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PubMed1996

Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression.

Nitric oxide (NO)-related activity has been shown to be protective against Plasmodium falciparum in vitro. It has been hypothesized, however, that excess NO production contributes to the pathogenesis of cerebral malaria. The purpose of this study was to compare markers of NO production [urinary and plasma nitrate + nitrite (NOx)], leukocyte-inducible nitric oxide synthase type 2 (NOS2), and plasma TNF-alpha and IL-10 levels with disease severity in 191 Tanzanian children with and without malaria. Urine NOx excretion and plasma NOx levels (corrected for renal impairment) were inversely related to disease severity, with levels highest in subclinical infection and lowest in fatal cerebral malaria. Results could not be explained by differences in dietary nitrate ingestion among the groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis, increased with disease severity. Leukocyte NOS2 antigen was detectable in all control children tested and in all those with subclinical infection, but was undetectable in all but one subject with cerebral malaria. This suppression of NO synthesis in cerebral malaria may contribute to pathogenesis. In contrast, high fasting NOx levels and leukocyte NOS2 in healthy controls and asymptomatic infection suggest that increased NO synthesis might protect against clinical disease. NO appears to have a protective rather than pathological role in African children with malaria.

Blotting, Western↗
PubMed2026

Malaria-GENOMAP: a web-based tool for exploring genomic variation of malaria parasites.

MOTIVATION: Malaria, caused by Plasmodium parasites, imposes a significant public health burden. While Plasmodium falciparum remains the primary target of elimination strategies due to its high mortality rate, lesser-known species such as P. malariae, P. vivax, and P. knowlesi continue to contribute to substantial human morbidity. Genomic approaches, including whole-genome sequencing, offer powerful tools for understanding the biology, transmission, and emerging drug resistance of these neglected Plasmodium species. However, there is an urgent need for informatic tools to summarize and visualize the high-dimensional and complex genomic data generated. RESULTS: We developed Malaria-GENOMAP, a user-friendly web-based tool, which integrates genomic variant data, such as allele frequencies, with geographical maps and chromosome-wide to gene views for in-depth exploration. The tool includes variation from P. knowlesi (n = 139), P. malariae (n = 158), P. ovale curtisi (n = 36), P. ovale wallikeri (n = 47), P. simium (n = 38), and P. vivax (n = 1359). It enables the investigation of population structure, geographic associations of mutations, and putative drug resistance markers, offering valuable insights for malaria control efforts. AVAILABILITY AND IMPLEMENTATION: Malaria-GENOMAP is available online at https://genomics.lshtm.ac.uk/malaria-genomaps.

Internet↗
PubMed2005

Molecular analysis of two local falciparum malaria outbreaks on the French Guiana coast confirms the msp1 B-K1/varD genotype association with severe malaria.

BACKGROUND: Plasmodium falciparum outbreaks can occur in the coastal area of French Guiana, where the population is essentially non-immune. Two sporadic outbreaks were observed, including one with severe malaria cases. To characterize these outbreaks and verify previous observations of specific genotype characteristics in severe malaria in this area, all cases from each outbreak were studied. METHODS: P. falciparum genotypes for six genetic loci were determined by PCR amplification from peripheral blood parasites. The msp1/block2 and msp2 genotypes were determined by DNA sequencing. Microsatellite and varD genotyping was based on size polymorphism and locus-specific amplification. RESULTS: The outbreak including severe malaria cases was associated with a single genotype. The other mild malaria outbreak was due to at least five distinct genotypes. CONCLUSION: Two distinct types of outbreak occurred despite systematic and sustained deployment of malaria control measures, indicating a need for reinforced vigilance. The varD/B-K1 msp1 linkage and its association with severe malaria in this area was confirmed.

Amino Acid Sequence↗
PubMed2006

Complexity of the malaria vectorial system in Cameroon: contribution of secondary vectors to malaria transmission.

Malaria transmission in Africa is a dynamic and complex system that is so far superficially understood. Further knowledge is required to improve control of the disease. In the present report, we highlight the contribution of the so-called "secondary" malaria vectors to the overall parasite transmission intensity in several sites across Cameroon, through a retrospective analysis of surveys from the Organisation de Coordination pour la lutte Contre les Endémies en Afrique Centrale database. In total, 48,490 female anophelines belonging to 21 different species were collected between October 1998 and March 2003. Anopheles gambiae Giles, Anopheles arabiensis Patton, Anopheles funestus Giles, Anopheles nili (Theobald), and Anopheles moucheti Evans represented 89% of the total anopheline fauna. Beside these major vectors, malaria parasites or their circumsporozoite proteins were found in nine secondary malaria vectors: Anopheles ovengensis Awono-Ambene et al., Anopheles carnevalei Brunhes et al., Anopheles coustani Laveran, Anopheles hancocki Edwards, Anopheles marshallii (Theobald), Anopheles paludis Theobald, Anopheles pharoensis Theobald, Anopheles wellcomei Theobald, and Anopheles ziemanni Grtünberg. The mean infection rate of secondary vectors (1.36%) was significantly (P < 0.001) lower than that of major vectors (3.08%). An. pharoensis and An. ovengensis were repeatedly found infected by Plasmodium falciparum Welch and contributed substantially to the total malaria transmission intensity in some areas where they were abundant. Both species have strong exophilic and/or exophagic habits such that they might elude vector control directed against endophilic and endophagic malaria vectors.

Animals↗
PubMed1996

The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and intrauterine growth retardation in rural Malawi.

While there is broad evidence for the adverse effects of Plasmodium falciparum infection in pregnancy, and the World Health Organization recommends preventive strategies, there is markedly reduced efficacy in sub-Saharan Africa of the most widely available, affordable and used antimalarial drug for chemoprophylaxis-chloroquine (CQ). During 1987-1990, we studied pregnant women in an area of high malaria endemicity in rural Malawi to compare the efficacy of CQ (the drug recommended by national policy) with mefloquine (MQ, a relatively new and highly effective antimalarial) in preventing low birth weight (LBW) due to prematurity and intrauterine growth retardation (IUGR). Among 1,766 women monitored during at least their last six weeks of pregnancy with observed ingestion of their regimen and facility delivery of a live born singleton, their babies had a mean +/- SD birth weight of 2,905 +/- 461 gm and 16.8% had LBW. In a multivariate analysis, factors significantly associated with LBW included: first birth (odds ratio [OR] = 4.27), female infant (OR = 2.92), maternal human immunodeficiency virus infection (OR = 2.66), low maternal weight (OR = 1.95), and placental blood P. falciparum infection (OR = 1.71). Factors significantly associated with IUGR-LBW included first birth, female infant, low maternal weight, and placental malaria. Factors significantly associated with preterm-LBW included maternal syphilis infection, umbilical cord blood malaria, first birth, low maternal weight, and female infant. Use of an effective antimalarial (MQ) was protective against LBW through its effect on reducing placental and umbilical cord blood malaria infection. The proportion of LBW babies born to women on MQ (12.5% [parity-adjusted for the population of delivering women]) was significantly lower than the proportion born to women on CQ (15.5%; P = 0.05). Effective prevention of malaria in pregnant women in malaria-endemic settings may reduce the likelihood of LBW by 5-14%, and may reduce the amount of preventable LBW by more than 30%. When evaluating antenatal care programs, health policy makers must consider providing an effective preventive drug (either MQ or other drugs identified in additional studies, e.g., sulfa-pyrimethamine compounds) as a means to prevent low birth weight and its consequences.

Adolescent↗
PubMed2002

Low antibody responses to variant surface antigens of Plasmodium falciparum are associated with severe malaria and increased susceptibility to malaria attacks in Gabonese children.

We measured the levels of IgG antibodies with specificity for the variant surface antigens (VSA) of Plasmodium falciparum in plasma samples from a cohort of Gabonese children participating in a longitudinal case-control malaria study. Children with mild malaria had significantly higher anti-VSA IgG responses than their matched counterparts with severe malaria, most markedly during convalescence and when they were healthy. Over the course of the study, almost twice as many children who presented initially with mild rather than severe malaria developed antibodies recognizing the VSA expressed by each of a panel of three isolates, and those with the highest anti-VSA IgG responses had the lowest malaria attack rates. The results suggest that the clinical outcome of P. falciparum infection in young African children depends on their ability to both develop and maintain a broad profile of anti-VSA IgG antibodies, and that this ability is diminished in children who have experienced a severe malaria attack.

Animals↗
PubMed2000

Cost-effectiveness of iron supplementation and malaria chemoprophylaxis in the prevention of anaemia and malaria among Tanzanian infants.

Prerequisites for effective interventions against severe anaemia and malaria among infants are economic evaluations to aid the setting of priorities and the making of health policy. In the present study we analysed the cost and effectiveness of three control strategies hypothetically delivered through the Expanded Programme on Immunization (EPI). For the prevention of severe anaemia and from the perspective of the health provider, the cost-effectiveness ratios were, respectively, US$ 8, US$ 9, and US$ 21 per disability-adjusted life year (DALY) for malaria chemoprophylaxis with Deltaprim (a combination of 3.125 mg pyrimethamine and 25 mg dapsone) + iron, Deltaprim alone, or iron supplementation alone. For malaria prevention, Deltaprim + iron cost US$ 9.7 per DALY and Deltaprim alone cost US$ 10.2 per DALY. From a sociocultural perspective the cost-effectiveness ratios ranged from US$ 9 to US$ 26 for severe anaemia prevention and from US$ 11 to US$ 12 for the prevention of clinical malaria. These ratios were highly cost-effective, as defined by the World Bank's proposed threshold of less than US$ 25 per DALY for comparative assessments. Furthermore, all the preventive interventions were less costly than the current malaria and anaemia control strategies that rely on clinical case management. This economic analysis supports the inclusion of both malaria chemoprophylaxis and iron supplementation delivered through EPI as part of the control strategies for these major killers of infants in parts of sub-Saharan Africa.

Anemia, Iron-Deficiency↗
PubMed1999

Cost and performance of malaria sector: a case study at Malaria Sector 11, Tak Province, Thailand.

The objective of this study was to assess the cost and performance of each operational unit at the malaria sector level and to calculate the unit cost of each activity accordingly. Data were collected at Malaria Sector No.11 situated at the western border of Thailand with Myanmar during the fiscal year of 1995. The unit cost was calculated by dividing the total cost of each activity by its output using appropriate units of analysis. The result showed that 67% of the total cost of malaria sector was labor cost and 45% of the total cost was allocated to diagnosis and treatment activities. Unit cost in terms of cost/visit, cost/case found, cost/case of falciparum malaria treated, cost/case of vivax malaria treated, cost/house spray and cost/impregnated net were US$1.85, 8.21, 10.07, 8.46, 2.24 and 1.54 respectively. The results of this study will provide important information as to the best use of limited available resources to determine which activities should be stopped, continued, increased or decreased at the malaria sector level.

Costs and Cost Analysis↗
PubMed1975

[Malaria in children, with special reference to cerebral malaria (author's transl)].

Those who live in areas where Malaria is endemic, acquire immunity by continuous contact. This immunity cannot be acquired during a short holiday. Children in endemic areas acquire a more severe form of malaria during the period of developing immunity and more often suffer complications like acute hemolytic anemia and, in the case of plasmodium falciparum infection, cerebral malaria. This is a report of 39 cases of cerebral malaria which corresponds to an acute encephslopathy with high temperatures, generalized tonic-clonic spasms and unconsciousness. All children were between 6 months and 5 years old. Cerebral malaria at higher ages is rarely seen in Malawi. But its frequency depends on the intensity of endemic infection and the geographic distribution of the types of malaria. 11 (29%) of the 39 children died. Treatment was with chloroquine against which there was no resistance in East Africa for falciparum infections and with plasmaexpanders. In 1 case permanent neurologic changes a spastic cerebral paresis, were seen. Unconsciousness lasting more than 36 hours appears to be a bad prognostic sign. The CSF is clear and normal except for an occasional rise in protein never higher than 90 mg%.

Age Factors↗
PubMed2003

Reduction of malaria during pregnancy by permethrin-treated bed nets in an area of intense perennial malaria transmission in western Kenya.

The impact of insecticide (permethrin)-treated bed nets (ITNs) on malaria in pregnancy was studied in a rural area in western Kenya with intense perennial malaria transmission. All households in 40 of 79 villages were randomized to receive ITNs by January 1997. The ITNs were distributed in control villages two years later. Complete data on birth outcome were available on 2,754 (89.6%) of 3,072 deliveries. Women (n = 780) were followed monthly throughout pregnancy in 19 of 79 villages. Among gravidae 1-4, ITNs were associated with reductions of 38% (95% confidence interval [CI] = 17-54%) in the incidence of malaria parasitemia and 47% (95% CI = 6-71%) in the incidence of severe malarial anemia (hemoglobin level < 8 g/dL with parasitemia) during pregnancy. At the time of delivery, mean hemoglobin levels were 0.6 g/dL (95% CI = 0.01-1.2 g/dL) higher, the prevalence of placental or maternal malaria was reduced by 35% (95% CI = 20-47%), and the prevalence of low birth weight was reduced by 28% (95% CI = 2-47%) in gravidae 1-4 from ITN villages. No beneficial impact was observed in gravidae five or higher. In areas of intense perennial malaria transmission, permethrin-treated bed nets reduce the adverse effect of malaria during the first four pregnancies.

Adult↗
PubMed2003

Mekong malaria. II. Update of malaria, multi-drug resistance and economic development in the Mekong region of Southeast Asia.

In an expansion of the first Mekong Malaria monograph published in 1999, this second monograph updates the malaria database in the countries comprising the Mekong region of Southeast Asia. The update adds another 3 years' information to cover cumulative data from the 6 Mekong countries (Cambodia, China/Yunnan, Lao PDR, Myanmar, Thailand, Viet Nam) for the six-year period 1999-2001. The objective is to generate a more comprehensive regional perspective in what is a global epicenter of drug resistant falciparum malaria, in order to improve malaria control on a regional basis in the context of social and economic change. The further application of geographical information systems (GIS) to the analysis has underscored the overall asymmetry of disease patterns in the region, with increased emphasis on population mobility in disease spread. Of great importance is the continuing expansion of resistance of P. falciparum to antimalarial drugs in common use and the increasing employment of differing drug combinations as a result. The variation in drug policy among the 6 countries still represents a major obstacle to the institution of region-wide restrictions on drug misuse. An important step forward has been the establishment of 36 sentinel sites throughout the 6 countries, with the objective of standardizing the drug monitoring process; while not all sentinel sites are fully operational yet, the initial implementation has already given encouraging results in relation to disease monitoring. Some decreases in malaria mortality have been recorded. The disease patterns delineated by GIS are particularly instructive when focused on inter-country distribution, which is where more local collaborative effort can be made to rationalize resource utilization and policy development. Placing disease data in the context of socio-economic trends within and between countries serves to further identify the needs and the potential for placing emphasis on resource rationalization on a regional basis. Despite the difficulties, the 6-year time frame represented in this monograph gives confidence that the now well established collaboration is becoming a major factor in improving malaria control on a regional basis and hopefully redressing to a substantial degree the key problem of spread of drug resistance regionally and eventually globally.

Animals↗
PubMed1985

Prospects of human malaria and Bancroftian filariasis infections in the Lower Rufiji Basin, Tanzania. I. Malaria.

Surveys for human malaria infections were conducted in the Lower Rufiji Basin in Tanzania, before and after the long rains in 1981. A multipurpose water resources development project has been planned in the area. Overall asexual malaria parasite, gametocyte and spleen rates of 38.6%, 3.8% and 21.1% respectively were observed before the long rains whilst respective parameters after the long rains were 44.5%, 2.8% and 17.3%. Malaria parasite species percentages of 95.5, 1.0, 0.2 and 3.4 were observed in respect of P. falciparum, P. malariae, P. ovale and mixed infections respectively for both periods. Malaria endemicity in the Lower Rufiji Basin ranges between mesoendemic to hyperendemic. Following implementation of the project, malaria is likely to become holoendemic.

Adolescent↗
PubMed1994

Correlation of malaria endemicity with An. culicifacies sibling species composition and malaria antibody profile in district Allahabad (U.P.).

Entomological, parasitological and serological surveys were conducted between October 1989 and November 1990 in 27 villages (population 33,250) belonging to three topographically different areas of district Allahabad, viz. Gangapar, Doaba and Yamunapar. A good correlation existed in all the three areas between malaria incidence vis-a-vis An. culicifacies sibling species composition and malaria antibodies titre in the populations. In Gangapar and Doaba villages, An. culicifacies densities were low and the proportions of vector species A and C were much less than that of species B, the non-vector species. Low endemicity of malaria was supported by low antibody titres observed in the population. In contrast, in Yamunapar villages An. culicifacies densities were high, species A and C together were almost equal to species B, and malaria incidence as well as antibody titre were high. Based on these observations, district Allahabad, Uttar Pradesh, could be divided into two zones, low malaria transmission zone--Gangapar and Doaba areas and high malaria transmission zone--Yamunapar area.

Adolescent↗
PubMed1994

Malaria chemosuppression during pregnancy. VI. Some epidemiological aspects of malaria in infants.

The possible influence of maternal malaria prophylaxis on infancy malaria was assessed in 241 infants. Mothers of 91 infants (PROG-cohort), 99 infants (CQ-cohort) and 51 infants (CQ+PROG-cohort) had received prophylaxis with daily proguanil, once weekly chloroquine, and the two drug combination respectively. Blood smears of infants were examined for parasitaemia once fortnightly. Parasitaemias were treated with either amodiaquine, Fansidar, or Fansidar-quinine combination. In all cohorts, the incidence of malaria parasitaemias within 3 months of age was high (overall mean = 63%). Chloroquine released from its tissue bound form in the CQ and CQ+PROG-cohorts did not have significant chemosuppressive effects on the parasitaemias. Acknowledging that the CQ-prophylaxis group simulated the hypothetical control group, the cohorts similarity in the pattern of parasitaemias suggested that effective maternal malaria chemoprophylaxis during pregnancy did not significantly influence infancy malaria. A sharp rise in incidence around 3 months was indicative of the waning effect of passive immunity. Sole dependence on sub-optimal active immunity led to another sharp rise in incidence from 9 months onwards. The high incidence of infancy malaria parasitaemias calls for increased vigilance in their early detection and effective treatment. Social-cultural factors within the communities may constrain effective disease management.

Age Factors↗
PubMed1998

'Anti-malaria month'--a step forward in multisectoral collaboration and community involvement in malaria control.

For a long time malaria control in India has largely been a government responsibility with little involvement of the community at large, and other sectors of the economy in the control efforts. There is now increasing realisation that involvement of the community and a multi-sectoral approach should be essential components of the malaria control strategy. The National Malaria Eradication Programme is accordingly laying greater emphasis on coordination with other sectors of the economy, and changing community perceptions and health-related behaviour. A massive programme of community mobilisation with this objective in view has been taken up since 1997. A major component of this community mobilisation programme is the observance of an 'Anti-Malaria Month', during which, country wide awareness campaigns are undertaken at all levels of implementation, to promote inter-sectoral collaboration and community action for malaria control. The present paper summarises the rationale and messages of the 'Anti-Malaria month'.

Animals↗
PubMed1997

[Malaria, anopheles, the anti-malaria campaign in French Guyana: between dogmatism and judgment].

The recrudescence of malaria in French Guiana involves both border regions. One notes the predominance of Plasmodium falciparum along the Maroni River on the Surinam frontier and the transmission of both Plasmodium falciparum and Plasmodium vivax in amerindian settlements along the Oyapock River on the Brazilian frontier. The main mosquito vector is the endoexophile species, Anopheles darlingi. The role of man-biting forest anophelines in malaria transmission is still unclear. At the present time, malaria control is based on curative treatment of the confirmed cases (approximately 4,000 cases a year by active and passive screening). Vector control is supported by annual houses insecticides spraying and, to a lesser degree, use of insecticide-impregnated bednets. The main limiting factors for successful control have been difficulty in implementing a strategy adapted to the cultures of the amerindian and bushnegro populations living on either side of the river-frontiers and in organizing effective cross-border cooperation. The alleged role of immigration in transmission dynamics has been more speculative than real. However the growth of the population and the increase of human activities inside rain forest areas have favorized Anopheles darlingi breeding by uncontrolled deforestation. This situation need to be monitored closely. Information campaigns to improve public awareness could be useful. Following measures could improve control in sparsely populated, remote areas: to promote an integrated preventive program for a real community-wide distribution of primary health care; to discontinue insecticides spraying in houses which is poorly accepted by the bushnegro population and unsuitable to the amerindian dwellings; to support the use of personal protection; to initiate an effective anopheline larvae control; to determine the impact of the transmission during day-time activities especially among very small settlements far from the main villages where members of the Djuka tribe practise slash-and-burn cultivation. Teledetection might be highly useful for monitoring the epidemiology of malaria in French Guiana and neighbouring countries. A change in the official administrative dogma and policy is necessary to optimize malaria control within the framework of regional cooperation between Brazil and the three Guianas.

Animals↗
PubMed1996

Phylogenetic relationship among the malaria parasites based on small subunit rRNA gene sequences: monophyletic nature of the human malaria parasite, Plasmodium falciparum.

We analyzed the small subunit ribosomal RNA (SSUrRNA) gene sequences from 13 malaria species parasitic to humans, chimpanzees/gorillas, Old World monkeys, rodents, birds, and lizards in order to reconstruct the phylogenetic relationships among the Plasmodium species. The SSUrRNA genes of Plasmodium vivax and P. ovale were sequenced by the dideoxy method in our laboratory; other sequences were retrived from GenBank. These sequences were aligned with the SSUrRNA gene sequence of outgroup species, Paramecium and Toxoplasma. After gaps and ambiguous regions were deleted, the aligned sequences were used for phylogenetic analysis by maximum likelihood and distance methods. The tree defines two major clades, the first with the bird and reptile parasites, the second with the rest of the species. The two bird parasites, P. gallinaceum and P. lophurae, do not closely cluster with human, chimpanzee/gorilla, Old World monkey, or rodent parasites, but cluster with the lizard parasites. P. vivax clusters with three Old World monkey parasites, P. cynomolgi, P. fragile, and P. knowlesi in decreasing order of closeness. P. ovale, while in a separate clade, is more closely related to P. vivax than to P. malarie or P. falciparum. P. malariae and P. berghei do not closely cluster with any of the other clades or with each other. Statistical analysis proves that the placement of P. falciparum in the bird malaria clade is less likely than in the mammalian malaria clade. Our analysis reveals that: (1) human malaria parasites have an evolutionary independent origin; (2) P. falciparum is most closely related to P. reichenowi and did not arise from lateral transfer of a bird parasite, as was previously suggested; and (3) the lizard malaria parasites are true members of the genus Plasmodium.

Animals↗
PubMed1999

Cloning and characterization of iron-containing superoxide dismutase from the human malaria species Plasmodium ovale, P. malariae and P. vivax.

The iron-containing superoxide dismutase (FeSOD) gene from three human malaria species, namely Plasmodium ovale, P. malariae and P. vivax, was amplified by polymerase chain reaction, cloned and then sequenced. Comparisons of their deduced amino acid sequences with that of the FeSOD from P. falciparum revealed a very low polymorphism at the FeSOD locus in human malaria species. One P. ovale and the P. vivax FeSOD genes presented the same nucleotide sequence as that of the P. falciparum strain HB3 whereas the second P. ovale and the P. malariae genes exhibited two punctual mutations. These mutations did not affect the function and structure of the enzyme. The FeSOD polymorphism was so low that no phylogenetic relationship among human malaria species could be proposed, but this conservative structure strengthened the potentiality of this enzyme as a possible target for antimalarial drugs.

Amino Acid Sequence↗