Morbidity burden of lymphatic filariasis (LF) relies on the information from the Mass Drug Administration (MDA) programme where Community Health Volunteers (CHVs) passively report cases identified. Consequently, the exact prevalence of morbidity cases is not always accurate. The use of mobile phone technology to report morbidity cases was piloted in Ghana using a text-based short messaging service (SMS) tool by CHVs. Though successful, illiterate CHVs could not effectively use the SMS tool. The aim of this study was to evaluate the use of a mobile phone-based Interactive Voice Response System (mIVRS) by CHVs in reporting LF morbidity cases and acute dermatolymphangioadenitis (ADLA) attacks in Ghana. The mIVRS was designed as a surveillance tool to capture LF data in Kassena Nankana Districts of Ghana. One hundred CHVs were trained to identify and report lymphedema and hydrocele cases as well as ADLA attacks by calling a hotline linked to the mIVRS. The system asked a series of questions about the disease condition. The ability of the CHV to report accurately was assessed and the data from the mIVRS were compared with the paper records from the CHVs and existing MDA programme records from the same communities and period. Higher numbers of lymphedema and hydrocele cases were recorded by the CHVs using the mIVRS (n = 590 and n = 103) compared to the paper-based reporting (n = 417 and n = 76) and the MDA records (n = 154 and n = 84). Female CHVs, CHVs above 40 years, and CHVs with higher educational levels were better at paper-based reporting (P = 0.007, P = 0.001, P = 0.049 respectively). The system, when fully developed and linked to national databases, may help to overcome underreporting of morbidity cases and ADLA attacks in endemic communities. The system has the potential to be further expanded to other diseases.

Approximately 51 million individuals suffer from lymphatic filariasis (LF) caused mainly by the filarial worm Wuchereria bancrofti. Mass drug administration (MDA) programs led to a significant reduction in the number of infected individuals, but the consequences of the treatment and clearance of infection in regard to host immunity remain uncertain. Thus, this study investigates the composition of myeloid-derived suppressor cells (MDSCs), macrophage subsets and innate lymphoid cells (ILCs), in patent (circulating filarial antigen (CFA)+ microfilariae (MF)+) and latent (CFA+MF−) W. bancrofti-infected individuals, previously W. bancrofti-infected (PI) individuals cured of the infection due to MDA, uninfected controls (endemic normal (EN)) and individuals who suffer from lymphoedema (LE) from the Western Region of Ghana. Frequencies of ILC2 were significantly reduced in W. bancrofti-infected individuals, while the frequencies of MDSCs, M2 macrophages, ILC1 and ILC3 were comparable between the cohorts. Importantly, clearance of infection due to MDA restored the ILC2 frequencies, suggesting that ILC2 subsets might migrate to the site of infection within the lymphatic tissue. In general, the immune cell composition in individuals who cured the infection were comparable to the uninfected individuals, showing that filarial-driven changes of the immune responses require an active infection and are not maintained upon the clearance of the infection.

: 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.

Chronic lymphedema caused by infection of Wuchereria bancrofti is a disfiguring disease that leads to physical disability, stigmatization, and reduced quality of life. The edematous changes occur mainly on the lower extremities and can progress over time due to secondary bacterial infections. In this study, we characterized participants with filarial lymphedema from Ghana and Tanzania as having low (stage 1–2), intermediate (stage 3–4), or advanced (stage 5–7) lymphedema to determine CD4⁺ T cell activation patterns and markers associated with immune cell exhaustion. A flow cytometry-based analysis of peripheral whole blood revealed different T cell phenotypes within participants with different stages of filarial lymphedema. In detail, increased frequencies of CD4⁺HLA-DR⁺CD38⁺ T cells were associated with higher stages of filarial lymphedema in patients from Ghana and Tanzania. In addition, significantly increased frequencies of CCR5⁺CD4⁺ T cells were seen in Ghanaian participants with advanced LE stages, which was not observed in the Tanzanian cohort. The frequencies of CD8⁺PD-1⁺ T cells were augmented in individuals with higher stage lymphedema in both countries. These findings show distinct activation and exhaustion patterns in lymphedema patients but reveal that immunological findings differ between West and East African countries.

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.

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. A retrospective cohort study was conducted using 104 archived plasma samples collected during the third wave of the pandemic in the Ashanti Region of Ghana. ELISA and Luminex assays were used to measure SARS-CoV-2-specific IgA and IgG, neutralizing antibodies, and helminth-specific IgG levels. The results indicated that the highest cumulative seroprevalence of helminths (61.5%) was observed in asymptomatic SARS-CoV-2-infected individuals. In comparison, mild and moderate COVID-19 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 helminths tested. Strikingly, co-exposure resulted in lower SARS-CoV-2-specific IgA/IgG expression and reduced neutralization potential. However, in the plasma of individuals co-seropositive for helminths and SARS-CoV-2, a significantly higher expression of Th2 cytokines and IL-10 over Th1 was observed compared to those who were SARS-CoV-2 positive alone. These data suggest that co-exposure to helminths could mitigate severe COVID-19 outcomes by reducing the Th1 and Th17 responses. Our study highlights the potential protective role of helminth co-infection against severe COVID-19, suggesting that helminth-induced immune modulation may improve clinical outcomes. These findings provide valuable insights for public health policies in helminth-endemic regions and underscore the importance of considering helminth co-infections in managing viral infections.