Manish Kakkar

Continuing challenge of infectious diseases in India

In India, the range and burden of infectious diseases are enormous. The administrative responsibilities of the health system are shared between the central (federal) and state governments. Control of diseases and outbreaks is the responsibility of the central Ministry of Health, which lacks a formal public health department for this purpose. Tuberculosis, malaria, filariasis, visceral leishmaniasis, leprosy, HIV infection, and childhood cluster of vaccine-preventable diseases are given priority for control through centrally managed vertical programmes. Control of HIV infection and leprosy, but not of tuberculosis, seems to be on track. Early success of malaria control was not sustained, and visceral leishmaniasis prevalence has increased. Inadequate containment of the vector has resulted in recurrent outbreaks of dengue fever and re-emergence of Chikungunya virus disease and typhus fever. Other infectious diseases caused by faecally transmitted pathogens (enteric fevers, cholera, hepatitis A and E viruses) and zoonoses (rabies, leptospirosis, anthrax) are not in the process of being systematically controlled. Big gaps in the surveillance and response system for infectious diseases need to be addressed. Replication of the model of vertical single-disease control for all infectious diseases will not be efficient or viable. India needs to rethink and revise its health policy to broaden the agenda of disease control. A comprehensive review and redesign of the health system is needed urgently to ensure equity and quality in health care. We recommend the creation of a functional public health infrastructure that is shared between central and state governments, with professional leadership and a formally trained public health cadre of personnel who manage an integrated control mechanism of diseases in districts that includes infectious and non-infectious diseases, and injuries.

Antibiotic resistance is the quintessential One Health issue

International Livestock Research Institute, Nairobi, Kenya; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; Université Libre de Bruxelles, Brussels, Belgium; Institute for Health Metrics and Evaluation, University of Washington, Seattle, USA; Oxford Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Oxford, UK; Research Group for Preventive Technology in Livestock, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand; Public Health Foundation of India, Delhi, India; Kenya Medical Research Institute, Nairobi, Kenya; Center for Disease Dynamics, Economics and Policy, Washington DC, USA; Food and Agriculture Organization of the United Nations, Rome, Italy; Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden; National Institute of Veterinary Research, Hanoi, Vietnam; Institute of Integrative Biology and Center for Adaptation to a Changing Environment, Swiss Federal Institute of Technology, Zurich, Switzerland; Centre for Immunity, Infection & Evolution, University of Edinburgh, Edinburgh, UK

Animal production and antimicrobial resistance in the clinic.

www.thelancet.com Vol 387 January 9, 2016 e1 One of the major public health challenges this century is the development of antimicrobial resistance in many important and common pathogens, such as Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. The Lancet Series on antimicrobials tackles the issue head-on by presenting evidence on universal access to antibiotics, sustainability, and eff ectiveness. The Series focuses on the use and misuse of antimicrobials in human medicine but does not ignore other sources of antimicrobial resistance development: waste and contamination from the pharmaceutical industry, animal agriculture, and the natural arms race that has been fought among microbes in the environment since the dawn of evolution. A substantial share of antimicrobial consumption is attributed to animal production. Recent fi ndings conservatively estimate that, from 2010 to 2030, global consumption of antimicrobials in livestock production will increase by two thirds, and that it will double in the rapidly growing economies of Brazil, Russia, India, China, and South Africa. In China, already the largest producer and user of antibiotics in the world, the livestock sector could consume a third of the antibiotics produced worldwide by 2030. Alison Holmes and colleagues suggest that misuse of antimicrobials in animal production is an evident and substantial driver of antimicrobial resistance. Other studies show how the global food trade can obscure the lines that connect antibiotic use in food-animal production with antibiotic-resistant human infections. The evidence that links antimicrobial use in animal production and the development of antimicrobial resistance in medically important pathogens is growing, thanks largely to advances in genetic analysis which allow the origins of genes conferring such resistance to be traced. Using whole-genome sequencing and phylogenetics, an international team of researchers described the evolution of meticillin-resistant S aureus (MRSA) in livestock from meticillin-susceptible S aureus in humans. This livestockassociated MRSA (clonal complex CC398) now frequently infects people both inside and outside of the livestock industry, and is an unequivocal example of the evolution of a multidrug-resistant pathogen that emerged in livestock and was subsequently transmitted to humans. Genetic fi ngerprinting and epidemiological studies have also established links between multidrug-resistant urinary tract infections and E coli from poultry. Moreover, a multicountry analysis of the human gut antibiotic resistome showed the abundance of resistant genes to be greatest for those antibiotics also used in animals. Whole-genome sequencing of samples along food systems can reveal and begin to quantify the two-way traffi c of antimicrobial-resistant bacteria between the farm and the clinic, but this will require sampling frames that account for the specifi cities of antimicrobial use, the complexity of environmental transmission pathways, and the vast diversity of animal production systems globally. While molecular epidemiology is bringing new clarity to this issue, some of the strongest evidence that links agricultural antibiotic use to antimicrobial resistance in people comes from simple, natural experiments involving the introduction or withdrawal of antimicrobials from food animals. For instance, the introduction of fl uoroquinolones to broiler chicken production in the USA was associated with a rapid increase in ciprofl oxacin-resistant campylobacteriosis in humans. Similarly, the voluntary withdrawal of ceftiofur in ovo injections in broiler chicken production in Canada resulted in a precipitous decrease in human infections caused by third-generation cephalosporinresistant Salmonella enterica. Despite these clear examples, there are insuffi cient data to resolve and quantify the total public health burden of antibiotic use in food-animal production. Antimicrobials are used for various reasons in animal production, including for growth promotion, disease prevention, and disease treatment. These uses involve diff erent classes of drugs applied at diff erent doses, and their relative importance and methods of implementation vary greatly across animal production systems and in diff erent parts of the world. The subtherapeutic use of antimicrobials to promote growth, in particular, comes under heavy criticism. In 2006, the European Union banned the use of antibiotics for growth promotion in livestock, and indications are, for example in the pork and poultry sectors in Denmark, that the prevalence of antimicrobial resistance among livestock has decreased since then. The use of antimicrobial growth promoters is still hotly debated in the USA, where non-binding guidance was issued in 2012 which recommended that livestock producers avoid using antibiotics as growth promoters. Animal production and antimicrobial resistance in the clinic

Dengue fever is massively under-reported in India, hampering our response

An estimated 20 000 people in India die each year from rabies,1 but in 2011 only 253 deaths were reported as having this cause.2 An estimated 100 000-200 000 people in India die annually from malaria,3 but in 2011 only 753 such deaths were reported.4 A recent spate of cases of dengue fever and a media outcry have brought the focus back to the widespread problem of under-reporting of cases of disease in India, linked to the ineffectiveness of our public health efforts.5 As of 26 November 37 070 cases of dengue fever had been reported this year in India.6 But a substantially bigger population is at risk, and India reported only an average of 4.2% of the total number of cases reported in the World Health Organization South East Asia region between 2000 and 2010.7 A study estimated that Thailand (population 70 million) had an annual incidence of more than 231 000 cases of symptomatic dengue in 2003-7.8 Given India’s population (1.2 billion) and environment, which is conducive to dengue, we should expect an incidence in India many times that of the Thai estimate. …

Moving from rabies research to rabies control: lessons from India

Background Despite the availability of effective interventions and public recognition of the severity of the problem, rabies continues to suffer neglect by programme planners in India and other low and middle income countries. We investigate whether this state of ‘policy impasse’ is due to, at least in part, the research community not catering to the information needs of the policy makers. Methods & Findings Our objective was to review the research output on rabies from India and examine its alignment with national policy priorities. A systematic literature review of all rabies research articles published from India between 2001 and 2011 was conducted. The distribution of conducted research was compared to the findings of an earlier research prioritization exercise. It was found that a total of 93 research articles were published from India since 2001, out of which 61% consisted of laboratory based studies focussing on rabies virus. Animals were the least studied group, comprising only 8% of the research output. One third of the articles were published in three journals focussing on vaccines and infectious disease epidemiology and the top 4 institutions (2 each from the animal and human health sectors) collectively produced 49% of the national research output. Biomedical research related to development of new interventions dominated the total output as opposed to the identified priority domains of socio-politic-economic research, basic epidemiological research and research to improve existing interventions. Conclusion The paper highlights the gaps between rabies research and policy needs, and makes the case for developing a strategic research agenda that focusses on rabies control as an expected outcome.

Acute Encephalitis Syndrome Surveillance, Kushinagar District, Uttar Pradesh, India, 2011–2012

In India, quality surveillance for acute encephalitis syndrome (AES), including laboratory testing, is necessary for understanding the epidemiology and etiology of AES, planning interventions, and developing policy. We reviewed AES surveillance data for January 2011–June 2012 from Kushinagar District, Uttar Pradesh, India. Data were cleaned, incidence was determined, and demographic characteristics of cases and data quality were analyzed. A total of 812 AES case records were identified, of which 23% had illogical entries. AES incidence was highest among boys <6 years of age, and cases peaked during monsoon season. Records for laboratory results (available for Japanese encephalitis but not AES) and vaccination history were largely incomplete, so inferences about the epidemiology and etiology of AES could not be made. The low-quality AES/Japanese encephalitis surveillance data in this area provide little evidence to support development of prevention and control measures, estimate the effect of interventions, and avoid the waste of public health resources.

Research Options for Controlling Zoonotic Disease in India, 2010–2015

Background Zoonotic infections pose a significant public health challenge for low- and middle-income countries and have traditionally been a neglected area of research. The Roadmap to Combat Zoonoses in India (RCZI) initiative conducted an exercise to systematically identify and prioritize research options needed to control zoonoses in India. Methods and Findings Priority setting methods developed by the Child Health and Nutrition Research Initiative were adapted for the diversity of sectors, disciplines, diseases and populations relevant for zoonoses in India. A multidisciplinary group of experts identified priority zoonotic diseases and knowledge gaps and proposed research options to address key knowledge gaps within the next five years. Each option was scored using predefined criteria by another group of experts. The scores were weighted using relative ranks among the criteria based upon the feedback of a larger reference group. We categorized each research option by type of research, disease targeted, factorials, and level of collaboration required. We analysed the research options by tabulating them along these categories. Seventeen experts generated four universal research themes and 103 specific research options, the majority of which required a high to medium level of collaboration across sectors. Research options designated as pertaining to ‘social, political and economic’ factorials predominated and scored higher than options focussing on ecological, genetic and biological, or environmental factors. Research options related to ‘health policy and systems’ scored highest while those related to ‘research for development of new interventions’ scored the lowest. Conclusions We methodically identified research themes and specific research options incorporating perspectives of a diverse group of stakeholders. These outputs reflect the diverse nature of challenges posed by zoonoses and should be acceptable across diseases, disciplines, and sectors. The identified research options capture the need for ‘actionable research’ for advancing the prevention and control of zoonoses in India.

Costs Analysis of a Population Level Rabies Control Programme in Tamil Nadu, India

The study aimed to determine costs to the state government of implementing different interventions for controlling rabies among the entire human and animal populations of Tamil Nadu. This built upon an earlier assessment of Tamil Nadus efforts to control rabies. Anti-rabies vaccines were made available at all health facilities. Costs were estimated for five different combinations of animal and human interventions using an activity-based costing approach from the provider perspective. Disease and population data were sourced from the state surveillance data, human census and livestock census. Program costs were extrapolated from official documents. All capital costs were depreciated to estimate annualized costs. All costs were inflated to 2012 Rupees. Sensitivity analysis was conducted across all major cost centres to assess their relative impact on program costs. It was found that the annual costs of providing Anti-rabies vaccine alone and in combination with Immunoglobulins was

Antibiotic resistance: mitigation opportunities in livestock sector development.

0.7 million (Rs 36 million) and

One Health approach to cost-effective rabies control in India.

2.2 million (Rs 119 million), respectively. For animal sector interventions, the annualised costs of rolling out surgical sterilisation-immunization, injectable immunization and oral immunizations were estimated to be