Pre-vaccination screening strategies for the use of the CYD-TDV dengue vaccine: A meeting report.

The first licensed dengue vaccine, CYD-TDV (Dengvaxia) is efficacious in seropositive individuals, but increases the risk for severe dengue in seronegative persons about two years after administration of the first dose. For countries considering the introduction of Dengvaxia, WHO recommends a pre-vaccination screening strategy whereby only persons with evidence of a past dengue infection would be vaccinated. Policy-makers need to consider the risk-benefit of vaccination strategies based on such screening tests, the optimal age to introduce the vaccine, communication and implementation strategies. To address these questions, the Global Dengue and Aedes-transmitted diseases Consortium (GDAC) organized a 3-day workshop in January 2019 with country representatives from Asia and Latin America. The meeting discussions highlighted many challenges in introducing Dengvaxia, in terms of screening test characteristics, costs of such tests combined with a 3-dose schedule, logistics, achieving high coverage rates, vaccine confidence and communication; more challenges than for any other vaccine introduction programme. A screening test would require a high specificity to minimize individual risk, and at the same time high sensitivity to maximize individual and population benefit. The underlying seroprevalence dependent positive predictive value is the best indicator for an acceptable safety profile of a pre-vaccination screening strategy. The working groups discussed many possible implementation strategies. Addressing the bottlenecks in school-based vaccine introduction for Dengvaxia will also benefit other vaccines such as HPV and booster doses for tetanus and pertussis. Levels of public trust are highly variable and context specific, and understanding of population perceptions and concerns is essential to tailor interventions, monitor and mitigate risks.

Estimating health service utilization for treatment of pneumococcal disease: the case of Brazil.

BACKGROUND: Health service utilization (HSU) is an essential component of economic evaluations of health initiatives. Defining HSU for cases of pneumococcal disease (PD) is particularly complex considering the varying clinical manifestations and diverse severity. OBJECTIVE: We describe the process of developing estimates of HSU for PD as part of an economic evaluation of the introduction of pneumococcal conjugate vaccine in Brazil. METHODS: Nationwide inpatient and outpatient HSU by children under-5 years with meningitis (PM), sepsis (PS), non-meningitis non-sepsis invasive PD (NMNS), pneumonia, and acute otitis media (AOM) was estimated. We assumed that all cases of invasive PD (PM, PS, and NMNS) required hospitalization. The study perspective was the health system, including both the public and private sectors. Data sources were obtained from national health information systems, including the Hospital Information System (SIH/SUS) and the Notifiable Diseases Information System (SINAN); surveys; and community-based and health care facility-based studies. RESULTS: We estimated hospitalization rates of 7.69 per 100,000 children under-5 years for PM (21.4 for children <1 years of age and 4.3 for children aged 1-4 years), 5.89 for PS (20.94 and 2.17), and 4.01 for NMNS (5.5 and 3.64) in 2004, with an overall hospitalization rate of 17.59 for all invasive PD (47.27 and 10.11). The estimated incidence rate of all-cause pneumonia was 93.4 per 1000 children under-5 (142.8 for children <1 years of age and 81.2 for children aged 1-4 years), considering both hospital and outpatient care. DISCUSSION: Secondary data derived from health information systems and the available literature enabled the development of national HSU estimates for PD in Brazil. Estimating HSU for noninvasive disease was challenging, particularly in the case of outpatient care, for which secondary data are scarce. Information for the private sector is lacking in Brazil, but estimates were possible with data from the public sector and national population surveys.

Cost-effectiveness analysis of universal childhood vaccination against varicella in Brazil.

This study conducts a cost-effectiveness analysis of a childhood universal varicella vaccination program in Brazil. An age and time-dependent dynamic model was developed to estimate the incidence of varicella for 30 years. Assuming a single-dose schedule; vaccine efficacy of 85% and coverage of 80%, the program could prevent 74,422,058 cases and 2905 deaths. It would cost R$ 3,178,396,110 and save R$ 660,076,410 to the society and R$ 365,602,305 to the healthcare system. The program is cost-effective (R$ 14,749 and R$ 16,582 per life-year saved under the societal and the healthcare system's perspective, respectively). The program's cost-effectiveness is highly sensitive to the vaccine price and number of doses.

Manifestations of Chagas disease (American trypanosomiasis) in patients with HIV/AIDS.

Between June 1989 and December 2005, an observational study of adults co-infected with HIV and Trypanosoma cruzi was conducted, to investigate the spectrum of manifestations of chronic Chagas disease (American trypanosomiasis) in the HIV-positive. The 31 men and 22 women investigated were aged 23-59 years. Each subject was investigated by ambulatory (Holter) and non-ambulatory electrocardiography, chest X-ray, oesophagography and echocardiography (to determine the clinical form of trypanosomiasis), by xenodiagnosis, blood culture and the microscopical examination of blood (to explore their T. cruzi parasitaemia), and by counting their CD4 T cells (to stage their HIV infection). The subjects were followed-up for 1-190 months (median = 58 months) and checked for re-activation of their Chagas disease, which was usually defined by the occurrence of unusual clinical manifestations and/or the detection, by microscopical examination, of trypanosomes in the blood or cerebrospinal fluid. Eleven (20.8%) of the subjects showed re-activation, another nine (17.0%) were found to have developed high T. cruzi parasitaemias but these were only detected by xenodiagnosis or culture, and 15 (28.3%) had illnesses typical of chronic Chagas disease in HIV-negative individuals, with low parasitaemias. Anti-T. cruzi therapy (benznidazole), recommended for 17 patients, resulted in the sustained reduction of parasitaemia in 11 of the 12 subjects who completed treatment. Chagas disease was the cause of death of eight of the 14 subjects who died during the study. Four of the women investigated gave birth, each to a single child, during follow-up, and three of the four babies showed evidence of the congenital transmission of T. cruzi.

Parasitemia por Trypanosoma cruzi em pacientes com doenca de Chagas cronica co-infectados por virus da imunodeficiencia humana (HIV) / Trypanosoma cruzi parasitemia in patients with chronic Chagas' disease and human immunodeficiency virus (HIV) coinfection

Avaliar a parasitemia por T.cruzi em individuos com doenca de Chagas cronica, comparando pacientes co-infectados pelo HIV e soronegativos para HIV; investigar a relacao entre a parasitemia e o numero de celulas T CD4+ no sangue, a carga viral de HIV no plasma e o diagnostico de aids; avaliar se ha um nivel de parasitemia indicativo da reativacao da tripanosomiase. Foram estudados 110 pacientes com doenca de Chagas cronica: 29 soropositivos e 81 soronegativos para HIV, com idade entre 25 e 61 anos. Os pacientes foram submetidos a tres avaliacoes seriadas com realizacao de xenodiagnostico in vitro, hemocultura para T.cruzi e pesquisa microscopica direta do prasito no sangue. A parasitemia foi significativamente mais frequente nos pacientes co-infectados por HIV(80,9 porcento) do que nos pacientes soronegativos para HIV (35,3 porcento). Os pacientes co-infectados por HIV apresentaram tambem niveis mais elevados de parasitemia. Nao foi observada correlacao entre a parasitemia e a contagem de celulas T CD4+, a carga viral de HIV ou o diagnostico de aids. Reativacao da doenca de Chagas foi diagnosticada em 17,2 porcento (5/29) dos pacientes co-infectados, tendo sido observadas formas oligossintomaticas. Diante de xenodiagnostico com mais de 20 porcento de ninfas positivas, deve-se considerar a possibilidade de reativacao da tripanosomiase. A co-infeccao por HIV resulta em exacerbacao da parasitemia por T.cruzi em pacientes com doenca de Chagas cronica.