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Orientadores : Rogério de Jesus Pedro, Luiz Candido de Souza Dias Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas Resumo: O nosso trabaIho foi desenvoIvido em 1988 e 1989, nos municípios de Pedro de Toledo e Itariri (Vale do Ribeira - S.P), região de baixa endemicidade para esquistossome mansônica, onde o hospedeiro intermediário é a Biomphalaria tenagophila. A população estudada, constituída por 322 portadores de Schistosoma mansoni e menores de 15 anos inclusive, após avaliação clínica e epidemiológica foi dividida em 3 grupos: 114 receberam oxamniquina (20mg/kg/peso), 102 praziquantel (60mg/kg/peso) e 106 associação dessas drogas na metade da dose. O diagnóstico parasitológico pré-tratamento e o acompanhamento para controle de cura (exame de fezes mensal nos 6 meses subseqüentes ao tratamento) foi realizado pelo exame de fezes quantitativo (método KATOKATZ - 3 lâminas). Em nossa amostragem a média de idade foi de 10 anos (DP=±3), com predomínio do sexo masculino (65.8%) e da raça branca (67,5%), distribuídos proporcionalmente entre as zonas rural e urbana. Antecedentes de tratamentos anteriores para esquistossomose foi observado em 24,5% dos indivíduos. A classificação epidemiológica demonstrou que 95,3% eram autóctones do Estado de São Paulo e 87,8% dos municípios em estudo. A avaliação clínica identificou 69.2% dos indivíduos com pelo menos uma das 12 queixas indagadas, destacando-se dor abdominal, diarréia, e presença de sangue e muco nas fezes. Ao exame físico encontramos a forma intestinal em 69,6%, hepatointestinal em 24,2% e hepatosplênica em 6,2%. Essa última forma provavelmente esteve superestimada. Ao exame parasitológico pré-tratamento, realizado em 126 indivíduos, observamos média geométrica de 25,1 ovos/g.d.f. (I.C.=4--167). Os efeitos colaterais, analisados em 248 pacientes, demonstrou que sonolência e tonturas foram significativamente mais freqüentes entre os que receberam prazíquantel quando comparados apenas aos medicados com a associação de drogas. Náuseas e vômitos também foram mais freqüentes entre os que receberam praziquantel em relação apenas aos medicados com oxamniquina. De maneira geraI foi observado menor tolerância ao uso do praziquantel isolado. O controle de cura parasitológíca em 101 indivíduos demonstrou a mesma eficácia para os 3 esquemas terapêuticos, com índices de cura de 67,6% para oxamniquina, 59,4% para o praziquantel e 66,7% para a associação de drogas. Redução na ovoposição entre os não curados foi notada para o prazíquanteI (68,9%) e para a associação (53,4%). A reavaliação médica, 6 meses após o tratamento, observamos melhora em relação à sintomatologia inicial embora as formas clínicas tenham se mantido nas mesmas proporções. Concluímos que: a doença apresentou-se com formas clínicas leves; a tolerância aos esquemas terapêuticos utilizados foi boa, embora menor com uso do praziquantel isolado; a eficácia entre os três tratamentos foi a mesma. Abstract: The present work was carried out in the years 1988 and 1989, in the municipalities of Pedro de Toledo and Itariri, (Ribeira Valley, São Paulo State, Brazil) in area of low transmission of shistosomiasis mansoni. The intermediate host was Biomphalaria tenagophila. 322 individuals of 15 years of age and less infected by Schistosoma mansoni were studied after clinical and epidemiological evaluation and the subjects were divided in 3 groups: 114 were treated with oxamniquine (20 mg/kg body weight), 102 with praziquantel (60 mg/ kg body weight) and 106 with combination of both drugs with half of the dosage. The parasitological diagnosis before treatment and the follow UP of control cure (monthly stool examinations during 6 months after treatment) were made by quantitative examination of faeces (KATO-KATZ method - 3 slides per person). Our sample showed average age of 10 years (SD±3), 65.8% of males and 67.5% of white race, proportionally distributed in rural and urban zones. 24.5% of studied patients were treated before our evaluation for schistosomiasis. The epidemiological classification demonstrated that 95.3% were autochthonous from São Paulo State and 87.8% from the studied municipalities. The clinical evaluation identified 69,2% of patients with at least one of 12 clinical signs and symptoms, among them the highest frequency were abdominal pain, diarrhea, presence of blood and mucus ín faeces. Physical examination showed 69.6% with the intestinal form, 24.2% with the hepatointestinal and 6,2% with the hepatosplenic form. The last one probably over estimated. The faeces examinations pre-treatment performed in 126 subjects geometric mean of 25.1 eggs per gramma of faeces (C.I.= 4--167) was revealed. The side effects in 248 patients showed that drowsiness and dizziness were significant statistically between the patients treated with praziquantel when compa red with those treated with drug combination. Nausea and vomiting were more frequent between those treated with praziquantel in comparison with patients treated with oxamníquine. Overall the praziquantel presented less tolerance than oxamniquine or the drug combination. The parasítological cure in 101 subjects demonstrated the same effícacy to 3 therapeutical modality with index of cure of 67.6% to oxamniquine, 59.4% to praziquantel and 66,7% to association of both. In those patients still excreting eggs after treatment, reductions in egg counts were observed: 68.9% to praziquantel and 53,4% to combination of both drugs. The medical evaluation, six months after treatment, was better than the initial symptomatology, however the clinical forms maintained the same proportions. We can conclude that: the schistosomiasis mansoni showed mild clinical forms, the tolerance of the therapeutical modality was satisfactory; thepraziquantel presented more side effects; the efficacy of the 3 modalities was the same. Mestrado Medicina Interna Mestre em Ciências Médicas

Introduction: Retention in HIV care prior to ART initiation is generally felt to be suboptimal, but has not been wellcharacterized. Methods: We examined data on 37,352 adult pre-ART patients (ART ineligible or unknown eligibility) who enrolled in care during 2005-2008 with > 1 clinical visit at 23 clinics in Mozambique.We defined loss to clinic (LTC) as > 12 months since the last visit among those not known to have died/transferred. Cox proportional-hazards models were used to examine factors associated with LTC, accounting for clustering within sites. Results: Of 37,352 pre-ART patients, 61% had a CD4 count within three months of enrolment (median CD4: 452, IQR: 345-611). 17,598 (47.1%) were ART ineligible and 19,754 (52.9%) were of unknown eligibility status at enrolment because of missing information on CD4 count and/or WHO stage. Kaplan-Meier estimates for LTC at 12 months were 41% (95% CI: 40.2-41.8) and 48% (95% CI: 47.2-48.8), respectively. Factors associated with LTC among ART ineligible patients included male sex (AHRmen_vs_non-pregnant women: 1.5; 95% CI: 1.4-1.6) and being pregnant at enrolment (AHRpregnant_vs_non-pregnant women: 1.3; 95% CI: 1.1-1.5). Older age, more education, higher weight and more advanced WHO stage at enrolment were independently associated with lower risks of LTC. Similar findings were observed among patients whose ART eligibility status was unknown at enrolment. Conclusions: Substantial LTC occurred prior to ART initiation among patients not yet known to be eligible for ART, including nearly half of patients without documented ART eligibility assessment. Interventions are needed to target pre-ART patients who may be at higher risk for LTC, including pregnant women and patients with less advanced HIV disease.

Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission. To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count>100 cells/µL or WHO stage IV. Mixed effects models were used to identify patient- and clinic-level factors associated with late ART initiation.The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.