Clinical relevance of low-density Plasmodium falciparum parasitemia in untreated febrile children: A cohort study.

BACKGROUND: Low-density (LD) Plasmodium infections are missed by standard malaria rapid diagnostic tests (standard mRDT) when the blood antigen concentration is below the detection threshold. The clinical impact of these LD infections is unknown. This study investigates the clinical presentation and outcome of untreated febrile children with LD infections attending primary care facilities in a moderately endemic area of Tanzania. METHODS/FINDINGS: This cohort study includes 2,801 febrile pediatric outpatients (median age 13.5 months [range 2-59], female:male ratio 0.8:1.0) recruited in Dar es Salaam, Tanzania between 01 December 2014 and 28 February 2016. Treatment decisions were guided by a clinical decision support algorithm run on a mobile app, which also collected clinical data. Only standard mRDT+ cases received antimalarials. Outcomes (clinical failure, secondary hospitalization, and death) were collected in follow-up visits or interviews on days 3, 7, and 28. After patient recruitment had ended, frozen blood from all 2,801 patients was tested for Plasmodium falciparum (Pf) by ultrasensitive-quantitative polymerase chain reaction (qPCR), standard mRDT, and "ultrasensitive" mRDT. As the latter did not improve sensitivity beyond standard mRDT, it is hereafter excluded. Clinical features and outcomes in LD patients (standard mRDT-/ultrasensitive-qPCR+, not given antimalarials) were compared with those with no detectable (ND) parasitemia (standard mRDT-/ultrasensitive-qPCR-) or high-density (HD) infections (standard mRDT+/ultrasensitive-qPCR+, antimalarial-treated). Pf positivity rate was 7.1% (n = 199/2,801) and 9.8% (n = 274/2,801) by standard mRDT and ultrasensitive qPCR, respectively. Thus, 28.0% (n = 76/274) of ultrasensitive qPCR+ cases were not detected by standard mRDT and labeled "LD". LD patients were, on average, 10.6 months younger than those with HD infections (95% CI 7.0-14.3 months, p < 0.001). Compared with ND, LD patients more frequently had the diagnosis of undifferentiated fever of presumed viral origin (risk ratio [RR] = 2.0, 95% CI 1.3-3.1, p = 0.003) and were more often suffering from severe malnutrition (RR = 3.2, 95% CI 1.1-7.5, p = 0.03). Despite not receiving antimalarials, outcomes for the LD group did not differ from ND regarding clinical failures (2.6% [n = 2/76] versus 4.0% [n = 101/2,527], RR = 0.7, 95% CI 0.2-3.5, p = 0.7) or secondary hospitalizations (2.6% [n = 2/76] versus 2.8% [n = 72/2,527], RR = 0.7,95% CI 0.2-3.2, p = 0.9), and no deaths were reported in any Pf-positive groups. HD patients experienced more secondary hospitalizations (10.1% [n = 20/198], RR = 0.3, 95% CI 0.1-1.0, p = 0.005) than LD patients. All the patients in this cohort were febrile children; thus, the association between parasitemia and fever cannot be investigated, nor can the conclusions be extrapolated to neonates and adults. CONCLUSIONS: During a 28-day follow-up period, we did not find evidence of a difference in negative outcomes between febrile children with untreated LD Pf parasitemia and those without Pf parasitemia. These findings suggest LD parasitemia may either be a self-resolving fever or an incidental finding in children with other infections, including those of viral origin. These findings do not support a clinical benefit nor additional risk (e.g. because of missed bacterial infections) to using ultrasensitive malaria diagnostics at a primary care level.

Neurocysticercosis in children presenting with afebrile seizure: clinical profile, imaging and serodiagnosis.

Neurocysticercosis (NCC) is one of the major causes of childhood seizures in developing countries including India and Latin America. In this study neurological pediatric cases presenting with afebrile seizures were screened for anti-Cysticercus antibodies (IgG) in their sera in order to estimate the possible burden of cysticercal etiology. The study included a total of 61 pediatric afebrile seizure subjects (aged one to 15 years old); there was a male predominance. All the sera were tested using a pre-evaluated commercially procured IgG-ELISA kit (UB-Magiwell Cysticercosis Kit ™). Anti-Cysticercus antibody in serum was positive in 23 of 61 (37.7%) cases. The majority of cases with a positive ELISA test presented with generalized seizure (52.17%), followed by complex partial seizure (26.08%), and simple partial seizure (21.73%). Headaches were the major complaint (73.91%). Other presentations were vomiting (47.82%), pallor (34.78%), altered sensorium (26.08%), and muscle weakness (13.04%). There was one hemiparesis case diagnosed to be NCC. In this study one child without any significant findings on imaging was also found to be positive by serology. There was a statistically significant association found between the cases with multiple lesions on the brain and the ELISA-positivity (p = 0.017). Overall positivity of the ELISA showed a potential cysticercal etiology. Hence, neurocysticercosis should be suspected in every child presenting with afebrile seizure especially with a radio-imaging supportive diagnosis in tropical developing countries or areas endemic for taeniasis/cysticercosis.

Neurocysticercoiis in children presenting with febrile seizure: clinical profiile, imaging and serodiagnosis / Neurocisticercose em crianças apresentando crises afebris: perfil clínico, imagem e sorodiagnóstico

Neurocysticercosis (NCC) is one of the major causes of childhood seizures in developing countries including India and Latin America. In this study neurological pediatric cases presenting with afebrile seizures were screened for anti-Cysticercus antibodies (IgG) in their sera in order to estimate the possible burden of cysticercal etiology. The study included a total of 61 pediatric afebrile seizure subjects (aged one to 15 years old); there was a male predominance. All the sera were tested using a pre-evaluated commercially procured IgG-ELISA kit (UB-Magiwell Cysticercosis Kit ™). Anti-Cysticercus antibody in serum was positive in 23 of 61 (37.7%) cases. The majority of cases with a positive ELISA test presented with generalized seizure (52.17%), followed by complex partial seizure (26.08%), and simple partial seizure (21.73%). Headaches were the major complaint (73.91%). Other presentations were vomiting (47.82%), pallor (34.78%), altered sensorium (26.08%), and muscle weakness (13.04%). There was one hemiparesis case diagnosed to be NCC. In this study one child without any significant findings on imaging was also found to be positive by serology. There was a statistically significant association found between the cases with multiple lesions on the brain and the ELISA-positivity (p = 0.017). Overall positivity of the ELISA showed a potential cysticercal etiology. Hence, neurocysticercosis should be suspected in every child presenting with afebrile seizure especially with a radio-imaging supportive diagnosis in tropical developing countries or areas endemic for taeniasis/cysticercosis.

Neurocisticercose é uma das causas mais comuns de crises em crianças em países em desenvolvimento incluindo Índia e América Latina. Neste estudo casos neurológicos pediátricos, apresentando crises afebris foram selecionados através de anticorpos anti-Cysticercus (IgG) no seu soro para avaliar possível etiologia de Cysticercus. O estudo incluiu total de 61 casos pediátricos de indivíduos com crises afebris (idade de um a 15 anos); houve predominância de pacientes do sexo masculino. Todos os soros foram testados usando um kit comercial IgG-ELISA (UB-Magiwell Cysticercosis kit™) avaliado previamente. O anticorpo anti-Cysticercus no soro foi positivo em 23 de 61 casos (37,7%). A maioria dos casos com teste de ELISA positivo apresentava crises generalizadas (52,17%), seguida por casos de crises parciais complexas (26,08%) e crises parciais simples (21,73%). Dores de cabeça foram a queixa principal (73,91%). Outras manifestações foram vômitos (47,82%), palidez (34,78%), sensório alterado (26,08%) e fraqueza muscular (13,04%). Houve um caso de hemiparesia diagnosticado como NCC. Neste estudo uma criança sem quaisquer achados significantes às imagens apresentou sorologia positiva. Houve associação estatística significante entre os casos com múltiplas lesões no cérebro e a positividade pelo ELISA (p = 0,017). No seu conjunto a positividade pelo ELISA demonstra etiologia potencial para a cisticercose. Portanto neurocisticercose deve ser suspeitada em qualquer criança apresentado crises afebris com imagem que sugira diagnóstico em países tropicais em desenvolvimento ou em áreas endêmicas para teníase/cisticercose.

[Life-threatening Plasmodium falciparum parasitemia, in an infant returning from the tropics]. / Paludisme grave avec hyperparasitémie, chez un nourrisson voyageur.

INTRODUCTION: Severe falciparum malaria is a polymorphous life-threatening disease. Hyperparasitemia is rare among non-immune children returning from tropical areas. CARE REPORT: We report a case of an infant returning from Ivory Coast who presented with fever, prostration and marked thrombocytopenia (22,000 platelets/mm(3)). Blood slide showed Plasmodium falciparum ring forms. Parasite density dramatically increased from 1.7% to 45%, and the child developed several features of severe malaria, according to WHO definition. CONCLUSION: In this non-immune infant, prostration and thrombopocytopenia seemed to be earlier predictors of severity than hyperparasitemia and other WHO criteria, which have not been yet validated in travelling children.

Convulsions with fever of acute onset in school-age children in Benin City, Nigeria.

Of 92 school-age children who had convulsions with fever (CWF) of acute onset, seen in a 1-year period in an emergency room in Benin City, Nigeria, 49 per cent had malaria parasitaemia, 15 per cent bacterial meningitis, 8 per cent focal extracranial infections, and 1 per cent bacteraemia while 27 per cent had acute fever of undetermined origin. The prevalence of meningitis increased with presence of temperature > or = 40 degrees C (P < 0.01), focal seizures (P < 0.05), and rousable coma (P < 0.05). Bacterial meningitis is an important illness in school-age children with CWF, although malaria parasitaemia is the commonest infection.