INTRODUCTION:

Acute respiratory infections (ARI) may cause inflammation of the respiratory tract anywhere from nose to alveoli, with a wide range of combination of symptoms and signs. ARI is often classified by clinical syndromes depending on the site of infection and is referred to as ARI of upper (AURI) or lower (ALRI) respiratory tract. The upper respiratory tract infections include common cold, pharyngitis and otitis media. The lower respiratory tract infections include epiglottitis, laryngitis, laryngotracheitis, bronchitis, bronchiolitis and pneumonia.

The clinical features include running nose, cough, sore throat, difficult breathing and ear problem. Fever is also common in acute respiratory infections. Most children with these infections have only mild infections, such as cold or cough. However, some children may have pneumonia which is a major cause of death. In less developed countries, measles and whooping cough are important cause of severe respiratory tract infection.

PROBLEM STATEMENT:

Every year ARI in young children is responsible for an estimated 3.9 million deaths worldwide. About 90 percent of the ARI deaths are due to pneumonia which is usually bacterial in origin. The incidence of ARI is similar in developed and developing countries may be as low as 3-4 percent, its incidence in developing countries range between 20 to 30 percent. This difference is due to high prevalence of malnutrition, low birth weight and indoor air pollution in developing countries.

ARI is an important cause of morbidity in the children. On an average, children below 5 years of age suffer about 5 episodes of ARI per child per year, thus accounting for about 238 million attacks. Consequently, although most of the attacks are mild and self limiting episodes, ARI is responsible for about 30-50 percent of visits to health facilities and for about 20-40 percent of admissions to hospitals¹. It is also a leading cause of disabilities including deafness as sequelae of otitis media².

Pneumonia kills more children than any other disease (more than AIDS, malaria and measles combined). More than 2 million children die from pneumonia each year, accounting for almost one in 5 under-five deaths worldwide. Yet, little attention is paid to this disease³. Streptococcus pneumoniae is a major cause of illness and death in children, as well as in adults. According to a WHO estimate, about 1.6 million cases of fatal pneumococcal disease occur worldwide, mostly in infants and elderly. In addition, immunocompromised individuals of all ages are at increased risk⁴. Likewise, haemophilus influenza type B (Hib) bacteria is estimated to cause 3 million cases of severe pneumonia and meningitis, and approximately 386,000 deaths per year in children under 5 years of age ⁵.

The key pneumonia indicators developed for prevention and treatment of pneumonia are shown in Table 1. It also shows the data pertaining to pneumonia from South-East Asia countries for the year 2000-2007.

In India, in the states and districts with high infant and child mortality rates, ARI is one of the major causes of death. ARI is also one of the major reasons for which children are brought to the hospitals and health facilities. Hospital records from states with high infant mortality rates show that up to 13% of inpatients deaths in paediatric wards are due to ARI.

The proportion of death due to ARI in the community is much higher as many children die at home ⁶. The reason for high case fatality may be that children are either not brought to the hospitals or brought too late.

Table 1-Key pneumonia indicators: mortality, prevention and treatment in South-East Asia countries (2000-2007) ⁷

Countries	Pneumonia deaths		Prevention					Treatment
	% of under 5 deaths due to pneumonia (2008)	Total number of pneumonia deaths in under 5 (2004)	% of children who are under weight, 0-59 months		% of infants who are exclusively breastfed (<6 months) (2000-2007)	% of one year old immunized against		% of under 5 with pneumonia takes to appropriate heath care provider (2000-2007)
	% of under 5 deaths due to pneumonia (2008)	Total number of pneumonia deaths in under 5 (2004)	Moderate to severe (2000-2007)	Severe (2000-2007)		Measles 2007	Hib 2007
India	20	410	46	18	46	67	-	69
Bangladesh	14	51	46	13	37	88	-	30
Bhutan	24	1	19	3	-	95	-	-
Indonesia	22	25	28	9	40	80	-	61
Myanmar	13	20	32	7	15	81	-	66
Maldives	16	0	30	7	10	97	-	22
Nepal	14	11	45	13	53	81	-	43
Sri Lanka	10	0	29	-	53	98	-	58
Thailand	10	2	9	-	5	96	-	84
World	18	2044	25	10	38	82	26	57

Epidemiological determinants

Agent factors

Table 2: The agents causing ARI, age group affected and clinical features⁹

Agent	Age group (s) most frequently affected		Characteristic clinical features
Bacteria
Bordetella pertussis	Infants and young children	Paroxysmal cough
Corynebacterium diphtheria	Children	Nasal/tonsillar/pharyngeal membranous exudates ± severe toxaemia
Haemophilus influenza	Adults	Acute exacerbations of chronic bronchitis pneumonia
	Children	Acute epiglottitis (H.influenzae type B)
Klebsiella pneumonia	Adults	Lobar pneumonia ± lung abscess
Legionella pneumopphila	Adults	Pneumonia
Staphylococcus pyogenes	All ages	Lobar and broncho-pneumonia (especially secondary to influenza) ± lung abscess
Streptococcus pneumonia	All ages	Pneumonia (lobar or multilobular) Acute exacerbations of chronic bronchitis
Streptococcus pyogenes	All ages	Acute pharyngitis and tonsillitis
Virus
Adenoviruses-endemic types (1,2,5)	Young children	Lower respiratory
Adenoviruses-endemic types (3,4,7)	Older children and young adults	Febrile pharyngitis and influenza-like illness
Enteroviruses (ECHO and Coxsackie)	All ages	Variable respiratory
Influenza A	All ages	Fever, aching, malaise, variable respiratory
Influenza B	All ages School children	Occasional primary pneumonia Secondary bacterial pneumonia in elderly
Influenza C	Rare	Mild upper respiratory
Measles	Young children	Variable respiratory with characteristic rash
Parainfluenza 1	Young children	Re-infection in later life
Parainfluenza 2	Young children	Mild upper respiratory
Parainfluenza 3	Infants	Bronchiolitis and pneumonia
Respiratory syncytial virus	Infants and young children	Severe bronchiolitis and pneumonia
Rhinoviruses (multiple serotypes)	All ages	Common cold
Coronavirus	All ages	Common cold
Other agents
Chlamydia type B (Psittacosis)	Adults exposed to infected birds	Influenza-like illness and atypical pneumonia
Coxiella burntti (Q fever)	Adults exposed to sheep and cattle	Atypical pneumonia
Mycoplasma pneumonia	School children and young adults	Febrile bronchitis and atypical pneumonia

Host factors

Small children can succumb to the disease within a matter of days. Case fatality rates are higher in young infants and malnourished children. Age-specific mortality rates show wide differences between countries. In general, rates tend to be high in infants and young children, and in the elderly in all countries, although the age group with the highest rates can differ. In developing countries where malnutrition and low birth weight is often a major problem, the rates in children tend to be the highest. By contrast, in developed countries respiratory infections are only exceptionally fatal in infants but are commonly terminal in the elderly.

Risk factors

Many risk factors for respiratory tract infections have been identified. They include not only the climate conditions but also the housing, level of industrialization and socio-economic development. In developing countries, overcrowded dwellings, poor nutrition, low birth weight and intense indoor smoke pollution underline the high rates.

Mode of transmission

All the causative organisms are normally transmitted by the airborne route. As most viruses do not survive for long outside the respiratory tract, the chain of transmission is maintained by direct person-to-person contact.

Control of Acute Respiratory Infections

Improving the primary medical services and developing better methods for early detection, treatment and where possible, prevention of acute respiratory infections is the best strategy to control ARI. Effective reduction of mortality due to pneumonia is possible if children suffering from pneumonia are treated correctly. Education of mother is also crucial since compliance with the treatment and seeking care promptly when signs of pneumonia are observed, are among the key factors which determine the outcome of disease. The recommendations by WHO for the management of acute respiratory infections in children and the practical guidelines for outpatients care are discussed below¹⁰. The same guidelines are followed in India ¹¹.

Clinical assessment

History taking and clinical assessment is very important in the management of the acute respiratory infections. Note the age of the child, for how long the child is coughing, whether the child is able to drink (if the child is aged 2 months upto 5 years), has the young infant stopped feeding well (child less than 2 months), has there been any antecedent illness such as measles, does the child have fever, is the child excessively drowsy or difficult to wake (if yes, for how long), did the child have convulsions, is there irregular breathing, short periods of not breathing or the child turning blue, any history of treatment of illness.

Physical examination

Look and listen for the following:

1. Count the breaths in one minute

2. Look for chest indrawing

3. Look and listen for stridor

4. Look for wheeze

5. See if the child is abnormally sleepy or difficult to wake

6. Feel for fever or low body temperature

7. Check for severe malnutrition

8. Cyanosis is a sign of hypoxia. Cyanosis must be checked in good light

Classification of illness

a. Child aged 2 months upto 5 years

1. Very Severe Disease

2. Severe Pneumonia

3. Pneumonia (not severe)

4. No Pneumonia: Cough or Cold

1. Very Severe Disease

Table 3: Management of Very Severe Disease ¹²

Signs	Not able to drink
	Convulsions
	Abnormally sleepy or difficult to wake
	Stridor in calm child
	Severe malnutrition
Classify As	Very Severe Disease
Treatment	Refer urgently to hospital
	Give first dose of an antibiotic
	Treat fever, if present
	Treat wheezing, if present
	If cerebral malaria is present, give an antimalarial

2. Severe Pneumonia (Table 4)

3. Pneumonia (not severe) (Table 4)

4. No Pneumonia: Cough or Cold (Table 4)

Table 4: Management of pneumonia in a child aged 2 months upto 5 years¹³

Signs	Chest indrawing (if also recurrent wheezing, go directly to treat wheezing)	No chest indrawing and fast breathing (50 per minute or more if child 2 months upto 12 months; 40 per minute or more if child 12 months upto 5 years).	No chest indrawing and No fast breathing (Less than 50 per minute, if child 2 months upto 12 months; less than 40 per minute if child is 12 months upto 5 years).
Classify as	Severe Pneumonia	Pneumonia	No pneumonia: Cough or Cold
Treatment	Refer Urgently to hospital Give first dose of an antibiotic Treat fever, if present (if referral is not feasible, treat with an antibiotic and follow closely)	Advise mother to give home care. Give an antibiotic. Treat fever, if present. Treat wheezing, if present. Advise mother to return with child in 2 days for reassessment, or earlier if the child is getting worse.	If coughing more than 30 days, refer for assessment. Asses and treat ear problem or sore throat, if present. Asses and treat other problems. Advice mother to give home care. Treat fever, if present. Treat wheezing, if present.
	Re-asses in 2 days a child who is taking an antibiotic for pneumonia
Signs	Worse Not able to drink Has chest indrawing Has other danger signs	The same	Improving Breathing slower Less fever Eating better
Treatment	Refer Urgently to hospital	Change antibiotic or Refer	Finish 5 days of antibiotic

b. Classifying illness of young infant

Table 5: Classification and Management of illness in young infants ¹⁴

Signs	Stopped feeding well Convulsions Abnormally sleepy or difficult to wake Stridor in calm child Wheezing Fever or low body temperature
Classify as	Very Severe Disease
Treatment	Refer Urgently to hospital Keep young infant warm Give first dose of an antibiotic
Signs	Severe chest indrawing or Fast breathing ( 60 per minute or more)	No severe chest indrawing and No fast breathing (less than 60 per minute)
Classify as	Severe Pneumonia	No Pneumonia: Cough or Cold
Treatment	Refer Urgently to hospital. Keep young infant warm Give first dose of an antibiotic (if referral is not feasible, treat with an antibiotic and follow closely).	Advise mother to give the following home care: -Keep young infant warm -Breast-feed frequently -Clear nose if it interferes with feeding Return quickly if:- Breathing becomes difficult Breathing becomes fast Feeding becomes a problem The young infant becomes sicker.

Treatment

a. Treatment for children aged 2 months upto 5 years

Table 6: Treatment of pneumonia daily dose schedule of cotrimoxazole ¹⁵

Age/Weight	Paediatric Tablet: Sulphamethoxazole 100 mg And Trimethoprim 20 mg	Paediatric syrup Each spoon (5 ml): Sulphamethoxazole 200 mg and Trimethoprim 40 mg
< 2 months (Wt. 3-5 kg)	One tablet twice a day	Half spoon (2.5 ml) twice a day
2-12 months (Wt. 6-9 kg)	Two tablets twice a day	One spoon (5 ml) twice a day
1-5 years (Wt. 10-19 kg)	Three tablets twice a days	One and half spoon (7.5 ml) twice a day

b. Pneumonia in young infants under 2 months of age

Table 7: Treatment of pneumonia in children aged less than 2 months ¹⁶

Antibiotic	Dose	Frequency
Antibiotic	Dose	Age < 7 days	Age 7 days to 2 months
Injection Benzyl Penicillin	50000 IU/Kg/Dose	12 hourly	6 hourly
Injection Ampicillin	50 mg/kg/dose	12 hourly	8 hourly
Injection Gentamycin	2.5 mg/kg/dose	12 hourly	8 hourly

Prevention of Acute Respiratory Infection

Present understanding of risks factors of respiratory tract infections in childhood indicates several approaches for primary prevention. In developing countries, improved living conditions, better nutrition and reduction of smoke pollution indoors will reduce the burden of mortality and morbidity associated with ARI. Other preventive measures include better MCH care. Immunization is an important measure to reduce cases of pneumonia which occur as a complication of vaccine preventable disease, especially measles. It is obvious that community support is essential to reduce the disease burden. Families with young children must be helped to recognize pneumonia. Health promotional activities are especially important in vulnerable areas ¹⁷.

Immunization

Vaccines hold promise of saving millions of children from dying of pneumonia. Three vaccines have potential of reducing deaths from pneumonia. These vaccines work to reduce the incidence of bacterial pneumonia.

1. Measles Vaccine

Pneumonia is a serious complication of measles and the most common cause of death associated with measles worldwide. Thus, reducing the incidence of measles in young children through vaccination would also help to reduce deaths from pneumonia. A safe and effective vaccine against measles is available for past 40 years. The coverage rate for this vaccine for the year 2006 is estimated to be 80 percent worldwide and 59 percent for India ¹⁸.

2. Hib Vaccine

Hib (Haemophilus influenza type B), is an important cause of pneumonia and meningitis among children in developing countries. Hib vaccine has been available for more than a decade. It reduces dramatically the incidence of Hib meningitis and pneumonia in infants and nasopharyngeal colonization by Hib bacteria. Its high cost has posted obstacle to its introduction in developing countries. While in developed countries the vaccination coverage was 82 percent during the year 2006; it was only 17 percent in developing countries and only 22 percent worldwide¹⁹. India has for the first time decided to vaccinate children against Hib bacteria and Tamil Nadu will be first state to vaccinate all newborns. Later on, the Hib immunization programme will cover the whole country²⁰. Health Ministry of India is planning to introduce pentavalent vaccine in its national immunization programme. It will combine DPT with hepatitis B and Hib bacteria vaccine²¹.

The vaccine is often given as combined preparation with DPT and poliomyelitis vaccine. Three or Four doses are given depending on the manufacturers and type of vaccine used, and is given intramuscularly. The vaccine schedule is at 6, 10 and 14 weeks of age or according to national immunization schedule. In many industrialized countries a booster dose is given between 12-18 months which provides additional benefit to limit burden of Hib disease among children. For children more than 12 months of age, who have not received their primary immunization series a single dose is sufficient for protection. The vaccine is not generally offered to children aged more than 24 months²².

No serious side-effects have been recorded, and no contraindications are known, except for hyper-sensitivity to previous dose of vaccine. All conjugate vaccine has an excellent safety record, and where tested, do not interfere substantially with immunogenicity of other vaccines given simultaneously²³.

3. Pneumococcal Pneumonia Vaccine

a. PPV23

For years, the polysaccharide non-conjugate vaccine containing capsular antigens of 23 serotypes against this infection have been available for adults and children over 2 years of age. Children under 2 years of age and immunocompromised individuals do not respond well to the vaccine. It is recommended for selected groups, e.g., those who have undergone splenectomy or have sickle-cell disease, chronic diseases of heart, lung, liver or kidney; diabetes mellitus, alcoholism, generalized malignancies, organ transplants etc. In some industrialized countries like USA, it is routinely advised for everyone aged above 65 years²⁴.

A dose of 0.5 ml of PPV23 contains 25 micrograms of purified capsular polysaccharide from each 23 serotypes. For primary immunization, PPV23 is administered as a single intra-muscular dose preferably in the deltoid muscle or as subcutaneous dose. The vaccine should not be mixed in the same syringe with other vaccines, for e.g. with influenza vaccine, but may be administered at the same time by separate injection in the other arm. Simultaneous administration does not increase adverse events or decrease the antibody response to either vaccine. Protective capsular type-specific antibody levels generally develop by the third week following vaccination²⁵.

Minor adverse reactions, such as transient redness and pain at the site of injection occur in 30-50 percent of those who have been vaccinated, more commonly following subcutaneous administration. Local reactions are more frequent in recipients of the 2^nd dose of the vaccine²⁶.

b. PCV-7

Only recently a new vaccine has been developed that is suitable for infants and toddlers, called Pneumococcal Conjugate Vaccine (PCV). It has been approved and is in use in routine immunization for children in many developed countries since year 2000²⁷. This new generation of conjugate pneumococcal vaccine contains 7 selected polysaccharides bound to protein carriers, and induce a T-cell dependent immune response²⁸. This vaccine is very effective at preventing pneumococcal pneumonia and meningitis, but only moderately effective at preventing otitis media. Unlike the adult polysaccharide vaccine, the paediatric conjugate vaccine decreases nasopharyngeal colonization of bacteria, which results in less transmission of disease to non-immunized children and adults (herd immunity)^{29, 30}.

The primary series of PCV-7 consists of 3-intramuscular doses administered to infants at 6, 10 and 14 weeks, a booster dose administered after 12 months of age may improve the immune response. The other schedule is at 2, 4 and 6 months of age, and a booster at 12-15 months. When the vaccine is initially introduced into childhood immunization programmes, a single catch-up dose of PCV-7 may be given to previously unimmunized children aged 12-24 months and to children aged 2-5 years considered to be at high risk. It is not known whether re-vaccination is necessary later in life. The duration of protection against invasive pneumococcal disease caused by vaccine serotypes is at least 2-3 years following primary PCV-7 immunization in infancy. However, PCV-7 immunogenicity data, as well as experience with other conjugate vaccines suggest, protection may last considerably longer³¹.

Mild reactions like erythema and tenderness to PCV-7 occur in upto 50 percent of recipients, but systemic reactions are unknown. Revaccination is not recommended for those, who had a anaphylactic reaction to initial dose.

CONCLUSION:

In conclusion, age and crowding measured in terms of nighttime crowding, as well as attending child-care centers, were risk factors for both upper and lower respiratory tract infections. For lower respiratory tract infections, smoking and gender had additional significant effects, while ethnicity and lack of breastfeeding were likely risk factors for lower respiratory tract infections. These findings have major public health implications. Although the burden of acute respiratory infections in Greenlandic children has for many years been high, Greenland today is a modern society. The risk factors for acute respiratory infections are related to child care, passive smoking, and in-house crowding in nuclear families rather than to poverty and a traditional way of life. However, these factors were not evaluated in the present study and should be addressed separately. With 80 percent of the children being passive smokers, smoking in the household should be strongly discouraged. Finally, the number of persons sleeping in the same room should, whenever possible, be reduced, and especially by children less than 5 years of age. Taken together, these measures may reduce the burden of illness in the youngest group of children.

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31. WHO (2007), Weekly Epidemiological Record, No. 12, 23^rd March, 2007.

Received on 14.01.2015 Accepted on 03.03.2015

Asian J. Res. Pharm. Sci. 5(1): Jan.-March 2015; Page 49-54

DOI: 10.5958/2231-5659.2015.00008.9