INTRODUCTION
Infections of the respiratory tract are the most common illnesses in humans, particularly among children. Though these are not very alarming in adults other than causing discomfort, in the extremes of age and in those with low respiratory reserve they cause considerable morbidity and mortality. Childhood acute respiratory infections, including pneumonia, is a significant public health problem in India.
Acute respiratory infections (ARIs) may cause inflammation of the respiratory tract anywhere from the nose to the alveoli, with a wide range of combination of symptoms and signs. Depending on the site of infection, ARIs are classified as acute upper respiratory tract infections (AURIs) or acute lower respiratory tract infections (ALRIs). The upper respiratory tract consists of the airways from the nostrils to the vocal cords in the larynx, including the paranasal sinuses and the middle ear. The lower respiratory tract covers the continuation of the airways from the trachea and bronchi to the bronchioles and the alveoli. The commonly occurring AURIs are common cold, pharyngitis, otitis media and sinusitis. The common ALRIs include epiglottitis, laryngitis, laryngotracheitis, bronchitis, bronchiolitis and pneumonia.1-7
Acute respiratory infections are not confined to the respiratory tract only, but have systemic effects because of possible extension of infection or microbial toxins, inflammation and reduced lung function. Diphtheria, pertussis (whooping cough) and measles are vaccine-preventable diseases that may have a respiratory tract component, but also affect other systems.1,2
PROBLEM STATEMENT
Acute respiratory infections in children under 5 years of age are a cause of concern all over the globe, particularly in developing countries. Except during the neonatal period, ARIs are the most common causes of both illness and mortality in children under five, who average 3 to 6 episodes of ARIs annually, regardless of where they live or what their economic situation is. Pneumonia alone is responsible for about one-fifth of the estimated 10.6 million deaths per year in this age group. The World Health Organization (WHO) estimates that 2 million children under 5 years of age 2die of pneumonia each year. It is estimated that Bangladesh, India, Indonesia and Nepal together account for 40% of the global ARI mortality.1,2,8
In India, the infant mortality rate (IMR) has declined from 139/1,000 live births in 1972 to 42/1,000 live births in 2009. There are wide inter and intra state variations in infant and child mortality. There are also variations between rural and urban India. For example, rural IMR is 55/1,000 live births as opposed to an urban IMR of 34/1,000 live births. A significant proportion of child deaths (over 50% of under-five mortality and 66% of infant mortality) occur in the neonatal period. Neonatal mortality rate is 35/1,000 live births and under five mortality rate is 74. A significant proportion of child deaths (over 50% of under-five mortality and 66% of infant mortality) occur in the neonatal period. According to WHO about 20% of all deaths in children under 5 years of age are due to ALRIs—pneumonia, bronchiolitis and bronchitis, 90% of which occur due to pneumonia.9-11
Acute respiratory infections is also an important cause of morbidity in children in India. Common illnesses in children under 3 years of age include fever (27%), acute respiratory infections (17%), diarrhea (13%) and malnutrition (43%). National Family Health Survey (NFHS) III carried out in 2005 to 2006, reported 5.8% children less than 5 years of age suffered from ARI, as diagnosed by cough and short, rapid breathing, in the preceding 2 weeks before the survey. The burden of disease in terms of episodes per child per year has been found to range from 0.03 to 0.52.12-14
ETIOLOGY
The vast majority of AURIs have a viral etiology. Rhinoviruses account for 25 to 30% of AURIs; respiratory syncytial viruses (RSVs), para influenza and influenza viruses, human metapneumovirus, and adenoviruses for 25 to 35%; corona viruses for 10%; and unidentified viruses for the remainder. Contrary to the general belief that RSV infection is a problem of the West, WHO has shown that even in the developing countries RSV is the main cause of respiratory infection, killing around 6 lakhs children annually. Among bacteria, group A streptococci take the lead, though Corynebacterium diphtheriae, N. meningitidis may also cause AURI. H. influenzae, pneumococcus and Staphylococcus aureus are responsible for superimposed infections, leading to complications related to ears, sinuses, mastoids, lymph nodes and lungs. Acute pharyngitis, in conjunction with the development of a membrane on the throat, is nearly always caused by Corynebacterium diphtheriae in developing countries.1,3,15
Both bacteria and viruses can cause pneumonia. Bacterial pneumonia is often caused by Streptococcus pneumoniae (pneumococcus) or Haemophilus influenzae, mostly type B (Hib) and occasionally by Staphylococcus aureus or other streptococci. Just 8 to 12 of the many types of pneumococcus cause most cases of bacterial pneumonia, although the specific types may vary between adults and children and between geographic locations. Other pathogens, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, cause atypical pneumonias. Their role as a cause of severe disease in children under five in developing countries is unclear. The most common causes of viral LRIs are RSVs, followed by parainfluenza 3viruses. Before the effective use of measles vaccine, the measles virus was the most important viral cause of respiratory tract-related morbidity and mortality in children in developing countries.1,12
According to a systematic review, childhood pneumonia in India is caused by bacteria, viruses, atypical organisms like Chlamydia and Mycoplasma, although the precise proportions in community and hospital-based studies is not clear. However, it appears that about 10 to 15% of childhood pneumonias are caused by H. influenzae and RSV each; and 12 to 35% by pneumococcus. Other important causes include S. aureus, Gram negative organisms (especially in younger infants), Mycoplasma and Chlamydia. Serotypes of S. pneumoniae causing childhood pneumonia are also not well identified. However, it is not possible to differentiate between bacterial and viral ARIs based on clinical signs or radiology.11,14
RISK FACTORS
The community-based NFHS-III survey reported that ARI affects all children, irrespective of socioeconomic status; however certain risk factors likely to be associated with occurrence of and death from ARI have emerged from various studies.13-15
Demographic and Socioeconomic Factors
Prevalence is higher in young age particularly during infancy, slightly higher among boys, in rural areas, among scheduled-tribe children and those with poor economic status. However, case fatality rate is higher in girls. The prevalence is lower with high parental education particularly among children of mothers who have at least completed high school.13,14,16-18
Environmental Factors
The prevalence is higher among those residing in lower standard of living households with presence of environmental pollution. Those using biomass or solid fuel and those exposed to environmental tobacco smoke, i.e. passive smoking show higher prevalence than those without such exposure or using cleaner fuels. Prevalence is also high in children of households keeping large animals. Living in overcrowded conditions and sharing of bedroom are likely to result in increased occurrence of ARI. Prevalence is lower in those living in households that use piped drinking water and water filter for the purification of water.11,13,14,17-19
Nutritional Factors
Low birth weight, malnutrition and hypovitaminosis A have been found to be risk factors of ARI. Non-breastfed children or those with discontinuation of breastfeeding in early infancy or delayed weaning are at higher risk of getting pneumonia. These children are also at a higher risk of death from pneumonia.11,184
Illness and Treatment Factors
Probable risk factors that have emerged as being significant are lack of immunization particularly measles, previous history of severe ARI and asthma, unresponsiveness to earlier treatment and use of non-allopathic medicine. Correction of these factors can probably reduce mortality due to ARI.17,18 5
The WHO 2008 report cited and categorized all these risk factors into three groups as:20
- Definite risk factors: Malnutrition (weight-for-age z-score <–2), low birth weight, lack of exclusive breastfeeding during first 4 months, lack of measles immunization, indoor air pollution, crowding.
- Likely risk factors: Parental smoking, zinc deficiency, maternal inexperience, co-morbidities.
- Possible risk factors: Maternal illiteracy, day-care attendance, rainfall (humidity), high altitude (cold air), vitamin A deficiency, higher birth order, outdoor air pollution.
INTERVENTIONS
Interventions to control ARIs can be divided into four basic categories: immunization against specific pathogens, early diagnosis and treatment of disease, improvement in nutrition and safer environment. The first two fall within the purview of the health system and will be discussed here, whereas the last two fall under public health and require multisectoral involvement.1
Immunization
Widespread use of vaccines against measles, diphtheria, pertussis, Hib, pneumococcus and influenza have the potential to substantially reduce the 6incidence of ARIs in children in developing countries. Of these three vaccines contribute the most to the reduction of deaths from pneumonia. These are measles, Haemophilus influenzae B and pneumococcus.
Measles immunization leads to significant decline in child mortality, at least partly mediated by its impact on reduction of complications, including pneumonia. The exact burden of Hib pneumonia in India is not clear. The vaccine is efficacious in reducing invasive Hib disease and Hib pneumonia and meningitis in research trials. However the overall effectiveness depends on the proportion of childhood pneumonia caused by Hib. Similarly for pneumococcal pneumonia the exact burden and the serotypes responsible for invasive disease in India are not known. Polymerase conjugate vaccine are efficacious in reducing disease caused by vaccine-serotypes, so the overall effectiveness against childhood pneumonia is dependent on the relative burden of pneumococcal pneumonia and the serotype coverage of the vaccine.14
Measles Vaccine2
Tissue culture vaccines, either chick embryo or human diploid cell line vaccines, presented as a freeze dried product are given at 9 months of age as recommended by WHO—expanded program on immunization. However, seroconversion may be poor due to presence of maternal antibodies. A second dose is therefore given a year later in many countries. The reconstituted vaccine is administered subcutaneously as a single dose of 0.5 mL. Measles vaccine can also be combined with other live-attenuated vaccines such as mumps and rubella (MMR) vaccine, measles and rubella (MR) vaccine and measles mumps, rubella and varicella vaccine (MMRV).
Currently three Hib conjugate vaccines are available for use in infants and young children.
Polysaccharide vaccine : The first Hib vaccine licensed was a pure polysaccharide vaccine. Similar to other polysaccharide vaccines, immune response to the vaccine was highly age-dependent. Children under 18 months of age did not produce a positive response for this vaccine. As a result, the age group with the highest incidence of Hib disease was unprotected, limiting the usefulness of the vaccine.
Conjugate vaccine : The shortcomings of the polysaccharide vaccine led to the production of the Hib polysaccharide-protein conjugate vaccine. Attaching Hib polysaccharide to a protein carrier greatly increased the ability of the immune system of young children to recognize the polysaccharide and develop immunity. There are currently three types of conjugate vaccine utilizing different proteins in the conjugation process, all of which are highly effective: tetanospasmin (also called tetanus toxin), mutant diphtheria protein and meningococcal group B outer membrane protein.
7Combination vaccines : Multiple combinations of Hib and other vaccines have been licensed, reducing the number of shots necessary to vaccinate a child. Hib vaccine is often given as a combined preparation with DPT vaccine. WHO has certified several Hib vaccine combinations, including a pentavalent diphtheria-pertussis-tetanus-hepatitis B-Hib, for use in developing countries. Three or four doses are given intramuscularly, depending on the manufacturer and type of vaccine. The vaccine schedule is at 6, 10 and 14 weeks of age. For children more than 12 months of age who have not received their primary immunization, a single dose is sufficient for protection.
Two kinds of vaccines are currently available against pneumococci: a 23-valent polysaccharide vaccine—pneumococcal pneumonia vaccine (PPV23), which is more appropriate for adults than children and a 7-valent protein-conjugated polysaccharide vaccine—pneumonia conjugate vaccine (PCV7). A 9-valent vaccine (9-PCV) has undergone clinical trials in The Gambia and South Africa, and an 11-valent vaccine (11-PCV) is being tried in the Philippines.
Polysaccharide vaccine: PPV23 is a polysaccharide non-conjugate vaccine containing capsular antigens. A dose of 0.5 mL of the vaccine contains 25 mg of purified capsular polysaccharide from each 23 serotype. It is administered to adults and children over 2 years of age, as a single intramuscular dose preferably in the deltoid muscle or may even be given subcutaneously. The vaccine should not be mixed in the syringe with other vaccines, but may be administered at the same time by separate injection in the other arm.
Conjugate vaccine: PCV7 or pneumococcal conjugate vaccine is suitable for infants and toddlers. This contains 7 selected polysaccharides bound to protein carriers and induces a T cell dependent immune response. These are 2 μg of capsular polysaccharides of serotypes 4, 9V, 14, 19F and 23F; 2 μg of oligosaccharide from 18C; and 4 μg of polysaccharide of serotype 6B in a 0.5 mL dose; each serotype is conjugated to the non-toxic diphtheria CRM 197 protein and adsorbed onto aluminium salt to enhance the antibody response. Unlike the polysaccharide, vaccine the conjugate vaccine decreases nasopharyngeal colonization of bacteria, which produces herd immunity, thereby resulting in less transmission of disease to non-immunized children and adults. The primary series is given as 3 intramuscular doses 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 to 15 months.
Availability of Vaccines in India
Hib vaccines are available in several formulations: monovalent, tetravalent (DTwP-Hib), pentavalent (DTwP-HepB/Hib) and in similar combinations with acellular pertussis vaccine. All three types of Hib vaccines from Indian manufacturers are licensed in the country. The vaccines are available in a variety of vial sizes. Prequalified pentavalent vaccines are available in single, two and 8ten-dose presentations. Indian manufacturers currently produce 4 million doses of Hib-containing vaccines each year for the private market. Pentavalent vaccine supply offered to The Global Alliance for Vaccines and Immunization (GAVI)—eligible countries from two multinational suppliers is currently 66 million doses per year. Supplier capacity is sufficient to meet the present and future demand for India, if given sufficient lead time to increase production. GAVI has been instrumental in funding of Hib vaccine for children in urban slums, promotion of safe injection practices and inclusion of auto-disabled syringes for childhood immunizations in India.23,24
Wyeth Pharmaceuticals produces a PCV-7, which is the only commercially available pneumococcal conjugate (protein linked to polysaccharide) vaccine. It protects against pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, 23F. The vaccine is licensed in more than 70 countries for use in children of less than 5 years of age and has been introduced into immunization program in more than a dozen high-income countries. PCV-7 in developing countries is not expected to confer the same level of immunity because the distribution of serotypes in most developing countries differs from that in the high-income countries. It does not provide protection against serotypes 1 and 5 that, together with serotype 14, are the most frequent isolates in GAVI-eligible countries. Nevertheless, in March 2007, WHO issued guidance calling for the introduction of pneumococcal conjugate vaccines into immunization program in developing countries, beginning with the currently licensed PCV-7.31. Other pneumococcal conjugate vaccines that expand the serotypes coverage of PCV-7 are in late stages of development. GAVI provides vaccines at heavily subsidized rate to developing countries and has approached the Government of India asking for non-binding expressions of interest in introducing pneumococcal vaccines.22,25
Vaccination Recommendations in India
Currently other than measles, diphtheria and pertussis, no other vaccine has been included in the primary immunization schedule of India. Hib vaccine is being given in some districts.
Hib Vaccine
The Hib and pneumococcal subcommittee of National Technical Advisory Group on Immunization (NTAGI) in India met in April 2008 and reviewed the available published and unpublished literature as well as consulted prominent Hib experts to make an informed decision regarding the introduction of Hib vaccine into the routine Universal Immunization Program (UIP) in India.23
The committee noted that Hib diseases burden is sufficiently high in India to warrant prevention by vaccination. Hib vaccines have been demonstrated to be safe, both globally and in India, and extremely efficacious in all settings where they have been used. Hib vaccine fits into the UIP immunization schedule. Several Indian manufacturers are currently producing Hib vaccines and a detailed analysis showed that supplier capacity would be sufficient to meet the present and future 9demand for India if given sufficient lead time to increase production. Recognizing that it is the poorest children that are most at risk, the Indian Academy of Pediatrics (IAP) has already recommended this vaccine for routine use in India. The NTAGI subcommittee also strongly recommended that Hib vaccine should immediately be introduced in India's UIP.23
Pneumococcal Vaccine
WHO considers the inclusion of this vaccine in National Immunization Programs as particularly high priority in countries with under 5 mortality > 50 per 1,000 live births or greater than 50,000 child deaths annually. With an infant mortality rate of 50 per 1,000 live births and under five mortality of 74, India meets the WHO's criteria for countries where pneumococcal vaccination should be a priority for introduction. However, there have been considerable debate over this issue and pneumococcal vaccine has not been considered a priority in India.22,26-28
CASE MANAGEMENT
Background
Reduction of infant and child mortality has been an important consideration of the health policy of Government of India and it has tried to address the issue right from the early stages of planned development.
The ARI Control Program was started in India in 1990. It sought to introduce scientific protocols for case management of pneumonia with co-trimoxazole. Initially 14 pilot districts were selected and later on 10 new districts were included in 1991. A review of the health facility done in 1992 revealed that although 87% of personnel were trained and the drug supply was regular yet there were problems in correct case classification and treatment.29
Since 1992, the Program was implemented as part of Child Survival and Safe Motherhood (CSSM) Program and later with Reproductive and Child Health (RCH) Program in 1997. Cotrimoxazole tablets are supplied as part of drug kit for use by different category of workers at subcenters and above, for managing cases of Pneumonia. Under RCH-II, activities have been implemented in an integrated way with other child health interventions. The Rapid Household Survey done in 2002, showed that utilization of government facilities for children with ARI was very low at 14%, whilst NFHS II data suggests that the proportion of children with ARI taken to a facility or provider was 64%.29,30
Subsequently in 2005, The National Rural Health Mission (NRHM) was launched that incorporated a complete restructuring of current strategies to achieve the goal of improved public health services. NRHM brought all the major national health program under one umbrella.31
Integrated Management of Neonatal and Childhood Illnesses (IMNCI) strategy is one of the main interventions under RCH II/NRHM. It is the Indian adaptation of the WHO-UNICEF generic Integrated Management of Childhood Illness (IMCI) strategy and is the centerpiece of newborn and child health strategy under Reproductive and Child Health II Program and National Rural Health 10Mission. IMNCI adopts a syndromic approach to case management according to algorithms provided. The strategy encompasses a range of interventions to prevent and manage the commonest major childhood illnesses, which cause death, i.e. neonatal illnesses, ARI, diarrhea, measles, malaria and malnutrition. The package of services is implemented at the level of household, subcenters and primary health centers.12
F-IMNCI is the integration of the facility based care package with the IMNCI package, to empower the health personnel with the skills to manage new born and childhood illness at the referral health facility like Community Health Centers, First Referral Units, District Hospitals and Medical College Hospitals. It helps to build capacities to handle referrals taking place from the community.32
IMNCI Plus indicates wider, comprehensive range of interlinked interventions that form the newborn and child health component of RCH II Program. It includes skilled care at birth, IMNCI including in patient care and immunization.12
Categorizations12
Depending on the age of the child various signs and symptoms differ in their degree of reliability, diagnostic value and importance. Therefore for management children are divided into two age groups:
- Young infant up to 2 months
- Children 2 months up to 5 years.
History Taking12
Proper history should be taken to 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 up to 5 years), has the young infant stopped feeding well (child less than 2 months of age), 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 taken during illness.
Physical Examination12
Look and listen for the following:
Count the breaths in one minute: To decide if the child has fast breathing. The child must be quiet and calm when you look and listen to his breathing. To count the number of breaths in one minute, use a watch with a second hand or a digital watch. Look for breathing movement anywhere on the child's chest or abdomen, which should be exposed for counting. Young infants usually breathe faster than older children do. The cut-off rate to identify fast breathing therefore depends on the age group.
Fast breathing is present when the respiratory rate is:
- 60 breaths per minute or more in a child less than 2 months of age
- 50 breaths per minute or more in a child aged 2 months up to 12 months
- 40 breaths per minute or more in a child aged 12 months up to 5 years.
11In a young infant, if the count is 60 breaths or more, the count should be repeated, because the breathing rate of a young infant is often irregular and erratic. The young infant may occasionally stop breathing for a few seconds, followed by a period of faster breathing. If the second count is also 60 breaths or more, the young infant has fast breathing.
Look for chest indrawing: Look for chest indrawing when the child breathes IN. Look at the lower chest wall (lower ribs). The young infant has chest indrawing if the lower chest wall goes IN when the infant breathes IN. Chest indrawing occurs when the effort the young infant needs to breathe in is much greater than normal. In normal breathing, the whole chest wall (upper and lower) and the abdomen move OUT when the young infant breathes IN.
Look and listen for stridor: A child with stridor makes a harsh noise, while breathing IN. Stridor occurs when there is narrowing of the larynx, trachea or epiglottis, which interferes with air entering the lungs. These conditions are often called croup.
Look for nasal flaring: Nasal flaring is widening of the nostrils when the young infant breathes IN.
Listen for grunting: Grunting is the soft, short sounds a young infant makes when breathing OUT. Grunting occurs when an infant is having difficulty in breathing.
Listen for wheeze: A child with wheezing makes a soft whistling noise or shows signs indicating breathing OUT is difficult. Wheezing is caused by narrowing of the air passage in the lungs.
Look and feel the child: See if the child is abnormally sleepy or difficult to wake, feel for fever or low body temperature, check for severe malnutrition or cyanosis.
Classification and Management of Illness12
The children are classified into three groups and color coded accordingly. The first group with very sick children, falling under the pink classification, needs urgent referral to higher level health facility. The second group, in the yellow classification, is treated at the outpatient department. The third group is coded green and these children can be managed at home.
Table 1.2 presents the salient features of the classification and management of the illness.
Treatment12
A. Young infant aged up to 2 months (Tables 1.3 and 1.4)
Referral is the best option for a young infant with possible serious bacterial infection. However, if referral is not possible, give oral amoxicillin every 8 hours and intramuscular gentamycin once daily.12
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Prevention of Low Blood Sugar
- If the child is able to breastfeedAsk the mother to breastfeed the child
- If the child is not able to breastfeedGive 20 to 50 mL (10 mL/kg) expressed breast milk or locally appropriate animal milk (with added sugar) before departure. If neither of these is available, give 20 to 50 mL (10 mL/kg) sugar water.14
Table 1.4 Oral antibiotics (Birth – 2 months) Cotrimoxazole(trimethoprim + sulfamethoxazole)Give 2 times daily for 5 daysAmoxycillinGive 3 times daily for 5 daysAge or weightAdult tabletSingle strength(80 mg trimethoprim + 400 mg sulfamethoxazole)Pediatric tablet(20 mg trimethoprim + 100 mg sulfamethoxazole)Tablet 250 mgSyrup125 mg in 5 mLBirth up to 1 month(< 3 kg)-1/2-1.25 mL1 month up to 2 months (3–4 kg)1/411/42.5 mLTo make sugar water: Dissolve 4 level teaspoons of sugar (20 g) in a 200 mL cup of clean water - If the child is not able to swallowGive 20 to 50 mL (10 mL/kg) of expressed breast milk or locally appropriate animal milk (with added sugar) or sugar water by nasogastric tube.
B. Child aged 2 months up to 5 years (Tables 1.5 and 1.6)
If referral is not possible:
- Repeat chloramphenicol injection every 12 hours for 5 days
- Then change to an appropriate oral antibiotic to complete 10 days of treatment.
Soothing the Throat
- Safe remedies to recommend
- Continue breastfeeding
- Honey, tulsi, ginger, herbal tea and other safe local home remedies
- Harmful remedies to discourage
- Preparations containing opiates, codeine, ephedrine and atropine.
SUMMARY AND CONCLUSION
Acute respiratory infections are deadly diseases that claim the lives of many infants and children under 5 years of age. These include the Acute Upper Respiratory Infections (AURIs), and the Acute Lower Respiratory Infections (ALRIs). The most common bacteria involved are Streptococcus pneumoniae (pneumococcus) or Haemophilus influenzae, mostly type B (Hib), and occasionally 15by Staphylococcus aureus or other streptococci.
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Viruses commonly responsible are respiratory syncytial viruses (RSVs), parainfluenza and influenza viruses. Atypical organisms like Chlamydia and Mycoplasma also sometimes cause pneumonia. Various socio-economic, demographic, environmental, nutritional and illness and treatment factors make the children of developing countries more vulnerable to these infections. Prevention of ARI is possible by immunizing the children at the appropriate age. The current immunization strategy protects against diphtheria, pertussis and measles. There has been strong recommendation for inclusion of vaccine for Hib in the immunization schedule. Pneumococcal pneumonia vaccine, in spite of fulfilling the criteria for recommendation as proposed by WHO, is under a lot of debate. Integrated Management of Neonatal and Childhood Illnesses, is 16a simple tool to bring down the morbidity and mortality due to ARI, through syndromic approach for identification of problems and their management.
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