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BACKGROUND: Yearly bronchiolitis and influenza-like illness epidemics in France often involve high morbidity and mortality, which severely impacts healthcare. Epidemics are declared by the French National Institute of Public Health based on syndromic surveillance of primary care and emergency departments (ED), using statistics-based alarms. Although the effective reproduction number (Rt) is used to monitor the dynamics of epidemics, it has never been used as an early warning tool for bronchiolitis or influenza-like illness epidemics in France.We assessed whether Rt is useful for detecting seasonal epidemics by comparing it to the tool currently used (MASS) by epidemiologists to declare epidemic phases. METHODS: We used anonymized ED syndromic data from the Île-de-France region in France from 2010 to 2022. We estimated Rt and compared the indication of accelerated transmission (Rt >1) to the MASS epidemic alarm time points. We computed the difference between those two time points, time to epidemic peak, and the daily cases documented at first indication and peak. RESULTS: Rt provided alarms for influenza-like illness and bronchiolitis epidemics that were, respectively, 6 days (IQR[4;8]) and 64 days (IQR[52;80]) - in median - earlier than the alarms provided by MASS. CONCLUSION: Rt detected earlier signals of bronchiolitis and influenza-like illness epidemics. Using this early-warning indicator in combination with others to declare an annual epidemic could provide opportunities to improve healthcare system readiness.
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BackgroundDuring the 2022 mpox outbreak in Europe, primarily affecting men who have sex with men, a limited number of cases among children and adolescents were identified. Paediatric cases from outbreaks in endemic countries have been associated with a higher likelihood of severe illness. Detailed clinical case descriptions and interventions in school settings before 2022 are limited.AimTo describe clinical characteristics of mpox cases among children (<â¯15 years) and adolescents (15-17 years) in the greater Paris area in France, and infection control measures in schools.MethodsWe describe all notified laboratory-confirmed and non-laboratory-confirmed cases among children and adolescents identified from May 2022 to July 2023, including demographic and clinical characterisation and infection control measures in school settings, i.e. contact tracing, contact vaccination, secondary attack rate and post-exposure vaccination uptake.ResultsNineteen cases were notified (13 children, 6 adolescents). Four adolescent cases reported sexual contact before symptom onset. Ten child cases were secondary cases of adult patients; three cases were cryptic, with vesicles on hands, arms and/or legs and one case additionally presented with genitoanal lesions. Five cases attended school during their infectious period, with 160 at-risk contacts identified, and one secondary case. Five at-risk contacts were vaccinated following exposure.ConclusionCases among children and adolescents are infrequent but require a careful approach to identify the source of infection and ensure infection control measures. We advocate a 'contact warning' strategy vs 'contact tracing' in order to prevent alarm and stigma. Low post-exposure vaccination rates are expected.
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Busca de Comunicante , Surtos de Doenças , Instituições Acadêmicas , Humanos , Adolescente , Masculino , Criança , Feminino , Surtos de Doenças/prevenção & controle , Paris/epidemiologia , Vacinação/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Seguimentos , Infecções Meningocócicas/prevenção & controle , Infecções Meningocócicas/epidemiologiaRESUMO
BackgroundWastewater surveillance is an effective approach to monitor population health, as exemplified by its role throughout the COVID-19 pandemic.AimThis study explores the possibility of extending wastewater surveillance to the Paris 2024 Olympic and Paralympic Games, focusing on identifying priority pathogen targets that are relevant and feasible to monitor in wastewater for these events.MethodsA list of 60 pathogens of interest for general public health surveillance for the Games was compiled. Each pathogen was evaluated against three inclusion criteria: (A) analytical feasibility; (B) relevance, i.e. with regards to the specificities of the event and the characteristics of the pathogen; and (C) added value to inform public health decision-making. Analytical feasibility was assessed through evidence from peer-reviewed publications demonstrating the detectability of pathogens in sewage, refining the initial list to 25 pathogens. Criteria B and C were evaluated via expert opinion using the Delphi method. The panel consisting of some 30 experts proposed five additional pathogens meeting criterion A, totalling 30 pathogens assessed throughout the three-round iterative questionnaire. Pathogens failing to reach 70% group consensus threshold underwent further deliberation by a subgroup of experts.ResultsSix priority targets suitable for wastewater surveillance during the Games were successfully identified: poliovirus, influenza A virus, influenza B virus, mpox virus, SARS-CoV-2 and measles virus.ConclusionThis study introduced a model framework for identifying context-specific wastewater surveillance targets for a mass gathering. Successful implementation of a wastewater surveillance plan for Paris 2024 could incentivise similar monitoring efforts for other mass gatherings globally.
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COVID-19 , SARS-CoV-2 , Águas Residuárias , Humanos , Águas Residuárias/virologia , Águas Residuárias/microbiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , SARS-CoV-2/isolamento & purificação , França/epidemiologia , Esportes , Saúde Pública , Pandemias , Esgotos/virologia , Paris/epidemiologia , Aniversários e Eventos Especiais , Vigilância em Saúde Pública/métodosRESUMO
A cluster of three confirmed autochthonous dengue cases was detected in October 2023 in the Val-de-Marne department neighbouring Paris, France. This marks the northernmost transmission of dengue in Europe reported to date. The epidemiological and microbiological investigations and the vector control measures are described. This event confirms the need for early case detection and response to contain dengue in Europe, especially given the 2024 Summer Olympic and Paralympic Games, when millions of visitors will visit the Greater Paris area.
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Aedes , Dengue , Esportes , Humanos , Animais , Paris/epidemiologia , Dengue/diagnóstico , Dengue/epidemiologia , Dengue/prevenção & controle , França/epidemiologia , Europa (Continente)/epidemiologia , Surtos de Doenças/prevenção & controleRESUMO
BackgroundLocally-acquired mpox cases were rarely reported outside Africa until May 2022, when locally-acquired-mpox cases occurred in various European countries.AimWe describe the mpox epidemic in France, including demographic and behavioural changes among a subset of cases, during its course.MethodsData were retrieved from the enhanced national surveillance system until 30 September 2022. Laboratory-confirmed cases tested positive for monkeypox virus or orthopoxviruses by PCR; non-laboratory-confirmed cases had clinical symptoms and an epidemiological link to a laboratory-confirmed case. A subset of ≥ 15-year-old male cases, notified until 1 August, was interviewed for epidemiological, clinical and sexual behaviour information. Association of symptom-onset month with quantitative outcomes was evaluated by t- or Wilcoxon tests, and with binary outcomes, by Pearson's chi-squared or Fisher exact tests.ResultsA total of 4,856 mpox cases were notified, mostly in Île-de-France region (62%; 3,025/4,855). Cases aged ≥ 15 years were predominantly male (97%; 4,668/4,812), with 37 years (range: 15-81) as mean age. Between May and July, among the subset interviewed, mpox cases increased in regions other than Île-de-France, and mean age rose from 35 (range: 21-64) to 38 years (range: 16-75; p = 0.007). Proportions of cases attending men-who-have-sex-with-men (MSM) meeting venues declined from 60% (55/91) to 46% (164/359; p = 0.012); median number of sexual partners decreased from four (interquartile range (IQR): 1-10) to two (IQR: 1-4; p < 0.001).ConclusionChanges in cases' characteristics during the epidemic, could reflect virus spread from people who were more to less behaviourally vulnerable to mpox between May and July, or MSM reducing numbers of sexual partners as recommended.
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Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Adolescente , Feminino , Homossexualidade Masculina , Comportamento Sexual , Surtos de Doenças , França/epidemiologiaRESUMO
BACKGROUND: In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. METHODS: The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. RESULTS: The proposed weight-based regimen has 5 dosing bands: (i) 5-7 kg, 5 mg, resulting in 0.71-1.0 mg/kg/day; (ii) 8-16 kg, 7.5 mg, 0.47-0.94 mg/kg/day; (iii) 17-40 kg, 15 mg, 0.38-0.88 mg/kg/day; (iv) 41-80 kg, 30 mg, 0.37-0.73 mg/kg/day; and (v) 81-100 kg, 45 mg, 0.45-0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6-11 months, 5 mg, 0.43-1.0 mg/kg/day; (ii) 1-5 years, 7.5 mg, 0.35-1.25 mg/kg/day; (iii) 6-14 years, 15 mg, 0.30-1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35-1.07 mg/kg/day. CONCLUSION: The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.
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Antimaláricos/administração & dosagem , Esquema de Medicação , Malária Vivax/prevenção & controle , Plasmodium vivax/efeitos dos fármacos , Primaquina/administração & dosagem , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: In 2017, New Caledonia experienced an outbreak of severe dengue causing high hospital burden (4379 cases, 416 hospital admissions, 15 deaths). We decided to build a local operational model predictive of dengue severity, which was needed to ease the healthcare circuit. METHODS: We retrospectively analyzed clinical and biological parameters associated with severe dengue in the cohort of patients hospitalized at the Territorial Hospital between January and July 2017 with confirmed dengue, in order to elaborate a comprehensive patient's score. Patients were compared in univariate and multivariate analyses. Predictive models for severity were built using a descending step-wise method. RESULTS: Out of 383 included patients, 130 (34%) developed severe dengue and 13 (3.4%) died. Major risk factors identified in univariate analysis were: age, comorbidities, presence of at least one alert sign, platelets count < 30 × 109/L, prothrombin time < 60%, AST and/or ALT > 10 N, and previous dengue infection. Severity was not influenced by the infecting dengue serotype nor by previous Zika infection. Two models to predict dengue severity were built according to sex. Best models for females and males had respectively a median Area Under the Curve = 0.80 and 0.88, a sensitivity = 84.5 and 84.5%, a specificity = 78.6 and 95.5%, a positive predictive value = 63.3 and 92.9%, a negative predictive value = 92.8 and 91.3%. Models were secondarily validated on 130 patients hospitalized for dengue in 2018. CONCLUSION: We built robust and efficient models to calculate a bedside score able to predict dengue severity in our setting. We propose the spreadsheet for dengue severity score calculations to health practitioners facing dengue outbreaks of enhanced severity in order to improve patients' medical management and hospitalization flow.
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Dengue/classificação , Dengue/diagnóstico , Dengue/epidemiologia , Dengue/patologia , Feminino , Hospitalização , Humanos , Masculino , Modelos Teóricos , Nova Caledônia/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , TriagemRESUMO
OBJECTIVE: To better understand the potential risks of Nipah virus emergence in Cambodia by studying different components of the interface between humans and bats. METHODS: From 2012 to 2016, we conducted a study at two sites in Kandal and Battambang provinces where fruit bats (Pteropus lylei) roost. We combined research on: bat ecology (reproductive phenology, population dynamics and diet); human practices and perceptions (ethnographic research and a knowledge, attitude and practice study); and Nipah virus circulation in bat and human populations (virus monitoring in bat urine and anti-Nipah-virus antibody detection in human serum). FINDINGS: Our results confirmed circulation of Nipah virus in fruit bats (28 of 3930 urine samples positive by polymerase chain reaction testing). We identified clear potential routes for virus transmission to humans through local practices, including fruit consumed by bats and harvested by humans when Nipah virus is circulating, and palm juice production. Nevertheless, in the serological survey of 418 potentially exposed people, none of them were seropositive to Nipah virus. Differences in agricultural practices among the regions where Nipah virus has emerged may explain the situation in Cambodia and point to actions to limit the risks of virus transmission to humans. CONCLUSION: Human practices are key to understanding transmission risks associated with emerging infectious diseases. Social science disciplines such as anthropology need to be integrated in health programmes targeting emerging infectious diseases. As bats are hosts of major zoonotic pathogens, such integrated studies would likely also help to reduce the risk of emergence of other bat-borne diseases.
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Quirópteros/virologia , Infecções por Henipavirus/psicologia , Infecções por Henipavirus/transmissão , Vírus Nipah/isolamento & purificação , Animais , Antropologia Cultural , Anticorpos Antivirais , Camboja/epidemiologia , Feminino , Frutas , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Henipavirus/epidemiologia , Infecções por Henipavirus/urina , Humanos , Masculino , Vírus Nipah/imunologia , Fatores de Risco , Zoonoses/virologiaRESUMO
In Cambodia, dengue outbreaks occur each rainy season (May-October) but vary in magnitude. Using national surveillance data, we designed a tool that can predict 90% of the variance in peak magnitude by April, when typically <10% of dengue cases have been reported. This prediction may help hospitals anticipate excess patients.
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Dengue/epidemiologia , Surtos de Doenças , Camboja/epidemiologia , Dengue/virologia , Vírus da Dengue/classificação , Humanos , Vigilância da População , Estações do Ano , SorogrupoRESUMO
We investigated dengue virus (DENV) and asymptomatic DENV infections in rural villages of Kampong Cham Province, Cambodia, during 2012 and 2013. We conducted perifocal investigations in and around households for 149 DENV index cases identified through hospital and village surveillance. We tested participants 0.5-30 years of age by using nonstructural 1 rapid tests and confirmed DENV infections using quantitative reverse transcription PCR or nonstructural 1-capture ELISA. We used multivariable Poisson regressions to explore links between participants' DENV infection status and household characteristics. Of 7,960 study participants, 346 (4.4%) were infected with DENV, among whom 302 (87.3%) were <15 years of age and 225 (65.0%) were <9 years of age. We identified 26 (7.5%) participants with strictly asymptomatic DENV infection at diagnosis and during follow-up. We linked symptomatic DENV infection status to familial relationships with index cases. During the 2-year study, we saw fewer asymptomatic DENV infections than expected based on the literature.
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Doenças Assintomáticas/epidemiologia , Vírus da Dengue , Dengue/epidemiologia , Dengue/virologia , Adolescente , Adulto , Fatores Etários , Camboja/epidemiologia , Criança , Pré-Escolar , Dengue/diagnóstico , Dengue/história , Surtos de Doenças , Feminino , História do Século XXI , Humanos , Masculino , Programas de Rastreamento , Vigilância em Saúde Pública , Vigilância de Evento Sentinela , Adulto JovemRESUMO
Longitudinal surveillance of 2 live bird markets in Cambodia revealed year-round, high co-circulation of H5, H7, and H9 influenza viruses. We detected influenza A viruses in 51.3% of ducks and 39.6% of chickens, and co-infections, mainly by H5 and H9 viruses, in 0.8% of ducks and 4.5% of chickens.
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Galinhas , Patos , Vírus da Influenza A/classificação , Influenza Aviária/virologia , Animais , Camboja/epidemiologia , Comércio , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/epidemiologia , Fatores de TempoRESUMO
Postexposure prophylaxis (PEP) prevents human rabies and is accessible in Cambodia principally in Phnom Penh, the capital. Timely, affordable access to PEP is a challenge for the mainly rural population. We aimed to identify districts independently associated with PEP noncompletion to position frontline vaccination centers. We analyzed the 2009-2013 database at the Rabies Prevention Center at the Institut Pasteur du Cambodge, Phnom Penh. Logistic regressions identified nongeographic determinants of PEP noncompletion as well as the districts that were independently associated with noncompletion after adjustment for these determinants. The influence of distance by road was estimated using a boosted regression-trees model. We computed a population attributable fraction (rabies index (RI)) for each district and developed a map of this RI distribution. A cartographic analysis based on the statistic developed by Getis and Ord identified clusters of high-RI districts. Factors independently associated with noncompletion were patients' district of residence, male sex, age 15-49 years, initial visit during rice harvest, the dog's status (culled or disappeared), and a prescribed PEP protocol requiring more than 3 PEP sessions (4 or 5). Four clusters of high-RI districts were identified using this analytical strategy, which is applicable to many vaccination or other health services. Positioning frontline PEP centers in these districts could significantly widen access to timely and adequate PEP.
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Mordeduras e Picadas/epidemiologia , Cães , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Profilaxia Pós-Exposição/estatística & dados numéricos , Raiva/prevenção & controle , Adolescente , Adulto , Animais , Mordeduras e Picadas/virologia , Camboja/epidemiologia , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Raiva/virologia , Vírus da Raiva , População Rural/estatística & dados numéricos , Adulto JovemRESUMO
Three-quarters of the estimated 390 million dengue virus (DENV) infections each year are clinically inapparent. People with inapparent dengue virus infections are generally considered dead-end hosts for transmission because they do not reach sufficiently high viremia levels to infect mosquitoes. Here, we show that, despite their lower average level of viremia, asymptomatic people can be infectious to mosquitoes. Moreover, at a given level of viremia, DENV-infected people with no detectable symptoms or before the onset of symptoms are significantly more infectious to mosquitoes than people with symptomatic infections. Because DENV viremic people without clinical symptoms may be exposed to more mosquitoes through their undisrupted daily routines than sick people and represent the bulk of DENV infections, our data indicate that they have the potential to contribute significantly more to virus transmission to mosquitoes than previously recognized.
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Vírus da Dengue/fisiologia , Dengue/transmissão , Dengue/virologia , Adolescente , Aedes/virologia , Animais , Criança , Dengue/sangue , Relação Dose-Resposta Imunológica , Feminino , Humanos , Masculino , Análise Multivariada , Análise de Regressão , Viremia/sangue , Viremia/virologiaRESUMO
We describe a retrospective study on circulation of Zika virus in Cambodia during 2007-2016 among patients with dengue-like symptoms and Aedes aegypti mosquitoes. Our findings suggest that Zika virus in Cambodia belongs to the Asia genotype, is endemic, has low prevalence, and has had low-level impact on public health.
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Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologia , Zika virus , Aedes/virologia , Animais , Camboja/epidemiologia , Genótipo , Geografia Médica , Humanos , Insetos Vetores/virologia , Filogenia , Vigilância da População , Prevalência , Estudos Retrospectivos , Proteínas não Estruturais Virais/genética , Zika virus/classificação , Zika virus/genética , Infecção por Zika virus/transmissãoRESUMO
Thirty-five human influenza A(H5N1) cases were reported in Cambodia during 2013-2014 after emergence of a clade 1.1.2 reassortant virus. We tested 881 villagers and found 2 cases of pauci- or asymptomatic infection. Seroprevalence after emergence of the reassortant strain (0.2%) was lower than the aggregate seroprevalence of 1.3% reported in earlier studies.
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Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/genética , Influenza Humana/transmissão , Influenza Humana/virologia , Vírus Reordenados , Animais , Camboja/epidemiologia , Geografia Médica , História do Século XXI , Humanos , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/história , Aves Domésticas , Estudos SoroepidemiológicosRESUMO
BACKGROUND: The diagnosis of tuberculosis in human immunodeficiency virus (HIV)-infected children is challenging. We assessed the performance of alternative specimen collection methods for tuberculosis diagnosis in HIV-infected children using Xpert MTB/RIF (Xpert). METHODS: HIV-infected children aged ≤13 years with suspected intrathoracic tuberculosis were enrolled in 8 hospitals in Burkina Faso, Cambodia, Cameroon, and Vietnam. Gastric aspirates were taken for children aged <10 years and expectorated sputum samples were taken for children aged ≥10 years (standard samples); nasopharyngeal aspirate and stool were taken for all children, and a string test was performed if the child was aged ≥4 years (alternative samples). All samples were tested with Xpert. The diagnostic accuracy of Xpert for culture-confirmed tuberculosis was analyzed in intention-to-diagnose and per-protocol approaches. RESULTS: Of 281 children enrolled, 272 (96.8%) had ≥1 specimen tested with Xpert (intention-to-diagnose population), and 179 (63.5%) had all samples tested with Xpert (per-protocol population). Tuberculosis was culture-confirmed in 29/272 (10.7%) children. Intention-to-diagnose sensitivities of Xpert performed on all, standard, and alternative samples were 79.3% (95% confidence interval [CI], 60.3-92.0), 72.4% (95% CI, 52.8-87.3), and 75.9% (95% CI, 56.5-89.7), respectively. Specificities were ≥97.5%. Xpert combined on nasopharyngeal aspirate and stool had intention-to-diagnose and per-protocol sensitivities of 75.9% (95% CI, 56.5-89.7) and 75.0% (95% CI, 47.6-92.7), respectively. CONCLUSIONS: The combination of nasopharyngeal aspirate and stool sample is a promising alternative to methods usually recommended by national programs. Xpert performed on respiratory and stools samples enables rapid confirmation of tuberculosis diagnosis in HIV-infected children. CLINICAL TRIALS REGISTRATION: The ANRS (Agence Nationale de Recherche sur le Sida) 12229 PAANTHER (Pediatric Asian African Network for Tuberculosis and HIV Research) 01 study is registered at ClinicalTrials.gov (NCT01331811).
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Infecções por HIV/complicações , Técnicas de Amplificação de Ácido Nucleico , Manejo de Espécimes , Tuberculose/diagnóstico , Adolescente , Secreções Corporais/microbiologia , Burkina Faso , Camboja , Camarões , Criança , Pré-Escolar , Coinfecção , DNA Bacteriano , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mycobacterium tuberculosis/genética , Sensibilidade e Especificidade , Tuberculose/complicações , VietnãRESUMO
Enterovirus 71 is reported to have emerged in Cambodia in 2012; at least 54 children with severe encephalitis died during that outbreak. We used serum samples collected during 2000-2011 to show that the virus had been widespread in the country for at least a decade before the 2012 outbreak.
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Encefalite/epidemiologia , Enterovirus Humano A/genética , Infecções por Enterovirus/epidemiologia , Adolescente , Camboja/epidemiologia , Criança , Pré-Escolar , Surtos de Doenças , Encefalite/virologia , Infecções por Enterovirus/virologia , Feminino , Humanos , Masculino , Estudos SoroepidemiológicosRESUMO
BACKGROUND: In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf. METHODS: By reviewing primaquine's pharmacology, we defined a therapeutic dose range of 0.15-0.38 mg base/kg (9-22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1-20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5-4 years (20.0 %, n = 5640), 5-12 years (9.1 %, n = 2559), 13-17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose. RESULTS: Four age-dosing bands were defined: (1) 0.5-4 years, (2) 5-9 years, (3) 10-14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st-99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15-0.38), (2) 0.29 (0.18-0.45), (3) 0.27 (0.15-0.39), and (4) 0.29 (0.20-0.42). CONCLUSIONS: This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides primaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations. Development of similar age-based dosing recommendations for Africa is needed.
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Antimaláricos/administração & dosagem , Malária Falciparum/tratamento farmacológico , Primaquina/administração & dosagem , Adolescente , Adulto , Fatores Etários , Camboja , Transmissão de Doença Infecciosa/prevenção & controle , Quimioterapia Combinada , Feminino , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/parasitologia , Humanos , Malária Falciparum/enzimologia , Malária Falciparum/prevenção & controle , Malária Falciparum/terapia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Although limited publications address clinical management of symptomatic patients with rabies in intensive care units, the overwhelming majority of human rabies cases occur in the rural setting of developing countries where healthcare workers are few, lack training and drugs. Based on our experience, we suggest how clinicians in resource-limited settings can make best use of essential drugs to provide assistance to patients with rabies and their families, at no risk to themselves. Comprehensive and compassionate patient management of furious rabies should aim to alleviate thirst, anxiety and epileptic fits using infusions, diazepam or midazolam and antipyretic drugs via intravenous or intrarectal routes. Although the patient is dying, respiratory failure must be avoided especially if the family, after being informed, wish to take the patient home alive for funereal rites to be observed. Healthcare staff should be trained and clinical guidelines should be updated to include palliative care for rabies in endemic countries.