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.

Reactivation of Chagas' disease in a human immunodeficiency virus-infected patient leading to severe heart disease with a late positive direct microscopic examination of the blood.

We report a human immunodeficiency virus (HIV)-infected man with chronic Chagas' disease who developed a congestive heart failure that could not be clinically controlled. Endomyocardial biopsy revealed severe myocarditis and the xenodiagnosis result was positive, but Trypanosoma cruzi by direct microscopic examination of the blood was found only four months after the symptoms had started. Treatment with benznidazole was effective in reducing parasitemia, stabilizing the clinical status, and controlling tissue damage related to the parasite. Although the finding of T. cruzi trypomastigotes by direct microscopic examination of the blood has been considered the mark of Chagas' reactivation in immunocompromised patients with chronic disease, in this case it was a late finding.

Clinical analysis and parasite genetic diversity in human immunodeficiency virus/Chagas' disease coinfections in Brazil.

To evaluate the possible role of parasitemia on Chagas' disease reactivation in Chagas' disease/human immunodeficiency virus (HIV) coinfection cases and the impact of HIV coinfection on Trypanosoma cruzi genetic diversity, 71 patients with Chagas' disease (34 HIV+ and 37 HIV-) were surveyed. Moreover, 92 T. cruzi stocks from 47 chronic chagasic patients (29 HIV+ and 18 HIV-) were isolated and analyzed by multilocus enzyme electrophoresis and a random amplified polymorphic DNA procedure. High parasitemia appeared to play a major role in cases of Chagas' disease reactivation. In HIV+ patients, the genetic diversity and population structure (clonality) of T. cruzi was similar to that previously observed in HIV- patients, which indicates that immunodepression does not modify drastically genotype repartition of the parasite. There was no apparent association between given T. cruzi genotypes and specific clinical forms of Chagas' disease/HIV associations.

Hyperlipidemia related to the use of HIV-protease inhibitors: natural history and results of treatment with fenofibrate.

Hyperlipidemia has been frequently recorded as a side effect of treating HIV patients with protease inhibitors (PI). This study was initiated to analyze the modifications on blood lipids in HIV-patients receiving PI and the safety and efficacy of the treatment with fenofibrate. Total (TC) and HDL-cholesterol, triglycerides (TG), and CD(4)(+) T-cell counts were measured in 30 HAART-naive patients (Group I) before and after PI introduction. In a second phase of the study, the effects of fenofibrate on lipids, CPK, CD(4)(+), and viral load were determined in 13 patients (Group II) with elevated TC or TG. In Group I, 60% of the patients showed TC or TG elevations. Average increments of 31% and 146% in TC and TG respectively (p<0.0006 and p<0.0001) were observed. In Group II, fenofibrate treatment was associated with decrements of 6.6% (TC) and 45.7% (TG) (p=0.07 and 0.0002) and no modifications on CPK, CD(4)(+), and viral load. In conclusion, hyperlipidemia is common during the treatment of HIV with protease inhibitors, and fenofibrate appears to be an effective and safe choice for its treatment.

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.

Follow-up of 18 patients with human immunodeficiency virus infection and chronic Chagas' disease, with reactivation of Chagas' disease causing cardiac disease in three patients.

A series of 18 patients with chronic Chagas' disease and human immunodeficiency virus infection were followed up for 2 to 66 months (median, 15.5 months). Artificial xenodiagnosis was positive for 81.3% and natural xenodiagnosis was positive for 81.8% of patients for whom they were performed; 81.8% of 11 patients had medium- or high-level parasitemia. Reactivation of Chagas' disease--direct microscopic examination of blood revealing parasites and, clinically, patients presenting with cardiac disease--occurred in three patients (16.7%). Specific antitrypanosomal treatment with benznidazole was effective in reducing the level of parasitemia and improving the clinical condition in three of the four patients treated.

[Predictive factors of abandoning treatment in tuberculosis patients]. / Fatores preditivos de abandono de tratamento por pacientes com tuberculose.

In spite of the efforts to control the spread of tuberculosis worldwide this disease remains one of the biggest problems in public health. Multiresistance has a dramatic effect in this scenario. Non compliance with treatment is directly related to disease spread and the appearance of multiresistance bacilli. Aiming to verify if it is possible to identify patients prone to non compliance from data obtained in the first visit we have studied a population enrolled in a prospective study. Among 257 consecutive patients evaluated between january 1991 and january 1994, we compared 87 patients that abandoned treatment before six months (group A) with 97 that completed six months of treatment (group C). The abandon rate in this group as 33.85% which is larger than 12.9% rate reported by the Health Ministry. Comparing A to C, only the prevalence of alcoholism (A 33.3% x C 22.5%, p = 0.015) and risk behavior for HIV infection (A 27.6% x C 10.2%, p = 0.046), as well as the frequency of non pulmonary disease (A 38.0% x C 24.5%, p = 0.034) were significantly different between both groups. Regarding the moment of abandon (0, 1st or 3rd month) there was no difference in the A group. We conclude that patients at high risk of abandoning tuberculosis treatment can be identified with data obtained at the first visit, allowing to establish a different policy such as supervised treatment for this population.

Simultaneous occurrence of acute myocarditis and reactivated Chagas' disease in a patient with AIDS.

Myocarditis is not an uncommon finding in autopsy series of patients with AIDS, although clinically important myocarditis is rarely noted. We describe a 50-year-old woman with AIDS and chronic chagasic megaesophagus, without previous cardiac abnormalities, who experienced reactivation of Chagas' disease, characterized by the finding of Trypanosoma cruzi via direct microscopic examination of the buffy coat, xenodiagnosis, and blood culture; she developed fatal acute myocarditis. Reactivation of Chagas' disease in patients with AIDS has been reported, but in the great majority of cases it has been associated with central nervous system involvement. In areas where Chagas' disease is endemic, reactivation may occur in patients with AIDS.

Neonatal rat exposure to pyrethroid and organophosphate insecticides: a physiological and biochemical trial of progeny

A manufactured product (Ectoplus R) composed by a cypermethrin (44,7 por cento) and dichlorvos (4,2 por cento) mixture was administered (10mg-day, orally, by gavage) to pregnant rats, during the periods of gestation+lactation, gestation, and lactation. Controlmothers received vehicle aqueous solution during the gestation+lactation period. With the progeny, in the 1-15 post-natal days (PND1-15) there were observed alterations in the periods of occurrence of teeth, hair, unfolding of ears, and in the developmental period for following reflexes: postural, palmar grasp, negative geotaxis, and acoustic startle reflex. After weaning (PND21), there were observed the presence of cypermethrin and dichlorvos in the blood brain and liver, decrease in weight of liver, of cholinesterase activity in the plasma, liver, and brain, and hepatic metabolizing activity of drugs, alterations of levels of gamma glutamyl transferase enzymes, of creatinine, and of potassium in the serum of the animals. In conclusion, neonatal exposure to a formulated mixture of cypermethrin and dichlorvos is inductive to alterations in characteristics that indicate somatic and neuromuscular development of the progeny, and in certain biochemical parameters. The results suggest that enzymatic assessment associated with somatic and neuromotor assessment can be important markers of developmental characteristics in neonatal toxicity by pesticide formulations based on mixtures of insecticides.

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.