Cytokine Gene Expression Profiles during HIV and Helminth Coinfection in Underprivileged Peri-Urban South African Adults.

BACKGROUND: Intestinal helminth parasites are potent stimulators of T helper type 2 (Th2) and regulatory Th3 anti-inflammatory immune responses, while human immunodeficiency virus (HIV) infections are activators of predominantly T helper type 1(Th1) pro-inflammatory responses. Studies investigating the immune profiles of individuals coinfected with helminths and HIV are scarce. Although it is well known that helminths cause a type 2 immune response during the chronic stage of infection that is characterised by Th2 cell differentiation, eosinophil recruitment, and alternative macrophage activation, the immune mechanisms that regulate tissue damage at the time of parasite invasion are poorly understood. AIM: The aim of the study was to determine the cytokine gene expression profiles during HIV and helminth coinfection in underprivileged South African adults living in a peri-urban area with poor sanitary conditions and a lack of clean water supply. METHOD: Study participants (n = 164) were subdivided into uninfected controls, HIV-infected, helminth-infected, and HIV and helminth-coinfected groups. The Kato-Katz and Mini Parasep techniques and Ascaris lumbricoides-specific Immunoglobulin E (IgE) and Immunoglobulin G4 (IgG4) levels were used to detect helminth infections. Participants' HIV status was determined using two HIV1/2 antibody test kits. RNA was isolated from white blood cells for cytokine (Th1-, Th2-, and Th17-related) and transcription factor gene expression profiling using real-time PCR. RESULTS: Multivariate regression data were adjusted for age, gender, BMI, antiretroviral treatment (ART), and nutritional supplement intake. The HIV and helminth-coinfected group had significantly higher tumour necrosis factor alpha (TNF-α) (adjusted ß = 0.53, p = 0.036), interleukin 2 (IL-2) (adjusted ß = 6.48, p = 0.008), and interleukin 17 (IL-17) (adjusted ß = 1.16, p = 0.001) levels and lower GATA binding protein 3 (GATA3) levels (adjusted ß = -0.77, p = 0.018) compared to the uninfected controls. No statistical significance was noted for Th2-related cytokines. CONCLUSION: The coinfected group had higher proinflammatory Th1- and Th17-related cytokine gene expression profiles compared to the uninfected controls. The findings suggest that pro-inflammatory responses are elevated during coinfection, which supports the hypothesis that helminths have a deleterious effect on HIV immune responses.

Cytokine Responses during Mycobacterium tuberculosis H37Rv and Ascaris lumbricoides Costimulation Using Human THP-1 and Jurkat Cells, and a Pilot Human Tuberculosis and Helminth Coinfection Study.

BACKGROUND: Helminth infections are widespread in tuberculosis-endemic areas and are associated with an increased risk of active tuberculosis. In contrast to the pro-inflammatory Th1 responses elicited by Mycobacterium tuberculosis (Mtb) infection, helminth infections induce anti-inflammatory Th2/Treg responses. A robust Th2 response has been linked to reduced tuberculosis protection. Several studies show the effect of helminth infection on BCG vaccination and TB, but the mechanisms remain unclear. AIM: To determine the cytokine response profiles during tuberculosis and intestinal helminth coinfection. METHODS: For the in vitro study, lymphocytic Jurkat and monocytic THP-1 cell lines were stimulated with Mtb H37Rv and Ascaris lumbricoides (A. lumbricoides) excretory-secretory protein extracts for 24 and 48 h. The pilot human ex vivo study consisted of participants infected with Mtb, helminths, or coinfected with both Mtb and helminths. Thereafter, the gene transcription levels of IFN-γ, TNF-α, granzyme B, perforin, IL-2, IL-17, NFATC2, Eomesodermin, IL-4, IL-5, IL-10, TGF-ß and FoxP3 in the unstimulated/uninfected controls, singly stimulated/infected and costimulated/coinfected groups were determined using RT-qPCR. RESULTS: TB-stimulated Jurkat cells had significantly higher levels of IFN-γ, TNF-α, granzyme B, and perforin compared to unstimulated controls, LPS- and A. lumbricoides-stimulated cells, and A. lumbricoides plus TB-costimulated cells (p < 0.0001). IL-2, IL-17, Eomes, and NFATC2 levels were also higher in TB-stimulated Jurkat cells (p < 0.0001). Jurkat and THP-1 cells singly stimulated with TB had lower IL-5 and IL-4 levels compared to those singly stimulated with A. lumbricoides and those costimulated with TB plus A. lumbricoides (p < 0.0001). A. lumbricoides-singly stimulated cells had higher IL-4 levels compared to TB plus A. lumbricoides-costimulated Jurkat and THP-1 cells (p < 0.0001). TGF-ß levels were also lower in TB-singly stimulated cells compared to TB plus A. lumbricoides-costimulated cells (p < 0.0001). IL-10 levels were lower in TB-stimulated Jurkat and THP-1 cells compared to TB plus A. lumbricoides-costimulated cells (p < 0.0001). Similar results were noted for the human ex vivo study, albeit with a smaller sample size. CONCLUSIONS: Data suggest that helminths induce a predominant Th2/Treg response which may downregulate critical Th1 responses that are crucial for tuberculosis protection.

Demographic profile of HIV and helminth-coinfected adults in KwaZulu-Natal, South Africa.

Background: Helminth and HIV infections are endemic among poor populations. Studies investigating the socio-demographic and economic risk factors associated with dual HIV and helminth coinfection are scarce. Objectives: This study aimed to describe risk factors associated with HIV and helminth coinfections among peri-urban South African adults residing in poorly developed areas with high poverty levels, lack of sanitation and a clean water supply. Method: Adult participants (n = 414) were recruited from clinics in the south of Durban, KwaZulu-Natal, South Africa. Participants' demographic, socio-economic, sanitation and household information, anthropometric measurements and HIV status were collected. Stool samples were donated for coproscopy to detect helminths using the Kato-Katz and Mini Parasep techniques. Blood was collected to confirm participants' HIV status and to determine Ascaris lumbricoides-specific immunoglobulin E (IgE) and immunoglobulin G4 (IgG4) levels to improve microscopy sensitivity. Results: Overall coinfection was 15%, and single helminth and HIV prevalence were 33% and 52%, respectively. Ascaris lumbricoides was predominant (18%). Univariate analysis of variance (ANOVA) showed that coinfection was 11.9% and 19.8%, respectively, among the 18-34 years and 35-59 years age groups (p = 0.0006), 16.4% and 19.9%, respectively, for the no income and < R1000.00 groups (p = 0.0358) and 22.8% and 17.1%, respectively, for the pit or public toilets and toilets not connected to sewage groups (p = 0.0007). Conclusion: Findings suggest that the dual infection with HIV and helminth infections among adults residing in under-resourced areas with poor sanitary conditions is frequent. Older age, poor toilet use and low income are associated with coinfection. More attention is required to break the cycle of coinfections and possible disease interactions. Contribution: The study highlights the importance of determining and treating helminth infections among adult population during HIV and helminth coinfection and the influence of poor sanitation and socioeconomic status on disease transmission.

Anaemia and Nutritional Status during HIV and Helminth Coinfection among Adults in South Africa.

Sub-Saharan Africa is burdened with helminthiasis and HIV/AIDS, and there is a significant overlap between these infections. However, little is known about the extent of anaemia and malnutrition in HIV/AIDS and helminth coinfected adults. The study investigated the anaemia profiles and nutritional status of HIV and helminth coinfected adult South Africans. Stool samples were collected from participants (N = 414) for parasite detection using the Kato−Katz and Mini Parasep® SF techniques. Blood was collected to determine participants' HIV status, micro- and macronutrients, haematological parameters, and Ascaris lumbricoides-specific IgE and IgG4 levels. Thereafter, participants were stratified into single infection (HIV or helminths), coinfection, and uninfected controls (no HIV and helminth) groups. The majority (74.9%) of participants had CD4 counts of >500 cells/µL, indicating no significant immunosupression. The coinfected group had an overall anaemia prevalence of 16.9%, which was lower than that of the HIV-infected group (44.6%) and higher than helminth infected group (15.4%). Overall helminth prevalence was 33%, with Ascaris lumbricoides being the most prevalent. The coinfected group also had lower vitamin A (p = 0.0107), calcium (p = 0.0002), and albumin (p < 0.0001) levels compared to HIV/helminth uninfected controls. Unexpectedly, the coinfected group had the highest serum iron levels, followed by the helminth-infected and control groups, both of which had similar iron levels, and finally, the HIV-infected group, which had the lowest iron levels (p = 0.04). Coinfected adults may be prone to micronutrient deficiency and anaemia. Further research and intervention programmes are required in this neglected field.

Immunological Interactions between Intestinal Helminth Infections and Tuberculosis.

Helminth infections are among the neglected tropical diseases affecting billions of people globally, predominantly in developing countries. Helminths' effects are augmented by coincident tuberculosis disease, which infects a third of the world's population. The role of helminth infections on the pathogenesis and pathology of active tuberculosis (T.B.) remains controversial. Parasite-induced suppression of the efficacy of Bacille Calmette-Guerin (BCG) has been widely reported in helminth-endemic areas worldwide. T.B. immune response is predominantly proinflammatory T-helper type 1 (Th1)-dependent. On the other hand, helminth infections induce an opposing anti-inflammatory Th2 and Th3 immune-regulatory response. This review summarizes the literature focusing on host immune response profiles during single-helminth, T.B. and dual infections. It also aims to necessitate investigations into the complexity of immunity in helminth/T.B. coinfected patients since the research data are limited and contradictory. Helminths overlap geographically with T.B., particularly in Sub-Saharan Africa. Each disease elicits a response which may skew the immune responses. However, these effects are helminth species-dependent, where some parasites have no impact on the immune responses to concurrent T.B. The implications for the complex immunological interactions that occur during coinfection are highlighted to inform government treatment policies and encourage the development of high-efficacy T.B. vaccines in areas where helminths are prevalent.

The challenges of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in low-middle income countries and possible cost-effective measures in resource-limited settings.

Diagnostic testing for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains a challenge around the world, especially in low-middle-income countries (LMICs) with poor socio-economic backgrounds. From the beginning of the pandemic in December 2019 to August 2021, a total of approximately 3.4 billion tests were performed globally. The majority of these tests were restricted to high income countries. Reagents for diagnostic testing became a premium, LMICs either cannot afford or find manufacturers unwilling to supply them with expensive analytical reagents and equipment. From March to December 2020 obtaining testing kits for SARS-CoV-2 testing was a challenge. As the number of SARS-CoV-2 infection cases increases globally, large-scale testing still remains a challenge in LMICs. The aim of this review paper is to compare the total number and frequencies of SARS-CoV-2 testing in LMICs and high-income countries (HICs) using publicly available data from Worldometer COVID-19, as well as discussing possible interventions and cost-effective measures to increase testing capability in LMICs. In summary, HICs conducted more SARS-CoV-2 testing (USA: 192%, Australia: 146%, Switzerland: 124% and Canada: 113%) compared to middle-income countries (MICs) (Vietnam: 43%, South Africa: 29%, Brazil: 27% and Venezuela: 12%) and low-income countries (LICs) (Bangladesh: 6%, Uganda: 4% and Nigeria: 1%). Some of the cost-effective solutions to counteract the aforementioned problems includes using saliva instead of oropharyngeal or nasopharyngeal swabs, sample pooling, and testing high-priority groups to increase the number of mass testing in LMICs.

SARS-CoV-2 and helminth co-infections, and environmental pollution exposure: An epidemiological and immunological perspective.

Soil-transmitted helminths infect billions of people globally, particularly those residing in low- and middle-income regions with poor environmental sanitation and high levels of air and water pollution. Helminths display potent immunomodulatory activity by activating T helper type 2 (Th2) anti-inflammatory and Th3 regulatory immune responses. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes Coronavirus disease 2019 (COVID-19), can exacerbate Th1/Th17 pro-inflammatory cytokine production in humans, leading to a cytokine storm. Air pollutants (particulate matter, oxygen radicals, hydrocarbons and volatile organic compounds) and water pollutants (metals and organic chemicals) can also intensify Th1/Th17 immune response and could exacerbate SARS-CoV-2 related respiratory distress and failure. The present review focused on the epidemiology of SARS-CoV-2, helminths and fine particulate matter 2.5 µm or less in diameter (PM2.5) air pollution exposure in helminth endemic regions, the possible immunomodulatory activity of helminths against SARS-CoV-2 hyper-inflammatory immune response, and whether air and water pollutants can further exacerbate SARS-CoV-2 related cytokine storm and in the process hinder helminths immunomodulatory functionality. Helminth Th2/Th3 immune response is associated with reductions in lung inflammation and damage, and decreased expression levels of angiotensin-converting enzyme 2 (ACE2) receptors (SARS-CoV-2 uses the ACE2 receptors to infect cells and associated with extensive lung damage). However, air pollutants are associated with overexpression of ACE2 receptors in the epithelial cell surface of the respiratory tract and exhaustion of Th2 immune response. Helminth-induced immunosuppression activity reduces vaccination efficacy, and diminishes vital Th1 cytokine production immune responses that are crucial for combating early stage infections. This could be reversed by continuous air pollution exposure which is known to intensify Th1 pro-inflammatory cytokine production to a point where the immunosuppressive activities of helminths could be hindered. Again, suppressed activities of helminths can also be disadvantageous against SARS-CoV-2 inflammatory response. This "yin and yang" approach seems complex and requires more understanding. Further studies are warranted in a cohort of SARS-CoV-2 infected individuals residing in helminths and air pollution endemic regions to offer more insights, and to impact mass periodic deworming programmes and environmental health policies.