Background/Objectives: Helminth infections, particularly prevalent in low- and middle-income countries, have been extensively studied for their effects on human health. With the emergence of new infectious diseases like SARS-CoV-2 and Ebola, their impact on disease outcomes become more apparent. While individual studies have explored the impact of helminth co-infections on disease severity and vaccine efficacy, the findings are often inconsistent and context-dependent. Furthermore, the long-term effects of helminth-mediated immunosuppression on vaccine efficacy and its broader implications for co-infections in endemic regions remain not fully understood. Methods: This systematic review conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines synthesizes the current evidence, identifies patterns, and highlights areas needing further research, offering a cohesive understanding of the topic. PubMed, Scopus, Google Scholar, and Cochrane Library were searched to include studies published from 2003 to February 2025. Results: Co-infection reveals a dual role of helminths in modulating immune responses, with both beneficial and detrimental interactions reported across studies. It may confer benefits against respiratory viral infections by muting hyper-inflammation associated with the severity of conditions like COVID-19, Influenza, and RSV. However, they can exacerbate disease outcomes in most bacteria and blood-borne viral conditions by impairing immune functions, such as neutrophil recruitment and antibody response, leading to more severe infections and higher viral loads. The stage of helminth infection also appears critical, with early-stage infections sometimes offering protection, while late-stage infections may worsen disease outcomes. Helminth infection can also negatively impact vaccine efficacy by suppressing B cell activity, reducing antibody levels, and decreasing vaccine effectiveness against infectious diseases. This immunosuppressive effect may persist after deworming, complicating efforts to restore vaccine efficacy. Maternal helminth infections also significantly influence neonatal immunity, affecting newborn vaccine responses. Conclusions: There is a need for targeted interventions and further research in helminth-endemic regions to mitigate the adverse effects on vaccine efficacy and improve public health outcomes.

: Filarial lymphedema (LE) remains a significant global problem despite the progress made toward elimination of lymphatic filariasis (LF). In Ghana, the main approach to LF is preventive chemotherapy, but this has minimal impact on individuals who have already developed LE. In 2018–2020, a 24-month randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of stringent hygiene measures using the Essential Package of Care with or without additional administration of doxycycline (DOX) to improve filarial leg LE. This study enrolled 356 participants with LE stages 1–3 from two districts in the Upper East Region of Ghana. In addition to regular training on appropriate care for their affected legs, participants were randomized to receive 6 weeks of either 200 mg/day DOX (n = 117), 100 mg/day DOX (n = 120), or matching placebo (n = 119). Participants were seen every 2 months, with clinical measurements done at 6, 12, 18, and 24 months to assess the status of affected legs. There was a trend toward later appearance of acute attacks after DOX, but surprisingly, DOX showed no effect on LE stage progression. In all groups, leg LE improvement was more common (DOX 200 mg: n = 23 [20%]; DOX 100 mg: n = 23 [19.5%]; placebo: n = 32 [27.4%]) than LE worsening (DOX 200 mg: n = 2 [1.7%]; DOX 100 mg: n = 3 [2.5%]; placebo: n = 2 [1.7%]). Overall, these data show a strong benefit from adherence to a strict hygiene protocol, with some added potential benefit for DOX in preventing acute attacks.

Background/Objectives: The COVID-19 pandemic has significantly impacted global health. However, Africa has reported relatively low numbers of cases and fatalities. Although the pandemic has largely receded, the reasons for its milder course on the African continent have not yet been fully clarified. This study explored the hypothesis that helminth co-infections may have contributed to these observations. Methods: A retrospective cohort study was conducted using 104 plasma samples collected during the third wave of the pandemic in the Ashanti Region of Ghana. Luminex assays were used to measure SARS-CoV-2-specific IgA and IgG, neutralizing antibodies, systemic cytokines and helminth-specific IgG. Results: The results indicated that the highest cumulative seroprevalence of helminths (61.5%) was observed in asymptomatic COVID-19 patients. In comparison, mild and moderate patients had helminth seropositivity rates of 43.8% and 34.5%, respectively, which were 1.4 and 1.8 times lower than those of the asymptomatic group, respectively. Notably, the two severe COVID-19 cases investigated were seronegative for all three of the helminths tested. Strikingly, co-exposure resulted in lower SARS-CoV-2-specific IgA/IgG expression and reduced neutralization potential. However, co-seropositive individuals for helminths and SARS-CoV-2 exhibited a higher expression of Th2 cytokines and IL-10 over Th1 cytokines compared to SARS-CoV-2-positive individuals alone. Conclusion: These data suggest that co-exposure to helminths could mitigate the severity of COVID-19 outcomes by reducing the Th1 and Th17 responses; this highlights the potential protective role of helminthiasis against severe COVID-19. These findings provide valuable insights for the development of public health policies in helminth-endemic regions and underscore the importance of considering helminth co-infections in managing viral infections. It also offers a plausible explanation for the milder disease severity observed in helminth-endemic regions while raising critical considerations regarding vaccine efficacy, as helminth-induced immune modulation may influence the magnitude and quality of vaccine-induced immune responses.

Background/Objectives: Although the COVID-19 pandemic has largely concluded, the varied trajectories it has followed in different regions of the world remain incompletely understood. Intensive research is needed to fully grasp its course and the implications for future global health challenges. Notably, the milder trajectory of the COVID-19 pandemic in Sub-Saharan Africa has defied initial predictions. An emerging body of evidence suggests that, in addition to the continent’s younger average age and the lower prevalence of relevant comorbidities, co-infections with helminths may have also impressively shaped the pandemic’s milder trajectory in the region. Indeed, helminths are renowned for their ability to modulate human immune responses, which, while potentially beneficial in limiting excessive inflammation, could also diminish vaccine efficacy and impede viral clearance. This study investigated different aspects of the intricate interactions between COVID-19 and Lymphatic Filariasis (LF), a helminth infection caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi, and Brugia timori and endemic to various regions in Sub-Saharan Africa and the tropics. Methods: For this purpose, samples of a larger and ongoing clinical trial (ethical approval codes: CHRPE/AP/525/17 and 325/21; trial registration number ISRCTN14042737) were collected from 222 individuals from endemic areas of Ghana, along with comprehensive clinical and demographic data. The samples include LF patients (n = 222) grouped according to their Lymphoedema (LE) stages, as well as COVID-19 vaccinated (n = 81) and non-vaccinated individuals (n = 141). All vaccinated participants received the COVID-19 vaccine ChAdOx1-S (also known as Vaxzevria) developed by the University of Oxford and AstraZenca. The expressions of SARS-CoV-2 and filarial-specific antibodies (IgG, IgA) were accessed using ELISA, while Luminex-based immunoassays were employed to measure the expression of SARS-CoV-2 variant-specific neutralizing antibodies. The interplay between vaccine responses and demographic factors was analyzed using group comparisons with the Kruskal-Wallis or Mann-Whitney U tests. Results: The results indicate that a remarkable portion of unvaccinated individuals (56% IgA seropositive, 39% IgG seropositive) developed antibodies against SARS-CoV-2 despite no confirmed infection. Notably, the study identified a robust antibody response to COVID-19 vaccination, which was independent of the degree of LF pathology or parasitic status. An important observation was the reduced SARS-CoV-2 antibody response in individuals seropositive for Ascaris lumbricoides (p = 0.0264), highlighting an interaction between roundworm infection and COVID-19. Conclusions: The study concludes that the ChAdOx1-S COVID-19 vaccine (AstraZeneca) triggers a strong immune response in LF patients; however, filarial and/or soil-transmitted helminth seropositivity might influence the COVID-19 infection-induced response. These findings emphasize the complexity of infectious disease dynamics in co-infected populations and the need to decipher parasite-induced immunomodulatory mechanisms on COVID-19 vaccination.

Lymphatic filariasis (LF) represents a parasitic disease caused by filarial nematodes. Although some infected individuals present an asymptomatic course, others suffer severe chronic lymphatic pathology, including lymphedema, hydrocele, and elephantiasis. Several studies have shown that host genetic factors influence LF susceptibility and chronic pathology. The current study aimed to conduct the first genome-wide association study to systematically determine LF susceptibility. We analyzed genome-wide single-nucleotide polymorphism data from 1459 LF cases and 1492 asymptomatic controls of West African (Ghanaian) descent. We identified two independent genome-wide significant associated genetic variants near the genes HLA-DQB2 (rs7742085) and HLA-DQA1 (rs4959107) contributing to LF and/or lymphedema susceptibility (P 1.30). We also observed suggestive evidence of LF associations (P <1.0 × 10^-6) at two non-HLA loci, near the genes ZFHX4-AS1 (rs79562145) and CHP2 (rs12933387). In contrast, we could not replicate any previously reported LF associations drawn from candidate gene association studies. On the polygenic level, we show that our genome-wide association study data explain 24-42% of LF heritability, depending on an assumed population prevalence of 0.5-5.0%. Our findings point to an involvement of HLA-mediated immune mechanisms in LF pathophysiology.

Onchocerciasis causes chronic systemic inflammation. Several studies have used markers such as haemato-biochemical indices to predict the occurrence of systemic inflammation. This study assessed the variability and predictability of haemato-biochemical indices and blood composite ratios (BCRs) in microfilariae positive (MF+) and microfilariae negative (MF-) subgroups of onchocercomata participants. One hundred and five (105) MF + and 34 MF- participants were retrospectively recruited into the study. Screening for the presence of O. volvulus microfilariae was done from skin snips taken from the left and right iliac crests of participants using established and approved protocols. Haematological and biochemical indices were measured using standard laboratory automated analyzers. Blood composite ratios (BCRs) were calculated as ratios of the absolute parameters involved. A significantly increased total WBC, absolute eosinophil, eosinophil percent and absolute basophil were observed in the MF + participants compared to MF- participants. Reduced gamma-glutamyl transferase (GGT) with increased estimated glomerular filtration rate (eGFR) was significantly associated with MF + participants compared to MF- participants. BCRs were significantly higher for eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), eosinophil-to-basophil ratio (EBR) and eosinophil-to-lymphocyte ratio (ELR) in MF + participants compared to MF- participants. After multivariate adjustment, onchocercomata participants with increased eosinophil counts (aOR = 13.86, 95% CI [2.07–92.90], p = 0.007), ENR x10 (aOR = 1.42, 95% CI [1.05–1.93], p = 0.025), EMR (aOR = 2.64, 95% CI [1.25–5.60], p = 0.011), EBR (aOR = 1.07, 95% CI [1.01–1.10], p = 0.020) and ELR x10 (aOR = 1.69, 95% CI [1.14–2.51], p = 0.009) were more likely to have microfilaridermia. Elevated eosinophil counts with higher ENR, EMR, EBR and ELR levels are significantly associated with microfilaridermia in onchocercomata participants. Combining BCRs with eosinophil count significantly led to an improvement in the conventional model for predicting microfilaridermia.