Neglected tropical diseases in Brazil

Poverty is intrinsically related to the incidence of Neglected Tropical Diseases (NTDs). The main countries that have the lowest human development indices (HDI) and the highest burdens of NTDs are located in tropical and subtropical regions of the world. Among these countries is Brazil, which is ranked 70th in HDI. Nine out of the ten NTDs established by the World Health Organization (WHO) are present in Brazil. Leishmaniasis, tuberculosis, dengue fever and leprosy are present over almost the entire Brazilian territory. More than 90% of malaria cases occur in the Northern region of the country, and lymphatic filariasis and onchocerciasis occur in outbreaks in a particular region. The North and Northeast regions of Brazil have the lowest HDIs and the highest rates of NTDs. These diseases are considered neglected because there is not important investment in projects for the development of new drugs and vaccines and existing programs to control these diseases are not sufficient. Another problem related to NTDs is co-infection with HIV, which favors the occurrence of severe clinical manifestations and therapeutic failure. In this article, we describe the status of the main NTDs currently occurring in Brazil and relate them to the HDI and poverty.

Accidental Epinephrine Administration

A administração intravenosa acidental de adrenalina é um erro raro mas potencialmente fatal. Descrevemos um caso de uma mulher de 74 anos que durante uma intervenção cirúrgica a uma Colelitíase recebeu por acidente 4 mg de adrenalina intravenosa em vez de Neostigmina, no despertar da anestesia. A doente apresentou um episódio de Taquicardia Supra Ventricular (TSV) juntamente com uma crise hipertensiva e sinais de perfusão periférica fracos. O tratamento adequado resultou numa recuperação favorável sem sequelas. Discutimos a gestão adequada desta complicação e possíveis mecanismos para evitar erro humano na administração de fármacos durante a anestesia.

Modulatory activity of antioxidants against the toxicity of Rifampicin in vivo

The World Health Organization (WHO) has shown concern about the burden of tuberculosis in the developing countries. Even though rifampicin is an effective drug in the management of tuberculosis, it has been documented to have some toxic effects in humans. Therefore, this study intends to investigate the modulatory effect of vitamins C and E on the hepatotoxicity, sperm quality and brain toxicity of Rifampicin. Forty Wistar albino rats were used, 10 animals per group. Group 1 animals received 0.3 mL of distilled water, the Group 2 animals received the therapeutic dose of rifampicin, Group 3 animals received therapeutic doses of rifampicin plus vitamin E, while Group 4 received therapeutic doses of rifampicin and vitamin C. The administration was performed orally during three months; the animals were sacrificed by cervical dislocation at the end of that period. Blood samples were collected and liver function and lipid profile was analyzed using fully automated clinical chemistry device. The liver, brain and reproductive organs underwent histopathological examination. Sperm samples were collected from the epididymis to achieve count and motility and morphological analysis. Results showed rifampicin alone to raise (p < 0.05) liver function enzymes (Aspartate amino transferase [AST], Serum alanine amino transferase [ALT] and Total Bilirubin) when compared with controls. While the vitamin E treated group showed remarkable protection, the vitamin C treated group showed questionable protection against the rifampicin induced liver damage. Sperm count results showed an important (p < 0.05) increase in the sperm quality in vitamin E and C treated groups. However, the vitamin E plus Rifampicin treated group showed increased lipid peroxidation. The histopathological findings revealed structural damages by rifampicin in liver, brain and epididymis while some remarkable architectural integrity was observed in the antioxidant-treated groups. It can be concluded that vitamin E or C improved sperm quality and protected against the brain damage caused by rifampicin. Moreover, vitamin E demonstrated remarkable hepatoprotection against rifampicin induced damage while vitamin C shows a questionable hepatoprotection.

Review of genitourinary tuberculosis with focus on end-stage renal disease

Tuberculosis (TB) is a current public health problem, remaining the most common worldwide cause of mortality from infectious disease. Recent studies indicate that genitourinary TB is the third most common form of extra-pulmonary disease. The diagnosis of renal TB can be hypothesized in a non-specific bacterial cystitis associated with a therapeutic failure or a urinalysis with a persistent leukocyturia in the absence of bacteriuria. We report on the case of a 33-year-old man who presented on admission end stage renal disease (ESRD) secondary to renal TB and a past history of pulmonary TB with important radiologic findings. The diagnosis was based on clinical findings despite all cultures being negative. Empiric treatment with tuberculostatic drugs was started and the patient became stable. He was discharged with no symptom, but without renal function recovery. He is on maintenance hemodialysis three times a week. TB is an important cause of kidney disease and can lead to irreversible renal function loss.

Optochiasmatic tuberculoma as the sole manifestation of late recurrent tuberculosis

Brain tuberculomas account for 10-20% of space occupying brain lesions in developing countries. Most lesions are observed at time of tuberculosis diagnosis or soon after starting treatment. We herein describe a 32 year-old patient with a 14-month history of headache and progressive visual loss. Her past medical history revealed pulmonary tuberculosis treated eight years before. A brain MRI showed a T1- and T2-weighted isointense contrast-enhancing lesion in the optic chiasm. A presumptive diagnosis of optochiasmatic tuberculoma was made and isoniazid, rifampin, pyrazinamide, and ethambutol were started. Despite treatment, the patient evolved to blindness. The prompt recognition of this condition is extremely important since the presence of optochiasmal enhancement is associated with blindness in patients with tuberculosis.

Tuberculosis among HIV-1-infected subjects in a tertiary out-patient service in São Paulo city, Brazil

TB is currently considered to be the most important infectious disease among HIV-1-infected subjects in developing countries, such as Brazil. A retrospective analysis of TB cases was performed, occurring from January 1995 to December 2010 in our cohort of 599 HIV positive patients. The primary outcome was the occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16 years, among 599 HIV positive patients in an open cohort setting in the city of Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB diagnosis was 146 and 186 cells/mm³, respectively. The mean HIV viral load was 5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was 1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The probability of surviving up to 10 years after diagnosis was 75% for TB patients as opposed to 96% for patients with other, non-TB opportunistic diseases (p = 0.03). TB can be considered a public health problem among people living with HIV in Brazil despite of the widespread use of antiretrovirals for the treatment of HIV infection/AIDS.

QUANTITATIVE REAL-TIME PCR (Q-PCR) FOR SPUTUM SMEAR DIAGNOSIS OF PULMONARY TUBERCULOSIS AMONG PEOPLE WITH HIV/AIDS

Objective: To assess quantitative real-time polymerase chain reaction (q-PCR) for the sputum smear diagnosis of pulmonary tuberculosis (PTB) in patients living with HIV/AIDS with a clinical suspicion of PTB.Method: This is a prospective study to assess the accuracy of a diagnostic test, conducted on 140 sputum specimens from 140 patients living with HIV/AIDS with a clinical suspicion of PTB, attended at two referral hospitals for people living with HIV/AIDS in the city of Recife, Pernambuco, Brazil. A Löwenstein-Jensen medium culture and 7H9 broth were used as gold standard.Results: Of the 140 sputum samples, 47 (33.6%) were positive with the gold standard. q-PCR was positive in 42 (30%) of the 140 patients. Only one (0.71%) did not correspond to the culture. The sensitivity, specificity and accuracy of the q-PCR were 87.2%, 98.9% and 95% respectively. In 39 (93%) of the 42 q-PCR positive cases, the CT (threshold cycle) was equal to or less than 37.Conclusion: q-PCR performed on sputum smears from patients living with HIV/AIDS demonstrated satisfactory sensitivity, specificity and accuracy, and may therefore be recommended as a method for diagnosing PTB.

TUBERCULOSIS INFECTION MIGHT INCREASE THE RISK OF INVASIVE CANDIDIASIS IN AN IMMUNOCOMPETENT PATIENT

Deep Candida infections commonly occur in immunosuppressed patients. A rare case of a multiple deep organ infection with Candida albicansand spinal tuberculosis was reported in a healthy young man. The 19-year-old man complained of month-long fever and lower back pain. He also had a history of scalded mouth syndrome. Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed using the culture of aspirates from different regions. Symptoms improved considerably after antifungal and antituberculous therapy. This case illustrates that infection with tuberculosis might impair the host's immune system and increase the risk of invasive candidiasis in an immunocompetent patient.

Evaluation of a new vaccine based on pDNA and recombinant protein against Helicobacter pylori

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Investigation and Control of a Large Outbreak of Multi-Drug Resistant Tuberculosis at a Central Lisbon Hospital

An increase in the number of new cases of tuberculosis (TB) combined with poor clinical outcome was identified among HIV-infected injecting drug users attending a large HIV unit in central Lisbon. A retrospective epidemiological and laboratory study was conducted to review all newly diagnosed cases of TB from 1995 to 1996 in the HIV unit. Results showed that from 1995 to 1996, 63% (109/173) of the Mycobacterium tuberculosis isolates from HIV-infected patients were resistant to one or more anti-tuberculosis drugs; 89% (95) of these were multidrug-resistant, i.e., resistant to at least isoniazid and rifampicin. Eighty percent of the multidrug-resistant strains (MDR) available for restriction fragment length polymorphism (RFLP) DNA fingerprinting clustered into one of two large clusters. Epidemiological data support the conclusion that the transmission of MDR-TB occurred among HIV-infected injecting drug users exposed to infectious TB cases on open wards in the HIV unit. Improved infection control measures on the HIV unit and the use of empirical therapy with six drugs once patients were suspected to have TB, reduced the incidence of MDR-TB from 42% of TB cases in 1996 to 11% in 1999.

The effect of phenolated "vaccines" against experimental T. cruzi infection in mice

"Vaccines" prepared from parasites of an avirulent cultivated Y strain of T. cruzi, suspended in phenolated 1/10.000 saline solution, with aluminum stearate, containing alive parasites, gave high degree of protection to mice against a posterior infection with virulent blood forms of the same parasites and strain. The degree of protection with 1/1000 and 1/10.000 phenol "vaccines", with no alive parasites, was very poor specially in the first group. The immunity seems to be related to the number of alive trypanosomes in the "vaccines".

HPV : devem os rapazes ser vacinados?

RESUMO - A infecção por Vírus do Papiloma Humano (Human Papillomavirus - HPV) é uma das doenças de transmissão sexual mais frequentes em todo o mundo. A descoberta de que esta infecção é responsável pelo carcinoma do colo do útero impulsionou o desenvolvimento de vacinas contra o HPV. Em Portugal, a vacina tetravalente contra o HPV faz parte do Plano Nacional de Vacinação, sendo administrada apenas a raparigas aos 13 anos de idade como medida profiláctica do carcinoma do colo do útero. Nos Estados Unidos da América, em Dezembro de 2010, a Food and Drugs Administration (FDA) aprovou o uso da vacina tetravalente na prevenção de lesões pré-cancerígenas e cancerígenas do ânus, tanto em rapazes como em raparigas, dos 9 aos 26 anos. A 25 de Outubro de 2011, o Advisory Committee on Immunization Practices (ACIP) recomendou que todos os rapazes de 11 e 12 anos sejam vacinados contra o HPV com a vacina tetravalente. Partindo desta realidade, o que se pretende com o presente trabalho é compilar evidência científica suficiente que permita ponderar mais aprofundadamente acerca das implicações, a partir de dados epidemiológicos e económicos, de se vacinar ou não os rapazes contra o HPV em Portugal. Em primeiro lugar recolheu-se evidência científica acerca da relação entre a infecção por HPV e o desenvolvimento de carcinomas de diversas regiões anatómicas. Em segundo lugar compilaram-se dados epidemiológicos sobre a incidência e sobrevivência associada aos diferentes tipos de tumores potencialmente associados à infecção por HPV, dando especial ênfase à realidade portuguesa. Em terceiro lugar enquadrou-se sucintamente a história da vacinação contra o HPV em Portugal e as vacinas existentes para prevenir esta infecção. Em quarto lugar foram revistos estudos de avaliação económica da vacinação contra o HPV quer em mulheres quer em homens, após uma introdução ao conceito de avaliação económica do medicamento. Em quinto lugar, foi feita uma estimativa dos custos com a vacinação dos rapazes contra o HPV durante os próximos 20 anos. Por último, procurou-se reflectir acerca das implicações de se alargar ou não a vacinação contra o HPV aos rapazes em Portugal.

Caracterização de estirpes Mycobacterium Tuberculosis da família Lisboa: análise de regiões de diferença e single nucleotide polymorphisms

Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia