RESUMO
The aim of this study was to describe a case of a patient with ocular toxoplasmosis, which has resulted in Kyrieleis plaques formation (segmental periarteritis associated with severe inflammation) and later follow-up and alternative treatment due to documented allergy to sulfonamide. A 33-year-old Brazilian woman diagnosed with acute toxoplasmosis, initially treated with sulfonamide, developed a critical cutaneous rash. Cotrimoxazole was changed to clindamycin and pyrimethamine, and prednisone was started. The medication was maintained for 45 days. Four months later, she developed retinal lesions suggestive of toxoplasmosis with Kyrieleis plaques in the upper temporal vessels. Pyrimethamine, clindamycin, and prednisone were initiated until healing. She presented reactivation months later, and a suppressive treatment with pyrimethamine was instituted for one year. This is the first report to use the combination of clindamycin with pyrimethamine in the treatment and recurrence prophylaxis for OT in a documented allergy to sulfonamide.
Assuntos
Clindamicina , Pirimetamina , Sulfonamidas , Toxoplasmose Ocular , Humanos , Feminino , Adulto , Pirimetamina/uso terapêutico , Pirimetamina/efeitos adversos , Toxoplasmose Ocular/tratamento farmacológico , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Clindamicina/uso terapêutico , Recidiva , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Brasil , Antiprotozoários/uso terapêutico , Antiprotozoários/efeitos adversos , Resultado do Tratamento , Prednisona/uso terapêuticoRESUMO
In 2018, a mass drug administration (MDA) campaign for malaria elimination was piloted in Haiti. The pilot treated 36,338 people with sulfadoxine-pyrimethamine (SP) and primaquine; no severe adverse events were detected. In 2020, another MDA campaign using the same medications was implemented to mitigate an upsurge in malaria cases during the COVID-19 pandemic. Four cases of Stevens-Johnson syndrome (SJS) were identified among the 42,249 people who took the medications. Three of these individuals required hospitalization; all survived. In addition to SP ingestion, an investigation of potential causes for increased SJS cases identified that all four cases had human leukocyte antigens A*29 and/or B*44:03, another known risk factor for SJS. Additionally, three of the four case individuals had antibodies to SARS-CoV-2, and the fourth may have been exposed around the same time. These findings raise the possibility that recent SARS-CoV-2 infection may have contributed to the increased risk for SJS associated with SP exposure during the 2020 campaign.
Assuntos
Antimaláricos , COVID-19 , Malária , Síndrome de Stevens-Johnson , Humanos , Primaquina/efeitos adversos , Antimaláricos/efeitos adversos , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/epidemiologia , Haiti/epidemiologia , Administração Massiva de Medicamentos , Pandemias , SARS-CoV-2 , Pirimetamina/efeitos adversos , Sulfadoxina/efeitos adversos , Combinação de Medicamentos , Malária/tratamento farmacológico , Malária/epidemiologia , Malária/prevenção & controleRESUMO
Background: The purpose of this study was to estimate the frequency and describe the adverse drug reactions (ADRs) associated with the classic treatment of ocular toxoplasmosis (OT), namely sulfadiazine, pyrimethamine, corticosteroids and folinic acid. Methods: We performed a descriptive study of a prospective cohort of patients with OT treated with the classic therapy. Data were collected during medical consultations and treatment. Results: Of the 147 patients studied, 85% developed one or more ADR. Women presented more ADRs than men (95% vs 77%). Of the total reactions (n=394), 82% were mild, but we found one life-threatening event (Stevens-Johnson syndrome). The most frequent types (71%) of ADRs were gastrointestinal, skin and neurological or psychiatric. The majority of ADRs (90.3%) occurred before the second week of treatment. A third of the patients were treated for the ADR and 10% dropped out of OT treatment. Most (70%) of the ADRs were characterized as being probably caused by the drugs and may be associated with prednisone, sulfadiazine and sulfadiazine/prednisone. Six percent of ADRs were not previously described, such as taste alteration, constipation/bloating, dyspnoea, sweating and somnolence. Conclusions: Our results suggest a high rate of ADRs to OT classic treatment, which requires careful follow-up in order to identify and treat ADRs early.
Assuntos
Antídotos/efeitos adversos , Antiprotozoários/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Toxoplasmose Ocular/tratamento farmacológico , Adolescente , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Antídotos/uso terapêutico , Antiprotozoários/uso terapêutico , Brasil/epidemiologia , Comorbidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Feminino , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirimetamina/efeitos adversos , Pirimetamina/uso terapêutico , Sulfadiazina/efeitos adversos , Sulfadiazina/uso terapêutico , Toxoplasmose Ocular/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: There are few studies reporting frequency and control of adverse events associated with congenital toxoplasmosis treatment. The objective of this study is to describe treatment adherence and adverse hematologic events in a cohort of children identified with congenital toxoplasmosis in Minas Gerais, Brazil. METHODS: Children were treated with sulfadiazine, pyrimethamine and folinic acid and were evaluated clinically and by laboratory tests at regular intervals. RESULTS: Of 146,307 live newborns who participated in the Neonatal Screening Program in Minas Gerais in 2006-2007, 190 had congenital toxoplasmosis. Among the 171 children whose treatment data were available, 73.1% completely adhered to antiparasitic therapy. Hematologic adverse events (macrocytic anemia and/or neutropenia and/or thrombocytopenia) were diagnosed in 44% of them. The most common adverse event was neutropenia (31%). In most cases, it was not severe and reversed after increase in folinic acid dosage (25.7%) or temporary treatment suspension (1.8%). No infections were observed in association with neutropenic events. Significant associations were detected between macrocytic anemia and lower weight Z score at first medical appointment (P = 0.03), and between severe neutropenia (<500/mm) and lower weight Z score toward the end of treatment (P = 0.04). CONCLUSIONS: The high frequency of hematologic adverse events found, especially in malnourished children, highlight the importance of careful monitoring of these children throughout treatment, as well as considering nutritional aspects and the need for higher doses of folinic acid. With adequate monitoring, antiparasitic treatment was feasible and relatively safe in the setting of this large screening program for congenital toxoplasmosis.
Assuntos
Antiprotozoários/efeitos adversos , Medula Óssea , Neutropenia/induzido quimicamente , Toxoplasmose Congênita/tratamento farmacológico , Toxoplasmose Congênita/epidemiologia , Antiprotozoários/uso terapêutico , Medula Óssea/efeitos dos fármacos , Medula Óssea/fisiopatologia , Brasil/epidemiologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Triagem Neonatal , Neutropenia/diagnóstico , Neutropenia/epidemiologia , Estudos Prospectivos , Pirimetamina/efeitos adversos , Pirimetamina/uso terapêutico , Sulfadiazina/efeitos adversos , Sulfadiazina/uso terapêutico , Toxoplasmose Congênita/complicaçõesRESUMO
OBJECTIVES: The objective of this study was to perform a systematic review and meta-analysis of the literature to evaluate the efficacy and safety of therapies for cerebral toxoplasmosis in HIV-infected adults. The pyrimethamine plus sulfadiazine (P-S) combination is considered the mainstay therapy for cerebral toxoplasmosis and pyrimethamine plus clindamycin (P-C) is the most common alternative treatment. Although trimethoprim-sulfamethoxazole (TMP-SMX) has potential advantages, its use is infrequent. METHODS: We searched PubMed and four other databases to identify randomized controlled trials (RCTs) and cohort studies. Two independent reviewers searched the databases, identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. RESULTS: Nine studies were included (five RCTs, three retrospective cohort studies and one prospective cohort study). In comparison to P-S, treatment with P-C or TMP-SMX was associated with similar rates of partial or complete clinical response [P-C: RR 0.87; 95% confidence interval (CI) 0.70-1.08; TMP-SMX: RR 0.97; 95% CI 0.78-1.21], radiological response (P-C: RR 0.92; 95% CI 0.82-1.03), skin rash (P-C: RR 0.81; 95% CI 0.56-1.17; TMP-SMX: RR 0.17; 95% CI 0.02-1.29), gastrointestinal impairment (P-C: RR 5.16; 95% CI 0.66-40.11), and drug discontinuation because of adverse events (P-C: RR 0.32; 95% CI 0.07-1.47). Liver impairment was more frequent with P-S than P-C (P-C vs. P-S: RR 0.48; 95% CI 0.24-0.97). CONCLUSIONS: The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed.
Assuntos
Antiprotozoários/efeitos adversos , Antiprotozoários/uso terapêutico , Infecções por HIV/complicações , Toxoplasmose Cerebral/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirimetamina/efeitos adversos , Pirimetamina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfadiazina/efeitos adversos , Sulfadiazina/uso terapêuticoRESUMO
Pyrimethamine (PYR) is a drug used in the treatment of newborn with congenital Toxoplasmosis. Even when PYR is highly specific against parasites, it may provoke neutropenia in the patients apart from other affectations, conditions that usually justify its suspension. Moreover, medication against congenital toxoplasmosis coincides with the proliferation stage of Sertoli and germ cells. Although, there are several reports on the effect of this drug on mature testes, records of its effects on the testes of young individuals yet in the process of growth are still lacking. This work was aimed to study the effects of in vivo administration of PYR in the first 21 days of life of male rat pups by evaluating their testicular alterations and its long-term sequels on fertility. Through the determination of the levels of seminiferous epithelium maturity, apoptotic index and cell proliferation index at 7, 14, 35 and 90 days post-natal using immunocytochemical studies. The fertility of the treated rats was evaluated at 90 days. PYR-treated animals were found to undergo some kind of delays in seminiferous epithelium maturity, decreased cell proliferation index and an increase in apoptosis when compared with the control (p < 0.05). Epididymal sperm counts were also affected (p < 0.05). The application of folic acid (FA) in newborns treated with PYR decreased the severity of the problem (p < 0.05). This study provides strong evidence that the effect of PYR on testicular development is specific. It reinforces the importance of FA application in neonates treated with PYR to prevent the effect of the later on spermatogenesis.
Assuntos
Fertilidade/efeitos dos fármacos , Antagonistas do Ácido Fólico/efeitos adversos , Pirimetamina/efeitos adversos , Epitélio Seminífero/efeitos dos fármacos , Testículo/patologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácido Fólico/farmacologia , Antagonistas do Ácido Fólico/farmacologia , Masculino , Pirimetamina/farmacologia , Ratos , Ratos Wistar , Células de Sertoli/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Testículo/citologia , Toxoplasmose/tratamento farmacológicoRESUMO
In 2001, Peru changed its treatment policy for uncomplicated Plasmodium falciparum malaria on the northern Pacific Coast to sulfadoxine-pyrimethamine with atresunate (SP-AS). Because Peru was the first country in the Americas to adopt this combination therapy, we established a surveillance system in the region to assess the frequency of new or worsening symptoms after starting therapy. Over a period of two years, 1,552, or approximately two-thirds of all patients with uncomplicated P. falciparum malaria who had received SP-AS on the northern coast were followed up. Of these, 8.8% reported at least one adverse effect, with the most common being vomiting, nausea, headache, abdominal pain, dizziness, and fever; no severe adverse effects related to SP-AS therapy were identified. Treatment of uncomplicated malaria with SP-AS was associated with a low frequency of mild adverse effects in Peru, and therefore should be considered as a first-line therapy in areas of the Americas where SP efficacy is still high.
Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Quimioterapia Combinada , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Artemisininas/administração & dosagem , Artemisininas/efeitos adversos , Artesunato , Combinação de Medicamentos , Humanos , Peru/epidemiologia , Pirimetamina/administração & dosagem , Pirimetamina/efeitos adversos , Sulfadoxina/administração & dosagem , Sulfadoxina/efeitos adversosRESUMO
To assist the Peruvian Ministry of Health in modifying the malaria treatment policy for their north Pacific coastal region, we conducted an in vivo efficacy trial of sulfadoxine-pyrimethamine (SP) and SP plus artesunate (SP-AS) for the treatment for uncomplicated Plasmodium falciparum infections. A total of 197 patients were randomized to therapy with either SP (25 mg/kg of the sulfadoxine component in a single dose on day 0) or a combination of SP plus AS (4 mg/kg on days 0, 1, and 2) and were followed for 28 days for symptoms and recurrence of parasitemia. No statistically significant differences between the two groups were observed on enrollment with respect to age, sex, history of malaria, or geometric mean parasite density. A total of 185 subjects completed the 28-day follow-up. Of the 91 subjects treated with SP alone, two had recurrences of parasitemia on day 7 and one on day 21. Of the 94 subjects treated with SP-AS, one had a recurrence of parasitemia on day 21. Fever and asexual parasite density decreased significantly more rapidly and the proportion of patients with gametocytemia on days 3-28 was significantly lower in subjects treated with combination therapy than in those who received SP alone. No severe adverse drug reactions were observed; however, self-limited rash and pruritus were significantly more common and an exacerbation of nausea, vomiting, and abdominal pain were observed significantly more frequently among patients who had received SP-AS. These results have contributed to a National Malaria Control Program decision to change to SP-AS combination therapy as the first-line treatment for uncomplicated P. falciparum malaria in northern coastal Peru in November 2001, making Peru the first country in the Americas to recommend this combination therapy.
Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Pirimetamina/uso terapêutico , Sesquiterpenos/uso terapêutico , Sulfadoxina/uso terapêutico , Adolescente , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Artemisininas/administração & dosagem , Artemisininas/efeitos adversos , Artesunato , Criança , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Peru , Pirimetamina/administração & dosagem , Pirimetamina/efeitos adversos , Sesquiterpenos/administração & dosagem , Sesquiterpenos/efeitos adversos , Sulfadoxina/administração & dosagem , Sulfadoxina/efeitos adversosRESUMO
Se comunica una paciente de 44 años de edad que presentaba lesiones kaposiformes profusas, manifestación cutánea infrecuente del síndrome antifosfolípido. Se describen las características clínicas, los hallazgos de laboratorio, así como el tratamiento de esta enfermedad multisistémica (AU)
Assuntos
Humanos , Adulto , Feminino , Síndrome Antifosfolipídica/diagnóstico , Anticorpos Antifosfolipídeos , Trombose/etiologia , Doença Medicamentosa , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/complicações , Fenotiazinas/efeitos adversos , Procainamida/efeitos adversos , Clorpromazina/efeitos adversos , Hidralazina/efeitos adversos , Clorotiazida/efeitos adversos , Etossuximida/efeitos adversos , Fenitoína/efeitos adversos , Penicilinas/efeitos adversos , Quinina/efeitos adversos , Quinidina/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Anticoncepcionais Orais Sintéticos/efeitos adversos , Estreptomicina/efeitos adversos , Pirimetamina/efeitos adversos , Interferon-alfa/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversosRESUMO
The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (Malarone) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9) or atovaquone/proguanil as before (n=5) (phase 2). In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] vs. 8% [1/13], P<0.0001). In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]). There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.