Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Allergy, Asthma & Clinical Immunology
Published in: Allergy, Asthma & Clinical Immunology 1/2018

Open Access 01-12-2018 | Research

Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminths attending Kampala International University Teaching Hospital, in Uganda

Authors: Richard Bwanika, Charles D. Kato, Johnson Welishe, Daniel C. Mwandah

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2018

Login to get access

Abstract

Background

Malaria and helminths share the same geographical distribution in tropical Africa. Studies of the interaction of helminth and malaria co-infection in humans have been few and are mainly epidemiological, with little information on cellular immune responses. This study aimed to determine Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminth attending Kampala International University Teaching Hospital (KIU).

Methods

A case control study of 240 patients were recruited at KIU teaching hospital. Patients with Plasmodium falciparum malaria were 55 (22.9%) and those with soil-borne helminths were 63 (26.3%). The controls were 89 (37.1%), while those co-infected with Plasmodium falciparum malaria and soil-borne helminths were 33 (13.8%). Cases were defined as having a positive blood smear for P. falciparum malaria, those with helminths or co-infections of the two. Negative controls were those with a negative blood smear for P. falciparum malaria and those with no stool parasitic infections. Patients presenting with signs and symptoms of malaria or those suspected of having helminths were recruited for the study. A panel of five cytokines (IFN-γ, TNF-α, IL-6, TGF-β and IL-10) were assayed from plasma samples in patients with and without Plasmodium falciparum malaria, patients with and without helminth, and then those co-infected with the two diseases diagnosis was done using thick blood smears stained with 10% Giemsa and stool examination was done following the Kato Katz technique following standard procedures.

Results

The prevalence of Plasmodium falciparum malaria by sex was 28 (11.7%) and 27 (11.3%) in male and female respectively. The overall prevalence of soil borne helminth was 26.3%, and among those harbouring helminths, 13.8% were co-infected with Plasmodium falciparum. Cytokine levels significantly differed across Plasmodium falciparum malaria, soil borne helminth infected patients and health controls for IFN-γ (P = 0.023), IL-10 (P = 0.008) and TGF-β (P = 0.0001). Cytokine levels significantly differed across Plasmodium falciparum malaria, soil borne helminth infected patients and patients co-infected with Plasmodium falciparum malaria and soil borne helminth for IL-10 (P = 0.004), IL-6 (P = 0.011) and TGF-β (P = 0.003).

Conclusion

An up-regulation of IFN-γ during Plasmodium falciparum malaria and an up-regulation of IL-10 and TGF-β in soil borne helminth infections was demonstrated. We demonstrate that co-infections of Plasmodium falciparum and soil borne helminth lead to an up-regulation of IL-10 and IL-6 and a down-regulation of TGF-β.
Trial registration No17/10-16
Literature
1.
World Health Organization (WHO 2014). World malaria report 2013. Geneva: World Health Organization; 2014.
2.
World Health Organization (WHO 2013). The World malaria report 2013. Geneva: World Health Organization; 2013.
3.
Hay SI, Okiro EA, Gething PW, Patil AP, Tatem AJ, Guerra CA. Estimating the global clinical burden of Plasmodium falciparum malaria in 2007. PLoS Med. 2010;7:750.
4.
Petney TN, Andrews RH. Multi parasite communities in animals and humans: frequency, structure and pathogenic significance. Int J Parasitol. 1998;28:377–93.CrossRefPubMed
5.
Kinung’hi SM, Magnussen P, Kaatano G, Kishamawe C, Vennervald BJ. Malaria and helminth co-infections in school and preschool children: a cross-sectional study in Magu district, north-western Tanzania. PLoS ONE. 2014;5:236–85.
6.
Rutagwera DG, Tylleskär T. Co-infection with malaria, hookworm and schistosomiasis among school children in Zambezi: a school-based rapid survey. Med J Zambia. 2014;39:18–23.
7.
Pullan RL, Smith JL, Jasrasaria R, Brooker SJ. Global numbers of infection and disease burden of soil transmitted helminth infections in 2010. Parasites Vectors. 2014;7:37.CrossRefPubMedCentralPubMed
8.
Bundy D, Medley G. Immuno-epidemiology of human geo helminthiasis: ecological and immunological determinants of worm burden. Parasitology. 1992;104:S105–19.CrossRefPubMed
9.
Nacher M, Gay F, Singhasivanon P, Krudsood S, Treeprasertsuk S, Mazier D. Ascaris lumbricoides infection is associated with protection from cerebral malaria. Parasite Immunol. 2000;22:107–13.CrossRefPubMed
10.
Spiegel A, Tall A, Raphenon G, Trape JF, Druilhe P. Increased frequency of malaria attacks in subjects co-infected by intestinal worms and Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 2003;97:198–9.CrossRefPubMed
11.
Degarege A, Legesse M, Medhin G, Animut A, Erko B. Malaria and related outcomes in patients with intestinal helminths: a cross-sectional study. BMC Infect Dis. 2012;12:291.CrossRefPubMedCentralPubMed
12.
Nacher M, Singhasivanon P, Yimsamran S, Manibunyong W, Thanyavanich N, Wuthisen P. Intestinal helminth infections are associated with increased incidence of Plasmodium falciparum malaria in Thailand. J Parasitol. 2002;88:55–8.CrossRefPubMed
13.
Nkuo-Akenji TK, Chi PC, Cho JF, Ndamukong KK, Sumbele I. Malaria and helminth co-infection in children living in a malaria endemic setting of mount Cameroon and predictors of anemia. J Parasitol. 2006;92:1191–5.CrossRefPubMed
14.
Brutus L, Watier L, Hanitrasoamampionona V, Razanatsoarilala H, Cot M. Confirmation of the protective effect of Ascaris lumbricoides on Plasmodium falciparum infection: results of a randomized trial in Madagascar. Am J Trop Med Hyg. 2007;77(6):1091–5.PubMed
15.
Sangweme DT, Midzi N, Zinyowera-Mutapuri S, Mduluza T, Diener-West M, Kumar N. Impact of schistosome infection on Plasmodium falciparum malariometric indices and immune correlates in school age children in Burma Valley, Zimbabwe. Med J Zambia. 2010;2:369–89.
16.
Degarege A, Animut A, Legesse M, Erko B. Malaria and helminth co-infections in outpatients of Alaba Kulito Health Center, southern Ethiopia: a cross sectional study. BMC Res Notes. 2010;3:143.CrossRefPubMedCentralPubMed
17.
Yatich NJ, Jolly PE, Funkhouser E, Agbenyega T, Rayner JC, Ehiri JE. The effect of malaria and intestinal helminth coinfection on birth outcomes in Kumasi, Ghana. Am J Trop Med Hyg. 2010;82:28–34.CrossRefPubMedCentralPubMed
18.
Abanyie FA, McCracken C, Kirwan P, Molloy SF, Asaolu SO, Holland CV. Ascaris co-infection does not alter malaria-induced anaemia in a cohort of Nigerian preschool children. Malar J. 2013;12(1):1.CrossRefPubMedCentralPubMed
19.
Shapiro AE, Tukahebwa EM, Kasten J, Clarke SE, Magnussen P, Olsen A. Epidemiology of helminth infections and their relationship to clinical malaria in southwest Uganda. Trans R Soc Trop Med Hyg. 2005;99:18–24.CrossRefPubMed
20.
Lyke KE, Dicko A, Dabo A, Sangare L, Kone A, Coulibaly D. Association of Schistosoma haematobium infection with protection against acute Plasmodium falciparum malaria in Malian children. Am J Trop Med Hyg. 2005;73:1124–30.PubMedCentralPubMed
21.
Lemaitre M, Watier L, Briand V, Garcia A, Le Hesran JY, Cot M. Coinfection with Plasmodium falciparum and Schistosoma haematobium: additional evidence of the protective effect of Schistosomiasis on malaria in Senegalese children. Am J Trop Med Hyg. 2014;90:329–34.CrossRefPubMedCentralPubMed
22.
Nacher M, Singhasivanon P, Silachamroon U, Treeprasertsuk S, Vannaphan S, Traore B. Helminth infections are associated with protection from malaria-related acute renal failure and jaundice in Thailand. Am J Trop Med Hyg. 2001;65:834–6.CrossRefPubMed
23.
Dolo H, Coulibaly YI, Dembele B, Konate S, Coulibaly SY, Doumbia SS. Filariasis attenuates anaemia and pro inflammatory responses associated with clinical malaria: a matched prospective study in children and young adults. PLoS Negl Trop Dis. 2012;6:e1890.CrossRefPubMedCentralPubMed
24.
Righetti AA, Glinz D, Adiossan LG, Koua AYG, Niamké S, Hurrell RF. Interactions and potential implications of Plasmodium falciparum-hookworm co infection in different age groups in south-central Côte d’Ivoire. Parasites Vectors. 2012;12:52.
25.
Artavanis-Tsakonas K, Tongren J, Riley E. The war between the malaria parasite and the immune system: immunity, immuno regulation and immunopathology. Clin Exp Immunol. 2003;133:145–52.CrossRefPubMedCentralPubMed
26.
Riley E, Wahl S, Perkins D, Schofield L. Regulating immunity to malaria. Parasite Immunol. 2006;28:35–49.CrossRefPubMed
27.
28.
Su Z, Segura M, Morgan K, Loredo-Osti JC, Stevenson MM. Impairment of protective immunity to blood-stage malaria by concurrent nematode infection. Infect Immun. 2005;73:3531–9.CrossRefPubMedCentralPubMed
29.
Day NP, Hien TT, Schollaardt T, Loc PP, Chuong LV, Chau TT, Mai NT, Phu NH, Sinh DX, White NJ, Ho M. The prognostic and pathophysiologic role of pro- and anti-inflammatory cytokines in severe malaria. J Infect Dis. 1999;180:1288–97.CrossRefPubMed
30.
Figueiredo CA, Barreto ML, Rodrigues LC, Cooper PJ, Silva NB, Amorim LD. Chronic intestinal helminth infections are associated with immune hyporesponsiveness and induction of a regulatory network. Infect Immun. 2010;78:3160–7.CrossRefPubMedCentralPubMed
31.
Turner JD, Faulkner H, Kamgno J, Cormont F, Van Snick J, Else KJ. Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. J Infect Dis. 2003;188:1768–75.CrossRefPubMed
32.
Turner JD, Jackson JA, Faulkner H, Behnke J, Else KJ, Kamgno J. Intensity of intestinal infection with multiple worm species is related to regulatory cytokine output and immune hyporesponsiveness. J Infect Dis. 2008;197:1204–12.CrossRefPubMed
33.
Wammes LJ, Hamid F, Wiria AE, De Gier B, Sartono E, Maizels RM. Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparum. Eur J Immunol. 2010;40:437–42.CrossRefPubMed
34.
Allen JE, Maizels RM. Diversity and dialogue in immunity to helminths. Nat Rev Immunol. 2011;11:375–88.CrossRefPubMed
35.
Cheesebrough M. Medical laboratory manual for tropical countries. Cambridge: Tropical Health Technology Publications and Butterworth-Heinemann; 2002.
36.
Sánchez-Arcila JC, Perce-da-Silva DD, Vasconcelos MP, Rodrigues-da-Silva RN, Pereira VA, Aprígio CJ. Intestinal parasites coinfection does not alter plasma cytokines profile elicited in acute malaria in subjects from endemic area of Brazil. Mediat Inflamm. 2014;20:14.
37.
World Health Organization. Bench aids for the diagnosis of intestinal parasites. Geneva: World Health Organisation; 1994.
38.
Kato CD, Alibu VP, Nanteza A, Mugasa CM, Matovu E. Interleukin (IL)-6 and IL-10 are up regulated in late stage Trypanosoma brucei rhodesiense sleeping sickness. PLoS Negl Trop Dis. 2015;10:e0118370.
39.
Agwu E, Tanayen G, Moazzam ML. Four-year health-point surveillance of human gastro-intestinal parasites among patients attending a clinic in Bushenyi, Uganda. Spec Parasites Pathog J SPPJ. 2015;1(1):0001–6.
40.
Mulu A, Legesse M, Erko B, Belyhun Y, Nugussie D, Shimelis T. Epidemiological and clinical correlates of malaria-helminth co-infections in Southern Ethiopia. Malar J. 2013;12:227.CrossRefPubMedCentralPubMed
41.
Florey LS, King CH, Van Dyke MK, Muchiri EM, Mungai PL, Zimmerman PA. Partnering parasites: evidence of synergism between heavy Schistosoma haematobium and Plasmodium species infections in Kenyan children. PLoS Negl Trop Dis. 2012;6:e1723.CrossRefPubMedCentralPubMed
42.
Luty AJ, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Migot-Nabias F, Deloron P, Nussenzweig RS, Kremsner PG. Interferon-gamma responses are associated with resistance to reinfection with Plasmodium falciparum in young African children. J Infect Dis. 1999;179:980–8.CrossRefPubMed
43.
Taylor-Robinson AW, Looker M. Sensitivity of malaria parasites to nitric oxide at low oxygen tensions. Lancet. 2013;351:1630.CrossRef
44.
Winkler S, Willheim M, Baier K, Schmid D, Aichelburg A, Graninger W, Kremsner PG. Reciprocal regulation of Th1- and Th2-cytokine-producing T cells during clearance of parasitemia in Plasmodium falciparum malaria. Infect Immun. 1998;66:6040–4.PubMedCentralPubMed
45.
O’Garra A, Vieira P. Regulatory T cells and mechanisms of immune System control. Nat Med. 2004;10:801–5.CrossRefPubMed
46.
Kulkarni AB, Letterio T, Thyagarajan JJ. Functions of cytokines within the TGF-beta superfamily as determined from transgenic and gene knock out studies in mice. Curr Mol Med. 2002;2:303–27.CrossRefPubMed
47.
Hartgers FC, Obeng BB, Kruize YC, Dijkhuis A, McCall M, Sauerwein RW, Luty AJ, Boakye DA, Yazdanbakhsh M. Responses to malarial antigens are altered in helminth-infected children. J Infect Dis. 2009;78:760–9.
48.
Clark IA, Rockett KA. The cytokine theory of human cerebral malaria. Parasitol Today. 1994;10:410–2.CrossRefPubMed
49.
Ho M, Sexton MM, Tongtawe P, Looareesuwan S, Suntharasamai P, Webster HK. Endogenous interleukin-10 modulates proinflammatory response in Plasmodium falciparum malaria. J Infect Dis. 1998;172:838–44.CrossRef
50.
Hartgers FC, Yazdanbakhsh M. Co-infection of helminths and malaria: modulation of the immune responses to malaria. Parasite Immunol. 2006;10:497–506.CrossRef
51.
Cliffe LJ, Humphreys NE, Lane TE, Potten CS, Booth C, Grencis RK. Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science. 2005;308:1463–5.CrossRefPubMed
52.
McDermott JR, Bartram RE, Knight PA, Miller HR, Garrod DR, Grencis RK. Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc Natl Acad Sci USA. 2003;100:7761–6.CrossRefPubMedCentralPubMed
53.
Penkowa, Polderman AM, Schulz-Key H, Soboslay PT. Prenatal immune priming with helminth infections: parasite-specific cellular reactivity and Th1 and Th2 cytokine responses in neonates. Trans R Soc Trop Med Hyg. 2003;55:732–9.
54.
S Rose-John, Tall A, Raphenon G, Trape JF, Druilhe P. Increased frequency of malaria attacks in subjects co-infected by intestinal worms and Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 2012;97:198–9.
Metadata
Title
Cytokine profiles among patients co-infected with Plasmodium falciparum malaria and soil borne helminths attending Kampala International University Teaching Hospital, in Uganda
Authors
Richard Bwanika
Charles D. Kato
Johnson Welishe
Daniel C. Mwandah
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Allergy, Asthma & Clinical Immunology / Issue 1/2018
Electronic ISSN: 1710-1492
DOI
https://doi.org/10.1186/s13223-018-0235-z

Other articles of this Issue 1/2018

Allergy, Asthma & Clinical Immunology 1/2018 Go to the issue

Research

Frequency of CD4+ and CD8+ T cells in Iranian chronic rhinosinusitis patients

Research

Practicalities of a reduced volume formulation of a C1-INH concentrate for the treatment of hereditary angioedema: real-life experience

Research

Self-reported questionnaire survey on the prevalence and symptoms of adverse food reactions in patients with chronic inhalant diseases in Tangshan city, China

Research

Severe, eosinophilic asthma in primary care in Canada: a longitudinal study of the clinical burden and economic impact based on linked electronic medical record data

Research

Common allergies in urban adolescents and their relationships with asthma control and healthcare utilization

Research

Environmental exposure to agrochemicals and allergic diseases in preschool children in high grown tea plantations of Sri Lanka