Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection

As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies

Inter-Relationships of Cardinal Features and Outcomes of Symptomatic Pediatric Plasmodium falciparum Malaria in 1,933 Children in Kampala, Uganda

Malaria remains a challenging diagnosis with variable clinical presentation and a wide spectrum of disease severity. Using a structured case report form, we prospectively assessed 1,933 children at Mulago Hospital in Kampala, Uganda with acute Plasmodium falciparum malaria. Children with uncomplicated malaria significantly differed from those with severe disease for 17 features. Among 855 children with severe disease, the case-fatality rate increased as the number of severity features increased. Logistic regression identified five factors independently associated with death: cerebral malaria, hypoxia, severe thrombocytopenia, leukocytosis, and lactic acidosis. Cluster analysis identified two groups: one combining anemia, splenomegaly, and leukocytosis; and a second group centered on death, severe thrombocytopenia, and lactic acidosis, which included cerebral malaria, hypoxia, hypoglycemia, and hyper-parasitemia. Our report updates previous clinical descriptions of severe malaria, quantifies significant clinical and laboratory inter-relationships, and will assist clinicians treating malaria and those planning or assessing future research (NCT00707200) (www.clinicaltrials.gov)

Strengthening the community health worker programme for health improvement through enhancing training, supervision and motivation in Wakiso district, Uganda

Objective: The objective of the project was to strengthen the community health worker (CHW) programme in Ssisa sub-county, Wakiso district, Uganda by providing a coherent, structured and standardized training, supervision and motivation package so as to enhance their performance. Results: The project trained all 301 CHWs who received non-financial incentives of t-shirts, gumboots and umbrellas, and 75 of them received solar equipment to support lighting their houses and charging phones. Twenty-four of the CHWs who had coordination roles received additional training. Three motorcycles were also provided to enhance transportation of CHW coordinators during their work including supervision. By end of the project, the CHWs had conducted 40,213 household visits, carried out health education sessions with 127,011 community members, and treated 19,387 children under 5 years of age. From the project evaluation, which used both quantitative and qualitative methods, 98% of the CHWs reported having improved competence in performance of their roles. In addition, the CHWs were highly motivated to do their work. The motorcycles were instrumental in supporting the work of CHW coordinators including monthly collection of reports and distribution of medicines. The project demonstrated that by improving training, supervision and motivation, performance of CHW programmes can be enhanced

Dysregulation of the haem-haemopexin axis is associated with severe malaria in a case-control study of Ugandan children.

BACKGROUND: Malaria is associated with haemolysis and the release of plasma haem. Plasma haem can cause endothelial injury and organ dysfunction, and is normally scavenged by haemopexin to limit toxicity. It was hypothesized that dysregulation of the haem-haemopexin pathway contributes to severe and fatal malaria infections. METHODS: Plasma levels of haemin (oxidized haem), haemopexin, haptoglobin, and haemoglobin were quantified in a case-control study of Ugandan children with Plasmodium falciparum malaria. Levels at presentation were compared in children with uncomplicated malaria (UM; n = 29), severe malarial anaemia (SMA; n = 27) or cerebral malaria (CM; n = 31), and evaluated for utility in predicting fatal (n = 19) vs non-fatal (n = 39) outcomes in severe disease. A causal role for haemopexin was assessed in a pre-clinical model of experimental cerebral malaria (ECM), following disruption of mouse haemopexin gene (hpx). Analysis was done using Kruskall Wallis tests, Mann-Whitney tests, log-rank tests for survival, and repeated measures ANOVA. RESULTS: In Ugandan children presenting with P. falciparum malaria, haemin levels were higher and haemopexin levels were lower in SMA and CM compared to children with UM (haemin, p \u3c 0.01; haemopexin, p \u3c 0.0001). Among all cases of severe malaria, elevated levels of haemin and cell-free haemoglobin at presentation were associated with subsequent mortality (p \u3c 0.05). Compared to ECM-resistant BALB/c mice, susceptible C57BL/6 mice had lower circulating levels of haemopexin (p \u3c 0.01), and targeted deletion of the haemopexin gene, hpx, resulted in increased mortality compared to their wild type littermates (p \u3c 0.05). CONCLUSIONS: These data indicate that plasma levels of haemin and haemopexin measured at presentation correlate with malaria severity and levels of haemin and cell-free haemoglobin predict outcome in paediatric severe malaria. Mechanistic studies in the ECM model support a causal role for the haem-haemopexin axis in ECM pathobiology

Reflecting strategic and conforming gendered experiences of community health workers using photovoice in rural Wakiso district, Uganda

BACKGROUND: Community health workers (CHWs) are an important human resource in Uganda as they are the first contact of the population with the health system. Understanding gendered roles of CHWs is important in establishing how they influence their performance and relationships in communities. This paper explores the differential roles of male and female CHWs in rural Wakiso district, Uganda, using photovoice, an innovative community-based participatory research approach. METHODS: We trained ten CHWs (five males and five females) on key concepts about gender and photovoice. The CHWs took photographs for 5 months on their gender-related roles which were discussed in monthly meetings. The discussions from the meetings were recorded, transcribed, and translated to English, and emerging data were analysed using content analysis in Atlas ti version 6.0.15. RESULTS: Although responsibilities were the same for both male and female CHWs, they reported that in practice, CHWs were predominantly involved in different types of work depending on their gender. Social norms led to men being more comfortable seeking care from male CHWs and females turning to female CHWs. Due to their privileged ownership and access to motorcycles, male CHWs were noted to be able to assist patients faster with referrals to facilities during health emergencies, cover larger geographic distances during community mobilization activities, and take up supervisory responsibilities. Due to the gendered division of labour in communities, male CHWs were also observed to be more involved in manual work such as cleaning wells. The gendered division of labour also reinforced female caregiving roles related to child care, and also made female CHWs more available to address local problems. CONCLUSIONS: CHWs reflected both strategic and conformist gendered implications of their community work. The differing roles and perspectives about the nature of male and female CHWs while performing their roles should be considered while designing and implementing CHW programmes, without further retrenching gender inequalities or norms

Neonatal seizures in a rural Kenyan District Hospital: aetiology, Incidence and outcome of hospitalization

<p>Abstract</p> <p>Background</p> <p>Acute seizures are common among children admitted to hospitals in resource poor countries. However, there is little data on the burden, causes and outcome of neonatal seizures in sub-Saharan Africa. We determined the minimum incidence, aetiology and immediate outcome of seizures among neonates admitted to a rural district hospital in Kenya.</p> <p>Methods</p> <p>From 1^stJanuary 2003 to 31^stDecember 2007, we assessed for seizures all neonates (age 0-28 days) admitted to the Kilifi District Hospital, who were resident in a defined, regularly enumerated study area. The population denominator, the number of live births in the community on 1 July 2005 (the study midpoint) was modelled from the census data.</p> <p>Results</p> <p>Seizures were reported in 142/1572 (9.0%) of neonatal admissions. The incidence was 39.5 [95% confidence interval (CI) 26.4-56.7] per 1000 live-births and incidence increased with birth weight. The main diagnoses in neonates with seizures were sepsis in 85 (60%), neonatal encephalopathy in 30 (21%) and meningitis in 21 (15%), but only neonatal encephalopathy and bacterial meningitis were independently associated with seizures. Neonates with seizures had a longer hospitalization [median period 7 days - interquartile range (IQR) 4 to10] -compared to 5 days [IQR 3 to 8] for those without seizures, <it>P </it>= 0.02). Overall, there was no difference in inpatient case fatality between neonates with and without seizures but, when this outcome was stratified by birth weight, it was significantly higher in neonates ≥ 2.5 kg compared to low birth weight neonates [odds ratio 1.59 (95%CI 1.02 to 2.46), <it>P </it>= 0.037]. Up to 13% of the surviving newborn with seizures had neurological abnormalities at discharge.</p> <p>Conclusion</p> <p>There is a high incidence of neonatal seizures in this area of Kenya and the most important causes are neonatal encephalopathy and meningitis. The high incidence of neonatal seizures may be a reflection of the quality of the perinatal and postnatal care available to the neonates.</p

A challenging response to a Lassa fever outbreak in a non endemic area of Sierra Leone in 2019 with export of cases to The Netherlands.

INTRODUCTION: On November 20, 2019, the Sierra Leone International Health Regulations (IHR) National Focal Point was notified of an exported case of Lassa fever in The Netherlands, by a Dutch doctor who previously practiced in a rural hospital in Sierra Leone. This report describes the extent of the outbreak, possible sources of infection, and the outbreak response measures taken. METHODS: Response measures implemented to control the outbreak included coordination across multiple countries and cities, outbreak investigation, active case finding, contact tracing and monitoring, laboratory investigation, and isolation and treatment of cases. RESULTS: We report a hospital-associated outbreak that resulted in 3 confirmed cases (health workers) and 2 probable cases (patients). The case fatality rate was 60%, whereas the secondary attack rate was 14%. Two cases involved exportations to The Netherlands. Failure to detect the index case and poor adherence to infection prevention and control (IPC) protocols contributed to disease spread. Pregnancy status and nonspecific signs and symptoms of the index case contributed to failure in early case detection. CONCLUSIONS: Rapid activation of national and subnational incident management systems resulted in rapid outbreak control. We recommend regular training for clinicians on surveillance and IPC protocols and strengthening in-country Lassa virus diagnostic capacity

Anti-retroviral drug resistance-associated mutations among non-subtype B HIV-1-infected Kenyan children with treatment failure

金沢大学大学院医学系研究科感染症制御学Recently increased availability of antiretroviral therapy (ART) has mitigated HIV-1/AIDS prognoses especially in resource poor settings. The emergence of ART resistance-associated mutations from non-suppressive ART has been implicated as a major cause of ART failure. Reverse transcriptase inhibitor (RTI)-resistance mutations among 12 non-subtype B HIV-1-infected children with treatment failure were evaluated by genotypically analyzing HIV-1 strains isolated from plasma obtained between 2001 and 2004. A region of pol-RT gene was amplified and at least five clones per sample were analyzed. Phylogenetic analysis revealed HIV-1 subtype A1 (n = 7), subtype C (n = 1), subtype D (n = 3), and CRF02_AG (n = 1). Before treatment, 4 of 12 (33.3%) children had primary RTI-resistance mutations, K103N (n = 3, ages 5-7 years) and Y181C (n = 1, age 1 year). In one child, K103N was found as a minor population (1/5 clones) before treatment and became major (7/7 clones) 8 months after RTI treatment. In 7 of 12 children, M184V appeared with one thymidine-analogue-associated mutation (TAM) as the first mutation, while the remaining 5 children had only TAMs appearing either individually (n = 2), or as TAMs 1 (M41L, L210W, and T215Y) and 2 (D67N, K70R, and K219Q/E/R) appearing together (n = 3). These results suggest that "vertically transmitted" primary RTI-resistance mutations, K103N and Y181C, can persist over the years even in the absence of drug pressure and impact RTI treatment negatively, and that appearing patterns of RTI-resistance mutations among non-subtype B HIV-1-infected children could possibly be different from those reported in subtype B-infected children. © 2007 Wiley-Liss, Inc