Streptococcus pneumoniae claims 1 million child deceases every twelvemonth worldwide ( 1 ) . Approximately 90 % of deceases occur in developing states. For every 1 kid that dies of pneumonia in a developed state, more than 2000 kids dice of pneumonia in developing states ( 2 ) .
The SAARC states overall are in the zone with high incidence of pneumococcal disease ( 1 ) but no survey has attempted to happen out the same. The child mortality rates ( & lt ; 5 ) are high in the part ; runing from 17/1000 for Srilanka to 149/1000 for Afghanistan. Pneumonia claims 11 % of U5 child deceases in India, Maldives, Bangladesh and Pakistan ; 23 % of U5 child deceases in Afghanistan and 19 % in Bhutan with lowest in Srilanka 6 % . ( 3 ) . Pneumonia is the taking cause of U5 decease in Pakistan ( 4 ) but merely 50 % receive antibiotic intervention ( 5 ) . The Million Death Study reported that pneumonia accounted for 27A·6 % deceases out of entire 12260 deceases in kids from 1-59 months ( 6 ) .
S. pneumoniae is one of the major causes of fatal pneumonias in kids ( 7 ) . Besides pneumonia S.pn is besides known to do meningitis which is another fatal status for kids. Many more diseases are to the name of S.pn like ague otitis media, joint gushs and bacteraemia etc. Estimates of pneumococcal disease load are needed so as to use the resources for kid endurance.
In Bangladesh, the theoretical account predicts a pneumococcal disease incidence of 3351 instances per 100,000 kids younger than 5 old ages. A population-based, active-surveillance, active-case sensing survey measured an invasive pneumococcal disease rate of 447 instances per 100,000 kids younger than 5 old ages ( 8 ) . Unfortunately the grounds for appraisal of pneumococcal disease in low/middle income states is less. The load of pneumococcal disease is highest in kids and the aged population in both more and less developed states. The intervention of pneumococcal infections is complicated by the world-wide outgrowth of opposition to penicillin and other antibiotics ( 9 ) .
The pneumococcal conjugate vaccinums are helpful but the effectivity of these vaccinums is dependent upon the pneumococcal disease load and serotype coverage of the vaccinum. ( 10 )
Aim:
The primary aims of this systematic reappraisal are
To cognize the load of invasive pneumococcal disease.
To find the demand for debut of pneumococcal conjugate vaccinum in the immunisation agenda.
Methods:
We performed a systematic hunt of the published literature and besides tried to get information about the unpublished literature from assorted research workers of the part.
Beginnings of Datas:
The hunts were current as of January 2013 and we identified articles with information on pneumococcal invasive disease among kids & lt ; 5 old ages of age. We searched 3 Databases: Pubmed, Embase and The Cochrane library. The mention lists of the obtained articles were farther searched for surveies. Non English articles were non included. The hunt inside informations are given in the appendix I. Searching were done by 2 writers ( NJ, HK ) . HK helped in obtaining full text articles.
Definitions Used:
SAARC states: South Asian Association for Regional Co-Operation includes Afghanistan, Pakistan, India, Nepal, Bhutan, Bangladesh, Srilanka and Maldives.
Burden of pneumococcal disease: We have defined load of pneumococcal disease as the figure of positive pneumococcal isolates from the suspected population.
Pneumonia:
Symptoms: cough or hard external respiration, and marks: external respiration & gt ; 50 breaths per minute for infant aged two months to less than one twelvemonth, take a breathing & gt ; 40 per minute for kid aged one to five old ages, and no thorax indrawing, stridor or danger marks. ( 11 )
Severe pneumonia:
Symptoms: cough or hard eupneic plus any general danger mark or chest indrawing or stridor in a unagitated kid. General danger marks for kids aged two months to five old ages: unable to imbibe or suckle ; pukes everything ; paroxysms ; lethargy or unconscious ( 11 ) .
Clinical diagnosing of meningitis is more straightforward than that of pneumonia. The definition of pneumonia is based on the incorporate direction of childhood infections ( IMCI ) attack, which includes other ague lower respiratory tract infections and deficiencies specificity. In add-on, aetiologic diagnosing of bacterial pathogens is easier in CSF than in blood.
Meningitis: ( 11 )
Suspected: Any individual with sudden oncoming of febrility ( & gt ; 38.5 A°C rectal or & gt ; 38.0 A°C axillary ) and one of the undermentioned marks: cervix stiffness, altered consciousness or other meningeal mark.
Probable: A suspected instance with cerebrospinal fluid ( CSF ) scrutiny demoing at least one of the followers:
cloudy visual aspect ;
leucocytosis ( & gt ; 100 cells/mm3 ) ;
leucocytosis ( 10-100 cells/ mm3 ) AND either an elevated protein ( & gt ; 100 mg/dl ) or decreased glucose ( & lt ; 40 mg/dl ) .
Confirmed: A instance that is laboratory-confirmed by turning ( i.e. culturing ) or placing ( i.e. by Gram discoloration or antigen sensing methods ) a bacterial pathogen ( Hib, Diplococcus pneumoniae or meningococcus ) in the CSF or from the blood, in a kid with a clinical syndrome consistent with bacterial meningitis ( WHO, 2003 ) .
Non Pneumonia Non Meningitis: All infections other than pneumonia and meningitis have been categorized under this header.
Invasive Pneumococcal disease: When Diplococcus pneumoniae has been identified from one of the otherwise unfertile sites of the organic structure like blood, CSF, pleural fluid etc either by civilization or by LAT/PCR or other technique.
The surveies where the defined instances have some other parametric quantities or if there were some other standards no effort was made to standardise them.
Inclusion standards:
Surveies ; prospective/retrospective ; with kids & lt ; 5years of age as /or portion of the studied population.
Surveies done in infirmary or community scene.
Surveies with possible informations available on S.pneumoniae isolated from kids & lt ; 5 old ages of age.
Surveies with at least 12 months of surveillance were included in order to get the better of the seasonal nature of pneumococcal diseases.
Surveies conducted in SAARC states.
The inclusion was decided by 2 writers ( NJ, KK ) and choice appraisal was done by 2 writers ( NJ, KK ) . Discrepancies, if any, were resolved by treatment with 3rd writer ( MS ) and the finding of fact was considered concluding.
If the exact information was non available we have contacted the writers and tried to decide the disagreements The surveies which have commented merely on pneumococcal serotypes & A ; /or antibiotic opposition have been excluded from pooled analysis. We excluded instance studies, columns, vaccinum surveies, literature reappraisals and the surveies in which nasopharyngeal aspirates, pharynx swabs or oropharyngeal swabs were the lone samples to find the causative being.
Data aggregation and direction:
Three writers ( BE ; AK, SS ) abstracted informations individually from the included surveies in a predesigned tabular array that included survey design, puting, no. of suspected instances, no. civilization samples taken & amp ; positive civilizations obtained, and no. positive civilizations for Diplococcus pneumoniae.
The information from Hospital based surveies and population based surveies were abstracted individually. To decide the disagreements sing the abstracted informations treatment with the other referees were done and consensus was reached. Sing some losing informations the writers were contacted and if the disagreements were non resolved they were non taken up for pooled analysis.
The community based surveies available merely give information about pneumococcal pneumonia instances in the community.
Datas analysis:
Data analysis was done utilizing CMA V2 by 4 writers ( NJ, MS, KK, and AA ) . The similar surveies were pooled together. Sub group analysis for finding the IPD load in India was done and besides sub-group analysis for finding IPD in kids & lt ; 5 old ages was done.
The community based surveies, infirmary based prospective and retrospective surveies have besides been analyzed individually.
Consequences:
Datas reviewed:
We found 700 published articles through electronics and manual searching. After rubric and abstract testing 40 full text articles were retrieved and 21 surveies ( 8, 12-31 ) were included for the reappraisal and 19 were excluded ( 32-50 ) ( fig 1 )
Community based surveies were non available from Afghanistan, India, Nepal, Bhutan & A ; Srilanka. Because the life conditions are about same and there is besides geographic similarity we have considered the surveies from Bangladesh and Pakistan as representative of the SAARC states.
Similarly there were no infirmary based surveies from Afghanistan and Bhutan so we have taken the surveies from remainder of the states and generalized them for these states.
We have included a sum of 21 surveies for this systematic reappraisal & A ; mentioned in tabular array I. The inclusion was decided by 3 writers ( MS, NJ, KK ) and quality marking was done by 3 writers ( MS, NJ, KK ) . The surveies with mark of 6 or more were considered to be good quality grounds.
Hospital Based Prospective Surveies:
SAARC states:
We identified 15 infirmary based prospective surveies ( 12-19, 22, 24-27, 29, 31 ) from assorted SAARC states and analyzed them for finding the invasive pneumococcal disease load in kids populating in these states and besides did a subgroup analysis for kids less than 5 old ages of age.
These surveies show that 3.5 % ( 95 % CI 1.9-6.4 ) of kids admitted to infirmaries with diagnosing of invasive diseases like terrible pneumonia or meningitis or sepsis are due to S. pn ( fig 3 ) . Eight surveies ( 13, 15, 16, 18, 24-27 ) show that 1.5 % ( 95 % CI 0.6-3.4 ) of kids admitted as terrible pneumonia have S. pn as the causative being ( Fig 5 ) . Ten surveies ( 12, 14, 16, 17, 19, 22, 24, 26, 27, 29 ) of the included surveies show that 7.6 % ( 95 % CI 4.1-13.7 ) of kids with likely or confirmed meningitis have S.pn as a causative being ( fig 7 ) . S.pn is one of the major bacteriums doing 20 % ( 95 % CI 12.9-29.9 ) of invasive bacterial diseases ( fig 4 ) . 11 % ( 95 % CI 6.5-17.9 ) of terrible bacterial pneumonia are caused by S.pn ( fig 6 ) . S.pn has been an aetiologic agent in 33.1 % ( 95 % CI 23.1-44.8 ) instances of bacterial meningitis ( fig 8 ) .
Children less than 5 old ages of age:
Out of the 15 surveies merely 11 surveies ( 13, 15, 17, 18, 22, 24-27, 29, 31 ) have clear information on invasive pneumococcal disease in kids less 5 old ages of age. The surveies show that S.pn causes 2.7 % ( 95 % CI 1.1-6.2 ) hospitalizations due to all invasive disease ; in kids & lt ; 5 old ages of age ( fig 9 ) . Merely 7 surveies ( 13, 15, 18, 24-27 ) had clear information on pneumococcal pneumonia in kids & lt ; 5 old ages of age and showed that 1.5 % ( 95 % CI 0.5-4.3 ) of terrible pneumonias are due to S.pn ( fig 11 ) . Similarly 6 surveies ( 17, 22, 24, 26, 29 ) showed that S.pn is the being responsible for 7.1 % ( 95 % CI 2.6-17.5 ) meningitis instances in the age group ( fig 13 ) .
S.pn remains the major bacterial cause of all invasive diseases in kids U5 old ages of age doing 19.2 % ( 95 % CI 11.5-30.3 ) of invasive bacterial diseases ( fig 10 ) . 10.8 % ( 95 % CI 6.4-17.6 ) terrible bacterial pneumonias are due to S.pn ( fig 12 ) and 35.1 % ( 95 % CI 22.1-50.8 ) of pyogenic meningitis is due to S.pn. ( fig 14 ) .
Bharat:
We found 9 surveies from India ( 12-19, 22 ) which showed that S.pn causes 7.9 % ( 95 % CI 3.8-15.7 ) of invasive diseases in kids ( fig 15 ) . S.pn has been an aetiologic agent in 3.9 % ( 95 % CI 1.2-11.7 ) kids with terrible pneumonia ( fig 17 ) and is besides a major bacterial cause of pneumonia in kids doing 14 % ( 95 % CI 5.8-30.1 ) of bacterial pneumonias ( fig 18 ) . S.pn has been a causative agent in 10.4 % ( 95 % CI 5.8-18.1 ) of kids with meningitis ( fig 19 ) and once more a major bacterial cause of pyogenic meningitis ( fig 20 ) . The hospital prevalence of S.pn in Indian kids is more than that of all other SAARC states.
Children less than 5 old ages of age:
Five surveies ( 13, 15, 17, 18, 22 ) gave clear information on pneumococcal diseases in kids under 5 twelvemonth of age in India. The image does non alter in this age group of Indian kids where S.pn is prevailing in 8.2 % ( 95 % CI 4.1-16.6 ) of all hospitalized kids with suspected invasive bacterial disease ( fig 21 ) and S.pn becomes a major bacterial cause of invasive bacterial diseases with 21.2 % ( 95 % CI 9.4-41.0 ) of all invasive bacterial diseases are due to S.pn ( fig22 ) . 5.4 % ( 95 % CI 2-14.1 ) of terrible pneumonias in infirmary wards are due to S. pn ( fig 23 ) & A ; 16.5 % ( 95 % CI 12.8-16.2 ) meningitis in kids less than 5 old ages describing to infirmaries are due to pneumococcus. In 13.6 % ( 95 % CI 5.5-29.8 ) of all bacterial pneumonia ( fig 24 ) & A ; 39.3 % ( 95 % CI 27.5-52.6 ) of pyogenic meningitis ( fig 26 ) S.pn has been isolated and is a major cause of these diseases in India.
Hospital Based Retrospective Surveies:
Two infirmary based retrospective surveies ( 21, 28 ) from India were included in this reappraisal. The pooling of these surveies together showed that 15.5 % ( 95 % CI 0.5-88 ) of invasive pneumococcal disease instances amongst the entire admitted patients with invasive bacterial diseases ( Fig 27 ) . The assurance intervals for this group are broad because one survey ( 21 ) which is merely on bacterial meningitis and has a little sample size with comparatively more proportion of pneumococcal isolates.
Population Based Surveies:
Four surveies ( 8, 20, 23, 30 ) from the SAARC states were included in the reappraisal. These surveies are from Pakistan and Bangladesh. These surveies merely discuss the kids under 5 old ages of age. These surveies show that approximately 13.4 % ( 95 % CI 6.7-25 ) of all invasive bacterial diseases in community are due to S. pn ( fig 29 )
Inference of all the analysis:
The consequence from the population based surveies ( 13.4 % ) is comparable to that from the infirmary based prospective surveies ( 19 % ) and besides to those obtained from retrospective surveies ( 15.5 % ) . The pneumococcal disease prevalence in SAARC states varies between 13 % - 19 % of all invasive bacterial diseases.
Discussion:
Our findings show that S. pn is prevailing in 19 % of all hospitalizations in kids of SAARC states and is hence one of the major cause of concern every bit far as child wellness is concerned. Pooling the Indian surveies we found that pneumococcal diseases are 25 % of all invasive bacterial diseases in kids of India. These figures might be an underestimation of the current state of affairs as the surveies discuss merely hospitalized instances, the milder signifiers may travel unreported. S.pn is a major bacterial cause for terrible pneumonia and besides for pyogenic meningitis in kids of this part. The community based surveies besides show that in 13 % of bacterial instances were due to S.pn but once more these surveies besides discussed the terrible diseases merely and did non describe the milder signifiers.
The consequences of our reappraisal are comparable to other reappraisals ( 1 ) which showed high prevalence of pneumococcal diseases in India. The consequences of community based surveies show that __ % of all bacterial invasive diseases in community are due to pneumococcus which is comparable to the consequence from the infirmary based prospective surveies.
An unpublished information from one site of a multicentric test ( ISPOT survey ) from India showed that approx 38 % of kids with terrible pneumonia ( Radiologically confirmed ) had S. pn isolated from the nasopharyngeal aspirates or pharynx swabs. The survey besides showed that unwritten Amoxil administered at place was effectual in handling terrible pneumonia. The No Shots survey from Pakistan ( 51 ) concluded that place intervention with high dose unwritten Amoxil in instances of terrible pneumonia is tantamount to WHO recommendations of hospitalizations and i/v antibiotics. Similarly in another survey from Pakistan showed that local wellness workers were able to handle terrible pneumonia instances at place with high dosage Amoxil ( 52 ) .
Survey from Bangladesh ( 53 ) reports the rhinal passenger car rate of 47 % and besides reports the early colonisation in rural population. The survey besides reports that 69 % of invasive strains were immune to cotrimoxazole.
The ANSORP survey reported 41 % non-susceptible strains to penincillin in Srilanka and approximately 4 % in India ( 54 ) . The IBIS survey ( 16 ) reported 60 % opposition to chloramphenicol, Principen, trimethoprim-sulfamethoxazole, or Erythrocin ; with 32 % isolates resistant to more than 3 antimicrobic drugs. Kunango et Al ( 55 ) reported that out of 150 clinical isolates from invasive pneumococcal infections, merely 11 ( 7.3 % ) isolates were comparatively immune to penicillin, although 64 were immune to one or more antibiotics particularly cotrimoxazole, Achromycin and Chloromycetin. In the ISCAP test ( 56 ) the opposition form of S. pneumoniae to assorted antibiotics was: cotrimoxazole 66.3 % , chloramphenicol 9.0 % , oxacillin 15.9 % and erythromycin 2.8 % .So the antibiotic opposition becomes another menace.
In India, the most common serogroups colonising the nasopharynx of kids are 6, 14, 19, and 15 ( 38, 57 ) . IBIS survey ( 16 ) studies serotype 1,6 and 19 to be the most common serotypes isolated from either blood or CSF samples of the kids with invasive disease. Rijal et Al ( 49 ) found that serotypes 1,5 & A ; 4 were most normally isolated from the patients of IPD and besides reported that 52 % of isolates were immune to cotrimoxazole.
Decision:
The systematic reappraisal concludes that S. pneumoniae is a major bacterial cause of invasive bacterial diseases in kids of SAARC states. The outgrowth of immune strains of Diplococcus pneumoniae are indicating towards the demand for revisiting the intervention recommendations and besides do a call for explicating preventative steps to decrease the prevalence of invasive pneumococcal diseases. The usage of antibiotic which is less immune and easy to administrate should be considered. Pneumococcal conjugate vaccinum, after cognizing the prevalent serotypes and there coverage, should be considered by the policy shapers.
Conflict of Interests: None stated
Role of the Funding Agency: The reappraisal was supported and funded by ICMR, New Delhi. The support bureau did non interfere with the reappraisal procedure or the consequences.
Recognitions: We would wish to thank Dr. Samir K Saha ( ICDDR, Bangladesh ) , Dr. Z.A. Bhutta & A ; Dr S.Q. Nizami ( AKU, Karachi, Pakistan ) for supplying us with their publications on pneumonia ; we would besides wish to thank Dr. Kay Dickerson of John Hopkins University U.S. for assisting us with the statistical methods.
