* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download The new global map of human brucellosis
Survey
Document related concepts
Trichinosis wikipedia , lookup
Meningococcal disease wikipedia , lookup
Onchocerciasis wikipedia , lookup
Neglected tropical diseases wikipedia , lookup
Bioterrorism wikipedia , lookup
Poliomyelitis eradication wikipedia , lookup
Sarcocystis wikipedia , lookup
Bovine spongiform encephalopathy wikipedia , lookup
Chagas disease wikipedia , lookup
Leptospirosis wikipedia , lookup
Schistosomiasis wikipedia , lookup
Dracunculiasis wikipedia , lookup
African trypanosomiasis wikipedia , lookup
Middle East respiratory syndrome wikipedia , lookup
Oesophagostomum wikipedia , lookup
Coccidioidomycosis wikipedia , lookup
Fasciolosis wikipedia , lookup
Transcript
Review The new global map of human brucellosis Georgios Pappas, Photini Papadimitriou, Nikolaos Akritidis, Leonidas Christou, Epameinondas V Tsianos The epidemiology of human brucellosis, the commonest zoonotic infection worldwide, has drastically changed over the past decade because of various sanitary, socioeconomic, and political reasons, together with the evolution of international travel. Several areas traditionally considered to be endemic—eg, France, Israel, and most of Latin America—have achieved control of the disease. On the other hand, new foci of human brucellosis have emerged, particularly in central Asia, while the situation in certain countries of the near east (eg, Syria) is rapidly worsening. Furthermore, the disease is still present, in varying trends, both in European countries and in the USA. Awareness of this new global map of human brucellosis will allow for proper interventions from international public-health organisations. Introduction USA Brucellosis is an old disease with minimal mortality. Yet human brucellosis remains the commonest zoonotic disease worldwide with more than 500 000 new cases annually,1–3 is associated with substantial residual disability,4 and is an important cause of travel-associated morbidity.5 The global epidemiology of the disease has drastically evolved over the past decade. We focus on the current global distribution of the disease and its relocation during the past decade, and attempt to explain the rationale behind this evolution and its possible future projections. Until the 1960s, most human cases in the USA were attributed to Brucella abortus, reaching a high of 6321 cases in 1947.27 A massive eradication campaign resulted in the elimination of cattle brucellosis and a substantial decline in the incidence of human disease. During the 1970s brucellosis was mainly attributed to Brucella suis, prevalent among abattoir workers.28 According to annual reports from the Centers for Disease Control and Prevention (Atlanta, GA),17 2215 cases were reported in the period 1973–82, and 1201 cases were reported between 1983 and 1992. 1056 cases were reported for the period 1993–2002, more than half deriving from Texas and California. The 136 cases and incidence of 0·48 cases per million for 2001 represent respective peaks since 1985 and 1983. A small decline was noted in 2002. Table 2 shows the average annual incidence per state for 1993–2002, and figure 2 depicts the incidence distribution per state. Global status Figure 1 depicts the incidence of human brucellosis worldwide. Table 1 shows the countries with the highest annual incidence of human brucellosis from 2000 onwards, as well as the incidence for selected other countries. Lancet Infect Dis 2006; 6: 91–99 GP, LC and EVT are at the First Division of Internal Medicine of the Medical School at the University of Ioannina, Greece; PP is at the Pediatrics Department of the University Hospital of Ioannina, Greece; and NK is at the Internal Medicine Department of the General Hospital “G Hatzikosta”, Ioannina, Greece. Correspondence to: Dr Georgios Pappas, Internal Medicine Department, University Hospital of Ioannina, 45110, Greece. Tel: +30 26510 49453; [email protected] Annual incidence of brucellosis per 1000 000 population 500 50–500 cases 10–50 2–10 2 Possibily endemic, no data Non-endemic/no data Figure 1: Worldwide incidence of human brucellosis http://infection.thelancet.com Vol 6 February 2006 91 Review Country and reference Incidence (annual cases per million of population) Europe Albania6 Bosnia and Herzegovina7 Denmark7 France7 Former Yugoslav Republic of Macedonia8 Georgia7 Germany7 Greece9 Ireland7 Italy10 Netherlands7 Norway7 Portugal11 Russia7 Serbia and Montenegro7 Spain12 Sweden7 Switzerland13 UK14 63·6 20·8 0·7 0·5 148 27·6 0·3 20·9 1·3 9 0·5 0·7 13·9 4·1 8·4 15·1 0·3 1·5 0·3 Africa Algeria8 Cameroon7 Egypt15 Eritrea16 Ethiopia7 Mali8 Namibia8 Tunisia7 Uganda7 84·3 Endemic, no specific data available 2·95 5·48 Endemic, no specific data available 2 4·9 35·4 0·9 North America Canada7 USA17 Mexico18 0·09 0·4 28·7 Central and South America Argentina8 Chile7 Colombia7 Guatemala16 Panama7 Peru7 8·4 0·6 1·85 15·7 10·1 34·9 (continues) (continued) Asia Afghanistan7 Armenia16 Azerbaijan8 China19 India Iraq7 Iran8 Israel7 Jordan20 Kazakhstan21 Korea, South7 Kuwait7 Kyrgyzstan16 Lebanon22 Mongolia23 Oman7 Pakistan Saudi Arabia24 Syria7 Tajikistan7 Turkey7 Turkmenistan7 United Arab Emirates25 Uzbekistan7 Oceania Australia26 3·8 31·3 52·6 8 No data available, possibly endemic 278·4 238·6 9·2 23·4 115·8 1 33·9 362·2 49·5 605·9 35·6 No data available, possibly endemic 214·4 1603·4 211·9 262·2 51·5 41 18 0·9 Table 1: Global incidence of human brucellosis the actual picture of brucellosis in the USA today is represented: a disease caused by B melitensis, affecting the Hispanic population, and localised in areas neighbouring Mexico.29,30 A recent report from San Diego, California showed a limited area where B abortus is prevalent.31 The disease is imported through the US/Mexican border by means of infected dairy products, particularly Mexican soft cheese.32–34 The increased incidence in Illinois remains of obscure aetiology. Latin America Most of the US cases are attributed to Brucella melitensis. 647 (79·4%) of the 815 patients for whom ethnicity was documented were of Hispanic origin. During 1993–2002, 46 states reported at least one case, and 26 states reported at least one case in 2002. Illinois, Florida, Texas, Arizona, Colorado, and California reported at least one case annually, while Maine, Vermont, Rhode Island, North Dakota, West Virginia, and Nevada reported no cases at all. The annual incidence is highest in Wyoming, although the small number of cases precludes evaluation of the clinical importance of this incidence. The average incidence is increased in North Carolina and Arkansas due to clusters of 27 cases in 1993 and nine cases in 2001, respectively. Most cases in northern states probably represent imported disease acquired through international travel or infected food preparations imported from endemic areas. This is not the case for west south central, mountain, and Pacific states, where 92 Mexico remains one of the most important reservoirs of human brucellosis. Data from the Mexican Ministry of Health’s epidemiology directorate18 for the years 1996–2003 show a decline until 2000, and a subsequent increase in the annual number of cases reported; 3008 cases were reported in 2003. Whether this increase is actual or related to improvements in notification systems35 cannot be determined. The disease is localised in two zones: the northern districts neighbouring the USA—eg, Coahuila, Nuevo Leon, Sonora, and Chihuahua (average annual incidence 186, 85, 57, and 54 cases per million respectively)—and northwestern and west central districts—eg, Sinaloa, Zacatecas, Durango, and Guanajuato (although the latter district exhibits a continuous incidence decline). The most important parameter of the epidemiology of human brucellosis in Mexico is the effect the endemicity of the northern districts exhibits on the epidemiology of the disease in the USA. Even strict border control cannot http://infection.thelancet.com Vol 6 February 2006 Review contain a zoonosis; thus eradication cannot be achieved by means of national control programmes, especially in areas where immigration is common. A global, or at least continental plan has to be undertaken to ensure eradication. Animal brucellosis exists throughout Central America36 but human disease is not endemic. Guatemala and Panama are exceptions, according to annual data from the World Organisation for Animal Health (OIE).7,8 South America has been traditionally considered an endemic area of human brucellosis, B melitensis being prevalent in Peru and west Argentina, and B abortus in east Argentina37,38 and other South American countries. Data from the OIE imply that brucellosis is still important in Peru and Argentina.8 There are no data available for Brazil, which hosts the largest commercial cattle population in the world, and is presumably at risk of increased prevalence of human B abortus disease. Under-reporting may be an obstacle in evaluating the true incidence in Brazil39 and neighbouring countries: brucellosis is not included in the notifiable diseases for which surveillance is active (even in Peru). With the exception of Peru and Argentina, South America should be excluded from the highly endemic global zones of human brucellosis. European Union/western Europe Brucellosis-free status has been granted by the European Union (EU) to Sweden, Denmark, Finland, Germany, the UK (excluding Northern Ireland), Austria, Netherlands, Belgium, and Luxembourg.40 Norway and Switzerland are also considered brucellosis-free countries. Most of these countries do report a small number of cases annually, mainly in travellers to endemic countries or immigrants from endemic areas.41,42 A B abortus epidemic has been evolving since 1998 in Northern Ireland, with 89 cases in total. Reemergence of human brucellosis does not seem possible in western Europe, especially since adequate surveillance systems exist. Eradication campaigns in southern European member countries will probably prevent trafficking of the disease inside the EU. The Mediterranean basin is an acknowledged endemic region of human brucellosis. The disease was initially described in Malta, where sporadic cases are noted nowadays. France is an example of successful eradication. More than 800 cases of human brucellosis were reported in 1976, declining to 405 cases in 1983, 125 cases in 1990, and 44 cases in 2000.43 According to OIE data for the following years, the annual number of cases reported remained low.7 Most of these cases are due to localised outbreaks in southern provinces, and are related to the consumption of dairy products imported from Spain. The evolution of eradication is also represented in regional distribution. Corsica reported most of the national cases during 1990–95, yet no cases were http://infection.thelancet.com Vol 6 February 2006 Area New England Maine New Hampshire Vermont Massachusetts Rhode Island Connecticut Mid-Atlantic New York New Jersey Pennsylvania East north central Ohio Indiana Illinois Michigan Wisconsin West north central Minnesota Iowa Missouri North Dakota South Dakota Nebraska Kansas South Atlantic Delaware Maryland DC Virginia West Virginia North Carolina South Carolina Georgia Florida East south central Kentucky Tennessee Alabama Mississippi West south central Arkansas Louisiana Oklahoma Texas Mountain Montana Idaho Wyoming Colorado New Mexico Arizona Utah Nevada Pacific Washington Oregon California Alaska Hawaii Total Number of cases 11 0 1 0 8 0 2 27 13 3 11 111 12 1 68 24 6 52 9 22 15 0 1 2 3 126 2 5 1 6 0 46 3 18 45 23 4 7 7 5 310 24 8 5 273 91 1 5 7 18 12 43 5 0 305 10 8 272 2 13 1056 Annual incidence (cases per million)* 0·08 0 0·08 0 0·13 0 0·06 0·07 0·07 0·04 0·09 0·25 0·11 0·02 0·57 0·24 0·11 0·28 0·19 0·77 0·27 0 0·13 0·12 0·11 0·26 0·27 0·1 0·19 0·09 0 0·61 0·08 0·23 0·3 0·14 0·1 0·13 0·16 0·18 1·03 0·95 0·18 0·15 1·38 0·54 0·11 0·41 1·46 0·45 0·69 0·92 0·24 0 0·7 0·17 0·24 0·83 0·33 1·09 0·39 *Average incidence for 1993–2002, derived from the annual summaries of notifiable disease of the Centers for Disease Control and Prevention.18 1998 population used in estimating incidence, as provided in the same source. Table 2: Reported cases and annual incidence of brucellosis in the USA, 1994–2003 93 Review Annual incidence of brucellosis per 1000 000 population 1 0·5–1 0·1–0·5 0·1 No cases Figure 2: Brucellosis incidence in the USA, 1993–2002 reported in the past 3 years. Small foci still exist in the southeastern provinces of Savoie and Alpes Maritimes. Although massive progress has been achieved in minimising human disease in Spain, the country still has one of the highest annual incidences in Europe. Data are available for 1997–2003 from the National Centre of Epidemiology.12 A substantial, consistent decline in annual number of cases is evident, reaching an all-time low of 642 cases in 2003. This decline is reflected in most autonomous communities. However, the annual incidence remains high in Andalusia, Castille-La Mancha, Aragon, and Castille-Leon (70, 68, 60, and 56 cases per million per year, respectively). The highest annual incidence is noted in Extremadura, but the situation in this region has been improving substantially throughout this period. Although the consistent decline in the incidence of human brucellosis in Spain underlines the systematic national approach towards disease control, Spain remains an endemic area. However, one can be confident that the situation will change, approaching the French situation, in the years to come. Portugal has achieved pronounced progress in minimising human brucellosis. Data from the Portuguese Ministry of Health11 for 1999–2003 indicate a steep decline in annual incidence, from 70 cases per million in 1999 to less than 14 cases per million in 2003. The progress is attributed to enhanced control in certain endemic northern and central districts. However, the situation has not improved substantially in southern regions—eg, the district of Alentejo, where the annual incidence remains high. This district neighbours the endemic region of Extremadura in Spain; as already discussed, the situation in Extremadura has improved in recent years, and it will be interesting to observe the dynamics of human disease trafficking, and particularly whether persistence of the disease in the Portuguese region will induce a resurgence in the Spanish region. 94 In Italy, a unique pattern in the epidemiology of human brucellosis has been observed between 1994 and 2003, according to data derived from the Italian Ministry of Health.10 A steady decline in the number of annual cases has been consistently observed over the past 30 years: in 1976, 3318 cases were reported in total, and by 1986 the annual number of cases dropped below 2000. A gradual, although inconsistent, decline was subsequently observed. However, the annual incidence of the disease has not dropped in a uniform fashion across the country: of the 520 cases reported in 2003, 488 (93·2%) were reported from four southern regions, compared with 63·7% in 1994. Sicily alone reported 57·6% of the 2003 cases. The average annual incidence for Sicily, Calabria, Puglia, and Campania was 111, 48, 44, and 37 cases per million, respectively. None of the northern and central regions reported more than ten cases in 2003, and these cannot be attributed to local epidemiological factors. In Italy, human brucellosis has travelled to the south, something explained by socioeconomic factors; the schism of Italy to the rich north and the poor south is nowhere more pronounced than in the incidence of human brucellosis. Greece remains in the list of the 25 countries with the highest incidence worldwide. The annual incidence, according to data from the Centre for Special Infections Control9 is gradually declining. Concern exists that these data may not represent the actual situation: the data is generally inconsistent—eg, in 1995 only six cases were officially reported. Under-reporting is also evident in the regional distribution of cases, since the annual number of cases reported for the northwestern region of Epirus represents a gross underestimation according to our personal experience and a recent epidemiological study in this area.44 One reason for poor reporting, apart from inadequate awareness from private sector practitioners, http://infection.thelancet.com Vol 6 February 2006 Review is that a percentage of new cases consists of patients living in southern Albania, who commonly seek medical advice in Greece. These patients are reported neither in Greece nor in Albania. Even with official estimates, the annual incidence in Epirus is high—over 70 cases per million per year. Various parameters account for the increased incidence in this region: illegal trafficking of herds or even dairy products through the Greek/Albanian border, inadequate implementation of control programmes,45 poor health literacy of both general population and medical practitioners, fear of economic losses through slaughtering of infected livestock belonging to patients undergoing epidemiological surveillance, and most importantly, the overall socioeconomic status of the area. A measure of the relation between brucellosis endemicity and socioeconomic status can be drawn from the gross domestic product (GDP) for certain endemic regions of the EU, such as Epirus. Figure 3 shows the GDP values of various EU regions: the endemic areas of Portugal and Greece are characteristically the poorest areas of the EU. The disease is also widespread on the Greek mainland, with the average annual incidence for Thessaly, northern Greece, and Peloponissos approaching 120, 51, and 48 cases per million, respectively. Figure 4 depicts the brucellosis free and endemic regions of western and southern Europe. The Balkan peninsula Apart from Greece, two other countries in the Balkan peninsula have the highest disease incidence in Europe. In the Former Yugoslav Republic of Macedonia, human brucellosis is almost an epidemic, although the annual incidence is gradually decreasing.8 The incidence is also high in Albania,6 where a substantial degree of under100 Incidence 80 Brucellosis status Endemic Brucellosis free Non-endemic Figure 4: Brucellosis status in Europe reporting exists due to inadequate health networks and patient migration to Greece. The effect such an endemic site exerts on neighbouring countries has been already discussed, but is further underlined by a recent increase in the reported cases from Bosnia-Herzegovina,7 and in the region of Kosovo, where, according to the data from OIE,7 the annual incidence for 2004 approached 20 cases per million. 60 Eastern Europe 40 20 0 40·0 60·0 80·0 100·0 120·0 140·0 GDP Figure 3: Gross domestic product and endemicity of brucellosis for EU regions and countries Gross domestic product (GDP) according to official EU data.46 Data as follows (in parentheses, endemicity in annual cases per million of population and GDP as the percentage of median EU GDP before the expansion, respectively). Greece: Thessaly (87·5/60·2), Epirus (31·4/54), northern Greece (24·6/65·2). Italy: Sicily (60·4/65·3), Calabria (19·9/62·1), Campania (15·6/65·1), Puglia (14·7/65), Piemonte (1·4/115·1), Lombardia (0·9/131·3), Toscana (0·6/111·1), Emilia Romana (0·5/126·2), Veneto (0·2/115·8). Portugal: Alentejo (56·2/56·9), central (27·5/56·9), north (8·4/56·9), Lisbon and Vale do Tejo (4·7/94·7). Spain: Extremadura (54·1/53·5), Castille-La Mancha (51·6/67·1), Andalusia (32·5/63·1), Castille-Leon (31/78), Catalonia (7·7/100·7), Madrid (5·2/112·4), Basque country (1·4/105·1). Denmark: (2·6/115·3). Germany: (0·3/100·4). France: (0·5/104·8). Ireland: (1·3/117·6). Sweden (0·3/106·1). UK: (0·3/105·4). http://infection.thelancet.com Vol 6 February 2006 Brucellosis is not endemic in eastern Europe. Characteristically in Poland, the disease is limited to veterinarians or is imported from Mediterranean countries.47 Brucellosis in Russia nowadays is mainly a disease of the Caucasian districts—eg, Dagestan, where the annual incidence exceeds 100 cases per million of population48—and districts neighbouring republics of the former Soviet Union with a high incidence of brucellosis. However, substantial under-reporting may also exist. Asia The middle east has traditionally been considered as an endemic area. Indeed, five of the ten countries with the highest incidence for human brucellosis are in this area. 95 Review Syria has the highest annual incidence worldwide, reaching an alarming 1603 cases per million per year according to data from OIE.7 The annual cases reported are practically doubling each year, although this may be attributed to enhanced surveillance. An increase in the annual number of cases reported has been also observed in Turkey, exceeding 15 000 cases in 2004.7 Brucellosis is particularly endemic in the poor eastern regions. Numerous reports have addressed the epidemiology of the disease in isolated areas from this region,49 although a coordinated national approach is still missing. The relation of poor socioeconomic status and brucellosis incidence, as outlined in the EU, probably applies here too: numerous studies focusing on seroprevalence, summarised by Cetinkaya and colleagues,50 show that the proximity of a region either to Europe or to Ankara is accompanied by lower seroprevalence rates, possibly due to enhanced application of the Turkish Brucellosis Challenge Project that has been running for the past 20 years.50 The situation in Iran is improving, according to data from the National Commission on Communicable Diseases Control. In 1989 the annual incidence exceeded 1000 cases per million;51 in 2003, the annual incidence had fallen to 238·6 cases per million.8 Still, human brucellosis remains a huge burden for this country. Data from OIE were recently made available for the incidence of human brucellosis in Iraq,7 underlining the huge endemicity of the disease in this region, despite ongoing attempts to control both animal and human disease.52,53 Whether control can be achieved in a state still plagued by war and famine is questionable; moreover, the endemicity of the disease in this area may raise concerns, since a purely endemic brucellosis case in an international soldier stationed in Iraq might cause alarm of a possible biowarfare incident. Similarly, the endemicity of the disease in Afghanistan cannot be disputed, although substantial data are lacking. The first official report from the OIE from the region, in 2004,7 with an estimated incidence of 3·8 cases per million of population, might be a gross underestimation of the actual incidence. Brucellosis is endemic in the southern region of Oman, with an annual incidence exceeding 1000 cases per million.7 Saudi Arabia is also a vast reservoir of human brucellosis. Regional endemicity varies in Saudi Arabia, partly according to climate factors: a rainy season in an area would result in increased grass growth and thus influx of shepherds and flocks.54 The increased incidence of brucellosis in this country is also attributed to massive importations of uncontrolled slaughter animals and inadequate quarantine procedures.55 The absence of health literacy, which could interrupt the direct link between animal and human disease, is also critical.56 96 In the United Arab Emirates, most cases are reported from Dubai,25 a popular international travel destination, underlining the importance of the disease in the field of travel medicine. Kuwait is a prime example of modification of the epidemiology of human brucellosis by political factors: 20 years ago, the annual incidence exceeded 500 cases per million, mainly due to widespread animal brucellosis.51 Massive loss of livestock during the 1991 Iraqi invasion resulted in a substantial decrease in human cases in the following years; however, this decrease was not sustained over time,7 and the region is still endemic. In Jordan, the estimated incidence of human brucellosis exceeded 300 annual cases per million in the recent past.57 Data from the Ministry of Health denotes ongoing control of the disease between 1996 and 2003.20 Similar control has been achieved in Israel, a country that can no longer be considered endemic.7 However, an increased number of cases reported by Palestine in recent years58 could endanger the continuing decline of brucellosis prevalence in Israel. Endemicity of the disease in Lebanon has been steady over the past 10 years, especially in the Beqaa region, according to data from the Ministry of Public Health.22 One distinct characteristic of the disease in this country is that the most cases are noted in female patients, by contrast with the rest of the world, possibly reflecting an increased transmission as a foodborne disease (via milk consumption) or increased participation of women in procedures associated with brucellosis transmission (eg, milking). Seven republics of the former Soviet Union are included in the 25 countries with the highest incidence of the disease worldwide, while another country of this region, Mongolia, is ranked second. The situation in central and western Asia is dramatic: in Kyrgyzstan, control of brucellosis has become a national priority, since the already extremely high prevalence may actually be tripling: more cases were reported in the first half of 2003 than in the whole of 2002.59 In Tajikistan and Kazakhstan the annual cases reported are rapidly increasing, according to OIE data, when compared with WHO data from 1993–98.60 A rapid increase can be observed in Mongolia according to data from the National Statistic Office for the period up to 2000.23 Data from the Ministry of Health of Azerbaijan for the years up to 2000 show that the annual incidence is declining.61 Data from OIE7,16 show a steady incidence pattern for Armenia, Georgia, Uzbekistan, and Turkmenistan. These countries have emerged as the most important loci of human brucellosis worldwide in recent years, and the seemingly uncontrollable, constantly increasing incidence poses a serious public-health problem, especially in the context of inadequately developed health-care networks. Moreover, since a substantial percentage of the population in these countries relies on http://infection.thelancet.com Vol 6 February 2006 Review livestock for their survival, the disease affects the economic stability of these countries. How did these new foci of brucellosis emerge? All of these countries were part of the former Soviet Union, or were Eastern bloc satellite states. The evolution from a socialist state to free market economy resulted in the loss of strict livestock control. Furthermore, the transition of the health system during this period precluded early recognition of the disease, or intervention for the emerging trends in human beings and animals.62 Economic instability precludes further planning of such interventions, even if proven cost effective.63 However, it is possible that the endemic was already underway, but under-reporting took place before political transition. Either way, central policy directly influenced the natural history of human brucellosis in these areas, and international intervention is urgently needed. Interest and financial and scientific support from international organisations could be of huge benefit for these countries, but has not yet emerged. Most data available about the prevalence of brucellosis in China are derived from the work of Deqiu and colleagues.64 A massive vaccination programme of the human population at risk of acquiring brucellosis took place between 1964 and 1976. The annual number of cases reported exhibited a gradual decline, reaching an all-time low of almost 500 cases in 1994. Thereafter annual number of cases increased, approaching 1500–3000, without a reciprocal increase in the prevalence of animal brucellosis. This discrepancy may be attributed to increased awareness and enhanced laboratory diagnosis; however, others propose a relation with climate factors such as the periodicity of the El Niño phenomenon.64 A steep increase in the reported cases of human brucellosis was noted during the first half of 2004, with cases for this period reaching 5753, according to the Chinese Ministry of Health.19 B melitensis is the commonest pathogen isolated, although B abortus and B suis prevail in certain provinces (Sichuan and Guangxi/Guangdong, respectively). The geographic distribution has also evolved, with the disease travelling south. Until 1980 the incidence was highest in the provinces of Inner Mongolia, Jilin, and Helongiiang, in northeastern China. However, in the past 15 years the prevalence is highest in the eastern central provinces of Shanxi, Hebei, and Henan. Tibet remains a region with increased endemicity. According to data from OIE,7 an increasing number of human cases of brucellosis has been noted during 2003–04 in South Korea, the aetiology and significance of which remains obscure. The disease is endemic in India, with numerous reports of cases from isolated areas in the literature,65 and an acknowledged prevalence of animal brucellosis,66 but official data of the incidence of human disease are http://infection.thelancet.com Vol 6 February 2006 lacking. Animal disease exists also in Pakistan, but there are no data for the incidence of human disease. Australia A limited number of cases of human brucellosis are reported annually from Australia, according to the National Notifiable Diseases Surveillance System,26 almost exclusively from the area of Queensland, one of the poorest areas of the country. Africa North Africa has been traditionally considered endemic for brucellosis. Data on the prevalence of the disease in Egypt are scarce, with reports from national authorities probably underestimating the true prevalence of the disease, since they are derived from selected medical institutions.16 There are also no official data for Morocco; the disease may be endemic along the Moroccan/Algerian border. Limited data exist about Libya, while the incidence in Tunisia may be an underestimate of the actual situation.7 Algeria has the tenth highest annual incidence worldwide,8 but the annual number of cases reported remained steady during the last decade. Various WHO programmes have focused on controlling brucellosis in these countries,51 although available data would support the urgent need for such intervention only for Algeria and Tunisia. Brucellosis exists throughout sub-Saharan Africa, but essentially nothing is known about its prevalence. Most African countries are of poor socioeconomic status, with people living with and by their livestock, while health networks and surveillance and vaccination programmes are virtually non-existent. Moreover, there are far more morbid endemic infectious diseases, particularly malaria. Most febrile patients in these countries are initially empirically diagnosed as suffering from malaria, and only a small part of non-responders may be further tested for brucellosis. Most of the data are derived from small seroepidemiological studies of patients with fever or high-risk populations.67 According to data from OIE for 2004,7 Cameroon, Ethiopia, Kenya, Nigeria, Tanzania, and Uganda reported the existence of human cases of brucellosis, while in 2003 similar reports8 existed for Burkina Faso, Republic of Congo, Eritrea, Mali, Namibia, and Swaziland. Ghana, Togo, and Chad are probably also endemic according to seroepidemiological studies.67,68 Brucellosis cannot be considered an emergency for Africa since there are other, more morbid, infectious priorities. Moreover, control of animal disease might incorporate the slaughtering of infected animals (since mass vaccination campaigns demand funds and adequate health-care networks), further compromising the socioeconomic status of the susceptible population; in Africa, one can assume, it is better to live with brucellosis than try to eradicate it and then starve to death. 97 Review Search strategy and selection criteria Data on the prevalence of human brucellosis for each country from 1990 onwards were sought from health ministries or other official national organisations, public-health international organisations, and the medical literature. Medical literature was searched through Medline (but also general search engines), using “brucella” or “brucellosis” and individual country and region names as keywords. PROMEDmail was also used, searching with the keywords “brucellosis” and individual country names. When available, official national data were used, even if not in concordance with data from international organisations. For countries without such official data, data from international organisations were used. Medical literature was used only when including epidemiological information, or (in the case of seroprevalence studies) in the absence of any other data regarding disease status in a country. Serial data on incidence were evaluated for the presence of epidemiological trends correlating with sanitary, socioeconomic, and political characteristics of individual countries. In calculating the annual incidence, when this information was not provided in the source references, population data derived from official publications such as the CIA World Factbook71 were used. Conclusions The traditional perception of human brucellosis, as reproduced in most reviews of the disease,69,70 is of a zoonotic disease prevalent in countries of the Mediterranean basin, the near east, South America, and possibly sub-Saharan Africa. Yet, in the past 15 years, the epidemiology of human brucellosis has evolved, reflecting alterations in socioeconomic parameters, improvements in recognition and notification systems, outcomes of ongoing eradication programmes of animal brucellosis, and the evolution of the “global village” through international tourism. New endemic foci have emerged, warranting eradication programmes that escape national boundaries. Financial and scientific support from international organisations should target the new endemic areas and become a global health priority. Enhanced surveillance of human brucellosis may be responsible for the alteration in the endemicity of the disease in certain countries, but this fact serves only to underline the magnitude of the problem and the possibility of it further inflating in the near future. The fact that the continuing existence of human (and animal) brucellosis extends beyond medical and veterinary duties and encompasses political factors goes to show that the eradication of the disease will not be an easy task for the future. Conflicts of interest We declare that we have no conflicts of interest. References 1 Corbel MJ. Brucellosis: an overview. Emerg Infect Dis 1997; 3: 213–21. 98 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Joint FAO/WHO expert committee on brucellosis. World Health Organ Tech Rep Ser 1986; 740: 1–132. Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. N Engl J Med 2005; 352: 2325–36. Solera J, Lozano E, Martinez-Alfaro E, Espinosa A, Castillejos ML, Abad L. Brucellar spondylitis: review of 35 cases and literature survey. Clin Infect Dis 1999; 29: 1440–49. Memish ZA, Balkhy HH. Brucellosis and international travel. J Travel Med 2004; 11: 49–55. World Organisation for Animal Health. Handistatus II: zoonoses (human cases): global cases of brucellosis in 2000. http://www.oie. int/hs2/gi_zoon_mald.asp?c_cont=6&c_mald=172&annee=2000 (accessed Dec 13, 2005). World Organisation for Animal Health. Handistatus II: zoonoses (human cases): global cases of brucellosis in 2004. http://www.oie. int/hs2/gi_zoon_mald.asp?c_cont=6&c_mald=172&annee=2004 (accessed Dec 13, 2005). World Organisation for Animal Health. Handistatus II: zoonoses (human cases): global cases of brucellosis in 2003. http://www.oie. int/hs2/gi_zoon_mald.asp?c_cont=6&c_mald=172&annee=2003 (accessed Dec 13, 2005). Centre for Special Infections Control. Annual reported cases of notifiable diseases. http://www.keel.org.gr/stanalysis (accessed Aug 1, 2005). Ministry of Health, Italy. Results of epidemiological research. http://www.ministerosalute.it/promozione/malattie/datidefcons. jsp (accessed Dec 13, 2005). Ministry of Health, Portugal. Doenças de Declaração Obrigatória, 1999-2003. http://www.dgsaude.pt/upload/membro.id/ficheiros/ i007192.pdf (accessed Dec 13, 2005). National Centre of Epidemiology, Spain. Obligatory notifiable diseases, 2003. http://cne.isciii.es/htdocs/ve/Edo2003.htm (accessed Dec 13, 2005). Swiss Federal Office of Public Health. Reports of infectious diseases. http://www.bag.admin.ch/infreporting/mv/e/index.htm (accessed Dec 13, 2005). UK Department for Environment Food and Rural Affairs. UK zoonoses reports. http://www.defra.gov.uk/animalh/diseases/ zoonoses/reports.htm (accessed Dec 13, 2005). Ministry of Health and Population, Egypt. Enhanced surveillance for communicable diseases. http://www.geis.fhp.osd.mil/GEIS/ Training/EgyptSurv2000.htm (accessed Dec 13, 2005). World Organisation for Animal Health. Handistatus II: zoonoses (human cases): global cases of brucellosis in 2002. http://www.oie. int/hs2/gi_zoon_mald.asp?c_cont=6&c_mald=172&annee=2002 (accessed Dec 13, 2005). Centers for Disease Control and Prevention. Summary of notifiable diseases, United States, 2003. http://www.cdc.gov/mmwr/sum mary.html (accessed Dec 13, 2005). Ministry of Health, Mexico. Epidemiological information. http:// www.dgepi.salud.gob.mx/infoepi/index.htm (accessed Dec 13, 2005) Xinhua News Agency. Health ministry increases efforts to contain brucellosis. http://service.china.org.cn/link/wcm/Show_Text?info_ id=115313&p_qry=brucellosis (accessed Dec 13, 2005) Ministry of Health, Jordan. Annual statistical report: notifiable communicable diseases. http://db-server.moh.gov.jo:7777/servlets/ svr_pack.Incidsrve (accessed Nov 24, 2005). White N. Kazakhstan in a fight against brucellosis. Casper-Star Tribune http://www.1wyo.net/KAZAKHSTAN/introduction.html (accessed Dec 14, 2005) Lebanese Ministry of Public Health, Epidemiology Surveillance Unit. http://www.public-health.gov.lb/esu/LEBANON.shtml (accessed Jan 3, 2006). Ebright JR, Altantsetseg T, Oyungerel R. Emerging infectious diseases in Mongolia. Emerg Infect Dis 2003; 9: 1509–15. World Organisation for Animal Health. Handistatus II: zoonoses (human cases): global cases of brucellosis 1998. http://www.oie. int/hs2/gi_zoon_mald.asp?c_cont=6&c_mald=172&annee=1998 (accessed Dec 14, 2005). United Arab Emirates Ministry of Health. Brucellosis distribution of reported cases by Medical District UAE 1994-2000. http://www. moh.gov.ae/moh_site/prev_med/anbk/statistics/comdis/zoono/ stat6/t1.htm (accessed Dec 14, 2005). http://infection.thelancet.com Vol 6 February 2006 Review 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 Australian Department of Health and Aging. National notifiable diseases system. http://www9.health.gov.au/cda/Source/Rpt_4_sel. cfm (accessed Dec 14, 2005). Wise RI. Brucellosis in the United States. Past, present, and future. JAMA 1980; 244: 2318–22. Buchanan TM, Hendricks SL, Patton CM, Feldman RA. Brucellosis in the United States, 1960–1972; An abattoir-associated disease. Part III. Epidemiology and evidence for acquired immunity. Medicine (Baltimore) 1974; 53: 427–39. Doyle TJ, Bryan RT. Infectious disease morbidity in the US region bordering Mexico, 1990–1998. J Infect Dis 2000; 182: 1503–10. Fosgate GT, Carpenter TE, Chomel BB, Case JT, DeBess EE, Reilly KF. Time-space clustering of human brucellosis, California, 1973–1992. Emerg Infect Dis 2002; 8: 672–78. Troy SB, Rickman LS, Davis, CE. Brucellosis in San Diego: epidemiology and species-related differences in acute clinical presentations. Medicine (Baltimore) 2005; 84: 174–87. Young EJ, Suvannoparrat U. Brucellosis outbreak attributed to ingestion of unpasteurized goat cheese. Arch Intern Med 1975; 135: 240–43. Thapar MK, Young EJ. Urban outbreak of goat cheese brucellosis. Pediatr Infect Dis 1986; 5: 640–43. Taylor JP, Perdue JN. The changing epidemiology of human brucellosis in Texas, 1977–1986. Am J Epidemiol 1989; 130: 160–65. Luna-Martinez JE, Mejia-Teran C. Brucellosis in Mexico: current status and trends. Vet Microbiol 2002; 90: 19–30. Moreno E. Brucellosis in Central America. Vet Microbiol 2002; 90: 31–38. Trujillo IZ, Zavala AN, Caceres JG, Miranda CQ. Brucellosis. Infect Dis Clin North Am 1994; 8: 225–41. Samartino LE. Brucellosis in Argentina. Vet Microbiol 2002; 90: 71–80. Poester FP, Goncalves VS, Lage AP. Brucellosis in Brazil. Vet Microbiol 2002; 90: 55–62. European Commission. Report on trends and sources of zoonotic agents in the European Union and Norway, 2003. Brucella. http:// europa.eu.int/comm/food/food/biosafety/salmonella/02_brucella_ 2003.pdf (accessed Dec 14, 2005). Eriksen N, Lemming L, Hojlyng N, Bruun B. Brucellosis in immigrants in Denmark. Scand J Infect Dis 2002; 34: 540–42. Al Dahouk S, Nockler K, Hensel A, et al. Human brucellosis in a nonendemic country: a report from Germany, 2002 and 2003. Eur J Clin Microbiol Infect Dis 2005; 24: 450–56. Institut de Veille Sanitaire, France. Brucellose. http://www.invs. sante.fr/surveillance/brucellose/default.htm (accessed Dec 24, 2005). Avdikou I, Maipa V, Alamanos Y. Epidemiology of human brucellosis in a defined area of northwestern Greece. Epidemiol Infect 2005; 133: 905–10. Godfroid J, Kasbohrer A. Brucellosis in the European Union and Norway at the turn of the twenty-first century. Vet Microbiol 2002; 90: 135–45. European Commission. Third report on economic and social cohesion. http://europa.eu.int/comm/regional_policy/sources/ docoffic/official/reports/cohesion3/cohesion3_en.htm (accessed Dec 14, 2005). Czerwinski M. Human brucellosis in Poland. Przegl Epidemiol 2005; 59: 323–25 (in Polish). Isaev AN, Omarieva EIa, Liamkin GA. Epidemiologic situation of brucellosis in the regions of the Republic of Dagestan affected by the flood of 2002. Zh Mikrobiol Epidemiol Immunobiol 2003; 6 (suppl): S78–81 (in Russian). Aygen B, Doganay M, Sumerkan B, Yildiz O, Kayabas U. Clinical manifestations, complications, and treatment of brucellosis: a retrospective evaluation of 480 patients. Med Malad Infect 2002; 32: 485–93. http://infection.thelancet.com Vol 6 February 2006 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 Cetinkaya F, Nacar M, Koc AN, Gokahmetoglou S, Aydin T. Prevalence of brucellosis in the rural area of Kayseri, Central Anatolia, Turkey. Turk J Med Sci 2005; 35: 121–26. Regional Animal Disease Surveillance and Control Network, Food and Agriculture Organization of the United Nations. A perspective of brucellosis surveillance in North Africa and Middle East. http://www.fao.org/WAICENT/FaoInfo/Agricult/AGA/AGAH/ID/ Radiscon/brucactsurv.pdf (accessed Dec 14, 2005). United States Agency for International Development. Iraq reconstruction and humanitarian relief weekly update number 34 (FY 2004). http://www.reliefweb.int/rw/rwb.nsf/ AllDocsByUNID/442ddae9e2c8c46a85256ea900679403 (accessed Jan 3, 2006). UN Office for the Coordination of Humanitarian Affairs. Iraq: new campaign to control brucellosis. http://www.irinnews.org/ report.asp?ReportID=47021&SelectRegion=Middle_East&SelectCo untry=IRAQ (accessed Dec 14, 2005). Elbeltagy KE. An epidemiological profile of brucellosis in Tabuk Province, Saudi Arabia. East Mediterr Health J 2001; 7: 791–98. Memish Z. Brucellosis control in Saudi Arabia: prospects and challenges. J Chemother 2001; 13 (suppl): S11–17. Bilal NE, Jamjoom GA, Bobo RA, Aly OF, el-Nashar NM. A study of the knowledge, attitude and practice (KAP) of a Saudi Arabian community towards the problem of brucellosis. J Egypt Public Health Assoc 1991; 66: 227–38. Issa H, Jamal M. Brucellosis in children in south Jordan. East Mediterr Health J 1999; 5: 895–902. Husseini AS, Ramlawi AM. Brucellosis in the West Bank, Palestine. Saudi Med J 2004; 25: 1640–43. UN Office for the Coordination of Humantiarian Affairs. Kyrgyzstan: focus on brucellosis in south. http://www.irinnews. org/report.asp?ReportID=37604&SelectRegion=Central_Asia (accessed Dec 14, 2005). WHO. Country reports: 8th report of the WHO surveillance programme for control of foodborne infections and intoxications in Europe, 1999–2000. http://www.who.int/foodsafety/publications/ foodborne_disease/dec2003/en (accessed Dec 14, 2005). Azerbaijan Republic, Ministry of Health. Infectious diseases (total). http://www.mednet.az (accessed Oct 3, 2005). Manaseki S. Mongolia: a health system in transition. BMJ 1993; 307: 1609–11. Roth F, Zinsstag J, Orkhon D, et al. Human health benefits from livestock vaccination for brucellosis: case study. Bull World Health Organ 2003; 81: 867–76. Deqiu S, Donglou X, Jiming Y. Epidemiology and control of brucellosis in China. Vet Microbiol 2002; 90: 165–82. Thakur SD, Thapliyal DC. Seroprevalence of brucellosis in man. J Commun Dis 2002; 34: 106–09. Renukaradhya GJ, Isloor S, Rajasekhar M. Epidemiology, zoonotic aspects, vaccination and control/eradication of brucellosis in India. Vet Microbiol 2002; 90: 183–95. McDermott JJ, Arimi SM. Brucellosis in sub-Saharan Africa: epidemiology, control and impact. Vet Microbiol 2002; 90: 111–34. Schelling E, Diguimbaye C, Daoud S, et al. Brucellosis and Q-fever seroprevalences of nomadic pastoralists and their livestock in Chad. Prev Vet Med 2003; 61: 279–93. Araj GF. Human brucellosis: a classical infectious disease with persistent diagnostic challenges. Clin Lab Sci 1999; 12: 207–12. Young EJ. An overview of human brucellosis. Clin Infect Dis 1995; 21: 283–89. Central Intelligence Agency. The world factbook. http://www.cia.gov/cia/publications/factbook/index.html (accessed Dec 13, 2005). 99