Pediatric Infectious Disease最新文献

Background and rationale

Pneumonia is responsible for about 1.4 million deaths in children under five years of age, mostly in developing countries, including India. In India, Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) are the common bacterial etiologic agents of pneumonia, and often cause abnormal chest radiology. Vaccine against HI has already been introduced in India. Pneumococcal conjugate vaccine (PCV) roll out will begin in 2017–2018 in a phased manner using Gavi funding.

Objectives

• (1)

  To estimate the annual incidence of radiological pneumonia in children between 2 and 59 months of age, in prespecified districts.

• (2)

  To document the clinical and demographic characteristics of cases of WHO-defined community-acquired pneumonia (CAP) with lower chest in-drawing (LCI) and severe CAP, by establishment of hospital-based surveillance network.

Study design

In a prospective design, surveillance for WHO-defined radiological pneumonia in patients hospitalized for CAP is being done in two districts each of Uttar Pradesh and Bihar. For this, a pneumonia surveillance network of public and private hospitals has been established. Data are abstracted from hospital records. One copy of routine chest X-ray is also collected, digitalized, and archived electronically. An independent panel of radiologists interprets the X-rays. Five milliliters of urine of a subset of cases is being stored at −20 °C for future antigen testing.

In Phase I, procedures were standardized, hospital network established, and recruitments initiated from Lucknow district. This was expanded in Phase II to include Etawah district, Uttar Pradesh and Patna and Darbhanga districts of Bihar.

Progress

A pneumonia surveillance network was established, having 120 health facilities in Lucknow, 60 in Patna, 64 in Darbhanga and 17 in Etawah. From 1st January 2015 to 30th April 2016, 745 CAP cases were enrolled in Lucknow. From 1st January to 30th April 2016 Patna recruited 229, Darbhanga 321 and Etawah 80 cases. Chest X-rays of all cases have been archived for interpretation by the panel of radiologists.

Implications

Baseline incidence of radiological pneumonia in Uttar Pradesh and Bihar will be estimated and follow-up data will enable assessment of the impact of PCV introduction.

Nepal adopted immunization program as expanded program on Immunization in 1977 and it is considered a successful program in Nepal for its role in the reduction of infant and under-five mortality in the country. Pneumonia is a major killer of children and Streptococcus pneumoniae is the common cause of it. Based on the studies done in Nepal covering the existing serotypes, National Committee on immunization practice recommended PCV 10 for its immunization program and it was rolled out in phase-wise manner to all over the country after its introduction in January 2015. The schedule of PCV 10 in the routine National Immunization Program of Nepal is 2p + 1 at 6 weeks, 10 weeks, and 9 months of age. Immunogenicity and impact study are ongoing and it is too early to comment on the further efficacy of this vaccine.

Disease surveillance has been long recognized as the cornerstones for the public health decision making practices. In the regions of high childhood morbidity and mortality there is an unmet need of continued disease surveillance to identify the causes for menace. Pneumococcal surveillance in India has been heterogeneous with very few examples of attempts. Driven by the gap in the knowledge of nationwide epidemiological distribution of serotype and antibiogram pattern of Streptococcus pneumoniae in India we attempted to provide the most appropriate study design to establish Alliance for Surveillance of Invasive Pneumococci (ASIP) network in the country which we hope on further optimization will be of benefit to all surveillances in future. The various components of surveillance and the experienced gained are described, as the progress made in the establishment of sentinel network followed by strengthening the laboratory diagnostic abilities and the data management of each surveillance center participating. For the surveillance to play a role in public healthcare it is important that the local capacity of surveillance in terms of public health force must be developed along with support from global development partners. Also, an integrated approach must be explored for the parallel surveillance systems.

Pneumococcus contributes to nearly 50% of severe cases of pneumonia and pneumonia deaths. This article presents a literature review of the impact of the pneumococcal vaccines namely PCV7, PCV10 and PCV13 on community acquired pneumonia (CAP). It appears that the quantum of reduction of CAP is much better with PCV13 than PCV10 in several countries. However, inclusion of either vaccine in the national immunisation programme in developing countries has the potential to save 0.3–0.5 million deaths and 7–8 million episodes of severe CAP.

Streptococcus pneumoniae infection causes a wide spectrum of diseases ranging from acute otitis media to Invasive Pneumococcal Disease (IPD) presenting as pneumonia, meningitis, joint effusions, bacteraemia and septicaemia. Pakistan was the first country in the South Asian region to introduce PCV-10 within the routine immunisation program. Government of Pakistan, with support from Gavi, the Vaccine Alliance and other partners, introduced PCV-10 in phased manner, starting October 2012. Vaccination schedules matched other age-appropriate vaccines offered within existing Routine Immunisation (RI) schedules and were offered at 6, 10 and 14 weeks after birth. Catch up immunization was not done. Few studies conducted before vaccine introduction showed that the burden of IPD and the serotype distribution was similar to other countries in the region. The selection of PCV-10 instead of PCV-13 in Pakistan's Expanded Programme for Immunization (EPI) was based largely on earlier availability of PCV-10, and the impression that there would be marginal gain in serotype coverage from a higher valence vaccine. A few studies are currently underway to assess the impact of PCV introduction in Pakistan's EPI.

Analysis of the published pneumococcal surveillance reports reveals variability and lack of long-term studies from India. The variability relates to case definition, characterization, surveillance, and laboratory methods. In the backdrop of scarcity of data, a multisite surveillance network study, PIDOPS Phase I, was launched in the year 2013 at 7 institutional and 51 sentinel sites.

During the course of the study, novel molecular techniques were developed and standardized for rapid, accurate detection and typing. 1504 serum samples from IPD pediatric subjects were analyzed with automated blood culture and qmPCR. 108 isolates and 456 positive serum samples were serotyped by Quellung and PCRSeqTyping, respectively. The isolates were tested for their MIC and Multilocus Sequence Typing.

The strength of this study was the use of advanced techniques providing comprehensive surveillance data and development of pan India referral system before the introduction of pneumococcal conjugate vaccine in the national immunization program.

Laboratory diagnosis of S. pneumoniae is of significance because of growing drug resistance, use of pneumococcal vaccines and etiological diagnosis cannot be made on clinical signs and symptoms. Despite its importance, current culture based diagnostic methods used for decades are less sensitive and fail to provide accurate burden data, effectiveness of control measures such as vaccination. The current reference standards for culture and serotyping are labor intensive, expensive and available only in few laboratories. To understand the etiology of pneumonia, epidemiology of infection and to evaluate vaccine effectiveness simple and efficient novel technologies needs to be the part of diagnostic protocol. This article summarizes newer methods and guidelines used for pneumococcal identification, serotyping and drug resistance testing.