EMERGING INFECTIONS

Dr Rosni Ibrahim

MED 2082

Infectious Disease Block

Learning objectives

• Define emerging / re-emerging infections.

• List the diseases of emerging / re-emerging infections.

• Discuss the emerging / re-emerging diseases in Malaysia and the world.

• Discuss the factors giving rise to the emerging / re-emerging infections.

• Explain the laboratory diagnosis of the emerging / re- emerging infections.

What is emerging infections

• Infectious diseases that have newly appeared in the population or have existed in the past but rapidly increasing in incidence (Morse 1995)

Re-emerging infections

• Incidence in humans has increased during the last 20 years or threatens to increase in the near future

• Existed in the past but are now rapidly increasing either in incidence or in geographical or human host range

Re-emergence of known viral diseases

• Development of resistance to vaccines or antiviral drugs.

• Breakdown of public health measures for previously controlled infections.

Emerging infections may be:

• The discovery that a known disease is caused by an infection, for example, finding out that something infectious can cause a long-term (chronic) disease. Kaposi’s Sarcoma in AIDS patients (HHV-8)

Emerging infections in Malaysia

Emerging diseases of veterinary and medical

importance in Malaysia

Highly pathogenic avian influenza (HPAI)

• highly infectious and contagious disease of poultry.

• The disease syndrome varies from subclinical to mild respiratory disease, loss of egg production and high mortality rates.

Influenza A H1N1 (swine flu)

• Pandemic outbreak since April 2009

• Malaysia – May 2009 (imported case)

• 1st local case/ transmission - June 2009

• Causative agent- Influenza A- RNA viruses of the family Orthomyxoviridae

• RNA virus-highly mutagenic

• Antigenic shift/antigenic drift

Avian salmonellosis (S. enteritidis/S.typhimurium)

• Salmonellosis is a disease due to Salmonella bacteria that cause infection and illness in both animals and human.

• S. enteritidis is associated primarily with poultry and eggs.

Salmonella typhi

•Increased in foreign worker especially among food handler

•Salmonella carrier

•Risk of food poisoning

Antibiotic resistance

• Emerge in environment due to inappropriate use of antibiotic

• The WHO estimates that 10 million people are dying of infectious diseases related to antibiotic resistance.

• Proper antibiotic guidelines needed to prevent the drug resistance.

Multi-resistant pathogen

• Methicillin/oxacillin-resistant Staphylococcus aureus (MRSA);

• Vancomycin-resistant enterococci (VRE);

• Extended-spectrum beta-lactamases (which are resistant to cephalosporins and monobactams) (ESBLs);

• Penicillin-resistant Streptococcus pneumoniae (PRSP);

• Multi-drug resistant tuberculosis (MDR-TB); and

• KPC- Klebsiella Pneumoniae Carbapenemase

• S. typhimurium - DT104 (resistant to five antibiotics namely ampicillin, chloramphenicol, streptomycin, sufonamides and tetracycline

Dengue

• The haemorrhagic form of dengue fever (DHF), was recognised as a new disease in the Philippines in 1953 and has been reported in India, Singapore, Indonesia, Vietnam, Cambodia and Sri Lanka including Malaysia.

Dengue infection

There are four antigenically distinct viral serotypes (DEN1,DEN2,DEN3,DEN4)

There is no cross-protective immunity with any of the viruses, so that it is possible for a person to acquire multiple dengue infections.

Dengue infectionsVector: Aedes aegyptiFlavivirus

Factors influence increased in dengue cases/reemerging dengue cases in Malaysia

•Rapid urbanisation-large human population-abundance of non-degradable containers-breading sites

•Under notification of dengue cases

•Breakdown in public health measures-poor vector control

•Deforestation/climate change

Chikungunya

• An outbreak of chikungunya virus occurred in

Klang, Malaysia, between December 1998 and February 1999.

• Causative agent-chikungunya virus (genus:Alphaviridae)

• The majority of the cases - adults

• clinical presentation was similar to dengue infections-fever, headache, joint pain

• Virus has been re-introduced into the country through the movement of immigrant workers from endemic country of Chikungunya (Africa, Tanzania)

Enterovirus 71 (EV71) infection

• Enteroviruses are frequently associated with the hot and humid climate of tropical countries in South-East Asia.

• Coxsackie A16 and Enterovirus71 infection is common in many countries in this region.

EV71-ssRNA virus Picornaviridae causes HFMD

• In the outbreak of hand, foot, and mouth disease (HFMD) in Malaysia (1998), a new clinical entity of encephalomyelitis emerged, which resulted in several deaths among children.

• Thirty-four deaths occurred in Sarawak, 4 deaths were reported in Kuala Lumpur.

Malaysian Nipah virus epidemic 1998-1999

• An outbreak of Nipah virus in Malaysia and Singapore

• Nipah virus takes its name from a village in Peninsular Malaysia where the virus was first isolated from a human victim.

• Nipah virus belongs to family Paramyxoviridae

• Virus aerosolisation caused infection of pigs

• Overcrowding results in viral transmission to pig handlers

• The virus persists in low numbers in the island flying fox Pteropus hypomelanus,a type of fruit bat and Malayan flying fox, Pteropus vampyrus

Of the 269 human cases of viral encephalitis associated with Nipah virus infection reported in Malaysia in 1999, 108 were fatal (Ministry of Health Malaysia, 2001).

Tuberculosis

• Malaysia is at high risk of TB emergence as the country is surrounded by many other countries with a high TB burden like Indonesia, Thailand, Philippines, Bangladesh and India where many foreign workers originated.

• Hence, rigorous screening of foreign labour is mandatory and the use of antibiotics must be strictly regulated and monitored.

• Sources from the Ministry of Health Malaysia indicate that the number of TB cases in Malaysia has risen from about 11,000 in 1990 to about 15,000 in 1999.

• Drug resistance among TB cases are also reported due to poor adherence to TB treatment and poor education about the disease.

Malaria

• In 2009, researchers at the University Malaysia showed that P.lasmodium knowlesi, a malaria parasite previously thought to mainly infect only monkeys found in the rainforests of Southeast Asia – was widespread amongst humans in Malaysia.

• Subsequent reports in neighbouring Southeast Asian countries have led to the recognition of P. knowlesi as the fifth cause of malaria in humans.

• Plasmodium falciparum cases also increases due to resistant to treatment-chloroquine resistance

Factors giving rise to the emerging / re-emerging infections

Migration

• rural to urban – rapid urbanisation

• consequences- overcrowded, lack of hygiene, inadequate water supply

• increased risk of airborne, waterborne & foodborne ds

• Uncontrolled urbanization with inadequate vector control- increase risk of DF/DHF

Travel

• For bussiness/pleasure

• Meningococcal meningitis has occurred after returning from Hajj

• ↑ incidence of TB and influenza transmission on long flights

• Kala azar among migrant- arthropods vector and masquitoes are present in international flight

Environmental changes

• Changes in ecology→increase population of animal reservoirs and vectors of infections

• Eg: Hanta virus infection assoc eith conversion of land to rice fields increase the population of field mouse (host)→human infections

• In Malaysia, much concern on development→negative effects on environment rather that ID eg; landslide

Human behaviour

• ↑ sexual promiscuity→ ↑ STD

• IVDU- HIV/AIDS, Hepatitis B,C

• HIV/AIDS- re-emergence of variety of other inf like mycobacterium, cryptococcosis, toxoplasmosis

Technological advance

• Modern food production- ↑ risk of contamination

• New diagnostic technology- identiication of previously unknown microbes eg HHV-6, Helicobacter pylori

• Medical technology

– People live longer- weak immune response

– Blood and organ transplatation- transmit infections

Other factors contribute to emerging infections-antimicrobial resistance

•Inappropriate use of antimicrobial

•Prescribed antibiotic in viral infection

•High technology-immunocompromised pts live longer-prone to get atypical/newly emerged infections-prone to get infections by MRO

laboratory diagnosis of the emerging / re-emerging infections

Importance of laboratory diagnosis

• The results will alter clinical or infection control management, or as needed for public health surveillance purposes.

• For infectious diseases, modern serological techniques, more and more based on recombinant antigens, are being proven to be specific, rapid and less labor intensive.

• PCR may prove very useful and rapid

• Conventional methods turned out to be either too insensitive (e.g., during the asymptomatic stage of HIV infection), too slow (e.g., mycobacterial culture) or too cumbersome to be used on a large scale (e.g., virus isolation).

Recommended laboratory testing in emerging infections

• Molecular testing-PCR-highly sensitive and specific

• Rapid test –for flu-need to confirm with PCR

• Dengue-NS1 antigen (indicated for case < 5 days)

• Antimicrobial resistance-susceptibility testing , gene detection by PCR

• Another important application of PCR is to monitor the emergence of mutations in the genome, for instance, the selection of resistant variants during antiviral/antibiotic therapy.

Disadvantages of PCR:

• Expensive-need special rooms, expensive reagent

• proper packaging of sample to prevent leaking, risk of contamination

• Immediate transportation as the microorganism eg RNA virus is labile

• Need experience and well trained staff

Factors affecting emerging infections

solution

Migration Proper health screening, vaccination

Travel Immunization, infection control measure

Urbanization Proper sanitation, adequate housing, good infrastructure

Human behaviour Education, behaviour modification

Antibiotic usage Judicious use of antibioticCorrect antibiotic for correct pathogen (with right dosage and route). Strengthen infection control measures

International Solutions to Emerging Infectious Diseases

• Strengthen international surveillance networks to issue early warning, detect, control, and reduce emerging infectious diseases.

• Improve international public health infrastructure eg special laboratory that capable of accurate and rapid diagnosis.

• Improve international capabilities to respond to disease outbreaks with adequate medical and veterinary resources and expertise.

• Strengthen international research efforts on emerging infectious diseases, giving priority to antibiotic-resistant strains of diseases.

• Focus attention and resources on training and developing medical and veterinary capability.

• Encourage national governments to improve their public health care systems, devote resources to eliminating or controlling causes of emerging infectious diseases and coordinate public health activities with WHO and other international communities.

• Develop better international standards, guidelines and recommendations.