Malaria in southern Mozambique: incidence of clinical malaria in children living in a rural community in Manhiça district

We estimated the incidence of clinical malaria episodes by weekly home-based active case detection between December 1996 and July 1999 in 2 groups of children in Manhi?a district in southern Mozambique. Cohort 1 comprised a random sample of children aged <10 years at recruitment and cohort 2 comprised newborns. A blood slide was taken if the axillary temperature was 7.5 degrees C or if the child was reported to have been febrile over the previous 24 h. A total of 1966 children were followed-up. Malaria occurred all year round. The number of clinical malaria episodes ranged from 0 to 6 per child. No clinical malaria episodes were detected in 71% of children or in children aged <2 months. Those aged 6 months to <4 years showed the highest incidence ranging from 0.65 to 0.74 episodes per 100 person-weeks at risk, indicating that infants and young children were at highest risk. Malaria transmission is perennial in this district of Mozambique with some seasonality. Significant differences were observed in the spatial incidence of malaria episodes in regions just a few miles apart with a higher incidence in children living near the river or in swampy areas. These findings strengthen the need for improved control measures targeted at infancy and early childhood.     

Acute bacterial meningitis among children, in Manhiça, a rural area in Southern Mozambique

INTRODUCTION: Acute bacterial meningitis (ABM) is one of the most severe diseases in Sub-Saharan Africa. Although data for the continent is very limited, more than one million cases are estimated per year, with mortality and life-long sequelae occurring in 50% of these cases. METHODS: As part of the clinical management of children admitted to the Manhi?a District Hospital, information on cases of ABM was recorded. We analysed data from June 1998 to November 2003. RESULTS: During the study period, 475 cerebrospinal-fluid (CSF) samples were collected from 20,173 children <15 years of age admitted to hospital. Culture results confirmed 71 (15%) cases of ABM. The most prevalent bacterial aetiologies were Streptotoccus pneumoniae (pneumococcus, n=31), Haemophilus influenzae (n=13) and Neisseria meningitis (n=8). Other important bacteria were Streptococcus sp. (n=7), Salmonella sp. (n=4) and Staphylococcus aureus (n=3). Crude incidence rates of ABM and pneumococcal meningitis were 20/100,000 and 10/100,000 children-year-at-risk, respectively. Incidences were more than three times higher in the <1 year age group. Overall case fatality rate was 36%, and was highest for H. influenzae and pneumococcal meningitis (55% and 45%, respectively, p=0.044). Pneumococcal susceptibility was 81% for oxacillin and 93% for chloramphenicol. For H. influenzae isolates, susceptibility was 54% for ampicillin and 62% for chloramphenicol. CONCLUSIONS: S. pneumoniae and H. influenzae are the main aetiologies responsible for the high burden of morbidity and mortality associated with ABM in rural Mozambique. These findings are important to evaluate treatment guidelines and potential impact of control measures.     

Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria

This paper reports a two‐phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine–pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of uncomplicated malaria, of three combinations: AQ + SP, artesunate (AR) + SP and AQ + AR. Based on the WHO (1996, WHO/MAL/96.1077) in vivo protocol, we conducted two open, randomized, clinical trials. Children aged 6–59 months with axillary body temperature ≥37.5 °C and non‐complicated malaria were randomly allocated to treatment groups and followed up for 21 days (first and second trial) and 28 days (first trial). The therapeutic efficacy of AQ (91.6%) was better than that of SP (82.7%) and CQ (47.1%). After 14 days, 69% of the strains were parasitologically resistant to CQ, 21.4% to SP and 26% to AQ. Co‐administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14‐day follow‐up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow‐up.     

Stabilization of HIV incidence in women of reproductive age in southern Mozambique

Introduction

The collection of incidence data on HIV infection is necessary to evaluate the status and dynamics of the epidemic and the effectiveness of intervention strategies. However, this is usually difficult in low‐income countries.

Methods

Five yearly point HIV prevalence estimations (in 1999, 2003, 2004, 2005 and 2008) were obtained for women between 15 and 45 years of age participating in three studies carried out for other purposes at the Antenatal Clinic (ANC) in Manhiça, Mozambique. HIV incidence was estimated between prevalence points using a previously validated methodology. Two methods were used, one based on mortality rates for three HIV epidemic scenarios, and the other based on survival information after infection. The pattern over time was captured by fitting a log‐regression model.

Results

The prevalence of HIV infection ranged from 12% in 1999 to 49% in 2008. The HIV incidence increased from approximately 3.5 cases per 100 person‐years in 2001 to 14 per 100 person‐years in 2004, with stabilization thereafter to levels of around 12 cases per 100 person‐years. The incidence estimates were comparable for the two methods used.

Conclusion

These findings indicate an increase in the prevalence and incidence of HIV infection among women of reproductive age over the 9 years of the analysis, with a plateau in the incidence of infection since 2005. However, the very high figures for both prevalence and incidence highlight the importance of the continuation of the prevention and treatment programmes that already exist, and suggest that implementation of preventive measures is needed in this area.     

Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control.     

Safety and immunogenicity of the RTS,S/AS02A candidate malaria vaccine in children aged 1-4 in Mozambique

BACKGROUND: The development of a malaria vaccine remains a public health priority for sub-Saharan Africa. RTS,S/AS02A candidate malaria vaccine has been shown to be safe and immunogenic in previous studies in adults and staggered dose-escalation studies in children in The Gambia. However, genetic features and the intensity of malaria transmission may modify the safety and immune response of a vaccine. OBJECTIVE: We carried out a phase I, double-blind randomized controlled trial in 60 children aged 1-4 in Mozambique to evaluate the safety, reactogenicity and immunogenicity of the paediatric vaccine dose (fixed 25 microg RTS,S in 0.25 ml) of RTS,S/AS02A, prior to undertaking a planned larger phase IIb proof-of-concept of efficacy study in the same population. METHOD: Children were randomized to receive either RTS,S/AS02A or Engerix-B vaccine. Monitoring of safety and reactogenicity included detailed clinical and laboratory analyses and assessment of adverse events (AEs). RESULTS: The RTS,S/AS02A was found to be safe and well tolerated. Serious adverse events were balanced between both groups and none was related to vaccination. The frequency of adverse events reported with RTS, S/AS02A was comparable to previous studies in children. Grade 3 AEs were infrequent (one case of pain, one of fever in each group and some swelling greater than 20 mm in diameter), transient and resolved without sequelae. RTS,S/AS02A was highly immunogenic for anti-circumsporozoite protein antibody response and induced a strong anti-hepatitis-B surface antigen response.     

The effects of short-term iron supplementation on iron status in infants in malaria-endemic areas

Iron deficiency and Plasmodium falciparum malaria are the two main causes of anemia in young children in region endemic for this disease. The impact on iron status of prophylactic oral iron supplementation (2 mg/kg/day from two to six months of age) and the duration of this effect were assessed in a group of 832 Tanzanian infants exposed to P. falciparum malaria. Iron parameters and red blood cell indices were assessed at 2, 5, 8, and 12 months of age. Infants who received iron supplements had a significantly lower prevalence of iron deficiency (P < 0.01 at 5 months and P < 0.001 at 8 and 12 months). Red blood cell indices (mean corpuscular volume, mean cell hemoglobin, and mean cell hemoglobin concentration) were increased in children receiving iron supplementation and they did not differ between those protected and unprotected against malaria. The prevalence of ferropenia was similar in children protected against malaria and in those who were not protected and did not receive iron supplements (34.7% versus 37.3% at 12 months of age). We concluded that iron supplementation between the ages of 2-6 months improves iron status at least up to 12 months of age. Malaria infection does not contribute to iron deficiency.     

Immunophenotyping of chimeric cells in localized scleroderma

OBJECTIVE: Localized scleroderma causes thickening of the skin due to excessive collagen deposition. This condition has clinical and histopathological similarities to chronic graft-vs-host disease. We wanted to identify whether chimeric cells are present in the affected tissue in localized scleroderma and to further investigate the role of chimerism by immunophenotyping the chimeric cells. We hypothesize that the presence of chimerism and immunotypic chimeric cells will lend to an understanding of the pathogenesis of localized scleroderma and possible mechanisms by which chimeric cells participate in autoimmunity. METHODS: We studied skin biopsies from 18 localized scleroderma patients and compared them with concurrent biopsies from unaffected skin in a subset of patients. Skin biopsies from morphoea and linear scleroderma patients were analysed for the presence of chimeric cells using male-female (X, Y) differences. Cell surface markers (CD4, CD8, CD19/20, CD68, S100, CD14 and CD56) were determined for cell phenotyping of chimeric cells. RESULTS: Overall, the affected tissue contained a greater number of lymphocytic inflammatory cells. In the affected tissue, 38% of the total chimeric cells were CD68+ (dendritic cell, monocyte and macrophage marker), 29% Langerin/S100+ (dendritic cell marker), 26% CD8+ (cytotoxic T-lymphocyte marker), 20% CD19/20+ (B-lymphocyte marker), 14% CD4+ (T-helper lymphocyte) and 0% CD56+ (natural killer cell marker). CONCLUSIONS: We report that not only are chimeric cells present in affected localized scleroderma lesions but they also are more likely to be dendritic cells and B lymphocytes suggesting a role in the pathogenesis of localized scleroderma.