Parasitological, Hematological and Biochemical Characteristics of a Model of Hyper-microfilariaemic Loiasis (Loa loa) in the Baboon (Papio anubis)

Abstract

BackgroundLoiasis, a filarial infection caused by Loa loa usually thought to cause relatively minor morbidity, can cause serious and often fatal reactions in patients carrying very high levels of circulating Loa loa microfilariae (mf) following administration of microfilaricidal drugs. An experimental model of this condition would greatly aid the definition of the optimal management of this important clinical presentation.Methodology/Principle FindingsFifteen baboons (Papio anubis) were infected with 600 infective larvae (L3) isolated from Chrysops vector flies. Animals were observed for any clinical changes; blood samples were collected every 1–2 months for 22 months, and analysed for parasitological, hematological and biochemical profiles using standard techniques. All animals became patent but remained clinically normal throughout the study. The parasitological pre-patent period was between 4–8 months, with a majority (60%) of animals becoming patent by 5 months post infection (MPI); all animals were patent by 8 MPI. Microfilarial loads increased steadily in all animals and reached a peak at 18 MPI. By 10 MPI >70% of animals had mf >8,000 mf/mL, and at 18 MPI >70% of animals had mf >30,000mf/mL with 50% of these animals with mf >50,000mf/mL. Absolute eosinophil, creatinine, Ca2+ and K+ levels were generally above normal values (NV). Positive associations were seen between microfilariaemia and eosinophilia, Hb, Ca2+, and gamma-GT values, whilst significant negative associations were seen between microfilariaemia and potassium, glucose and mononuclear leukocyte levels.ConclusionsInfection of splenectomised baboons with L. loa can induce levels of circulating microfilariae, and corresponding haematological profiles, which parallel those seen in those humans in danger of the severe post-microfilariacide clinical responses. Utilization of this experimental model could contribute to the improved management of the loiasis related adverse responses in humans.

The Population Biology and Transmission Dynamics of Loa loa

“…Such variability in infection intensities has also been observed in more recent work, where a number of baboons, all infected with 600 L3 larvae, displayed as much as a 50-fold difference in their resulting microfilarial loads [29] (such a phenomenon is similar to that observed for Ascaris suum in experimentally and naturally infected pigs [30]). There is, however, some positive correlation between the number of worms harboured and the resulting concentration of microfilariae in the blood, with other research also involving experimental infection of primates demonstrating that, whilst monkeys inoculated with 200 L3 larvae had, on average, higher concentrations of microfilariae than those inoculated with 75 L3 larvae, there was significant overlap between infection intensities observed across the two groups [25].…”

Potential Role for Flubendazole in Limiting Filariasis Transmission: Observations of Microfilarial Sensitivity

“…Loa loa. Microfilaremic blood was acquired from experimentally infected baboons 24 using animal procedures in accordance with animal care and use protocols at the National Institutes of Health (USA). Ethical approval for the use of baboons in this study was obtained from the Ministry of Scientific Research and Innovation of Cameroon.…”

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial load reduction, haematological and biochemical parameters and histopathological changes following treatment

“…The acquisition, care and ethical concerns on the use of these animals have already been described in the preceding paper [ 22 ]. The animals for this study were gotten from the 15 baboons that had been characterised parasitologically, biochemically and haematologically in the preceding paper [ 22 ].…”

“…The biochemical parameters were quantified using spectrophotometric kits obtained from HUMAN ( www.human.de , Germany) as per the manufacturer’s instructions. The parasitological, haematological and biochemical analyses were performed on the pre- and post-treatment samples as described previously in Wanji et al ., [ 22 ].…”

“…loa infected people as the parasite in this animal behaves essentially in the same way as it does in the drill. The use of baboons in biomedical research is accepted by the International Union for Conservation of Nature (IUCN) [ 21 ] and so Wanji et al developed a hyper-microfilaraemic Loa /baboon ( Papio anubis ) experimental model and characterized it parasitologically, haematologically and biochemically [ 22 ]. In this model microfilariaemia increases steadily in all infected animals and reaches a peak at 18 months post infection (MPI); by 10 MPI >70% of animals have mf > 8,000 mf/mL, at 18 MPI >70% of animals have mf >30,000mf/mL and 50% of animals have mf >50,000mf/mL.…”