Janice Taverne

MVI and GlaxoSmithKline

The worlds largest vaccine manufacturer, GlaxoSmithKline, has received US

Tanzania phases out chloroquine for the treatment of malaria

6.7 million from the Malaria Vaccine Initiative (MVI) to accelerate the development and clinical testing of a malaria vaccine that could save the lives of millions of children in Africa. The RTS,S vaccine against Plasmodium falciparum is circumsporozoite-based and comprises recombinant protein antigens combined with hepatitis B-surface antigen and an adjuvant; it showed promise in a small trial conducted by the Walter Reed Army Institute of Research on army volunteers. In a field trial with adult men in The Gambia, sponsored by the European Commission and the WHO, 65% were protected for a short time. [For details about the vaccine see Kester, K.E. et al. (2001) J. Infect. Dis. 183, 640–647; for details of the partnership, see http://www.malariavaccine.org]. JT

Trypanosomes on the Web

The Tanzanian Health Ministry plans to use sulfadoxine pyrimethamine (brand names include Falcidin, Fansidar, Laridox, Malostat, Orodar and Metakelfinl) instead of chloroquine by August 2001, because of the spread of chloroquine resistance. A spokesman for the ministry said that the percentage of malaria parasites resistant to chloroquine in Tanzania rose from 5% in 1960 to 52% in 1990. The WHO recommends a change of drug when resistance reaches 25%. Tanzania is the second country in Africa to announce that it is abandoning the use of chloroquine, Kenya having decided to do so two years ago. (source: ProMED-mail). JT

Anopheles gambiae genome

Hugely confused exchanges took place in July, again on ProMED, following news that ‘Ten Royal Bengal tigers died at an Indian zoo and more are struggling for life in a case baffling veterinarians.’ The Nandankanan Zoo, in Bhubaneshwar, capital of Orissa state, has Indias largest collection of Royal Bengal tigers and the worlds largest collection of white tigers. (There are fewer than 200 white tigers left in the world and only about 5000–7000 wild tigers.) Another press report said the tigers had contracted sleeping sickness and were being given antibiotics. Necropsies indicated that ‘they had all died of the same disease, despite the antibiotics.’ Then the speculation began. Which trypanosome? and how was it transmitted?One contributor asked was it Trypanosoma evansi, T. vivax, T. cruzi or T. equiperdum? T. vivax infects mainly ruminants. T. evansi infects camels in Africa, but a wider range of hosts in Asia, e.g. water buffaloes, pigs, cattle, sheep and goats. T. equiperdum affects only equines and is sexually transmitted. ‘If the parasite can be isolated and grown there are nowadays enough methods which distinguish the different species.’ There are no tsetse in India. (See D.J. Rogers and S.E. Randolph, Distribution of tsetse and ticks in Africa, past, present and future. Parasitol. Today 9, 266–271, 1993; G. Hendrickx et al., The spatial pattern of trypanosomosis prevalence predicted with the aid of satellite imagery. Parasitology 120, 121–134, 2000.) The ProMED moderator suggested three possible methods of transmission: if Asian – through the bite of a blood-sucking fly carrying a parasite from a local host reservoir; if African or American – through a fly infected by an exotic host species in the zoo; or by dirty needles already used on the infected exotic animal.Simon Reid, a vet from Murdoch University, Western Australia, thought it likely to be T. evansi, endemic in India and transmitted by tabanid biting flies. Perhaps the tigers were infected by tabanids that had been feeding on infected ruminants housed nearby. But oral transmission is thought to be the main route of infection for carnivores (C.A. Hoare, The Trypanosomes of Mammals. A Zoological Monograph. Blackwell Scientific). More likely, the tigers were infected by eating freshly killed meat from a ruminant infected with T. evansi and ‘treatment of ALL remaining animals with a curative trypanocidal drug should be effective at halting this outbreak. Cymelarsan is effective at a dose rate between 0.75–1 mg kg−1 and should be safe to use in tigers.’

Flying through the Web

A project to sequence the 260 million base pairs of Anopheles gambiae, the most important insect vector of the malaria parasite in sub-Saharan Africa, was recently agreed by an international network of researchers at a meeting at the Institut Pasteur, France. The first version of the genome, which will be freely available on public databases, should be ready by the end of 2001 and should cost less than US

Swan-song – ‘after many a summer dies the swan’: ParaSite - the final one

10 million. The initial work, to be carried out by Celera Genomics and Genoscope (the French National Sequencing Centre), will use the ‘Whole Genome Shotgun’ technique. Sequence closure and finishing will be performed by Genoscope, the Institute for Genomic Research, the European Bioinformatics Institute and other groups from France, Greece, Germany, UK and the USA. The French Government will provide funds for part of the project, and other sources of finance, including the European Union and USA agencies, are being approached. It is hoped that this collaboration will eventually cover other Anopheles spp. JT

Itchy mosquitoes on the Net

Bruno Gottstein and Heinz Sager (Berne University, Switzerland) reported to ProMED-mail in February that while monitoring foxes from Basel for the prevalence of Echinococcus multilocularis, a fox that had been shot in December 2000 was found carrying the lungworm Angiostrongylus vasorum, a helminth rarely found in Switzerland, except in dogs that had come from endemic areas in other parts of Europe. They later found another infected fox from the same place, so were asking vets to look out for the nematode in the local dog population and to inform them of cases. Hugh Whitney (Newfoundland Department of Forest Resources & Agrifoods, Canada) said that the only known North American focus of the nematode is Newfoundland, where it is present in red foxes and dogs, is commonly known as French Heartworm and its intermediate host is a slug or a snail.

Travelling mosquitoes on the Net

Unlike the mosquito set, this list is thoroughly international and is not dominated by people from the USA; indeed, malaria has received much publicity worldwide since the inception of ParaSite, not only because the genome of Plasmodium falciparum and of its vector have now been sequenced. Inevitably, information about different drugs was requested here, by lay people and by experts, and especially on artemisinin derivatives. Why should they not be used for prophylaxis, argued one maverick: if you are a traveler, ignore all prophylaxis and ‘Take an Artenam treatment when you get back home’, thus avoiding possible side effects of other drugs and discouraging the development of resistance – a suggestion frowned upon by the authorities. For treatment, many were enthusiastic about combinations of artemisinin with other drugs, chiefly ‘art-lap-dap’ (artemisinin derivative plus chlorproguanil–dapsone). Drug resistance is a continuing worry and the mechanisms involved in the development of chloroquine resistance in particular were discussed at some length. As for vaccines, Patarroyos was controversial, the effectiveness of irradiated sporozoites was mentioned and the pros and cons – and ethics – of transmission-blocking vaccines were mulled over. Not surprisingly, the subject of bednets came up time and time again. However, the longest running battle was about the proposal that DDT should be banned worldwide: this ended in May 1999, with an open letter to the DDT treaty diplomats, signed by an overwhelming number of malariologists who opposed the plan.Finally, which subjects can be guaranteed to stimulate parasitologists to take to their computers? Apart from drink (in the form of tonic water, its quinine content and effectiveness against malaria) and sex (malaria is more prevalent in males than in females, and the same is true for the related genus Leucocytozoon in birds), the other issues have been words, their precise meaning and derivation, evolution and history. Thus, the proper usage of the words clone, isolate and ‘strain’ has often arisen, the evolution of trypanosomes and of the Plasmodium spp., the cladistics of mosquito families and the many millions of years since Caenorhabditis elegans diverged from Heterodera glycines (soya bean cyst nematode) have been argued over. Our interest in human history has extended from discussion of malaria therapy for syphilis in 1922, Ronald Ross and his sparrows in 1897, coping with mosquitoes in the New World in the 1800s, the first description of a Phlebotomine sandfly in 1691, right back to the impact of malaria in ancient Greece and Rome, the earliest description of the use of qing hao in 168BC and evidence that Egyptian mummies suffered from malaria.

Circadian rhythms and screwworm on the Net

The proposal that a recent increase in the number of cases of leishmaniasis in Colombia can be explained by large numbers of combatants (two main guerrilla groups plus right-wing paramilitaries and the Colombian armed forces) now spending more time in the forest at night is flawed, said Bruce Alexander (Fiocruz University, Belo Horizonte, Brazil). The conflict has lasted >40 years and guerrillas and paramilitaries do not normally seek treatment in places where they would appear on official records. Anyway, reports of 5000–6000 cases a year are probably a considerable underestimate. An increase in urban areas could be a result of displaced people from rural areas seeking treatment in cities for existing infections, yet urbanization of several vector species has happened in Brazil and could have happened in Colombia. Control measures are hampered if the view prevails that all transmission takes place within forests. Phlebotomine sandflies (Lutzomyia spp. are the main vector) readily enter houses, particularly those surrounded by coffee plantations, and preventive measures are possible. Philippe Desjeux (WHO, Geneva, Switzerland) warmly supported Alexander: although deforestation was supposed to reduce the incidence of cutaneous leishmaniasis in several countries in South America, it has in fact led to a domestication of transmission. Plantation of new crops close to houses and the presence of rodents attracted by this source of food have created a major risk of transmission in and around houses, an increase in the number of cases, a wider age distribution and more frequent infections within families. It has, however, made vector control easier.

Eaten alive on the Net

Malaria discussion group (http://www.wehi.edu.au/)How numbers should be collectedLisa Ranford Cartwright (University of Glasgow, UK) was giving a lecture and wanted to know the number of cases of Plasmodium vivax, Plasmodium ovale and Plasmodium malariae reported annually, ‘a paper/website/publication that makes some sort of estimate’ would do. WHO was a possible, she was told, but Patricia Graves warned her that incidences fluctuate: ‘For example, Indias big epidemic in the 70s was predominantly P. vivax, with a ratio of about 1 Pf to 10 Pv. Now it is about 1:1…in Solomon Islands, the ratio of Pf:Pv in 1999 varied by province from 1.2:1 to 4.3:1, [in] 1996 it varied from 0.5:1 to 2.6:1, with Pv predominant in half the provinces’. Over the same period, the overall annual incidence of malaria in the Solomon Islands fell from 207 to 144 per 1000. Because of these fluctuations, she is ‘conducting a one-person campaign’ for the incidence of Plasmodium falciparum and P. vivax cases to be reported per 1000 rather than as a percentage of P. falciparum, which is commonly done but misleading.‘Behold I show you a mystery’ – Nosocomial malaria in the UKIn January 2002, when a man in hospital for an orthopaedic procedure developed P. falciparum malaria, it was deemed a hospital-acquired infection because he had no known relevant risk factors (ProMED-mail). No parasites were seen in blood films and no antibodies were detected in samples from staff and patients who were examined to see how the infection could have been transmitted, although one health care worker who had left had yet to be contacted. (Semi-immune people who are asymptomatic may not have parasitaemia but would have high levels of anti-parasite antibody.) When the moderator speculated that it might be a case of ‘airport malaria’ or, perhaps, of transmission through blood transfusion, Michael Lilley, Specialist Registrar in Public Health Medicine for the UK region concerned, stated that the man had been in hospital for about five weeks before he developed malaria and had not received a blood transfusion. Experts had told him that there were no mosquitoes capable of transmitting the parasite in that county; however, one patient being treated for malaria had been discharged 48 hours before the new case had been admitted. Neil Cameron (University of Stellenbosch, South Africa) said airport malaria is not so confined: ‘In South Africa we get “taxi” malaria…many hours drive from a malarious area. And malaria mosquitoes have been packed into travellers’ suitcases and lived to tell the tale.’ Perhaps a traveller, whether a doctor, visitor or patient, had brought in an infected mosquito from an airport? Tuan-Gee Yap (PTU Health Project Medical Centre, Hong Kong) said transmission via improperly sterilized instruments had not been mentioned: ‘experts should be able to tell us how long the falciparum parasite can survive’. A hospital in Taiwan had a disastrous outbreak of nosocomial falciparum malaria seven to eight years ago, when about ‘ten patients contracted it with fairly high mortality…infected via a short plastic tubing that was part of a contraption to facilitate delivery of intravenous injections during magnetic resonance imaging.’ (For a report of UK infections, see Eurosurveillance Weekly at http://www.eurosurv.org/)History of efforts to control malariaAre there websites that focus on this topic? Derek Willis (Harvard University, USA) was particularly interested in ‘colonial efforts’, especially in Mombasa in Kenya and in Malaysia. He was also interested in good books covering the period before 1955, but did not explain why only those places or why that date. Titles of books were e-mailed to him, but nobody mentioned specific websites. (However, there is a long list of references to overall strategies related to the control of malaria at http://www.anopheles.com/programmaticref.html.)Ted Nye (University of Otago, New Zealand) recommended The Prevention of Malaria by Ronald Ross (Murray, 1910). ‘In fact it goes a long way further back, well before the mosquito/malaria connection was known. Thus Alphonse Laveran was writing on the subject in Maladies et Epidemies des Armees Masson 1875, even before he had discovered the parasite in 1880. Pringle was also writing in the 18thC.’ (One might add that is all quite a long time before 1955 too!) Babatunde Fakunle (Shell IA Hospital, Port Harcourt, Nigeria) thought that all the ‘historical information you need’ is covered by Mosquitoes, Malaria and Man: A History of the Hostilities Since 1880 by Gordon Harrison (1978, E.P. Dutton). Robert Desowitz recommended the report of a Rockefeller Foundation Conference – Dealing with malaria in the last 60 years: aims, methods and results [(2000) Parassitologia 42, 3–182]. This report contains many interesting papers for those of a historical bent, for example: Malaria in inter-war British India by W.S. Bynum; US Army and malaria control in World War II by C.W. Hays; Quinine (Cinchona); and the incurable malaria: India in 1900–1930s by V.R. Muraleedharan, which gives an idea of the amount of quinine required for the whole country and how much it would have cost. There are even two papers especially for Willis: The malaria cauldron of Southeast Asia; conflicting strategies of contiguous nation states by C. Kidson et al., and Malaria control in East Africa: the Kampala conference and the Pare-Taveta scheme: a meeting of common and high ground by M.J. Dobson et al. This last paper tells of the fierce argument that took place in 1950 about whether or not to try and control mosquitoes by spraying DDT because there were concerns that intervention in areas of high transmission might lead to loss of naturally acquired immunity, which would be followed by an enormous resurgence of malaria if the control strategies failed. The final paper The malaria vaccine: seventy years of the great immune hope by R.S. Desowitz himself, is a nice history of exactly what its title says.ParaSite was compiled from the Internet by Janice Taverne (janice.taverne@lineone.net)