits and to prepare
Amoani et al. BMC Infectious Diseases          (2021) 21:332 Page 3 of 8
thin and thick blood film slides. Malaria parasitaemia was assessed by multivariate regression analysis adjusting
was also detected by light microscopy and P. falcip- for age and sex with the endemic negative control group as
arum-specific 18S rRNA gene PCR [16]. Stool hook- the reference. Wilcoxon signed ranks test was used to as-
worm infection was detected by the Kato-Katz method sess if there was any significant difference in antibody levels
and PCR for speciation [16]. About 5ml of venous blood before and after albendazole treatment. P values < 0.05 were
was collected by venipuncture using Becton Dickinson considered statistically significant.
Vacutainer Hemogard SST® tubes (Becton Dickson and
Company, Temse, Belgium) for serum separation from Results
study participants). Blood samples were obtained prior Demographic and clinical characteristics of study
to hookworm treatment with a single dose of albenda- participants
zole (400 mg) and 3 weeks (21 days) after treatment. The A prevalence of 10.5% (103/984) for hookworm infection
blood sample were separated by centrifugation, and the and 12.4% (122/984) for P. falciparum infection were
serum were stored at − 80 °C until ready to be used for observed [16]. Of these subjects who were infected with
the immunological assays. malaria; 59 were only P. falciparum (Pf), and 63 were
co-infected with both hookworm and P. falciparum (Na/
Malaria antibody measurement in sera Pf). Thirty-six uninfected subjects were randomly se-
Serum antibodies to the malaria antigens (MSP3, lected to serve as uninfected (EC) assay controls (n = 36).
GLURP and GMZ2) were measured using a modified The mean age of 16.2 years (yrs.), 25.5 yrs., 36.3 yrs. were
version of a quantitative ELISA [18]. GLURP and MSP3 recorded for Pf, Na/Pf and EC, respectively for the par-
are components in the developmental stages of P. falcip- ticipants [22]. P. falciparum parasite density was signifi-
arum [19]. GLURP is an Escherichia coli recombinant cantly lower in the co-infected group than in those
protein containing the conserved non-repeat N-terminal singly infected with only P. falciparum, as indicated in
region (amino acids 25–514) [20]. The MSP3 antigen is Table 1. Other soil transmitted helminths observed by
a long synthetic peptide called LR55 (amino acids 181– microscopy were either present as mono-infections:
276) of the merozoite surface protein 3 [21]. GMZ2, Hymenolepis nana (Hn) (3.9%), Taenia solium (Ts)
contains conserved fragments of two P. falciparum asex- (0.8%), Trichuris trichiura (Tt) (1.8%) and Ascaris lum-
ual blood-stage antigens, Glutamate-Rich Protein bricoides (Al) (0.5%) or coinfections with hookworm
(GLURP) and MSP3 [5]. Briefly, ELISA plates (Nunc, (Na/Hn = 1.1%; Na/Ts = 0.3%; Na/ Tt = 0.6%; Na/Al =
Maxisorp, Fisher Scientific, USA) were coated with 0.3%) [16]. Subjects with these helminths, either as
0.5 μg/ml of the recombinant antigens. Individual and mono-infections or co-infections with Na were excluded
positive control serum samples were diluted at 1:200 for from further analysis. PCR analysis confirmed all hook-
IgM and 1:100 for IgG1and IgG3. Bound antibodies were worm infections were due to only Necator americanus
detected by horse-radish conjugated sheep anti-human (Na) and none to be A. duodenale [16].
IgG1, and IgG3 (1:1000) (The Binding Site, Birmingham,
UK) or goat anti-human IgM (1: 5000) (Invitrogen, Association between anti-GMZ2, MSP3 and GLURP R0
USA). Color development was by TMB (3,3′,5,5′-tetra- antibody levels and age
methylbenzidine) substrate (Kem-En-Tec Diagnosis A/S, The relationship between anti-GMZ2, MSP3 and GLURP
Taastrup, Denmark) and the reaction stopped with 0.2 R0 antibody levels and age was assessed by linear regression
M H2SO4. Optical density (OD) values were read at 450 analysis. Increasing age was associated with a significant in-
nm with a reference wavelength of 570 nm with an auto- crease in IgG3 (r2 = 0.039, p = 0.034) against GMZ2 (Fig. 1).
mated ELISA reader (BioTek 405, USA). The OD values There was also a significant increase in IgG3 (r2 = 0.089,
obtained were converted into arbitrary units (AU) using p = 0.013) levels against GLURP R0 with age (Fig. 1b). No
the four-parameter curve fitting software (ADAMSEL, significant association was observed between MSP3 anti-
version 1.1 build 40© 2009 EJ Remarque). The two time body level and age in this cohort (Fig. 1c). This analysis was
point samples for each individual were tested on the done from the pre-treatment data.
same ELISA plate to avoid differences that may have
been due to inter-plate variations. Antibody responses against GMZ2 and constituent
antigens among infection groups
Statistical analyses Antibody levels against GMZ2, MSP3 and GLURP R0
Data analysis was performed using R version 3.6. 0 (https:// were compared among individuals with different infec-
www.Rproject.org/). Arbitrary antibody units (AU) were tion statuses in the study population by Multivariate
transformed into Log10 units. Linear regression was used to Multiple Linear Regression MMLR (Table 2). Malaria
determine the association between antibody level and age. parasite density had no significant effect in the prelimin-
Association between antibody levels and infection status arily analysis and was therefore excluded from the
Amoani et al. BMC Infectious Diseases          (2021) 21:332 Page 4 of 8
Table 1 Socio-demographic characteristics of the study population
P. falciparum only (59) Na - Pf (co-infected)(63) EC group (36) Na only P-value
Male n (%) 20 (33.9) 43 (68.3) 16 (44.4) 17 (42.5) –
Female n (%) 39 (66.1) 20 (31.7) 20 (55.6) 23 (57.5)
Age (Mean ± S.D) 16.2 ± 14.26 16.19 ± 10.55 36.32 ± 19.27 31.88 ± 18.71 < 0.0001a
Pf density (Mean ± S.D) 1481 ± 3263 794.4 ± 2021 – – 0.1621b
a Analysis was done using ANOVA; b Analysis was done using Unpaired T-test. Analysis was done only on Pre-treatment data
MMLR analysis. In general, the N. americanus- P. falcip- (p > 0.05). Furthermore, no significant difference was ob-
arum (Na-Pf) co-infected individuals had higher anti- served for any of the MSP3 antibodies among Pf or Na/
body levels to all the three antigens compared to the EC Pf groups and the endemic negative control group
individuals. Individuals with Na-Pf co-infection had sig- (Table 2). This analysis was done from the pre-
nificantly higher IgG3 levels against GMZ2 than the treatment data.
negative endemic control group (p = 0.046). Also, IgG1
levels were significantly higher against GLURP-R0 anti- Effect of Albendazole treatment on antibody levels
gens (p = 0.019). There was no significant difference in against GMZ2 and constituent antigens in Na/Pf co-
the IgM and IgG1 levels against GMZ2 between the Pf infected group
and EC group (p > 0.05) or the Na/Pf and EC group Treating Na/Pf co-infected individuals with albendazole
(p > 0.05). Also, there was no significant difference in led to a significant reduction of IgG1 (p = 0.002) and
the IgM and IgG3 levels against GLURP R0 between the IgG3 (p = 0.041) levels against GMZ2, and IgG3 (p =
Pf and EC group (p > 0.05) or the Na/Pf and EC group 0.024) levels against GLURP R0. There were also
Fig. 1 Isotype IgM and IgG sub-class levels in relation to age. Plots are shown (from top to bottom) for IgM, IgG1 and IgG3, levels against age
(years), respectively for: a GMZ2, b GLURP R0 and c MSP3. r2 and p-values obtained from linear regressions are shown for each plot. Analysis was
done for individuals who were single infected with P, falciparum or coinfected with hookworm. Figure 1 analysis was done for the
pre-treatment data
Amoani et al. BMC Infectious Diseases          (2021) 21:332 Page 5 of 8
Table 2 Antibody responses against GMZ2 and constituent antigens in relation to malaria and hookworm infections
P. falciparum only Na + Pf (co-infected)
Antibody Antigen β (95%CI) p-Value β (95%CI) p-Value
IgG1 GMZ2 0.01 (−0.66, 0.69) 0.967 −0.41 (−1.08. 0.26) 0.233
GLURP-R0 0.39 (−0.33, 1.53) 0.184 0.82 (0.31, 1.51) 0.019
MSP3 −0.26 (− 0.80, 0.28) 0.346 0.23 (− 0.32, 0.78) 0.402
IgG3 GMZ2 0.30 (−0.57, 1.18) 0.495 0.3 (1.04, 1.10) 0.046
GLURP-R0 0.26 (−0.61, 1.14) 0.554 0.61 (−0.38, 1.60) 0.226
MSP3 0.37 (−0.17, 1.72) 0.358 0.24 (−0.53, 1.01) 0.537
IgM GMZ2 0.13 (−0.26, 0.53) 0.503 0.05 (−.030, 0.40) 0.774
GLURP-R0 0.08 (−0.66, 0.49) 0.771 0.26 (−0.24, 0.78) 0.300
MSP3 −0.01 (− 0.32, 0.29) 0.924 0.13 (− 0.22, 0.49) 0.458
Multivariate multiple linear regression analysis adjusting for age and sex. β Estimated effect of covariate on antibody level, CI Confidence interval, Na Na, Necator
americanus, Pf Plasmodium falciparum. Arbitrary antibody unit were log10 transformed. EC group was set as reference for the model. Analysis was done only on
pre-treatment data
significant reduction in IgM and IgG1 (p < 0.001) levels against GLURP R0. These antibodies are known to be
against MSP3 following albendazole treatment in the associated with protection against malaria [1, 23–25].
same individuals (Table 3). Ascaris lumbricoides co-infection with malaria were also
found to show an increased anti-gametocyte immune re-
Discussion sponse compared to the uninfected participants [4].
Concurrent infection with malaria and hookworm is These findings suggest that the presence of the N. amer-
common among people living in Kintampo North icanus worm may boost the antimalarial specific IgG1
Municipality, and this may affect immune responses and and IgG3 antibody responses against malaria. This is
clinical outcomes of these infections. The immune re- supported by our previous findings that P. falciparum
sponses to hookworm infection may have a “bystander” parasitaemia was lower in co-infected individuals com-
effect on antimalarial immunity. In this study IgG1, pared to those with mono-infections [16]. However, our
IgG3 and IgM responses to the GMZ2 malaria vaccine findings conflict with other helminth-malaria parasite
candidate and constituent antigens were studied before co-infection study by Courtin et al. [26], who found
and after anthelmintic treatment with albendazole. Schistosoma haematobium infection led to significant re-
Our result showed that the co-infected individuals had duction in Plasmodium falciparum-specific IgG re-
higher levels of IgG3 antibodies against GMZ2 and IgG1 sponses levels directed to MSP-1 and to GLURP
Table 3 Effect of albendazole treatment on antibody levels against GMZ2 and constituent in Na/Pf co-infected individuals
Vaccine antigens Pretreatment (n = 57) Post treatment (n = 57) P-value
(Median [IQR]) (Median [IQR])
GMZ2
IgG1 38.2(10.2,90.6) 30.0(11.2,66.8) 0.002
IgG3 34.6(4.5, 142.0) 28.3(2.7121.3) 0.041
IgM 192.5(137.3326.2) 212.6(106.9400.0) 0.403
GLURP R0
IgG1 8.5(2.6,29.0) 8.2(0.9,24.3) 0.647
IgG3 14.3(2.0,45.4) 13.6(3.00,30.6) 0.024
IgM 155.8(88.8375.1) 139.5(81.2, 385.8) 0.184
MSP3
IgG1 56.2(28.5143.8) 41.7(28.0,52.7) < 0.001
IgG3 44.9(8.3167.2) 50.1(23.9, 128.2) 0.130
IgM 332.8(269.2452.8) 36.3(10.6149.2) < 0.001
Values are median (quartile). P-values were calculated using the Wilcoxon Signed Ranks Test
This analysis was done for those with hookworm and malaria parasites co-infection; pre-treatment (n = 57) and post-treatment (n = 57). Six individuals were lost
during the post-treatment follow up
Abbreviations: LQ Lower Quartile, UQ Upper Quartile
Amoani et al. BMC Infectious Diseases          (2021) 21:332 Page 6 of 8
antigens. Another study in Zimbabwe, rather reported increased level of IL10 in P. falciparum and N. ameri-
no association between Schistosoma infection and canus co-infection, which significantly decreased after
humoral response to malaria parasites [27]. Furthermore, successful albendazole, treatment [16]. Since IL10 is
Esen et al. [28], found significantly lower antibody re- known to provide help for B cells to produce antibodies
sponse against GMZ2 and GLURP antigens after vaccin- [26], this may explain both the increased malarial anti-
ation with the malaria vaccine candidate GMZ2 in bodies in co-infected individuals and the decrease in
individual who had T. trichiura present during vaccin- antibody levels observed after hookworm treatment.
ation. The observation from these studies indicate that
helminths co-infection with P. falciparum may have Conclusion
varying antibody production against malaria antigens. This study revealed stronger antibody response against
These variations in the findings could be due to the dif- malaria vaccine candidate antigens (GMZ2 and GLURP
ferences in the biology and the anatomical position of R0) in the presence of N. americanus infection. How-
the adult worms in the host, difference in the age of ever, treatment of hookworm/malaria co-infection re-
study participants and study design. sulted in a reduction in antibody responses against
The study found no significant association with anti- GMZ2 and constituent antigens. These findings require
body response against MSP3 antigen in the co-infected further assessment of hookworm/malaria co-infection on
individual, this corroborate with studies by M Esen, B efficient treatment of malaria using malaria antigens as
Mordmuller, PM de Salazar, AA Adegnika, ST Agnandji, vaccine candidate.
F Schaumburg, AB Hounkpatin, S Bruckner, M Theisen,
S Belard, et al. [3], who reported no significant effect of Acknowledgements
T. trichiura on anti-MSP3 antibody concentration. Pre- The authors are grateful to communities within the Kintampo North
sumably, MSP3 may be the less immunogenic part of Municipality (KNM) as well as research assistants and volunteers whocontributed in diverse ways for successful implementation of the study.
the vaccine [29, 30].
The study found a significantly positive association be- Authors’ contributions
tween the antibody levels (IgG3, and IgM) and age Conceived and designed the experiments: Benjamin Amoani, BG, SAS, EKA,
against GMZ2, and constituent antigens. This finding is SVN, PB, TSA, Benjamin Ahenkorah, CS, DD, MT, MC, MW, Bright AduPerformed the experiments: Benjamin Amoani, Benjamin Ahenkorah, SAS,
consistent with studies by K Marsh, RH Hayes, DC Car- EKA, SVN and PB. Analyzed the data: TSA, Benjamin Amoani, CS, DD, SAS,
son, L Otoo, F Shenton, P Byass, F Zavala and BM and BG Wrote the first draft of the manuscript: MT, MC, MW, Benjamin
Greenwood [31] who reported a positive correlation be- Ahenkorah, DB, BG, SAS, Contributed to the writing of the manuscript:Benjamin Amoani, SAS, SVN, TSA, CS, DD, MT, MC, MW, Bright Adu. Agree
tween antibody titers and age, D Dodoo, A Aikins, KA with manuscript results and conclusions: Benjamin Amoani, BG, SAS, EKA,
Kusi, H Lamptey, E Remarque, P Milligan, S Bosomprah, SVN, PB, TSA, Benjamin Ahenkorah, CS, DD, MT, MC, MW, Bright Adu Enrolled
R Chilengi, YD Osei and BD Akanmori [25] and B Adu, patients: Bright Adu, PB, TSA, SAS, DD, Benjamin Amoani, CS, and MW. Theauthor(s) read and approved the final manuscript.
MK Cherif, S Bosomprah, A Diarra, FK Arthur, EK
Dickson, G Corradin, DR Cavanagh, M Theisen, SB Sir- Funding
ima, et al. [18], also reported high levels of IgM against Funding for this study was provided by the National Institutes of Health
MSP3 and GLURP with age among Ghanaian children. (NIH); grant # 1 R01A1099623 awarded to Michael Wilson. The sponsor had
no role in study design, data collection, analysis or interpretation, or writing
These results are consistent with the hypothesis that im- of the manuscript.
munity to malaria is largely effected through antibody-
mediated mechanisms and that protective antibody Availability of data and materials
levels to relevant antigens increase with age of an indi- All data generated or analyzed during this study are included in this
published article and can be requested from corresponding author.
vidual co-infected with other parasites [32]. The weak
association observed between antibody levels and age in Declarations
our study population may be due to the fact that most
of the study participants were older and may have Consent for publications
Not Applicable.
greater cumulative exposure to the malaria parasite with
already developed acquired immunity compared to chil- Ethics approval and consent to participate
dren [33]. The study was approved by the Noguchi Memorial Institute for Medical
The IgG1 and IgG3 antibody levels measured against Research Ethical Review Committee (FWA#: 00001824). Informed consent
was obtained from all adult subjects and parent or legal guardian of under
GMZ2, were significantly decreased after albendazole 18 subjects. A written informed consent form was provided to each
treatment. Also, IgG3 response to GLURP R0 and IgG1 participant for their consent before being recruited into the study. All
and IgM responses to MSP3 were significantly decreased methods were carried out in accordance with relevant guidelines and
regulations.
after treatment. Helminth infections are usually associ-
ated with a predominantly Th2-type of immune re- Competing interests
sponse [34]. In our previous study, we observed an Authors have declared that no conflicts of interest exist.
Amoani et al. BMC Infectious Diseases          (2021) 21:332 Page 7 of 8
Author details 13. Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao S. Hookworm
1Department of Biomedical Science, School of Allied Health Sciences, infection. N Engl J Med. 2004;351(8):799–807. https://doi.org/10.1056/
University of Cape Coast, Cape Coast, Ghana. 2Department of Molecular NEJMra032492.
Medicine, School of Medical Sciences, Kwame Nkrumah University of Science 14. Mutapi F, Ndhlovu PD, Hagan P, Spicer JT, Mduluza T, Turner CM, et al.
and Technology, Kumasi, Ghana. 3Department of Immunology, Noguchi Chemotherapy accelerates the development of acquired immune responses
Memorial Institute for Medical Research, College of Health Sciences, to Schistosoma haematobium infection. J Infect Dis. 1998;178(1):289–93.
University of Ghana, Legon, Ghana. 4Department of Optometry, School of https://doi.org/10.1086/517456.
Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana. 15. Scott JT, Turner C, Mutapi F, Woolhouse ME, Chandiwana SK, Mduluza T,
5Department of Microbiology and Immunology, School of Medical Sciences, et al. Dissociation of interleukin-4 and interleukin-5 production following
University of Cape Coast, Cape Coast, Ghana. 6Department of Physician treatment for Schistosoma haematobium infection in humans. Parasite
Assistant, School of Allied Health Sciences, University of Cape Coast, Cape Immunol. 2000;22(7):341–8. https://doi.org/10.1046/j.1365-3024.2000.00311.x.
Coast, Ghana. 7Department of Medical Laboratory Science, Bolgatanga 16. Amoani B, Adu B, Frempong MT, Sarkodie-Addo T, Nuvor SV, Abu EK, et al.
Technical University, Bolgatanga, Upper East Region, Ghana. 8Department of Cytokine profiles of Necator americanus and plasmodium falciparum co-
Biostatistics, School of Public Health, University of Ghana, Accra, Ghana. infected patients in rural Ghana. Cytokine: X. 2019;1(4):100014. https://doi.
9Department for Congenital Disorders, Statens Serum Institut, Copenhagen, org/10.1016/j.cytox.2019.100014.
Denmark. 10Centre for Medical Parasitology at Department of International 17. Amoani B, Adu B, Frempong MT, Sarkodie-Addo T, Nuvor SV, Wilson MD,
Health, Immunology, and Microbiology, University of Copenhagen, and et al. Levels of serum eosinophil cationic protein are associated with
Department of Infectious Diseases, Copenhagen University Hospital, hookworm infection and intensity in endemic communities in Ghana. PLoS
Rigshospitalet, Copenhagen, Denmark. 11Partnerships for Global Health, One. 2019;14(9):e0222382. https://doi.org/10.1371/journal.pone.0222382.
Department of Pediatrics, Yale School of Medicine, Yale University, New 18. Adu B, Cherif MK, Bosomprah S, Diarra A, Arthur FK, Dickson EK, et al.
Haven, CT, USA. 12Parasitology Department, Noguchi Memorial Institute for Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and
Medical Research, College of Health Sciences, University of Ghana, Legon, the risk of malaria in children living in hyperendemic (Burkina Faso) and
Ghana. hypo-endemic (Ghana) areas. Malar J. 2016;15(1):123.
19. Theisen M, Soe S, Jessing SG, Okkels LM, Danielsen S, Oeuvray C, et al.
Received: 13 November 2020 Accepted: 30 March 2021 Identification of a major B-cell epitope of the plasmodium falciparum
glutamate-rich protein (GLURP), targeted by human antibodies mediating
parasite killing. Vaccine. 2000;19(2–3):204–12. https://doi.org/10.1016/S02
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