Immunological interactions in helminths-SARS CoV-2 coinfection: Could old enemy be a friend today?

Helminths are metazoan parasites affecting about one third of the worldwide population. Chronic helminth infections (CHIs) confer immunological tolerance to harmless and self-antigens mediated by regulatory T cells (Treg) that are up-regulated. In coronavirus disease 2019 (COVID-19), abnormal adaptive immune response and unrestrained innate immune response could result in local and systemic immune-mediated tissue damage. COVID-19 and CHIs establish complicated immune interactions due to SARS-CoV-2-induced immunological stimulation and CHIs-induced immunological tolerance. However, COVID-19 severity in patients with CHIs is mild, as immuno-suppressive anti-inflammatory cytokines counterbalance the risk of cytokine storm. Here, an overview of the interplay between helminths and COVID-19 severity is given. CHIs through helminth-derived molecules may suppress SARS-CoV-2 entry and associated hyperinflammation through attenuation of the TLR4/NF-kB signalling pathway. In addition, CHIs may reduce the COVID-19 severity by reducing the SARS-CoV-2 entry points at ACE2/DPP4/CD147 axis in the initial phase and immunomodulation in the late phase of the disease by suppressing TLR4/NF-kB signalling pathway.

Precision mapping of schistosomiasis and soil-transmitted helminthiasis among school age children at the coastal region, Kenya.

BACKGROUND: Accurate mapping of schistosomiasis (SCH) and soil transmitted helminths (STH) is a prerequisite for effective implementation of the control and elimination interventions. A precision mapping protocol was developed and implemented in the coastal region of Kenya by applying the current World Health Organization (WHO) mapping guide at a much lower administrative level (ward). METHODS: A two-stage cluster survey design was undertaken, with 5 villages in each ward selected. From within each village 50 households were randomly selected, and a single child between the ages of 8 and 14 sampled following appropriate assent. The prevalence and intensity of infection of Schistosoma mansoni and STH were determined using the Kato-Katz method (single stool, duplicate slides) and urine filtration for S. haematobium. RESULTS: Of the 27,850 school age children sampled, 6.9% were infected with at least one Schistosoma species, with S. haematobium being the most common 6.1% (95% CI: 3.1-11.9), and Tana River County having highest prevalence 19.6% (95% CI: 11.6-31.3). Prevalence of any STH infection was 5.8% (95% CI: 3.7-8.9), with Lamu County having the highest prevalence at 11.9% (95% CI: 10.0-14.1). The most prevalent STH species in the region was Trichuris trichiura at 3.1% (95% CI: 2.0-4.8). According to the WHO threshold for MDA implementation, 31 wards (in 15 sub-Counties) had a prevalence of ≥10% for SCH and thus qualify for annual MDA of all age groups from 2 years old. On the other hand, using the stricter Kenya BTS MDA threshold of ≥2%, 72 wards (in 17 sub-Counties) qualified for MDA and were targeted for treatment in 2021. CONCLUSIONS: The precision mapping at the ward level demonstrated the variations of schistosomiasis prevalence and endemicity by ward even within the same sub-counties. The data collected will be utilized by the Kenyan Ministry of Health to improve targeting.

Gastrointestinal helminths increase Bordetella bronchiseptica shedding and host variation in supershedding.

Co-infected hosts, individuals that carry more than one infectious agent at any one time, have been suggested to facilitate pathogen transmission, including the emergence of supershedding events. However, how the host immune response mediates the interactions between co-infecting pathogens and how these affect the dynamics of shedding remains largely unclear. We used laboratory experiments and a modeling approach to examine temporal changes in the shedding of the respiratory bacterium Bordetella bronchiseptica in rabbits with one or two gastrointestinal helminth species. Experimental data showed that rabbits co-infected with one or both helminths shed significantly more B. bronchiseptica, by direct contact with an agar petri dish, than rabbits with bacteria alone. Co-infected hosts generated supershedding events of higher intensity and more frequently than hosts with no helminths. To explain this variation in shedding an infection-immune model was developed and fitted to rabbits of each group. Simulations suggested that differences in the magnitude and duration of shedding could be explained by the effect of the two helminths on the relative contribution of neutrophils and specific IgA and IgG to B. bronchiseptica neutralization in the respiratory tract. However, the interactions between infection and immune response at the scale of analysis that we used could not capture the rapid variation in the intensity of shedding of every rabbit. We suggest that fast and local changes at the level of respiratory tissue probably played a more important role. This study indicates that co-infected hosts are important source of variation in shedding, and provides a quantitative explanation into the role of helminths to the dynamics of respiratory bacterial infections.

The effect of compliance to Hand hygiene during COVID-19 on intestinal parasitic infection and intensity of soil transmitted helminthes, among patients attending general hospital, southern Ethiopia: Observational study.

BACKGROUND: Intestinal parasitic infection (IPIs) is one of the major health problems in Sub -Saharan Africa where water, sanitation and hygiene practices are inadequate. Taking into account the national level implementation of intensive hand hygiene against COVID-19 pandemic and general protective effect this study assessed its effect on intestinal parasite. OBJECTIVE: This study aim to investigate the effect of compliance to hand hygiene practice on the prevalence of intestinal parasitic infection (IPIs) and intensity of Soil transmitted helminthes (STH) among patients attending tertiary care hospital in southern Ethiopia. METHODS: Observational study was conducted from June to September 2021. Data on socio demographic, hand hygiene practice and intestinal parasite (prevalence and intensity of helminthic infection) was collected from randomly selected and consented patients. Compliance to hand hygiene practice was assessed using pre-tested questionnaire. Fresh stool sample from each participant was examined by direct wet mount, concentration and Ziehl-Neelson (ZN) staining technique to detect intestinal parasite. Intensity of STH measurements was done through direct egg-count per gram using Kato Katz methods. Data analysis was done using SPSS version 25. Odds ratio with 95% confidence interval was used to measure association and p-value <0.05 was considered as statistically significant. RESULTS: The study population (N = 264) consisted of 139(52.65%) male and 125 (47.34%) female with the mean ages of 36 ±16.12(±SD). The proportion of good compliance to hand hygiene during COVID-19 to was 43.93% (95%CI: 37% to 47) and prevalence of intestinal parasite was 26.14% (95%CI:21.2% to 31.75) comprising 23.48% intestinal protozoa and 6.43% of soil transmitted helminthic infection. Gardia lamblia, Entamoeba histolytica/dispar, Ascaris lumbricoides were the common parasite in the study area with prevalence of 15.53%, 6.44%, and 1.52% respectively. Prevalence of intestinal parasite among participants with good compliance to hand hygiene group and poor compliance to hand hygiene were (14.65% vs. 35.13%)(AOR: 0.48,95%CI:0.13 to 0.68) (p = 0.002) implying that good compliance to hand hygiene can reduce the risk of IPIs by 52%. Moreover significantly lower odds of intestinal protozoa among good compliance to hand hygiene group than the control (OR:0.38; (95%CI: 0.20 to 0.71);P = 0.001. However, no significant difference in the odds of intensity of STH infection in good compliance hand hygiene and poor compliance group. The result of this study also confirmed the association between intestinal parasitic infections and younger /adolescent age, education status, habit of eating raw vegetable and figure nail status. CONCLUSION: Good hand hygiene compliance during COVID-19 significantly associated with reduction of intestinal parasitic infection. This finding highlights the secondary protective effect of improved hand hygiene against IPIs and suggest it can used in augmenting the existing parasitic control strategies in the study setting.

Pre-existing helminth infection impairs the efficacy of adjuvanted influenza vaccination in mice.

The world health organization estimates that more than a quarter of the human population is infected with parasitic worms that are called helminths. Many helminths suppress the immune system of their hosts to prolong their survival. This helminth-induced immunosuppression "spills over" to unrelated antigens and can suppress the immune response to vaccination against other pathogens. Indeed, several human studies have reported a negative correlation between helminth infections and responses to vaccinations. Using mice that are infected with the parasitic nematode Litomosoides sigmodontis as a model for chronic human filarial infections, we reported previously that concurrent helminth infection impaired the vaccination-induced protection against the human pathogenic 2009 pandemic H1N1 influenza A virus (2009 pH1N1). Vaccinated, helminth-infected mice produced less neutralizing, influenza-specific antibodies than vaccinated naïve control mice. Consequently helminth-infected and vaccinated mice were not protected against a challenge infection with influenza virus but displayed high virus burden in the lung and a transient weight loss. In the current study we tried to improve the vaccination efficacy using vaccines that are licensed for humans. We either introduced a prime-boost vaccination regimen using the non-adjuvanted anti-influenza vaccine Begripal or employed the adjuvanted influenza vaccine Fluad. Although both strategies elevated the production of influenza-specific antibodies and protected mice from the transient weight loss that is caused by an influenza challenge infection, sterile immunity was not achieved. Helminth-infected vaccinated mice still had high virus burden in the lung while non-helminth-infected vaccinated mice rapidly cleared the virus. In summary we demonstrate that basic improvements of influenza vaccination regimen are not sufficient to confer sterile immunity on the background of helminth-induced immunosuppression, despite amelioration of pathology i.e. weight loss. Our findings highlight the risk of failed vaccinations in helminth-endemic areas, especially in light of the ongoing vaccination campaign to control the COVID-19 pandemic.

Increasing efficiencies from integrating control and elimination programmes for soil-transmitted helminths and schistosomiasis.

Attention is now beginning to focus on implementation of the new WHO NTD Roadmap (2021-2030), which presents single disease alliances and coalitions with an opportunity to consider novel ways to integrate and adapt control and elimination programmes to meet the new goals. This discussion piece links the parasitic worm diseases, caused by soil-transmitted helminths and schistosomes, highlighting that neglected tropical disease-control programmes could potentially benefit from greater cohesion and innovation, especially when increasing efforts to achieve elimination goals.

Community Drug Distributor Knowledge, Attitudes, and Motivation Surrounding Mass Drug Administration for Soil-Transmitted Helminths in India.

Background: DeWorm3 is an ongoing multi-country community-based cluster-randomized trial assessing the feasibility of interrupting transmission of soil-transmitted helminths (STH) with community-wide mass drug administration (cMDA). In Tamil Nadu, India, community drug distributors (CDDs) worked with DeWorm3 field staff to counsel community members and deliver door-to-door deworming treatment. As CDDs were likely to influence successful delivery of cMDA, we describe drivers of CDDs' knowledge, attitudes, and motivation toward delivery of cMDA. Methods: In this convergent mixed-methods study, a questionnaire on STH and cMDA was administered to 104 CDDs and 17 focus group discussions (FGDs) were conducted. Key outcomes in the quantitative and qualitative analyses included CDDs' knowledge about STH and cMDA and attitudes toward cMDA for STH. Univariate and multivariable logistic regression analyses were performed to determine the strength of associations between independent and outcome variables. The FGDs were analyzed using a priori thematic coding. Results: CDDs who completed at least secondary school education [adjusted odds ratio (aOR): 2.71, 95% CI: 1.16-6.33] and had prior experience in health programs (aOR: 2.72, 95% CI: 1.15-6.44) were more knowledgeable about STH and cMDA. CDDs belonging to the scheduled castes and scheduled tribes (aOR: 2.37, 95% CI: 1.04-5.39), and to households engaged in a skilled occupation (aOR: 2.77, 95% CI: 1.21-6.34) had a more positive attitude toward cMDA for STH. The FGDs showed that while there were myths and misconceptions about STH, many CDDs believed that the adult population in their communities were infected with STH, and that a door-to-door drug delivery strategy would be optimal to reach adults. Conclusions: Educational and socioeconomic backgrounds and experience in health programs should be considered while designing CDD trainings. Along with cMDA delivery for STH, as CDD do share community myths and misconceptions around STH, they should be proactively addressed during the CDD training to strengthen competency in counseling.

Specificity of SARS-CoV-2 Antibody Detection Assays against S and N Proteins among Pre-COVID-19 Sera from Patients with Protozoan and Helminth Parasitic Infections.

We aimed to assess the specificity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody detection assays among people with tissue-borne parasitic infections. We tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 neutralization antibody detection kit [cPass], Abbott SARS-CoV-2 IgG assay [Abbott Architect], and Standard Q COVID-19 IgM/IgG combo rapid diagnostic test [SD RDT IgM/SD RDT IgG]) among 559 pre-COVID-19 seropositive sera for several parasitic infections. The specificity of assays was 95 to 98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95% CI, 75 to 95]) and visceral leishmaniasis (SD RDT IgG; 80% [95% CI, 30 to 99]), and from patients with recent malaria in areas of Senegal where malaria is holoendemic (ranging from 91% for Abbott Architect and SD RDT IgM to 98 to 99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all ≥96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98 to 100%. The majority (>85%) of false-positive results were positive by only one assay. The specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.

Progress towards control and elimination of neglected tropical diseases targeted by preventive chemotherapy in São Tomé e Príncipe.

The São Tomé e Príncipe government is committed to achieving neglected tropical disease (NTD) control and elimination as a public health problem by 2025. In 2014, the Ministry of Health led a national survey to determine the prevalence of soil-transmitted helminths (STHs) and schistosomiasis across the country. Following this survey, a preventive chemotherapy (PC) campaign with mebendazole and praziquantel reached 31 501 school-age children in 2015. A follow-up 2017 survey to determine the impact of the intervention showed success in controlling schistosomiasis, as no infections were found, but limited impact on STHs, with prevalence similar to pretreatment levels. The survey also investigated the prevalence of a third NTD, lymphatic filariasis (LF), which was found to be endemic in the country. Since then the Ministry of Health has developed the Strategic Plan for the Fight Against Neglected Tropical Diseases 2019-2025 and identified gaps to be addressed. This narrative review systematises the existing literature reporting on the epidemiology of NTDs for which there are PC programs in São Tomé e Príncipe. PubMed was searched for relevant papers that measured the prevalence of LF, schistosomiasis and STHs. Additionally, data provided by the Ministry of Health surveys were analysed. Finally, we discuss current NTD control, including the impact of the coronavirus disease 2019 pandemic and identify priorities for program strengthening and operational research.

Immunomodulation of COVID-19 severity by helminth co-infection: Implications for COVID-19 vaccine efficacy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging virus in late 2019 causing coronavirus disease 2019 (COVID-19), has caused a catastrophic effect, resulting in an unprecedented global crisis. The immunopathology of COVID-19 appears to be clearly associated with a dysregulated immune response leading to organ failure and death. Similarly, over two billion people worldwide are infected with helminth, with those living in low-middle-income countries disproportionately affected. Helminth infections have been shown to possess immunomodulatory effects in several conditions. Helminth co-infection in COVID-19 patients is one of the potential reasons for global attention to answer why COVID-19 severity is still lower in helminth endemic countries. Recent studies have shown that helminth endemic countries showed fewer cases and deaths so far and helminth co-infection might reduce the severity of COVID-19. Moreover, lessons from other diseases with helminth co-infection have been shown to substantially reduce vaccine efficacy that could also be implicated for COVID-19. This immunomodulatory effect of helminth has intended and unintended consequences, both advantageous and disadvantageous which could decrease the severity of COVID-19 and COVID-19 vaccine efficacy respectively. Herewith, we discuss the overview of COVID-19 immune response, immunomodulatory effects of helminth co-infections in COVID-19, lessons from other diseases, and perspectives on the efficacy of COVID-19 vaccines.

Gross ways to live long: Parasitic worms as an anti-inflammaging therapy?

Evolutionary medicine argues that disease can arise because modern conditions do not match those in which we evolved. For example, a decline in exposure to commensal microbes and gastrointestinal helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders (the hygiene hypothesis). Accordingly, probiotic therapies that restore 'old friend' microbes and helminths have been explored as Darwinian treatments for these disorders. A further possibility is that loss of old friend commensals also increases the sterile, aging-associated inflammation known as inflammaging, which contributes to a range of age-related diseases, including cardiovascular disease, dementia, and cancer. Interestingly, Crowe et al., 2020 recently reported that treatment with a secreted glycoprotein from a parasitic nematode can protect against murine aging by induction of anti-inflammatory mechanisms. Here, we explore the hypothesis that restorative helminth therapy would have anti-inflammaging effects. Could worm infections provide broad-spectrum protection against age-related disease?

Shift in parasitic infections during the Corona pandemic: a hospital-based retrospective study.

The Corona pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) calls on the Saudi government to take action to control the infection. The government closed borders, prohibited travel, limited outdoor movements, and told primary and secondary care facilities to reduce all regular non-urgent health services. It is not known whether these measures have impacted the prevalence of parasitic intestinal infections. This study has therefore been carried out to investigate this issue. Dataset of 217 stool samples submitted to the King Faisal Medical Complex (KFMC) Microbiology Laboratory in Taif, Saudi Arabia for parasitological examination during the pandemic (January-June 2020) and 649 samples submitted during the corresponding months of the previous year (January-June 2019) were extracted and analyzed. Overall, 24.1% (209/866) of samples were parasitespositives; 26.6% (173/649) before and 16.5% (36/217) during the pandemic, with 79% reduction. There was a significant difference in gender-parasitism between the two periods where the majority of parasitism were for males (p<0.001). Infections were frequent in patients aged 5- 14 years both before (84/649; 12.9%) and during (12/217; 5.5%) the pandemic, with significant difference observed between the two cohorts (p<0.002). Moreover, the majority of infected patients were non-Saudi (67.9%; 142/209), with a significant difference in nationality reported, (p=0.024). Protozoa were identified in 21.8% (189) of all samples investigated, of which, Blastocystis hominis, Entamoeba coli, Giardia lamblia, Entamoeba histolytica/dispar and Cryptosporidium species were identified in 6.1% (53), 5.4% (47), 5.0% (44), 2.8% (25), and 2.3% (20), respectively. Helminths were diagnosed in 2.3% (20/866) of samples. Eggs of hookworm, Ascaris, Taenia spp, and Hymenolepis nana were detected in 0.9% (8), 0.5% (5), 0.3% (3) and 0.4% (4), respectively. In parallel with our research hypothesis, a substantial decrease in the burden of intestinal parasitic infections was recorded with the lock-down measures taken during the Corona pandemic.

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.