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Emerging bacterial diseases in India


Emerging and re-emerging bacterial diseases in India

Emeritus Professor (National Academy of Medical Sciences), Senior Consultant, Dr B L Kapur Memorial Hospital, 5, Pusa Road, New Delhi 110 005, India (Fax, 91-11-24655226; Email There has been a remarkable progress in the prevention, control and even eradication of infectious diseases with improved hygiene and development of antimicrobials and vaccines.However, infectious diseases still remain a leading cause of global disease burden with high morbidity and mortality especially in the developing world. Furthermore, there have been threats of new diseases during the past three decades due to the evolution and adaptation of microbes and the re-emergence of old diseases due to the development of antimicrobial resistance and the capacity to spread to new geographic areas. The impact of the emerging and re-emerging diseases in India has been tremendous at socioeconomic and public health levels. Their control requires continuing surveillance, research and training, better diagnostic facilities and improved public health system. Emerging and reemerging zoonotic diseases, foodborne and waterborne diseases and diseases caused by multiresistant organisms constitute the major threats in India. This review of bacterial emerging and re-emerging diseases should be of critical importance to microbiologists, clinicians, public health personnel and policy makers in India.
[Chugh T D 2008 Emerging and re-emerging bacterial diseases in India; J. Biosci. 33 549555]



In 1948, the US Secretary of State remarked the conquest of all infectious diseases was imminent. In 1962, F M Burnet, the Nobel Prize winner, made an optimistic statement To write about infectious disease is almost to write of something that has passed into history..., the most likely forecast about the future of infectious disease, is that it will be very dull. In December 1967, the US Surgeon General William Stewart declared victory by announcing The war against infectious diseases has been won. However, infectious diseases are a dominant public health problem even in the 21st century. The World Health Organisation estimates 25% of the total 57 million annual deaths that occur worldwide are caused by microbes and this proportion is signicantly higher in the developing world. In the landmark report to Institute of Medicine (1992) in the US, Joshua Lederberg and Robert Shope identied the emerging microbial threats and attributed to the emergence of new pathogens due to microbial evolution

and adaptation, change in human behaviour, population movement, civil unrest and industrial, agricultural and economic development. Interspecies navigation and Kingdom jumping are responsible for the new microbes. Major societal determinants of these infections are population growth, ageing population, poverty and malnutrition, internally displaced persons due to conicts, environmental pollution and global warming. The new megacities have crowding, inadequate infrastructure, poor sanitation and watersupply and poverty that amplify transmission of infectious diseases. Emerging infections are new diseases that have not been previously described (table 1) and re-emerging are the ones which were seen earlier but have now reappeared in a more virulent form or in a new epidemiological setting after a period of decline or disappearance (e.g. inuenza A, tuberculosis, malaria and dengue). The breakdown and complacency of public health measures for previously controlled infections, population movements, socioeconomic disruptions and development of antimicrobial resistance due to overuse of these durgs in

Control of infections; emerging infections; re-emerging infections; Southeast Asia and global prevalence

Abbreviations used: AMR, antimicrobial resistance; EHEC, enterohaemorrhagic Escherichia coli; VISA, vancomycin intermediate resistant S. aureus; PUO, pyrexia of unknown origin J. Biosci. 33(4), November 2008, 549555, Indian Academy ofNovember 2008 J. Biosci. 33(4), Sciences 549

Table1. Major emerging infectious agents Year identied 1972 1973 1975 1976 1977 1977 1977 1977 1980 1982 Agent Small round viruses Rotaviruses Parvo virus B-19 Cryptosporidium parvum Ebola virus Legionella pneumophila Hantaan virus Campylobacter spp Human T-lymphotropic virus (HTLV -1) Borrelia burgdorferi

T D Chugh

Year identied 1983 1983 1983 1988 1989 1992 1992 1996 1997 1999

Agent Human immunodeciency viruses Escherichia coli 0157:H7 Helicobacter pylori Hepatitis E Virus Hepatitis C virus Vibrio cholerae 0139 Bartonella henselae Prion Inuenza A virus (H5N1) Ehrlichia ewingii

humans and animals and microbial adaptability have led to the reemergence of these diseases. Only bacterial emerging and re-emerging diseases commonly seen in India are discussed in this review. Other microbial diseases; viral, parasitic and mycobacterial, will be reviewed in the companion publications. 2. Zoonotic diseases

The signicance of zoonoses in the emergence of human infections cannot be overstated. Around 61% human microbial pathogens and 73% emerging human pathogens identied during the past two decades are zoonotic (Gregar 2007). Medical anthropologists have identied anthropogenic changes in landuse and agriculture, suburbinisation, habitat destruction, increase demand for animal protein, use of bushmeat, live animal transport and domestication of animals around 10000 years ago and the exotic pet trade biggest conduits for zoonotic disease transmission. This transmission may be bidirectional with molecular-typed conrmations observed in bovine and human tuberculosis. Though poorly documented, zoonosis is a major public health problem in India. Zoonotic diseases assume a great public health importance as approximately 80% population in India lives in close contact with domesticated animals and poultry and there is also an abundance of vectors. 2.1 Plague

The changes in rodent ecology has been identied as the risk factor for reemergence of plague. It has caused 12 million deaths in India since the rst recorded case in 1896 in Bombay (John 1996). After the last laboratory-conrmed case was reported in 1966 in Karnataka, there was a lull for almost three decades till two outbreaks were reported during August-October in 1994, an outbreak of pneumonic plague in Surat, Gujarat and the second outbreak of bubonic plague in Beed, Maharashtra. There were a total of 54 deaths (52 in Surat) and 876 seropositive cases; 596 in Maharashtra, 151 in Gujarat, 68 in Delhi, 50 in Karnataka, 10 in Uttar Pradesh and 1 in Madhya Pradesh. Mahesh et al (2005) did molecular detection of 18 Yersinia pestis isolates from the sputa of pneumonic plague patients, using monoclonal antibodies against the recombinant plasminogen activator protein of the pathogen. Gupta and Sharma (2007) reported an outbreak of 16 conrmed cases of pneumonic plague seen during 2002 in Himachal Pradesh. A previous outbreak of 22 similar but unconrmed cases was reported in this region during 1983. An outbreak of bubonic plague was reported in Uttaranchal in 2004. The control measures require early clinical suspicion, prompt laboratory diagnosis, strict isolation of patients of pneumonic plague,appropriate antibiotic therapy and case contact management. A vaccine is available for persons who have repeated contact with the pathogen. The best plague prevention strategy is an aggressive rodent population control. 2.2 Leptospirosis

Plague is an ancient disease which caused three pandemics since the 6th century but the global transmission has been low in recent years. It is a bacterial zoonosis with rodents being the principle reservoir. The black rat (Rattus rattus) and oriental rat ea (Xenopsylla cheopis) are notorious reservoir and transmitting agent for human plague in India.
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Leptospirosis is an emerging global public health problem. The disease is caused by Leptospira interrogans naturally seen in rodents. These parasitise kidneys and are excreted in rat urine. Man and cattle are incidental hosts. They get infected by contact with water or soil contaminated with

Emerging bacterial diseases in India rat urine. The farm workers, sewer workers, shermen and miners are at high risk of infection. Due to difcult laboratory diagnosis and a lack of awareness, the real magnitude of the disease remains unknown. International Leptospirosis Society conducted three recent worldwide surveys and estimate about half a million severe cases of the disease worldwide annually (Hartskeer 2006). Taylor and Goyle (1931) rst described the disease in Andaman Islands, India. They reported 60 cases conrmed by serology and isolated the causative agent in 26. The 1980s witnessed a sudden increase in leptospirosis and seroepidemiologic and clinical studies show that the disease is endemic in Andaman Islands and southern states of India. Sehgal (2006) has reviewed the epidemiological pattern of disease in India .The seroprevalence is reported to be high (52.7%) among high-risk population of these Islands and 19.8% and 9.3% in Madras and Bangalore respectively. L interrogans serovar valbuzzi of serogroup Grippolyphosa is the causative agent in human patients and rodents. Outbreaks were reported from Mysore, Gujarat, Nagpur and Andamans in 1997. There was a severe outbreak in Mumbai in May 2000 and Kerala in August 2000, causing signicant mortality. An outbreak of leptospirosis was also reported in 102 cases in Mumbai following prolonged water logging due to heavy rainfall during July, 2002. Leptospirosis is widespread in animals in other regions as well- West Bengal, Bihar, Punjab, Haryana and Andhra Pradesh and has been reported to be a common cause of acute renal failure in south India (WHO 2006). 2.3 Brucellosis


origion (PUO) in Kashmir (Kadri et al 2000). Mantur et al 2007 have done extensive serological and microbiological studies in Karnataka. They reported seroprevalence of 1.6% by standard agglutination test (> 1:160) and isolated B. melitensis in 43 pediatric patients during a period of 13 years. During the same period they diagnosed 492 adult patients. Agasthya et al (2007) examined 618 sera from various professionals at risk and 15.69% tested positive. These studies clearly show a high prevalence of the disease in various parts of India (Smits and Kadri 2005). Vaccination with B. abortus 19BA, and hygienic measures can protect the persons who are at occupational risk. 2.4 Anthrax

Brucellosis affects primarily the livestock and is transmitted to humans by ingestion, close contact, inhalation or accidental inoculation. The prevalence of brucellosis in different geographical areas varies with standards of personal and environmental hygiene, animal husbandry practices, species of the causative agent and local methods of food processing. Brucella melitensis is the prevalent species seen in man and causes a more severe form of disease. Dogs are carriers of Brucella canis which can be transmitted to humans. India has an enormous cattle wealth. The disease has been repeatedly reported in the animals in India. However, very few human studies have been undertaken. It is estimated that the true incidence is 25 times higher than the reported cases due to underdiagnosis. Mathur (1964) from north India reported seroprevalence of 8.5% among dairy workers and 4.2% in aborted women. He also isolated Brucella spp from the blood of 7 human cases. Thakur and Thapliyal (2002) reported a seroprevalence of 17.39% in eld veterinarians and abattoir workers. Seropositive cases were seen in 28 of 414 (7.0%) patients of PUO in Varanasi (Sen et al 2002) and 28 of 3532 (0.8%) patients of pyrexia of unknown

Anthrax is an ancient disease commonly seen in domestic herbivorous animals. The cattle, sheep, goats and horses are very susceptible to natural infection and the disease is rapidly fatal due to severe septicemia. This was the rst microbial disease where the causative organisms were seen under the microscope, the rst pathogen grown in vitro, the rst disease where the four Kochs postulates were proven by animal inoculation and the rst disease where a bacterial vaccine was developed. Human anthrax is most prevalent when direct human contact with infected animals occurs. Anthrax spores are transmitted by contact with infected carcasses, hides, hairs or bonemeal. It is endemic in countries like India, Pakistan, Iran, Russia, Latin America and Central Africa. Live attenuated spore vaccine for domestic animals can successfully control disease and stop transmission to humans. The control of the disease requires a coordination between public health, agriculture and animal husbandry departments and the industry. The potential use of anthrax bacillus in bioterrorism is a genuine concern. Penicillinresistant virulent strains have been produced in vitro and are now seen in clinical practice as well. The disease is endemic in Tamil Nadu, Karnataka and Andhra Pradesh (Kumar et al 2000). Thappa and Karthikeyan (2001) have reviewed the subject in Indian subcontinent. Sarada et al (1999) reported 70 cases of anthrax seen at Christian Medical College, Vellore and 112 cases of anthrax in surrounding places. The majority of cases are cutaneous anthrax. However, human cases of intestinal, septicemic, meningeal, pulmonary and gastrointestinal anthrax have also been reported. Ichhpujani et al (2004) reported an outbreak of human anthrax in Mysore with four deaths after consuming diseased deer meat. However, animal anthrax has been recognized by veterinarians in all parts of India. Control measures are: immunization of high-risk individuals, disposal of animal carcasses and subsequent disinfection and mandatory reporting of all human cases and unexplained sudden animal deaths.
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552 2.5 Rickettsial diseases

T D Chugh infected water; Pacini in 1854, rst described comma shaped bacteria in intestinal contents of cases of cholera and Robert Koch in 1883, showed that cholera was caused by these bacilli, V cholerae. The rst six pandemics of cholera originated in Bengal and occurred between 1817 to 1923 and the seventh pandemic started in 1961 in Indonesia. These spread to southeast Asia, Middle East, East Africa, Europe and Americas (Guerrant 2006). The last decade of the 20th century witnessed a sharp increase in the global re-emergence of cholera. In September 1992, V. cholerae O139 Bengal (the rst non-O1) appeared in south India. This spread to the rest of India and Bangladesh. Subsequent outbreaks due to this organism were reported in Nepal, Pakistan, southeast Asian countries and Japan. Some cases were also reported on the west coast of the United States, England, Germany and Switzerland. The genome of V. cholerae is in a state of constant ux, resulting in the reemergence and displacement of serotypes Inaba and Ogawa. The conversion of Ogawa to Inaba serotype occurs at a rate of 105 due to mutation in the gene and in vivo selection due to immune response during the course of clinical disease. Das and Gupta (2005) reported the diversity of V. cholerae isolated in Delhi during 19922000. Narang et al (2008) described the changing patterns of V. cholerae in Sevagram, Maharashtra seen, between 19902005. Mathur et al (2003) have discussed the epidemiology of V. cholerae and Aeromonas in a ve year prospective study in Mumbai. 3.3 Listeria monocytogenes

Rickettsial diseases have a global distribution and recent reports suggest their continuing presence in India as well. The reported numbers are an underestimate as there are no community-based studies and there is a lack of availability of conrmatory laboratory tests. Batra (2007) has reviewed its prevalence in Himalayas, Kerala and Tamil Nadu. Studies in these geographic areas have reported the high magnitude of scrub typhus, spotted fever and Indian tick typhus (R. conorii). The rickettsiae are transmitted by arthropod vectors (lice, ticks, ees or mites). Man is an accidental host except for louse-borne epidemic typhus caused by R. prowazekii. The control requires interruption of vector transmission from the reservoir. 3. Emerging foodborne and waterborne diseases

Foodborne microbial diseases account for 20 million cases annually in the world and their incidence is increasing. Nearly half of all known foodborne pathogens have been discovered during the past 25 years. 3.1 Enterohaemorrhagic Escherichia coli

It causes no signs of illness in its natural host, cattle and sheep, but has a low infectious dose in humans where it causes haemorrhagic colitis and haemolytic uraemic syndrome. It was rst described in 1982 associated with consumption of undercooked beef. Ground beef is the most common vehicle for its transmission but can occur in vegetarian and non-beefeating communities, through exposure to fruits, vegetables or water contaminated by bovine or infected human feces. The manure-contaminated irrigation was the source of the largest recorded outbreak affecting more than 7000 children who had consumed contaminated sprouts in Japan. Isolation of Enterohaemorrhagic Escherichia coli (EHEC) in beef, cattle stools and in human patients of diarrhoea have been reported in India. Non-O157 EHEC were reported in 1.4% of stools from cases of bloody diarrhoea in Kolkata (Ministry of Health and Welfare 2006). EHEC O157 sorbitol phenotype have been isolated from the Ganges River, Varanasi by Hamner et al (2007). The detection of potentially pathogenic O157:H7 in river water is alarming. Some antibiotics enhance EHEC toxin production and induce verotoxin-phages which enhance environmental stability. 3.2 Vibrio cholerae

Listerosis is an emerging zoonotic disease. It is estimated that L. monocytogenes is responsible for 28% deaths due to foodborne illnesses in the United States. The organism is unbiquitous and inherently robust and can thus survive food-processing and refrigeration of contaminated meat and dairy products. Carriage of the pathogen has been reported in feces and genital tract of 5-10% humans. There has been a signicant decline in the disease in countries where active surveillance and sale of dairy products and meat have been regulated. In India, very few studies have been done. Bhujwala et al in 1970s reported L monocytogenes in cervical secretions of 1.3-3% of cases with bad obstetrical history but none of the 125 samples of cerebrospinal uid obtained from cases of meningitis were positive. Thomas et al (1981) in a prospective study of 1300 newborns found the pathogen in only two cases. 3.4 Campylobacter spp

Cholera is one of the oldest recorded infectious diseases. John Snow rst demonstrated the spread of disease by
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Campylobacter spp. are signicant zoonotic poultry pathogens and are the leading cause of bacterial

Emerging bacterial diseases in India gastroenteritis in the world. Poultry carrying the organism remain healthy carriers and transmit by fecal shedding. Around 2.5 million human infections are reported annually in the United States. The disease is more common in children and there is an emergence of uorquinolone resistance. In developing countries it is reported in 520% in childhood diarrhoea. Jain et al (2005) reported isolation of C. jejuni in 13.5% of the diarrhoea patients and this was more frequent than combined Salmonella and Shigella infections (4.3%; P < 0.001). 4. Drug-resistant bacteria


Antimicrobial resistance (AMR) in hospitals and community poses a public health problem (Moellering 2007). The fecal ora and upper respiratory tract commensals constitute the reservoir for resistant genes. Increased travel and movement of food-stuffs are risks for the spread of resistant genes. Chugh (2008) has reviewed the global status of AMR in various pathogens. Woodford (2007) has identied the existence of multiresistant clones of common pathogens. Staphylococcus aureus is a devastating human pathogen and is the modern Ghengis Khan(Chugh 2007). It is now the most frequently identied drug-resistant pathogen. The prevalence of methicillin resistant S aureus (MRSA) has been on the increase and varies in different hospitals in India. More recently community-acquired MRSA outbreaks have been reported (lineage USA 400 MW2 and USA 300). Emergence of vancomycin intermediate resistant S. aureus (VISA), vancomycin resistant S. aureus (VRSA) and vancomycin resistant enterococci (VRE) has led to clinical failures of glycopeptides. The usefulness of penicillin in the management of gonorrhoea is increasingly compromised due to emergence of penicillinase-producing gonococci (PPNG) and chromosomally mediated resistance (CMRNG). In India, the information is incomplete. Bala et al (2007) have reviewed the changing pattern of AMR of N. gonorrhoea and the emergence of ceftriaxone-less-susceptible strains. However, no treatment failures have been reported as yet with parenteral ceftriaxone though higher doses are required. Meningococci have repeatedly caused outbreaks and the disease is endemic in Delhi, Haryana, Uttar Pradesh, Rajasthan, Chandigarh, Jammu and Kashmir and West Bengal. Serogroup A has been the causative agent in most cases. It carries a mortality of ~10% and another 11-19% develop sequelae. The organism developed resistance to sulphonamides during 1950s and 1960s. Reduced penicillin susceptibility (MIC >0.25 mg/l) due to altered PBP2 and plasmid-mediated -lactamase production with consequent treatment failures and higher rates of complications have been reported. Manchanda and Bhalla (2006) reviewed the present status of AMR in N. meningitidis in India and reported

the emergence of 6 clinical isolates of N. meningitidis group A nonsusceptible to cefotaxime and ceftriaxone associated with therapeutic failure. Sulphadiazine resistance was reported in an outbreak in Delhi in 1985-6. A study of 96 culture positive cases from Punjab reported all isolates sensitive to penicillin, chloramphenicol, ampicillin and sulphadiazine. In a recent outbreak in Delhi in early 2005, all isolates were susceptible to penicillin, ampicillin, rifampicin and ceftriaxone. However, all were resistant to cotrimoxazole and two-thirds were non-susceptible to ciprooxacin. Singhal et al (2007) have reported ciprooxacin-resistant meningococci in an outbreak in Delhi. Enteric fever is endemic in India. It is underdiagnosed due to lack of culture facilities and poor sensitivity and specicity of Widal test. Resistance of Salmonella typhi and S. paratyphi A to chloramphenicol, ampicillin and cotrimoxazole is widespread. Low level uorquinolone resistance is now common and leads to treatment failures and higher incidence of relapses. Rodrigues et al (2003) have discussed the present status of the problem in India. The growing AMR in Shigella isolates is worrying as resistance to azithromycin, ceftriaxone and ciprooxacin has been on the increase. The emergence and high prevalence of extended-spectrum lactamases, Amp C lactamase and carbapenemases in the hospitals and the community in enteric bacteria and nonfermenters is a cause of concern. These have spread in humans, food-producing- animals and domestic pets (Rahman et al 2007). Various strategies to contain AMR include surveillance, hospital infection control, promotion of rational use of antibacterials, development of rapid diagnostics, vaccines and new drugs based on our new knowledge of human and bacterial genomes. It is estimated that two-thirds of the global antibiotic production is used in animal husbandry for growth-promotion non-therapeutic purposes. The overuse of antibiotics selects the drug-resistant zoonotic pathogens. Humans get exposed to them through meat, vegetables and water contaminated by animal waste. 5. Melioidosis

There is a growing evidence that the disease is an emerging global problem. The causative pathogen, Burkholderia pseudomallei, is an environmental saprophyte in rice paddies, wet soil, mud and pooled surface water. It causes suppurative chronic infection characterized by septicemia and focal abscesses in liver, spleen and other viscera. The disease has been documented from Tamilnadu and Karnataka. Lack of adequate healthcare facilities in rural population, low index of clinical suspicion and nonavailability of diagnostic tests probably contribute to the paucity of reports from the Indian subcontinent. Indians may be at a greater risk of disease than Malays and Chinese.
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Table 2. Chronic diseases with infectious etiology Microbe Helicobacter pylori Human papilloma virus Hepatitis B/C viruses Epstein-Bar virus Human T lymphotropic virus type I Disease

T D Chugh

Microbe Human herpes virus 8 Borrelia burgdorferi Tropheryma whippelii Chlamydia pneumoniae

Disease Kaposis sarcoma Lyme arthritis Whipples disease Atherosclerosis

Peptic ulcer, gastric carcinoma Cervical, anal, vulvar carcinoma Liver cirrhosis, hepatocellular carcinoma B-cell lymphoma, nasopharyngeal carcinoma Adult T-cell leukemia

The association of the disease with diabetes mellitus is high. The disease in India has been reviewed by Vidyalakshmi et al (2007). The rst culture-proven case in India was a child in Maharashtra in 1990. Isolated cases have been reported from Orissa, Assam, West Bengal and Andhra Pradesh. A series of culture-proven 28 patients collected during Dec 1993 to Dec 2002 in Vellore (Jesudason et al 2003) and a cluster of 25 cases during a span of only 14 months from June 2005 to July 2006 in Mangalore have been reported. Given the environmental conditions and a large pool of diabetics in India, there is probably an underestimate of the disease. 6. Chronic and neoplastic diseases



The present status of emerging and re-emerging bacterial diseases in India has been reviewed. The true prevalence of many such diseases is not known. Since we live in a global village, we cannot afford to be complacent about the tremendous economic, social and public health burden of these diseases. Effective surveillance is the key to their early containment. There is a need to develop epidemiology at the community level and improved diagnostic facilities which should be rapid, specic, simple and affordable. The strategy to combact these diseases needs a strong public health structure, effective risk communication, epidemic preparedness and rapid response.

A number of chronic and neoplastic diseases are now associated with microbial infections (table 2). It is estimated that approximately 1 in 6 of all human malignancies are related to microbial agents, the most signicant being gastric and hepatocellular carcinoma and cervical cancer. There is a possibility of development and use of vaccines to prevent hepatitis B, human papilloma virus and Helicobacter pylori infections. Ramakrishna (2006) has discussed the high prevalence of H. pylori infection in India. The seroprevalence rate in children varies up to 50%, increases slowly and steadily to ~ 90% in the young adults and remains constant in later years. It has been implicated in the causation of peptic ulcers, gastric carcinoma, lymphoma, bile duct cancer and even vascular disease. The high prevalence of resistance to metronidazole, clarithromycin and amoxicillin has led to failure of eradication of H. pylori infection. The resistance shows geographic variation being higher in south than north India. There is also a high rate of reinfections in Indian subjects (60%). There is a global evidence that persistent infection with Chlamydia pneumoniae is associated with pathogenesis of coronary artery disease. There have been serological, molecular, immunohistological and electron microscopic studies from India to show its association with coronary artery disease in patients with and without conventional risk factors and patients with calcication in coronary artery atherosclerosis (Jha et al 2007).
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