Summary Background Despite widespread use of intrapartum antibiotic prophylaxis, group B streptococcus remains a leading cause of morbidity and mortality in infants in Europe, the Americas, and ...Australia. However, estimates of disease burden in many countries outside of these regions is not available. We aimed to examine the current global burden of invasive disease and the serotype distribution of group B streptococcus isolates. Methods We searched Medline, Embase, and Wholis databases for studies on invasive early-onset (day 0–6) and late-onset (day 7–89) group B streptococcal disease. Eligible studies were those that described incidence, deaths, or serotypes. We also reviewed reference lists and contacted experts to seek unpublished data and data missed by our search. Random effects meta-analysis was used to pool data. Findings 74 studies met the inclusion criteria; 56 studies reported incidence, 29 case fatality, and 19 serotype distribution. An additional search for studies that reported serotype distribution from Jan 1, 1980, yielded a total of 38 articles. Only five low-income countries were represented in the review and contributed 5% weight to the meta-analysis. 47 (69%) studies reported use of any intrapartum antibiotic prophylaxis. Substantial heterogeneity existed between studies. Mean incidence of group B streptococcus in infants aged 0–89 days was 0·53 per 1000 livebirths (95% CI 0·44–0·62) and the mean case fatality ratio was 9·6% (95% CI 7·5–11·8). Incidence of early-onset group B streptococcus (0·43 per 1000 livebirths 95% CI 0·37–0·49) and case fatality (12·1%, 6·2–18·3) were two-times higher than late-onset disease. Serotype III (48·9%) was the most frequently identified serotype in all regions with available data followed by serotypes Ia (22·9%), Ib (7·0%), II (6·2%), and V (9·1%). Studies that reported use of any intrapartum antibiotic prophylaxis were associated with lower incidence of early-onset group B streptococcus (0·23 per 1000 livebirths 95% CI 0·13–0·59) than studies in which patients did not use prophylaxis (0·75 per 1000 livebirths 0·58–0·89). Interpretation More high-quality studies are needed to accurately estimate the global burden of group B streptococcus, especially in low-income countries. A conjugate vaccine incorporating five serotypes (Ia, Ib, II, III, V) could prevent most global group B streptococcal disease. Funding Child Epidemiology Reference Group (CHERG), WHO.
Summary Background Powders containing iron and other micronutrients are recommended as a strategy to prevent nutritional anaemia and other micronutrient deficiencies in children. We assessed the ...effects of provision of two micronutrient powder formulations, with or without zinc, to children in Pakistan. Methods We did a cluster randomised trial in urban and rural sites in Sindh, Pakistan. A baseline survey identified 256 clusters, which were randomly assigned (within urban and rural strata, by computer-generated random numbers) to one of three groups: non-supplemented control (group A), micronutrient powder without zinc (group B), or micronutrient powder with 10 mg zinc (group C). Children in the clusters aged 6 months were eligible for inclusion in the study. Powders were to be given daily between 6 and 18 months of age; follow-up was to age 2 years. Micronutrient powder sachets for groups B and C were identical except for colour; investigators and field and supervisory staff were masked to composition of the micronutrient powders until trial completion. Parents knew whether their child was receiving supplementation, but did not know whether the powder contained zinc. Primary outcomes were growth, episodes of diarrhoea, acute lower respiratory tract infection, fever, and incidence of admission to hospital. This trial is registered with ClinicalTrials.gov , number NCT00705445. Results The trial was done between Nov 1, 2008, and Dec 31, 2011. 947 children were enrolled in group A clusters, 910 in group B clusters, and 889 in group C clusters. Micronutrient powder administration was associated with lower risk of iron-deficiency anaemia at 18 months compared with the control group (odds ratio OR for micronutrient powder without zinc=0·20, 95% CI 0·11–0·36; OR for micronutrient powder with zinc=0·25, 95% CI 0·14–0·44). Compared with the control group, children in the group receiving micronutrient powder without zinc gained an extra 0·31 cm (95% CI 0·03–0·59) between 6 and 18 months of age and children receiving micronutrient powder with zinc an extra 0·56 cm (0·29–0·84). We recorded strong evidence of an increased proportion of days with diarrhoea (p=0·001) and increased incidence of bloody diarrhoea (p=0·003) between 6 and 18 months in the two micronutrient powder groups, and reported chest indrawing (p=0·03). Incidence of febrile episodes or admission to hospital for diarrhoea, respiratory problems, or febrile episodes did not differ between the three groups. Interpretation Use of micronutrient powders reduces iron-deficiency anaemia in young children. However, the excess burden of diarrhoea and respiratory morbidities associated with micronutrient powder use and the very small effect on growth recorded suggest that a careful assessment of risks and benefits must be done in populations with malnourished children and high diarrhoea burdens. Funding Bill & Melinda Gates Foundation.
Antibiotic resistance—the need for global solutions Laxminarayan, Ramanan, PhD; Duse, Adriano, MD; Wattal, Chand, MD ...
Lancet. Infectious diseases/The Lancet. Infectious diseases,
12/2013, Letnik:
13, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Summary The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are ...evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.
Summary Background Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the ...aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. Methods The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0–59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. Findings We enrolled 9439 children with moderate-to-severe diarrhoea and 13 129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium , enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella . Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni ). Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8·5, 95% CI 5·8–12·5, p<0·0001); most deaths (167 87·9%) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio HR 1·9; 0·99–3·5) and typical enteropathogenic E coli (HR 2·6; 1·6–4·1) in infants aged 0–11 months, and Cryptosporidium (HR 2·3; 1·3–4·3) in toddlers aged 12–23 months. Interpretation Interventions targeting five pathogens (rotavirus, Shigella , ST-ETEC, Cryptosporidium , typical enteropathogenic E coli ) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. Funding The Bill & Melinda Gates Foundation.
Summary Background Childhood diarrhoea can be caused by many pathogens that are difficult to assay in the laboratory. Molecular diagnostic techniques provide a uniform method to detect and quantify ...candidate enteropathogens. We aimed to develop and assess molecular tests for identification of enteropathogens and their association with disease. Methods We developed and assessed molecular diagnostic tests for 15 enteropathogens across three platforms—PCR-Luminex, multiplex real-time PCR, and TaqMan array card—at five laboratories worldwide. We judged the analytical and clinical performance of these molecular techniques against comparator methods (bacterial culture, ELISA, and PCR) using 867 diarrhoeal and 619 non-diarrhoeal stool specimens. We also measured molecular quantities of pathogens to predict the association with diarrhoea, by univariate logistic regression analysis. Findings The molecular tests showed very good analytical and clinical performance at all five laboratories. Comparator methods had limited sensitivity compared with the molecular techniques (20–85% depending on the target) but good specificity (median 97·3%, IQR 96·5–98·9; mean 95·2%, SD 9·1). Positive samples by comparator methods usually had higher molecular quantities of pathogens than did negative samples, across almost all platforms and for most pathogens (p<0·05). The odds ratio for diarrhoea at a given quantity (measured by quantification cycle, Cq) showed that for most pathogens associated with diarrhoea—including Campylobacter jejuni and Campylobacter coli, Cryptosporidium spp, enteropathogenic Escherichia coli , heat-stable enterotoxigenic E coli , rotavirus, Shigella spp and enteroinvasive E coli , and Vibrio cholerae —the strength of association with diarrhoea increased at higher pathogen loads. For example, Shigella spp at a Cq range of 15–20 had an odds ratio of 8·0 (p<0·0001), but at a Cq range of 25–30 the odds ratio fell to 1·7 (p=0·043). Interpretation Molecular diagnostic tests can be implemented successfully and with fidelity across laboratories around the world. In the case of diarrhoea, these techniques can detect pathogens with high sensitivity and ascribe diarrhoeal associations based on quantification, including in mixed infections, providing rich and unprecedented measurements of infectious causes. Funding Bill & Melinda Gates Foundation Next Generation Molecular Diagnostics Project.
Shigellosis Kotloff, Karen L; Riddle, Mark S; Platts-Mills, James A ...
The Lancet (British edition),
02/2018, Letnik:
391, Številka:
10122
Journal Article
Recenzirano
Shigellosis is a clinical syndrome caused by invasion of the epithelium lining the terminal ileum, colon, and rectum by Shigella species. Although infections occur globally, and in people of all ...ages, endemic infections among children aged 1–4 years living in low-income and middle-income settings constitute most of the disease burden. The versatile manifestations of these highly contagious organisms range from acute watery diarrhoea to fulminant dysentery characterised by frequent scant bloody stools with fever, prostration, and abdominal cramps. A broad array of uncommon, but often severe, intestinal and extraintestinal complications can occur. Despite marked reductions in mortality during the past three decades, there are roughly 164 000 annual deaths attributable to shigellosis. Intercontinental dissemination of multiresistant shigella strains, facilitated by travellers and men who have sex with men, has prompted new recommendations for antibiotic therapy. Awareness of disease burden and the emerging threats posed by shigella have accelerated interest in development of shigella vaccines, many of which are being tested in clinical trials.
Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation ...and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age.
The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged <5 y old experiencing MSD and for 12,390 asymptomatic age, gender, and neighborhood-matched controls. An MSD case was defined as a child with a diarrheal illness <7 d duration comprising ≥3 loose stools in 24 h and ≥1 of the following: sunken eyes, skin tenting, dysentery, intravenous (IV) rehydration, or hospitalization. Site-specific conditional logistic regression models were used to explore the association between sanitation and hygiene exposures and MSD. Most households at six sites (>93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1-2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India.
This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved.
The WHO recommends oral amoxicillin for pneumonia with tachypnea, yet trial data show that withholding amoxicillin may be noninferior to using amoxicillin. In this double-blind trial, children 2 to ...59 months of age in low-income communities in Pakistan were assigned to a 3-day course of placebo or amoxicillin. The noninferiority of placebo was not shown.
Background. Diarrhea is a leading cause of illness and death among children aged <5 years in developing countries. This paper describes the clinical and epidemiological methods used to conduct the ...Global Enteric Multicenter Study (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the population-based burden, microbiologic etiology, and adverse clinical consequences of acute moderate-to-severe diarrhea (MSD) among a censused population of children aged 0-59 months seeking care at health centers in sub-Saharan Africa and South Asia. Methods. GEMS was conducted at 7 field sites, each serving a population whose demography and healthcare utilization practices for childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year from selected health centers serving each site in each of 3 age strata (0-11, 12-23, and 24-59 months), along with 1-3 matched community controls. Cases and controls supplied clinical, epidemiologic, and anthropometric data at enrollment and again approximately 60 days later, and provided enrollment stool specimens for identification and characterization of potential diarrheal pathogens. Verbal autopsy was performed if a child died. Analytic strategies will calculate the fraction of MSD attributable to each pathogen and the incidence, financial costs, nutritional consequences, and case fatality overall and by pathogen. Conclusions. When completed, GEMS will provide estimates of the incidence, etiology, and outcomes of MSD among infants and young children in sub-Saharan Africa and South Asia. This information can guide development and implementation of public health interventions to diminish morbidity and mortality from diarrheal diseases.
Pakistan was one of the first South-Asian countries to introduce the ten-valent pneumococcal conjugate vaccine (PCV10) at the national level, using a 3+0 schedule without catchup, in 2013.
From ...2014-18, fifteen children <2 years old were recruited every week in Matiari, Sindh, and nasopharyngeal swabs were collected. The samples were cultured, and pneumococcus was further serotyped through multiplex PCR at the Aga Khan University Hospital as per the method described by the Centers for Disease Control and Prevention, USA.
Pneumococcus was detected in 2370/3140 (75%) children. Vaccine type (VT) and non-vaccine type (NVT) serotypes were carried by 379 and 1990 children. There was a significant decline in VT carriage (by 40.3%, p-value <0.001), whereas overall NVT carriage remained the same. The prevalence of VT serotypes 6B, 9V/9A, and 19F showed a significant decline by 58.8%, 79.3%, and 56%, respectively. The prevalence of NVT serotypes 19A, 21, and 10A increased by 70%, 33.3%, and 65.6%, respectively, whereas serotypes 13 and 9N/9L decreased by 53.4% and 51.8%, respectively. Serotype-specific vaccine effectiveness estimates that reached statistical significance were for 9V/9A (VE = 65.0, 95% CI 26.0-83.5%), 19F (VE = 55.3, 95% CI 15.5-76.4%) and for the vaccine related serotype 6A (VE = 28.4, 95% CI 0.9-48.2%).
The emergence of NVT serotypes, primarily 19A replacing VT serotypes in this rural community, necessitates continuous monitoring of serotypes in the carriage and invasive disease to evaluate the utility of existing vaccine formulations.
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