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[Congenital malaria due to Plasmodium falciparum and Plasmodium malariae].

Increasing tourism and growing numbers of immigrants from malaria-endemic countries are leading to a higher importation rate of rare tropical disorders in European countries. We describe, to the best of our knowledge, the first case of connatal malaria in Austria. The patient is the first child of a 24 year old mother who was born in Ghana and immigrated to Austria one and a half years before delivery. She did not stay in an endemic region during this period and did not show fever or any other signs of malaria. The boy was healthy for the first six weeks of his life. In the 8th week of life he was admitted to our hospital due to persistent fever of unknown origin. On physical examination he showed only mild splenomegaly. Routine laboratory testing revealed mild hemolytic anemia with a hemoglobin value of 8.3 g/l. In the blood smear Plasmodium falciparum and Plasmodium malariae were detected. Oral therapy with quinine hydrochloride was successful and blood smears became negative for Plasmodia within 6 days. This case shows that congenital malaria can occur in children of clinically healthy women who were born in malaria-endemic areas even one and a half year after they have immigrated to non-endemic regions.

Adult↗

Artemether-lumefantrine for treating uncomplicated falciparum malaria.

BACKGROUND: Artemether-lumefantrine is being promoted by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority over existing treatment regimens. OBJECTIVES: To compare artemether-lumefantrine with other antimalarial drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (April 2002), the Cochrane Controlled Trials Register (Issue 2, 2002), MEDLINE (1966 to April 2002), EMBASE (1988 to April 2002), conference proceedings, and reference lists of articles. We contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination). DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. Adverse event information was collected from the studies. MAIN RESULTS: Eight trials (2117 participants) met the inclusion criteria. In the four studies against single agents, failure rates for artemether-lumefantrine tended to be higher in comparisons against sulfadoxine-pyrimethamine, halofantrine, and mefloquine. This difference was statistically significant for mefloquine. When compared with chloroquine, artemether-lumefantrine was better in two studies, but the failure rate for chloroquine at these sites was over 50%. All single agent studies used four doses of artemether-lumefantrine. In comparisons against combination treatment, three trials tested artemether-lumefantrine against mefloquine-artesunate and showed that artemether-lumefantrine was inferior for day 28 cure (Relative Risk 6.33, 95% confidence interval 3.08 to 13.01). If this comparison is confined to the two trials where participants received six doses, artemether-lumefantrine was associated with higher cure rates, but this was not statistically significant (Relative Risk 4.20, 95% confidence interval 0.55 to 31.93). REVIEWER'S CONCLUSIONS: Artemether-lumefantrine is more effective than chloroquine in chloroquine resistant areas. Artemether-lumefantrine is less effective than mefloquine or mefloquine combined with artesunate. We found no evidence to confirm or refute whether artemether-lumefantrine was better than sulfadoxine-pyrimethamine.

Antimalarials↗

Apheresis for severe malaria complicated by cerebral malaria, acute respiratory distress syndrome, acute renal failure, and disseminated intravascular coagulation.

Malaria has become a very uncommon disease in Italy. Recently a variety of circumstances, such as travel to tropical countries as well as immigration from Asia and Africa, have combined to increase the number of malaria cases recorded annually. In this report we describe the use of red cell exchange transfusion and plasma exchange in the treatment of a patient with hyperparasitemic malaria (51% erythrocytes or more parasitized). When first observed the patient was in shock and had signs of cerebral malaria, disseminated intravascular coagulation, and acute respiratory distress syndrome, which in the following 2 days were complicated by acute renal failure. After mefloquine therapy combined with 3 red blood cell exchanges, 2 plasma exchanges, and 10 dialysis sessions over 14 days, the patient recovered completely. This case of severe malaria with multiple complications, treated with mefloquine in conjunction with both exchange transfusion and plasmapheresis, had a successful outcome and lends further support to the possible beneficial role of exchange transfusion in complicated malaria.

Acute Disease↗

Randomised double-blind placebo-controlled trial of SPf66 malaria vaccine in children in northwestern Thailand. Shoklo SPf66 Malaria Vaccine Trial Group.

BACKGROUND: Previous efficacy trials of SPf66 malaria vaccine have produced conflicting results in different populations. We report a randomised double-blind trial of the SPf66 vaccine conducted in Karen children aged 2-15 living in a malarious region of northwestern Thailand. Recombinant hepatitis B vaccine was used as a comparator. METHODS: The study had a power of 90% to detect an efficacy of 30%, defined as a reduction in the incidence of first cases of symptomatic falciparum malaria after three doses of vaccine. 1221 children received three immunisations and were eligible for the primary efficacy analysis. Intense active and passive case detection continued over 15 months of follow-up. FINDINGS: The SPf66 vaccine was well tolerated, although 26 children had mild or moderately severe local or systemic allergic reactions, compared with none in the comparator group. The vaccine was immunogenic; after three doses, 73% of recipients had seroconverted. There were no deaths due to malaria during the study. During the 15-month period of evaluation there were 379 first cases of symptomatic falciparum malaria (195 in the SPf66 recipients, 184 in the comparator group); an SPf66 efficacy of -9% (95% CI -33 to 14, p = 0.41). No significant differences between the two study groups in parasite density or any other measure of malaria-related morbidity were detected. INTERPRETATION: These findings are consistent with a recent study showing lack of efficacy of SPf66 among Gambian infants and differ from earlier positive reports from South America and evidence of borderline efficacy from Tanzania. We conclude that SPf66 does not protect against clinical falciparum malaria and that further efficacy trials are not warranted.

Adolescent↗

Malaria outbreak in a malaria-free region in Oman 1998: unknown impact of civil war in Africa.

Beginning in April 1998, the surveillance system in Dhofar region, Oman, detected malaria cases among individuals who had no risk factors for the acquisition of malaria. An investigation was conducted to describe the outbreak and to identify its possible causes. A malaria case was defined as an unexplained fever (>38 degrees C) in a resident of the Dhofar region from April to September 1998. The investigation consisted of enhanced passive case detection, active case finding through contact screening, mass blood survey and school survey. Also an entomological survey was conducted and meteorological data was reviewed. Over a period of seven months, 1279 patients with fever were examined for malaria parasites. Sixty-five cases were positive; 60 (92%) males and 5 (8%) females. Cases occurred in all age groups (range: 2-63 years, median 25 years). Most cases were among illegal Somali immigrants (28, 43%) followed by Omanis (20, 31%). Out of the 2323 slides collected from the community and 2487 from school children, 21 slides were positive. All of them were from illegal immigrants. The entomological survey detected three vectors, previously found in the region: A. d'thali, A. sergenti and A. stephensi. Although the region is classified as a malaria-free region, it has the potential for malaria introduction. This outbreak most likely occurred due to the influx of hundreds of illegal Somali immigrants due to the civil war into the Dhofar region, providing a sufficient number of gametocyte carriers for local anopheline mosquitoes to feed on.

Adolescent↗

Mothers' perceptions and knowledge on childhood malaria in the holendemic Kibaha district, Tanzania: implications for malaria control and the IMCI strategy.

Prior to an intervention on improving the quality of malaria case management, we assessed mothers' abilities to recognize nonsevere and severe/complicated malaria in children when a child has fever with other physiological and behavioural symptoms associated with malaria. Malaria was mentioned as the commonest febrile illness (94. 1%), convulsions the least (11.4%). Fever and enteric symptoms featured as the most important symptoms of childhood malaria at frequencies of 93.5% and 73.8%, respectively. The need for laboratory diagnosis was very high (98.3%), the reason being to get accurate diagnosis and treatment (89.4%). Poor outcome of treatment was ascribed to incorrect diagnosis and prescription, noncompliance at home and ineffective drugs (62.1%). Most mothers (86.6%) would take antipyretic measures first when a child has fever, and subsequently the majority (92.9%) would seek care at a modern health facility. About 50% of the mothers would give traditional treatments for childhood convulsions and wait till fits cease before the next action. A high proportion of the mothers (75%) held the belief that an injection in a child with high fever would precipitate convulsions or death. The implications of these findings for chemotherapeutic malaria control in holoendemic areas within the context of the Integrated Management of Childhood Illnesses (IMCI) strategy are discussed.

Adolescent↗

Determinants of variant surface antigen antibody response in severe Plasmodium falciparum malaria in an area of low and unstable malaria transmission.

The variant surface antigens (VSA) of infected erythrocytes are important pathogenic markers, a set of variants (VSA(SM)), were assumed to be associated with severe malaria (SM), while SM constitutes clinically diverse forms, such as, severe malarial anemia (SMA) and cerebral malaria (CM). This study was conducted in Eastern Sudan, an area of seasonal and unstable malaria transmission. Parasites and plasma were obtained from patients with different clinical grades of malaria, and flow cytometry was used for analysis of VSA antibody (Ab) response. We found that individuals recognized a broader range of isolates had a higher level of VSA Ab against the recognized isolates (correlation coefficient, 0.727, P<0.001). Unexpectedly, at the time of malaria diagnosis, plasma from patients with CM recognized a significantly larger number of isolates than did the plasma from patients with SMA (P<0.001). Parasites obtained from patients with SMA or from children were better recognized than isolates obtained from patients with uncomplicated malaria or from adults, P<0.001, P=0.021, respectively. Taken together, the above findings suggest that the limitations in the VSA immunoglobulin G repertoire were most probably contributing to the pathogenesis of SMA but not to that of CM.

Adolescent↗

Progress toward a malaria vaccine: efficient induction of protective anti-malaria immunity.

Malaria can be a very severe disease, particularly in young children, pregnant women (mostly in primipara), and malaria naïve adults, and currently ranks among the most prevalent infections in tropical and subtropical areas throughout the world. The widespread occurrence and the increased incidence of malaria in many countries, caused by drug-resistant parasites (Plasmodium falciparum and P. vivax) and insecticide-resistant vectors (Anopheles mosquitoes), indicate the need to develop new methods of controlling this disease. Experimental vaccination with irradiated sporozoites can protect animals and humans against the disease, demonstrating the feasibility of developing an effective malaria vaccine. However, developing a universally effective, long lasting vaccine against this parasitic disease has been a difficult task, due to several problems. One difficulty stems from the complexity of the parasite's life cycle. During their life cycle, malaria parasites change their residence within the host, thus avoiding being re-exposed to the same immunological environment. These parasites also possess some distinct antigens, present at different life stages of the parasite, the so-called stage-specific antigens. While some of the stage-specific antigens can induce protective immune responses in the host, these responses are usually genetically restricted, this being another reason for delaying the development of a universally effective vaccine. The stage-specific antigens must be used as immunogens and introduced into the host by using a delivery system that should efficiently induce protective responses against the respective stages. Here we review several research approaches aimed at inducing protective anti-malaria immunity, overcoming the difficulties described above.

Animals↗

[Treatment of malaria in children: 1. Uncomplicated malaria].

Malaria is a worldwide epidemic causing high morbidity and mortality especially in children younger than 5 years. In France the incidence of pediatric malaria has constantly increased up to 1500 cases in the last two years, due to Plasmodium falciparum in more than 80% of cases. According to current recommendations, any patient with clinical suspicion or confirmed diagnosis of malaria must be hospitalized for treatment. Halofantrine is the most widely used antimalarial for treatment of uncomplicated P. falciparum malaria in children. However due to halofontrine-related cardiotoxicity some teams recommend mefloquine as the first-line drug despite disadvantages related to its poorly adapted formulation and adverse gastrointestinal effects in young children. Treatment of malaria involving other plasmodium species is still based on chloroquine. Likewise the World Health Organization continues to recommend chloroquine as the first-line agent for uncomplicated malaria in endemic zones with moderate chloroquine resistance. Amodiaquin or sulfadoxine-pyrimethamine combination may be used either in case of failure or as first-line agents in zones with high chloroquine resistance. In case of multiple resistance, quinine may be used alone or in association with an antimicrobial. Other drug therapies such as combinations using artemisinine derivatives have been shown to be highly effective for control of clinical symptoms and parasitemia. Widespread use of these therapies to prevent the appearance and extension of resistance is now undergoing evaluation.

Animals↗

Quartan malaria--an investigation on the incidence of Plasmodium malariae in Bisra PHC, District Sundargarh, Orissa.

A longitudinal study on the incidence of P. malariae was taken up from September 1988 to December 1989 in Bisra block, District Sundargarh, Orissa covering 38,615 population, which is mainly tribal. The area is a known hard-core malarious region in the Garhjat hill range in eastern India. In this study, out of 22,217 blood smears examined through weekly active surveillance, 7362 (33.1%) were found malaria parasite positive. Out of the total positive cases, 82 (1.1%) were P. malariae. These occurred mostly (91.4%) in persons below 40 years of age and children below 9 years accounted for 36.6% of total quartan malaria cases. In this age group the disease was found to be associated with splenomegaly (average enlarged spleen 2.07; spleen rate 45.9%) and 9 out of 13 mixed infections of P. malariae with P. falciparum and/or P. vivax were detected from this age group. This is the first report of quartan malaria from this area.

Adolescent↗

Highlands malaria: malaria in Enga Province of Papua New Guinea.

Malaria is endemic in valleys below 1600m in Enga Province of the Highlands of Papua New Guinea. However because malaria is unstable in character and levels of transmission fluctuate, endemicity cannot be precisely categorized. Falciparum malaria epidemics are lethal here and malaria is an important disease among the people dwelling below 1600m. Possibly because of this most of the population live above 1600m where malaria transmission is less likely. In some areas however malaria may be transmitted around 1800m.

Adolescent↗

Human immune responses against sexual stages of malaria parasites: considerations for malaria vaccines.

Studies on the natural immune responses to the sexual stages of malaria parasites have been reviewed in the context of human malaria transmission-blocking vaccines. Antibodies against the sexual stages of the malaria parasite, gametocytes and gametes, are readily evoked by natural malaria infections. These antibodies that suppress infectivity at high concentrations can, at low concentrations, enhance the development of the parasite in the mosquito; however, because enhancing antibodies are prevalent during natural malaria infections, it is likely that a vaccine would rapidly boost these antibodies to blocking levels. The immunogenicity of sexual stage antigens appears to be constrained in the human host, probably due to T epitope polymorphism and MHC restriction in humans. These constraints apply mainly to those antigens that are sensitive targets of host immunity such as the gamete surface antigens and not to internal gamete antigens, indicating that antigenic polymorphism may have evolved in response to immune selection pressure. Evidence for immunosuppression of the host by exposure to endemic malaria is presented and its consequences on vaccine development are discussed.

Animals↗

Local understanding, perceptions and reported practices of mothers/guardians and health workers on childhood malaria in a Tanzanian district--implications for malaria control.

Knowledge on local understanding, perceptions and practices of care providers regarding management of childhood malaria are needed for better malaria control in urban, peri-urban and rural communities. Mothers of under five children attending five purposively selected public health facilities in the Kibaha district, Tanzania, were invited to participate in 10 focus group discussions (FGDs). The health workers of these facilities were included in six other FGDs to elicit their professional views. Analysis was done using interpretative and qualitative approaches. Both health workers and all mothers were clear about the signs and symptoms of homa ya malaria, a description consistent with the biomedical definition of mild malaria. Although most of the mothers related this to mosquito bites, some did not. Mothers also described a severe childhood illness called degedege, consistent with convulsions. Most of the mothers failed to associate this condition with malaria, believing it is caused by evil spirits. Urinating on or fuming the child suffering from degedege with elephant dung were perceived to be effective remedies while injections were considered fatal for such condition. Traditional healers were seen as the primary source of treatment outside homes for this condition and grandmothers and mother in-laws are the key decision makers in the management. Our findings revealed major gaps in managing severe malaria in the study communities. Interventions addressing these gaps and targeting mothers/guardians, mother in-laws, grandmothers and traditional healers are needed.

Adult↗

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 Manhiça 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.

Animals↗

Unstable malaria in Sudan: the influence of the dry season. Malaria in areas of unstable and seasonal transmission. Lessons from Daraweesh.

Most studies of the natural history of Plasmodium falciparum infection have been performed in areas of stable malaria transmission and the acquisition of immunity to malaria in individuals who live in such areas is well documented. For the past 10 years, we have monitored host-parasite relationships in an area characterized by unstable and seasonal malaria of low transmission intensity. The work was performed in the village Daraweesh located in north-eastern Sudan 16 km from Gedaref town. The climate of the region is characterized by well-defined wet and dry periods with a short rainy season followed by a long dry season. In some years the rains fail and there is little precipitation even during the wet season. Malaria cases are rare in the dry season and during droughts. In years with rains, falciparum malaria sweeps through Daraweesh during the wet season and 20-40% of the entire population suffer at least 1 attack of malaria. All age-groups are affected, but the risk of getting a clinical attack is about twice as high in the age-group from 5 to 20 years as in adults aged above 30 years. Serological data and evidence obtained by polymerase chain reaction indicate that only about half of new blood-stage infections cause clinical disease. Together these findings suggest that many new infections are controlled immunologically and that individuals aged over 30 years are more successful in controlling infections than are teenagers. Parasite strains collected in Daraweesh are genotypically diverse and it is likely that the outcome of new P. falciparum infections depends on the preparedness of the host immune system to mount an attack against polymorphic or variable antigens expressed by the infecting parasite.

Adolescent↗

The use of a GIS-based malaria information system for malaria research and control in South Africa.

The paper aims to outline the innovative development and application of a Geographical Information System based Malaria Information System for malaria research and control in South Africa. This system is a product of collaboration between the Malaria Control Programmes and the Malaria Research Programme of the Medical Research Council of South Africa. The ability of such a system to process data timeously into a usable format is discussed, as well as its relevance to malaria research, appropriate malaria control measures, tourism, and social and economic development.

Communicable Disease Control↗

Inoculum size, incubation period and severity of malaria. Analysis of data from malaria therapy records.

The size of the infecting inoculum may influence the severity of malaria, but evidence is scarce. Malaria therapy records provide a unique source of information on induced malaria in people. The therapy was given to large numbers of neurosyphilis patients and the malaria was left untreated as long as possible. Data from patients treated at the Horton Hospital, Epsom 1923-60 with a single strain of vivax malaria were analysed to assess the influence of inoculum size on severity of disease. Malaria was induced by mosquito bite, blood inoculation or direct sporozoite inoculation. The different measures of inoculum size were inversely correlated with pre-patent period, as expected. Overall, information was available on a total of 563 non-immune patients who were not treated during the first 5 days of patent parasitaemia. No strong or consistent relationships were found between measures of inoculum size and any of the measures of severity used: neither parasitaemia levels, nor peak fevers, nor number of paroxysms of fever. In the largest data set, longer pre-patent periods were associated with tertian fever, spontaneous recovery and less use of modifying treatment. Difficulties in interpreting the results are discussed, particularly with respect to misclassification of both exposure and outcome variables. While an inoculum size-severity relationship cannot be ruled out, a strong relationship is very unlikely.

Adolescent↗

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.

Adolescent↗