Effectiveness of remote screening for diabetic retinopathy among patients referred to Mozambican Diabetes Association (AMODIA): a retrospective observational study.

AIMS: Diabetes represents a growing public health problem in sub-Saharan Africa, where diabetic retinopathy (DR) is a major cause of permanent visual loss. We reported the results of a remote screening of DR among urbanized Mozambican people with diabetes. METHODS: We retrospectively collected retinal images and clinical characteristics from 536 patients screened for DR in Maputo (Mozambique), over a period of 2 years (2018-2019). Retinal photographs were captured, digitally stored, and scored locally and by an expert ophthalmologist in Italy remotely. RESULTS: The overall prevalence of DR was 29% with sight-threatening forms accounting for 8.1% of that number. Inter-reader agreement between the local and the Italian ophthalmologists was poor (k < 0.2). Patients with DR were older, had a longer duration of disease, worse glycaemic control, and a higher prevalence of comorbidities. In the multivariate logistic regression analysis, HbA1c, diabetes duration, and coronary heart disease (CHD) were associated with DR. CONCLUSION: Prevalence of DR among urbanized Mozambican patients was similar to that observed in Western countries. Telediagnosis might partially overcome the paucity of local ophthalmologists with experience in DR.

Plano estrategico Multissectorial de prevenção e controlo de doenças não transmissíveis / Multisectoral strategic plan for the prevention and control of non-communicable diseases

A morte prematura por Doenças Não Transmissíveis (DNTs), continua a ser um dos principais desafios para o desenvolvimento a nível global, ceifando por ano perto de 15 milhões de vidas em idades compreendidas entre 30 e 70 anos. Moçambique não permanece inócuo pois já é notável a transição epidemiológica com o duplo peso das doenças transmissíveis e não transmissíveis. Em África o peso das Doenças Cardiovasculares, Diabetes Mellitus, Doenças Respiratórias Crónicas e o Cancro tem estado a aumentar de forma desproporcional entre os países de baixa e média renda, afetando sobretudo os grupos populacionais mais pobres e vulneráveis, impulsionado por factores como a pobreza, a globalização do mercado, o comércio de produtos prejudiciais à saúde, a crescente urbanização, crescimento e envelhecimento da população. Em Moçambique, à semelhança de muitos países, o desenvolvimento económico está a trazer grandes benefícios, mas também mudanças negativas na dieta e estilos de vida. É estimado que cerca de um terço das mortes no país sejam causadas pelas DNTs, e o risco de mortalidade prematura, ou seja, o risco de morte por DNTs antes dos 70 anos de idade, é de 18%. Este facto é preocupante pois maioria destas mortes prematuras e incapacidade por DNTs, pode ser evitada ou adiada através da redução da exposição aos factores de risco como consumo excessivo de álcool, consumo do tabaco, dieta não saudável e inatividade física.

Medical Curricula on Intimate Partner Violence in Mozambique.

INTRODUCTION: The aim of the study described in this paper is to screen medical curricula in relation to the attention paid to intimate partner violence, by applying a framework derived from the international literature. MATERIAL AND METHODS: We screened curricula of five Mozambican medical schools based on a state-of-the-art intimate partner violence curriculum framework. The latter framework was based on a review of the literature. RESULTS: Few medical schools of Mozambique could be identified addressing intimate partner violence in their curriculum. When tackled, intimate partner violence content is mostly dealt within the context of Obstetrics and Gynaecology, Community Health and Forensic Medicine rotations. Intimate partner violence contents are integrated as stand-alone modules in some specific subjects. In none of the schools, specific teachers teaching intimate partner violence could be identified. No time allocation was specified to address the topic; no teaching and learning strategies could be identified invoking awareness or supporting basic knowledge acquisition; additionally, hardly any information about related assessment methods was found. Only in one medical school was the subject part of the formal curriculum. DISCUSSION: Intimate partner violence content is hardly and inconsistently addressed. The limited intimate partner violence content tracked in the Mozambican medical schools' curricula, mainly addresses violence in general, for instance as identified in Orthopaedics or Surgery contexts and sexual violence in Obstetrics and Gynaecology. The inclusion of elements of intimate partner violence in the curriculum remains restricted, questioning the impact of medical education of future practitioners' competencies. CONCLUSION: Critical changes are needed in medical curricula to match the current epidemiology of intimate partner violence in Mozambique.

Introdução: O objetivo do estudo descrito neste artigo foi o de examinar os currículos de medicina quanto à atenção dada aos conteúdos sobre a Violência Perpretada pelo Parceiro Íntimo em Moçambique, aplicando uma ferramenta de comparação derivada da literatura internacional. Material e Métodos: Examinámos os currículos de cinco escolas médicas moçambicanas com base numa estrutura curricular da Violência Perpretada pelo Parceiro Íntimo de última geração. A ferramenta de comparação foi baseada numa revisão da literatura anterior. Resultados: Poucas escolas de medicina de Moçambique podem ser identificadas abordando a Violência Perpretada pelo Parceiro Íntimo no seu currículo. Se abordada, a Violência Perpretada pelo Parceiro Íntimo é mais tratada no contexto de Ginecologia e Obstetricia, Saúde Comunitária e Medicina legal. Os conteúdos da Violência Perpretada pelo Parceiro Íntimo são integrados como módulos autónomos em algumas disciplinas específicas. Nenhum dos curriculos identificou professores específicos que leccionam Violência Perpretada pelo Parceiro Intimo. Não foi especificada a alocação de tempo para abordar o tópico; estratégias de ensino e aprendizagem, sensibilização e aquisição de conhecimentos básicos; e dificilmente informação sobre métodos de avaliação específicos. Apenas numa escola de medicina, o assunto fazia parte do currículo formal. Discussão: O conteúdo da Violência Perpretada pelo Parceiro Íntimo é dificil e inconsistentemente tratado. O conteúdo limitado da Violência Perpretada pelo Parceiro Íntimo rastreado nos currículos das escolas médicas moçambicanas aborda principalmente a violência em geral, por exemplo, conforme identificado em contextos de ortopedia ou cirurgia e violência sexual em Ginecologia e Obstetrícia. A implementação no currículo permanece restrita, questionando o impacto da educação médica nas competências dos futuros profissionais. Conclusão: São necessárias mudanças críticas nos currículos médicos para corresponder à actual epidemiologia da Violência Perpretada pelo Parceiro Íntimo em Moçambique.

Directriz de garantia da qualidade do diagnóstico laboratorial da malária em moçambique / Warranty Guideline Diagnosis Quality Malaria Laboratory in Mozambique

A malária é um problema de saúde pública em Moçambique sendo endémica em todo o país, variando de zonas de baixa a alta endemicidade. As condições climáticas como a temperatura e a precipitação e as condições ambientais como locais propícios para a reprodução do vector contribuem para esta endemicidade. Segundo dados do Inquérito Nacional sobre Indicadores da Malária ­ IIM de 2018 ­ a prevalência da malária em crianças entre os 6-59 meses por teste de diagnóstico rápido foi de 39%...

Medical curricula on intimate partner violence in mozambique

Introduction: The aim of the study described in this paper is to screen medical curricula in relation to the attention paid to intimate partner violence, by applying a framework derived from the international literature. Material and Methods: We screened curricula of five Mozambican medical schools based on a state-of-the-art intimate partner violence curriculum framework. The latter framework was based on a review of the literature. Results: Few medical schools of Mozambique could be identified addressing intimate partner violence in their curriculum. When tackled, intimate partner violence content is mostly dealt within the context of Obstetrics and Gynaecology, Community Health and Forensic Medicine rotations. Intimate partner violence contents are integrated as stand-alone modules in some specific subjects. In none of the schools, specific teachers teaching intimate partner violence could be identified. No time allocation was specified to address the topic; no teaching and learning strategies could be identified invoking awareness or supporting basic knowledge acquisition; additionally, hardly any information about related assessment methods was found. Only in one medical school was the subject part of the formal curriculum. Discussion: Intimate partner violence content is hardly and inconsistently addressed. The limited intimate partner violence content tracked in the Mozambican medical schools' curricula, mainly addresses violence in general, for instance as identified in Orthopaedics or Surgery contexts and sexual violence in Obstetrics and Gynaecology. The inclusion of elements of intimate partner violence in the curriculum remains restricted, questioning the impact of medical education of future practitioners' competencies. Conclusion: Critical changes are needed in medical curricula to match the current epidemiology of intimate partner violence in Mozambique

Introdução: O objetivo do estudo descrito neste artigo foi o de examinar os currículos de medicina quanto à atenção dada aos conteúdos sobre a Violência Perpretada pelo Parceiro Íntimo em Moçambique, aplicando uma ferramenta de comparação derivada da literatura internacional. Material e Métodos: Examinámos os currículos de cinco escolas médicas moçambicanas com base numa estrutura curricular da Violência Perpretada pelo Parceiro Íntimo de última geração. A ferramenta de comparação foi baseada numa revisão da literatura anterior. Resultados: Poucas escolas de medicina de Moçambique podem ser identificadas abordando a Violência Perpretada pelo Parceiro Íntimo no seu currículo. Se abordada, a Violência Perpretada pelo Parceiro Íntimo é mais tratada no contexto de Ginecologia e Obstetricia, Saúde Comunitária e Medicina legal. Os conteúdos da Violência Perpretada pelo Parceiro Íntimo são integrados como módulos autónomos em algumas disciplinas específicas. Nenhum dos curriculos identificou professores específicos que leccionam Violência Perpretada pelo Parceiro Intimo. Não foi especificada a alocação de tempo para abordar o tópico; estratégias de ensino e aprendizagem, sensibilização e aquisição de conhecimentos básicos; e dificilmente informação sobre métodos de avaliação específicos. Apenas numa escola de medicina, o assunto fazia parte do currículo formal. Discussão: O conteúdo da Violência Perpretada pelo Parceiro Íntimo é dificil e inconsistentemente tratado. O conteúdo limitado da Violência Perpretada pelo Parceiro Íntimo rastreado nos currículos das escolas médicas moçambicanas aborda principalmente a violência em geral, por exemplo, conforme identificado em contextos de ortopedia ou cirurgia e violência sexual em Ginecologia e Obstetrícia. A implementação no currículo permanece restrita, questionando o impacto da educação médica nas competências dos futuros profissionais. Conclusão: São necessárias mudanças críticas nos currículos médicos para corresponder à actual epidemiologia da Violência Perpretada pelo Parceiro Íntimo em Moçambique

Gaps in Medical Students' Competencies to Deal With Intimate Partner Violence in Key Mozambican Medical Schools.

Purpose: The researchers aimed to identify the gaps in competencies designed to help medical students to deal with Intimate Partner Violence (IPV) in key Mozambican medical schools curricula. Method: A survey was administered to 3rd and 6th-year medical students (N387), enrolled in five medical schools in Mozambique. The instrument focused on mapping students' perceived mastery of their knowledge, skills, and attitudes related to IPV. Results: In total, 387 medical students (RR 66%) participated in the survey. The overall mean perceived mastery of IPV competence was 36.18 (SD = 24.52) for knowledge, 32.01 (SD = 27.37) for skills, and 43.47 (SD = 27.58) for attitudes. Though 6th-year students reported a significantly higher mastery level, it is still below a mastery-learning benchmark of 80%. Conclusions: Medical students report critically low levels in their mastery of IPV- related competencies. This implies a need for a more comprehensive approach to developing knowledge, skills, and attitudes to deal with the victims of IPV.

BE-SMART (Basal Early Strategies to Maximize HbA1c Reduction with Oral Therapy): Expert Opinion.

The past three decades have seen a quadruple rise in the number of people affected by diabetes mellitus worldwide, with the disease being the ninth major cause of mortality. Type 2 diabetes mellitus (T2DM) often remains undiagnosed for several years due to its asymptomatic nature during the initial stages. In India, 70% of diagnosed diabetes cases remain uncontrolled. Current guidelines endorse the initiation of insulin early in the course of the disease, specifically in patients with HbA1c > 10%, as the use of oral agents alone is unlikely to achieve glycemic targets. Early insulin initiation and optimization of glycemic control using insulin titration algorithms and patient empowerment can facilitate the effective management of uncontrolled diabetes. Early glucose control has sustained benefits in people with diabetes. However, insulin initiation, dose adjustment, and the need to repeatedly assess blood glucose levels are often perplexing for both physicians and patients, and there are misconceptions and concerns regarding its use. Hence, an early transition to insulin and ideal intensification of treatment may aid in delaying the onset of diabetes complications. This opinion statement was formulated by an expert panel on the basis of existing guidelines, clinical experience, and economic and cultural contexts. The statement stresses the timely and appropriate use of basal insulin in T2DM. It focuses on the seven vital Ts-treatment initiation, timing of administration, transportation and storage, technique of administration, targets for titration, tablets, and tools for monitoring.Funding: Sanofi.

Characteristics, prevalence, and outcomes of diabetic foot ulcers in Africa. A systemic review and meta-analysis.

BACKGROUND: Among non-communicable diseases, diabetes represents a growing public health problem in Africa, where diabetes-related needs remain mostly unmet and the disabling features of foot are worsened by hygienic, cultural, and healthcare issues. We aimed to review clinical characteristics, prevalence, and outcomes of patients with diabetic foot ulcer in Africa. METHODS: We searched the literature for cross-sectional and longitudinal studies reporting the characteristics of patients with diabetic foot in African countries, with a particular focus on ulcer prevalence, amputation rate, and mortality. FINDINGS: Fifty-five full-text papers and ten abstracts were retrieved, reporting data from 19 African countries on 56,173 diabetic patients. According to the data collected, the overall prevalence of foot ulcers was 13% and increased over time, especially since 2001. Approximately 15% of patients with foot lesions underwent major amputation and 14.2% died during hospitalization. In patients with diabetic ulcers, insulin therapy was uncommon and neuropathy was the most common predisposing factor, but the prevalence of peripheral arterial disease correlated with amputation rates. Amputation and mortality decreased over time, probably as result of the implementation of screening programs in the last ten years. Mortality was directly related to previous amputation. INTERPRETATION: The diabetic foot disease in Africa is a growing problem and is burden by high rate of in-hospital mortality. Educational interventions and screening programs including evaluation of the vascular status may play a crucial role to counter diabetic foot disease in Africa.

Normas de manejo da diabetes Mellitus e Hiperatenção arterial 1 edição / Guidelines for the Management of Diabetes Mellitus and Arterial Hypertension 1 edition

Em Moçambique, as doenças crónicas constituem importante causa de morbilidade, de mortalidade precoce e de incapacidade física, particularmente em pessoas em idade produtiva. Este facto contribui significativamente para a redução da produtividade e por conseguinte com impacto no desenvolvimento do país. Com o intuito de garantir medidas de prevenção, diagnóstico e tratamento precoces da Diabetes Mellitus e da Hipertensão Arterial nas unidades sanitárias, são elaboradas as presentes normas de tratamento destas doenças crónicas. Estas normas são dirigidas aos trabalhadores de saúde envolvidos no diagnóstico e tratamento da Diabetes e da Hipertensão em todas as unidades sanitárias e poderão ser de utilidade para médicos, estudantes dos cursos de Medicina, Técnicos e Agentes de Medicina. Sendo a DM e a HTA doenças crónicas e considerando o seu impacto na saúde global, todos os clínicos devem assumir uma postura de responsabilidade, cumprindo e fazendo cumprir rigorosamente estas normas para benefício da comunidade e da saúde pública no nosso País. Como qualquer documento normativo, as presentes normas não são um documento acabado, esperando-se por isso a contribuição de todos que as utilizem para a sua progressiva melhoria

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria at sentinel sites in Mozambique, 2015.

The resistance of Plasmodium falciparum to anti-malarial drugs continues to challenge malaria control. We assessed the therapeutic efficacy and safety of artemether-lumefantrine (AL), the first-line treatment of uncomplicated P. falciparum malaria, in children under five years of age in Mozambique. We conducted a prospective one-arm study to evaluate the clinical and parasitological efficacy of AL over 28days at four sentinel sites, using the WHO protocol for assessing the efficacy of antimalarial treatment. msp1, msp2 and glurp genes were analysed by DNA polymerase chain reaction (PCR) to differentiate recrudescence from re-infection with malaria parasites. Haemoglobin concentration was recorded at baseline and on days 7, 14 and 28. A total of 349 children with uncomplicated falciparum malaria were recruited at the four sentinel sites. Adequate clinical and parasitological response to AL on day 28 follow-up varied from 96.3% to 100% after correction by PCR. The drug was well tolerated, and no adverse event related to the drug was reported. AL, the current first-line treatment for uncomplicated falciparum malaria in Mozambique, remains highly efficacious at the study sites. Monitoring of the efficacy of the recommended antimalarial drugs should be continued in order to detect any emerging threat to their efficacy. TRIAL REGISTRATION NUMBER: ACTRN12616001680459.

Normas de tratamento da malária em moçambique, 3ª edição / Malaria treatment standards in mozambique

A malária é uma das principais causas de morbilidade e de mortalidade em Moçambique, particularmente em crianças menores. É a causa mais comum de procura de cuidados médicos, nas consultas externas e de internamento, nas unidades sanitárias do país. A mulher grávida constitui o principal grupo de risco em adultos. A malária é também um problema socioeconómico, uma vez que interfere negativamente no desenvolvimento do País, mantendo o ciclo doença/pobreza devido ao elevado absentismo escolar e laboral bem como a perda de mão-de-obra laboral. O manejo de casos de Malária, consiste no diagnóstico atempado por microscopia ou teste de diagnóstico rápido, suportados por um controlo de qualidade e de um tratamento imediato e correcto com medicamentos eficazes. A presente edição das Normas de Tratamento da Malária contém a actualização das recomendações da OMS baseadas nas novas evidências particularmente relacionadas com o diagnóstico, doses e indicações de tratamento nas crianças e grávidas. Têm como finalidade garantir o uso racional dos medicamentos e são dirigidas a todos profissionais envolvidos no diagnóstico e tratamento da Malária em todas as unidades sanitárias e comunidade (agentes Polivalentes elementares). Servirá ainda aos estudantes dos cursos de Medicina, Técnicos e Agentes de Medicina curativa e enfermeiros Sendo a malária uma doença endémica e de grande impacto em Moçambique, todos os profissionais devem assumir uma postura de responsabilidade, implementando e fazendo cumprir rigorosamente estas normas para benefício da comunidade e da saúde pública no nosso País, de modo a maximizar o benefício dos medicamentos e evitar o surgimento de resistência aos antimaláricos.

In vivo efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated falciparum malaria in children: a multisite, open-label, two-cohort, clinical trial in Mozambique.

BACKGROUND: Mozambique adopted artemisinin-based combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria in the year 2006, and since 2009 artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) have been proposed as alternative first-line treatments. A multicentre study was conducted in five sites across the country to assess the in vivo efficacy and tolerability of these two drugs. METHODS: Children aged six to 59 months with uncomplicated malaria were recruited between June 2011 and January 2012 in five sites across Mozambique (Montepuez, Dondo, Tete, Chokwe, and Manhiça), and treated with AL or ASAQ in a non-randomized study. Follow-up was organized following standard WHO recommendations for in vivo studies, and included daily visits during the three-day-long supervised treatment course, followed by weekly visits up to day 28. The study primary outcome was the day 28 PCR-corrected early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF), and adequate clinical and parasitological response (ACPR). PCR was performed centrally for all cases of recurrent parasitaemia from day 7 onwards to distinguish recrudescence from re-infection. RESULTS: Four-hundred and thirty-nine (AL cohort; five sites) and 261 (ASAQ cohort, three sites) children were recruited to the study. Day 28 PCR-corrected efficacy for AL was 96.0% (335/339; 95% CI: 93.4-97.8), while for ASAQ it was 99.6% (232/233; 95% CI: 97.6-99.9). The majority of recurring parasitaemia cases throughout follow-up were shown to be re-infections by PCR. Both drugs were well tolerated, with the most frequent adverse event being vomiting (AL 4.5% [20/439]; ASAQ 9.6% [25/261]) and no significant events deemed related to the study drugs. CONCLUSION: This study confirms that both AL and ASAQ remain highly efficacious and well tolerated for the treatment of uncomplicated malaria in Mozambican children. Studies such as these should be replicated regularly in the selected surveillance sentinel sites to continuously monitor the efficacy of these drugs and to rapidly detect any potential signs of declining efficacy to ACT, the mainstay of malaria treatment.

Diabetes Mellitus tipo 1 no Hospital Central de Maputo: Prevalência de hipertensão e complicações oculares / Type 1 Diabetes Mellitus at the Maputo Central Hospital: Prevalence of hypertension and sight complications

O artigo apresenta resultados de um estudo cujo objectivo era determinar o peso da Diabetes Mellitus (DM) tipo 1 entre os doentes com patologia endócrina e a prevalência de hipertensão arterial e complicações oculares no Hospital Central de Maputo (HCM). Do ponto de vista metodológico, a população de estudo foi constituída por cerca de 191 doentes consecutivos com diabetes mellitus tipo 1, observados na consulta de endocrinologia do HCM e na Associação Moçambicana dos Diabéticos, no período de Março de 2006 e Março 2011. A análise estatística dos dados foi feita com recurso ao pacote estatístico SPSS for windows 17.0. Como Resultado, observa-se que a DM tipo 1 representou cerca de 10% dos casos de DM observados no HCM durante o período em referência. Observa-se ainda uma prevalência relativamente elevada da hipertensão arterial (9,9% sistólica e 8,9% diastólica); diferentes tipos de complicações oculares em 14,7% dos doentes de estudo. Também conclui-se que os principais factores de risco para a HTA constituíram a idade em anos e o índice de massa corporal, enquanto que os principais factores de risco para as complicações oculares foram a idade e a duração da doença para a retinopatia diabética (p <.000) e duração da doença para a catarata (p< .001). A Diabetes mellitus tipo 1 constitui um importante problema endócrino nas consultas de especialidade no HCM e apresenta-se com elevada taxa de HTA e complicações oculares.

The article presents results from a study aimed at determining the weight of Diabetes Mellitus (DM) type 1 among patients with endocrine pathologies and the prevalence of hypertension and sight complications in the Maputo Central Hospital (HCM). The research population consisted of 191 consecutive patients with diabetes mellitus type 1 who were observed during endocrinology consultation at the HCM and the Diabetic Mozambican Association, between March 2006 and March 2011. The statistical data was analyzed using SSPS for Windows 17.0. Results showed that DM type 1 represented about 10% of the DM observed cases at the HCM during the period in question. A relatively high prevalence of hypertension was also observed (9.9% systolic and 8.9% diastolic); different types of sight complications were observed in 14.7% of the patients. The study concluded that the main risk factors that cause HTA are age and the body mass index, while that main risk factors for sight complications are age and the duration of the pathology for diabetes retinopathy (p <.000) and the duration of the pathology for cataract (p <.001). the DM type 1 constitutes the most important endocrine problem in the specialized consultations at the HCM and it shows a high rate of HTA and sight complications.

Prozone in malaria rapid diagnostics tests: how many cases are missed?

BACKGROUND: Prozone means false-negative or false-low results in antigen-antibody reactions, due to an excess of either antigen or antibody. The present study prospectively assessed its frequency for malaria rapid diagnostic tests (RDTs) and Plasmodium falciparum samples in an endemic field setting. METHODS: From January to April 2010, blood samples with P. falciparum high parasitaemia (≥ 4% red blood cells infected) were obtained from patients presenting at the Provincial Hospital of Tete (Mozambique). Samples were tested undiluted and 10-fold diluted in saline with a panel of RDTs and results were scored for line intensity (no line visible, faint, weak, medium and strong). Prozone was defined as a sample which showed no visible test line or a faint or weak test line when tested undiluted, and a visible test line of higher intensity when tested 10-fold diluted, as observed by two blinded observers and upon duplicate testing. RESULTS: A total of 873/7,543 (11.6%) samples showed P. falciparum, 92 (10.5%) had high parasitaemia and 76 were available for prozone testing. None of the two Pf-pLDH RDTs, but all six HRP-2 RDTs showed prozone, at frequencies between 6.7% and 38.2%. Negative and faint HRP-2 lines accounted for four (3.8%) and 15 (14.4%) of the 104 prozone results in two RDT brands. For the most affected brand, the proportions of prozone with no visible or faint HRP-2 lines were 10.9% (CI: 5.34-19.08), 1.2% (CI: 0.55-2.10) and 0.1% (CI: 0.06-0.24) among samples with high parasitaemia, all positive samples and all submitted samples respectively. Prozone occurred mainly, but not exclusively, among young children. CONCLUSION: Prozone occurs at different frequency and intensity in HRP-2 RDTs and may decrease diagnostic accuracy in the most affected RDTs.

A country-wide malaria survey in Mozambique. II. Malaria attributable proportion of fever and establishment of malaria case definition in children across different epidemiological settings.

BACKGROUND: Protection against clinical malaria episodes is acquired slowly after frequent exposure to malaria parasites. This is reflected by a decrease with increasing age in both parasite density and incidence of clinical episodes. In many settings of stable malaria transmission, the presence of asymptomatic malaria parasite carriers is common and the definition of clinical malaria remains uncertain. METHODS: Between February 2002 and April 2003, a country-wide malaria survey was conducted in 24 districts of Mozambique, aiming to characterize the malaria transmission intensities and to estimate the proportion of fever cases attributable to malaria infections in order to establish the malaria case definition. A total of 8,816 children less than ten years of age were selected for the study. Axillary temperature was measured in all participating subjects and finger prick blood collections were taken to prepare thick and thin films for identification of parasite species and determination of parasite density. The proportion of fever cases attributable to malaria infection was estimated using a logistic regression of the fever on a monotonic function of the parasite density and, using bootstrap facilities, bootstrapped estimated confidence intervals, as well as the sensitivity and specificity for different parasite density cut-offs were produced. RESULTS: Overall, the prevalence of Plasmodium falciparum was 52.4% (4,616/8,816). The prevalence of fever (axillary temperature >or= 37.5 degrees C) was 9.4% (766/8,816). Fever episodes peaked among children below 12 months of life [15.1% (206/1,517)]. The lowest fever prevalence of 5.9% (67/1,224) was recorded amongst children between five and seven years of age. Among 4,098 parasitized children, 498/4,098 (13.02%) had fever. The prevalence of malaria infections associated with fever peaked among children in the less than twelve months age group and thereafter decreased rapidly with increasing age (p < 0.001). High parasite densities were significantly associated with fever (p < 0.04). The proportion of fever attributed to malaria was 37.8% (95% CI 32.9% - 42.7%). An age-specific pattern was observed with significant variations across different regions in the country. In general, among children less than 12 months of life, the proportion of fever attributed to malaria infection was 43.5% (95% CI 25.8% - 61.2%), in children aged between 12 and 59 months of age was 39.6% (95% CI 30.3% - 48.9%), and among children aged between 5 and 10 years old was 21.5% (95% CI 11.6% - 31.4%). CONCLUSION: This study confirms that malaria remains a major cause of febrile illness during childhood. It also defines the relation between parasite density and fever and how this varies with age and region. This may help guide case definition for clinical trials of preventive tools, as well as provide definitions that may improve the precision of measurement of the burden of disease.

A country-wide malaria survey in Mozambique. II. Malaria attributable proportion of fever and establishment of malaria case definition in children across different epidemiological settings

Background: Protection against clinical malaria episodes is acquired slowly after frequent exposure to malaria parasites. This is reflected by a decrease with increasing age in both parasite density and incidence of clinical episodes. In many settings of stable malaria transmission, the presence of asymptomatic malaria parasite carriers is common and the definition of clinical malaria remains uncertain. Methods: Between February 2002 and April 2003, a country-wide malaria survey was conducted in 24 districts of Mozambique, aiming to characterize the malaria transmission intensities and to estimate the proportion of fever cases attributable to malaria infections in order to establish the malaria case definition. A total of 8,816 children less than ten years of age were selected for the study. Axillary temperature was measured in all participating subjects and finger prick blood collections were taken to prepare thick and thin films for identification of parasite species and determination of parasite density. The proportion of fever cases attributable to malaria infection was estimated using a logistic regression of the fever on a monotonic function of the parasite density and, using bootstrap facilities, bootstrapped estimated confidence intervals, as well as the sensitivity and specificity for different parasite density cut-offs were produced. Results: Overall, the prevalence of Plasmodium falciparum was 52.4% (4,616/8,816). The prevalence of fever (axillary temperature ≥ 37.5°C) was 9.4% (766/8,816). Fever episodes peaked among children below 12 months of life [15.1% (206/1,517)]. The lowest fever prevalence of 5.9% (67/ 1,224) was recorded amongst children between five and seven years of age. Among 4,098 parasitized children, 498/4,098 (13.02%) had fever. The prevalence of malaria infections associated with fever peaked among children in the less than twelve months age group and thereafter decreased rapidly with increasing age (p < 0.001). High parasite densities were significantly associated with fever (p < 0.04). The proportion of fever attributed to malaria was 37.8% (95% CI 32.9% ­ 42.7%). An age-specific pattern was observed with significant variations across different regions in the country. In general, among children less than 12 months of life, the proportion of fever attributed to malaria infection Page 1 of 7 (page number not for citation purposes)Malaria Journal 2009, 8:74 http://www.malariajournal.com/content/8/1/74 was 43.5% (95% CI 25.8% ­ 61.2%), in children aged between 12 and 59 months of age was 39.6% (95% CI 30.3% ­ 48.9%), and among children aged between 5 and 10 years old was 21.5% (95% CI 11.6% ­ 31.4%). Conclusion: This study confirms that malaria remains a major cause of febrile illness during childhood. It also defines the relation between parasite density and fever and how this varies with age and region. This may help guide case definition for clinical trials of preventive tools, as well as provide definitions that may improve the precision of measurement of the burden of disease.

Functional variants of the angiotensinogen gene determine antihypertensive responses to angiotensin-converting enzyme inhibitors in subjects of African origin.

OBJECTIVE: To determine whether the response to angiotensin-converting enzyme inhibitor (ACEI) monotherapy in subjects of African origin is determined by genetic variants within the angiotensinogen (AGT) gene. METHODS: A total of 194 hypertensive patients of African ancestry were recruited from district clinics in Johannesburg, South Africa. Eighty patients received open-label ACEI (enalapril or lisinopril) monotherapy, and 114 open-label calcium antagonist (nifedipine) as a drug class comparator. Twenty-four hour ambulatory blood pressure (ABP) monitoring was performed at baseline (off medication) and after 2 months of therapy. DNA was analysed for functional variants (-217G-->A and -20A-->C) of the AGT gene. The impact of genotype on ABP responses to ACEI monotherapy or calcium antagonists; and on plasma aldosterone and renin levels after ACEI monotherapy was assessed. RESULTS: Adjusting for baseline ABP and type of ACEI in the ACEI-treated group, the -217G-->A variant predicted ABP responses to ACEI (n = 77; P < 0.01), but not to nifedipine (n = 108). ACEI in patients with the AA genotype of the -217G-->A variant failed to elicit an antihypertensive response [change in ABP, mmHg: systolic blood pressure (SBP) +0.84 +/- 2.89, P = 0.78; diastolic blood pressure (DBP) -0.47 +/- 1.74, P = 0.79]. In contrast, those patients with at least one copy of the -217G allele developed a 7.23 +/- 1.55 and 5.38 +/- 1.12 mmHg decrease (P < 0.0001) in SBP and DBP, respectively, after ACEI administration. Similarly, the -20A-->C variant predicted ABP responses to ACEI monotherapy (P < 0.01) but not to nifedipine. Moreover, patients who were AA genotype for both variants failed to develop an antihypertensive response to ACEI (change in ABP, mmHg: SBP +1.06 +/- 3.05, P = 0.73; DBP -0.39 +/- 1.83, P = 0.83); whereas patients with at least one copy of both the -217G and the -20C allele developed substantial decreases in ABP (change in ABP, mmHg: SBP -14.08 +/- 3.72, P < 0.0001; DBP -9.62 +/- 2.74, P < 0.0001). Patients with at least one copy of the -217G allele demonstrated a significant reduction in the aldosterone-to-renin ratio (-0.098 +/- 0.035, P < 0.01), whereas in those patients who were -217AA genotype the ratio was unchanged (-0.03 +/- 0.16, P = 0.85). CONCLUSION: Functional variants of the AGT gene contribute to the variability of antihypertensive responses to ACEI monotherapy in individuals of African ancestry, with genotype determining whether or not responses occur.

Impact of renin-angiotensin-aldosterone system gene variants on the severity of hypertension in patients with newly diagnosed hypertension.

BACKGROUND: The severity of hypertension has prognostic significance. Previous studies have assessed the relationship between renin-angiotensin-aldosterone system (RAAS) genotype and the severity of hypertension in either treated patients or those who have only recently discontinued treatment. METHODS: We assessed the impact of RAAS genotype on ambulatory and office blood pressure (BP) in 231 newly diagnosed hypertensive patients of African ancestry who had never received therapy. Subjects were genotyped for variants of the angiotensin-converting enzyme (insertion/deletion), angiotensinogen (M235T, -20A-->C), and aldosterone synthase (CYP11B2)(-344C-->T) genes. RESULTS: The CYP11B2 gene polymorphism was associated with systolic BP (SBP). In comparison to subjects with at least one copy of the -344C allele (n = 75), patients who were homozygous for the -344T allele (n = 156) had both higher ambulatory SBP (150 +/- 1 v 144 +/- 1 mm Hg, P =.002 before and P =.01 after adjusting for multiple genotyping) and office SBP (163 +/- 2 v 156 +/- 2 mm Hg, P =.01 before and P =.05 after adjusting for multiple genotyping). Neither the angiotensin-converting enzyme insertion/deletion nor the angiotensinogen gene polymorphisms were associated with ambulatory or office SBP or diastolic BP (DBP). The CYP11B2 gene variant also did not affect DBP. CONCLUSION: A variant within the CYP11B2 locus has a clinically important impact on the severity of SBP changes in individuals with newly diagnosed hypertension who are of African ethnicity.

Angiotensinogen gene promoter region variant modifies body size-ambulatory blood pressure relations in hypertension.

BACKGROUND: The extent to which genes modify the relationship between risk factors for hypertension and blood pressure (BP) is unclear. As angiotensinogen is expressed in adipose tissue and angiotensinogen (AGT) gene promoter variants influence the production of angiotensinogen, we evaluated the role of AGT gene variants as potential modifiers of body size-BP relations. METHODS AND RESULTS: Five hundred twenty-one hypertensives of African origin sampled from a group with a high mean body mass index (BMI) had 24-hour ambulatory BP (ABP) measurements determined off therapy and were genotyped for the AGT -6G-->A, -532C-->T, -20A-->C, and 704T-->C (M235T) gene variants. Genotypes were also determined in 547 control subjects of African origin who had a normal clinic BP. The -6A and -532C alleles were concordant with the M235T variant. Although AGT gene variants had no independent effects on either the presence of hypertension or ABP values in hypertensives, the -20A-->C polymorphism had a marked influence on the relation between ambulatory systolic BP and BMI. This relation was present in patients homozygous for the -20A allele (n=399, r=0.23, P<0.0001), but absent in those with at least one copy of the -20C allele (n=122, r=0.01, P=0.89). The M235T polymorphism did not impact on the BMI-BP relation. Specificity of the -20A-->C polymorphism effect on the BMI-BP relation is further indicated by the lack of effect on the systolic BP-age relation. CONCLUSION: An AGT gene promoter region variant is an important modifier of the relation between body size and BP. Hence, these data corroborate the notion that genetic modifiers can produce a profound impact on BP-phenotypic relations.

Association between an atrial natriuretic peptide gene polymorphism and normal blood pressure in subjects of African ancestry.

AIM: The roles of the atrial natriuretic peptide (ANP) gene and the clearance receptor of the ANP (NPRC) gene in hypertensive groups of African ancestry are unclear. The aim of the present study was to assess the relationship between both ANP and NPRC gene polymorphisms and hypertension in Black South Africans. METHODS: 298 patients, diagnosed as having essential hypertension according to 24-hour ambulatory blood pressure (BP) measurements (mean daytime diastolic BP> 90 mm Hg) whilst off medication, and 278 normotensive control subjects of a similar African ancestry, were genotyped for polymorphic markers in intron 2 (which is in complete linkage disequilibrium with a potentially functional exon 1 variant) and exon 3 (which leads to the extension of ANP by two additional arginines) of the ANP gene. Moreover, 64 hypertensives and 63 control from the same groups were genotyped for the cis-acting promoter/enhancer element of the NPRC gene. RESULTS: No relationship between the exon 3 variant and either the presence (odds ratio = 1.075) or the severity (24-hour BP) of hypertension was noted. The intron 2 polymorphism occurred at a low frequency in the control group (frequency of subjects heterozygous for the variant = 6.1%), but was almost absent in the hypertensive group (frequency of heterozygotes = 1.7%). Consequently, a relationship between a normal BP and the intron 2 variant was noted (odds ratio = 0.28, confidence interval = 0.10-0.76, p < 0.01, <1% chance of false positive results). The NPRC gene variant occurred with an equally low frequency in both the hypertensive (4.7%) and the control (4.8%) groups. CONCLUSIONS: The results of the present study suggest that the ANP, but not the NPRC locus contributes to BP in subjects of African ancestry.