With the advent of COVID-19, the MDA program in filarial endemic communities in Ghana have been halted in compliance with COVID-19 protocols of shelter in place and social distancing. This study observed more women with symptomatic LF than men, as shown by the demographic data. This observation is not uncommon as others have reported the same in other LF-endemic areas . Similarly, most of the study participants were in their active years (50 years and below, 67.5%). Our findings corroborated previous studies with a high frequency of younger populations in endemic communities with LF morbidity [11, 12], thus presenting a unique challenge to the most endemic communities if adequate control measures are not quickly implemented.
In the present study, we observed increased LF attacks reported as a result of MDA interruption due to the COVID-19 pandemic among LF patients in south-western Ghana. MDA programs in filarial endemic regions rely on ivermectin and albendazole as the mainstay intervention against filarial infections . Ivermectin is widely available, inexpensive, easy to administer, and has a wide safety margin . Ivermectin is an effective macrocyclic lactone in reducing microfilariae levels, i.e., towards a break in human filarial infection transmission. Thus, disruption of MDA activities could prolong timelines for LF elimination . Aside its microfilaricidal activities, ivermectin is reported to offer other benefits especially for people living with the end stage of the LF pathology, who are likely to be negative for the active infection by reducing filarial attacks . In the current study area, ivermectin is distributed annually around March to control LF transmission. With the MDA interruption, the reported increased LF attacks could be worrying given the excruciating pain and discomfort associated with LF attacks , suggesting that urgent attention should be given to individuals suffering from human lymphatic filarial infections living in LF-endemic communities. Of note, this study's findings are important and urgent, suggesting that sustained interruption of the MDA interruption in endemic communities could further worsen the plight of these LF patients as filarial attacks could increase.
Next, MDA interruption was recounted to increase the frequency of LF pains experienced by the patients, and these pains were positively associated with MDA interruption during the COVID-19 pandemic. It is well-described that LF attacks are accompanied by pains . Some LF patients do experience, which could be so high that victims would have to be admitted at the health facility to receive some form of relief [16, 17]. Unfortunately, with the increased cases of COVID-19, which burdens the local health facilities, more attention is given to individuals presenting with symptoms of SARS-COV-2, thus further frustrating the ability of LF pathology patients with attacks to visit the health facilities to receive the needed treatment.
Ivermectin is known to reduce pains by inhibiting NF-kappa B's activity, a transcription factor, and MAP-kinases, which are known to drive inflammation [14, 18]. It has been demonstrated to have anti-inflammatory and immunomodulatory actions in several in vitro and animal models . Not only do ivermectin-derivatives control nuclear transcription factors as indicated above, but there are also reports of its ability to suppress pro-inflammatory cytokine secretion (interleukin-1 β and tumour necrosis factor-α, TNF- α) by 30% and heightens the immunoregulatory cytokine interleukin (IL)-10, an in vitro model of lipopolysaccharide (LPS) induced-inflammation . Furthermore, ivermectin-treated mice showed better survival rates with a decrease in pro-inflammatory cytokines, TNF-α and IL-1, IL-6 compared to controls following a lethal dose of LPS . Interestingly, the therapeutic benefits of ivermectin works across all stages of LF pathogenesis . This may be explained by ivermectin's multi-pronged effects, which range from direct parasite inhibition to immunomodulation to mitigation of cell access, as demonstrated by in vitro, in silico, and animal studies . In addition, ivermectin has been demonstrated to show anti-viral activity, suggesting the potential use of this drug in LF endemic areas with high COVID-19 cases could have multiple benefits .
Furthermore, the present study also showed that individuals with LF pathology had a perceived LF transmission increase should MDA interruption continue for a long time. The findings confirm previous reports where a halt in MDA was projected to increase transmission in endemic areas and the frequency of filarial attacks and cases of other helminth infections such as lice . It is important to understand the impact of COVID-19 on the transmission dynamics of lymphatic filariasis in endemic regions. While interruption of MDA in LF endemic communities could result in a resurgence of the disease , it can also provide several research opportunities to reassess the microfilarial levels before resuming the intervention, providing data that would otherwise be difficult to obtain.
Although not directly assessed, participants reported a perceived increase of LF transmission in endemic regions could also suggest their understanding of LF transmission and its causative agents. Previous studies have documented limited knowledge and perception of LF in endemic communities [22, 23]. Therefore the high frequency of individuals' perception of LF transmission may indicate the impact of health promotion and educational campaigns in endemic areas.
It is important to note that shift in attention, logistics, and human resources from filarial control program to COVID-19 control, while undoubtedly necessary, if not carefully reviewed, could be disadvantageous by denying individuals living in LF-endemic communities the opportunity of receiving timely anti-filarial treatment. Complexing the situation further is the similarity between malaria and LF infection symptoms, where both are characterized by increased body temperature (fever), headache, and chills . Thus, based on this, many LF patients with these symptoms may be prevented from visiting local clinics, given the stigma associated with COVID-19 [25, 26].