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Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls.

Inflammatory cytokines play an important role in human immune responses to malarial disease. However, the role of these mediators in disease pathogenesis, and the relationship between host protection and injury remains unclear. A total of 248 cases of severe Plasmodium falciparum malaria among children aged 3 months to 14 years residing in Bandiagara, Mali, were matched to cases of uncomplicated malaria and healthy controls. Using modified World Health Organization criteria for defining severe malaria, we identified 100 cases of cerebral malaria (coma, seizure, and obtundation), 17 cases of severe anemia (hemoglobin, <5 g/dl), 18 cases combined cerebral malaria with severe anemia, and 92 cases with hyperparasitemia (asexual trophozoites, >500,000/mm3). Significantly elevated levels (given as geometric mean concentrations in picograms/milliliter) of interleukin-6 (IL-6; 485.2 versus 54.1; P = <0.001), IL-10 (1,099.3 versus 14.1; P = <0.001), tumor necrosis factor alpha (10.1 versus 7.7; P = <0.001), and IL-12(p70) (48.9 versus 31.3; P = 0.004) in serum were found in severe cases versus healthy controls. Significantly elevated levels of IL-6 (485.2 versus 141.0; P = <0.001) and IL-10 (1,099.3 versus 133.9; P = <0.001) were seen in severe malaria cases versus uncomplicated malaria controls. Cerebral malaria was associated with significantly elevated levels of IL-6 (754.5 versus 311.4; P = <0.001) and IL-10 (1,405.6 versus 868.6; P = 0.006) compared to severe malaria cases without cerebral manifestations. Conversely, lower levels of IL-6 (199.2 versus 487.6; P = 0.03) and IL-10 (391.1 versus 1,160.9; P = 0.002) were noted in children with severe anemia compared to severe malaria cases with hemoglobin at >5 g/dl. Hyperparasitemia was associated with significantly lower levels of IL-6 (336.6 versus 602.1; P = 0.002). These results illustrate the complex relationships between inflammatory cytokines and disease in P. falciparum malaria.

Adolescent↗

Rapid urban malaria appraisal (RUMA) I: epidemiology of urban malaria in Ouagadougou.

BACKGROUND: Rapid urbanization in sub-Saharan Africa has a major impact on malaria epidemiology. While much is known about malaria in rural areas in Burkina Faso, the urban situation is less well understood. METHODS: An assessment of urban malaria was carried out in Ouagadougou in November -December, 2002 during which a rapid urban malaria appraisal (RUMA) was applied. RESULTS: The school parasitaemia prevalence was relatively high (48.3%) at the cold and dry season 2002. Routine malaria statistics indicated that seasonality of malaria transmission was marked. In the health facilities, the number of clinical cases diminished quickly at the start of the cold and dry season and the prevalence of parasitaemia detected in febrile and non-febrile cases was 21.1% and 22.0%, respectively. The health facilities were likely to overestimate the malaria incidence and the age-specific fractions of malaria-attributable fevers were low (0-0.13). Peak prevalence tended to occur in older children (aged 6-15 years). Mapping of Anopheles sp. breeding sites indicated a gradient of endemicity between the urban centre and the periphery of Ouagadougou. A remarkable link was found between urban agriculture activities, seasonal availability of water supply and the occurrence of malaria infections in this semi-arid area. The study also demonstrated that the usage of insecticide-treated nets and the education level of family caretakers played a key role in reducing malaria infection rates. CONCLUSION: These findings show that determining local endemicity and the rate of clinical malaria cases are urgently required in order to target control activities and avoid over-treatment with antimalarials. The case management needs to be tailored to the level of the prevailing endemicity.

Antimalarials↗

Rapid Urban Malaria Appraisal (RUMA) III: epidemiology of urban malaria in the municipality of Yopougon (Abidjan).

BACKGROUND: Currently, there is a significant lack of knowledge concerning urban malaria patterns in general and in Abidjan in particular. The prevalence of malaria, its distribution in the city and the fractions of fevers attributable to malaria in the health facilities have not been previously investigated. METHODS: A health facility-based survey and health care system evaluation was carried out in a peripheral municipality of Abidjan (Yopougon) during the rainy season of 2002, applying a standardized Rapid Urban Malaria Appraisal (RUMA) methodology. RESULTS: According to national statistics, approximately 240,000 malaria cases (both clinical cases and laboratory confirmed cases) were reported by health facilities in the whole of Abidjan in 2001. They accounted for 40% of all consultations. In the health facilities of the Yopougon municipality, the malaria infection rates in fever cases for different age groups were 22.1% (under one year-olds), 42.8% (one to five years-olds), 42.0% (> five to 15 years-olds) and 26.8% (over 15 years-olds), while those in the control group were 13.0%. 26.7%, 21.8% and 14.6%, respectively. The fractions of malaria-attributable fever were 0.12, 0.22, 0.27 and 0.13 in the same age groups. Parasitaemia was homogenously detected in different areas of Yopougon. Among all children, 10.1% used a mosquito net (treated or not) the night before the survey and this was protective (OR = 0.52, 95% CI 0.29-0.97). Travel to rural areas within the last three months was frequent (31% of all respondents) and associated with a malaria infection (OR = 1.75, 95% CI 1.25-2.45). CONCLUSION: Rapid urbanization has changed malaria epidemiology in Abidjan and endemicity was found to be moderate in Yopougon. Routine health statistics are not fully reliable to assess the burden of disease, and the low level of the fractions of malaria-attributable fevers indicated substantial over-treatment of malaria.

Adolescent↗

Malaria epidemiological situation in Italy and evaluation of malaria incidence in Italian travelers.

BACKGROUND: Malaria was endemic throughout the country until it was eradicated nearly 50 years ago. Since then, mainly imported malaria cases have been reported to the National Health Service, with an increasing trend. The aim of this study was to present a detailed analysis of the current epidemiological situation of malaria in Italy, and to make a first attempt to calculate the incidence of malaria in Italian international travelers. METHODS: An archive of confirmed malaria cases is available at the Istituto Superiore di Sanità (ISS), the National Institute of Health of Italy, based on the mandatory report system. Data from each case report reported to the ISS from 1989 to 1997 have been analyzed. An evaluation of malaria incidence in Italian travelers has been also performed for the same period, based on the statistics provided by the Ministry of Transport. RESULTS: From 1989 to 1997, a total of 5,898 microscopically confirmed malaria cases have been reported. Of these, 5,773 (97.9%) were imported cases, 106 cases (1.8%) were relapses of Plasmodium vivax or Plasmodium ovale infections, and 19 cases (0.3%) occurred in subjects who had never been out of Italy. During the period of study, 55 deaths due to Plasmodium falciparum malaria were reported, with a mean fatality rate of 1.2%. Malaria incidence in Italians who traveled to Africa was estimated to be 1.5/1000. These figures appeared to be 10-20 and 30-40 times greater than that recorded in travelers to Asia (0.11/1000) and Central-South America (0.04/1000) respectively. CONCLUSIONS: From 1989 to 1997, there has been a remarkable increase in the total number of imported malaria cases in Italy, which reached a peak of more than 800 cases/year in 1997. A constant increase in the number of cases affecting foreigners has been reported, while the cases among Italians have remained stable. From 1989 to 1997 the number of Italian intercontinental travelers has nearly doubled, but malaria incidence has remained quite stable.

Adult↗

[Malaria in Israel--can severe malaria related morbidity and mortality be prevented?].

Malaria was eradicated in Israel about 50 years ago. Despite this, the number of cases of malaria in Israel has been increasing in the past few years due to imported malaria from endemic countries. Although malaria is a preventable and treatable disease, severe and fatal cases of malaria occur every year. The majority of malaria cases occur in travelers who did not take prophylaxis. Therefore, there is a tendency to blame them for their severe disease. However, malaria morbidity and mortality increases with any delay in diagnosis and treatment. Hence, it should be emphasized, that there are three links to this chain: the patient who did not take malaria prophylaxis, the physician who failed to consider malaria as the diagnosis of a febrile patient who had just returned from an endemic area, and finally, the hospitals that usually do not store anti-malarial medication. Action should therefore be taken on three levels: first and most easily remedied--hospitals should have anti-malarial medication available by law. Second are the physicians who must be educated with regard to the risk of malaria in returning travelers, and methods of diagnosis. Thirdly, efforts must continue to increase compliance of malaria prophylaxis among travelers to endemic areas.

Antimalarials↗

Epidemiology of malaria transmission and development of natural immunity in a malaria-endemic village, San Dulakudar, in Orissa state, India.

We describe the epidemiology of malaria in San Dulakudar, a village in Sundargarh District in the state of Orissa in eastern India. Malaria transmission is perennial with Plasmodium falciparum, accounting for greater than 80% of malaria cases. Transmission intensity varies with season with high transmission after the monsoon rains in autumn and winter, low transmission in summer, and intermediate transmission in spring. The anthropophagic mosquito Anopheles fluviatilis was identified as the main vector for malaria transmission. Based on observations of spleen rates and supported by data on malaria parasite prevalence and malaria incidence, San Dulakudar can be classified as a hyperendemic area for P. falciparum malaria. Parasite prevalence and malaria incidence rates decrease with age, suggesting that residents of San Dulakudar develop immunity to malaria. The study demonstrates the presence of regions in the Indian subcontinent such as Sundargarh District where P. falciparum is the primary cause of malaria and where malaria transmission rates are comparable to those found in many parts of Africa.

Adolescent↗

Malaria mimicry with tumor necrosis factor. Contrasts between species of murine malaria and Plasmodium falciparum.

Because Plasmodium berghei ANKA induces cerebral malaria and P. vinckei does not, the former has often been studied as a model for human falciparum malaria. It lacks, however, many of the systemic changes seen in the human disease. Because both of these murine models and the human disease have now been defined in terms of excess tumor necrosis factor (TNF) production, the authors have more closely examined the two murine models in this light to see which provides the better overall model for falciparum malaria. Administering TNF to malaria-infected mice did not cause cerebral symptoms nor breakdown of the blood-brain barrier, which is the hallmark of P. berghei ANKA cerebral malaria and is generally absent in human cerebral malaria. Tumor necrosis factor did, however, induce hypoglycemia and liver injury, pathology that is seen in terminal P. vinckei and falciparum malaria, but is absent in terminal P. berghei ANKA malaria. Plasma TNF and interleukin-6 (IL-6) also were found to be consistently higher in infections caused by P. vinckei than in those caused by P. berghei ANKA. The pathology of P. vinckei malaria is thus consistent with raised systemic levels of TNF and other cytokines, as is falciparum malaria. The authors therefore conclude that P. vinckei malaria, although lacking a cerebral component, is the better model for the human disease.

Animals↗

Deployment of early diagnosis and mefloquine-artesunate treatment of falciparum malaria in Thailand: the Tak Malaria Initiative.

BACKGROUND: Early diagnosis and treatment with artesunate-mefloquine combination therapy (MAS) have reduced the transmission of falciparum malaria dramatically and halted the progression of mefloquine resistance in camps for displaced persons along the Thai-Burmese border, an area of low and seasonal transmission of multidrug-resistant Plasmodium falciparum. We extended the same combination drug strategy to all other communities (estimated population 450,000) living in five border districts of Tak province in northwestern Thailand. METHODS AND FINDINGS: Existing health structures were reinforced. Village volunteers were trained to use rapid diagnostic tests and to treat positive cases with MAS. Cases of malaria, hospitalizations, and malaria-related deaths were recorded in the 6 y before, during, and after the Tak Malaria Initiative (TMI) intervention. Cross-sectional surveys were conducted before and during the TMI period. P. falciparum malaria cases fell by 34% (95% confidence interval [CI], 33.5-34.4) and hospitalisations for falciparum malaria fell by 39% (95% CI, 37.0-39.9) during the TMI period, while hospitalisations for P. vivax malaria remained constant. There were 32 deaths attributed to malaria during, and 22 after the TMI, a 51.5% (95% CI, 39.0-63.9) reduction compared to the average of the previous 3 y. Cross-sectional surveys indicated that P. vivax had become the predominant species in Thai villages, but not in populations living on the Myanmar side of the border. In the displaced persons population, where the original deployment took place 7 y before the TMI, the transmission of P. falciparum continued to be suppressed, the incidence of falciparum malaria remained low, and the in vivo efficacy of the 3-d MAS remained high. CONCLUSIONS: In the remote malarious north western border area of Thailand, the early detection of malaria by trained village volunteers, using rapid diagnostic tests and treatment with mefloquine-artesunate was feasible and reduced the morbidity and mortality of multidrug-resistant P. falciparum.

Adult↗

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 6. The impact of the interventions on mortality and morbidity from malaria.

The effects of insecticide-impregnated bed nets on mortality and morbidity from malaria have been investigated during one malaria transmission season in a group of rural Gambian children aged 6 months to 5 years. Sleeping under impregnated nets was associated with an overall reduction in mortality of about 60% in children aged 1-4 years. Mortality was not reduced further by chemoprophylaxis with Maloprim given weekly by village health workers throughout the rainy season. Episodes of fever associated with malaria parasitaemia were reduced by 45% among children who slept under impregnated nets. The addition of chemoprophylaxis provided substantial additional benefit against clinical attacks of malaria; 158 episodes were recorded among 946 children who slept under impregnated nets but who also received chemoprophylaxis. Chemoprophylaxis reduced the prevalence of splenomegaly and parasitaemia at the end of the malaria transmission season by 63% and 83% respectively. Thus, insecticide-impregnated bed nets provided significant protection in children against overall mortality, mortality attributed to malaria, clinical attacks of malaria, and malaria infection. The addition of chemoprophylaxis provided substantial additional protection against clinical attacks of malaria and malaria infection but not against death.

Antimalarials↗

Plasmodium falciparum malaria in south-west Nigerian children: is the polymorphism of ICAM-1 and E-selectin genes contributing to the clinical severity of malaria?

Plasmodium falciparum malaria remains a major public health hazard in sub-Saharan African children. While the factors that determine the variations in clinical outcome of a malaria have not been completely defined, both host and parasite factors, as well as the complex molecular interactions between them have been implicated. The cyto-adherent properties of the P. falciparum-infected red blood cells are considered as key properties in the pathogenesis of malaria and the polymorphisms of the host adhesion molecules could contribute to the severity of malaria. Clinical information and blood samples were collected from 223 children from Ibadan (south-west Nigeria), median age of 34.5 months, presenting with different clinical manifestations of malaria--clinically asymptomatic parasitism (ACP), acute uncomplicated malaria (UM) and severe malaria (SM)--as defined by WHO criteria. The polymorphisms of genes coding for four human adhesion molecules at six different loci (ICAM-1 exons 2, 4 and 6, E-selectin exon 2, CD36 exon 10, and PECAM exon 3) were studied. DNA samples were prepared for further genotyping of the six exons mentioned above by PCR-RFLPs using the appropriate restriction digests for each loci. The ICAM-1 exon 4 locus was monomorphic. All the other loci were at Hardy-Weinberg equilibrium (HWE). The E-selectin locus had very low heterozygosity (approximately 0.06) in contrast to the other loci under study (0.23-0.44). Once the data was further processed for covariates (age and parasite density) and taking as the reference category the ACP group, results show that in the presence of the G allele at the ICAM-1 exon 6 there is an increased risk (3.6 times) of severe malaria. As far as the T allele in the E-selectin exon is concerned, the number of sampled DNAs with the T allele within both the UM and SM categories is too low for drawing any relevant conclusion at this stage. In conclusion, these results suggest that genetic polymorphisms at host adhesion molecules loci are an important variable in the susceptibility to severe malaria. Further studies of host loci are needed to further delineate which polymorphisms are associated with severe malaria and increase our knowledge of the biology of host-parasite interactions.

Child, Preschool↗

Malaria morbidity, mortality and pregnancy outcome in areas with different levels of malaria transmission in Uganda: a hospital record-based study.

A retrospective hospital record-based study for Uganda was conducted in Hoima district (an area of stable malaria transmission) and in Kabale district (an area of unstable malaria transmission). In-patient and maternity ward registers for January 1997-December 1998 were reviewed and malaria admissions, mortality, abortions, stillbirths and birthweights were recorded. Data were analysed in relation to rainfall patterns. Admissions due to malaria were significantly higher at Hoima compared to Kabale hospital in 1997 (P < 0.0001). However, the situation reversed in 1998 with significantly more malaria cases registered at Kabale compared to Hoima hospital (P < 0.0001). The increase at Kabale hospital in 1998 was attributed to increased and prolonged rains during 1997 (E1 Niño). Pregnancy was a risk factor for admission with malaria at Kabale, but not at Hoima. Anaemia was significantly more common among patients admitted to hospital at Hoima compared to Kabale in 1997 and 1998 (P < 0.0001 and P = 0.02, respectively). The rate of low birthweight (birthweight < 2.5 kg) was significantly higher among primigravidae and multigravidae at Hoima hospital compared to Kabale hospital (P < 0.0001). There were significantly more stillbirths at Kabale compared to Hoima hospital (P < 0.0001). Routine hospital data such as birthweight and number of malaria cases can provide information on the level of malaria transmission useful for the health services to target appropriate malaria interventions and allocate resources to control outbreaks of malaria epidemics.

Adolescent↗

Malaria diagnosis and treatment under the strategy of the integrated management of childhood illness (IMCI): relevance of laboratory support from the rapid immunochromatographic tests of ICT Malaria P.f/P.v and OptiMal.

The algorithm developed for the integrated management of childhood illness (IMCI) provides guidelines for the treatment of paediatric malaria. In areas where malaria is endemic, for example, the IMCI strategy may indicate that children who present with fever, a recent history of fever and/or pallor should receive antimalarial chemotherapy. In many holo-endemic areas, it is unclear whether laboratory tests to confirm that such signs are the result of malaria would be very relevant or useful. Children from a holo-endemic region of Tanzania were therefore checked for malarial parasites by microscopy and by using two rapid immunochromatographic tests (RIT) for the diagnosis of malaria (ICT Malaria P.f/P.v and OptiMal. At the time they were tested, each of these children had been targeted for antimalarial treatment (following the IMCI strategy) because of fever and/or pallor. Only 70% of the 395 children classified to receive antimalarial drugs by the IMCI algorithm had malarial parasitaemias (68.4% had Plasmodium falciparum trophozoites, 1.3% only P. falciparum gametocytes, 0.3% P. ovale and 0.3% P. malariae). As indicators of P. falciparum trophozoites in the peripheral blood, fever had a sensitivity of 93.0% and a specificity of 15.5% whereas pallor had a sensitivity of 72.2% and a specificity of 50.8%. The RIT both had very high corresponding sensitivities (of 100.0% for the ICT and 94.0% for OptiMal) but the specificity of the ICT (74.0%) was significantly lower than that for OptiMal (100.0%). Fever and pallor were significantly associated with the P. falciparum asexual parasitaemias that equalled or exceeded the threshold intensity (2000/microl) that has the optimum sensitivity and specificity for the definition of a malarial episode. Diagnostic likelihood ratios (DLR) showed that a positive result in the OptiMal test (DLR = infinity) was a better indication of malaria than a positive result in the ICT (DLR = 3.85). In fact, OptiMal had diagnostic reliability (0.93) which approached that of an ideal test and, since it only detects live parasites, OptiMal is superior to the ICT in monitoring therapeutic responses. Although the RIT may seem attractive for use in primary health facilities because relatively inexperienced staff can perform them, the high cost of these tests is prohibitive. In holo-endemic areas, use of RIT or microscopical examination of bloodsmears may only be relevant when malaria needs to be excluded as a cause of illness (e.g. prior to treatment with toxic or expensive drugs, or during malaria epidemics). Wherever the effective drugs for the first-line treatment of malaria are cheap (e.g. chloroquine and Fansidar), treatment based on clinical diagnosis alone should prove cost-saving in health facilities without microscopy.

Algorithms↗

Urban malaria in the Sahel: prevalence and seasonality of presumptive malaria and parasitaemia at primary care level in Chad.

OBJECTIVE: To assess malaria prevalence rates and seasonal patterns among clinically diagnosed malaria cases at the level of primary care facilities in an urban Sahelian setting. METHOD: Screening all patients consulting two private and two governmental providers on a randomly selected weekday over a period of 9 months. Patients with presumptive malaria underwent a blood test. RESULTS: Of 1658 patients included in the survey, 47% were clinically diagnosed and treated as malaria cases. Malaria was more often diagnosed by private providers. There were no clear seasonal patterns in presumptive malaria. A 30% of clinically diagnosed cases were positive for Plasmodium (all falciparum) by thick film examination. Thus, false positive cases constituted more than 70% of the clinically diagnosed malaria cases. The highest positive prevalence rates were found at the end and shortly after the rainy season (44%-47%) and the lowest during the dry season (2%). CONCLUSIONS: Clinical diagnosis of malaria has a very low positive predicted value in this low endemicity urban setting, and its low specificity leads to inappropriate care for a large proportion of patients. This has a major impact on economic costs for health services and households. In the Sahel, systematic use of microscopy-based diagnosis and/or rapid diagnostic tests should be considered to appropriately manage malaria and non-malaria cases.

Adolescent↗

Prevalence of malaria parasitemia among clients seeking treatment for fever or malaria at drug stores in rural Tanzania 2004.

OBJECTIVE: To determine the prevalence of malaria parasitemia and other common illnesses among drug store clients in one rural community, with a view to the potential role of specialist drug stores in expanding coverage of effective malaria treatment to households in highly endemic areas. METHOD: Follow-back study of 2466 client visits selected from all 10 drug stores operating in the town of Ikwiriri between May 30 and August 31 2004. Of these, 521 (21.2%) were made by or on behalf of persons ill with fever or malaria. Two hundred and ninety three were eligible as residents of the surrounding nine villages and all agreed to participate in the study. Each patient was evaluated by a clinical officer and provided a blood sample for malaria on the day of the shop visit, either at the shop or at home. RESULTS: Only 50 (17.1%) visits by or on behalf of febrile patients resulted in the purchase of an antimalarial drug, while an antipyretic medication was obtained at 226 visits (77.1%). Clinicians diagnosed malaria in 63.8% of patients. Malaria parasites were identified in blood film samples from 24.2% (95% CI: 19.6, 29.5). This is double the parasite prevalence rate of 10.7% (95% CI: 8.6, 13.1) obtained from a household survey of 1004 healthy individuals selected from these villages at the same time. It is not significantly lower than the prevalence observed among 880 clients presenting with fever at health facilities in the district: 29.7% (95% CI: 23.0, 37.3). The prevalence of malaria parasitemia among children younger than 5 years whose families sought fever treatment from drug stores (42.1%; 95% CI: 31.4, 53.5) was equal to that of children presenting with fever at health facilities (42.5%; 95% CI: 25.0, 62.2). CONCLUSIONS: Currently, drug store clients do not obtain malaria-specific treatment in the majority of cases where it might be warranted. Parasitological findings indicate that drug store clients, especially children, are as likely to be infected with malaria as patients seeking care for similar illnesses at health facilities. Drug stores may be attractive partners for policy makers eager to engage the private retail sector in expanding coverage of malaria treatment.

Adult↗

The gamma/delta T-cell response to Plasmodium falciparum malaria in a population in which malaria is endemic.

Frequencies and absolute numbers of peripheral gamma/delta T cells have been reported to increase after episodes of Plasmodium falciparum malaria in adults with limited or no previous malaria exposure. In contrast, little is known about the gamma/delta T-cell response to malaria in children from areas where malaria is endemic, who bear the burden of malaria-related morbidity and mortality. We investigated the gamma/delta T-cell response in 19 Ghanaian children from an area of hyperendemic, seasonal malaria transmission. The children presented with cerebral malaria (n = 7), severe malarial anemia (n = 5), or uncomplicated malaria (n = 7) and were monitored from admission until 4 weeks later. We found no evidence of increased frequencies of gamma/delta T cells in any of the patient groups, whereas one adult expatriate studied in Ghana and three adults admitted to the hospital in Copenhagen, Denmark, all with uncomplicated, primary P. falciparum malaria, showed increased gamma/delta T-cell frequencies similar to those previously reported. All patients had lowered absolute numbers of peripheral gamma/delta T cells at admission, changing to increased numbers by days 7 to 14 and then returning to normal levels. The study raises questions regarding age and degree of previous exposure as determinants of malaria-induced gamma/delta T-cell responses.

Adult↗

Rapid Urban Malaria Appraisal (RUMA) II: epidemiology of urban malaria in Dar es Salaam (Tanzania).

BACKGROUND: The thinking behind malaria research and control strategies stems largely from experience gained in rural areas and needs to be adapted to the urban environment. METHODS: A rapid assessment of urban malaria was conducted in Dar es Salaam in June-August, 2003 using a standard Rapid Urban Malaria Appraisal (RUMA) methodology. This study was part of a multi-site study in sub-Saharan Africa supported by the Roll Back Malaria Partnership. RESULTS: Overall, around one million cases of malaria are reported every year by health facilities. However, school surveys in Dar es Salaam during a dry spell in 2003 showed that the prevalence of malaria parasites was low: 0.8%, 1.4%, 2.7% and 3.7% in the centre, intermediate, periphery and surrounding rural areas, respectively. Health facilities surveys showed that only 37/717 (5.2%) of presenting fever cases and 22/781 (2.8%) of non-fever cases were positive by blood slide. As a result, malaria-attributable fractions for fever episodes were low in all age groups and there was an important over-reporting of malaria cases. Increased malarial infection rates were seen in persons who travelled to rural areas within the past three months. A remarkably high coverage of insecticide-treated nets and a corresponding reduction in malarial infection risk were found. CONCLUSION: The number of clinical malaria cases was much lower than routine reporting suggested. Improved malaria diagnosis and re-defined clinical guidelines are urgently required to avoid over-treatment with antimalarials.

Adolescent↗

ABO phenotypes and malaria related outcomes in mothers and babies in The Gambia: a role for histo-blood groups in placental malaria?

BACKGROUND: Host susceptibility to P.falciparum is critical for understanding malaria in pregnancy, its consequences for the mother and baby, and for improving malaria control in pregnant women. Yet host genetic factors which could influence placental malaria risk are little studied and there are no reports of the role of blood group polymorphisms on pregnancy outcomes in malaria endemic areas. This study analyses the association between ABO blood group phenotypes in relation to placental malaria pathology. METHODS: A total of 198 mother/child pairs delivering in Banjul and the Kombo-St Mary District (The Gambia) were analysed. ABO blood group was measured by agglutination. Placental malaria parasites wee enumerated and the presence of malaria pigment noted. Birth anthropometry was recorded and placental weight. Maternal and infant haemoglobin was measured. RESULTS: 89 (45%) subjects were primiparae and 110 (55%)multiparae. The ABO phenotype distribution was 38(A), 52(B), 6(AB) and 102(O). Placental histo-pathology showed active placental malaria in 74 (37%), past infection in 42 (21%) and no infection in 82 cases (41%). In primiparae blood group O was associated with a higher risk of active infection (OR = 2.99; 95% CI = 1.24-7.25), and a lower risk of past infection (OR = 0.31, 0.10-1.01, p < 0.05). In multiparae the O phenotype was associated with reduced prevalence of active or past placental infection (OR = 0.45; 95% CI 0.21-0.98). The mean feto-placental weight ratio was significantly higher in multiparae with group O women compared to non-O phenotypes (5.74 vs 5.36; p = 0.04). Among primiparae with active placental infection, mean birth weight was higher in children of mothers with the O phenotype (p = 0.04). CONCLUSION: These results indicate that blood group O was significantly associated with increased placental malaria infection in primiparae and reduced risk of infection in multiparae. This parity related susceptibility was not present with other ABO phenotypes. Cell surface glycans, such as ABO and related antigens have special relevance in reproductive biology and could modulate specific cell interactions as those associated with the pathogenesis of placental malaria.

ABO Blood-Group System↗

Maternal malaria and gravidity interact to modify infant susceptibility to malaria.

BACKGROUND: In endemic areas, placental malaria due to Plasmodium falciparum is most frequent and severe in first-time mothers, and increases the risk of infant mortality in their offspring. Placental malaria may increase the susceptibility of infants to malaria parasitemia, but evidence for this effect is inconclusive. METHODS AND FINDINGS: During 2002-2004, we monitored parasitemia in 453 infants, including 69 who were born to mothers with placental malaria, in a region of northeastern Tanzania where malaria transmission is intense. We used a Cox proportional hazards model to evaluate the time from birth to first parasitemia, and a generalized estimating equations logistic regression model to evaluate risk of any parasitemia throughout the first year of life. Compared with infants whose mothers did not have placental malaria at delivery ("PM-negative"), offspring of mothers with placental malaria at delivery ("PM-positive") were 41% more likely to experience their first parasitemia at a younger age (adjusted hazard ratio [AHR] = 1.41, 95% confidence interval [CI] 1.01-1.99). The odds of parasitemia throughout infancy were strongly modified by the interaction between placental malaria and gravidity (p for interaction = 0.008, Type 3 likelihood ratio test). Offspring of PM-negative primigravidae had lower odds of parasitemia during infancy (adjusted odds ratio [AOR] = 0.67, 95% CI 0.50-0.91) than offspring of PM-negative multigravidae, and offspring of PM-positive primigravidae had the lowest odds (AOR = 0.21, 95% CI 0.09-0.47). In contrast, offspring of PM-positive multigravidae had significantly higher odds of parasitemia (AOR = 1.59, 95% CI 1.16-2.17). CONCLUSION: Although parasitemia is more frequent in primigravid than multigravid women, the converse is true in their offspring, especially in offspring of PM-positive women. While placental malaria is known to increase mortality risk for first-born infants, it surprisingly reduced their risk of parasitemia in this study. Placental malaria of multigravidae, on the other hand, is a strong risk factor for parasitemia during infancy, and therefore preventive antimalarial chemotherapy administered to multigravid women close to term may reduce the frequency of parasitemia in their offspring.

Adult↗