Innovative tools for assessing risks for severe adverse events in areas of overlapping Loa loa and other filarial distributions: the application of micro-stratification mapping

Abstract

BackgroundThe wide distribution of Loa loa infection (loiasis) throughout the Democratic Republic of Congo (DRC) is a major obstacle to the plans to eliminate onchocerciasis and lymphatic filariasis (LF) because the standard drug regime is dependent on ivermectin, which cannot be used in co-endemic areas due to the risk of severe adverse events (SAEs). A better understanding of the micro-epidemiology, overlapping low and high risk areas, and how they relate to SAEs is critical to ensure safe and effective treatment.FindingsBased on published data from the Bas Congo Province in DRC, this study used geographical information systems (GIS) to re-map and analyse onchocerciasis and loiasis prevalence (<20%, 20 to 40%, >40%) at 144 sites in relation to health district areas reporting SAEs. The new maps highlighted the contrasting patterns of the high prevalence sites, and significant geographical overlap between low onchocerciasis and high loiasis sites. Statistical analyses found that sites with medium to high loiasis prevalence were 10 to 16 times more likely to be in a SAE area than those with low prevalence of loiasis. Sites where both onchocerciasis and loiasis prevalence was >20% were also associated with SAE areas.ConclusionsCollaborative efforts between the national onchocerciasis and LF programmes are critical as plans to scale interventions are moving forward and thus, alternative strategies needed in loiasis co-endemic areas which may include the new L. loa test and treat strategy using the Cellscope, or interventions such as integrated vector management, or anti Wolbachia therapy using doxycycline.

The genome of Onchocerca volvulus, agent of river blindness

“…Furthermore, the presence of purine-nucleoside phosphorylase (EC 2.4.2.1)—enabling the conversions of guanine and adenine to deoxyguanosine and deoxyadenosine, respectively—ensures O. volvulus is robust to the deletion of ribonucleoside-diphosphate reductase (EC 1.17.4.1). Given the strikingly different pathways involved in the production of purines for the two species, any reliance by O. volvulus on this alternative pathway could be exploited to selectively target O. volvulus 7 , a credible prospect because inhibitors of purine-nucleoside phosphorylase already exist 38 .…”

“…Ivermectin is solely microfilaricidal, which means it must be given over decades, past the lifespan of the long-lived adult worms 5,6 . Moreover, in much of Central Africa where Loa loa is co-endemic with O. volvulus , ivermectin cannot be used due to the risk of Loa -associated irreversible neurological severe adverse events and death 7 . Despite its success in Latin America and small foci in Africa, elimination of onchocerciasis in Africa is unlikely to be achieved within the proposed timeframes solely through MDA with ivermectin 8 .…”

The Population Biology and Transmission Dynamics of Loa loa

“…Given the often high levels of co[ 2 8 8 _ T D $ D I F F ] -infection with onchocerciasis that exist in populations [79,90], the significant number of people with onchocerciasis who have already received ivermectin, and the commitment to ensure those still infected with O. volvulus receive the necessary treatment [91], it is likely that many individuals currently infected with L. loa will receive, or have already received, ivermectin. Is there a subset of the human population who is genuinely amicrofilaraemic, or is this observation due to the limited sensitivity of the currently available microscopy-based diagnostics?…”

Multidimensional complexities of filariasis control in an era of large-scale mass drug administration programmes: a can of worms

“…Recent studies on SAEs in Bas Congo, DRC [ 48 ], have shown that the events are associated with areas considered to be at lower risk with a RAPLOA prevalence of between 20-40%, but were found to be 10–16 times higher than elsewhere. This implies that the RAPLOA estimated prevalence is not necessarily the primary indicator of SAE risk, but rather the intensity of infection in individuals when they have high parasitaemias of L. loa (≥30,000 mf/ml) [ 49 ].…”