238 Update TRENDS in Parasitology Vol.23 No.6

References1 Geary, T.G. (2005) Ivermectin 20 years on: maturation of a wonder

drug. Trends Parasitol. 21, 530–5322 Boussinesq, M. et al. (2006) What are the mechanisms associated

with post-ivermectin serious adverse events? Trends Parasitol. 22,244–246

Corresponding author: Parkinson, M. (michael.parkinson@dcu.ie).Available online 11 April 2007.

www.sciencedirect.com

3 Mackenzie, C.D. et al. (2003) Possible pathogenic pathways in theadverse clinical events seen following administration of ivermectinto onchocerciasis patients. Filaria J. 2, S5

1471-4922/$ – see front matter � 2007 Elsevier Ltd. All rights reserved.

doi:10.1016/j.pt.2007.04.007

Controlling fasciolosis in the Bolivian Altiplano

Michael Parkinson1, Sandra M. O’Neill2 and John P. Dalton3

1 School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland2 School of Nursing, Dublin City University, Glasnevin, Dublin 9, Ireland3 Institute for the Biotechnology of Infectious Diseases, University of Technology Sydney, Ultimo, Sydney, NSW 2071, Australia

Figure 1. Infection rates of fasciolosis in the Bolivian Altiplano. Infection rate is

Liver fluke disease, or fasciolosis, is a global problem oflivestock and causes losses of US$3 billion annually [1].Recently, it has emerged as a major health problem inmany countries, including Iran, Peru, Cuba, Bolivia andEgypt. Every year an estimated 2.4 million people areinfected worldwide and a further 180 million people areat risk of infection [1]. The highest prevalence of fasciolosisin humans is found in the Altiplano region of northernBolivia [2,3]; this article highlights the need for a controlstrategy in this region. The disease causes serious illhealth with extensive haemorrhaging and inflammationof the liver, and thickening and dilation of the bile ductsand gallbladder.

In the Bolivian Altiplano, the zone of high infection inhumans stretches >30 km along the narrow corridor ofBatallas from Lake Titicaca to La Paz [2] (Figure 1). Theareas with the highest prevalence of fasciolosis in humans(reaching 60%) are also those with high animal (25% cattleand 70% sheep) infection [4,5]. In most regions of the Alti-plano, animal pasturing is free and this leads to infectedanimals contaminating pastures andwater sources that areused by humans. Fluke eggs released by infected mammalshatch and then formmiracidia, which invade the snail hostand subsequently develop to erupt as free-swimming cer-cariae. These cercariae settle and encyst on vegetation orremain on the water surface to form metacercaria that areinfectious to mammals when ingested.

The Altiplano consists of poor rural communities ofsubsistence farmers who rely on the land and their live-stock to survive and have somewhat primitive farm-man-agement practices, which are unlikely to change inthe near future. Although the use of molluscicides andthe elimination of snail habitats have been successful insome trematode control programs, such as the control ofschistosomiasis in China [6], they would be too costly,labour intensive and logistically difficult to use in theBolivian Altiplano, where precipitation is high and snailslive over a broad area. A fasciolosis-control programmemust, therefore, focus on flukicide drug treatment andeducation.

Infection is highly age related, with the highestprevalence in children between eight and eleven yearsold [2,4]. Children of this age commonly work in the fieldsminding livestock and are more likely than adults toacquire infection through habitually eating aquatic plantsand by drinking water from sources that are contaminatedwith metacercariae [1,4]. Accordingly, drug treatmentshould be particularly focused towards children inhigh-risk areas (local schools being a focal point). Thiscould be effective alongside a health-education programmethat delivers the correct message on how fasciolosis isspread from animal to human and that links the diseaseand the resulting illness [7]. Treatment with the flukicidetriclabendazole is the most effective means for clearingliver fluke infection in cattle, sheep and humans (althoughit is not yet registered for human use in Bolivia) [4]. Se-lective chemotherapy of humans with triclabendazole overa four-year period has been effective in reducing the preva-lence of fasciolosis in humans in the Nile delta, Egypt [8].With the support from government and local health

related to the size of the circle: black circles indicate an infection rate of 10–61.5%

and red circles indicate an infection rate of <10%. Green shading indicates level

areas of the Altiplano and brown shading indicates elevated regions. Scale

bar = 10 km.

Update TRENDS in Parasitology Vol.23 No.6 239

centres, a similar strategy of annual screening and se-lective treatment of infected individuals (and also concur-rent mass animal treatment) should have a major impacton disease prevalence in the Bolivian Altiplano. Becausetriclabendazole is the only safe drug for humans, animalscould be treated with another (e.g. clorsulon) to avoid thedevelopment of drug resistance that has appeared inEurope and elsewhere.

Although new drugs and combinations of old drugs arebeing developed [9], a commercially available vaccine forfasciolosis in animals would offer a better way to controlinfection, although realistically this is still five to ten yearsaway [10]. A recent European Union-funded DeLiverproject (http://www.deliver-project.eu) is performing vac-cine trials in sheep, cattle and goats in Europe, SouthAmerica and Australia with recombinant Fasciola hepa-tica molecules such as cysteine proteases, fatty acid bind-ing protein and peroxiredoxin. Previous trials have shownsignificant protection rates in livestock with thesevaccines, with an additional transmission-blocking benefitbecause viable eggs released from vaccinated animals arereduced by 50–97% [10].

For the future long-term control of fasciolosis in humansin the Bolivian Altiplano, separation of animals fromvegetation and water sources that are used by humansplus the provision of water pumps to supply uncontami-nated drinking water would be sufficient.

Corresponding author: Horn, D. (david.horn@lshtm.ac.uk).Available online 11 April 2007.

www.sciencedirect.com

References1 Mas-Coma, S. et al. (2005) Fascioliasis and other plant-borne

trematode zoonoses. Int. J. Parasitol. 35, 1255–12782 Parkinson, M. et al. (2006) Endemic human fasciolosis in the Bolivian

Altiplano. Epidemiol. Infect. 26, 1–63 Bjorland, J. et al. (1995) An outbreak of acute fascioliasis amongAymara

Indians in the Bolivian Altiplano. Clin. Infect. Dis. 21, 1228–12334 WHO (2007) Report of the WHO informal meeting on use of

triclabendazole in fascioliasis control, World Health Organization(http://www.who.int/neglected_diseases/preventive_chemotherapy/WHO_CDS_NTD_PCT_2007.1.pdf)

5 Buchon, P. et al. (1997) Fascioliasis in cattle in the human highendemic region of the Bolivian northern Altiplano. Research andReviews in Parasitology 57, 71–83

6 Xianyi, C. et al. (2005) Schistosomiasis control in China: the impact of a10-year World Bank loan project (1992–2001). Bull. World HealthOrgan. 83, 43–48

7 MacPherson, C.N. (2005) Human behaviour and the epidemiology ofparasitic zoonoses. Int. J. Parasitol. 35, 1–13

8 Curtale, F. et al. (2005) Control of human fascioliasis by selectivechemotherapy: design, cost and effect of the first public health,school-based intervention implemented in endemic areas of the Niledelta, Egypt. Trans. R. Soc. Trop. Med. Hyg. 99, 599–609

9 Harder, A. (2002) Chemotherapeutic approaches to trematodes (exceptschistosomes) and cestodes: current level of knowledge and outlook.Parasitol. Res. 88, 587–590

10 McManus, D.P. and Dalton, J.P. (2007) Vaccines against the zoonotictrematodes Schistosoma japonicum, Fasciola hepatica and Fasciolagigantica. Parasitology 133, S543–S561

1471-4922/$ – see front matter � 2007 Elsevier Ltd. All rights reserved.

doi:10.1016/j.pt.2007.04.002

Research Focus

Introducing histone modification in trypanosomes

David Horn

London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK

Nuclear DNA is wrapped around histones. Vigorousresearch over the past decade has established a centralrole for histone post-translational modification in con-trolling the DNA–protein interactions that are requiredfor successful growth and propagation. Recent worknow provides a description of acetylated and methylatedresidues in the divergent trypanosome core histones.Future studies should provide insights into the genomicdistribution of each modification and their roles ingrowth and pathogenesis.

Histone modificationEukaryotic nuclearDNA iswound around core nucleosomalhistone octamers, which contain two copies of each histone:H2A, H2B, H3 and H4. Histones are conserved, abundant,small, basic proteins and the chromatin complex is thenatural substrate for all the regulatory factors that interactwith nuclear DNA. Over the past decade, a huge volumeof research has established a central role for covalent

post-translational modification (PTM) of core histones inmodulating these interactions. In particular, acetylation(Ac) on e-amino groups of lysine (K) and methylation (Me)of lysine or arginine (R) have a conserved role in regulatinggeneexpressionat the level of transcription initiationand/orelongation. Addition of such small chemical groups alsoregulates DNA replication, recombination and repair. Intrypanosomatids, packaging in chromatin enables 20 cm ofDNA to reside in a 2 mm diameter nucleus. Trypanosoma-tids branched from the eukaryotic lineage early; therefore,progress in studying PTM in trypanosomatids has beendelayed because the epitopes that are recognized by thepanels of PTM-specific antibodies that are available forother eukaryotes are not present [1]. This means thattrypanosome PTM must be characterized de novo. Thisarticle focuses on two recent publications that report suchcharacterization in Trypanosoma brucei [2] and Trypano-soma cruzi [3], although the discussion is also relevant toother trypanosomatids.

Most histone PTMs generate binding platforms forregulatory factors [4] and at least one (H4-K16-Ac, i.e.histone H4 with an acetylation of the lysine at posi-tion 16) alters higher-order chromatin compaction [5].