Comparison of static and dynamic models of maternal immunization to prevent infant pertussis in Brazil

BackgroundThis paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile.MethodsWe defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models’ different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated.ResultsThe dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90–95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models’ estimates over their different time horizons are compared at infant coverage < 90–95%, their projections fall in the same range.ConclusionsStatic models may serve to explore an intervention’s cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally.Clinical Trial registryClinical Trial registry name and registration number: Not applicable.     

Cost-effectiveness of maternal pertussis immunization: Implications of a dynamic transmission model for low- and middle-income countries

ObjectiveThis study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model.MethodsWe developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY).ResultsThe dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90–95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model’s time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage.ConclusionA dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90–95%.     

Income inequality and homicide rates in Rio de Janeiro, Brazil.

OBJECTIVES: This study determined the effect of income inequality on homicide rates in the state of Rio de Janeiro, Brazil. METHODS: We conducted an ecological study at 2 geographical levels, municipalities in the state of Rio de Janeiro and administrative regions in the municipality of Rio de Janeiro. The association between homicide and income inequality was tested by multiple regression procedures, with adjustment for other socioeconomic indicators. RESULTS: For the municipalities of Rio de Janeiro State, no association between homicide and income concentration was found an outcome that can be explained by the municipalities' different degrees of urbanization. However, for the administrative regions in the city of Rio de Janeiro, the 2 income inequality indicators were strongly correlated with the outcome variable (P < .01). Higher homicide rates were found precisely in the sector of the city that has the greatest concentration of slum residents and the highest degree of income inequality. CONCLUSIONS: The findings suggest that social policies specifically aimed at low-income urban youth, particularly programs to reduce the harmful effects of relative deprivation, may have an important impact on the homicide rate.     

Income inequality and health: the case of Rio de Janeiro

This ecological analysis addresses the association between income inequality and health status in the municipality of Rio de Janeiro. Data were analyzed using geo-processing and multiple regression techniques. The following health indicators were used: infant mortality rate; standardized mortality rate; life expectancy at birth; and homicide rate among 15-29-year-old males. Patterns of income inequality were assessed through income distribution indicators: Gini index, Robin Hood index, and top 10 %/bottom 40% average income ratio. The results indicate significant correlations between income distribution indicators and health indicators, providing additional empirical evidence of the association between health status and income inequality. For the homicide rate, the effect of the indicator "density of slum residents" was also relevant, suggesting that further deterioration in health standards may be due to social disruption of deprived communities and the resultant increase in criminal activity. The geo-epidemiological analysis presented here highlights the association between adverse health outcomes and residential concentration of poverty. Social policies focused on slum residents are needed to reduce the harmful effects of relative deprivation.     

COVID-19 Treatment: Drug Safety Prior to Conception and During Pregnancy and Breastfeeding

In December 2019, a new viral respiratory infection known as coronavirus disease 2019 (COVID-19) was first diagnosed in the city of Wuhan, China. COVID-19 quickly spread across the world, leading the World Health Organization to declare it a pandemic on March 11, 2020. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a similar virus to those involved in other epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Epidemiological studies have shown that COVID-19 frequently affects young adults of reproductive age and that the elderly and patients with chronic disease have high mortality rates. Little is known about the impact of COVID-19 on pregnancy and breastfeeding. Most COVID-19 cases present with mild flu-like symptoms and only require treatment with symptomatic relief medications, whereas other cases with COVID-19 require treatment in an intensive care unit. There is currently no specific effective treatment for COVID-19. A large number of drugs are being used to fight infection by SARS-CoV-2. Experience with this therapeutic arsenal has been gained over the years in the treatment of other viral, autoimmune, parasitic, and bacterial diseases. Importantly, the search for an effective treatment for COVID-19 cannot expose pregnant women infected with SARS-CoV-2 to the potential teratogenic risks of these drugs. Therefore, it is necessary to determine and understand the safety of anti-COVID-19 therapies prior to conception and during pregnancy and breastfeeding.Key words: COVID-19, SARS-CoV-2, antiviral, pregnancy, breastfeeding     

Encephalopathy with focal lesions due to Mycoplasma pneumoniae

Mycoplasma pneumoniae infections usually produce respiratory symptoms, that only exceptionally involve the nervous system. In this case, the infection generally causes an encephalitic picture characterized by impaired consciousness and seizures, and by normal or non-specific neuroradiological findings. However, four cases of M. pneumoniae infection associated with symmetrical lesions in the putamen and its external surrounding areas, and with extrapiramidal symptoms, have been recently published. We present the case of a patient with a clinical picture characterized by confusion, fever, and seizures, associated with a M. pneumoniae infection. The MRI study showed two symmetrical lesions that involved the areas just outside the putamen and disappeared coinciding with her clinical improvement. The present case would support that the encephalopathy associated with the M. pneumoniae infection shows a tendency to involve a particular region of the brain. Our case might represent the minimal expression of these characteristic lesions, which in the most benign cases would involve the areas immediately outside the putamen, and in other instances the putamen as well.     

Human plasma kallikrein and tissue kallikrein binding to a substrate based on the reactive site of a factor Xa inhibitor isolated from Bauhinia ungulata seeds

Kunitz type Bauhinia ungulata factor Xa inhibitor (BuXI) was purified from B. ungulata seeds. BuXI inactivates factor Xa and human plasma kallikrein (HuPK) with Ki values of 18.4 and 6.9 nM, respectively. However, Bauhinia variegata trypsin inhibitor (BvTI) which is 70% homologous to BuXI does not inhibit factor Xa and is less efficient on HuPK (Ki = 80 nM). The comparison between BuXI and BvTI reactive site structure indicates differences at Met59, Thr66 and Met67 residues. The hydrolysis rate of quenched fluorescence peptide substrates based on BuXI reactive site sequence, Abz-VMIAALPRTMFIQ-EDDnp (leading peptide), by HuPK and porcine pancreatic kallikrein (PoPK) is low, but hydrolysis is enhanced with Abz-VMIAALPRTMQ-EDDnp, derived from the leading peptide shortened by removing the dipeptide Phe-Ileu from the C-terminal portion, for HuPK (Km = 0.68 microM, k(cat)/Km = 1.3 x 10(6) M(-1) s(-1)), and the shorter substrate Abz-LPRTMQ-EDDnp is better for PoPK (Km = 0.66 microM, k(cat)/Km = 2.2 x 10(3) M(-1) s(-1)). The contribution of substrate methionine residues to HuPK and PoPK hydrolysis differs from that observed with factor Xa. The determined Km and k(cat) values suggest that the substrates interact with kallikreins the same as an enzyme and inhibitor interacts to form complexes.     

Independent Associations of the HLA-B27 Antigen and the Complement Haplotype SC21 in Chronic Anterior Uveitis

There is evidence of an association between major histocompatibility complex (MHC) genes and acute anterior uveitis; here the authors report the frequency of class I and class III MHC phenotypes in 32 Mexican mestizo patients with chronic anterior uveitis and compared them to those present in 100 ethnically matched healthy controls. Results showed in patients statistically significant increased frequencies of HLA-B(27) antigen (pC=0.02, OR=6.33, 95+ CI:1.63-26.47) and the complotype SC(21) (pC=0.04, OR=4.5, 95+ CI:1.40-14.67); the authors found a decreased frequency of HLA-B(35) (p=0.006, OR=0.10, 95+ CI: 0.00-0.65) as compared to normal controls. None of the individuals bearing the SC(21) complotype were positive for HLA-B(27), suggesting independent roles of the class I and class III antigens in the genetic susceptibility to chronic anterior uveitis.     

Recovery from Duret hemorrhage: a rare complication after craniotomy--case report

A 44-year-old female presented with Duret hemorrhage due to transtentorial herniation by extradural hematoma as a complication after craniotomy for treatment of spontaneous middle cranial fossa cerebrospinal fluid leakage through the oval window. Brain computed tomography revealed linear hemorrhage in the midbrain and the rostral pons. She awoke after 2 weeks in a coma, despite showing ocular bobbing and bilateral intranuclear ophthalmoplegia. She was discharged from the hospital with minimal neurological defects. Duret hemorrhage is usually fatal, but this case shows that early surgical decompression is the most important factor to avoid the worst sequelae.