Table 5.

Immunological research of co-infection between TB and parasitic diseases

Country	Year of report	Tuberculosis	Parasitic disease/species	Subject	Conclusions	No. of reference
France	2003	PTB	American cutaneous leishmaniasis	A 44-year-old man with triple infection of cutaneous leishmaniasis, lepromatous leprosy, and PTB	Unresponsiveness to IL-12 of patient’s T cells after stimulation with Leishmania guyanensis, M. bovis bacille Calmette-Guerin, and M. leprae antigens suggested the inability to mount an appropriate Th cell response to upregulate the IL-12 receptor expression.	[14]
Gambia	1999	M. TB	Malaria	Review	Malarial parasites can decrease their vertebrate host’s effective humoral and cellular immune responses to M. TB.	[35]
USA	2004	M. TB	Plasmodium yoelii NL	Mice	Co-infected mice were less able to contain growth of M. TB in lung, spleen, and liver and had increased mortality.	[36]
Thailand	2006	M. TB	Plasmodium falciparum	HSP70 (M. TB) and ATPBP (Plasmodium falciparum)	HSP70 and ATPBP share a common molecular function as ATP binding resulting from purine nucleotide binding. Therefore, a competitive antagonist effect between both molecules can be expected.	[37]
Germany	2012	M. TB	Plasmodium berghei NK65	An experimental mouse model of co-infection	Co-infection exacerbated chronic TB while rendering mice less refractory to Plasmodium. Co-infected animals presented with enhanced inflammatory immune responses as reflected by exacerbated leukocyte infiltrates, tissue pathology and hypercytokinemia accompanied by altered T-cell responses.	[38]
Unknown	1989	PTB	Opisthorchiasis	173 patients with PTB complicated by opisthorchiasis	Among them, activity of the α1-proteinase inhibitor was more frequently higher and carriers of two markers i.e. Hp 2–2 and Gc 1–1 were more frequent.	[39]
Unknown	1992	PTB	Opisthorchiasis	12 PTB patients concurrent with opisthorchiasis	When the course of TB is aggravated by opisthorchiasis invasion, the number of cases of antibacterial therapy intolerance increases and prognosis of the diseases deteriorates. It was shown that the antibacterial and anthelminthic therapy had a favourable clinical and immunologic effect.	[40]
Unknown	1992	M. TB	Opisthorchiasis	Animal	In comparison with the groups of animals with monoinvasion and monoinfection, at the acute invasive phase of mixed pathology (2 weeks) the activity of the host’s immune system increases, while the biological activities of both pathogens decrease; however, at the subacute phase (2.5 months), all were contrary respectively.	[41]
Russia	2003	TB	Opisthorchiasis	Golden hamsters with SRBC parasitocenosis	In cases of mixed pathology, at the acute stage of invasion, the immune system showed increased responses with respect to specific and heterologous antigens; in the chronization of invasion the formation of antibodies to heterologous antigens (SRBC) and the level of specific antiopisthorchiasis and anti-TB immune responses decreased together.	[42]
China	2009	PTB	Echinococcosis	A 18 years old male and a 36 years female	As the echinococcosis chronicity increased, the immune profile in both subjects changed from a Th1 to Th2 response. Such an elevated Th2 immune profile, with subsequent suppression of the Th1 immune response, is a common feature of chronic helminth infections.	[27]
USA	2012	M. TB	Litomosoides sigmodontis	Cotton rats with chronic L. sigmodontis infection and uninfected controls were challenged with M. TB by intranasal inoculation.	Chronic filarial infections do not exacerbate M. TB infection in the cotton rat model. It may be possible to develop worm-derived therapies for autoimmune diseases that do not substantially increase the risk for infections.	[43]
USA	2012	M. TB	Filarial infections	Review	Filarial infections very clearly alter the magnitude and quality of the mycobacteria-specific cytokine responses, responses that have been typically associated with control of these intracellular pathogens.	[44]
Denmark	2007	TB	Intestinal helminth	Review	Co-infections cause a range of immunomodulation characterized by enhanced Th2-type cytokine profiles, high IgE levels and upregulated regulatory T-cell activity, as well as chronic immune activation.	[45]
Brazil	2007	PTB	Intestinal helminth	40 PTB patients and 25 healthy controls	Compared to either TB patients or healthy controls, co-infected patients’ absolute frequencies of CD3+, CD4+, CD8+, NK T cell and CD4+CD25high T cell increased. Differences in CD4 T cell frequencies were accompanied by lower IFN-γ and elevated and sustained IL-10 levels in WB cultures from co-infected patients compared to TB patients.	[46]
Mexico	2012	TB	Helminthic infections	Review	Helminths very clearly alter the magnitude of the mycobacteria-specific cytokine responses, altering the control of the mycobacteria growth. Mycobacteria-induced immune responses are suppressed by helminth infections.	[47]
USA	2012	TB	Helminths	Review	Helminth-induced Th2 and T reg responses impinge on host resistance against M. TB infection. Th1 response is reduced in helminth co-infected hosts. Helminth-induced alternatively activated macrophages contribute to enhanced susceptibility to TB.	[48]
Brazil	2002	BCG vaccination	Ascaris lumbricoides, Entamoeba histolytica, and Strongyloides stercoralis	14 male students aged 12–15 years: 7 having protozoan or helminthic infections and 7 free of intestinal parasites	Th2-like IL-10 responses induced by intestinal parasites may interfere in BCG-induced Th1-like IFN-γ response. Intestinal parasitic infections may significantly alter the protective immune response to BCG vaccination.	[49]
Sweden	2005	BCG vaccination to protect against M. TB	S. mansoni	BCG vaccinated mice with prior S. mansoni infection	S. mansoni infection reduces the protective efficacy of BCG vaccination against M. TB possibly by attenuation of protective immune responses to mycobacterial antigens and/or by polarizing the general immune responses to the Th2 profile.	[50]
USA	2011	TB vaccines in protecting against M. TB	Plasmodium yoelii NL	TB vaccines in a co-infection mouse model of two pathogens	The effectiveness of novel TB vaccines in protecting against TB was unaffected by a primary malaria co-infection in a mouse model of PTB.	[51]

Abbreviations: PTB = pulmonary tuberculosis; M. leprae = mycobacterium leprae; M. TB = mycobacterium tuberculosis; SRBC = sheep red blood cells; IL = interleukin; Th = T helper; Treg = T regulatory; NL = non-lethal; HSP = heat shock protein; ATP = adenosine triphosphate; ATPBP = ATP-binding protein; Ig = immunoglobulin; CD = cluster of differentiation; NK = natural killer; IFN = interferon; WB = whole blood; BCG = Bacillus Calmette-Guerin; L. sigmodontis = litomosoides sigmodontis; S. mansoni = schistosoma mansoni.