Treatment course: 5 days

M2 Inhibitors (effective against influenza A only)
Amantadine (Symmetrel)

• <10y/o: 5mg/kg/d up to 150mg in 2 div doses (include those older than 10 but <40kg)
• 10y/o and above: 100mg bd
• 65y/o and above: 100mg/d or less
• *consult package insert if CrCl <50ml/min

Rimantadine (Flumadine)

• use in children <13y/o: off-label
• 13y/o and above: 100mg bd
• 65y/o and above: 100mg/d
• *hepatic dysfunction, CrCl <10ml/min: reduce to 100mg/d

 

Neuraminidase Inhibitors (effective against influenza A & B)
Oseltamivir (Tamiflu)

• 0 to <12 months: 3mg/kg bd
  12 months & above:

• 15kg or less: 30mg bd
• 15-23kg: 45mg bd
• 23-40kg: 60mg bd
• >40kg and adults: 75mg bd
• *reduce dose if CrCl <30ml/min

Zanamivir (Relenza)

• 7y/o and above: 10mg (2 inhalations) bd

 
Ref:

1. CDC: Table: Recommended Daily Dosage of Seasonal Influenza Antiviral Medications for Treatment and Chemoprophylaxis for the 2008-09 Season—United States. Available at:
   http://www.cdc.gov/flu/professionals/antivirals/dosagetable.htm#table

2. CDC: Table: Antiviral medication dosing recommendations for treatment or chemoprophylaxis of 2009 H1N1 infection. Available at:
   http://www.cdc.gov/h1n1flu/recommendations.htm#table1

Conventional formulations
Fansidar: sulfadoxine 500mg + pyrimethamine 25mg

Malarone: atovaquone 250mg + proguanil 100mg
(paeds Malarone tab: atovaquone 62.5mg + proguanil 25mg)

Maloprim: dapsone 100mg + pyrimethamine 12.5mg
 

Artemisinin-based
Coartem (Riamet): artemether 20mg + lumefantrine 120mg

Artekin: dihydroartemisinin 40mg + piperaquine 320mg

DNP: dihydroartemisinin 160mg + naphthoquine 400mg + trimethoprim 200mg

fluvax® 2009/2010 (CSL, Australia)
(from package insert, March 2009)

Vaccine type: purified, inactivated, split virion vaccine
Composition: conforms to requirements of the Vaccines and Related Biological Products Advisory Committee (VRBPAC) for northern hemisphere winter of 2009/2010

• A/Brisbane/59/2007(IVR-148) or A/Brisbane/59/2007(H1N1)-like
• A/Uruguay/716/2007(NYMC X-175C) or A/Brisbane/10/2007(H3N2)-like
• B/Brisbane/60/2008 or B/Brisbane/60/2008-like

Dosage:

• 6-35months: 0.25ml
• >36months & adults: 0.5ml
• single dose sufficient; however in children <9 years lacking prior antigenic exposure, and in those with impaired immunity, two doses are recommended separated by at least 4 weeks.
• intramuscular or deep subcutaneous injection

Contraindicated in:

• anaphylaxis to egg/chicken, neomycin, polymyxin B
• acute febrile illness (fever >38.5c)

Use in pregnancy/lactation:

• category B2 (no convincing evidence of risk to foetus)
• may be offered to pregnant women who will be in 2nd or 3rd trimester during influenza season, including those in the 1st trimester at the time of vaccination

Some common side effects:

• common: injection site inflammation, influenza-like illness
• rare: neuralgia, paresthesia, convulsions, transient thrombocytopenia
• very rare: encelphalomyelitis, GBS, vasculitis with renal involvement

drug interactions:

• may impair P450 metabolism of warfarin, theophylline, phenytoin, phenobarbitone, cabamazepine

WHO recommends YF vaccination for travel to:
AFRICA: Angola | Benin | Burkina Faso | Burundi | Cameroon | Central African Republic | Chad | Congo | Cote d’Ivoire | Democratic Republic of the Congo | Equatorial Guinea | Ethiopia | Gabon | Gambia | Ghana | Guinea | Guinea-Bissau | Kenya | Liberia | Mali | Mauritania | Niger | Nigeria | Rwanda | Sao Tome and Principe | Senegal | Sierra Leone | Somalia | Sudan (except Khartoum) | Togo | Uganda | United Republic of Tanzania

AMERICAS: Argentina (north and northeastern forested areas, including Iguacu Falls and all areas bordering Brazil and Paraguay) | Bolivia (except: La Paz, Sucre) | Brazil (except: Rio de Janeiro, Sao Paulo, Salvador, Recife, Fortaleza) | Colombia | Ecuador (except: Guayaquil, Quito, Galapagos Islands) | French Guiana | Guyana | Panama (except: Canal Zone, Panama City, San Blas Islands) | Paraguay | Peru (except: Cuzco, Machu Picchu) | Suriname | Trinidad and Tobago (except Tobago only) | Venezuela

 

The following countries require documentary proof of YF vaccination from all incoming travelers:

1. *ICVP (International Certificate of Vaccination or Prophylaxis) for yellow fever MUST be completed; is valid ten days after vaccination and for a period of ten years. Available online from the WHO Press or the US Government Bookstore. A PDF copy may also be downloaded here.

2. Note: most countries, including Singapore, require proof of valid vaccination against yellow fever for travelers arriving from, or having transited through, a country within the YF-endemic zone. However, the countries listed below require all arriving travelers to have documentation of yellow fever vaccination regardless whether they are arriving from a yellow fever-endemic or non-endemic country.

AFRICA: Angola | Benin | Burkina Faso | Burundi | Cameroon | Central African Republic | Chad | Congo | Cote d’Ivoire | Democratic Republic of the Congo | Gabon | Ghana | Liberia | Mali | Mauritania (except: from non-endemic zone staying < 2 weeks) | Niger | Rwanda | Sao Tome and Principe | Sierra Leone | Togo

AMERICAS: French Guiana | Bolivia (unless affidavit signed exempting the state from liability)
 
Ref:

1. CDC Travelers’ Health — Yellow Book 2008. Chap 4: Prevention of Specific Infectious Diseases: Yellow Fever [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; 2007 June 20. [updated 2009 Apr 17; cited 2009 Apr 22]. Available from:
   http://wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx

2. WHO: International Health Regulations (IHR) | International Certificate of Vaccination or Prophylaxis (ICVP) [Internet]. World Health Organisation. Available from:
   http://www.who.int/ihr/travel/icvp/en/

3. CDC Travelers’ Health — Yellow Book 2008. Chap 5: Yellow Fever Vaccine Requirements and Information on Malaria Risk and Prophylaxis, By Country [Internet]. Atlanta (GA): Centers for Disease Control and Prevention. [cited 2009 May 27]. Available from:
   http://wwwn.cdc.gov/travel/yellowbook/ch5/malaria-yellow-fever-table.aspx

(from Ministry of Health circular, Singapore)
wef 1 Jan 2014: Medisave use for seasonal influenza vaccination will be allowed for the high-risk groups who are at increased risk of influenza-related complications.
(updated in MOH circular 42/2013 dated 6 Sep 2013)

• persons ages 65 years and above, regardless of health condition
• children 6 months to 59 months (<5 years)
• chronic heart or lung diseases, including asthma
• chronic metabolic diseases (eg. diabetes mellitus), renal, neurologic, hepatic, or haematologic disorders, or immunosuppression (including immunosuppression caused by medications or HIV)
• children and teenagers (up to 18 years) receiving long-term acetylsalicylic acid and who may be at risk for developing Reye’s syndrome after influenza infection
• women at all stages of pregnancy
• persons receiving intermediate and long term care services

Influvac® 2009/2010 (Solvay, Netherlands)
(from package insert, April 2009)

Vaccine type: viral surface antigen (haemagglutinin & neuraminidase)
Composition: complies with WHO recommendation for N hemisphere 2009/2010
Dosage:

• 6-35months: 0.25ml or 0.5ml (clinical data limited)
• >36months & adults: 0.5ml
• single dose vaccine; however in children who have not previously been vaccinated, 2nd dose (booster) should be given after an interval of at least 4 weeks
• intramuscular or deep subcutaneous injection

Seroprotection: achieved in 2-3 weeks, duration 6-12 months

Contains traces of:

• egg ovalbumin, chicken protein (propagated in fertilised hens’ eggs)
• formaldehyde
• gentamicin
• polysorbate 80, cetyltrimethylammonium bromide

Use in pregnancy/lactation:

• may be considered from 2nd trimester
• if medical condition increases risk of complication from influenza, vaccine may be warranted regardless of stage of pregnancy
• may be used during lactation

Some common side effects:

• headache, myalgia, arthralgia, fever, malaise, fatigue
• local: redness, swelling, pain, ecchymosis, induration
• rare: neuralgia, encelphalomyelitis, GBS

Catch-up pneumococcal vaccination for children under 5:
PCV (13-valent pneumococcal conjugate vaccine eg. Prevenar ®)

MOH (Ministry of Health, Singapore) recommends catch-up immunisation for all previously unimmunised children under 5 years of age (updated Jan 2011).
(for recommended schedule from Wyeth, see here)

For previously unimmunised children:

• <12 months old: 2 doses + 1 booster
  recommended interval between first & 2nd doses: 8 weeks (minimum 4 weeks)
  minimum interval between second dose & booster: 8 weeks

• 12-23 months old: 1 dose + 1 booster (prev single dose only)
  minimum interval between doses: 8 weeks

• 24-59 months old: single dose only
• 24-59 months old with expected suboptimal response: 1 dose + 1 booster
  minimum interval between doses: 8 weeks
  eg. asplenia, splenic dysfunction, immunocompromised

 
Previous recommendation (Nov 2009) superseded.

• <1 year old: as per primary series, 2 doses + 1 booster
  recommended interval between D1 and D2: 8 weeks (minimum 4 weeks)
  minimum interval between D2 and booster: 8 weeks

• 1-5 years old: single dose of PCV
• 1-5 years old with expected suboptimal response: 2 doses, interval 8 weeks between (eg. asplenia, splenic dysfunction, immunocompromised)

Pneumococcal vaccination for adults
PPSV23 (23-valent pneumococcal polysaccharide vaccine, eg. Pneumovax 23, Pneumo23):

Single dose only:

• 2-5 years old in high-risk groups*: in addition to PCV
• 2-64 years old in high-risk groups*
• all elderly 65 years and older

one-time revaccination after 5 years:

• persons aged 2-64 years with medical indications: chronic renal failure or nephrotic syndrome; functional or anatomic asplenia (eg. sickle cell disease or splenectomy); or immunocompromising conditions
• elderly persons who previously received PPSV23 before the age of 65 are recommended for another dose if at least 5 years have passed since previous vaccination

Booster every 5 years:
not routine; recommended only for individuals with asplenia, splenic dysfunction and chronic renal disease

*High-risk groups:

1. Chronic illnesses
   • chronic respiratory disease (incl. COPD, chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis, interstitial lung fibrosis, pneumoconiosis, bronchopulmonary dysplasia; children with neuromuscular disease eg. cerebral palsy with risk of aspiration, or respiratory conditions caused by aspiration)
   • chronic heart disease (incl. ischaemic heart disease, congenital heart disease, hypertensive heart disease, chronic heart failure)
   • chronic renal disease (incl. nephrotic syndrome, chronic renal failure, renal transplant)
   • chronic liver disease and alcoholism (incl. biliary atresia, cirrhosis, chronic hepatitis)
   • diabetes mellitus
2. Cochlear implants
3. Cerebrospinal fluid leaks
4. Anatomic or functional asplenia (incl. homozygous sickle cell disease, coeliac syndrome)
5. Immunocompromised patients (incl. HIV infection, asplenia, splenic dysfunction, undergoing chemotherapy, likely to be on systemic steroid therapy more than a month at a dose equivalent to prednisolone at >=20mg/d (any age), or for children under 20kg at a dose of >=1mg/kg/day)

 
Ref:

1. MOH Circular 42/2013: Pneumococcal and Seasonal Influenza Vaccinations (MH 34:03). Ministry of Health, Singapore. 6 September 2013.

2. MOH Circular 103/2009: Pneumococcal Vaccination (MH 34:55/2). Ministry of Health, Singapore. 13 Oct 2009.

from: the National Childhood Immunisation Programme, NCIP updated Nov 2009
**revised: 11 Nov 2011, effective 1 Dec 2011
***updated: 23 May 2013, effective 1 Jun 2013

Age	BCG	HepB	DTaP	Polio	Hib	5in1	6in1	Mod	PCV	MMR
birth	1					BCG	BCG	BCG
birth		D1				HepB	HepB	HepB
1 month		D2				HepB		HepB
2 month							6in1
3 month			D1	D1-IPV***	D1***	5in1		5in1	D1
4 month			D2	D2-IPV***	D2	5in1	6in1	5in1
5 month		(D3)	D3	D3-IPV***		5in1		6in1	D2
6 month		D3			D3	HepB	6in1
12 month									b1	D1**
15-18 month										D2**
18 month			b1	b1-IPV***	b1	5in1	5in1	5in1
6-7year (Pr1)				b2***		*	*	*		D2
10-11year (Pr5)			b2**	b3 b2-OPV***		*	*	*

 
Legend:

D = dose number (primary schedule)
b = booster
BCG = Bacille Calmette Guérin (tuberculosis vaccine)
DTaP = diphtheria, tetanus, acellular pertussis
Polio = polio vaccine (oral Sabin OPV or injectable Salk IPV)
Hib = Haemophilus influenza B (NCIS from 1 Jun 2013)
PCV = pneumococcal conjugate vaccine

• BCG 1 dose is always given at birth regardless of regime

• measles, diphtheria vaccinations are mandated by law (Infectious Disease Act, IDA). BCG, Hep B, DTaP, Polio, MMR, PCV, Hib should be routinely offered as standard of care in Singapore unless contraindicated. HPV is recommended for females 9-26y/o.

• ***from 1 Jun 2013, all vaccines in the NCIS can be paid for using Medisave.
• in addition, the following vaccines are fully subsidised for children who are Singapore citizens, at all polyclinics: BCG, DTP, polio, MMR

• **b2 of DTaP previously required Td-containing vaccine (reduced diphtheria component); as of 1 Dec 2011 a combined TdaP vaccine is recommended

• TDaP comes combined with IPV as Infanrix-IPV; OPV carries a minute risk of vaccine-associated paralytic poliomyelitis (VAPP).

• ***from 1 June 2013, the OPV-based polio vaccination schedule has been updated to a 5-dose regime: IPV for D1-D3 + b1; OPV for b2 at 10-11y/o.

• IPV is contraindicated in allergy to streptomycin, polymyxin B, neomycin

• Hib:*** children who previously received DTaP & OPV but have not completed primary and/or booster doses should complete their vaccination series up to first booster dose at 18m with DTp, IPV and Hib combination vaccines. Catch-up doses for Hib are not required for those who did not receive earlier doses.

• 5in1: DTaP comes combined with IPV and Hib as Infanrix-IPV+Hib (5-in-1 vaccine); this regime utilises 5-in-1 and Hep B vaccine only.

• 6in1: DTaP comes combined with IPV, Hib and Hep B vaccine as Infanrix hexa (6-in-1 vaccine); this regime utilises 6-in-1 and Hep B vaccine only, and boasts a total of only 4 injections in place of the conventional 6 injections in the first 6 months of life.

• Mod(modified): a regime started with Hep B vaccine and 5-in-1 may be completed with 6-in-1 which replaces the final dose of both; this reduces the total jab count by 1 (to a total of 5).

• *: the recommended schedules for 5-in-1 and 6-in-1 finish at 6 months with a booster dose at 18 months; after that the schedules follow the usual vaccination programme. Boostrix-IPV may be used for the DTaP-IPV booster at 11 years.

• minimum interval between 1st & 2nd doses of Hep B-containing vaccine is 4 weeks; between 1st & 3rd doses is 16 weeks

• children born to Hep B positive mothers should receive monovalent Hep B vaccine for D1 and D2; 6-in-1 vaccine can be used for D3.

• PCV: PCV7 (Prevenar®) has been superceded by PCV13. PCV7 covers serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. In addition, PCV13 covers 1, 3, 5, 6A, 7F and 19A. Serotype 19A is believed to be an emerging serotype responsible for serious invasive pneumococcal disease.

 

Ref:

1. MOH Circular No.15/2013: Changes To The National Childhood Immunisation Schedule (MH 34:09/1 V16). MInistry of Health, Singapore. 23 May 2013.
2. MOH Circular 27/2011: Changes in National Childhood Immunisation Schedule (MH 34:09/1). Ministry of Health, Singapore. 11 Nov 2011.
3. MOH Circular 103/2009: Pneumococcal Vaccination (MH 34:55/2). Ministry of Health, Singapore. 13 Oct 2009.
4. Polyclinic (NHG) Child Health Services website: http://www.nhgp.com.sg/Our_Services/General_Medical_Services/Child_Health_Services/

Central & South America
at highest risk: Bolivia | Brazil | Colombia | Ecuador | Peru
also at risk: Panama | Venezuela | Guyana | Suriname | French Guiana | Paraguay | Argentina (Northern border)

Africa
(generally countries within a band 15degN to 10degS of the equator)
at highest risk: Togo | Mali | Senegal | Burkina Faso | Cameroon | Benin | Sierra Leone | Nigeria | Liberia | Guinea | Ghana | Cote d’Ivoire
 

The following countries in Africa are not endemic for yellow fever:
Northern Africa: Western Sahara | Morocco | Algeria | Libya | Gibralta (UK) | Malta | Tunisia | Egypt | Eritrea | Djibouti
Southern Africa: Namibia | Botswana | Zambia | Malawi | Mozambique | Zimbabwe | South Africa | Lesotho | Swaziland
Madagascar
 

Ref:

1. CDC Travelers’ Health — Yellow Book 2008. Chap 4: Prevention of Specific Infectious Diseases: Yellow Fever [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; 2007 June 20. [updated 2009 Apr 17; cited 2009 Apr 22]. Available from:
   http://wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx

2. News release: More funding urged for yellow fever vaccine stockpile [Internet]. Geneva: World Health Organisation; 26 May 2009 [cited 27 May 2009].

• malaria endemic areas (see WHO world map)

• Anopheles mosquitoes bite between dusk and dawn; the lifetime range of flight of an Anopheles mosquito is 1km. Hence, daytime side trips to areas where malaria is endemic present little risk, if the traveler restricts nighttime hours to air-conditioned hotels or other environments where there are few mosquitoes.

• travel restricted to capital cities and other urban areas (as is typical of business travel) is associated with an insignificant risk of malaria, despite the risk in areas nearby, with the exception of sub-Saharan Africa and certain cities in India.

• take into account the possibility of deviation from the preset itinerary brought to the pretravel consultation.

 
Non-pharmacological interventions

• wear long sleeves, long pants, and fully closed shoes with socks after dark.

• use permethrin-treated mosquito nets if accommodations are neither well screened nor air-conditioned.

• repellent containing 30-50% DEET (N,N-diethyl-3-methylbenzamide) should be applied to exposed areas of skin every 4-6 hours; more frequent applications is required for agents containing lower concentrations.
  Children: up to 30% DEET is considered to be safe (higher concentrations have not been tested).
  Pregnancy: up to 20% DEET has been shown to be safe.

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