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.     

Prevalence of HIV and malaria: a cross-sectional study on Bioko Island,Equatorial Guinea

Malaria and HIV are two of the most severe public health problems in Africa. However, epidemiological data on Bioko Island is scarce. To investigate the prevalence of malaria and HIV infections and assess association of malaria and HIV infections and possible confounding factors, we performed a cross-sectional survey of people of malaria-endemic Bioko Island, Equatorial Guinea. A cross-sectional study of 1 526 subjects was carried out to determine the prevalence of malaria and HIV infection in Malabo region hospital on Bioko Island. Questionnaires were administered and venous blood samples were drawn for malaria parasites and HIV detection. The prevalence of participants infected with malaria and HIV in this area were 13.8% and 6.6% respectively. The average prevalence of co-infection for malaria and HIV was 0.92%. HIV-infection was significantly associated with the age and gender. Malaria infections were significantly associated with the age. This study showed that the prevalence of HIV and malaria on Bioko Island was higher than expected, although the co-infection prevalence of malaria and HIV was low. The results also indicated that malaria and HIV infections lead to more public health risk to youngsters and women.     

Epidemiology of congenital malaria in Nigeria: a multi-centre study

Objective To determine the burden of congenital malaria in newborns in Nigeria. Methods In a prospective multi‐centre study, 1875 consecutive mother–baby pairs were enrolled over a continuous 12‐month period. Blood smears were prepared from mothers, neonates, placental aspirates and cord blood within 4 h of delivery. Outcome variables were patent parasitaemia in the mother, placenta, cord and neonate in addition to maternal and neonatal haematocrit. Results Patent parasitaemia was detected in 95 neonates (5.1%). The occurrence varied between study centres, but was found year round in all sites. The mean parasite density among infected neonates was low (48 asexual forms per μl, range 8–200/μl). Maternal and placental parasitaemia were the most important risk factors for patent neonatal parasitaemia (P < 0.0001). Spontaneous clearance of parasitaemia occurred in 62.1% of neonates before day 2. 33.7% were symptomatic within 3 days of birth. Conclusion Congenital malaria is often asymptomatic, clears spontaneously and may not warrant treatment. However, newborns with unexplained fever and refusal to feed in malaria endemic areas should be tested for malaria.     

From the Cover: Modeling malaria genomics reveals transmission decline and rebound in Senegal

To study the effects of malaria-control interventions on parasite population genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium falciparum collected in Thiès, Senegal between 2006 and 2013. The parasite samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the samples grouped into subsets with identical barcodes, varying in size by year and sometimes persisting across years. The barcodes also formed networks of related groups. Analysis of 164 completely sequenced parasites revealed extensive sharing of genomic regions. In at least two cases we found first-generation recombinant offspring of parents whose genomes are similar or identical to genomes also present in the sample. An epidemiological model that tracks parasite genotypes can reproduce the observed pattern of barcode subsets. Quantification of likelihoods in the model strongly suggests a reduction of transmission from 2006–2010 with a significant rebound in 2012–2013. The reduced transmission and rebound were confirmed directly by incidence data from Thiès. These findings imply that intensive intervention to control malaria results in rapid and dramatic changes in parasite population genomics. The results also suggest that genomics combined with epidemiological modeling may afford prompt, continuous, and cost-effective tracking of progress toward malaria elimination.Intensive intervention to reduce the burden of malaria has proven successful in a number of countries in Africa (1). In certain regions of Senegal, implementation of a redesigned National Malaria Control Program (NMCP) in 2006 that included rapid diagnostic tests, artemisinin combination therapies, enhanced insecticide-treated bed nets, and indoor residual spraying resulted in a more than 95% decrease in the number of confirmed cases by 2009 (2). We had been collecting parasite samples in one of these regions annually since 2006. These samples afford a unique opportunity to determine the extent to which intensive intervention is manifested in genetic changes in the parasite population. Genetic changes would be expected to include bottlenecks in the parasite population size, increased random genetic drift, reduced genetic variation, greater self-fertilization during transmission, and increased allele sharing and identity by descent.A key question for tracking malaria elimination is whether such genomic changes would be large enough to be detected in a cost-effective manner in samples of reasonable size. If changes in parasite population genomics took place rapidly enough after intervention, and if they were large enough to be detected, then parasite genomics could play an important role in malaria elimination. Given sufficiently rapid onset and detectability of changes in parasite genomics, an epidemiological model that incorporates parasite genotypes could in principle be used to estimate the epidemiological parameters that most closely match the genomic observations. Estimates of epidemiological parameters such as transmission intensity would aid in understanding the disease situation on the ground, so that the efficacy of intervention strategies could be evaluated in real time and adjustments made as necessary. This approach could prove especially useful in regions of low transmission where classical epidemiological approaches can be applied only with great difficulty and in regions that are not easily or safely accessed by personnel committed to malaria control.In this paper, we show that data from a barcode of 24 SNPs in longitudinal samples from Thiès, Senegal over an 8-y period of moderate numbers of samples (100–200 samples/y) reveals rapid and easily detectable signals of changes in parasite population genomics following enhanced intervention. Moreover, an epidemiological model that incorporates parasite genotypes can reproduce the observed barcode patterns. Estimates of epidemiological parameters in the transmission model using likelihoods strongly suggest a reduction of transmission from 2006–2010 with a significant rebound in 2012–2013. The decrease in transmission of malaria in 2006–2010 after enhanced intervention followed by a rebound in 2012–2013 was confirmed directly by incidence data from Thiès. Our findings suggest that genomics combined with epidemiological modeling may afford rapid, continuous, and cost-effective tracking of progress toward malaria elimination.     

Patterns in age-specific malaria incidence in a population exposed to low levels of malaria transmission intensity

The population of the northern part of the province of KwaZulu Natal in South Africa has experienced low levels of malaria transmission intensity for many years. We investigated the widely held assumption that individuals in this population do not develop clinical tolerance to infection with Plasmodium falciparum. We calculated malaria incidence rates by 5-year age groups from a comprehensive small area malaria reporting system and from national census data for the period from mid-1990 to mid-1999. Incidence rates were plotted against age groups for each of the nine malaria seasons, and by quintile of crude incidence rate. These show that age-specific incidence varied considerably in areas of high incidence and in years of high incidence. In these areas malaria incidence rose with age until the late teens, and either remained constant or decreased in young adults. This finding appears to be consistent with results from settings of much higher transmission intensities which show that clinical tolerance to infection with P. falciparum in adults may be acquired as a result of a small number of infective bites in early childhood and implies that even in this relatively low transmission area, there is an asymptomatic reservoir of infection in older people. The results also show that in high incidence subregions the lowest incidences are reported for children under 5 years of age, which may be the result of greater protection offered to this age group by malaria vector control through indoor house spraying.     

Reliability of malaria microscopy in epidemiological studies: results of quality control

To assess the interrater reproducibility of malaria microscopy in epidemiological studies, 711 thick blood films from population-based surveys were randomly selected and reread by 4 experienced microscopists. Sample estimates of the prevalence of P. falciparum infection, geometric mean parasite density and the proportion of samples above various parasite density cut-off levels were almost identical in the routine and quality control readings. Differences were, however, encountered in the sample estimates for gametocyte ratio, proportion of mixed infection and average density index. In all three cases the quality control result was significantly higher than the routine evaluation. On the level of the individual slide there was good interrater agreement for the presence of P. falciparum infections (Kappa index kappa = 0.79) which was even better when parasite densities between 4 and 100/microl were excluded (kappa = 0.94). With respect to the assessment of parasite density, a high level of disagreement was found. While the mean difference between the two readings was not different from 0, the second reading was between 0.12 and 10 times that of the first. However, the level of disagreement significantly fell with increasing parasite densities. Thus malaria microscopy is very reliable for the estimation of parasite ratios and geometric mean parasite densities within and between studies as long as the same methodology is used, but tends to underestimate the gametocyte ratio and proportion of mixed infections. Care must be taken, however, when individual parasite density is related to other explanatory variables, due to the high degree of variability in the parasite enumeration.     

The molecular epidemiology of malaria

This review discusses how the use of molecular genetic techniques such as the polymerase chain reaction are helping in the management and prevention of malaria.     

People's perception of malaria in Mbarara,Uganda

To understand people's perceptions of malaria and their implications for control programmes, we held focus group discussions (FGDs) and conducted semi-structured interviews (SSIs) with community members in Mbarara, Uganda. Mosquitoes were perceived as the cause or transmitters of malaria but the causation/transmission model of people differed from biomedical facts. Convulsions, a common complication of malaria, were perceived as a supernatural ailment, best treated by traditional medicine, as was splenomegaly. More than 70% of the patients with malaria had treatment from non-public health sources. This included self-treatment (13%), use of traditional healers (12%) and use of private medical practitioners/pharmacists (69%). Although 26% (887/3309) used bednets to prevent malaria, only 7% of the nets were impregnated with insecticide. People who did not use bednets cited discomfort because of heat/humidity and their high cost as reasons. To improve malaria control in this area, people need to be educated on the connection between mosquitoes and malaria and on seeking biomedical treatment for convulsions. The malaria control programme could collaborate with traditional and private health care providers to increase promotion of insecticide-impregnated mosquito nets.     

Knowledge, attitudes and practices relevant to malaria control in remote island populations of manus, papua new Guinea

A community-based cross-sectional survey of 262 participants in four island communities of Manus, Papua New Guinea was conducted using a structured questionnaire to examine possible factors of malaria prevalence, including education experiences, knowledge, attitudes, and preventive behaviors, in relation to antimalarial antibody titers. Bivariate and multivariate analyses revealed that micro-environmental conditions caused inter-community differences in malaria prevalence. Ninety-nine percent of the subject villagers recognized mosquito bites as a cause of malaria transmission, which explains the high possession rate of bednets. There was a significant correlation between malaria education experience at schools and knowledge (p < 0.01) and between knowledge and bednet use (p < 0.05). However, regular bednet users were only 35% of the total, due primarily to feelings of discomfort, heat, and stuffiness inside the bednet. Villagers' behavior of consulting an aid post orderly (APO) in case of high fever significantly lowered the titer level (p < 0.05), while their bednet use did not. This unexpected result was attributable to inappropriate bednet use and to daily living patterns, including both subsistence and social activities. We conclude that information regarding lifestyles and attitudes toward bednet use as well as malaria education experience at schools are particularly important for practical malaria prevention.     

Antibody responses to Plasmodium falciparum gametocyte antigens during and after malaria attacks in schoolchildren from Madang, Papua New Guinea

Sera from 49 school children in Madang, Papua New Guinea with malaria and follow-up sera from 40 of these cases were tested by competitive ELISA for antibodies capable of inhibiting binding of eight monoclonal antibodies (MoAbs) to Plasmodium falciparum gametocytes. The proportion of sera inhibiting each MoAb ranged from 31.2% to 85.7%. At follow-up, the proportion of inhibitory sera decreased for 3 MoAbs, did not change significantly for 4 MoAbs and increased for one MoAb. When sera were grouped according to whether the follow-up blood slide was positive or negative, further trends emerged for MoAbs against the gamete surface antigen Pfs 48/45. Antibody levels to the IA3-B8 epitope decreased in follow-up positive cases, but remained unchanged for follow-up negative cases. The converse was observed for the IIC5-B10 epitope with an increase of antibody in follow-up positive cases and no change in the negative cases. Amount of antibody to the 3G12/58 epitope decreased when the follow-up was negative but not when it was positive. Increase in antibody to the 3E12/58 epitope occurred at the follow-up sample irrespective of the blood slide result. Thus four distinct patterns of longitudinal antibody response were observed against four epitopes on the same molecule.     

Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia

Plasmodium falciparum infection can lead to deadly complications such as severe malaria-associated anaemia (SMA) and cerebral malaria (CM). Children with severe malaria have elevated levels of circulating immune complexes (ICs). To further investigate the quantitative differences in antibody class/subclass components of ICs in SMA and CM , we enrolled 75 children with SMA and 32 children with CM from hospitals in western Kenya and matched them to 74 and 52 control children, respectively, with uncomplicated symptomatic malaria. Total IgG IC levels were always elevated in children with malaria upon enrolment, but children with CM had the highest levels of any group. Conditional logistic regression showed a borderline association between IgG4-containing IC levels and increased risk of SMA (OR = 3·11, 95% CI 1·01–9·56, P  = 0·05). Total IgG ICs (OR = 2·84, 95% CI 1·08–7·46, P  = 0·03) and IgE-containing ICs (OR = 6·82, OR 1·88–24·73, P  ≤ 0·01) were associated with increased risk of CM. These results point to differences in the contribution of the different antibody class and subclass components of ICs to the pathogenesis of SMA and CM and give insight into potential mechanisms of disease.     

A theoretical framework for the immunoepidemiology of Plasmodium falciparum malaria

Molecular genetic analyses of P. falciparum have led to the cloning and sequencing of a number of antigens that are potential candidates for vaccination against malaria. Seroepidemiological studies in endemic areas have attempted to assess the relative importance of these antigens in protection against malaria. In this paper, we attempt to evaluate the relative contributions of conserved and strain-specific immune responses by modelling their influence of age-specific patterns of infection and disease. The modelling exercises in this paper clearly demonstrate that the observed patterns of age-prevalence are best explained by proposing that the accumulation to a threshold of an immune response against a conserved determinant is required for protection against infection, while ‘anti-disease’ immunity develops more linearly with exposure. This is compatible with the conjecture that the parasite population is structured into several independently transmitted strains, that each confers some degree of ‘anti-disease’ immunity, but does not protect against further infection by the same strain. Within this framework, the average duration of parasitaemia increases with age, as previously encountered strains endure for longer periods at a subclinical level. Indirect evidence for the increase in duration of parasitaemia with age may be obtained from a comparison of age-prevalence curves between dry and rainy seasons. By using mathematical methods to structure epidemiological and immunological information, we provide a coherent theoretical framework for the dissection of the important components of naturally acquired immunity to malaria.     

Two fatal autochthonous cases of airport malaria,Belgium, 2020

We report an outbreak investigation of two fatal cases of autochthonous Plasmodium falciparum malaria that occurred in Belgium in September 2020. Various hypotheses of the potential source of infection were investigated. The most likely route of transmission was through an infectious exotic Anopheles mosquito that was imported via the international airport of Brussels or the military airport Melsbroek and infected the cases who lived at 5 km from the airports. Based on genomic analysis of the parasites collected from the two cases, the most likely origin of the Plasmodium was Gabon or Cameroon. Further, the parasites collected from the two Belgian patients were identical by descent, which supports the assumption that the two infections originated from the bite of the same mosquito, during interrupted feeding. Although airport malaria remains a rare event, it has significant implications, particularly for the patient, as delayed or missed diagnosis of the cause of illness often results in complications and mortality. Therefore, to prevent such severe or fatal outcomes, we suggest a number of public health actions including increased awareness among health practitioners, especially those working in the vicinity of airports, and increased surveillance of exotic mosquito species at airports.     

Estimates of the burden of malaria morbidity in Africa in children under the age of 5 years

Objective To estimate the direct burden of malaria among children younger than 5 years in sub‐Saharan Africa (SSA) for the year 2000, as part of a wider initiative on burden estimates. Methods A systematic literature review was undertaken in June 2003. Severe malaria outcomes (cerebral malaria, severe malarial anaemia and respiratory distress) and non‐severe malaria data were abstracted separately, together with information on the characteristics of each study and its population. Population characteristics were also collated at a national level. A meta‐regression model was used to predict the incidence of malaria fevers at a national level. For severe outcomes, results were presented as median rates as data were too sparse for modelling. Results For the year 2000, an estimated 545 000 (uncertainty interval: 105 000–1 750 000) children under the age of 5 in SSA experienced an episode of severe malaria for which they were admitted to hospital. A total of 24 000 (interquartile range: 12 000–37 000) suffered from persistent neurological deficits as a result of cerebral malaria. The number of malaria fevers associated with high parasite density in under‐5s in SSA in 2000 was estimated as 115 750 000 (uncertainty interval: 91 243 000–257 957 000). Conclusion Our study predicts a lower burden than previous estimates of under‐5 malaria morbidity in SSA. As there is a lack of suitable data to enable comprehensive estimates of annual malaria incidence, we describe the information needed to improve the validity of future estimates.     

The effect of malaria on mortality in a cohort of HIV-infected Ugandan adults

OBJECTIVES: To investigate the effects of malaria parasitaemia and clinical malaria on mortality in HIV seropositive and seronegative adults. METHODS: A cohort of adults in rural Uganda were followed from 1990 to 1998. Participants attended routine clinic visits every 3 months and also when sick (interim visits). Information was collected on HIV serostatus, history of fever, current fever and malaria parasite levels. Malaria was categorized as any parasitaemia, significant parasitaemia (>/=1.25 x 10(6) parasites/ml at routine or >/=50 parasites per 200 white blood cells at interim visits) or clinical malaria. The effect of malaria on all-cause mortality was assessed using Cox models. RESULTS: The 222 HIV seropositive participants made 2762 routine visits and 1522 interim visits. During follow-up, of the 211 participants with full records, 69% had at least one episode of parasitaemia, 51% experienced significant parasitaemia and 28% had clinical malaria. There were 90 deaths in 922 person-years of observation. There were no significant associations between numbers of visits with any parasitaemia, significant parasitaemia or clinical malaria on mortality rates. The highest mortality rates were observed in those making four or more routine visits with significant parasitaemia [adjusted mortality rate ratio (RR) 3.27 compared with those making 0 such visits; P=0.078] and those making two or more visits with clinical malaria (adjusted RR 2.23; P=0.093). There was no significant interaction between any malaria category and HIV serostatus. Conclusion We found no evidence of a strong detrimental effect of malaria on all-cause mortality in HIV seropositive adults in this setting.     

Level and dynamics of malaria transmission and morbidity in an equatorial area of South Cameroon

We conducted parasitological and entomological malaria surveys among the population of Mengang district in southern Cameroon to analyse the relationship between malaria transmission intensity and malaria morbidity. We investigated two adjacent areas which differ 10-fold in transmission intensity [annual entomological inoculation rate (EIR) 17 vs. 170], but have very similar Plasmodium falciparum malariometric profiles with parasite prevalences of 58 vs. 64%, high parasitaemia prevalences (> 1000 parasites/microl) of 15 vs. 16% and the same morbidity of 0.17-0.5 attacks/person/year. Plasmodium malariae prevalence was 14 vs. 16%. One possible explanation is that the similarity of the duration of the short and high transmission seasons in both areas is equally, if not more, significant for parasitological and clinical profiles as the annual EIR. We discuss the relationships between variations in transmission levels, parasitaemia and clinical incidence, and draw parallels to similar situations elsewhere.     

Parasite-specific lactate dehydrogenase for the diagnosis of Plasmodium falciparum infection in an endemic area in West Uganda

The measurement of parasite lactate dehydrogenase (pLDH) has been presented as an easy and rapid method for the diagnosis of malaria in humans. In order to evaluate the sensitivity and specificity of such a test we examined blood samples from 429 Ugandan patients. While pLDH activity was significantly linked to parasitaemia, sensitivity and specificity were found to be rather low at 58.8 and 62.2% respectively. The positive and negative predictive values failed to meet necessary standards. We conclude that the methods of measurement of pLDH activity in malaria infection, although potentially useful for the fast diagnosis of malaria, need to be improved to be of true value in endemic areas.     

Alpha+ -thalassaemia and pregnancy in a malaria endemic region of Papua New Guinea

The effect of maternal alpha+ -thalassaemia on pregnancy was assessed in the north coastal region of Papua New Guinea (PNG), where malaria is hyperendemic and alpha+ -thalassaemia is extremely common. In a prospective study of 987 singleton hospital deliveries, we correlated maternal alpha-globin genotype with markers of reproductive fitness (age in primigravidae, gravidity, pregnancy interval and the number of miscarriages and stillbirths), Plasmodium falciparum(P. falciparum) infection of the mother and placenta, maternal haemoglobin, preterm delivery and birthweight. The frequency of the -alpha genotype in mothers was 0.61. Markers of reproductive fitness were similar in women with and without alpha+ -thalassaemia. Median haemoglobin concentration during pregnancy and after delivery was about 1.0 g/dl lower in homozygous alpha+ -thalassaemia than in women with a normal alpha- globin genotype (P < or = 0.001). The frequency of placental P. falciparum infection and systemic malaria infection after delivery showed no consistent relationship to alpha-globin genotype. The frequency of preterm delivery and low birthweight did not vary significantly according to maternal alpha-globin genotype. Maternal alpha+ -thalassaemia does not affect reproductive fitness or susceptibility to malaria during pregnancy. Although median haemoglobin concentration was significantly lower in mothers homozygous for alpha+ -thalassaemia than those with a normal alpha-globin genotype, this did not result in an adverse outcome of pregnancy.     

1980 - 2012 年韶关市疟疾流行病学特征分析

目的总结分析广东省韶关市1980—2012年疟疾流行特点,为韶关市2014年消除疟疾提供参考依据。方法采用描述性流行病学方法,对韶关市1980—2012年疟疾防治总结和中国疾病预防控制中心疾病监测信息报告管理系统的疟疾疫情报告进行分析。结果1980—2012年韶关市累计共报告疟疾病例3094例,其中,间日疟3041例,输人性恶性疟4例,未分型49例;年平均报告疟疾病例94例,年平均疟疾发病率2．78／10万。其中1982年报告疟疾发病最多为651例,年发病率最高为14．13／10万;2006—2011年仅2008年报告1例疟疾病例,其余5年均没有病例报告。1980—2012年,5—11月份报告疟疾病例2625例,占总病例数的84．84％（2625／3094）。男女性别比为4．34：1。在报告疟疾病例3094例中,发病年龄主集中在20～45岁年龄组,共报告疟疾病例2486例,占总病例数的80．34％。1980—2012年,全市共血检475337人次,检出疟原虫阳性2127例次,平均阳性率为0．45％。1980—1994年,居民原虫率调查,共血检31139人次,检出阳性474例次,阳性率1．52％。结论韶关市1980—2012年疟疾发病逐年下降,20～45岁年龄组是疟疾的好发年龄组;近几年疟疾病例均为输入性病例,疫情平稳。