Death to Onchocerciasis and Lymphatic Filariasis
Lymphatic filariasis (LF) in Africa is caused by Wuchereria bancrofti and is transmitted mainly by Anopheles or Culex mosquitoes. In 2000, the World Health Organization (WHO) launched an elimination program for LF that was based on annual mass drug administration (MDA) of albendazole (ALB, 400 mg) plus ivermectin (150–200 μg/kg) in countries where onchocerciasis is coendemic with LF, and with ALB plus diethylcarbamazine (DEC) in countries with no onchocerciasis.
However, the presence of Loa loa in Central Africa prevents the widespread use of ivermectin for LF elimination in areas that are not already receiving ivermectin for onchocerciasis control, because ivermectin sometimes causes serious adverse events including potentially fatal encephalopathy in individuals with high L. loa microfilaremia.
In 2012, the WHO proposed a provisional strategy for controlling LF in areas with coendemic loiasis but where onchocerciasis is absent. This consisted of MDA using ALB (preferably with semiannual delivery) together with integrated vector management.
With financial support from the Bill and Melinda Gates Foundation, the DOLF project launched two community trials to evaluate the impact of the WHO’s provisional strategy. One study site was located in Seke Pembe in the Republic of Congo, and the other in two neighboring villages (Misay and Mbunkimi) in the Democratic Republic of Congo (DRC). The whole population aged ≥2 years was treated with ALB every six months and examined every year to measure the proportion of subjects with circulating filarial antigens (CFA), the proportion of microfilaremic individuals among the latter, and the prevalence of soil-transmitted helminthiases (infections with Ascaris lumbricoides, Trichuris trichiura and hookworms).
In Seke Pembe, the prevalence of filarial antigenemia decreased from 17.3% (baseline, in 2012), to 16.6% (2013), 6.3% (2014), 4.7% (2015), and 2.8% in 2019 (no examination was done between 2015 and 2019); and the microfilaremia prevalence decreased from 5.3% to 0.3% between 2012 and 2015. No microfilaremic subject was found in 2019, six months after the 14th ALB MDA. In the DRC site, the initial (2014) prevalence rates of antigenemia and microfilaremia were higher (31.6% and 12.0%, respectively) than in Seke Pembe. In 2018, six months after the 8th round of MDA, these values were lowered to 8.5% and 0.9%, respectively.
Regarding STH, the prevalence of A. lumbricoides in Seke Pembe decreased from 56.5% in 2012 to 12.9% in 2015 and 13.6% in 2019; in this setting, the prevalence of T. trichiura decreased from 78.6%, 59.4% and 42.9%, respectively, at the same time points. The initial prevalence of hookworm infection was low (6.5%) and no hookworm egg was detected in 2014 and 2015. In the DRC site, hookworm, A. lumbricoides and T. trichiura infection prevalence rates decreased from 58.6% to 21.2%, from 14.0% to 1.6% and from 4.1% to 2.9%, respectively, between 2014 and 2018. In both study sites, the decrease in the intensities of infection (eggs per gram of stool) also decreased significantly.
The data collected during the DOLF study were also used to demonstrate the interest to read CFA detecting tests semi-quantitatively (either visually or by a spectrodensitometer), that there is a familial aggregation and heritability of W. bancrofti infection, that age, sex, and occupation-dependent exposure to mosquitoes are important risk factors for infection with W. bancrofti, that clearance of W. bancrofti and STH infections after repeated rounds of MDA with ALB is closely related to individual adherence, and that infection with W. bancrofti or hookworm had no significant effect on pregnancy course and pregnancy outcome in women. Other ancillary studies are ongoing.
The DOLF project, led by Prof. Gary Weil (Washington University School of Medicine, St. Louis, Missouri, USA), is a collaborative multi-country research project including many teams (https://dolfproject.wustl.edu/). The community trials with ALB alone involved the TransVIHMI Research Unit, the Ministry of Health and Population of the Republic of Congo, the Ministry of Health of the DRC, and the Institut National de Recherche Biomédicale (INRB) in Kinshasa (DRC).