Spatial-temporal analysis of hospitalizations with death caused by oral cancer in Brazil and its correlation with the expansion of healthcare coverage.

BACKGROUND: Oral cancer (OC) is a growing public health problem worldwide. In Brazil, the National Oral Health Policy, implemented in 2004, expanded access to oral health services and prioritized OC care. However, it is not known whether this expansion resulted in a reduction in hospital admissions with death. This study aimed to analyze the proportion of hospital admissions who progressed to death due to OC in Brazil from 2007 to 2019 and its correlation with the coverage of health services. MATERIAL AND METHODS: This study is an ecological, longitudinal, and analytical study of hospital admissions with death due to OC recorded in the Brazilian Hospital Information System. The following analyses were performed: descriptive, spatial (choropleth maps and Moran index), and negative binomial regression, with a hierarchical approach, estimating crude and adjusted regression coefficients (ß) and respective 95% confidence intervals (95% CI) (alpha=5%). RESULTS: In 2019, Moran's index (I) of spatial autocorrelation showed a negative association between hospital admissions with death and dentist surgeon/inhabitant rate (I=-0.176), physician/inhabitant rate (I=-0.157), family health strategy (FHS) coverage (I=-0.080), oral health team (OHT) coverage (I= -0.129), dental specialty centers (DSC)/inhabitant rate (I= -0.200), and oncology bed/inhabitant rate (I= -0.101). In the adjusted regression analysis, the proportion of hospitalizations with deaths caused by OC was higher in Brazilian states with a lower medical ̸inhabitant ratio (ß= -0.014; p=0.040), a lower dentists/inhabitant ratio (ß= -0.720; p=0.045), a lower number of DSC (ß= -0.004; p<0.000), a lower amount paid per hospitalization (ß= -10.350; p<0.001), and a lower number of biopsies (ß= -0.00008; p=0.010). The proportion of hospitalizations that progressed to death showed a positive association with the number of days of hospitalization (ß= 0.00002; p=0.002). CONCLUSIONS: Increased health care coverage has decreased serious hospital admissions with deaths caused by OC in Brazil.

Serious adverse events associated with yellow fever 17DD vaccine in Brazil: a report of two cases.

BACKGROUND: The yellow fever vaccine is regarded as one of the safest attenuated virus vaccines, with few side-effects or adverse events. We report the occurrence of two fatal cases of haemorrhagic fever associated with yellow fever 17DD substrain vaccine in Brazil. METHODS: We obtained epidemiological, serological, virological, pathological, immunocytochemical, and molecular biological data on the two cases to determine the cause of the illnesses. FINDINGS: The first case, in a 5-year-old white girl, was characterised by sudden onset of fever accompanied by headache, malaise, and vomiting 3 days after receiving yellow fever and measles-mumps-rubella vaccines. Afterwards she decompensated with icterus and haemorrhagic signs and died after a 5-day illness. The second patient-a 22-year-old black woman-developed a sore throat and fever accompanied by headache, myalgia, nausea, and vomiting 4 days after yellow fever vaccination. She then developed icterus, renal failure, and haemorrhagic diathesis, and died after 6 days of illness. Yellow fever virus was recovered in suckling mice and C6/36 cells from blood in both cases, as well as from fragments of liver, spleen, skin, and heart from the first case and from these and other viscera fragments in case 2. RNA of yellow fever virus was identical to that previously described for 17D genomic sequences. IgM ELISA tests for yellow fever virus were negative in case 1 and positive in case 2; similar tests for dengue, hantaviruses, arenaviruses, Leptospira, and hepatitis viruses A-D were negative. Tissue injuries from both patients were typical of wild-type yellow fever. INTERPRETATION: These serious and hitherto unknown complications of yellow fever vaccination are extremely rare, but the safety of yellow fever 17DD vaccine needs to be reviewed. Host factors, probably idiosyncratic reactions, might have had a substantial contributed to the unexpected outcome.

Studies on the periodicity and intravascular distribution of Wuchereria bancrofti microfilariae in paired samples of capillary and venous blood from Recife, Brazil.

We examined the periodicity and intravascular distribution of Wuchereria bancrofti microfilariae (mf) and determined the effect of these parasite properties on the accuracy of blood filming and filtration methods for diagnosis of bancroftian filariasis in the endemic area of Recife, Brazil. Microfilariae in both venous and capillary blood exhibited a nocturnal periodicity pattern with a relatively high amplitude. Overall, capillary blood contained approximately 1.25 times the number of mf present at the same time in the same volume of venous blood. However, the ratio of mf present in capillary and venous blood varied over a 24-hour period, so that the fewest mf were present in the capillary bed of the skin at the time when biting activity of the local Culex vector is the lowest. Twenty or 60 microliters blood films did not reliably detect carriers with fewer than 100 or 60 mf/ml venous blood, respectively, and were thus inadequate for the identification of low density mf carriers. In contrast, all carriers with > 1 mf/20 or 60 microliters blood smear at night could be identified during daytime hours by filtration of 1 micromilligram venous blood.

Comparative efficacy of three different diethylcarbamazine regimens in lymphatic filariasis.

To assess the efficacy of diethylcarbamazine (DEC) in clearing Wuchereria bancrofti microfilariae (mf) from the circulation, we conducted a single blind hospital-based therapeutic trial of 3 DEC regimens. All patients were assessed by filtration of 1 mL of venous blood taken before and 1, 3, 6 and 12 months after DEC administration. The efficacy of a 12 d course of 6 mg/kg DEC once daily was identical to that of a similar course with 2 mg/kg given 3 times daily, indicating that split-dose treatment does not improve mf clearance over single daily drug administration. Microfilarial densities in patients treated only once with 6 mg/kg DEC remained significantly higher at 1, 3, and 6 months after treatment. However, all 3 treatment regimens proved equally effective in controlling microfilaraemia after 12 months, when 41, 42 and 40% of patients in the 3 treatment groups were amicrofilaraemic. These results suggest that a single DEC dose of 6 mg/kg administered annually or biannually may be a suitable regimen to control bancroftian filariasis in Recife, Brazil.

Treatment of bancroftian filariasis in Recife, Brazil: a two-year comparative study of the efficacy of single treatments with ivermectin or diethylcarbamazine.

The effectiveness of single oral doses of ivermectin (200 or 400 micrograms/kg) and diethylcarbamazine (DEC, 6 mg/kg), preceded 4 d earlier by either placebo or very small doses of these drugs, was compared, over a 2-year period, in a double-blind trial in 67 microfilaraemic Brazilian men with bancroftian filariasis. Regimens containing ivermectin alone decreased the number of microfilariae significantly faster and more effectively for the first month after treatment than regimens containing DEC alone, but the latter were significantly more effective throughout the second year after treatment (1.7-8.2% of pretreatment levels with DEC vs. 12.6-30.8% with ivermectin during that period); the higher ivermectin dose showed a tendency towards more effectiveness than the lower dose. Most effective was the combination of ivermectin (20 micrograms/kg) followed 4 d later by DEC (6 mg/kg), with reduction of microfilaraemia to 2.4% of pretreatment levels at 2 years. Adverse reactions were well tolerated with all regimens, the reactions being significantly more generalized (i.e., fever) following ivermectin and localized (i.e., scrotal inflammatory nodules around dying adult worms) following DEC. Further trials of single-dose combination therapy vs. single high doses of ivermectin or DEC should determine the ideal regimen for treatment and control of bancroftian filariasis.

Tolerance of diethylcarbamazine by microfilaraemic and amicrofilaraemic individuals in an endemic area of Bancroftian filariasis, Recife, Brazil.

To determine the tolerance to diethylcarbamazine (DEC) treatment of patients with Bancroftian filariasis, 193 individuals (138 asymptomatic microfilaraemic, 30 amicrofilaraemic diseased patients and 25 asymptomatic amicrofilaraemic endemic residents) were enrolled in a prospective trial with different dose schedules, in a hospital and outpatient clinic setting in Brazil. Systemic adverse reactions, localized adverse reactions, and side effects, related to microfilariae, adult worms and the drug itself, were evaluated. Systemic reactions occurred irrespective of the DEC dose and schedule in about 40% of the microfilariae carriers, but not in amicrofilaraemic diseased patients or residents; they usually consisted of microscopic haematuria, followed by fever and malaise. Localized reactions were manifested by the appearance of inflammatory reactions, mainly in the scrotal area. Nodules containing degenerating adult worms developed mainly in the scrotal lymphatics of microfilaraemic patients, diseased amicrofilaraemic patients, and residents. Drowsiness, which increased with higher doses of DEC, was the most common side effect in both microfilaraemic and amicrofilaraemic individuals, followed by nausea and gastric upset. The results indicate that the occurrence of systemic and local adverse reactions was unrelated to either the dose of DEC or the pretreatment microfilarial density. The severity of systemic reactions was proportional to the microfilarial density. Side effects were dependent on the drug dosage irrespective of infection status.

Ivermectin treatment of bancroftian filariasis in Recife, Brazil.

To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 micrograms/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment, the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife, Brazil. Follow-up at one year indicated equivalent efficacy for the 20-, 100-, and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means of 13-25% of pretreatment levels. Adverse clinical reactions (predominantly fever, headache, weakness, and myalgia) occurred to some degree in almost all patients but generally lasted only 24-48 hr and were easily managed symptomatically. Adverse reactions were significantly milder in those receiving the lowest (20 micrograms/kg) ivermectin dose, and they were significantly correlated with individuals' pretreatment microfilaremia levels in all groups. Posttreatment eosinophilia was a regular feature of the response to treatment, with the magnitude and kinetics also proportional to pretreatment microfilarial levels. Transient pulmonary function abnormalities (16 of 42, 38%), liver enzyme elevations (10 of 43, 23%), and hematuria (9 of 42, 22%) developed posttreatment, but all cleared without significant complications. The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin, that the drug's systemic adverse reactions are essentially those resulting from parasite clearance, and that the intensity of these reactions can be significantly reduced by using the low (20 micrograms/kg) dose of ivermectin. This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications.

Wuchereria bancrofti: freeze-fracture study of the epicuticle of microfilariae.

The freeze-fracture technique was used to analyze the surface of microfilariae of Wuchereria bancrofti. The examination of thin sections showed that the epicuticle is formed by two closely apposed membrane-like structures, appearing as hepta-laminated structures. Freeze-fracture replicas revealed the presence of two fracture faces. The outer one is smooth but presents rosette-like structures. The inner face, which is in contact with the hypodermal cells, presents a large number of particles.

Immunocytochemical localization of surface and intracellular antigens recognized by human sera in microfilariae of Wuchereria bancrofti.

Sera from patients with various clinical pictures of lymphatic filariasis, including tropical pulmonary eosinophilia (TPE), were used for the localization of surface and intracellular antigens in microfilariae of Wuchereria bancrofti embedded in Lowicryl K4M. Very few or no antigenic sites were located on the outer face of the sheath. The most inner layer, as well as the space between the cuticle and the sheath, was intensely labeled. Sera from TPE patients intensely labeled the cuticle and the cytoplasm of muscle cells.

Wuchereria bancrofti microfilarial density of autochthonous cases and natural Culex infectivity rates in northeast Brazil.

Autochthonous Wuchereria bancrofti microfilaraemic cases from three neighbouring cities of Northeast Brazil (Recife, Jaboatao and Olinda) were selected from thick smear or filtration positive individuals and classified by their microfilarial (mf) densities through polycarbonate membrane blood filtration. Individuals were subdivided into two groups: autochthonous cases without any previous specific drug administrations (group A) and those with one or more previous DEC treatments (group B). In Recife, unlike Jaboatao and Olinda (P less than 0.05), the majority of autochthonous cases were over 20 years old and no microfilaraemics were found under the age of 10. The majority of cases in Recife had lower levels of mf density (66.6%), while in Jaboatao and Olinda higher mf carriers (65.6%) prevailed when group A (n = 141) individuals were rearranged in mf density above and below 500 mf ml-1 (P less than 0.01). All subjects in group B (n = 110) had less than 501 mf ml-1 and the great majority less than 100 mf ml-1, but a significant difference (P less than 0.05) between Recife and the two other cities was observed. Captured mosquitoes in Recife, Jaboatao and Olinda totalled 7856, 8010 and 8003 respectively. The infectivity rate found in Recife (0.61%) was significantly lower than in Jaboatao (1.21%) and Olinda (1.31%) (P less than 0.001). The authors discuss the possible influences of previous disease control programmes (medicated salt and individual treatments) applied only to the city of Recife in relation to the outcome of this investigation.

Immunocytochemical localization of surface antigens in microfilariae of Wuchereria bancrofti.

Antigenic sites were localized on the surface structure (sheath and cuticle) of microfilariae of Wuchereria bancrofti using sera from microfilaraemic and amicrofilaraemic patients using antibodies associated to colloidal gold particles and transmission electron microscopy. No labeling was observed on the surface of intact parasites. Microfilariae without the sheath and isolated sheath were obtained by ultrasound treatment. Using these preparations labeling of the inner portion of the sheath was observed when sera from amicrofilaraemic patients were used. Labeling of the cuticle surface was observed mainly in the regions of the cuticular annulations.

Fine structure and localization of anionic sites on the surface of microfilaria of Wuchereria bancrofti.

The fine structure of the sheath and the cuticle of microfilaria of Wuchereria bancrofti was analysed and the results obtained were compared with those from other filarial parasites. Cationized ferritin particles bind to the surface of the sheath and the epicuticle. No binding of colloidal iron hydroxyde particles to the microfilaria surface was observed. Reaction product indicative of carbohydrates containing vic-glycol groups was not observed in thin sections of microfilaria submitted to the periodic acid-thiosemicarbazide-silver proteinate technique. The results obtained are discussed in relation to previous studies using lectins.