Clinical manifestations of severe malaria in the highlands of southwestern Uganda

Epidemics of malaria have occurred in highland areas of East Africa since the 1980s, but the clinical spectrum of severe malaria in these areas has not been described. Over a 17-month period from 2001 to 2002, we assessed 117 consecutive patients admitted to Kabale Hospital in highland Uganda who met the World Health Organization 2000 criteria for severe malaria. Sixty-six persons (56.4%) were age 5 years or older, and 51 (43.6%) were under 5 years of age. Fever, vomiting, and cough were the most frequent symptoms. Hepatomegaly and splenomegaly were infrequent. Prostration was the most frequent manifestation of severe malaria in children under 5 years of age (45.1%) and persons 5 years or older (65.2%), followed by respiratory distress (29.4%) and severe anemia (19.6%) in children under 5 years, and respiratory distress (15.2%) and impaired consciousness (13.6%) in persons 5 years or older. Strictly defined cerebral malaria was uncommon (3.4%). In a multivariate regression model, children under 5 years were more likely than persons 5 years or older to present with severe anemia (OR 5.2, 95% confidence interval [CI] 1.2-21.9) and respiratory distress (OR 3.5, 95% CI 1.3-11.1) and less likely to present with prostration (OR 0.3, 95% CI 0.1-0.7) and impaired consciousness (OR 0.2, 95% CI 0.0-0.9). In highland Uganda, severe malaria often occurs in persons older than 5 years of age. "Typical" signs like splenomegaly are frequently absent, prostration is the major manifestation, and other manifestations vary in frequency according to age.     

Scaling Up Malaria Control in Zambia: Progress and Impact 2005�C2008

Zambia national survey, administrative, health facility, and special study data were used to assess progress and impact in national malaria control between 2000 and 2008. Zambia malaria financial support expanded from US$9 million in 2003 to US$ ~40 million in 2008. High malaria prevention coverage was achieved and extended to poor and rural areas. Increasing coverage was consistent in time and location with reductions in child (age 6–59 months) parasitemia and severe anemia (53% and 68% reductions, respectively, from 2006 to 2008) and with lower post-neonatal infant and 1–4 years of age child mortality (38% and 36% reductions between 2001/2 and 2007 survey estimates). Zambia has dramatically reduced malaria transmission, disease, and child mortality burden through rapid national scale-up of effective interventions. Sustained progress toward malaria elimination will require maintaining high prevention coverage and further reducing transmission by actively searching for and treating infected people who harbor malaria parasites.     

Differences in presentation of severe malaria in urban and rural Gabon

There are rare comparative studies of the clinical and laboratory features of severe and moderate malaria, including predictors of poor outcome, in rural and urban areas for regions of high malaria transmission. We therefore studied 2,235 children hospitalized for malaria in a rural (Lambaréné) and an urban (Libreville) area in Gabon between January 2001 and December 2002. From children screened, 33% and 48% were hospitalized for malaria in Libreville and Lambaréné, respectively (P < 0.001). Two malaria clinical groups were identified according to the World Health Organization 2000 classification of severe malaria. In both areas, severe malaria was characterized by a high proportion of severe anemia. The case fatality rate was 5-fold lower in Lambaréné than in Libreville (1% versus 5%; P < 0.0001). In both sites, cerebral malaria associated with respiratory distress was the most important predictor of fatal malaria (odds ratio = 10.7, 95% confidence interval = 4.8-23.8 P < 0.0001).     

The clinical impact of combining intermittent preventive treatment with home management of malaria in children aged below 5 years: cluster randomised trial

Objective To investigate the impact of seasonal intermittent preventive treatment (IPTc) on malaria‐related morbidity in children <5 years of age who already had access to home‐based management of malaria (HMM) for presumptive treatment of fevers. Method Thirty community‐based drug distributors (CDDs) from all 13 communities of a rural subdistrict in Ghana were trained to provide prompt treatment for presumptive malaria using artesunate‐amodiaquine (AS+AQ) to all children under 5 years of age. Six communities were randomised to also receive bimonthly courses of seasonal IPTc with AS+AQ in May, July and September of 2007. The primary outcome was the incidence rate of febrile episodes diagnosed presumptively as malaria by the CDDs in the communities in each intervention group. Cross‐sectional surveys were conducted to determine the prevalence of parasitaemia and anaemia among the study children. Results During the 6 months in which IPTc was delivered, incidence of fevers in communities given HMM+IPTc was lower than in communities given HMM alone, but this difference was not statistically significant (protective efficacy: 37.0%(95% CI: ?9.7 to 63.8; P = 0.14). However, incidence of presumptive malaria was significantly lower in IPTc communities when only children who received all three courses of IPTc were included in the analysis: protective efficacy 61.5% (95% CI:31.2–78.5; P = 0.018). Protection with IPTc was not followed by rebound morbidity in the following year. At the end of the intervention period, prevalence of asymptomatic parasitaemia was lower in communities that had received IPTc, but there were no differences in anaemia or haemoglobin concentration. Conclusion In this study area, incidence of fevers was lower in communities given three courses of IPTc during the time of peak transmission than in communities that received only HMM. However, high levels of coverage for IPTc will be necessary for maximum impact.     

Association of intraleukocytic Plasmodium falciparum malaria pigment with disease severity, clinical manifestations, and prognosis in severe malaria

Peripheral parasite density of Plasmodium falciparum is used as an indicator of malaria disease severity, but does not quantify central sequestration, which is important in the pathogenesis of severe disease. Malaria pigment, recognizable within the cytoplasm of phagocytic cells by light microscopy may represent a peripheral marker for parasite biomass. One hundred seventy-two index cases of severe malaria and 172 healthy age-, residence-, and ethnicity-matched controls with uncomplicated malaria in Bandiagara, Mali were analyzed prospectively for presence of malaria pigment. The presence of polymorphonuclear cell (PMN) and monocyte pigment was strongly associated with severe disease compared with uncomplicated malaria. Total PMN pigment burden in children with severe malaria was higher in those with cerebral manifestations and with combined cerebral manifestations and severe anemia (hemoglobin < or = 5 g/dL) but was not associated with hyperparasitemia (> 500,000 asexual forms/mm3). Additionally, pigmented PMNs/mm3 was associated with a fatal outcome in patients with severe malaria. This study validates the presence of malaria pigment in monocytes and neutrophils as a marker for disease severity, and demonstrates that pigmented neutrophils are associated with cerebral malaria and with death in children with severe malaria.     

Role of influenza and other respiratory viruses in admissions of adults to Canadian hospitals

Objective We sought to estimate age‐specific hospitalization rates attributed to influenza and other virus for adults. Methods Admissions from Canada’s national hospitalization database (Canadian Institute of Health Information), from 1994/95 to 1999/2000, were modeled as a function of proxy variables for influenza, respiratory syncytial virus (RSV) and other viral activity, seasonality and trend using a Poisson regression model and stratified by age group. Results The average annual influenza‐attributed hospitalization rate for all adults, 20 years of age or older, over the study period, which included three severe seasons, was an estimated 65/100 000 population (95% CI 63–67). Among persons aged 65 and over, 270–340 admissions per 100 000 population per year were attributed to influenza, while 30–110, 60–90 and 130–350 per 100 000 were attributed to RSV, parainfluenza (PIV) and other respiratory viruses, respectively. Although marked season‐to‐season variation in age‐specific hospitalization rates attributable to influenza was observed in persons 50 years of age and older, increasing risk with age was preserved at all time periods. Conclusions Influenza, RSV, PIV and other respiratory viruses were all associated with morbidity requiring hospitalization, while influenza was responsible for peak respiratory admissions. The burden of health care utilization associated with respiratory viruses is appreciable beginning in the sixth decade and increases significantly with age.     

Leprosy trends in Zambia 1991–2009

Objective To document leprosy trends in Zambia over the past two decades to ascertain the importance of leprosy as a health problem in Zambia. Methods Retrospective study covering the period 1991–2009 of routine national leprosy surveillance data, published national programme review reports and desk reviews of in‐country TB reports. Results Data reports were available for all the years under study apart from years 2001, 2002 and 2006. The Leprosy case notification rates (CNR) declined from 2.73/10 000 population in 1991 to 0.43/10 000 population in 2009. The general leprosy burden showed a downward trend for both adults and children. Leprosy case burden dropped from approximately 18 000 cases in 1980 to only about 1000 cases in 1996, and by the year 2000, the prevalence rates had fallen to 0.67/10 000 population. There were more multibacillary cases of leprosy than pauci‐bacillary cases. Several major gaps in data recording, entry and surveillance were identified. Data on disaggregation by gender, HIV status or geographical origin were not available. Conclusion Whilst Zambia has achieved WHO targets for leprosy control, leprosy prevalence data from Zambia may not reflect real situation because of poor data recording and surveillance. Greater investment into infrastructure and training are required for more accurate surveillance of leprosy in Zambia.     

中国华支睾吸虫病疾病负担估算及其变化趋势分析

目的 估算全国华支睾吸虫病疾病负担及其变化趋势,分析其空间分布特征,为该病防治提供科学依据.方法 基于1988-1992、2001-2004年和2014-2016年3次全国人体重要寄生虫病现状调查华支睾吸虫感染率数据和国家统计局人口学数据,将伤残调整寿命年(disability-adjusted life year,D...     

Short report: hepatitis b infection and severe Plasmodium falciparum malaria in Vietnamese adults

We investigated the prevalence of infection with hepatitis B virus among adult Vietnamese patients hospitalized for severe Plasmodiumfalciparum malaria. Sera from patients admitted with severe malaria in Ho Chi Minh City, Vietnam, between May 1991 and January 1996 were assayed for hepatitis B surface antigen (HB(s)Ag) by a commercial enzyme-linked immunosorbent assay kit. The overall prevalence of HB(s)Ag was 23.77% (77 of 324). This was higher than reported estimates of prevalence in the general catchment population for the study hospital (mean, 9.8%; range, 9-16%). No association was found between risk of death caused by severe malaria and HB(s)Ag. Patients admitted with cerebral malaria had a slightly greater risk of registering positive for HB(s)Ag (relative risk, 1.28; 95% confidence interval, 1.04-1.58) relative to other manifestations of severe malaria. Chronic infection with hepatitis B virus may be a risk factor for severe malaria.     

Prolongation of the corrected QT interval in adult patients with anti‐Ro/SSA–positive connective tissue diseases

Objective

Newborns of mothers positive for anti‐Ro/SSA autoantibodies may develop a series of electrocardiographic (EKG) disturbances. Prolongation of the corrected QT (QTc) interval was recently reported in a significant proportion of children with maternally acquired anti‐Ro/SSA antibodies, with a concomitant disappearance of EKG abnormalities and acquired maternal autoantibodies during the first year, suggesting a direct, reversible electrophysiologic effect of anti‐Ro/SSA antibodies on the ventricular repolarization. On this basis, we investigated whether these antibodies may also affect cardiac repolarization in anti‐Ro/SSA–positive adult patients with connective tissue diseases.

Methods

Fifty‐seven patients with connective tissue diseases were selected: 31 had anti‐Ro/SSA antibodies and 26 did not (controls). In all subjects, we analyzed the QTc interval, heart rate variability, and signal‐averaged high‐resolution EKG recording.

Results

Anti‐Ro/SSA–positive patients showed a significant prolongation of the mean QTc interval compared with the controls (mean ± SD 445 ± 21 versus 419 ± 17 msec; P = 0.000005). Eighteen of the 31 anti‐Ro/SSA–positive patients (58%) and none of the 26 anti‐Ro/SSA–negative patients had QTc values above the upper limit of normal (440 msec). Both groups had a reduction in heart rate variability, with a prevalence for the sympathetic nervous system and a high incidence of ventricular late potentials; these values were not significantly different between the 2 groups.

Conclusion

Adult patients with anti‐Ro/SSA–positive connective tissue diseases showed a high prevalence of QTc interval prolongation. This feature, with the concomitant abnormalities in the autonomic tone and ventricular late excitability observed in all patients studied, suggests that anti‐Ro/SSA–positive patients may have a particularly high risk of developing life‐threatening arrhythmias.

     

Viewpoint: do we have enough data to estimate the current burden of tuberculosis? The example of Bangladesh

Objective National tuberculosis (TB) programmes need accurate estimates of the burden of TB in order to assess case detection, and progress towards the millennium development goals (MDGs). We reviewed nationwide epidemiological data on TB burden in Bangladesh to decide whether additional information is needed, in order to assess the current burden of TB. Method We collected all nationwide epidemiological information: notification data for the period 1995–2004; reports of TB prevalence surveys in 1964–1966 and 1987–1988 and a tuberculin survey in 1964–1966. Data were evaluated for usefulness to provide information about the current burden of TB. Results The TB prevalence surveys from 1964 to 1966 and 1987 to 1988 provide very different results, respectively, 127/100 000 and 471/100 000 smear positives. In 1964–1966, the annual risk of infection was 0.6% in the 5‐ to 9‐year age group and 1.2% in those aged between 10 and 14 years. The notification data show an increase from 18/100 000 in 1995 to 46/100 000 smear positives in 2004. Conclusion Interpretation and extrapolation of the existing epidemiological data of Bangladesh to estimate the current burden of TB is difficult. Many of the 22 high‐burden countries have as few or even less survey data than Bangladesh. To enable the evaluation of progress towards the MDGs and to be able to assess the global burden of TB, epidemiological surveys are needed.     

Anti-Ro/SSA-associated corrected QT interval prolongation in adults: the role of antibody level and specificity

Objective

Recent evidence suggests that anti‐Ro/SSA antibodies, strongly associated with the development of congenital heart block, may also be arrhythmogenic for the adult heart. In fact, anti‐Ro/SSA–positive patients with connective tissue disease (CTD) frequently display corrected QT (QTc) prolongation associated with an increase in ventricular arrhythmias. However, QTc prolongation prevalence markedly differs throughout the studies (10–60%), but the reason why is not yet clear. The aim of this study was to evaluate whether anti‐Ro/SSA–associated QTc prolongation in adult patients with CTD is related to antibody level and specificity.

Methods

Forty‐nine adult patients with CTD underwent a resting 12‐lead electrocardiogram recording to measure QTc interval, and a venous withdrawal to determine anti‐Ro/SSA antibody level and specificity (anti–Ro/SSA 52 kd and anti–Ro/SSA 60 kd) by immunoenzymatic methods and Western blotting.

Results

In our population, a direct correlation was demonstrated between anti–Ro/SSA 52‐kd level and QTc duration (r = 0.38, P = 0.007), patients with a prolonged QTc had higher levels of anti–Ro/SSA 52 kd with respect to those with a normal QTc (P = 0.003), and patients with a moderate to high level (≥50 units/ml) of anti–Ro/SSA 52 kd showed a longer QTc interval (P = 0.008) and a higher QTc prolongation prevalence (P = 0.008) than those with a low positive/negative level (<50 units/ml). On the contrary, no association was found between QTc and anti–Ro/SSA 60‐kd level.

Conclusion

In anti‐Ro/SSA–positive adult patients with CTD, the occurrence of QTc prolongation seems strictly dependent on the anti–Ro/SSA 52‐kd level. This finding, possibly explaining the different QTc prolongation prevalence reported, strengthens the hypothesis that an extremely specific autoimmune cross‐reaction is responsible for the anti‐Ro/SSA–dependent interference on ventricular repolarization.     

Australia’s national trends in the incidence of Type 1 diabetes in 0–14‐year‐olds, 2000–2006

Aims To determine the national incidence of Type 1 diabetes in children aged 0–14 years and examine trends in incidence between 2000 and 2006 by age, sex and calendar year. Methods Case ascertainment was from the Australian National Diabetes Register, a prospective population‐based incidence register established in 1999, with two sources of ascertainment: the National Diabetes Services Scheme and the Australasian Paediatric Endocrine Group’s state‐based registers. Denominator data were from the Australian Bureau of Statistics. Results There were 6350 new cases of Type 1 diabetes (3323 boys and 3027 girls). Case ascertainment was 97.1% complete using the capture–recapture method. The mean adjusted incidence rate for 2000–2006 was 21.6 per 100 000 person‐years [95% confidence interval (CI) 21.0, 22.1], and increased from 19.8 in 2000 to 23.4 per 100 000 in 2006, an average increase of 2.8% (95% CI 1.5, 4.1) per year. Mean incidence for the 7‐year period increased with age, and was significantly higher in boys aged 0–4 years and 10–14 years than in girls of the same age. Conclusions The incidence of Type 1 diabetes among 0–14‐year‐olds in Australia is very high compared with available data from many other countries. The rate of increase observed globally in the last decade has continued well into this decade in Australia. The rising incidence cannot be explained by changes in genetic susceptibility; there is an urgent need to examine the environmental factors that have contributed to this increase. The findings of this study also have important implications for resource planning.     

Incidence of pneumonia,bacteremia, and invasive pneumococcal disease in Pakistani children

Objective To determine the incidence of pneumonia, bacteremia, and invasive pneumococcal disease (IPD) in Pakistani children <5 years old. Methods Household surveillance from 1st February 2007 to 12th May 2008 was conducted in two low‐income, coastal communities of Karachi. Community health workers referred each sick child <5 years old to the local clinic. Blood culture was obtained whenever possible from children meeting inclusion criteria. Results Overall, 5570 children contributed 3949 observation years. There were 1039 clinical cases of pneumonia, of which 54 were severe pneumonia and four cases of very severe disease according to WHO criteria. The overall pneumonia incidence was 0.26 (95% CI: 0.25–0.28) episodes per child‐year. A pathogen was isolated from the blood of 29 (2.8%) pneumonia cases. Bacteremia incidence was 912 (95% CI: 648–1248) episodes per 100 000 child‐years with a case fatality rate of 8%. The detected IPD incidence was 25 (95% CI: 1–125) episodes per 100 000 child‐years. The under‐five mortality rate was 55 per 1000 live births, with pneumonia causing 12 (22%) deaths among children <5 years old. Conclusion Clinical pneumonia is common in Pakistani children, with one in four deaths attributable to the disease. Bacteremia occurs at a high rate but surveillance for pneumococcus underestimates the burden of IPD.     

Changing pattern of malaria in Bissau, Guinea Bissau

Objective To describe the epidemiology of malaria in Guinea‐Bissau, in view of the fact that more funds are available now for malaria control in the country. Methods From May 2003 to May 2004, surveillance for malaria was conducted among children less than 5 years of age at three health centres covering the study area of the Bandim Health Project (BHP) and at the outpatient clinic of the national hospital in Bissau. Cross‐sectional surveys were conducted in the community in different malaria seasons. Results Malaria was overdiagnosed in both health centres and hospital. Sixty‐four per cent of the children who presented at a health centre were clinically diagnosed with malaria, but only 13% of outpatient children who tested for malaria had malaria parasitaemia. Only 44% (963/2193) of children admitted to hospital with a diagnosis of malaria had parasitaemia. The proportion of positive cases increased with age. Among hospitalized children with malaria parasitaemia, those less than 2 years old were more likely to have moderate anaemia (RR = 1.27; 95% CI: 1.02–1.56) (P = 0.03) or severe anaemia (RR = 1.67; 95% CI: 1.25–2.24) (P = 0.0005) than older children. The prevalence of malaria parasitaemia in the community was low (3%, 53/1926). Conclusion In Bissau, the prevalence of malaria parasitaemia in the community is now low and malaria is over‐diagnosed in health facilities. Laboratory support will be essential to avoid unnecessary use of the artemisinin combination therapy which is now being introduced as first‐line treatment in Bissau with support from the Global Fund.     

Outcome of pregnancies in patients with anti‐SSA/Ro antibodies: A study of 165 pregnancies,with special focus on electrocardiographic variations in the children and comparison with a control group

Objective

Aside from congenital heart block (CHB), sinus bradycardia and prolongation of the corrected QT (QTc) interval have been reported in infants born to mothers with anti‐SSA antibodies. To assess the pathologic nature of these manifestations, this study focused on electrocardiographic (EKG) variations in these children, comparing them with findings in a control group.

Methods

We studied 165 consecutive pregnancies in 106 anti‐SSA–positive women with connective tissue diseases (CTDs). EKGs obtained on 58 children of this group were compared with those obtained on 85 infants born to mothers with CTD who were negative for both anti‐SSA and anti‐SSB.

Results

No statistically significant difference was seen between the 2 study groups with regard to gestational age, prematurity, birth weight, age of the children at the time of EKG, age of the mothers, or treatments received by the mothers during their pregnancies. Seven of 137 children developed cutaneous neonatal lupus syndrome; 1 child developed CHB (CHB risk of 1 in 99 [1%] if only the first prospectively observed pregnancy in women without a history of CHB is included in the analysis). For EKGs recorded during the first 2 months of life, the mean ± SD PR interval was 96 ± 16 msec in the anti‐SSA–positive group and 96 ± 13 msec in the anti‐SSA–negative group (P = 0.84), with mean QTc values of 397 ± 27 and 395 ± 25 msec (P = 0.57) and mean heart rates of 141 ± 23 and 137 ± 21 beats per minute (P = 0.20), respectively. No difference in the PR interval, QTc interval, or heart rate was observed for EKGs obtained between 2 and 4 months of life. When EKGs obtained at 0–2 months were compared with those obtained at 2–4 months, a physiologic prolongation of the QTc interval was observed in both study groups. No sudden infant death or symptomatic arrhythmia occurred during the first year of life.

Conclusion

The EKG findings in children of anti‐SSA–positive and anti‐SSA–negative mothers were not significantly different. Our results suggest that the prolongation of the QTc interval and sinus bradycardia that have recently been reported in children of mothers with anti‐SSA antibodies occur independently of the anti‐SSA antibodies. The pathologic nature of these EKG variations was not confirmed by our controlled study.

     

Insecticide-treated bednets reduce mortality and severe morbidity from malaria among children on the Kenyan coast

New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub-Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m²) among a rural population on the Kenyan Coast. Between 1991 and 1993 continuous community-based demographic surveillance linked to hospital-based in-patient surveillance identified all mortality and severe malaria morbidity events during a 2-year period among a population of over 11 000 children under 5 years of age. In July 1993, 28 randomly selected communities were issued ITBN, instructed in their use and the nets re-impregnated every 6 months. The remaining 28 communities served as contemporaneous controls for the following 2 years, during which continuous demographic and hospital surveillance was maintained until the end of July 1995. The introduction of ITBN led to significant reductions in childhood mortality (PE 33%, CI 7–51%) and severe, life-threatening malaria among children aged 1–59 months (PE 44%, CI 19–62). These findings confirm the value of ITBN in improving child survival and provide the first evidence of their specific role in reducing severe morbidity from malaria.     

The changing epidemiology of malaria in Ifakara Town, southern Tanzania

Between 1995 and 2000 there were marked changes in the epidemiology of malaria in Ifakara, southern Tanzania. We documented these changes using parasitological and clinical data from a series of community- and hospital-based studies involving children up to the age of 5 years. There was a right shift and lowering in the age-specific parasite prevalence in the community-based cohort studies. The incidence of clinical malaria in placebo-receiving infants in additional study cohorts dropped from 0.8 in 1995 to 0.43 episodes per infant per year in 2000, an incidence rate ratio of 0.53 (95% confidence interval: 0.404, 0.70, P<0.0001). At the same time, there was an increase in the total number of malaria admissions and a marked right shift in the age pattern of these admissions (median age in 1995 1.55 years vs. 2.33 in 2000, P<0.0001). However, the burden of malaria deaths remained in infants. We discuss how these dramatic changes in the epidemiology of malaria may have arisen from the use of currently available malaria control tools. Caution is required in the interpretation of hospital-based data as it is likely to underestimate the impact of anaemia on mortality in the community, where most paediatric deaths occur. Even in low/moderate malaria transmission settings, where older children suffer most malaria episodes, targeting effective malaria control at infants may produce important reductions in infant mortality caused by malaria.     

High titers of IgG antibodies against Plasmodium falciparum serine repeat antigen 5 (SERA5) are associated with protection against severe malaria in Ugandan children

Plasmodium falciparum serine repeat antigen (SERA5) is a promising asexual blood stage malaria candidate vaccine. However, there is a paucity of information about natural immune responses to SERA5 in children from malaria-endemic regions. We undertook a hospital-based case-control study of severe malaria in Apac District, Northern Uganda, in children 6-59 months of age. The commonest symptoms observed in children with severe malaria (SM) were respiratory distress (53.4%) and prostration (40.4%) followed by circulatory collapse (7.4%), severe anemia (Hb < 5 g/dL, 7.0%), and seizures (2.6%). None of the SM children had impaired consciousness, coma, or cerebral malaria. We measured serum IgG antibodies using a recombinant construct of SERA5 (SE36) in enzyme-linked immunosorbent assays. High titers of IgG anti-SE36 were associated with protection against severe malaria in children under 5 years old.