[Emergencies in infectious diseases]. / Infektiologische Notfälle.

This article aims to provide an overview of common and high-impact medical emergencies that require prompt and effective infectious diseases management. In the described clinical scenarios of malaria, sepsis, necrotizing fasciitis, and meningitis the authors have emphasized the crucial importance of rapid and accurate diagnosis, as well as appropriate treatment from the perspective of infectious diseases. All of these emergencies demand a high degree of clinical suspicion for accurate diagnosis. Some of them also necessitate the involvement of other medical disciplines, such as neurology in the case of meningitis or surgery for necrotizing fasciitis. Additionally, implementing the right empiric antibiotic regimen or, in the case of malaria, antiparasitic treatment is crucial for improving patient outcomes. As patients with these diagnoses may present at any outpatient department, and efficient and quick management is essential, a deep understanding of diagnostic algorithms and potential pitfalls is of the utmost importance.

Active case detection and treatment of malaria in pregnancy using LAMP technology (LAMPREG): a pragmatic randomised diagnostic outcomes trial-study protocol.

INTRODUCTION: Malaria is one of the major public health problems in sub-Saharan Africa. It contributes significantly to maternal and fetal morbidity and mortality in affected countries. This study aims to evaluate the impact of enhanced case detection using molecular testing called loop-mediated isothermal amplification (LAMP) on birth outcomes in a prospective study design. METHODS AND ANALYSIS: A pragmatic randomised diagnostic outcomes trial will be conducted in several health institutes in different Ethiopian regions. Women (n=2583) in their first and second trimesters of pregnancy will be included in the study and individually randomised to the standard of care or enhanced case detection arms, and followed until delivery. Enrolment will encompass the malaria peak transmission seasons. In the standard of care arm, a venous blood sample will be collected for malaria diagnosis only in symptomatic patients. In contrast, in the intervention arm, mothers will be tested by a commercially available Conformité Européene (CE)-approved LAMP malaria test, microscopy and rapid diagnostic test for malaria regardless of their symptoms at each antenatal care visit. The primary outcome of the study is to measure birth weight. ETHICS AND DISSEMINATION: The study was approved by the following ethical research boards: Armauer Hansen Research Institute/ALERT Ethics Review Committee (FORM AF-10-015.1, Protocol number PO/05/20), the Ethiopia Ministry of Science and Higher Education National Research Ethics Review Committee (approval SRA/11.7/7115/20), the Ethiopia Food and Drug Administration (approval 02/25/33/I), UCalgary Conjoint Health Research Ethics Board (REB21-0234). The study results will be shared with the institutions and stakeholders such as the Ethiopia Ministry of Health, the Foundation for Innovative Diagnostics, WHO's Multilateral initiative on Malaria - Tropical Diseases Research (TDR-MIM), Roll Back Malaria and the Malaria in Pregnancy Consortium. The study results will also be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03754322.

The mechanisms of action of Plasmodium infection against cancer.

Our murine cancer model studies have demonstrated that Plasmodium infection activates the immune system that has been inhibited by cancer cells, counteracts tumor immunosuppressive microenvironment, inhibits tumor angiogenesis, inhibits tumor growth and metastasis, and prolongs the survival time of tumor-bearing mice. Based on these studies, three clinical trials of Plasmodium immunotherapy for advanced cancers have been approved and are ongoing in China. After comparing the mechanisms of action of Plasmodium immunotherapy with those of immune checkpoint blockade therapy, we propose the notion that cancer is an ecological disease and that Plasmodium immunotherapy is a systemic ecological counterattack therapy for this ecological disease, with limited side effects and without danger to public health based on the use of artesunate and other measures. Recent reports of tolerance to treatment and limitations in majority of patients associated with the use of checkpoint blockers further support this notion. We advocate further studies on the mechanisms of action of Plasmodium infection against cancer and investigations on Plasmodium-based combination therapy in the coming future. Video Abstract.

Mesenchymal Stem Cells: A Novel Therapeutic Approach to Enhance Protective Immunomodulation and Erythropoietic Recovery in Malaria.

Mesenchymal stem cells (MSCs) are self-renewing, multi-potent heterogeneous stem cells that display strong tissue protective and restorative properties by differentiating into cells of the mesodermal lineages. In addition to multi-lineage differentiation capacity, MSCs play important roles in regulating immune responses, inflammation, and tissue regeneration. MSCs play a role in the outcome of the pathogenesis of several infectious diseases. A unique subset of MSCs accumulates in secondary lymphoid organs during malaria disease progression. These MSCs counteract the capacity of malaria parasites to subvert activating co-stimulatory molecules and to regulate expression of negative co-stimulatory molecules on T lymphocytes. Consequently, MSCs have the capacity to restore the functions of CD34+ haematopoietic cells and CD4+ and CD8+ T cells during malaria infection. These observations suggest that cell-based therapeutics for intervention in malaria may be useful in achieving sterile clearance and preventing disease reactivation. In addition, MSCs provide host protection against malaria by reprogramming erythropoiesis through accelerated formation of colony-forming-units-erythroid (CFU-E) cells in the bone marrow. These findings suggest that MSCs are positive regulators of erythropoiesis, making them attractive targets for treatment of malarial anemia. MSC-based therapies, unlike anti-malarial drugs, display therapeutic effects by targeting a large variety of cellular processes rather than a single pathway. In the present review we focus on these recent research findings and discuss clinical applications of MSC-based therapies for malaria.

Transfusion management of severe anaemia in African children: a consensus algorithm.

The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40-60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mortality, depending on fever status (>37·5°C). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all 3196 children receiving an initial transfusion there was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice.

Transcriptome dynamics of CD4+ T cells during malaria maps gradual transit from effector to memory.

The dynamics of CD4+ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4+ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (TH1) and follicular helper T (TFH) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated TH1 and TFH trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between TFH and central memory were revealed, with antimalarials modulating these responses and boosting TH1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4+ T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene-gene correlations ( http://haquelab.mdhs.unimelb.edu.au/cd4_memory/ ).

Malaria elimination using the 1-3-7 approach: lessons from Sampov Loun, Cambodia.

BACKGROUND: Cambodia has targeted malaria elimination within its territory by 2025 and is developing a model elimination package of strategies and interventions designed to achieve this goal. METHODS: Cambodia adopted a simplified 1-3-7 surveillance model in the Sampov Loun operational health district in western Cambodia beginning in July 2015. The 1-3-7 approach targets reporting of confirmed cases within one day, investigation of specific cases within three days, and targeted control measures to prevent further transmission within seven days. In Sampov Loun, response measures included reactive case detection (testing of co-travelers, household contacts and family members, and surrounding households with suspected malaria cases), and provision of health education, and insecticide-treated nets. Day 28 follow up microscopy was conducted for all confirmed P. falciparum and P. falciparum-mixed-species malaria cases to assess treatment efficacy. RESULTS: The number of confirmed malaria cases in the district fell from 519 in 2015 to 181 in 2017, and the annual parasite incidence (API) in the district fell from 3.21 per 1000 population to 1.06 per 1000 population. The last locally transmitted case of malaria in Sampov Loun was identified in March 2016. In response to the 408 index cases identified, 1377 contacts were screened, resulting in the identification of 14 positive cases. All positive cases occurred among index case co-travelers. CONCLUSION: The experience of the 1-3-7 approach in Sampov Loun indicates that the basic essential malaria elimination package can be feasibly implemented at the operational district level to achieve the goal of malaria elimination in Cambodia and has provided essential information that has led to the refinement of this package.

Avaliação do cumprimento das atividades de monitoramento do tratamento e de verificação de cura da malária / Evaluación del cumplimiento de las actividades de seguimiento del tratamiento de la malaria y verificación de la curación / Assessment of compliance with malaria treatment monitoring and cure verification activities

RESUMO Objetivo: Avaliar o cumprimento das atividades de monitoramento do tratamento e verificação de cura pelos profissionais do Programa de Controle da Malária. Método: Trata-se de pesquisa avaliativa, realizada por meio de observação sistemática, com auxílio de formulário com escala Likert, adotando escore numérico para avaliar o cumprimento das atividades. A coleta dos dados foi realizada no município amazônico de Cruzeiro do Sul no estado do Acre. Os dados foram analisados por meio de estatística descritiva. Resultados: Foram observados 15 agentes de controle de endemias, 5 enfermeiros e 5 microscopistas, no desempenho de suas funções no programa. As atividades de monitoramento do tratamento e verificação de cura obtiveram os respectivos percentuais totais de cumprimento: 72,0% e 12,1%. Os microscopistas, avaliados em 9 atividades, obtiveram maior percentual de cumprimento de atividades, enquanto que enfermeiros e agentes de controle de endemias tiveram índice de cumprimento parcial ou não realizam determinadas atividades. Conclusão: O Programa de Controle da Malária apresenta desempenho abaixo do preconizado, não atendendo ao padrão ouro estabelecido, podendo significar a manutenção ou a elevação dos casos de malária.

RESUMEN Objetivo: Evaluar el cumplimiento de las actividades de seguimiento del tratamiento y verificación de curación por parte de los profesionales del Programa de Control de la Malaria. Método: Se trata de una investigación evaluativa, realizada a través de la observación sistemática, con la ayuda de una forma de escala Likert, adoptando una puntuación numérica para evaluar el cumplimiento de las actividades. La recolección de datos se realizó en el municipio amazónico de Cruzeiro do Sul en el estado de Acre. Los datos se analizaron mediante estadística descriptiva. Resultados: Se observaron 15 agentes de control endémico, 5 enfermeros y 5 microscopistas en el desempeño de sus funciones en el programa. Las actividades de seguimiento del tratamiento y verificación de curación obtuvieron los respectivos porcentajes totales de cumplimiento: 72,0% y 12,1%. Los microscopistas, evaluados en 9 actividades, obtuvieron un mayor porcentaje de cumplimiento de las actividades, mientras que las enfermeras y agentes de control endémico tuvieron una tasa de cumplimiento parcial o no realizaron determinadas actividades. Conclusión: El Programa de Control de la Malaria se desempeña por debajo del nivel recomendado, sin cumplir con el estándar de oro establecido, lo que puede significar mantener o aumentar los casos de malária.

ABSTRACT Objective: To assess compliance with treatment monitoring and cure verification activities by Malaria Control Program professionals. Method: This is an evaluation research carried out through systematic observation, with the aid of a Likert-type scale form, adopting a numerical score to assess the fulfillment of activities. Data collection was carried out in the Amazonian municipality of Cruzeiro do Sul in Acre State. Data were analyzed using descriptive statistics. Results: Fifteen endemic disease control agents, five nurses and five microscopists were observed in the performance of their functions in the program. Treatment monitoring and cure verification activities obtained the respective total compliance percentages of 72.0% and 12.1%. Microscopists, assessed in 9 activities, obtained a higher percentage of compliance with activities, while nurses and endemic disease control agents had a partial compliance rate or did not perform certain activities. Conclusion: Malaria Control Program performs below the recommended level, not meeting the established gold standard, which may mean maintaining or increasing malaria cases.

Investigating the impact of enhanced community case management and monthly screening and treatment on the transmissibility of malaria infections in Burkina Faso: study protocol for a cluster-randomised trial.

INTRODUCTION: A large proportion of malaria-infected individuals in endemic areas do not experience symptoms that prompt treatment-seeking. These asymptomatically infected individuals may retain their infections for many months during which sexual-stage parasites (gametocytes) are produced that may be transmissible to mosquitoes. Reductions in malaria transmission could be achieved by detecting and treating these infections early. This study assesses the impact of enhanced community case management (CCM) and monthly screening and treatment (MSAT) on the prevalence and transmissibility of malaria infections. METHODS AND ANALYSIS: This cluster-randomised trial will take place in Sapone, an area of intense, highly seasonal malaria in Burkina Faso. In total, 180 compounds will be randomised to one of three interventions: arm 1 - current standard of care with passively monitored malaria infections; arm 2 - standard of care plus enhanced CCM, comprising active weekly screening for fever, and detection and treatment of infections in fever positive individuals using conventional rapid diagnostic tests (RDTs); or arm 3 - standard of care and enhanced CCM, plus MSAT using RDTs. The study will be conducted over approximately 18 months covering two high-transmission seasons and the intervening dry season. The recruitment strategy aims to ensure that overall transmission and force of infection is not affected so we are able to continuously evaluate the impact of interventions in the context of ongoing intense malaria transmission. The main objectives of the study are to determine the impact of enhanced CCM and MSAT on the prevalence and density of parasitaemia and gametocytaemia and the transmissibility of infections. This will be achieved by molecular detection of infections in all study participants during start and end season cross-sectional surveys and routine sampling of malaria-positive individuals to assess their infectiousness to mosquitoes. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the London School of Hygiene and Tropical Medicine (LSHTM) (Review number: 14724) and The Centre National de Recherche et de Formation sur le Paludisme institutional review board (IRB) (Deliberation N° 2018/000002/MS/SG/CNRFP/CIB) and Burkina Faso national medical ethics committees (Deliberation N° 2018-01-010).Findings of the study will be shared with the community via local opinion leaders and community meetings. Results may also be shared through conferences, seminars, reports, theses and peer-reviewed publications; disease occurrence data and study outcomes will be shared with the Ministry of Health. Data will be published in an online digital repository. TRIAL REGISTRATION NUMBER: NCT03705624.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis / Das descrições de Charcot à compreensão atual dos sintomas neuropsiquiátricos na esclerose múltipla

ABSTRACT Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

RESUMO Os distúrbios neuropsiquiátricos na esclerose múltipla são conhecidos desde a descrição clínico-patológica original de Charcot no final do século XIX. Charcot nas últimas décadas de sua vida se envolveu no campo da neuropsiquiatria. Isso produziu uma batalha de escolas rivais na época que ainda ecoa até hoje. A intuição de Charcot, incluindo a linha de pensamento de Babinski, um de seus discípulos mais famosos, foi a teoria correta da conexão entre os transtornos do humor e muitas das doenças do sistema nervoso. A preocupação da Medicina em estabelecer uma relação entre transtornos do humor e doenças vem das idades antiga e média, com referências encontradas na doutrina hipocrática. No entanto, foi apenas na segunda metade do século XIX e início do século XX que, com as descobertas de Charcot essa discussão foi realizada de maneira estruturada, estabelecendo os fundamentos da neuropsiquiatria.

Different doses of vitamin C supplementation enhances the Th1 immune response to early Plasmodium yoelii 17XL infection in BALB/c mice.

Vitamin C (ascorbate) is maintained at high levels in most immune cells and can affect many aspects of the immune response. Here, we evaluated the effect of vitamin C supplementation on the immune response to Plasmodium yoelii 17XL (P. yoelii 17XL) infection in BALB/c mice. Two orally administered doses (25 mg/kg/day and 250 mg/kg/day) of vitamin C significantly reduced levels of parasitemia during the early stages of P. yoelii 17XL infection. The numbers of activated Th1 cells and macrophages in the groups receiving vitamin C supplementation were both higher than those in the untreated group. Meanwhile, vitamin C administration reduced the levels of tumor necrosis factor α secreted by splenocytes. Vitamin C also regulated the protective anti-malarial immune response by increasing the number of plasmacytoid dendritic cells, as well as the expression of dendritic cell maturation markers, such as major histocompatibility complex class II and cluster of differentiation 86. In conclusion, the doses of vitamin C (25 mg/kg/day, 250 mg/kg/day) during the early stages of malaria infection may better enhance host protective immunity, but have no dose dependence.

Unresolved Splenomegaly in Recently Resettled Congolese Refugees - Multiple States, 2015-2018.

In 2014, panel physicians from the International Organization for Migration (IOM), who conduct Department of State-required predeparture examinations for U.S.-bound refugees at resettlement sites in Uganda, noticed an unusually high number of Congolese refugees with enlarged spleens, or splenomegaly. Many conditions can cause splenomegaly, such as various infections, liver disease, and cancer. Splenomegaly can result in hematologic disturbances and abdominal pain and can increase the risk for splenic rupture from blunt trauma, resulting in life-threatening internal bleeding. On CDC's advice, panel physicians implemented an enhanced surveillance and treatment protocol that included screening for malaria (through thick and thin smears and rapid diagnostic testing), schistosomiasis, and several other conditions; treatment of any condition identified as potentially associated with splenomegaly; and empiric treatment for the most likely etiologies, including malaria and schistosomiasis. CDC recommended further treatment for malaria with primaquine after arrival, after glucose-6-phosphate dehydrogenase testing, to target liver-stage parasites. Despite this recommended treatment protocol, 35 of 64 patients with available follow-up records had splenomegaly that persisted beyond 6 months after resettlement. Among 85 patients who were diagnosed with splenomegaly through abdominal palpation or ultrasound at any point after resettlement, 53 had some hematologic abnormality (leukopenia, anemia, or thrombocytopenia), 16 had evidence of current or recent malaria infection, and eight had evidence of schistosomiasis. Even though primaquine was provided to a minority of patients in this cohort, it should be provided to all eligible patients with persistent splenomegaly, and repeated antischistosomal therapy should be provided to patients with evidence of current or recent schistosomiasis. Given substantial evidence of familial clustering of cases, family members of patients with known splenomegaly should be proactively screened for this condition.

Aspidosperma pyrifolium, a medicinal plant from the Brazilian caatinga, displays a high antiplasmodial activity and low cytotoxicity.

BACKGROUND: Several species of Aspidosperma plants are referred to as remedies for the treatment of malaria, especially Aspidosperma nitidum. Aspidosperma pyrifolium, also a medicinal plant, is used as a natural anti-inflammatory. Its fractionated extracts were assayed in vitro for activity against malaria parasites and for cytotoxicity. METHODS: Aspidosperma pyrifolium activity was evaluated against Plasmodium falciparum using extracts in vitro. Toxicity towards human hepatoma cells, monkey kidney cells or human monocytes freshly isolated from peripheral blood was also assessed. Anti-malarial activity of selected extracts and fractions that presented in vitro activity were tested in mice with a Plasmodium berghei blood-induced infection. RESULTS: The crude stem bark extract and the alkaloid-rich and ethyl acetate fractions from stem extract showed in vitro activity. None of the crude extracts or fractions was cytotoxic to normal monkey kidney and to a human hepatoma cell lines, or human peripheral blood mononuclear cells; the MDL50 values of all the crude bark extracts and fractions were similar or better when tested on normal cells, with the exception of organic and alkaloidic-rich fractions from stem extract. Two extracts and two fractions tested in vivo caused a significant reduction of P. berghei parasitaemia in experimentally infected mice. CONCLUSION: Considering the high therapeutic index of the alkaloidic-rich fraction from stem extract of A. pyrifolium, it makes the species a candidate for further investigation aiming to produce a new anti-malarial, especially considering that the active extract has no toxicity, i.e., no mutagenic effects in the genototoxicity assays, and that it has an in vivo anti-malarial effect. In its UPLC-HRMS analysis this fraction was shown to have two major components compatible with the bisindole alkaloid Leucoridine B, and a novel compound, which is likely to be responsible for the activity against malaria parasites demonstrated in in vitro tests.

Recidiva de Malária: relato de caso / Malaria recurrence: case report

A malária caracteriza-se pela invasão de parasitas do gênero Plasmodium, considerada a principal parasitose tropical e uma das mais frequentes no mundo. Este relato tem como objetivo descrever um caso de malária, encontrado numa zona não endêmica, onde o paciente apresentou recidiva para P. vivax. Relato de caso: V.C.B, masculino, 63 anos. Apresentou sintomas de febre, dores de cabeça, tremores e sudorese, dez meses após uma viagem à Amazônia. O paciente foi encaminhado para exames, sendo diagnosticado com recidiva para o Plasmodium vivax. Considerações finais: É de extrema importância que profissionais e estudantes da saúde saibam diagnosticar corretamente a malária, assim como a possível presença de recidivas, a fim de minimizar erros de diagnóstico e uma correta profilaxia para o paciente.

The use of cytapheresis in the treatment of infectious diseases.

Cytapheresis (removal of cellular blood components) has been employed for treatment of infectious diseases since the 1960s. Techniques have included thrombocytapheresis (buffy coat apheresis) for loiasis, erythrocytapheresis for malaria and babesiosis, and leukocytapheresis for pertussis-associated lymphocytosis. Published data on these applications is largely limited to case level data and small observational studies; as such, recommendations for or against the use of cytapheresis in the treatment of infections have been extrapolated from these limited (and at times flawed) data sets. Consequently, utilization of cytapheresis in many instances is not uniform between institutions, and typically occurs at the discretion of treating medical teams. This review revisits the existing literature on the use of cytapheresis in the treatment of four infections (loasis, malaria, babesiosis, and pertussis) and examines the rationale underlying current treatment recommendations concerning its use.

Immune checkpoint blockade in infectious diseases.

The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus. These pathways are important for preventing immune-driven pathology but can also limit immune-mediated clearance of the infection. The recent success of immune checkpoint blockade in cancer therapy suggests that targeting these pathways would also be effective for preventing and treating a range of infectious diseases. Here, we review our current understanding of immune checkpoint pathways in the pathogenesis of infectious diseases and discuss the potential for therapeutically targeting these pathways in this setting.

Small-quantity lipid-based nutrient supplements containing different amounts of zinc along with diarrhea and malaria treatment increase iron and vitamin A status and reduce anemia prevalence, but do not affect zinc status in young Burkinabe children: a cluster-randomized trial.

BACKGROUND: We assessed the effects of providing a package of interventions including small-quantity lipid-based nutrient supplements (SQ-LNS) containing 0, 5 or 10 mg zinc and illness treatment to Burkinabe children from 9 to 18 months of age, on biomarkers of zinc, iron and vitamin A status at 18 months and compared with a non-intervention cohort (NIC). METHODS: Using a two-stage cluster randomized trial design, communities were randomly assigned to the intervention cohort (IC) or NIC, and extended family compounds within the IC were randomly assigned to different treatment groups. IC children (n = 2435) were provided with 20 g SQ-LNS/d containing 0, 5 or 10 mg zinc, 6 mg of iron and 400 µg of vitamin A along with malaria and diarrhea treatment. NIC children (n = 785) did not receive the intervention package. At 9 and 18 months, hemoglobin (Hb), zinc, iron and vitamin A status were assessed in a sub-group (n = 404). Plasma concentrations of zinc (pZC), ferritin (pF), soluble transferrin receptor (sTfR) and retinol-binding protein (RBP) were adjusted for inflammation. RESULTS: At baseline, 35% of children had low adjusted pZC (<65 µg/dL), 93% were anemic (Hb <110 g/L), 25% had low adjusted pF (<12 µg/L), 90% had high adjusted sTfR (>8.3 mg/L) and 47% had low adjusted RBP (<0.94 µmol/L), with no group-wise differences. Compared with the NIC, at 18 months IC children had significantly lower anemia prevalence (74 vs. 92%, p = 0.001) and lower iron deficiency prevalence (13% vs. 32% low adjusted pF and 41% vs. 71% high adjusted sTfR, p < 0.001), but no difference in pZC. Mean adjusted RBP was greater at 18 months in IC vs. NIC (0.94 µmol/L vs. 0.86 µmol/L, p = 0.015), but the prevalence of low RBP remained high in both cohorts. Within the IC, different amounts of zinc had no effect on the prevalence of low pZC or indicators of vitamin A deficiency, whereas children who received SQ-LNS with 10 mg zinc had a significantly lower mean pF at 18 months compared to children who received SQ-LNS with 5 mg zinc (p = 0.034). CONCLUSIONS: SQ-LNS regardless of zinc amount and source provided along with illness treatment improved indicators of iron and vitamin A status, but not pZC. TRIAL REGISTRATION: NCT00944281 (July 21, 2009).

Factors associated with timely treatment of malaria in the Brazilian Amazon: a 10-year population-based study / Factores asociados con el tratamiento oportuno de la malaria en la Amazonia brasileña: estudio de 10 años basado en la población / Fatores associados ao tratamento precoce da malária na Amazônia brasileira: um estudo populacional de 10 anos

ABSTRACT Objective To identify factors associated with timely treatment of malaria in the Brazilian Amazon. Malaria, despite being treatable, has proven difficult to control and continues to be an important public health problem globally. Brazil accounted for almost half of the 427 000 new malaria cases notified in the Americas in 2013. Methods This was a cross-sectional study using secondary data on all notified malaria cases for the period from 2004 - 2013. Timely treatment was considered to be all treatment started within 24 hours of symptoms onset. Multivariate logistic regression was used to identify independent factors associated with timely treatment. Results The proportion of cases starting treatment on a timely basis was 41.1%, tending to increase in more recent years (OR = 1.40; 95%CI: 1.37 - 1.42 in 2013). Furthermore, people starting within < 24 hours were more likely to: reside in the states of Rondônia (OR = 1.50; 95%CI: 1.49 - 1.51) or Acre (OR = 1.53; 95%CI: 1.55 - 1.57); be 0 - 5 years of age (OR = 1.39; 95%CI: 1.34 - 1.44) or 6 - 14 years of age (OR = 1.34; 95%CI: 1.32 - 1.36); be indigenous (OR = 1.41; 95%CI: 1.37 - 1.45); have a low level of schooling (OR = 1.20; 95%CI: 1.19 - 1.22); and be diagnosed by active detection (OR = 1.39; 95%CI: 1.38 - 1.39). Conclusion In the Brazilian Amazon area, individuals were more likely to have timely treatment of malaria if they were young, residing in Acre or Rondônia states, have little schooling, and be identified through active detection. Identifying groups vulnerable to late treatment is important for preventing severe cases and malaria deaths.

RESUMEN Objetivo Determinar los factores asociados con el tratamiento oportuno de la malaria en la Amazonia brasileña. La malaria, a pesar de que es tratable, ha resultado difícil de controlar y sigue siendo un problema importante de salud pública mundial. En Brasil se notificaron casi la mitad de los 427 000 nuevos casos de malaria en la Región de las Américas en el 2013. Métodos Se realizó un estudio transversal que utilizó datos secundarios de todos los casos notificados de malaria en el período 2004-2013. Se entendió como tratamiento oportuno todo tratamiento iniciado en las 24 horas posteriores a la aparición de los síntomas. Para determinar los factores independientes asociados con el tratamiento oportuno, se usó el método de regresión logística multifactorial. Resultados La proporción de casos en los que se inició el tratamiento oportunamente fue de 41,1%, con una tendencia ascendente en los últimos años (razón de posibilidades [OR] = 1,40; IC 95%: 1,37 - 1,42 en el 2013). Además, en las personas que comenzaron el tratamiento menos de 24 horas después de la aparición de los síntomas era mayor la probabilidad de que residieran en los estados de Rondônia (OR = 1,50; IC 95%: 1,49 - 1,51) o Acre (OR = 1,53; IC 95%: 1,55 - 1,57); también era mayor la probabilidad de que tuvieran entre 0 y 5 años (OR = 1,39; IC 95%: 1,34 - 1,44) o entre 6 y 14 años (OR = 1,34; IC 95%: 1,32 - 1,36); fueran indígenas (OR = 1,41; IC 95%: 1,37 - 1,45); tuvieran un nivel bajo de escolarización (OR = 1,20; IC 95%: 1,19 - 1,22) y hubieran sido diagnosticadas por detección activa (OR = 1,39; IC 95%: 1,38 - 1,39). Conclusiones En la zona de la Amazonia brasileña, era más probable que las personas que iniciaban oportunamente el tratamiento contra la malaria fueran jóvenes, residieran en los estados de Acre o Rondônia, tuvieran un nivel bajo de escolarización y fueran detectadas mediante la detección activa. La identificación de los grupos vulnerables al tratamiento tardío es importante para prevenir los casos graves y las muertes por malaria.

RESUMO Objetivo Identificar os fatores associados ao tratamento precoce da malária na Amazônia brasileira. Embora seja tratável, a malária tem sido difícil de controlar e continua a representar um importante problema de saúde pública em escala mundial. Em 2013, o Brasil registrou quase a metade dos 427.000 novos casos de malária notificados nas Américas. Métodos Este foi um estudo transversal que utilizou dados secundários sobre todos os casos de malária notificados no período de 2004 a 2013. O tratamento precoce foi definido como todo tratamento iniciado nas primeiras 24 horas desde o surgimento dos sintomas. Utilizamos a regressão logística multivariada para identificar fatores independentes associados ao tratamento precoce. Resultados A proporção de casos que iniciaram tratamento precoce foi de 41,1%, tendendo a aumentar em anos mais recentes (odds ratio [OR] = 1,40; IC 95%: 1,37 - 1,42 em 2013). Além disso, as pessoas que iniciaram o tratamento em menos de 24 horas tiveram maior probabilidade de: residir nos estados de Rondônia (OR = 1,50; IC 95%: 1,49 - 1,51) ou Acre (OR = 1,53; IC 95%: 1,55 - 1,57); ter entre 0 e 5 anos de idade (OR = 1,39; IC 95%: 1,34 - 1,44) ou entre 6 e 14 anos de idade (OR = 1,34; IC 95%: 1,32 - 1,36); ser indígena (OR = 1,41; IC 95%: 1,37 - 1,45); ter um baixo nível de escolaridade (OR = 1,20; IC 95%: 1,19 - 1,22); e ser diagnosticado por meio da detecção ativa (OR = 1,39; IC 95%: 1,38 - 1,39). Conclusão Na região da Amazônia brasileira, as pessoas têm uma maior probabilidade de receber tratamento precoce para a malária se forem jovens, residirem nos estados do Acre ou de Rondônia, tiverem um baixo nível de escolaridade e forem identificadas através da detecção ativa. A identificação de grupos vulneráveis ao tratamento tardio é importante para prevenir os casos graves e as mortes decorrentes da malária.

Hematologic Changes Associated with Specific Infections in the Tropics.

Anemia frequently accompanies and plays a minor role in the presentation and course of infection, whether parasitic, bacterial, or viral. However, a variety of infections, many of which are common in Africa and Asia, cause specific hematologic syndromes. The pathophysiology of these syndromes is complex, and to some extent, reduced red cell production may form part of an innate protective host response to infection. Across the world and in endemic areas, malaria is the most important among this group of infections and forms a major part of everyday practice.