- Email: [email protected]
Recent advances in tropical medicine
Transactions of the Royal Society of Tropical Medicine and Hygiene (2009) 103, 647—652
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/trst
REVIEW
Recent advances in tropical medicine夽 Anthony W. Solomon, Shevanthi Nayagam, Geoffrey Pasvol ∗ Department of Infection and Tropical Medicine, Imperial College London, Lister Unit, Northwick Park Hospital, Harrow HA1 3UJ, UK Received 27 November 2008; received in revised form 19 January 2009; accepted 20 January 2009 Available online 23 February 2009
KEYWORDS Tropical medicine; Resistance; Malaria; HIV/AIDS; Tuberculosis; Communicable diseases, emerging
Summary There have been significant advances in both the classical and neglected tropical diseases, with Guinea worm looking set to be the next disease after smallpox to be eradicated. Aided by a combination of enhanced understanding of the biology of the pathogens, intensification of immunisation activities or mass drug administration, together with the development of synergies with control programmes for co-endemic tropical diseases, polio, lymphatic filariasis, trachoma and onchocerciasis all appear to be in global decline, with good prospects for eventual successful elimination. While the global incidence of new cases of leprosy continues to decrease, the focus of leprosy control efforts has shifted following more widespread recognition that cure of infection does not necessarily prevent disability. Expansion in funding for HIV/AIDS and malaria provides some grounds for optimism about the control of these diseases. However, ongoing education and access remain essential to increasing the uptake of HIV testing and decreasing transmission. Meanwhile, the rise of drug-resistant tuberculosis and malaria is concerning, and the emergence of the highly pathogenic avian influenza A and re-emergence of viruses such as chikungunya and West Nile virus, without significant recent progress in vaccine development, pose additional ongoing challenges to tropical medicine physicians worldwide. © 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
1. Malaria 1.1. Drug resistance 夽
A previous version of this paper was published (prior to peer review) in the journal Medicine [Solomon A, Nayagam S, Pasvol G. What’s new in tropical medicine. Medicine 2009;1:51—4]. It is published here with permission of the publisher of both journals, Elsevier, and with the agreement of the editors of Medicine and Transactions of the Royal Society of Tropical Medicine and Hygiene. ∗ Corresponding author. Tel.: +44 (0)20 8869 2831; fax: +44 (0)20 8869 2836. E-mail address: [email protected] (G. Pasvol).
Clinical resistance has arisen to all classes of antimalarials used to date, barring the artemisinin derivatives. Chloroquine resistance is now virtually universal in Plasmodium falciparum and the efficacy of sulfadoxine-pyrimethamine (Fansidar) has become increasingly compromised. Monotherapy and widespread, indiscriminate use of antimalarials have encouraged the selection of drug-resistant strains. Encouragingly, chloroquine-sensitive P. falciparum has reemerged in Malawi 13 years after chloroquine was
0035-9203/$ — see front matter © 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.trstmh.2009.01.018
648
A.W. Solomon et al.
abandoned, but the clinical application of this observation has yet to be realised.1 Whether the complete eradication of malaria is a realistic goal remains to be seen.2
release by peripheral blood T-cells) in formats that can be practically and economically deployed in resource-poor settings.9,10
1.2. Antimalarial combinations
2.2. Control
To maximise the effectiveness of treatment and to delay the development of resistance to newer drugs, treatment with combinations of antimalarial drugs is now recommended.3 Artemisinin derivatives rapidly clear malaria parasites from the blood and combinations including these drugs (e.g. artesunate with amodiaquine or mefloquine, and artemether with lumefantrine) have been strongly endorsed by WHO since 2001.4 Non-artemisinin-containing combinations (e.g. sulfadoxine-pyrimethamine with amodiaquine) are advised only if artemisinin-based combination therapy (ACT) is unavailable or unaffordable. Affordability remains an issue, as ACTs are nearly 10 times as expensive as previous first-line choices. Despite this, since 2001, 41 of 54 African countries in which malaria is endemic have changed their malaria treatment protocols to make ACTs first-line. The impact of these changes on morbidity and mortality has yet to be documented. Whilst data exist to support the preferential use of artesunate over quinine for the initial treatment of severe malaria in adults, the results of an equivalence study in African children are awaited.5
After increasing through the 1990s and early 2000s as a result of the HIV pandemic and the break-up of the Soviet Union, amongst other factors, the per capita global incidence of TB now appears to be in decline. In 2005 there were an estimated 8.8 million new cases and 1.6 million deaths.11 In 2006 the WHO launched the Stop Tuberculosis Strategy, a six-point plan aiming to reduce TB prevalence and mortality to less than 50% of 1990 levels by 2015.12 It is currently too early to assess the global impact of this strategy, but pilot studies in Thailand suggest that it may enhance case-finding (including in the private sector) and help patients diagnosed with TB engage with HIV services.13
1.3. Control An international commitment to halve the burden of malaria by 2015 has been supported by considerable increases in funding for malaria control. Recent analysis, however, suggests that for the 1.4 billion people exposed to stable P. falciparum malaria risk there is an annual budget of US$1 billion dedicated for control — less than US$1 per person at risk per year.6
2.3. MDR- and XDR-TB Multidrug-resistant TB (MDR-TB) is caused by Mycobacterium tuberculosis resistant to both rifampicin and isoniazid; extensively drug-resistant TB (XDR-TB) is resistant to isoniazid, rifampicin and fluoroquinolones and either aminoglycosides or capreomycin or both. Such strains have emerged because of inadequate treatment regimens and poor compliance, and pose a serious threat to TB control worldwide. WHO estimates that in 2004, 4.3% of all cases of TB were due to MDR-TB.14 XDR-TB has now been identified in more than 40 countries. Relatively few laboratories are able to test the susceptibility of M. tuberculosis isolates to second-line drugs, so population-based data are generally lacking. Improved diagnostic facilities and expanded access to second- and third-line drugs are needed, since XDR-TB is associated with extremely high mortality.15
1.4. Knowlesi malaria Malaria in humans due to a fifth malarial species, P. knowlesi, has now been well documented in Malaysian Borneo and Peninsular Malaysia. Recent evidence indicates that it may be more widespread even than this. Often misdiagnosed as P. malariae, P. knowlesi is capable of causing severe disease and even death.7,8
2. Tuberculosis 2.1. Diagnosis Owing to the insensitivity of direct microscopy of clinical samples and the widespread unavailability, imperfect sensitivity and long lag-time of mycobacterial culture, the diagnosis of tuberculosis (TB) continues to be based on clinical presentation and the Mantoux test, a semi-quantitative test that has remained essentially unchanged since its development 100 years ago. Both positive and negative Mantoux results must be interpreted with caution. There is an urgent need for the development of improved diagnostic tests (based, for example, on the detection of ␥-interferon
3. HIV/AIDS The annual HIV/AIDS estimates released by UNAIDS suggest that in 2007 there were 33.2 million individuals living with HIV, of whom 15.4 million were women and 2.5 million were children aged less than 15 years.16 The 2007 total global prevalence figure is 16% less than the corresponding estimate for 2006, a decrease that is primarily attributed to improvements in the mathematical models used to calculate the likely prevalence in India and sub-Saharan Africa. Although UNAIDS has been criticised for the way in which it calculates and interprets its estimates,17,18 it is encouraging that current data suggest that prevalence is beginning to plateau. Access to and uptake of HIV testing remain major barriers to control. In sub-Saharan Africa fewer than 10% of those infected with HIV know they are infected.19 The availability of antiretroviral drugs to those in developing countries is also problematic; although treatment coverage was declared a global health emergency in 2003, WHO’s commitment to increase antiretroviral treatment coverage from 300 000 to 3 million people in low- and middle-income countries by
Recent advances in tropical medicine the end of 2005 (the ‘3 by 5’ target) was not fulfilled. By December 2005 approximately 1.3 million people in low- and middle-income countries were receiving antiretrovirals.
4. Emerging and re-emerging diseases 4.1. Avian influenza Highly pathogenic avian influenza A (H5N1) virus emerged in Southeast Asia in late 2003, causing disease in birds and then in humans. By January 2008 there had been 352 human cases in 14 countries, resulting in 219 deaths.20 Most people infected had been in close contact with poultry, but in September 2004 the first reasonably conclusive cases of person-to-person transmission were reported between members of a family living in Thailand.21 The virus is not yet pandemic, mainly because current strains are not efficient at person-to-person spread.22 Vaccines are in development. International guidelines for the pharmacological management of H5N1 were published in January 2007, recommending oseltamivir for treatment of confirmed cases and oseltamivir or zanamivir as chemoprophylaxis in household or close family contacts.23 The quality of direct evidence supporting these recommendations is acknowledged to be low.
4.2. Chikungunya Chikungunya (‘that which bends up’ — referring to the crippling arthralgia that infection may produce) is a disease caused by an alphavirus transmitted by Aedes spp. mosquitoes. The first recorded epidemic was in Tanzania in 1952—3. Severe polyarthralgia, fever and a maculopapular rash are the most prominent clinical features. Treatment is supportive; vaccine trials are in progress. In March 2005 a chikungunya epidemic began on the Indian Ocean island of Reunion. More than 266 000 people were infected, peaking in February 2006.24 The virus spread to India, causing more than 1.3 million cases,25 and from there to Italy, resulting in 205 cases by September 2007.26
4.3. West Nile virus First isolated in Uganda in 1937, West Nile virus is a flavivirus that has long caused sporadic outbreaks of a febrile illness in Africa, the Mediterranean and eastern Europe.27 In humans, West Nile virus may also result in neuroinvasive disease (meningitis, encephalitis or acute flaccid paralysis). The virus emerged in the Americas for the first time in New York City in 1999 and subsequently spread in the USA, causing major declines in several North American bird species and seasonal epidemics in humans. During this outbreak a newly dominant genotype (WN02) emerged that has a significantly shorter incubation period in the vector, culicine mosquitoes.28 From January to November 2007, 3304 cases were reported to the Centers for Disease Control (CDC) from 43 states in the USA; 93 were fatal.29
649
5. Polio In 1988 polio was scheduled for global eradication by the year 2000.30 As a result of intensive international efforts the annual number of cases worldwide declined from an estimated 350 000 in 1998 to 719 in 2000, an encouraging decrease of 99.7%.31 Completing the process of eradication has proved difficult, however. In Nigeria, immunisation activities were suspended in 2003 and 2004 because of rumours that vaccines were adulterated with anti-fertility drugs or HIV.32 This interruption in control efforts has led to outbreaks as far afield as Indonesia, Botswana and Saudi Arabia. Other challenges to the global eradication campaign include political instability, conflict, fatigue in communities and vaccination teams, difficulties in sustaining surveillance in remote and underprovided communities, and an increasing awareness of vaccine-associated paralytic poliomyelitis (VAPP) in 2—4 vaccinees per million.33,34 In January 2008 poliovirus was still considered endemic in four countries (Pakistan, Afghanistan, India and Nigeria), while another five countries had active transmission of imported virus; a total of 1083 cases due to wild virus were confirmed during 2007.31 For the last 7 years the annual number of cases has ranged between 483 (in 2001) and 1997 (in 2006). In response, an integrated global network for molecular surveillance of each wild virus isolate has been constructed to monitor progress, understand local and international transmission pathways, and propose appropriate control strategies. In some conflict areas it has been possible to suspend hostilities to permit national immunisation days to proceed.33
6. Leprosy Unlike polio, for which eradication was set for 2000, leprosy was scheduled for global ‘elimination as a public health problem’ by the same year — defined as the reduction in prevalence to less than one case per 10 000 persons, based on the hypothesis that at this prevalence or lower, transmission would be interrupted. This target raised the profile of leprosy as a disease and galvanised control efforts. Unfortunately, determining leprosy elimination using prevalence as the criterion is problematic; the disease may have an incubation period of up to 20 years and certifying successful elimination, as the WHO did in May 2001, led to reduction in both clinical service provision and funding for leprosy research.35,36 The campaign approach has now been discontinued and the ongoing focus is the timely detection of new cases, early treatment with effective chemotherapy, prevention of disability and provision of rehabilitation. Case detection (rather than prevalence) will be the main indicator used to monitor progress. In 2006, 259 017 new cases of leprosy were registered worldwide, a decrease of 13% compared with 2005, continuing a steady decline that has been sustained during the current decade.37 Only four countries of the 122 that were leprosy-endemic in 1985 had a registered prevalence of leprosy of more than one case per 10 000 population: Brazil, the Democratic Republic of Congo, Mozambique and Nepal.37 The prospects for maintaining progress against leprosy seem good; humans are the main
650
A.W. Solomon et al.
reservoir of infection, free multidrug therapy has been available since 2000 and drug-resistant strains of Mycobacterium leprae have not yet proven problematic.
macrofilaricide44 or chemotherapy targeted against Wolbachia (a bacterial endosymbiont of O. volvulus),45 may be required.46
7. Schistosomiasis
9. Lymphatic filariasis
The Schistosomiasis Control Initiative (SCI) has made considerable progress in the control of this infection in Africa.38 By mid 2008 approximately 40 million treatments had been administered in six countries, reaching over 20 million individuals, although approximately 10 times this number of people are thought to need treatment. In every case praziquantel has been co-administered with the anthelminthic albendazole, but from 2007 onwards the emphasis changed and a ‘rapid impact’ package of up to four drugs is now offered, as appropriate, so that schistosomiasis, intestinal helminths, trachoma, lymphatic filariasis and onchocerciasis can be controlled in an integrated attack on neglected tropical diseases (NTDs). The aim is to bring donated drugs to the poorest populations of subSaharan Africa at an estimated cost of 25 pence per person annually.
Lymphatic filariasis affects more than 120 million people, of whom over 40 million are debilitated or disfigured by the disease. It is caused by infection with the nematode worms Wuchereria bancrofti, Brugia malayi or B. timori, the microfilariae of which are spread by a variety of mosquito vector species in defined geographical areas. The main aims of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) are to interrupt transmission of infection and to alleviate suffering and disability produced by the disease in the 83 countries in which it is endemic. Mass drug administration (MDA) to reduce transmission (and therefore morbidity) is conducted through the annual distribution of single doses of two microfilaricidal drugs for at least 5 years: diethylcarbamazine plus albendazole, or ivermectin plus albendazole in areas in which onchocerciasis is co-endemic. Since the initiation of GPELF in 2000 there has been a rapid expansion in MDA programmes, from 12 countries covering 3 million people in 2000, to 44 countries covering 258 million people by the end of 2006.47 These efforts have produced significant gains. In Egypt, studies in sentinel villages suggest that five rounds of MDA with >80% coverage may have been sufficient to eliminate the infection in most endemic localities in the country.48 A possible alternative or adjunctive approach to MDA, as with onchocerciasis, is to administer antibiotics active against Wolbachia, essential bacterial endosymbionts of adult filariae. This approach has gained some support from recent randomised controlled trial data.49
8. Blindness due to trachoma and onchocerciasis In 2002, trachoma and onchocerciasis accounted for about 3.6% and 0.8% of the total global burden of blindness, respectively.39 Both are scheduled for elimination by 2020 as part of the WHO-supported global initiative, VISION 2020: the Right to Sight. Significant progress has been made in controlling both diseases.40 Trachoma, caused by ocular strains of Chlamydia trachomatis, is endemic in over 50 countries41 and leads to irreversible blindness. Prevention is based on the ‘SAFE’ strategy, which involves: Surgery for advanced disease, Antibiotics to clear infection, Facial cleanliness and Environmental improvement to reduce transmission. In 2006, Morocco became the first country to eliminate trachoma using this strategy; Ghana, Mauritania, Nepal and Vietnam are on track to achieve elimination by 2010. Onchocerciasis, or river blindness, due to infection with the nematode Onchocerca volvulus, is transmitted through the bite of the blackfly, Simulium. By spraying larvicides from aircraft over blackfly breeding sites and by population-based distribution of the microfilaricide ivermectin, the Onchocerciasis Control Program (OCP) (1974—2002) achieved cessation of transmission in nearly all areas of 10 of the 11 West African countries in which it operated. The African OCP, launched in 1995, currently protects 40 million people in 19 countries through communitydirected ivermectin distribution. The latter programme is scheduled to close in 2010; there has been a recent call for it to extend its working life to at least 2015 and enlarge its activities to include pockets of residual disease activity in former OCP countries.42 Alarmingly, there is some recent evidence from Ghana of a reduction in ivermectin’s ability to block the release of intrauterine microfilariae by adult female worms43 although, oddly, the microfilaricidal action of the drug appears undiminished. New tools such as anthelminthic vaccines, a safe
10. Dracunculiasis (Guinea worm) Nine countries, all in sub-Saharan Africa, are still considered to have endemic dracunculiasis. The number of cases reported dropped from 892 055 in 1989 to 10 674 in 2005 and rose again to 25 217 in 2006, probably because of better reporting from the eradication programme in Sudan.50 Ministers of health from the remaining endemic countries have declared their commitment to global eradication of dracunculiasis by 2009.51 Considerable effort will be required to achieve this goal, particularly in Ghana and Sudan.51 However, there are no technical constraints to eradication. Contracted by drinking water containing copepods infected with larval Dracunculus medinensis, the disease could be eradicated in the remaining 4086 endemic villages by the provision of safe water supplies such as boreholes, education of the community about not swimming or wading in sources of drinking water, and universal filtering of drinking water through finely woven cloth.
11. Conclusions Guinea worm looks set to be the next disease after smallpox to be eradicated. Aided by a combination of enhanced understanding of the biology of the pathogens, intensification of immunisation activities or mass drug administration,
Recent advances in tropical medicine and the development of synergies with control programmes for co-endemic tropical diseases, polio, lymphatic filariasis, trachoma and onchocerciasis all appear to be in global decline, with good prospects for eventual elimination. While the global incidence of new cases of leprosy also continues to decrease, the focus of leprosy control efforts has shifted following more widespread recognition that cure of infection does not prevent disability in the affected individual. Expansion in funding for HIV/AIDS and malaria provides some grounds for optimism for the control of these diseases. Meanwhile, the rise of drug-resistant TB and emerging and re-emerging viruses pose additional ongoing challenges to tropical medicine physicians worldwide. Funding: None. Conflicts of interest: None declared. Ethical approval: Not required.
References 1. Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, et al. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 2006;355:1959—66. 2. Feachem R, Sabot O. A new global malaria eradication strategy. Lancet 2008;371:1633—5. 3. White NJ. Qinghaosu (artemisinin): the price of success. Science 2008;320:330—4. 4. WHO. Antimalarial drug combination therapy: report of a WHO technical consultation. Geneva: World Health Organization; 2001. 5. Dondorp A, Nosten F, Stepniewska K, Day N, White N. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 2005;366:717—25. 6. Snow RW, Guerra CA, Mutheu JJ, Hay SI. International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmission. PLoS Med 2008;5:e142. 7. Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 2004;363:1017—24. 8. Cox-Singh J, Davis TM, Lee KS, Shamsul SS, Matusop A, Ratnam S, et al. Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis 2008;46:165—71. 9. Getahun H, Harrington M, O’Brien R, Nunn P. Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet 2007;369:2042—9. 10. Pai M, Dheda K, Cunningham J, Scano F, O’Brien R. T-cell assays for the diagnosis of latent tuberculosis infection: moving the research agenda forward. Lancet Infect Dis 2007;7:428—38. 11. WHO. Global tuberculosis control: surveillance, planning, financing. Geneva: World Health Organization; 2007. 12. WHO. The Stop TB Strategy: building on and enhancing DOTS to meet the TB-related Millennium Development Goals. Geneva: World Health Organization; 2006. 13. Varma JK, Wiriyakitjar D, Nateniyom S, Anuwatnonthakate A, Monkongdee P, Sumnapan S, et al. Evaluating the potential impact of the new Global Plan to Stop TB: Thailand, 2004—2005. Bull World Health Organ 2007;85:586—92. 14. Zignol M, Hosseini MS, Wright A, Weezenbeek CL, Nunn P, Watt CJ, et al. Global incidence of multidrug-resistant tuberculosis. J Infect Dis 2006;194:479—85.
651 15. Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 2006;368:1575— 80. 16. UNAIDS. AIDS epidemic update: December 2007. Geneva: UNAIDS/World Health Organization; 2007. 17. Chin J. The AIDS pandemic: the collision of epidemiology with political correctness. Abingdon: Radcliffe Publishing; 2007. 18. Kmietowicz Z. Former UN envoy attacks UNAIDS for its ‘‘catatonic passivity’’. BMJ 2007;335:1111. 19. WHO. HIV/AIDS: WHO’s contribution to universal access to HIV/AIDS prevention, treatment and care. Report by the secretariat. Geneva: World Health Organization; 2006. 20. WHO. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Geneva: World Health Organization; 2008. http://www.who.int/csr/disease/avian influenza/country/cases table 2008 01 23/en/index.html [accessed 8 January 2009]. 21. Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthavathana P, et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005;352: 333—40. 22. Poland GA. Vaccines against avian influenza – a race against time. N Engl J Med 2006;354:1411—3. 23. Schunemann HJ, Hill SR, Kakad M, Bellamy R, Uyeki TM, Hayden FG, et al. WHO rapid advice guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis 2007;7:21—31. 24. National Travel Health Network and Centre. Chikungunya virus. London: NaTHNaC; ©2006. http://www.nathnac.org/pro/ clinical updates/chik 210706.htm [accessed 8 January 2009]. 25. Charrel RN, de Lamballerie X, Raoult D. Chikungunya outbreaks — the globalization of vectorborne diseases. N Engl J Med 2007;356:769—71. 26. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M, et al. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 2007;370:1840—6. 27. Kramer LD, Li J, Shi PY. West Nile virus. Lancet Neurol 2007;6:171—81. 28. Moudy RM, Meola MA, Morin LL, Ebel GD, Kramer LD. A newly emergent genotype of West Nile virus is transmitted earlier and more efficiently by Culex mosquitoes. Am J Trop Med Hyg 2007;77:365—70. 29. West Nile virus update — United States, January 1—November 13, 2007. MMWR Morb Mortal Wkly Rep 2007;56:1191—2. 30. World Health Assembly. Global eradication of poliomyelitis by the year 2000. Geneva: 41st World Health Assembly; 1988. Resolution WHA41.28. 31. WHO. Wild poliovirus 2000—2007. Geneva: World Health Organization; 2008. http://www.polioeradication.org/content/ general/casecount.pdf [accessed 8 January 2009]. 32. Jegede AS. What led to the Nigerian boycott of the polio vaccination campaign? PLoS Med 2007;4:e73. 33. Pallansch MA, Sandhu HS. The eradication of polio — progress and challenges. N Engl J Med 2006;355:2508—11. 34. WHO. Cessation of routine oral polio vaccine (OPV) use after global polio eradication. Geneva: World Health Organization; 2005. WHO/POLIO/05.02. 35. Lockwood DN, Suneetha S. Leprosy: too complex a disease for a simple elimination paradigm. Bull World Health Organ 2005;83:230—5. 36. Leprosy elimination not yet in sight. Lancet Infect Dis 2005; 5:321. 37. Global leprosy situation, 2007. Wkly Epidemiol Rec 2007; 82:225—32. 38. Fenwick A. Waterborne infectious diseases — could they be consigned to history? Science 2006;313:1077—81.
652 39. Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, et al. Global data on visual impairment in the year 2002. Bull World Health Organ 2004;82:844—51. 40. World Health Organization. State of the world’s sight: VISION 2020: the Right to Sight 1999—2005. Geneva: World Health Organization/International Agency for the Prevention of Blindness; 2005. 41. Mariotti SP. New steps toward eliminating blinding trachoma. N Engl J Med 2004;351:2004—7. 42. Amazigo U, Boatin B. The future of onchocerciasis control in Africa. Lancet 2006;368:1946—7. 43. Osei-Atweneboana MY, Eng JK, Boakye DA, Gyapong JO, Prichard RK. Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two-phase epidemiological study. Lancet 2007;369:2021—9. 44. Hopkins AD. Ivermectin and onchocerciasis: is it all solved? Eye 2005;19:1057—66.
A.W. Solomon et al. 45. Taylor MJ, Bandi C, Hoerauf A. Wolbachia bacterial endosymbionts of filarial nematodes. Adv Parasitol 2005;60:245—84. 46. Hotez PJ. Control of onchocerciasis — the next generation. Lancet 2007;369:1979—80. 47. Global programme to eliminate lymphatic filariasis. Wkly Epidemiol Rec 2007; 82:361—80. 48. Ramzy RM, El Setouhy M, Helmy H, Ahmed ES, Abd Elaziz KM, Farid HA, et al. Effect of yearly mass drug administration with diethylcarbamazine and albendazole on bancroftian filariasis in Egypt: a comprehensive assessment. Lancet 2006;367:992—9. 49. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A. Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebocontrolled trial. Lancet 2005;365:2116—21. 50. Dracunculiasis eradication. Global surveillance summary, 2006. Wkly Epidemiol Rec 2007;82:133—40. 51. Dracunculiasis eradication: ministerial meeting, Geneva, 16 May 2007. Wkly Epidemiol Rec 2007;82:236—7.
available at www.sciencedirect.com
journal homepage: www.elsevierhealth.com/journals/trst
REVIEW
Recent advances in tropical medicine夽 Anthony W. Solomon, Shevanthi Nayagam, Geoffrey Pasvol ∗ Department of Infection and Tropical Medicine, Imperial College London, Lister Unit, Northwick Park Hospital, Harrow HA1 3UJ, UK Received 27 November 2008; received in revised form 19 January 2009; accepted 20 January 2009 Available online 23 February 2009
KEYWORDS Tropical medicine; Resistance; Malaria; HIV/AIDS; Tuberculosis; Communicable diseases, emerging
Summary There have been significant advances in both the classical and neglected tropical diseases, with Guinea worm looking set to be the next disease after smallpox to be eradicated. Aided by a combination of enhanced understanding of the biology of the pathogens, intensification of immunisation activities or mass drug administration, together with the development of synergies with control programmes for co-endemic tropical diseases, polio, lymphatic filariasis, trachoma and onchocerciasis all appear to be in global decline, with good prospects for eventual successful elimination. While the global incidence of new cases of leprosy continues to decrease, the focus of leprosy control efforts has shifted following more widespread recognition that cure of infection does not necessarily prevent disability. Expansion in funding for HIV/AIDS and malaria provides some grounds for optimism about the control of these diseases. However, ongoing education and access remain essential to increasing the uptake of HIV testing and decreasing transmission. Meanwhile, the rise of drug-resistant tuberculosis and malaria is concerning, and the emergence of the highly pathogenic avian influenza A and re-emergence of viruses such as chikungunya and West Nile virus, without significant recent progress in vaccine development, pose additional ongoing challenges to tropical medicine physicians worldwide. © 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
1. Malaria 1.1. Drug resistance 夽
A previous version of this paper was published (prior to peer review) in the journal Medicine [Solomon A, Nayagam S, Pasvol G. What’s new in tropical medicine. Medicine 2009;1:51—4]. It is published here with permission of the publisher of both journals, Elsevier, and with the agreement of the editors of Medicine and Transactions of the Royal Society of Tropical Medicine and Hygiene. ∗ Corresponding author. Tel.: +44 (0)20 8869 2831; fax: +44 (0)20 8869 2836. E-mail address: [email protected] (G. Pasvol).
Clinical resistance has arisen to all classes of antimalarials used to date, barring the artemisinin derivatives. Chloroquine resistance is now virtually universal in Plasmodium falciparum and the efficacy of sulfadoxine-pyrimethamine (Fansidar) has become increasingly compromised. Monotherapy and widespread, indiscriminate use of antimalarials have encouraged the selection of drug-resistant strains. Encouragingly, chloroquine-sensitive P. falciparum has reemerged in Malawi 13 years after chloroquine was
0035-9203/$ — see front matter © 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.trstmh.2009.01.018
648
A.W. Solomon et al.
abandoned, but the clinical application of this observation has yet to be realised.1 Whether the complete eradication of malaria is a realistic goal remains to be seen.2
release by peripheral blood T-cells) in formats that can be practically and economically deployed in resource-poor settings.9,10
1.2. Antimalarial combinations
2.2. Control
To maximise the effectiveness of treatment and to delay the development of resistance to newer drugs, treatment with combinations of antimalarial drugs is now recommended.3 Artemisinin derivatives rapidly clear malaria parasites from the blood and combinations including these drugs (e.g. artesunate with amodiaquine or mefloquine, and artemether with lumefantrine) have been strongly endorsed by WHO since 2001.4 Non-artemisinin-containing combinations (e.g. sulfadoxine-pyrimethamine with amodiaquine) are advised only if artemisinin-based combination therapy (ACT) is unavailable or unaffordable. Affordability remains an issue, as ACTs are nearly 10 times as expensive as previous first-line choices. Despite this, since 2001, 41 of 54 African countries in which malaria is endemic have changed their malaria treatment protocols to make ACTs first-line. The impact of these changes on morbidity and mortality has yet to be documented. Whilst data exist to support the preferential use of artesunate over quinine for the initial treatment of severe malaria in adults, the results of an equivalence study in African children are awaited.5
After increasing through the 1990s and early 2000s as a result of the HIV pandemic and the break-up of the Soviet Union, amongst other factors, the per capita global incidence of TB now appears to be in decline. In 2005 there were an estimated 8.8 million new cases and 1.6 million deaths.11 In 2006 the WHO launched the Stop Tuberculosis Strategy, a six-point plan aiming to reduce TB prevalence and mortality to less than 50% of 1990 levels by 2015.12 It is currently too early to assess the global impact of this strategy, but pilot studies in Thailand suggest that it may enhance case-finding (including in the private sector) and help patients diagnosed with TB engage with HIV services.13
1.3. Control An international commitment to halve the burden of malaria by 2015 has been supported by considerable increases in funding for malaria control. Recent analysis, however, suggests that for the 1.4 billion people exposed to stable P. falciparum malaria risk there is an annual budget of US$1 billion dedicated for control — less than US$1 per person at risk per year.6
2.3. MDR- and XDR-TB Multidrug-resistant TB (MDR-TB) is caused by Mycobacterium tuberculosis resistant to both rifampicin and isoniazid; extensively drug-resistant TB (XDR-TB) is resistant to isoniazid, rifampicin and fluoroquinolones and either aminoglycosides or capreomycin or both. Such strains have emerged because of inadequate treatment regimens and poor compliance, and pose a serious threat to TB control worldwide. WHO estimates that in 2004, 4.3% of all cases of TB were due to MDR-TB.14 XDR-TB has now been identified in more than 40 countries. Relatively few laboratories are able to test the susceptibility of M. tuberculosis isolates to second-line drugs, so population-based data are generally lacking. Improved diagnostic facilities and expanded access to second- and third-line drugs are needed, since XDR-TB is associated with extremely high mortality.15
1.4. Knowlesi malaria Malaria in humans due to a fifth malarial species, P. knowlesi, has now been well documented in Malaysian Borneo and Peninsular Malaysia. Recent evidence indicates that it may be more widespread even than this. Often misdiagnosed as P. malariae, P. knowlesi is capable of causing severe disease and even death.7,8
2. Tuberculosis 2.1. Diagnosis Owing to the insensitivity of direct microscopy of clinical samples and the widespread unavailability, imperfect sensitivity and long lag-time of mycobacterial culture, the diagnosis of tuberculosis (TB) continues to be based on clinical presentation and the Mantoux test, a semi-quantitative test that has remained essentially unchanged since its development 100 years ago. Both positive and negative Mantoux results must be interpreted with caution. There is an urgent need for the development of improved diagnostic tests (based, for example, on the detection of ␥-interferon
3. HIV/AIDS The annual HIV/AIDS estimates released by UNAIDS suggest that in 2007 there were 33.2 million individuals living with HIV, of whom 15.4 million were women and 2.5 million were children aged less than 15 years.16 The 2007 total global prevalence figure is 16% less than the corresponding estimate for 2006, a decrease that is primarily attributed to improvements in the mathematical models used to calculate the likely prevalence in India and sub-Saharan Africa. Although UNAIDS has been criticised for the way in which it calculates and interprets its estimates,17,18 it is encouraging that current data suggest that prevalence is beginning to plateau. Access to and uptake of HIV testing remain major barriers to control. In sub-Saharan Africa fewer than 10% of those infected with HIV know they are infected.19 The availability of antiretroviral drugs to those in developing countries is also problematic; although treatment coverage was declared a global health emergency in 2003, WHO’s commitment to increase antiretroviral treatment coverage from 300 000 to 3 million people in low- and middle-income countries by
Recent advances in tropical medicine the end of 2005 (the ‘3 by 5’ target) was not fulfilled. By December 2005 approximately 1.3 million people in low- and middle-income countries were receiving antiretrovirals.
4. Emerging and re-emerging diseases 4.1. Avian influenza Highly pathogenic avian influenza A (H5N1) virus emerged in Southeast Asia in late 2003, causing disease in birds and then in humans. By January 2008 there had been 352 human cases in 14 countries, resulting in 219 deaths.20 Most people infected had been in close contact with poultry, but in September 2004 the first reasonably conclusive cases of person-to-person transmission were reported between members of a family living in Thailand.21 The virus is not yet pandemic, mainly because current strains are not efficient at person-to-person spread.22 Vaccines are in development. International guidelines for the pharmacological management of H5N1 were published in January 2007, recommending oseltamivir for treatment of confirmed cases and oseltamivir or zanamivir as chemoprophylaxis in household or close family contacts.23 The quality of direct evidence supporting these recommendations is acknowledged to be low.
4.2. Chikungunya Chikungunya (‘that which bends up’ — referring to the crippling arthralgia that infection may produce) is a disease caused by an alphavirus transmitted by Aedes spp. mosquitoes. The first recorded epidemic was in Tanzania in 1952—3. Severe polyarthralgia, fever and a maculopapular rash are the most prominent clinical features. Treatment is supportive; vaccine trials are in progress. In March 2005 a chikungunya epidemic began on the Indian Ocean island of Reunion. More than 266 000 people were infected, peaking in February 2006.24 The virus spread to India, causing more than 1.3 million cases,25 and from there to Italy, resulting in 205 cases by September 2007.26
4.3. West Nile virus First isolated in Uganda in 1937, West Nile virus is a flavivirus that has long caused sporadic outbreaks of a febrile illness in Africa, the Mediterranean and eastern Europe.27 In humans, West Nile virus may also result in neuroinvasive disease (meningitis, encephalitis or acute flaccid paralysis). The virus emerged in the Americas for the first time in New York City in 1999 and subsequently spread in the USA, causing major declines in several North American bird species and seasonal epidemics in humans. During this outbreak a newly dominant genotype (WN02) emerged that has a significantly shorter incubation period in the vector, culicine mosquitoes.28 From January to November 2007, 3304 cases were reported to the Centers for Disease Control (CDC) from 43 states in the USA; 93 were fatal.29
649
5. Polio In 1988 polio was scheduled for global eradication by the year 2000.30 As a result of intensive international efforts the annual number of cases worldwide declined from an estimated 350 000 in 1998 to 719 in 2000, an encouraging decrease of 99.7%.31 Completing the process of eradication has proved difficult, however. In Nigeria, immunisation activities were suspended in 2003 and 2004 because of rumours that vaccines were adulterated with anti-fertility drugs or HIV.32 This interruption in control efforts has led to outbreaks as far afield as Indonesia, Botswana and Saudi Arabia. Other challenges to the global eradication campaign include political instability, conflict, fatigue in communities and vaccination teams, difficulties in sustaining surveillance in remote and underprovided communities, and an increasing awareness of vaccine-associated paralytic poliomyelitis (VAPP) in 2—4 vaccinees per million.33,34 In January 2008 poliovirus was still considered endemic in four countries (Pakistan, Afghanistan, India and Nigeria), while another five countries had active transmission of imported virus; a total of 1083 cases due to wild virus were confirmed during 2007.31 For the last 7 years the annual number of cases has ranged between 483 (in 2001) and 1997 (in 2006). In response, an integrated global network for molecular surveillance of each wild virus isolate has been constructed to monitor progress, understand local and international transmission pathways, and propose appropriate control strategies. In some conflict areas it has been possible to suspend hostilities to permit national immunisation days to proceed.33
6. Leprosy Unlike polio, for which eradication was set for 2000, leprosy was scheduled for global ‘elimination as a public health problem’ by the same year — defined as the reduction in prevalence to less than one case per 10 000 persons, based on the hypothesis that at this prevalence or lower, transmission would be interrupted. This target raised the profile of leprosy as a disease and galvanised control efforts. Unfortunately, determining leprosy elimination using prevalence as the criterion is problematic; the disease may have an incubation period of up to 20 years and certifying successful elimination, as the WHO did in May 2001, led to reduction in both clinical service provision and funding for leprosy research.35,36 The campaign approach has now been discontinued and the ongoing focus is the timely detection of new cases, early treatment with effective chemotherapy, prevention of disability and provision of rehabilitation. Case detection (rather than prevalence) will be the main indicator used to monitor progress. In 2006, 259 017 new cases of leprosy were registered worldwide, a decrease of 13% compared with 2005, continuing a steady decline that has been sustained during the current decade.37 Only four countries of the 122 that were leprosy-endemic in 1985 had a registered prevalence of leprosy of more than one case per 10 000 population: Brazil, the Democratic Republic of Congo, Mozambique and Nepal.37 The prospects for maintaining progress against leprosy seem good; humans are the main
650
A.W. Solomon et al.
reservoir of infection, free multidrug therapy has been available since 2000 and drug-resistant strains of Mycobacterium leprae have not yet proven problematic.
macrofilaricide44 or chemotherapy targeted against Wolbachia (a bacterial endosymbiont of O. volvulus),45 may be required.46
7. Schistosomiasis
9. Lymphatic filariasis
The Schistosomiasis Control Initiative (SCI) has made considerable progress in the control of this infection in Africa.38 By mid 2008 approximately 40 million treatments had been administered in six countries, reaching over 20 million individuals, although approximately 10 times this number of people are thought to need treatment. In every case praziquantel has been co-administered with the anthelminthic albendazole, but from 2007 onwards the emphasis changed and a ‘rapid impact’ package of up to four drugs is now offered, as appropriate, so that schistosomiasis, intestinal helminths, trachoma, lymphatic filariasis and onchocerciasis can be controlled in an integrated attack on neglected tropical diseases (NTDs). The aim is to bring donated drugs to the poorest populations of subSaharan Africa at an estimated cost of 25 pence per person annually.
Lymphatic filariasis affects more than 120 million people, of whom over 40 million are debilitated or disfigured by the disease. It is caused by infection with the nematode worms Wuchereria bancrofti, Brugia malayi or B. timori, the microfilariae of which are spread by a variety of mosquito vector species in defined geographical areas. The main aims of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) are to interrupt transmission of infection and to alleviate suffering and disability produced by the disease in the 83 countries in which it is endemic. Mass drug administration (MDA) to reduce transmission (and therefore morbidity) is conducted through the annual distribution of single doses of two microfilaricidal drugs for at least 5 years: diethylcarbamazine plus albendazole, or ivermectin plus albendazole in areas in which onchocerciasis is co-endemic. Since the initiation of GPELF in 2000 there has been a rapid expansion in MDA programmes, from 12 countries covering 3 million people in 2000, to 44 countries covering 258 million people by the end of 2006.47 These efforts have produced significant gains. In Egypt, studies in sentinel villages suggest that five rounds of MDA with >80% coverage may have been sufficient to eliminate the infection in most endemic localities in the country.48 A possible alternative or adjunctive approach to MDA, as with onchocerciasis, is to administer antibiotics active against Wolbachia, essential bacterial endosymbionts of adult filariae. This approach has gained some support from recent randomised controlled trial data.49
8. Blindness due to trachoma and onchocerciasis In 2002, trachoma and onchocerciasis accounted for about 3.6% and 0.8% of the total global burden of blindness, respectively.39 Both are scheduled for elimination by 2020 as part of the WHO-supported global initiative, VISION 2020: the Right to Sight. Significant progress has been made in controlling both diseases.40 Trachoma, caused by ocular strains of Chlamydia trachomatis, is endemic in over 50 countries41 and leads to irreversible blindness. Prevention is based on the ‘SAFE’ strategy, which involves: Surgery for advanced disease, Antibiotics to clear infection, Facial cleanliness and Environmental improvement to reduce transmission. In 2006, Morocco became the first country to eliminate trachoma using this strategy; Ghana, Mauritania, Nepal and Vietnam are on track to achieve elimination by 2010. Onchocerciasis, or river blindness, due to infection with the nematode Onchocerca volvulus, is transmitted through the bite of the blackfly, Simulium. By spraying larvicides from aircraft over blackfly breeding sites and by population-based distribution of the microfilaricide ivermectin, the Onchocerciasis Control Program (OCP) (1974—2002) achieved cessation of transmission in nearly all areas of 10 of the 11 West African countries in which it operated. The African OCP, launched in 1995, currently protects 40 million people in 19 countries through communitydirected ivermectin distribution. The latter programme is scheduled to close in 2010; there has been a recent call for it to extend its working life to at least 2015 and enlarge its activities to include pockets of residual disease activity in former OCP countries.42 Alarmingly, there is some recent evidence from Ghana of a reduction in ivermectin’s ability to block the release of intrauterine microfilariae by adult female worms43 although, oddly, the microfilaricidal action of the drug appears undiminished. New tools such as anthelminthic vaccines, a safe
10. Dracunculiasis (Guinea worm) Nine countries, all in sub-Saharan Africa, are still considered to have endemic dracunculiasis. The number of cases reported dropped from 892 055 in 1989 to 10 674 in 2005 and rose again to 25 217 in 2006, probably because of better reporting from the eradication programme in Sudan.50 Ministers of health from the remaining endemic countries have declared their commitment to global eradication of dracunculiasis by 2009.51 Considerable effort will be required to achieve this goal, particularly in Ghana and Sudan.51 However, there are no technical constraints to eradication. Contracted by drinking water containing copepods infected with larval Dracunculus medinensis, the disease could be eradicated in the remaining 4086 endemic villages by the provision of safe water supplies such as boreholes, education of the community about not swimming or wading in sources of drinking water, and universal filtering of drinking water through finely woven cloth.
11. Conclusions Guinea worm looks set to be the next disease after smallpox to be eradicated. Aided by a combination of enhanced understanding of the biology of the pathogens, intensification of immunisation activities or mass drug administration,
Recent advances in tropical medicine and the development of synergies with control programmes for co-endemic tropical diseases, polio, lymphatic filariasis, trachoma and onchocerciasis all appear to be in global decline, with good prospects for eventual elimination. While the global incidence of new cases of leprosy also continues to decrease, the focus of leprosy control efforts has shifted following more widespread recognition that cure of infection does not prevent disability in the affected individual. Expansion in funding for HIV/AIDS and malaria provides some grounds for optimism for the control of these diseases. Meanwhile, the rise of drug-resistant TB and emerging and re-emerging viruses pose additional ongoing challenges to tropical medicine physicians worldwide. Funding: None. Conflicts of interest: None declared. Ethical approval: Not required.
References 1. Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, et al. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 2006;355:1959—66. 2. Feachem R, Sabot O. A new global malaria eradication strategy. Lancet 2008;371:1633—5. 3. White NJ. Qinghaosu (artemisinin): the price of success. Science 2008;320:330—4. 4. WHO. Antimalarial drug combination therapy: report of a WHO technical consultation. Geneva: World Health Organization; 2001. 5. Dondorp A, Nosten F, Stepniewska K, Day N, White N. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 2005;366:717—25. 6. Snow RW, Guerra CA, Mutheu JJ, Hay SI. International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmission. PLoS Med 2008;5:e142. 7. Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 2004;363:1017—24. 8. Cox-Singh J, Davis TM, Lee KS, Shamsul SS, Matusop A, Ratnam S, et al. Plasmodium knowlesi malaria in humans is widely distributed and potentially life threatening. Clin Infect Dis 2008;46:165—71. 9. Getahun H, Harrington M, O’Brien R, Nunn P. Diagnosis of smear-negative pulmonary tuberculosis in people with HIV infection or AIDS in resource-constrained settings: informing urgent policy changes. Lancet 2007;369:2042—9. 10. Pai M, Dheda K, Cunningham J, Scano F, O’Brien R. T-cell assays for the diagnosis of latent tuberculosis infection: moving the research agenda forward. Lancet Infect Dis 2007;7:428—38. 11. WHO. Global tuberculosis control: surveillance, planning, financing. Geneva: World Health Organization; 2007. 12. WHO. The Stop TB Strategy: building on and enhancing DOTS to meet the TB-related Millennium Development Goals. Geneva: World Health Organization; 2006. 13. Varma JK, Wiriyakitjar D, Nateniyom S, Anuwatnonthakate A, Monkongdee P, Sumnapan S, et al. Evaluating the potential impact of the new Global Plan to Stop TB: Thailand, 2004—2005. Bull World Health Organ 2007;85:586—92. 14. Zignol M, Hosseini MS, Wright A, Weezenbeek CL, Nunn P, Watt CJ, et al. Global incidence of multidrug-resistant tuberculosis. J Infect Dis 2006;194:479—85.
651 15. Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 2006;368:1575— 80. 16. UNAIDS. AIDS epidemic update: December 2007. Geneva: UNAIDS/World Health Organization; 2007. 17. Chin J. The AIDS pandemic: the collision of epidemiology with political correctness. Abingdon: Radcliffe Publishing; 2007. 18. Kmietowicz Z. Former UN envoy attacks UNAIDS for its ‘‘catatonic passivity’’. BMJ 2007;335:1111. 19. WHO. HIV/AIDS: WHO’s contribution to universal access to HIV/AIDS prevention, treatment and care. Report by the secretariat. Geneva: World Health Organization; 2006. 20. WHO. Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. Geneva: World Health Organization; 2008. http://www.who.int/csr/disease/avian influenza/country/cases table 2008 01 23/en/index.html [accessed 8 January 2009]. 21. Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthavathana P, et al. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med 2005;352: 333—40. 22. Poland GA. Vaccines against avian influenza – a race against time. N Engl J Med 2006;354:1411—3. 23. Schunemann HJ, Hill SR, Kakad M, Bellamy R, Uyeki TM, Hayden FG, et al. WHO rapid advice guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus. Lancet Infect Dis 2007;7:21—31. 24. National Travel Health Network and Centre. Chikungunya virus. London: NaTHNaC; ©2006. http://www.nathnac.org/pro/ clinical updates/chik 210706.htm [accessed 8 January 2009]. 25. Charrel RN, de Lamballerie X, Raoult D. Chikungunya outbreaks — the globalization of vectorborne diseases. N Engl J Med 2007;356:769—71. 26. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning M, et al. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet 2007;370:1840—6. 27. Kramer LD, Li J, Shi PY. West Nile virus. Lancet Neurol 2007;6:171—81. 28. Moudy RM, Meola MA, Morin LL, Ebel GD, Kramer LD. A newly emergent genotype of West Nile virus is transmitted earlier and more efficiently by Culex mosquitoes. Am J Trop Med Hyg 2007;77:365—70. 29. West Nile virus update — United States, January 1—November 13, 2007. MMWR Morb Mortal Wkly Rep 2007;56:1191—2. 30. World Health Assembly. Global eradication of poliomyelitis by the year 2000. Geneva: 41st World Health Assembly; 1988. Resolution WHA41.28. 31. WHO. Wild poliovirus 2000—2007. Geneva: World Health Organization; 2008. http://www.polioeradication.org/content/ general/casecount.pdf [accessed 8 January 2009]. 32. Jegede AS. What led to the Nigerian boycott of the polio vaccination campaign? PLoS Med 2007;4:e73. 33. Pallansch MA, Sandhu HS. The eradication of polio — progress and challenges. N Engl J Med 2006;355:2508—11. 34. WHO. Cessation of routine oral polio vaccine (OPV) use after global polio eradication. Geneva: World Health Organization; 2005. WHO/POLIO/05.02. 35. Lockwood DN, Suneetha S. Leprosy: too complex a disease for a simple elimination paradigm. Bull World Health Organ 2005;83:230—5. 36. Leprosy elimination not yet in sight. Lancet Infect Dis 2005; 5:321. 37. Global leprosy situation, 2007. Wkly Epidemiol Rec 2007; 82:225—32. 38. Fenwick A. Waterborne infectious diseases — could they be consigned to history? Science 2006;313:1077—81.
652 39. Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, et al. Global data on visual impairment in the year 2002. Bull World Health Organ 2004;82:844—51. 40. World Health Organization. State of the world’s sight: VISION 2020: the Right to Sight 1999—2005. Geneva: World Health Organization/International Agency for the Prevention of Blindness; 2005. 41. Mariotti SP. New steps toward eliminating blinding trachoma. N Engl J Med 2004;351:2004—7. 42. Amazigo U, Boatin B. The future of onchocerciasis control in Africa. Lancet 2006;368:1946—7. 43. Osei-Atweneboana MY, Eng JK, Boakye DA, Gyapong JO, Prichard RK. Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two-phase epidemiological study. Lancet 2007;369:2021—9. 44. Hopkins AD. Ivermectin and onchocerciasis: is it all solved? Eye 2005;19:1057—66.
A.W. Solomon et al. 45. Taylor MJ, Bandi C, Hoerauf A. Wolbachia bacterial endosymbionts of filarial nematodes. Adv Parasitol 2005;60:245—84. 46. Hotez PJ. Control of onchocerciasis — the next generation. Lancet 2007;369:1979—80. 47. Global programme to eliminate lymphatic filariasis. Wkly Epidemiol Rec 2007; 82:361—80. 48. Ramzy RM, El Setouhy M, Helmy H, Ahmed ES, Abd Elaziz KM, Farid HA, et al. Effect of yearly mass drug administration with diethylcarbamazine and albendazole on bancroftian filariasis in Egypt: a comprehensive assessment. Lancet 2006;367:992—9. 49. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A. Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebocontrolled trial. Lancet 2005;365:2116—21. 50. Dracunculiasis eradication. Global surveillance summary, 2006. Wkly Epidemiol Rec 2007;82:133—40. 51. Dracunculiasis eradication: ministerial meeting, Geneva, 16 May 2007. Wkly Epidemiol Rec 2007;82:236—7.