Thursday, May 9, 2013

New emerging strain of H7N9


Avian Influenza A (H7N9)


Avian Influenza A (H7N9) is a subgroup of influenza viruses that normally circulate among birds. There are many strains of H7N9. Despite the fact that this virus does not normally infect human, human infection with H7N9 continues to be reported in China. To date, there are a total of 131 confirmed cases of avian influenza A (H7N9) in China (8 May 2013). There are 32 fatalities, 55 patients are hospitalized and 44 patients have been discharged.  Eight provinces in China are affected (Anhui, Fujian, Henan, Hunan, Jiangsu, Jiangxi, Shandong and Zhejiang).


Case definition:

Confirmed Case: A patient with novel influenza A (H7N9) virus infection that is confirmed by CDC’s Influenza Laboratory or a CDC certified public health laboratory using methods agreed upon by CDC and CSTE.1

Probable Case: A patient with illness compatible with influenza for whom laboratory diagnostic testing is positive for influenza A, negative for H1, negative for H1pdm09, and negative for H3 by real-time reverse transcriptase polymerase chain reaction (RT-PCR), and therefore unsubtypeable.

Case Under Investigation: A patient with illness compatible with influenza meeting either of the following exposure criteria and for whom laboratory confirmation is not known or pending, or for whom test results do not provide a sufficient level of detail to confirm novel influenza A virus infection.

   A patient who has had recent contact (within ≤ 10 days of illness onset) with a confirmed or probable case of infection with novel influenza A (H7N9) virus.
OR

   A patient who has had recent travel (within ≤ 10 days of illness onset) to a country where human cases of novel influenza A (H7N9) virus have recently been detected or where novel influenza A (H7N9) viruses are known to be circulating in animals.

Transmission:

At the moment, there is no person-person transmission reported but many people infected with H7N9 are reported to have contact with poultry. People can get infected when they touch an infected bird or contaminated environment and then touch their eyes, nose or mouth. Virus can be found in huge amount in birds’ dropping and mucus.

Symptoms:

Symptoms include fever, cough and shortness of breath. The disease may progress to severe pneumonia, acute respiratory distress syndrome, septic shock, multi-organ failure and death.

Diagnostic tool:

Currently, the only test available to detect H7N9 is real-time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCT). Samples from respiratory tract (eg: nose, throat, lung) are taken and brought to public health lab. The results typically ready within 4 hours.

Treatment:

Basically, there was no early data available for the early use of neuraminidase inhibitor in those who are infected with H7N9. Lab testing with functional assay indicates that H7N9 is susceptible with neuraminidase inhibitor but resistant to adamantanes (eg: amantadine, rimantadine).  The clinical benefit is greatest when it is administered early (within 48 hours) but the drug must be given as soon as possible for those who are indicated even though the onset of disease has been more than 48 hours.  

The group of people who are indicated for the use of neuraminidase inhibitor:

a.     Confirmed case
b.     Probable case
c.      H7N9 cases under investigation.

Patients who are at high risk for developing complication when contracting H7N9:

a.     Age less than 2 years old or ≥ 65 years old.
b.     Patient younger than 19 years old who is on long-term aspirin medication.
c.      Alaska natives or American Indians.
d.     Patient with underlying medical conditions.
e.     Pregnant women or postpartum (within two weeks after delivery) women.
f.      Immunosuppressed patients – under immunosuppressed drug or HIV.
g.     Morbidly obese (BMI≥40)
h.     Resident of nursing home or other chronic care facilities. 

The duration of neuraminidase inhibitor:

5 days but can be extended in severely ill patients and immunosuppressed patients.




Special precaution:

a.     Age ≥ 65 years old: No dosage reduction is required if age alone is considered.
b.     Pregnancy: The dose is similar to non-pregnant women. Pregnancy category C medication. Zanamivir is more preferable than oseltamivir due to its limited systemic absorption.
c.      Impaired renal function: No dose adjustment is recommended by manufacturer for inhaled zanamivir. Oseltamivir dose should be reduced if creatinine clearance is 10-30 ml per minute. The dose should be reduce of 75 mg twice daily to 75 mg once daily.

Vaccine:

There is no vaccine available at the moment.

References:
1.  Avian Influenza A H7N9. Centers for Disease Control and Prevention.   
     (http://www.cdc.gov/flu/avianflu/h7n9-virus.htm)(accessed 9 May 2013)
2.  Avian Influenza A(H7N9). Ministry of Health Malaysia. 
     (http://www.moh.gov.my/press_releases/401)(accessed 9 May 2013)

Wednesday, May 8, 2013

Acute gastroenteritis in children: WHO 2005, NSW Health 2010, AMMCOP/MPA 2011



Definition:

Diarrhea is three or more loose or watery stool in a day. However, the consistency of stool is more important than the frequency (WHO 2005). The main problem with acute diarrhea is rapid fluid loss and electrolyte loss. The volume of fluid loss can vary from 5 ml/kg BW/day to ≥ 200 ml/kg BW/day. Moreover, diarrhea can be the initial signs of non gastro-intestinal tract illness such meningitis, otitis media, bacterial pneumonia, urinary tract infection and  intussusceptions. 


Clinical types of diarrheal diseases (WHO 2005):

1.     Acute watery diarrhea (including cholera): It is usually lasts several hours to days. The main danger is dehydration. Weight loss may occur if feeding is not continued.
2.     Acute bloody diarrhea (or dysentery): The main dangers are intestinal mucosal damage, sepsis and malnutrition. Dehydration can also occur.
3.     Persistent diarrhea: Diarrhea that lasts 14 days or longer. The main danger is malnutrition and serious non-intestinal infection. Dehydration can also occur.
4.     Diarrhea with severe malnutrition (marasmus or kwashiorkor): The main dangers are severe systemic infection, dehydration, heart failure and mineral and vitamin deficiency. 

Etiology (WHO 2005, AMMCOP/MPA 2011):

The most common causative agent in both developed and developing countries is rotavirus. Other enteric viruses that can cause diarrhea include norovirus, adenovirus, calicivirus and astrovirus.  In developed countries, childhood diarrhea are caused mainly by enteric viruses rather than bacterial pathogens. In developing countries, bacterial pathogens such as E.coli, non-typhoidal Salmonella, Shigella species and Campylobacter species are important etiologic agents other than enteric viruses. 

In Malaysia, the most common causes of viral origin diarrhea are rotavirus, norovirus and enteric adenovirus. The most common causes of bacterial diarrhea is non-typhoidal Salmonella, followed by Campylobacter, Shigella and E.coli. 

Assesment:

History: Ask the mother or other caretaker about:
·      Assess the onset, duration, frequency, quantity and character of both vomiting (presence of bile, blood) and diarrhea (presence of blood, mucus).
·      Presence of other clinical symptoms such fever, cough or other important problems (convulsion, recent measles).
·      Recent oral intake – types and amount (including breast milk and other fluids or foods).
·      Urine output.
·      Weight before illness (if available)
·      Past medical history (underlying medical problems, history of other recent infections, medication, immune-compromised state)
·      Social history
·      Immunization history.

Physical examination: (WHO 2005, AMMCOP/MPA 2011)
Assess the state of perfusion: (PALS, APLS)
Sign of shock: tachycardia, cold extremities, prolonged capillary filling time (>2 seconds), weak peripheral pulse, depressed mental state with or without hypotension.
.     Any child with shock go straight to treatment Plan C.
OR you can also use the WHO chart below to assess the degree of dehydration and then choose the treatment plan A, B or C, as needed. (WHO, 2005)

Other than that, we must also examine other aspects such as: (College of Paediatrics, Academy of Medicine of Malaysia I Malaysian Paediatric Association, 2011)
·      Mucous membrane – moist or dry
·      Vital signs (temperature, heart rate, respiratory rate, and blood pressure)
·      Respiratory pattern
·      Bowel sound
·      Inspection of stool
Estimation of fluid deficit:

World Health Organization, 2005:


College of Paediatrics, Academy of Medicine of Malaysia I Malaysian Paediatric Association, 2011 (AMMCOP/MPA 2011):



Viral vs Bacterial Causes (AMMCOP/MPA 2011):

Viral:
Associated with more significant vomiting and respiratory symptoms.
Rotavirus can cause severe vomiting and dehydration.
Bacterial:
Associated with fever (>39°C), abdominal pain, overt fecal blood, CNS involvement such as irritability, apathy, seizures or coma.
 Howerer, the clinical features of both viral and bacterial can overlap.

Diagnostic tools:
1.     Stool: Stool culture is indicated if profuse watery stools (cholera),  bloody diarrhea, mucous in stool, severe and prolonged diarrhea, immune-compromised children as well as parasites.
2.     Urine: Specific gravity is beneficial for children with severe dehydration who is under rehydration therapy.
3.     Blood: Urea, sodium, potassium, bicarbonate, pH, complete blood count (if bacterial sepsis is suspected), glucose monitoring (girls younger than 5 years with vomiting), calcium, magnesium (in young infants).

Management of Diarrhea:

AMMCOP/MPA 2011:
 
Malaysian Paediatric protocol:

PLAN C: TREAT SEVERE DEHYDRATION QUICKLY (Resuscitation)
1.     Start intravenous (IV) or intraosseous (IO) fluid immediately.
If patient can drink, give ORS by mouth while the drip is being set up.
2.     Initial fluids for resuscitation of shock: 20 ml/kg of NaCl 0.9% or Hartmann solution as a rapid IV bolus. Repeated if necessary until patient is out of shock or if fluid overload is suspected. Review patient after each bolus.

3.     Calculate the fluid needed over the next 24 hours:
Fluid for Rehydration (also called fluid deficit) + Maintenance (minus the fluids given for resuscitation).

Fluid for Rehydration: percentage dehydration X body weight in grams.
Maintenance fluid (NaCl 0.45 / D5%)
1st 10 kg = 100 ml/kg;

10-20 kg = 1000 ml/day + 50 ml/kg for each kg above 10 kg
>20 kg = 1500 ml/day + 20 ml/kg for each kg above 20 kg

New South Wales Health, 2010:


WHO 2005:



Adjunctive therapy:
1.     Antibiotics: It not routinely reccomended but is indicated in some cases such as Shigella dysentery; cholera; when diarrhea is associated with other acute infection such as UTI and pneumonia; salmonella in a very young baby (<3 achlorhydia.="" ill="" immunocompromised="" immunosupression="" months="" o:p="" systemically="">
2.     Anti-emetics: It is not recommended by CDC 2003, WHO 2005, ESPGHAN2008, New South Wales Health 2010, AMMCOP/MPA 2011.
Anti-emetic such as dimenhydrinate, domperidone, metochlopramide and promethazine are not reccomended because they can cause sedation (that can interfere oral rehydration therapy), increase frequency of diarrhea or lead to fluid and toxic retention that would be eliminated through vomiting.
3.     Anti-diarrheal agents: anti-motility (loperamide; imodium, diphenoxylate HCL; Lomotil), adsorbants (Kaolin-pectin) and anti-secretory (Bismuth subsalicylate) are not recommended by CDC 2003, WHO 2005, ESPGHAN2008, New South Wales Health 2010, AMMCOP/MPA 2011.
i.               Anti-motility:
Antimotility is not recommended as these drugs can lead to sedation, severe paralytic ileus, central nervous system toxicity and prolonged infection.
a.     Loperamide (Imodium®) – decrease frequency and duration of diarrhea but have serious side effects (lethargy and death) especially in young children (< 3 years).
b.     Diphenoxylate HCL (Lomotil®) – anti-peristaltic, mask water loss, prolong intestinal transit time, increases direct contact between intestinal epithelium and noxious agents. Furthermore, it has narrow therapeutic range therefore it can increase the risk of side effects and overdose.
ii.              Intraluminal agents:
a.     Silicates-koalin/pectin – it can bind microorganisms or their products, it can increase stool consistency but not losses of water and electrolytes. Other than that, it can also decrease drug and nutrients absorptions.
b.     Silicates-diosmectite – it can bind selected bacterial pathogens and rotavirus, restore the integrity of damaged intestinal epithelium, reduce stool output and duration. It may be used as adjunctive to ORS. No side effects observed. 
iii.            Anti-secretory:
a.     Enkephalinase inhibitors (racecadotril ®) – it significantly reduce stool output, well tolerated and no side effects. This is recommended as an adjunctive therapy.
iv.             Probiotics and prebiotics:
a.     Probiotics:
The effect of probitoics are strain-specific and dose specific. The recommendation is the use of strains with proven efficacy and in appropriate doses.
b.     Prebitoics
Prebiotics are defined as non-digestible food compounds that beneficially affect the host by selectively stimulating the growth and/or activity of one or of a limited number of bacteria in the large intestine, thereby improving the health of the host. Not all types of prebiotics are the same or have similar effect.

It is not recommended at the moment as an adjunctive therapy for acute diarrhea.

Nutritional Therapy / Special Infant Formula:
For patients who are still breast-fed, they should continue breastfeeding. For those who are formula-fed, the need of dilution is not recommended. According to Brown KH et al, child fed with undiluted formula resulted in a significant body weight catch up but a slight increase in stool frequency compared to those fed with diluted formula.

Zinc
According to WHO 2005 and UNICEF, zinc is recommended as universal treatment in children with diarrhea. The use of zinc in children without severe malnutrition did not prove to be beneficial. AMMCOP/MPA 2011 does not recommend the use of zinc in children with acute diarrhea who are not malnourished.

Prevention (WHO 2005, AMMCOP/MPA 2011):

1.     Breastfeeding. (WHO 2005). This practice should be done immediately after birth. The exclusive breastfeeding should be six months. The advantages of this practice are the protection of children against the risk of allergy early in life, aid in child spacing and protection against infection other than diarrhea such as pneumonia.
2.     Improved feeding technique
3.     Use of safe water
4.     Hand washing
5.     Food safety (WHO 2005)
There are several key messages regarding the preparation and consumption of foods:
a.     Do not eat raw food, except undamaged fruits and vegetables that are peeled and eaten immediately.
b.     Wash hand thoroughly after defecation and before food preparation.
c.     Cook food until it is hot throughout.
d.     Eat food while it is still hot or rehear thoroughly before eating.
e.     Wash and dry thoroughly all cooking and serving utensils after use.
f.      Keep cooked food and clean utensil separately from uncooked food and potentially contaminated utensils.
g.     Keep food from flies.
6.     Use of latrines/toilet and safe disposal of stools (WHO 2005). This is important in order to prevent the spread of pathogen via contact with contaminated stools. In case of access to clean, designated latrine is not available, people should have designated place and bury the feces immediately.
7.     Measles immunization. (WHO 2005) It can reduce the incidence and severity of diarrheal diseases.
8.   Rotavirus immunization (AMMCOP/MPA 2011). It should be considered as part of rotavirus prevention in Malaysian children. First dose should be given at the age of 6-12 weeks. Full schedule should be completed by the age of 8 months for RotaTeq ®(3 doses) and 6 months for Rotarix ® (2 doses).