Hospitalizations and deaths due to pertussis in children from 1996 to 2013☆ / Internações e óbitos por coqueluche em crianças no período entre 1996 e 2013

ABSTRACT OBJECTIVES: To assess temporal trends of hospitalizations and deaths from pertussis in Brazilian children in the period of 1996-2013. METHODS: This was a descriptive ecological study of temporal trends, based on the DATASUS database. The number of hospitalizations and deaths from pertussis in children up to 19 years of age from January 1996 to December 2013 was obtained. Descriptive statistics were applied for data analysis. RESULTS: During the study period, a total of 19,047 hospital admissions from pertussis were recorded, of which 88.2% occurred in infants younger than 1 year. In the period 1996-2010, the mean annual number of admissions was 755, ranging from a maximum of 1179 in 2004 to a minimum of 400 in 2010. There was an increase of admissions in the last three consecutive years (2011, 2012, and 2013) with 1177, 2954 and 3589 hospitalizations, respectively. There were 498 deaths from pertussis throughout the study period, of which 96.8% occurred in children younger than one year. There was an increase in the number of deaths from pertussis in children in the years 2011, 2012, and 2013, with 40, 93, and 87 recorded deaths, respectively. The increase in hospitalizations and deaths from pertussis in children occurred in all regions of the country, with the highest increase observed in the Southeast, North and Northeast regions. CONCLUSIONS: There was a substantial increase in hospitalizations and deaths from pertussis in children for three consecutive years (2011, 2012, and 2013) in all Brazilian regions. The most affected age group was that of children younger than one year.

RESUMO OBJETIVOS: Avaliar a tendência temporal de internações e óbitos por coqueluche em crianças brasileiras de 1996 a 2013. MÉTODOS: Trata-se de um estudo ecológico descritivo de tendência temporal, baseado no banco de dados Datasus. Foram extraídos os números de internações e de óbitos por coqueluche em crianças até 19 anos de janeiro de 1996 a dezembro de 2013. A estatística descritiva foi aplicada para análise de dados. RESULTADOS: No período estudado foram registradas 19.047 internações por coqueluche, das quais 88,2% foram de lactentes menores de um ano. De 1996 a 2010, o número médio anual de internações foi de 755 e oscilou entre o máximo de 1.179 em 2004 e o mínimo de 400 em 2010. Houve um acréscimo de internações nos últimos três anos consecutivos (2011, 2012 e 2013), com 1.177, 2.954 e 3.589 registros, respectivamente. Ocorreram 498 óbitos por coqueluche em todo o período estudado, dos quais 96,8% eram menores de um ano. Houve acréscimo no número de óbitos por coqueluche em crianças em 2011, 2012 e 2013, com 40, 93 e 87 registrados, respectivamente. O aumento de internações e óbitos por coqueluche em crianças ocorreu em todas as regiões do país e houve maior acréscimo nas regiões Sudeste e Norte-Nordeste. CONCLUSÕES: Houve um aumento substancial de internações e de óbitos por coqueluche em crianças por três anos consecutivos (2011, 2012 e 2013) em todas as regiões brasileiras. A faixa etária mais atingida foi a de menores de um ano.

Hospitalizations and deaths due to pertussis in children from 1996 to 2013.

OBJECTIVES: To assess temporal trends of hospitalizations and deaths from pertussis in Brazilian children in the period of 1996-2013. METHODS: This was a descriptive ecological study of temporal trends, based on the DATASUS database. The number of hospitalizations and deaths from pertussis in children up to 19 years of age from January 1996 to December 2013 was obtained. Descriptive statistics were applied for data analysis. RESULTS: During the study period, a total of 19,047 hospital admissions from pertussis were recorded, of which 88.2% occurred in infants younger than 1 year. In the period 1996-2010, the mean annual number of admissions was 755, ranging from a maximum of 1179 in 2004 to a minimum of 400 in 2010. There was an increase of admissions in the last three consecutive years (2011, 2012, and 2013) with 1177, 2954 and 3589 hospitalizations, respectively. There were 498 deaths from pertussis throughout the study period, of which 96.8% occurred in children younger than one year. There was an increase in the number of deaths from pertussis in children in the years 2011, 2012, and 2013, with 40, 93, and 87 recorded deaths, respectively. The increase in hospitalizations and deaths from pertussis in children occurred in all regions of the country, with the highest increase observed in the Southeast, North and Northeast regions. CONCLUSIONS: There was a substantial increase in hospitalizations and deaths from pertussis in children for three consecutive years (2011, 2012, and 2013) in all Brazilian regions. The most affected age group was that of children younger than one year.

Suffer the Infants: A Severe Case of Pertussis in Oregon, 2012.

Pertussis remains a public health concern in Oregon, especially among young infants. The disease can be severe in this age group and is associated with a high inpatient cost. This report describes an Oregon infant who was hospitalized with pertussis for 90 days, required extracorporeal oxygenation for 43 days, suffered complications including stroke, and had hospital charges totaling $1.5 million. Pertussis morbidity among young infants argues for vaccination of women during each pregnancy and of infants beginning promptly at two months of age.

Estimation of the serial interval of pertussis in Dutch households.

Increasing incidence has led to the re-appearance of pertussis as a public health problem in developed countries. Pertussis infection is usually mild in vaccinated children and adults, but it can be fatal in infants who are too young for effective vaccination (≤3 months). Tailoring of control strategies to prevent infection of the infant hinges on the availability of estimates of key epidemiological quantities. Here we estimate the serial interval of pertussis, i.e., the time between symptoms onset in a case and its infector, using data from a household-based study carried out in the Netherlands in 2007-2009. We use statistical methodology to tie infected persons to probable infector persons, and obtain statistically supported stratifications of the data by person-type (infant, mother, father, sibling). The analyses show that the mean serial interval is 20 days (95% CI: 16-23 days) when the mother is the infector of the infant, and 28 days (95% CI: 23-33 days) when the infector is the father or a sibling. These time frames offer opportunities for early mitigation of the consequences of infection of an infant once a case has been detected in a household. If preventive measures such as social distancing or antimicrobial treatment are taken promptly they could decrease the probability of infection of the infant.

Acellular pertussis vaccines in China.

In China, whole-cell pertussis (Pw) vaccines were produced in the early 1960s and acellular pertussis (Pa) vaccines were introduced in 1995. Pa vaccines have now almost completely replaced Pw vaccines in the national immunization program. To strengthen the regulation of vaccines used in China, a vaccine lot release system was established in 2001 and Pa vaccines have been included in the system since 2006. This paper mainly described the current status of production and the quality control measures in place for Pa vaccines; and analyses quality control test data accumulated between 2006 and 2010.

[Laboratory assessment problems of the efficacy of acellular pertussis vaccines]. / Problemy laboratoryjnej oceny skutecznosci bezkomórkowych szczepionek przeciw krztuscowi.

Although composition of acellular pertussis vaccines is better defined than whole-cell vaccines, differences in the formulation, content, and detoxification of pertussis vaccine antigens led to a unique character of each of differently produced acellular vaccine. Currently used methods for laboratory evaluation of whole-cell pertussis vaccine efficacy were found not suitable for acellular vaccines. There is a strong need to perform analysis and evaluation of the safety and efficacy profiles of acellular pertussis vaccines combined with other vaccine antigens (e.g. Hib) both before and after conjugation. Mechanisms of interactions seen after conjugation inducing weaker immunogenicity or efficacy are still poorly recognized.

Comparison of the bioactivity of reference preparations for assaying Bordetella pertussis toxin activity in vaccines by the histamine sensitisation and Chinese hamster ovary-cell tests: assessment of validity of expression of activity in terms of protein concentration.

Pertussis toxin (PT) in its detoxified form is an important antigenic component of both acellular and whole cell pertussis vaccines. Limits on the content of active PT in acellular vaccines are set in official monographs (EP, WHO, USP) and evidence of compliance is therefore, required by regulatory authorities. The two assay methods which are currently used by most manufacturers and official national control laboratories to monitor residual PT activity in acellular pertussis vaccines (and also in whole cell vaccines) are histamine sensitising (HIST) assays and Chinese hamster ovary (CHO) cell assays. Currently, different reference preparations of PT are used by individual laboratories for these tests. We therefore organised an international collaborative study to examine, by these two assay methods, two freeze-dried purified preparations of PT, one preparation in ampoules coded JNIH-5 and one preparation in ampoules coded 90/518, together with in-house reference (IHR) preparations in current use. Data from this study confirm that both JNIH-5 and 90/518 show biological activity both in HIST assays and in CHO-cell assays. Both HSD50 and ED50 values obtained in this study differ significantly between laboratories and thus show that biological activity is not determined by the nominal masses of preparations. Estimates of relative potency of 90/518 in terms of JNIH-5 per ampoule for the HIST assays do not differ significantly between laboratories. The overall mean estimates of relative potency of 90/518 in terms of JNIH-5 do not differ significantly between the two methods. Data from this study further indicate that the biological activity of different preparations was not directly related to their stated protein content. The use of protein content to indicate the level of PT activity in different preparations would give misleading results. Thus, use of a common standard is shown to greatly improve between laboratory agreement of estimates.

Pertussis vaccines: past, present and future in Australia.

In August 1997, a workshop was convened by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases to consider current issues in the use of pertussis vaccines and implications for the Australian immunisation schedule. Topics covered included the history, efficacy and reactogenicity of whole-cell and acellular vaccines and vaccine schedules. Acellular pertussis vaccine is preferred by the National Health and Medical Research Council for the primary course as well as the 18 month and 4-5 year old childhood doses. At the time of the workshop, a 3-component acellular vaccine (DTPa) had been approved (licensed) in Australia for all doses in the childhood schedule. It was the first vaccine subject to a cost-effectiveness evaluation under the new vaccine funding arrangements. Issues considered in the evaluation of the cost-effectiveness of the vaccine were discussed. These included comparative efficacy, adverse events and compliance, and the question of community as well as individual benefit from the use of the vaccine.

Development of pertussis serological potency test. Serological assessment of antibody response induced by whole cell vaccine as an alternative to mouse protection in an intracerebral challenge model.

The current potency test for pertussis vaccines, the mouse protection test (MPT), has many disadvantages. However, no alternative is yet available. The purpose of this study is to develop a serological alternative for the MPT based on in vitro assessment of the humoral immune response against pertussis in mice. After immunization with pertussis whole cell vaccine, the MPT shows a normal primary and secondary antibody response. Moreover, the i.c. challenge has a distinct booster effect on the pertussis IgG response. The relationship between the concentration of IgG antibodies against the surface-antigens of pertussis bacteria and the survival of mice after the i.c. challenge was demonstrated in a modified MPT (R = 0.91). To this end a protecting antibody level of > or = 45 EU/ml was selected as a level at which concentration most of the mice survived. Survival of mice in the MPT could be predicted, based on the antibody concentration at the day of challenge. Potencies estimated with the predicted and actual survival corresponded well (P = 0.990). This confirmed the essential role of vaccine induced pertussis antibodies in the protection against a lethal i.c. challenge and offered a possibility to develop a pertussis potency test based on serology. We developed a model in which mice (20-24 g) are immunized (i.p.) with graded doses of vaccine and bled after four weeks. Sera are titrated in Bordetella pertussis whole cell ELISA and potency based on vaccine dose dependent antibody response is estimated by means of a parallel line analysis. The potency of vaccines tested in the Pertussis Serological Potency Test (PSPT) and MPT are significantly similar, a P-value of 0.92 was found by means of the chi 2 test. Compared to the MPT, the PSPT is more reproducible as is indicated by its smaller 95% confidence intervals. Moreover, by using the PSPT the animal distress can be reduced to an acceptable level and the PSPT also results in a reduction of more than 25% in use of mice.

Studies on the minimal number of animals required to achieve assurance of satisfactory potency in diphtheria and tetanus vaccines.

The purpose of the potency test for adsorbed diphtheria and tetanus vaccines prescribed in the European Pharmacopoeia is to provide 97.5% assurance that the minimum requirement for potency is exceeded. In order to achieve this the use of at least six groups of sixteen guinea pigs or mice is prescribed. In some formulations, particularly of combined vaccines, the potency exceeds the minimum requirements by a very large margin and the numbers of animals used in the test appear to be unnecessarily large. Data are presented which show that 97.5% assurance of satisfactory potency can be consistently achieved with substantially smaller numbers of animals than are used at present. It is suggested that the prescription of large numbers of animals in routine issue tests for diphtheria and tetanus vaccines is unnecessary and inappropriate except in cases where the potency of the vaccine is in dispute.

Potency measurement of pertussis vaccines and consistency in production.

If one accepts the minimum requirement of 4 i.u. shd-1 for the potency of pertussis vaccine--and there is no convincing evidence to reject this--the usual MPT with 20 mice per dilution offers a sufficient guarantee that no vaccines with too low potency will be accepted, provided that the consistency in production has been sufficiently proven. As higher concentrations than necessary should be avoided in view of the undesirable side-effects, the establishment of requirements for the lower level of the 95% confidence limits might, however, entail exactly this risk.