Hypoxaemia in young Kenyan children with acute lower respiratory infection.

OBJECTIVES--To determine the prevalence, clinical correlates, and outcome of hypoxaemia in acutely ill children with respiratory symptoms. DESIGN--Prospective observational study. SETTING--Paediatric casualty ward of a referral hospital at 1670 m altitude in Nairobi, Kenya. SUBJECTS--256 Infants and children under 3 years of age with symptoms of respiratory infection. MAIN OUTCOME MEASURES--Prevalence of hypoxaemia, defined as arterial oxygen saturation < 90% determined by pulse oximetry, and condition of patient on the fifth day after admission. RESULTS--Over half (151) of the children were hypoxaemic, and short term mortality was 4.3 times greater in these children. In contrast, the relative risk of a fatal outcome in children with radiographic pneumonia was only 1.03 times that of children without radiographic pneumonia. A logistic regression model showed that in 3-11 month old infants a respiratory rate > or = 70/min, grunting, and retractions were the best independent clinical signs for the prediction of hypoxaemia. In the older children a respiratory rate of > or = 60/min was the single best clinical predictor of hypoxaemia. The presence of hypoxaemia predicted radiographic pneumonia with a sensitivity of 71% and specificity of 55%. CONCLUSIONS--Over half the children presenting to this referral hospital with respiratory symptoms were hypoxaemic. A group of specific clinical signs seem useful in predicting hypoxaemia. The clear association of hypoxaemia with mortality suggests that the detection and effective treatment of hypoxaemia are important aspects of the clinical management of acute infections of the lower respiratory tract in children in hospital in developing regions.     

Oral zinc and common childhood infections—An update

Zinc is an essential micronutrient important for growth and for normal function of the immune system. Many children in developing countries have inadequate zinc nutrition. Routine zinc supplementation reduces the risk of respiratory infections and diarrhea, the two leading causes of morbidity and mortality in young children worldwide. In childhood diarrhea oral zinc also reduces illness duration and risk of persistent episodes. Oral zinc is therefore recommended for the treatment of acute diarrhea in young children. The results from the studies that have measured the therapeutic effect of zinc on acute respiratory infections, however, are conflicting. Moreover, the results of therapeutic zinc for childhood malaria also are so far not promising.This paper gives a brief outline of the current evidence from clinical trials on therapeutic effect of oral zinc on childhood respiratory infections, pneumonia and malaria and also of new evidence of the effect on serious bacterial illness in young infants.     

Epidemiology of Acute Respiratory Infections in Children in Guangzhou: A Three-Year Study

Acute Respiratory Infections (ARI) are some of the most common human diseases worldwide. However, they have a complex and diverse etiology, and the characteristics of the pathogens involved in respiratory infections in developing countries are not well understood. In this work, we analyzed the characteristics of 17 common respiratory pathogens in children (≤14 years old) with ARI in Guangzhou, southern China over a 3-year period using real-time polymerase chain reaction. Pathogens were identified in 2361/4242 (55.7%) patients, and the positivity rate varied seasonally. Ten of the 17 pathogens investigated showed positivity rates of more than 5%. The most frequently detected pathogens were respiratory syncytial virus (768/2361, 32.5%), influenza A virus (428/2361, 18.1%), enterovirus (138/2361, 13.3%), Mycoplasma pneumoniae (267/2361, 11.3%) and adenovirus (213/2361, 9.0%). Co-pathogens were common and found in 503 of 2361 (21.3%) positive samples. When ranked according to frequency of occurrence, the pattern of co-pathogens was similar to that of the primary pathogens, with the exception of human bocavirus, human coronavirus and human metapneumovirus. Significant differences were found in age prevalence in 10 of the 17 pathogens (p≤0.009): four basic patterns were observed, A: detection rates increased with age, B: detection rates declined with age, C: the detection rate showed distinct peaks or D: numbers of patients were too low to detect a trend or showed no significant difference among age groups (p>0.05). These data will be useful for planning vaccine research and control strategies and for studies predicting pathogen prevalence.     

Ex-ante Inequality of Opportunity in Child Malnutrition: New Evidence from Ten Developing Countries in Asia

This study explores the inequality of opportunity in child malnutrition in ten developing countries in Asia, where a high proportion of children still remain vulnerable to food insecurity. This study takes account of multidimensional aspects of household and parental socio-economic status, and partitions children into distinct types through a data-driven clustering method. This is followed by a comparison of the malnutrition rates between types. Next, we decompose the observed disparity into the factors that are associated with the between-type disparity in malnutrition rates through a non-linear decomposition method. The results indicate that in all 10 countries, significant between-type disparities are found. We find the largest difference in Pakistan as 21.7 percentage points and the smallest difference in Maldives as 5.9 percentage points. In five of the ten countries, the difference in household affluence explains the largest part of the observed between-type disparity. All the results suggest that priority should be given to protecting children from marginalised households in order to mitigate the inequality in child health.     

Seasonal Influenza Vaccination for Children in Thailand: A Cost-Effectiveness Analysis

Background

Seasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV) or trivalent live-attenuated influenza vaccine (LAIV) in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly.

Methods and Findings

We developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions about contact patterns between age groups.

Conclusions

Vaccinating school-aged children with LAIV is likely to be cost-effective in Thailand in the short term, though the long-term consequences of such a policy cannot be reliably predicted given current knowledge of influenza epidemiology and immunology. Our work provides a coherent framework that can be used for similar analyses in other low- and middle-income countries.     

The epidemiology of pneumococcal infection in children in the developing world.

Pneumonia causes about three million deaths a year in young children, nearly all of which are in developing countries. Streptococcus pneumoniae (the pneumococcus) is the most important bacterial cause of pneumonia in young children and so is likely to be responsible for a high proportion of these deaths. The pneumococcus is also responsible for a substantial proportion of the 100,000-500,000 deaths that occur from meningitis in children each year. The incidence of invasive pneumococcal disease in children in the developing world is several times higher than in industrialized countries. This discrepancy may, in part, be due to socio-economic differences but genetic factors may also play a role. Children with sickle cell disease have a substantially increased risk of invasive pneumococcal infection and a search is being made for other possible genetic risk factors. Infection with human immunodeficiency virus (HIV) also predisposes to invasive pneumococcal disease and so the incidence of this disease in young children is expected to rise as increasing numbers of African and Asian children are born with a perinatally acquired HIV infection. Until recently, pneumococcal infections could be treated effectively with penicillin, a cheap and safe antibiotic. However, pneumococci that are resistant to penicillin are becoming prevalent in many countries, necessitating a change to more costly antibiotics which may be beyond the reach of the health services of poor, developing countries. The spread of antibiotic resistance has provided an added stimulus to the development of vaccines that might be able to prevent pneumococcal disease in infants. Recently developed polysaccharide-protein conjugate vaccines show promise and are now undergoing field trials. How deployment of these vaccines will influence the balance between invasive pneumococcal infections and asymptomatic nasopharyngeal carriage of pneumococci is uncertain.     

Modeling epidemics caused by respiratory syncytial virus (RSV)

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in children. In this paper we use models of RSV transmission to interpret the pattern of seasonal epidemics of RSV disease observed in different countries, and to estimate epidemic and eradication thresholds for RSV infection. We compare the standard SIRS model with a more realistic model of RSV transmission in which individuals acquire immunity gradually after repeated exposure to infection. The models are fitted to series of monthly hospital case reports of RSV disease from developed and developing countries. The models can explain many of the observed patterns: regular yearly outbreaks in some countries, and in other countries cycles of alternating larger and smaller annual epidemics, with shifted maxima in alternate years. Previously these patterns have been attributed to the transmission of different strains of RSV. In some countries the timing of epidemics is not consistent with increased social contact among school children during term time being the major driving mechanism. Climatic factors appear to be more important. Qualitatively different models gave equally good fits to the data series, but estimates of the transmission parameter were different by a factor of 4. Estimates of the basic reproduction number (R(0)) ranged from 1.2 to 2.1 with the SIRS model, and from 5.4 to 7.1 with the model with gradual acquisition of partial immunity.     

Outbreak of tuberculosis after minimal exposure to infection.

The identification of a case of respiratory tuberculosis in a swimming-baths attendant whose sputum was smear positive was followed by intensive contact tracing of children aged 8-11 years who had visited the baths. An outbreak was discovered that otherwise might not have been detected. Out of 3764 children, 108 (2.9%) had evidence of infection: there were 16 cases of tuberculosis, of which 11 were symptomless but showed lesions on chest radiography, and a further 92 with tine test grade 3 or 4 without clinical or radiological signs. The contact of these children with the index case was apparently minimal. Early detection, isolation, and treatment of infectious cases of respiratory tuberculosis and vigorous contact tracing should be given more priority in tuberculosis control.     

Changes in haemoglobin binding curve and oxygen transport in chronic hypoxic lung disease.

Direct measurements of the factors determining blood oxygen transport in 10 patients with chronic hypoxic respiratory failure led to the conclusion that wide differences in the position of their oxygen binding curves, due to spontaneous differences in red-cell 2, 3-diphosphoglycerate, had little effect on oxygen delivery to the tissues, as assessed by the mixed venous oxygen tension when they were breathing air. This result arises from the shape of the oxygen binding curve. A drug which could shift the curve to the right would help tissue oxygenation in cardiogenic and other forms of shock, when a low cardiac output can not be improved though arterial blood can be well oxygenated.     

Production, characterization, and application of antibodies against heat-labile type-I toxin for detection of enterotoxigenic Escherichia coli

Strains of enterotoxigenic Escherichia coli (ETEC) are responsible for significant rates of morbidity and mortality among children, particularly in developing countries. The majority of clinical and public health laboratories are capable of isolating and identifying Salmonella, Shigella, Campylobacter, and Escherichia coli O157:H7 from stool samples, but ETEC cannot be identified by routine methods. The method most often used to identify ETEC is polymerase chain reaction for heat-stable and heat-labile enterotoxin genes, and subsequent serotyping, but most clinical and public health laboratories do not have the capacity or resources to perform these tests. In this study, polyclonal rabbit and monoclonal mouse IgG2b antibodies against ETEC heat-labile toxin-I (LT) were characterized and the potential applicability of a capture assay was analyzed. IgG-enriched fractions from rabbit polyclonal and the IgG2b monoclonal antibodies recognized LT in a conformational shape and they were excellent tools for detection of LT-producing strains. These findings indicate that the capture immunoassay could be used as a diagnostic assay of ETEC LT-producing strains in routine diagnosis and in epidemiological studies of diarrhea in developing countries as enzyme linked immunosorbent assay techniques remain as effective and economical choice for the detection of specific pathogen antigens in cultures.     

Efficacy of a Low-Cost Bubble CPAP System in Treatment of Respiratory Distress in a Neonatal Ward in Malawi

Background

Respiratory failure is a leading cause of neonatal mortality in the developing world. Bubble continuous positive airway pressure (bCPAP) is a safe, effective intervention for infants with respiratory distress and is widely used in developed countries. Because of its high cost, bCPAP is not widely utilized in low-resource settings. We evaluated the performance of a new bCPAP system to treat severe respiratory distress in a low resource setting, comparing it to nasal oxygen therapy, the current standard of care.

Methods

We conducted a non-randomized convenience sample study to test the efficacy of a low-cost bCPAP system treating newborns with severe respiratory distress in the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi. Neonates weighing >1,000 g and presenting with severe respiratory distress who fulfilled inclusion criteria received nasal bCPAP if a device was available; if not, they received standard care. Clinical assessments were made during treatment and outcomes compared for the two groups.

Findings

87 neonates (62 bCPAP, 25 controls) were recruited. Survival rate for neonates receiving bCPAP was 71.0% (44/62) compared with 44.0% (11/25) for controls. 65.5% (19/29) of very low birth weight neonates receiving bCPAP survived to discharge compared to 15.4% (1/13) of controls. 64.6% (31/48) of neonates with respiratory distress syndrome (RDS) receiving bCPAP survived to discharge, compared to 23.5% (4/17) of controls. 61.5% (16/26) of neonates with sepsis receiving bCPAP survived to discharge, while none of the seven neonates with sepsis in the control group survived.

Interpretation

Use of a low-cost bCPAP system to treat neonatal respiratory distress resulted in 27% absolute improvement in survival. The beneficial effect was greater for neonates with very low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could reduce neonatal mortality in developing countries.     

Detecting bacteriuria in a primary maternal and child health care programme

Urinary tract infection in pregnancy has not been adequately dealt with in developing countries, though its consequences are well recognised. This is primarily because of constraints on resources coupled with a lack of technological infrastructure. An evaluation of the Griess test for the mass screening of urinary tract infection among antenatal women was carried out prospectively using a case-control method.The Griess test was found to be a valid, reliable, and economical screening test for urinary tract infection which can be integrated into a primary maternal and child health care programme.     

Carriage of Streptococcus pneumoniae and Other Respiratory Bacterial Pathogens in Low and Lower-Middle Income Countries: A Systematic Review and Meta-Analysis

Background

Infection with Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide, especially in low income countries where pneumococcal conjugate vaccines (PCVs) are still underused. In countries where PCVs have been introduced, much of their efficacy has resulted from their impact on nasopharyngeal carriage in vaccinated children. Understanding the epidemiology of carriage for S. pneumoniae and other common respiratory bacteria in developing countries is crucial for implementing appropriate vaccination strategies and evaluating their impact.

Methods and Findings

We have systematically reviewed published studies reporting nasopharyngeal or oropharyngeal carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Neisseria meningitidis in children and adults in low and lower-middle income countries. Studies reporting pneumococcal carriage for healthy children <5 years of age were selected for a meta-analysis. The prevalences of carriage for S. pneumoniae, H. influenzae, and M. catarrhalis were generally higher in low income than in lower-middle income countries and were higher in young children than in adults. The prevalence of S. aureus was high in neonates. Meta-analysis of data from young children before the introduction of PCVs showed a pooled prevalence estimate of 64.8% (95% confidence interval, 49.8%–76.1%) in low income countries and 47.8% (95% confidence interval, 44.7%–50.8%) in lower-middle income countries. The most frequent serotypes were 6A, 6B, 19A, 19F, and 23F.

Conclusions

In low and lower-middle income countries, pneumococcal carriage is frequent, especially in children, and the spectrum of serotypes is wide. However, because data are limited, additional studies are needed to adequately assess the impact of PCV introduction on carriage of respiratory bacteria in these countries.     

Global approach to reducing lead exposure and poisoning

Lead poisoning is an important environmental disease that can have life-long adverse health effects. Most susceptible are children, and most commonly exposed are those who are poor and live in developing countries. Studies of children's blood-lead levels (BLLs) are showing cognitive impairment at increasingly lower BLLs. Lead is dangerous at all levels in children. The sources of lead exposure vary among and within countries depending on past and current uses. Sources of lead may be from historic contamination, recycling old lead products, or from manufacturing new products. In all countries that have banned leaded gasoline, average population BLLs have declined rapidly. In many developing countries where leaded gasoline is no longer used, many children and workers are exposed to fugitive emissions and mining wastes. Unexpected lead threats, such as improper disposal of electronics and children's toys contaminated with lead, continue to emerge. The only medical treatment available is chelation, which can save lives of persons with very high BLLs. However, chelating drugs are not always available in developing countries and have limited value in reducing the sequelae of chronic low dose lead exposure. Therefore, the best approach is to prevent exposure to lead. Because a key strategy for preventing lead poisoning is to identify and control or eliminate lead sources, this article highlights several major sources of lead poisoning worldwide. In addition, we recommend three primary prevention strategies for lead poisoning: identify sources, eliminate or control sources, and monitor environmental exposures and hazards.     

An epidemiological study of respiratory syncytial virus associated hospitalizations in Denmark

Respiratory syncytial virus (RSV) is the primary cause of hospitalization for acute respiratory tract illness in general and specifically for bronchiolitis in young children. The link between RSV bronchiolitis and reactive airway disease is not completely understood, even though RSV bronchiolitis is frequently followed by recurrent episodes of wheezing. Therapy with ribavirin does not appear to significantly reduce long-term respiratory outcome of RSV lower respiratory tract infection, and corticosteroid or bronchodilator therapy may possibly improve outcomes only on a short-term basis. No vaccine against RSV is yet available. It is not known whether prophylaxis with RSV intravenous immune globulin or palivizumab can reduce postbronchiolitic wheezing.     

Age-specific variation in the secular trend for stature: A comparison of samples from industrialized and nonindustrialized regions

Age-specific secular trend patterns for children in industrialized world regions have a regular pattern, beginning low at age 6 and increasing to a maximum at age 10 to 14, then declining. While magnitude differs, the patterns are ordinarily parallel, especially in the female samples. However, age-specific secular trend values for children from developing regions, or from areas of industrialized countries not benefitting substantially from development, are irregular in pattern and magnitude. Consequently, it is difficult to predict age at maximal secular change. We suggest that fluctuating environmental circumstances in these developing countries influence growth and, hence, the pattern of secular trend. As more stable environmental conditions relating to growth are present in the industrialized countries, this leads to more stable patterns of growth and age-specific patterns of secular change.     

Investigations into the systemic production of aldehyde-derived peroxidation products in a murine model of acute iron poisoning: a dose response study

Acute iron poisoning remains a leading cause of morbidity and mortality in pre-school aged children in North America. Acute iron poisoning leads to organ damage, such as respiratory difficulties, cardiac arrhythmias, and possible death. The mechanism of iron toxicity is not fully understood, though it is thought that free iron is able to catalyze the production of harmful oxygen free radicals, which can damage all biochemical classes including lipid membranes, proteins, and DNA. Accordingly, we hypothesized that acute iron loading results in dose-dependent increases in oxygen free radical production, as quantified by the cytotoxic aldehydes hexanal, 4-hydroxynonenal, and malondialdehyde, in an experimental murine model. In support of our hypothesis, significant dose-dependent increases in all aldehydes investigated were reported in comparison to controls (p < 0.001). This murine model will assist in providing a better understanding of possible mechanism(s) of injury and organ dysfunction following acute iron poisoning, and for the development and evaluation of treatment regimes.     

Diphtheria remains a threat to health in the developing world--an overview

Changes in the epidemiology of diphtheria are occurring worldwide. A large proportion of adults in many industrialized and developing countries are now susceptible to diphtheria. Vaccine-induced immunity wanes over time unless periodic booster is given or exposure to toxigenic Corynebacterium diphtheriae occurs. Immunity gap in adults coupled with large numbers of susceptible children creates the potential for new extensive epidemics. Epidemic emergencies may not be long in coming in countries experiencing rapid industrialization or undergoing sociopolitical instability where many of the factors thought to be important in producing epidemic such as mass population movements and difficult hygienic and economic conditions are present. The continuous circulation of toxigenic C. diphtheriae emphasizes the need to be aware of epidemiological features, clinical signs, and symptoms of diphtheria in vaccine era so that cases can be promptly diagnosed and treated, and further public health measures can be taken to contain this serious disease. This overview focused on worldwide data obtained from diphtheria with particular emphasis to main factors leading to recent epidemics, new clinical forms of C. diphtheriae infections, expression of virulence factors, other than toxin production, control strategies, and laboratory diagnosis procedures.     

Breast cancer in South Asia: A Bangladeshi perspective

South Asian countries are facing a hidden breast cancer epidemic. A significant proportion of the breast cancer cases occur in premenopausal women. Knowledge of the various aspects of breast cancer in different geographical regions is limited in South Asia. In this article, we review the Bangladeshi perspective of the epidemiology, risk factors, pathology, diagnosis and treatment of breast cancer. As in other developing countries, because of the lack of breast cancer awareness in Bangladeshi population and inadequate access to health care, most patients are diagnosed at an advanced stage of the disease. Early detection has a crucial impact on overall treatment outcomes. To battle against breast cancer in resource-limited countries like Bangladesh, it is not feasible to set up a parallel health service system solely dedicated to cancer. Therefore, a cost-effective public health strategy is needed which could reach a large number of women in the country. Considering all these issues, we propose an innovative female-based primary healthcare approach focused on awareness, screening and early detection of breast cancer in Bangladesh. This preventive strategy could be a model for other resource-limited developing countries.     

Prevalence and Correlation of Infectious Agents in Hospitalized Children with Acute Respiratory Tract Infections in Central China

Acute respiratory tract infections (ARTIs) are associated with significant morbidity and mortality worldwide, especially in children under the age of 5 years. Almost 2 million children die from ARTIs each year, and most of them are from developing countries. The prevalence and correlation of pathogens in ARTIs are poorly understood, but are critical for improving case prevention, treatment, and management. In this study, we investigated the prevalence and correlation of infectious agents in children with ARTIs. A total of 39,756 children with one or more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis, herpangina, pneumonia, and bronchiolitis, were enrolled in the study. All patients were hospitalized in Wuhan Children’s Hospital between October 1, 2010 and September 30, 2012, and were evaluated for infectious agents. Pathogens, including Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened simultaneously in patient blood samples using anti-pathogen IgM tests. Regression analysis was used to reveal correlations among the pathogens. Our results showed that one or more pathogens were identified in 10,206 patients, and that Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading infectious agents. Mixed-infections of pathogens were detected in 2,391 cases, with Mycoplasma pneumoniae as the most frequent pathogen. The most common agents in the co-infections were Mycoplasma pneumoniae and influenza B virus. Regression analysis revealed a linear correlation between the proportion of mixed infections and the incidence of multi-pathogen infections. The prevalence of infectious agents in children with ARTIs was determined. Equations were established to estimate multiple infections by single-pathogen detection. This revealed a linear correlation for pathogens in children with ARTIs. This study provides useful information for improving case prevention and management.