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      Programmatic Effectiveness of a Pediatric Typhoid Conjugate Vaccine Campaign in Navi Mumbai, India

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          Abstract

          Background

          The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the Navi Mumbai Municipal Corporation (NMMC) implemented a typhoid conjugate vaccine (TCV) campaign. The campaign targeted all children aged 9 months through 14 years within NMMC boundaries (approximately 320 000 children) over 2 vaccination phases. The phase 1 campaign occurred from 14 July 2018 through 25 August 2018 (71% coverage, approximately 113 420 children). We evaluated the phase 1 campaign's programmatic effectiveness in reducing typhoid cases at the community level.

          Methods

          We established prospective, blood culture–based surveillance at 6 hospitals in Navi Mumbai and offered blood cultures to children who presented with fever ≥3 days. We used a cluster-randomized (by administrative boundary) test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched test-positive, culture-confirmed typhoid cases with up to 3 test-negative, culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression.

          Results

          Between 1 September 2018 and 31 March 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (programmatic effectiveness, 56%; 95% confidence interval [CI], 25% to 74%; P = .002). Cases aged ≥5 years were 0.37 times as likely (95% CI, .19 to .70; P = .002) and cases during the first year of surveillance were 0.30 times as likely (95% CI, .14 to .64; P = .002) to live in vaccine campaign communities.

          Conclusions

          Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.

          Abstract

          In 2018, the Navi Mumbai Municipal Corporation conducted a typhoid conjugate vaccine campaign in half of its communities. Using a test-negative design, we estimate the campaign reduced typhoid risk by 56% (25%–74%) in vaccinated communities compared with noncampaign communities.

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          Most cited references39

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          The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease. We present the estimates of typhoid and paratyphoid fever burden from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, and the approach taken to produce them. Methods For this systematic analysis we broke down the relative contributions of typhoid and paratyphoid fevers by country, year, and age, and analysed trends in incidence and mortality. We modelled the combined incidence of typhoid and paratyphoid fevers and split these total cases proportionally between typhoid and paratyphoid fevers using aetiological proportion models. We estimated deaths using vital registration data for countries with sufficiently high data completeness and using a natural history approach for other locations. We also estimated disability-adjusted life-years (DALYs) for typhoid and paratyphoid fevers. Findings Globally, 14·3 million (95% uncertainty interval [UI] 12·5–16·3) cases of typhoid and paratyphoid fevers occurred in 2017, a 44·6% (42·2–47·0) decline from 25·9 million (22·0–29·9) in 1990. Age-standardised incidence rates declined by 54·9% (53·4–56·5), from 439·2 (376·7–507·7) per 100 000 person-years in 1990, to 197·8 (172·0–226·2) per 100 000 person-years in 2017. In 2017, Salmonella enterica serotype Typhi caused 76·3% (71·8–80·5) of cases of enteric fever. We estimated a global case fatality of 0·95% (0·54–1·53) in 2017, with higher case fatality estimates among children and older adults, and among those living in lower-income countries. We therefore estimated 135·9 thousand (76·9–218·9) deaths from typhoid and paratyphoid fever globally in 2017, a 41·0% (33·6–48·3) decline from 230·5 thousand (131·2–372·6) in 1990. Overall, typhoid and paratyphoid fevers were responsible for 9·8 million (5·6–15·8) DALYs in 2017, down 43·0% (35·5–50·6) from 17·2 million (9·9–27·8) DALYs in 1990. Interpretation Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death, with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to drive the greatest improvements in the global burden of the disease. Funding Bill & Melinda Gates Foundation.
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            First confirmed case of COVID-19 infection in India: A case report

            Sir, Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome (SARS)-CoV1. On December 31, 2019, China informed the World Health Organization (WHO) about cases of pneumonia of unknown aetiology detected in Wuhan city, Hubei province of China. From December 31, 2019 to January 3, 2020, a total of 44 patients with pneumonia of unknown aetiology were reported to the WHO by the national authorities in China2. During this period, the causal agent was not identified. The cases initially identified had a history of exposure to the Huanan Seafood Wholesale Market3. The most common clinical features of the early clinical cases from Wuhan, China, were fever (98.6%), fatigue (69.6%) and dry cough (59.4%)4. The second meeting of the Emergency Committee convened by the WHO Director-General under the International Health Regulations (2005) regarding the outbreak of novel coronavirus 2019 in the People's Republic of China on January 30, 2020, declared COVID-19 outbreak as Public Health Emergency of International Concern (PHEIC)5. As on February 17, 2020, except China, 25 other countries have been affected by COVID-19 outbreak with 70,635 confirmed cases and 1,772 deaths in China. Outside China, 794 cases were reported with three deaths6. We present here the first case of COVID-19 infection reported in Kerala, India. On January 27, 2020, a 20 yr old female presented to the Emergency Department in General Hospital, Thrissur, Kerala, with a one-day history of dry cough and sore throat. There was no history of fever, rhinitis or shortness of breath. She disclosed that she had returned to Kerala from Wuhan city, China, on January 23, 2020 owing to COVID-19 outbreak situation there. She was asymptomatic between January 23 and 26. On the 27th morning, she felt a mild sore throat and dry cough. She did not give a history of contact with a person suspected or confirmed with COVID-19 infection. She did not visit the Huanan Seafood Wholesale Market, however, she gave a history of travel from Wuhan to Kunming by train where she noticed people with respiratory symptoms in railway station and train. She received the instructions from the Kerala State authorities to visit a healthcare facility if she develops any symptoms because of the travel history to China. In the Emergency department in General Hospital, she was afebrile with a pulse rate of 82/min, blood pressure 130/80 mmHg, temperature 98.5°F and oxygen saturation 96 per cent while the patient was breathing ambient air. Lung auscultation revealed normal breath sounds with no adventitious sounds. In view of her travel history from Wuhan, the district rapid response team decided to admit her in an isolation room which was designated for the corona epidemic. An oropharyngeal swab was obtained and was sent to the ICMR-National Institute of Virology (NIV), Pune, for the detection of viral respiratory pathogens on January 27, 2020. Three millilitres each of EDTA blood and plain blood samples were also collected and sent to NIV, Pune, where COVID-19 was diagnosed using real time reverse transcription PCR. Specimen collection was done on day 0 (admission) and every alternate day. Urine and stool samples were also sent for detailed evaluation. She was started on azithromycin (500 mg), cetirizine (10 mg) and saline gargle. Over the next three days, her symptoms improved. Her oropharyngeal swab result was reported by the NIV, Pune, to District Control Cell on January 30, 2020 as positive for COVID-19 infection. The details of basic laboratory investigations done on days 3, 7 and 20 of illness are shown in the Table. On day 1 of illness, the total white blood cell count was towards the low normal side, but on days 5 and 20, the count showed a rise which was consistent with a viral infection. Erythrocyte sedimentation rate was highest on day 7. The rest of the investigations were normal. She was referred to the Government Medical College, Thrissur, Kerala on January 31, 2020, and was admitted in isolation block designated for corona infection. By this time, the outbreak monitoring unit of the institution had brought out a detailed policy regarding the standard operating procedures including infection control measures to be followed in the isolation block. On presentation, she had only mild sore throat and rhinitis. She was conscious, oriented, afebrile, with pulse rate 76/min, blood pressure 100/70 mmHg, respiratory rate 12/min and oxygen saturation 97 per cent in the ambient air. General examination revealed no significant findings. She was started on oseltamivir and symptomatic measures. She gradually improved over the three days and became asymptomatic on February 3, 2020 and became negative for COVID-19 infection on day 19 of her illness. The oropharyngeal swabs for diagnosis of COVID-19 infection were collected on days 1, 4, 5, 7 and every alternate day, i.e. days 9, 11, 13 and so on after the onset of illness. The initial swabs remained positive till day 17 after which the swabs on days 19, 21 and 23 were negative and the patient was discharged. She was discharged from the hospital on February 20, 2020. Table Clinical laboratory report of the patient Measure Days of illness 1 5 14 24 Haemoglobin (g/dl) 10.8 12.2 12.1 11.3 Total WBC count (cells/μl) 5300 7300 7400 8500 Differential count Polymorphs-46 Polymorphs-47 Polymorphs-50- Polymorphs-56- Lymphocytes-47 Lymphocytes-42 Lymphocytes-46 Lymphocytes-36 Monocytes-7 Monocytes-11 Monocytes-4 Monocytes-8 Platelet count (×106 cells/μl) 2.88 3.6 3 3.9 ESR 13 44 33 80 Urine routine Normal Normal Normal Normal Random blood sugar (mg/dl) 89 82 83 95 Blood urea (mg/dl) 22 14 14 14 Serum creatinine (mg/dl) 0.7 0.8 0.7 0.6 Serum sodium (mmol/l) 136 135 134 134 Serum potassium (mmol/l) 4.3 4.4 4.2 4.3 Total bilirubin (mg/dl) 0.7 0.4 0.5 0.4 Direct bilirubin (mg/dl) 0.2 0.2 0.2 0.2 Total protein (g/dl) 6.1 6.8 6.2 7.8 Serum albumin (g/dl) 3.9 4 3.4 4.8 Alanine aminotransferase (IU/l) 15 13 16 16 Aspartate aminotransferase (IU/l) 19 21 23 22 Alkaline phosphatase (IU/l) 113 110 116 150 WBC, white blood cell; ESR, erythrocyte sedimentation rate A detailed contact tracing was done by the Community Medicine department of the Government Medical College, Thrissur, with the District Health Authorities. Those identified were followed up for 28 days for any symptoms. All healthcare workers in the isolation block also were followed up for 14 days.
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              Typhoid fever in children aged less than 5 years.

              Calculation of the incidence of typhoid fever during preschool years is important to define the optimum age of immunisation and the choice of vaccines for public-health programmes in developing countries. Hospital-based studies have suggested that children younger than 5 years do not need vaccination against typhoid fever, but this view needs to be re-examined in community-based longitudinal studies. We undertook a prospective follow-up study of residents of a low-income urban area of Delhi, India, with active surveillance for case detection. A baseline census was undertaken in 1995. Between Nov 1, 1995, and Oct 31, 1996, we visited 8172 residents of 1820 households in Kalkaji, Delhi, twice weekly to detect febrile cases. Blood samples were obtained from febrile patients, and those who tested positive for Salmonella typhi were treated with ciprofloxacin. 63 culture-positive typhoid fever cases were detected. Of these, 28 (44%) were in children aged under 5 years. The incidence rate of typhoid per 1000 person-years was 27.3 at age under 5 years, 11.7 at 5-19 years, and 1.1 between 19 and 40 years. The difference in the incidence of typhoid fever between those under 5 years and those aged 5-19 years (15.6 per 1000 person-years [95% CI 4.7-26.5]), and those aged 19-40 years (26.2 [16.0-36.3]) was significant (p<0.001 for both). The difference between the incidence of typhoid at 5-19 years and the incidence at 19-40 years was also significant (10.6 [6.3-14.8], p<0.001). Morbidity in those under 5 and in older people was similar in terms of duration of fever, signs and symptoms, and need for hospital admission. Our findings challenge the common view that typhoid fever is a disorder of school-age children and of adults. Typhoid is a common and significant cause of morbidity between 1 and 5 years of age. The optimum age of typhoid immunisation and the choice of vaccines needs to be reassessed.
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                Author and article information

                Contributors
                Journal
                Clin Infect Dis
                Clin Infect Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                01 July 2023
                22 March 2023
                22 March 2023
                : 77
                : 1
                : 138-144
                Affiliations
                Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California, USA
                Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California, USA
                Global Immunization Division, Center for Global Health, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
                Ministry of Health & Family Welfare, Government of India , New Delhi, India
                World Health Organization-Country Office for India , National Public Health Surveillance Project, New Delhi, India
                World Health Organization-Country Office for India , National Public Health Surveillance Project, New Delhi, India
                Global Immunization Division, Center for Global Health, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
                Global Immunization Division, Center for Global Health, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
                World Health Organization-Country Office for India , National Public Health Surveillance Project, New Delhi, India
                Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California, USA
                Global Immunization Division, Center for Global Health, Centers for Disease Control and Prevention , Atlanta, Georgia, USA
                World Health Organization-Country Office for India , National Public Health Surveillance Project, New Delhi, India
                Department of Pediatrics, NMMC General Hospital , Navi Mumbai, India
                Dr. Yewale Multispecialty Hospital for Children , Navi Mumbai, India
                Department of Pediatrics, MGM New Bombay Hospital , MGM Medical College, Navi Mumbai, India
                Dr. Joshi's Central Clinical Microbiology Laboratory , Navi Mumbai, India
                Department of Pediatrics & Neonatology, Dr. D.Y. Patil Medical College and Hospital , Navi Mumbai, India
                Rajmata Jijau Hospital, Airoli (NMMC) , Navi Mumbai, India
                Department of Microbiology, Dr. D.Y. Patil Medical College and Hospital , Navi Mumbai, India
                Department of Pediatrics, Mathadi Trust Hospital , Navi Mumbai, India
                Department of Microbiology, MGM New Bombay Hospital , Navi Mumbai, India
                National Institute of Cholera and Enteric Diseases, Indian Council of Medical Research , Kolkata, India
                World Health Organization South-East Asia Regional Office , New Delhi, India
                World Health Organization-Country Office for India , National Public Health Surveillance Project, New Delhi, India
                World Health Organization-Country Office for India , National Public Health Surveillance Project, New Delhi, India
                Dr. Yewale Multispecialty Hospital for Children , Navi Mumbai, India
                Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California, USA
                World Health Organization-Country Office for India , National Public Health Surveillance Project, New Delhi, India
                National Institute of Cholera and Enteric Diseases, Indian Council of Medical Research , Kolkata, India
                Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine , Stanford, California, USA
                Author notes
                Correspondence: Seth A. Hoffman, Division of Infectious Diseases & Geographic Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Lane Building, 134, Stanford, CA 94305, USA ( sethhoffman@ 123456stanford.edu ).
                Current affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California, USA
                Current affiliation: Johnson & Johnson Global Public Health, New Brunswick, New Jersey, USA
                Current affiliation: U.S. Centers for Disease Control and Prevention, Gaborone, Botswana

                World Health Organization, India Hypertension Control Initiative, New Delhi, India

                Potential conflicts of interest. K. D. reports support for attending meetings and/or travel by their employer (the CDC). S. P. L. reports support for attending meetings and/or travel from the Bill & Melinda Gates Foundation (conferences where some of the work from this project were reported). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

                Author information
                https://orcid.org/0000-0002-7881-3605
                https://orcid.org/0000-0001-5385-899X
                Article
                ciad132
                10.1093/cid/ciad132
                10320126
                36947143
                d6336f15-415c-40a8-88d0-a7a202cee97b
                © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 22 October 2022
                : 27 January 2023
                : 08 May 2023
                Page count
                Pages: 7
                Categories
                Major Article
                Original Article
                AcademicSubjects/MED00290
                Editor's Choice

                Infectious disease & Microbiology
                typhoid fever, salmonella typhi,vaccines,global health,india
                Infectious disease & Microbiology
                typhoid fever, salmonella typhi, vaccines, global health, india

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