Background
Brucellosis, a common zoonotic disease also referred to as Bang's disease, Crimean fever, Gibraltar fever, Malta fever, Maltese fever, Mediterranean fever, rock fever, and undulant fever, remains a major burden in both human and domesticated animal populations worldwide, especially in the Mediterranean region, Asia, the Middle East, Sub-Saharan Africa, Latin America and the Balkan Peninsula [
1-
3]. Causing more than 500,000 new human cases worldwide annually [
2], Brucellosis is directly transmitted to humans via contact with animals that carry the pathogenic bacteria
Brucella or infectious material during animal husbandry and meat processing, or indirectly through the consumption of unpasteurized dairy products [
4]. Infection among different animal species is mostly attributed to different infectious agents in the genus
Brucella (
B.). The primary causative agents include
B. melitensis (sheep and goats),
B. ovis (sheep and goat),
B. abortus (cattle),
B. suis (swine), and
B. canis (dog) [
4-
6], although more have been detected in both domesticated and wildlife species [
7,
8]. Brucellosis itself yields low mortality rates, but it can cause substantial disabilities and weaknesses to the human immune system [
9]. The clinical presentation can be acute, subacute or chronic, varying from joint, muscle and back pain to flu-like symptoms, and even more serious conditions in different organ systems [
10]. However, it most commonly targets the reproductive system, resulting in up to a 40% increase in fetal wastage during the early stages of pregnancy and up to 2% of fetal deaths during the later stages of pregnancy for expectant women [
11].
Details of production, multiplication and spread of the
Brucella spp. among livestock have been described elsewhere [
12], but a brief summary is given here. Initially,
B. abortus replicates itself in regional lymph nodes of cows. Uterine infection occurs during the second trimester and is followed by placental inflammation that develops into placental disruption and endometritis ultimately leading to fetal death, after which the fetus is normally retained 1 to 3 days in utero and delivered with numerous bacteria expelled from the genital tract and spread out by various pathways. Brucellosis is detrimental to human health, and can lead to reductions in livestock production and subsequent economic losses, reduced milk/meat production, time lost by patients from normal daily activities, and increased medical costs [
13,
14]. Combination therapy with long-acting oxytetracycline and streptomycin has shown to moderate the effectiveness of the disease resulting in a reduction of shedding in most cows and complete elimination of infection in some cows. However, due to low treatment success rates, many countries (e.g., United States, European Union member countries, Australia and New Zealand) adopted eradication programs to slaughter the infected cows and quarantine the exposed herdmates until they could either be slaughtered or recertified as Brucellosis-free [
12,
15,
16].
In China, Brucellosis remains a major public health issue. Previous studies indicated that human Brucellosis was endemic in 25 of 32 provinces (or autonomous regions) of mainland China [
17]. Inner Mongolia Autonomous Region has been most severely affected by Brucellosis in both humans and livestock since 1999, reporting the largest number of human Brucellosis cases across China [
18,
19], and accounting for approximately 40% of the total reported cases in China during 1999–2008 [
18,
20], 47.2% in 2010 [
21], and almost 50% during 2005–2010 [
19]. However, few efforts have been specifically focused on the distribution of human Brucellosis cases in Inner Mongolia. One recent study revealed potential relationships between the incidence of human Brucellosis cases in China and some environmental factors, including temperature, rainfall, hours of sunshine, relative humidity and average wind velocity [
22], but additional research is needed.
The goal of this study is two-fold: 1) examine the spatio-temporal distribution of reported human Brucellosis cases and incidence rates across Inner Mongolia during 1950–2010 and 2) examine the association of environmental factors with human Brucellosis occurrences in Inner Mongolia. Geographic Information Systems (GIS), remote sensing (RS), exploratory spatial data analysis (ESDA) and ecological niche modeling (ENM) were utilized to achieve the goals of this study.
Discussions
Multiple studies have explored the spatial patterns of human Brucellosis in various countries including Azerbaijan [
4], Italy [
52], Germany [
53], United States [
54], Ecuador [
36], and mainland China [
14,
19,
55]. However, the most suitable study area for Brucellosis in China, Inner Mongolia, has not been well-studied. Moreover, limited efforts have primarily focused on the environmental dynamics of human Brucellosis occurrences [
22]. To fill the gaps, this study systematically examined the spatial-temporal distribution of reported human Brucellosis cases and incidence rates at the municipal level from 1950 to 2010 and at the county level from 2006 to 2010, as well as the impacts of environmental and socioeconomic factors on human Brucellosis occurrences at point-level and county-level locations.
The study represents the first effort to combine GIS, RS and ENM techniques for the study of human Brucellosis. With the rapid spread of advanced spatial techniques and fast growing volume of high-resolution spatio-temporal data, GIS and RS are playing an increasingly vital role in medical geography and spatial epidemiology over recent years. GIS and RS provide a powerful toolset and diversity of data sources for ENM; ENM in turn has advanced conventional spatio-temporal analysis by adding more mathematical and computational complexity.
The probability of presence for human Brucellosis based on the ENM represents the extent of the similarity of environmental and socioeconomic conditions at each location to those most suitable for human Brucellosis. The locations with high predicted probability of presence do not necessarily have a large number of reported cases in the past. They may just have suitable conditions and, consequently, the potential for future occurrences. Pilot surveillance programs should be launched to determine if any under reporting or reporting biases exists at those locations.
From the perspective of historical variations, although there has been a surprising increase from 1950 to 2010, increasing accessibility to health facilities for diagnosis and reporting may be partly responsible for the perceived increase in human Brucellosis cases, especially in Brucellosis epidemic regions where the incidence rates of human Brucellosis cases increased dramatically between 2001 and 2010 (e.g., Hulunbuir and Xinli Gol). The number of health facilities has also dramatically increased and improved in Inner Mongolia since 2003 when reporting networks were established. Surveillance is typically based on the diagnosis of human cases in the nearest health facilities, which are then communicated to the IMCDC by municipal health departments and subsequently forwarded to the CCDC through the National Notifiable Disease Surveillance System. This procedure may be affected by a lack of accurate diagnosis, imprecise symptoms, uneven case detection efforts, and reporting bias; therefore a spatially smoothed approach was used for reducing spurious outliers. Reporting bias may also, to some extent, result in a mismatch between highly-suspected occurrence points and areas with high risk for Brucellosis predicted by ENM models.
Inner Mongolia is well-known for its extensive prairies and grass-fed livestock including cattle and sheep, which are often the carriers for the bacteria
Brucella. The region contained approximately 18.2% of the total sheep population during 2005–2010, larger than any other province in mainland China [
56]. Consequently, Inner Mongolia is considered a focal area for the study of human Brucellosis. A descriptive study in Inner Mongolia revealed that occupation (agriculture worker, shepherd, butcher, slaughter-house worker, and cattle dealer), risky practices (handling of ruminant abortions, skinning of stillborn lambs and kids, and crushing the umbilical cord of newborn lambs and kids with teeth), and certain dietary preferences (consuming unpasteurized and unboiled milk and fresh cheese) were correlated with the occurrence of Brucellosis in humans [
18]. Larger numbers of reported human cases during 1999–2008 occurred predominantly in a specific gender (male, 70.2%) and age range (30–59 years old, 64.7%) and is likely a result of these groups participating in risky occupations and practices. Occupational features of Brucellosis also help to explain why more cases are reported in the east (humid, grassland-dominant) than west (arid and semiarid, desert-dominant) and in rural areas over urban areas. Additional educational programs should be launched, specifically aimed at enhancing the awareness of work-place Brucellosis prevention for certain groups.
Brucellosis is most often carried by domesticated animals and evidence from a model of animal-human Brucellosis transmission shows that 90% of human Brucellosis cases are small-ruminant derived in Mongolia [
6]. In China, higher incidence rates of human Brucellosis were positively associated with the density of sheep and goats [
22] and approximately 84.5% of the total human cases were found to be infected by
B. melitensis [
17]. Especially in Inner Mongolia, this proportion reached 90.25% or higher during 1996–2010 [
21]. Therefore, small ruminant density in 2005 is used as an indicator for the possibility of human occurrences, and sheep and goats are combined to represent small ruminant densities in 2010 when small ruminant density is not available. Cattle was not associated with human Brucellosis occurrences in a previous study in China [
22]. In addition to livestock density, nomadicity might play an important role in the transmission of Brucellosis among animals in Inner Mongolia through the mixing of herds, which can affect the transmission in humans. This is a limitation of this study due to the complex movement of livestock.
The vaccination rate for sheep in Inner Mongolia was previously only 31.6% [
25]. A study concluded that vaccinating adult sheep alone is insufficient in eradicating Brucellosis based on the prediction that Brucellosis would persist for a long period of time even though all sheep were supposedly vaccinated twice per year [
21]. Since 2011, the government in Inner Mongolia began to require vaccinations for all sheep twice per year. Given that infected sheep are still common across Inner Mongolia, especially amongst local herdsman, simultaneous disinfection and vaccination was suggested, as well as regular sheep surveillance which has been realized for some areas in China [
21].
Environmental modeling for human Brucellosis is uncommon because Brucellosis is not as climate-sensitive as some infectious diseases, such as malaria [
57,
58] and dengue fever [
45,
59] among other diseases. However, varying environmental conditions can result in a lack of water or grass in the pasturing areas, which increases disease susceptibility in animals with low resistance. Altitude especially can play an important role in the types of vegetation that can grow in certain areas, precipitation levels, temperature ranges, and other environmental conditions important to the survival and transmission of
Brucella. Consequently, altitude was the most influential abiotic variable within the ENM. Additionally, Brucellosis is capable of being transmitted by fomites. The
Brucella organism can survive for several months in water, aborted fetuses, manure, hay, contaminated equipment and clothes, and especially in conditions with high humidity, low temperature, and no sunlight [
5]. Although the theory is on a micro-level, similar environmental impacts have been revealed by a macro-level study, where lower temperature and less sunshine in winter and spring, and a 1–2 month incubation period have been associated with epidemic peaks from March to August, especially in the month of May [
22]. Inhabitants of Inner Mongolia also spend more time working outside during epidemic months than during the harsh winter months, increasing their exposure to Brucellosis infection. In addition to environmental and biological determinants of the organism, different cultural and livestock management practices among communities in the highlands might impact differences in risk factors, but these differences warrant additional epidemiological field work before they can be confirmed.
After Inner Mongolia, the five provinces with the most human Brucellosis cases reported during 2005–2010 (Shannxi, Heilongjiang, Hebei, Jilin and Shanxi) all share a border with Inner Mongolia, which was also detected as the primary cluster of incidence rates [
55] and accounted for most major occurrences of human Brucellosis cases in China [
19]. Therefore, the ENM prediction was extended outside of Inner Mongolia to all bordering counties. Some human cases were previously reported in non-epidemic parts of China, such as Guangdong and Fujian provinces in southeastern China, which might be attributed to increased transportation of un-quarantined and unvaccinated animals and travelling of people from epidemic areas [
11,
18,
22]. It is recommended to examine travel history as part of a more inclusive epidemiological investigation in non-endemic regions.
A major limitation of the study pertains to the quality of disease data that were available (as is the case with most ENM and SDM research [
47-
51]) because the true occurrence locations were not available. Brucellosis is not a contagious disease among humans, so predicting the high risk areas of human Brucellosis requires knowledge of the locations where people are most likely infected. The dasymetric procedure provided a much more certain location-to-environment relationship for modeling purposes and was superior to the alternative use of average environmental conditions at the county or municipal levels. According to the study of the occupation of patients during the 1991–2005 period in Inner Mongolia, peasants and herders consisted of 79.36% of all cases [
25]. This provided further evidence in selecting appropriate locations for human Brucellosis. Other limitations include the inability to consider the differences in the accessibility to health facilities and diagnostic services between the counties reporting larger and smaller numbers of human cases.
This study provides a new direction for human Brucellosis research and greatly contributes to our knowledge of the roles that various environmental and socioeconomic factors play in the distribution and spread of human Brucellosis occurrences. Moreover, the output of this study will promote comparisons with future research at an international scale and provide a new perspective to inform decision-making in the field of public health in Inner Mongolia. This study also serves as a predecessor to broader and more in-depth studies of human Brucellosis in Inner Mongolia. Expansions in both spatial and temporal scales are warranted and could provide further insight.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
PJ designed this study and acquired data. PJ and AJ were responsible for all analyses, interpretation of data, and drafting and revising the manuscript. Both authors read and approved the final manuscript.
Peng Jia is a graduate student in the Department of Geography and Anthropology at Louisiana State University. He specializes in GIS, remote sensing, medical geography, spatio-temporal analysis, and measurement of health care utilization.
Timothy Andrew Joyner is an assistant professor in the Department of Geosciences at East Tennessee State University. He specializes in GIS, geospatial analysis, geohazards, medical geography, and spatial modeling.