Diagnosing human African trypanosomiasis in Angola using a card agglutination test: observational study of active and passive case finding strategies.

OBJECTIVE: To assess the operational feasibility of detecting human African trypanosomiasis by active and passive case finding using the card agglutination test with serial dilution of serum to guide treatment. SETTING: Trypanosomiasis control programme in the Negage focus, northern Angola, during a period of civil war. DESIGN: Observational study. PARTICIPANTS: 359 patients presenting themselves to health centres with symptoms (passive case finding) and 14,446 people actively screened in villages. MAIN OUTCOME MEASURES: Whole blood and serological tests at different dilutions using the card agglutination test, and detection of parasites by microscopy. RESULTS: Active case finding identified 251 people with a positive card agglutination test result, 10 of whom had confirmed parasites. In those presenting for investigation 34 of 51 with a positive card agglutination test result at the dilution of 1:8 or more used to guide treatment had parasites in blood, lymph node fluid, or cerebrospinal fluid, compared with 10 of 76 in those detected by active case finding: positive predictive values of 67% for passive case detection and 13% for active case detection. Only at a cut-off dilution more than 1:32 was the positive predictive value in active case detection reasonable (46%) and at this dilution 40% of microscopically proved cases were missed. CONCLUSIONS: The card agglutination test is useful for initial screening in active detection of cases with human African trypanosomiasis but, given the toxicity of the drugs, serology using the card agglutination test should be not used alone to guide treatment after active case finding. A second confirmatory test is needed

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia, A double-blind, randomised, placebo-controlled trial

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. Methods: In this multicenter, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with Covid-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need of supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. Results: Overall, 112 of 151 (75.4%) patients in the pulse methylprednisolone arm and 111 of 150 (75.2%) in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups [15 days (95% confidence interval (CI), 13.0 to 17.0) and 16 days (95%CI, 13.8 to 18.2); hazard ratio (HR), 0.92; 95% CI 0.71-1.20; p=0.528]. No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to Intensive Care Unit with orotracheal intubation or death (20.0% versus 16.1%; HR, 1.26; 95%CI, 0.74-2.16; p=0.176), or overall mortality (10.0% versus 12.2%; HR, 0.83; 95%CI, 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia. Message of the study: Pulse glucocorticoid therapy is used for severe and/or life threatening immuno-inflammatory diseases. The addition of pulse glucocorticoid therapy to the standard low dose of dexamethasone scheme was not of benefit in patients with COVID-19 pneumonia

Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria

Cally Roper and colleagues analyze the distribution of sulfadoxine resistance mutations and flanking microsatellite loci to trace the emergence and dispersal of drug-resistant Plasmodium falciparum malaria in Africa

Monitoring for multidrug-resistant Plasmodium falciparum isolates and analysis of pyrimethamine resistance evolution in Uige province, Angola.

OBJECTIVES: To assess the extent of drug resistance in Uige through molecular genetic analysis and to test whether the dhfr triple mutant alleles present in Angola are of southeast Asian origin. METHODS: Seventy-one samples of blood from children admitted to the Pediatric Emergency Unit of Uige Provincial Hospital in 2004 were screened for resistance mutations at pfcrt, pfmdr1, pfdhfr, pfdhps and pfATPase6. RESULTS: Mutations in pfcrt (codon76), pfmdr1 (codon86), pfdhfr (codons 51, 59, 108) and pfdhps (codons 436, 437) were common. Among the 66 isolates for which we were able to determine complete genetic information 13.7% carried all seven of these mutations. Flanking microsatellite analysis revealed the triple mutant pfdhfr was derived from the southeast Asian lineage, while the N51I+S108N double mutant pfdhfr alleles are a local origin. pfATPase6 mutations were rare and S769N was not found. CONCLUSION: The parasite population of Uige Angola has high frequency mutations in pfcrt, dhfr and dhps associated with resistance to chloroquine and sulphadoxine pyrimethamine, reflecting past reliance on these two drugs which were the mainstay of treatment until recently. Our findings show that drug resistance in Uige has occurred through a combination of local drug pressure and the regional and international dispersal of resistance mutant alleles

Multiple sclerosis in South America: month of birth in different latitudes does not seem to interfere with the prevalence or progression of the disease

Objective To assess whether the month of birth in different latitudes of South America might influence the presence or severity of multiple sclerosis (MS) later in life. Methods Neurologists in four South American countries working at MS units collected data on their patients' month of birth, gender, age, and disease progression. Results Analysis of data from 1207 MS patients and 1207 control subjects did not show any significant variation in the month of birth regarding the prevalence of MS in four latitude bands (0–10; 11–20; 21–30; and 31–40 degrees). There was no relationship between the month of birth and the severity of disease in each latitude band. Conclusion The results from this study show that MS patients born to mothers who were pregnant at different Southern latitudes do not follow the seasonal pattern observed at high Northern latitudes

Esclerose multipla na America do Sul: mes de nascimento em diferentes latitudes nao parece interferir com a prevalencia ou progressao da doenca

Objective To assess whether the month of birth in different latitudes of South America might influence the presence or severity of multiple sclerosis (MS) later in life. Methods Neurologists in four South American countries working at MS units collected data on their patients' month of birth, gender, age, and disease progression. Results Analysis of data from 1207 MS patients and 1207 control subjects did not show any significant variation in the month of birth regarding the prevalence of MS in four latitude bands (0–10; 11–20; 21–30; e 31–40 degrees). There was no relationship between the month of birth and the severity of disease in each latitude band. Conclusion The results from this study show that MS patients born to mothers who were pregnant at different Southern latitudes do not follow the seasonal pattern observed at high Northern latitudes.Objetivo Avaliar se o mês de nascimento em diferentes latitudes da América do Sul pode influenciar a presença ou gravidade da esclerose múltipla (EM) na vida. Método Neurologistas de quatro países da América do Sul trabalhando em unidades de EM coletaram os dados de seus pacientes com referência ao mês de nascimento, gênero, idade e progressão da doença. Resultados A análise dos dados mostrou que, para 1207 pacientes com EM e 1207 controles, não havia diferença significativa no mês de nascimento com relação à prevalência de EM em quatro zonas de latitude (0–10; 11–20; 21–30; e 31–40 graus). Não houve relação entre o mês de nascimento e a gravidade da doença em nenhuma destas zonas. Conclusão Os resultados deste estudo mostram que pacientes com EM nascidos de mães grávidas em diferentes latitudes sul não seguem o padrão dos resultados sazonais encontrados nas latitudes norte.57357