Measuring Maternal Mortality: Three Case Studies Using Verbal Autopsy with Different Platforms

Background

Accurate measurement of maternal mortality is needed to develop a greater understanding of the scale of the problem, to increase effectiveness of program planning and targeting, and to track progress. In the absence of good quality vital statistics, interim methods are used to measure maternal mortality. The purpose of this study is to document experience with three community-based interim methods that measure maternal mortality using verbal autopsy.

Methods

This study uses a post-census mortality survey, a sample vital registration with verbal autopsy, and a large-scale household survey to summarize the measures of maternal mortality obtained from these three platforms, compares and contrasts the different methodologies employed, and evaluates strengths and weaknesses of each approach. Included is also a discussion of issues related to death identification and classification, estimating maternal mortality ratios and rates, sample sizes and periodicity of estimates, data quality, and cost.

Results

The sample sizes vary considerably between the three data sources and the number of maternal deaths identified through each platform was small. The proportion of deaths to women of reproductive age that are maternal deaths ranged from 8.8% to 17.3%. The maternal mortality rate was estimable using two of the platforms while obtaining an estimate of the maternal mortality ratio was only possible using one of the platforms. The percentage of maternal deaths due to direct obstetric causes ranged from 45.2% to 80.4%.

Conclusions

This study documents experiences applying standard verbal autopsy methods to estimate maternal mortality and confirms that verbal autopsy is a feasible method for collecting maternal mortality data. None of these interim methods are likely to be suitable for detecting short term changes in mortality due to prohibitive sample size requirements, and thus, comprehensive and continuous civil registration systems to provide high quality vital statistics are essential in the long-term.     

Quality of Artemisinin-Based Combination Formulations for Malaria Treatment: Prevalence and Risk Factors for Poor Quality Medicines in Public Facilities and Private Sector Drug Outlets in Enugu,Nigeria

BackgroundArtemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates.MethodsACAs were purchased using three sampling approaches - convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified.ResultsContent analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified.ConclusionRandomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained.     

Assessing the potential for Grey Squirrels Sciurus carolinensis to compete with birds at supplementary feeding stations

Supplementary feeding of birds, particularly in urban areas, is often associated with increased population size and fecundity. In the UK, the non‐native Grey Squirrel Sciurus carolinensis is common in rural and urban habitats. It exploits supplementary feeders and may induce interference competition by excluding birds, but empirical evidence of this is unavailable. Using controlled model presentation experiments, we demonstrate that Grey Squirrels could reduce bird use of supplementary feeders and induce interference competition. Total bird resource use was reduced by 98% and most species exhibited similar sensitivities. The likelihood and magnitude of interference competition will depend on how rapidly displaced birds find alternative food sources; it will be greatest where there are high Grey Squirrel densities and few supplementary feeders. Other studies suggest that supplementary feeding increases Grey Squirrel numbers, and the species is also predicted to expand its non‐native range across most of Europe. Our data indicate that Grey Squirrels may eventually alter the net effect of supplementary feeding on bird populations across the European continent; increased use of squirrel‐proof feeders may help to minimize such effects.     

S-nitrosothiols increases cystic fibrosis transmembrane regulator expression and maturation in the cell surface

S-nitrosothiols (SNOs) are endogenous signaling molecules with a broad spectrum of beneficial airway effects. SNOs are normally present in the airway, but levels tend to be low in cystic fibrosis (CF) patients. We and others have demonstrated that S-nitrosoglutathione (GSNO) increases the expression, maturation, and function of wild-type and mutant F508del cystic fibrosis transmembrane conductance regulator (CFTR) in human bronchial airway epithelial (HBAE) cells. We hypothesized that membrane permeable SNOs, such as S-nitrosoglutathione diethyl ester (GNODE) and S-nitroso-N-acetyl cysteine (SNOAC) may be more efficient in increasing the maturation of CFTR. HBAE cells expressing F508del CFTR were exposed to GNODE and SNOAC. The effects of these SNOs on the expression and maturation of F508del CFTR were determined by cell surface biotinylation and Western blot analysis. We also found for the first time that GNODE and SNOAC were effective at increasing CFTR maturation at the cell surface. Furthermore, we found that cells maintained at low temperature increased cell surface stability of F508del CFTR whereas the combination of low temperature and SNO treatment significantly extended the half-life of CFTR. Finally, we showed that SNO decreased the internalization rate of F508del CFTR in HBAE cells. We anticipate identifying the novel mechanisms, optimal SNOs, and lowest effective doses which could benefit cystic fibrosis patients.     

Breath Formate Is a Marker of Airway S-Nitrosothiol Depletion in Severe Asthma

Background

Children with severe asthma have poor symptom control and elevated markers of airway oxidative and nitrosative stress. Paradoxically, they have decreased airway levels of S-nitrosothiols (SNOs), a class of endogenous airway smooth muscle relaxants. This deficiency results from increased activity of an enzyme that both reduces SNOs to ammonia and oxidizes formaldehyde to formic acid, a volatile carboxylic acid that is more easily detected in exhaled breath condensate (EBC) than SNOs. We therefore hypothesize that depletion of airway SNOs is related to asthma pathology, and breath formate concentration may be a proxy measure of SNO catabolism.

Methods and Findings

We collected EBC samples from children and adolescents, including 38 with severe asthma, 46 with mild-to-moderate asthma and 16 healthy adolescent controls, and the concentration of ionic constituents was quantified using ion chromatography. The concentrations of EBC components with volatile conjugates were log-normally distributed. Formate was the principal ion that displayed a significant difference between asthma status classifications. The mean EBC formate concentration was 40% higher in samples collected from all asthmatics than from healthy controls (mean = 5.7 µM, mean±standard deviation = 3.1−10.3 µM vs. 4.0, 2.8−5.8 µM, p = 0.05). EBC formate was higher in severe asthmatics than in mild-to-moderate asthmatics (6.8, 3.7−12.3 µM vs. 4.9, 2.8−8.7 µM, p = 0.012). In addition, formate concentration was negatively correlated with methacholine PC₂₀ (r = −0.39, p = 0.002, asthmatics only), and positively correlated with the NO-derived ion nitrite (r = 0.46, p<0.0001) as well as with total serum IgE (r = 0.28, p = 0.016, asthmatics only). Furthermore, formate was not significantly correlated with other volatile organic acids nor with inhaled corticosteroid dose.

Conclusions

We conclude that EBC formate concentration is significantly higher in the breath of children with asthma than in those without asthma. In addition, amongst asthmatics, formate is elevated in the breath of those with severe asthma compared to those with mild-to-moderate asthma. We suggest that this difference is related to asthma pathology and may be a product of increased catabolism of endogenous S-nitrosothiols.     

Sex-determined differential mortality of milkweed bugs, Oncopeltus fasciatus (hemiptera), to aflatoxins

Studies on the aflatoxins, toxic metabolites of Aspergillus flavus and A. parasiticus, have involved test systems ranging from cell cultures to laboratory animals. This work reports on the differential response by sex of Oncopeltus fasciatus to aflatoxin B₁ (AFB₁). Young adult milkweed bugs were chosen randomly from our stock colony and housed in glass culture jars. Triplicate sets of experimental animals were fed 5 μg/ml of AFB₁ in their liquid diet. The first death for the experimental females occurred at day 4, and at 10 days for the experimental males. A 50% lethality level for experimental females developed by day 8. Males subjected to the same concentration achieved a 50% lethality level at day 24. For the females the LD₅₀ occurred after consuming 0.49 μg/ml of AFB₁. The results indicate that adult female milkweed bugs were hypersensitive to AFB₁ as compared to adult males. This organism is more sensitive than the American cockroach and less sensitive than the fruitfly, housefly, and honeybee to toxic aflatoxicosis. Even the female is not sufficiently sensitive to rate highly as a bioassay organism for AFB₁. The extreme difference in mortality between the sexes is significant, unusual, and unexplained.     

Low functional diversity and no redundancy in British avian assemblages

1. Spatial and temporal patterns in functional diversity can reveal the patterns and processes behind community assembly and whether ecological redundancy exists. Here, we analyse functional diversity in British avian assemblages over a period of about 20 years. 2. Functional diversity is generally lower than expected by chance, indicating that assemblages contain species with relatively similar functional traits. One potential explanation is filtering for traits suitable to particular habitats, though other explanations exist. 3. There was no evidence of ecological redundancy over the 20 years. In fact, changes in functional diversity were almost exactly proportional to changes in species richness. 4. The absence of functional redundancy results from little redundancy intrinsic to the species' functional relationships and also because compositional change was nonrandom. Observed extinction and colonization events caused greater changes in functional diversity than if these events were random. 5. Our findings suggest that community assembly is influenced by the traits of species and that observed changes in functional diversity provide no reason to believe that the functioning of natural systems is buffered against change by ecological redundancy.