Estimating diarrhea mortality among young children in low and middle income countries

Background

Diarrhea remains one of the leading causes of morbidity and mortality among children under 5 years of age, but in many low and middle-income countries where vital registration data are lacking, updated estimates with regard to the proportion of deaths attributable to diarrhea are needed.

Methods

We conducted a systematic literature review to identify studies reporting diarrhea proportionate mortality for children 1–59 mo of age published between 1980 and 2009. Using the published proportionate mortality estimates and country level covariates we constructed a logistic regression model to estimate country and regional level proportionate mortality and estimated uncertainty bounds using Monte-Carlo simulations.

Findings

We identified more than 90 verbal autopsy studies from around the world to contribute data to a single-cause model. We estimated diarrhea proportionate mortality for 84 countries in 6 regions and found diarrhea to account for between 10.0% of deaths in the Americas to 31.3% of deaths in the South-east Asian region.

Discussion

Diarrhea remains a leading cause of death for children 1–59 mo of age. Published literature can be used to create a single-cause mortality disease model to estimate mortality for countries lacking vital registration data.     

Reliability of recording uterine cancer in death certification in France and age-specific proportions of deaths from cervix and corpus uteri

French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.     

Latex agglutination test for diagnosing pneumococcal pneumonia in children in developing countries.

OBJECTIVE--To prepare and assess the sensitivity and specificity of a latex agglutination test specific for the serotype of antigen in diagnosing pneumococcal pneumonia in Gambian children. DESIGN--Comparison of agglutination test specific for serotype with culture of blood and lung aspirates, countercurrent immunoelectrophoresis, and commercial latex agglutination tests in diagnosing pneumococcal pneumonia. Cross reaction studies and investigation of 102 control children to determine specificity of agglutination test specific for serotype. SETTING--General medical ward of Medical Research Council laboratories, The Gambia. PATIENTS--101 Gambian children aged between 2 months and 10 years admitted with severe pneumonia. INTERVENTIONS--Serum samples were boiled and treated with edetic acid, and urine samples were boiled and concentrated 25 times before testing. END POINT--A latex agglutination test specific for the serotype of pneumococcal antigen that is sensitive and highly specific for detecting pneumococcus in the urine of patients with pneumococcal pneumonia. MEASUREMENTS AND MAIN RESULTS--Concentrated urine samples from 16 of the 21 children (76%) with pneumococcal pneumonia established by results of culture of blood or lung aspirates gave a positive result with the agglutination test specific for serotype, whereas only four of the 102 urine samples obtained from control children without pneumonia gave positive results. The serotypes of antigens detected in the urine of children with pneumococcal pneumonia and the serotypes of pneumococci isolated from cultures of blood or lung aspirates were the same in all cases. CONCLUSIONS--When performed on urine samples the agglutination test specific for serotype has a high specificity and is more sensitive than culture of blood or lung aspirates, commercial agglutination tests, or countercurrent immunoelectrophoresis in identifying pneumococcal pneumonia. It is easy to use and should be especially useful in communities with limited laboratory facilities.     

Hyponatraemia and death or permanent brain damage in healthy children.

OBJECTIVE--To determine if hyponatraemia causes permanent brain damage in healthy children and, if so, if the disorder is primarily limited to females, as occurs in adults. DESIGN--Prospective clinical case study of 16 affected children and a review of 24,412 consecutive surgical admissions at one medical centre. PATIENTS--16 children (nine male, seven female; age 7 (SD 5) years) with generally minor illness were electively hospitalised for primary care. Consultation was obtained for the combination of respiratory arrest with symptomatic hyponatraemia (serum sodium concentration less than or equal to 128 mmol/l). MAIN OUTCOME MEASURES--Presence, gender distribution, and classification of permanent brain damage in children with symptomatic hyponatraemia in both prospective and retrospective studies. RESULTS--By retrospective evaluation the incidence of postoperative hyponatraemia among 24,412 patients was 0.34% (83 cases) and mortality of those afflicted was 8.4% (seven deaths). In the prospective population the serum sodium concentration on admission was 138 (SD 2) mmol/l. From three to 120 inpatient hours after hypotonic fluid administration patients developed progressive lethargy, headache, nausea, and emesis with an explosive onset of respiratory arrest. At the time serum sodium concentration was 115 (7) mmol/l and arterial oxygen tension 6 (1.5) kPa. The hyponatraemia was primarily caused by extrarenal loss of electrolytes with replacement by hypotonic fluids. All 16 patients had cerebral oedema detected at either radiological or postmortem examination. All 15 patients not treated for their hyponatraemia in a timely manner either died or were permanently incapacitated by brain damage. The only patient treated in a timely manner was alive but mentally retarded. CONCLUSIONS--Symptomatic hyponatraemia can result in high morbidity in children of both genders, which is due in large part to inadequate brain adaptation and lack of timely treatment.     

Anergy or cell death induced by low physiological temperature in mitogen-stimulated human T lymphocytes

1. 1. Human T cell proliferation is suppressed at 27°C, and is both diminished and delayed at 32°C.

2. 2. Temperature shift-up and viability assays indicated that concanavalin A stimulation at 27°C induced cell death in contrast to a transient unresponsiveness (anergy) induced by monoclonal anti-CD3 antibody (CD3) and the superantigen, staphylococcal exterotoxin B.

3. 3. Phytohemagglutinin also induced cell death at 27°C; however, some cells remained viable and proliferation occurred when such cultures were subsequently moved to 37°C.

4. 4. Low temperature suppression of T cell activation was not overcome by a mixture of phorbol ester and calcium ionophore indicating a probable block post-protein kinase C activation. This was confirmed in temperature shift-down assays where incubation for 18–24 h at 37°C was required to bypass the block at 27°C.

5. 5. With the exception of CD3, stimulation at 27°C with the mitogens resulted in interleukin-2 secretion, indicating that the low temperature block(s) is a relatively late event in cell activation.

     

Germanium in ginseng is low and causes no sodium and water retention or renal toxicity in the diuretic-resistant rats

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes.     

Etiology and treatment of pneumonia in children]

The most widespread pathogens of pneumonia in children i.e. Streptococcus pneumoniae and Haemophilus influenzae and their antibiotic susceptibility are described. The ways of selecting starting antibacterial drugs for the treatment of community-acquired and hospital pneumonia are recommended proceeding from the original findings and some literature data. Oral drugs for the treatment of uncomplicated pneumonia are shown to be preferential. In the treatment of nosocomial or hospital pneumonia the starting regimen should allow for the previous antibacterial therapy.     

阿莫西林克拉维酸钾或头孢他啶联合布地奈德对肺炎患儿的疗效

目的 探讨阿莫西林克拉维酸钾或头孢他啶联合布地奈德对肺炎患儿的治疗效果及对肠道微生物的影响。 方法 选择2016年9月至2018年12月我院儿科收治的90例肺炎患儿为研究对象,入选患儿随机分为对照组(n=45)和研究组(n=45)。另外选取本院同期健康体检的40例儿童为健康组。对照组患儿接受头孢他啶联合布地奈德疗法,研究组患儿采用阿莫西林克拉维酸钾联合布地奈德疗法。连续治疗7 d后,比较两组患儿临床疗效、临床症状(发热、咳嗽、啰音及扁桃体充血)消失时间及不良反应,同时比较各组患儿肠道微生物(乳杆菌、双歧杆菌、真杆菌、肠杆菌及肠球菌)变化情况。 结果 研究组患儿总有效率为95.56%,对照组总有效率为91.11%,两组比较差异无统计学意义(χ2=0.714,P=0.398)。研究组患儿发热、咳嗽、啰音及扁桃体充血消失时间与对照组比较差异无统计学意义(均P>0.05)。治疗前,研究组和对照组患儿肠道菌群数量与健康组比较差异无统计学意义(均P>0.05)。治疗后,研究组和对照组患儿肠道菌群数量与健康组比较差异有统计学意义(均P0.05)。研究组(8.89%)和对照组(13.33%)总不良反应率比较差异无统计学意义(P>0.05)。 结论 阿莫西林克拉维酸钾联合布地奈德治疗小儿肺炎疗效显著,能有效缩短患儿临床症状持续时间,其疗效与头孢他啶联合布地奈德疗效相当,且药物副作用较小,但对肠道菌群平衡有破坏作用。因此,扶植肠道菌群可以作为综合治疗的一部分。     

MazF-mediated cell death in Escherichia coli: a point of no return

mazEF is a stress-induced toxin-antitoxin module, located on the chromosome of Escherichia coli, that we have previously described to be responsible for programmed cell death in E. coli. mazF specifies a stable toxin, and mazE specifies a labile antitoxin. Recently, it was reported that inhibition of translation and cell growth by ectopic overexpression of the toxin MazF can be reversed by the action of the antitoxin MazE ectopically overexpressed at a later time. Based on these results, it was suggested that rather than inducing cell death, mazF induces a state of reversible bacteriostasis (K. Pederson, S. K. Christensen, and K. Gerdes, Mol. Microbiol. 45:501-510, 2002). Using a similar ectopic overexpression system, we show here that overexpression of MazE could reverse MazF lethality only over a short window of time. The size of that window depended on the nature of the medium in which MazF was overexpressed. Thus, we found "a point of no return," which occurred sooner in minimal M9 medium than it did in the rich Luria-Bertani medium. We also describe a state in which the effect of MazF on translation could be separated from its effect on cell death: MazE overproduction could completely reverse the inhibitory effect of MazF on translation, while not affecting the bacteriocidic effect of MazF at all. Our results reported here support our view that the mazEF module mediates cell death and is part of a programmed cell death network.     

Estimating in vivo death rates of targets due to CD8 T-cell-mediated killing

Despite recent advances in immunology, several key parameters determining virus dynamics in infected hosts remain largely unknown. For example, the rate at which specific effector and memory CD8 T cells clear virus-infected cells in vivo is hardly known for any viral infection. We propose a framework to quantify T-cell-mediated killing of infected or peptide-pulsed target cells using the widely used in vivo cytotoxicity assay. We have reanalyzed recently published data on killing of peptide-pulsed splenocytes by cytotoxic T lymphocytes and memory CD8 T cells specific to NP396 and GP276 epitopes of lymphocytic choriomeningitis virus (LCMV) in the mouse spleen. Because there are so many effector CD8 T cells in spleens of mice at the peak of the immune response, NP396- and GP276-pulsed targets are estimated to have very short half-lives of 2 and 14 min, respectively. After the effector numbers have diminished, i.e., in LCMV-immune mice, the half-lives become 48 min and 2.8 h for NP396- and GP276-expressing targets, respectively. Analysis of several alternative models demonstrates that the estimates of half-life times of peptide-pulsed targets are not affected when changes are made in the model assumptions. Our report provides a unifying framework to compare killing efficacies of CD8 T-cell responses specific to different viral and bacterial infections in vivo, which may be used to compare efficacies of various cytotoxic-T-lymphocyte-based vaccines.