Impact of malaria on the brain and its prevention.
Explore the source record for details and available documents.
Africa↗
Biomedical subjects
M E Molyneux
Publications and source records attributed to M E Molyneux.
Clinical presentation and outcome of Pneumocystis carinii pneumonia in Malawian children.
BACKGROUND: Necropsy studies from Africa have shown that Pneumocystis carinii pneumonia (PCP) is common in infants with HIV infection. We aimed to describe the rate, clinical presentation, and outcome of PCP in young Malawian children with acute severe pneumonia. METHODS: Children aged between 2 months and 5 years who were in hospital with a diagnosis of severe pneumonia were admitted to a study ward for clinical monitoring. We carried out blood culture, immunofluorescence on nasopharyngeal aspirate samples to test for PCP, polymerase chain reaction to detect HIV, and chest radiography. FINDINGS: 16 cases of PCP were identified among 150 children with radiologically confirmed severe pneumonia. All were HIV-positive and younger than 6 months. 21 children had bacterial pneumonia (including one who was also PCP positive) and 114 were not confirmed. The most common bacterial pathogens among children without PCP were Streptococcus pneumoniae (eight) and non-typhoidal salmonellae (seven). On admission, children with confirmed PCP had a lower mean age, body temperature, and oxygen saturation than children with bacterial pneumonia and were less likely to have a focal abnormality on auscultation. Oxygen requirements were much greater in children with PCP than those with bacterial pneumonias (96 of 105 hospital days vs 15 of 94, p<0.0001). Ten of 16 children with PCP and six of 21 with bacterial pneumonia died (relative risk 2.19 [95% CI 1.0-4.7]). The overall case-fatality rate of severe pneumonia was 22%. In addition to a strong association with PCP, a fatal outcome was significantly and independently associated with HIV infection (2.98 [1.1-7.9]) and with age under 6 months (2.76 [1.0-5.2]). INTERPRETATION: PCP is common and contributes to the high mortality from pneumonia in Malawian infants. Clinical features are helpful in diagnosis. The study highlights the impact of HIV infection and difficult issues of management in countries with few resources.
AIDS-Related Opportunistic Infections↗
Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria.
Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparum can adhere to specific receptors on host cells, an important virulence factor enabling parasites to accumulate in various organs. We report here that most P. falciparum isolates from infected placentae can bind to hyaluronic acid, a newly discovered receptor for parasite adhesion that is present on the placental lining. In laboratory isolates selected for specific high-level adhesion, binding to hyaluronic acid could be inhibited by dodecamer or larger oligosaccharide fragments or polysaccharides, treatment of immobilized receptor with hyaluronidase, or treatment of infected erythrocytes with trypsin. In vitro flow-based assays demonstrated that high levels of adhesion occurred at low wall shear stress, conditions thought to prevail in the placenta. Our findings indicate that adhesion to hyaluronic acid is involved in mediating placental parasite accumulation, thus changing the present understanding of the mechanisms of placental infection, with implications for the development of therapeutic and preventative interventions.
Animals↗
Bacteremia in febrile Malawian children: clinical and microbiologic features.
BACKGROUND: There are no published data for the incidence or etiology of childhood bacteremia in Malawi. We describe the clinical and microbiologic features of children admitted to hospital from whom blood cultures yielded bacterial pathogens. METHODS: Any neonate or child admitted to the pediatric wards of the Queen Elizabeth Central Hospital had a blood culture taken in the event of fever without obvious clinical explanation. Clinical and microbiologic data were prospectively collected for children with a significant positive culture. RESULTS: Between September, 1996, and August, 1997, we processed 2,123 cultures. Of these, 365 (17.2%) grew a pathogen. Non-typhi salmonellae (NTS) and enteric Gram-negative bacilli constituted 67.4% of isolates, and Streptococcus pneumoniae constituted 16.4%. More than two-thirds of NTS episodes coincided with the peak malaria transmission season (January to June); 67% of bacteremic children were malnourished, 28% severely so. Patients with NTS bacteremia were significantly more likely to have coincident malaria and to have splenomegaly and anemia than children with other infecting organisms. The overall mortality was 38% but varied considerably according to age and nutritional status. Prior antibiotic use, coincident malaria or meningitis did not adversely affect outcome. In vitro resistance to the commonly available antibiotics ampicillin and trimethoprim-sulfamethoxazole was found in 76 and 71% of NTS isolates. Screening tests for penicillin resistance suggested a rate of 21% among pneumococci. CONCLUSIONS: Bacteremia is common in hospitalized Malawian children and has a high mortality. There are high rates of resistance to some of the commonly used antibacterial agents.
Adolescent↗
Anaemia in pregnancy in southern Malawi: prevalence and risk factors.
OBJECTIVE: To determine prevalence of anaemia in pregnancy in southern Malawi, and to establish if an 'at risk' group can be identified for targeted intervention. DESIGN: Prospective cross-sectional study. SETTING: A semi-urban hospital and a rural health clinic in southern Malawi. POPULATION: Pregnant women attending the antenatal clinic for their booking visit. METHODS: Haemoglobin concentration (g/dL) measured from a capillary blood sample (fingerprick) by battery operated HemoCue machine. RESULTS: In urban Blantyre 57% of women were anaemic by WHO standards (haemoglobin < 11.0 g/dL) and 3.6% were severely anaemic (haemoglobin < 7.0 g/dL). The prevalence was higher in the rural area; 72% and 4.0%, respectively. Primiparae were at slightly increased risk for overall anaemia and severe anaemia but the effect of targeting this group alone for interventions would mean at least 65% of anaemic women and over half of the women with severe anaemia would be excluded. When the effect of age was examined separate from gravidity, adolescents were not found to be at increased risk of anaemia. Anaemia was more prevalent in the wet season and in women who booked late for antenatal care. CONCLUSION: The prevalence of anaemia in pregnancy in our population is unacceptably high and deserves more attention. Prophylaxis of all women rather than an 'at risk' group based on age or gravidity is recommended.
Adolescent↗
Plasmodium falciparum rosette formation is uncommon in isolates from pregnant women.
We examined the formation of Plasmodium falciparum erythrocyte rosettes using parasite isolates from placental or peripheral blood of pregnant Malawian women and from peripheral blood of children. Five of 23 placental isolates, 23 of 38 maternal peripheral isolates, and 136 of 139 child peripheral isolates formed rosettes. Placental isolates formed fewer rosettes than maternal isolates (range, 0 to 7. 5% versus 0 to 33.5%; P = 0.002), and both formed fewer rosettes than isolates cultured from children (range, 0 to 56%; P < 0.0001). Rosette formation is common in infections of children but uncommon in pregnancy and rarely detected in placental isolates.
Animals↗
Co-trimoxazole in HIV-1 infection.
Explore the source record for details and available documents.
AIDS-Related Opportunistic Infections↗
The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration.
OBJECTIVES: This study was undertaken to determine the relative effect of malaria infection on HIV concentration in blood plasma, and prospectively to monitor viral concentrations after antimalarial therapy. DESIGN: A prospective, double cohort study was designed to compare the blood HIV-1 RNA concentrations of HIV-positive individuals with and without acute malaria illness. Subjects were followed for 4 weeks after successful malaria therapy, or for 4 weeks from enrollment (controls). METHODS: Malawian adults with symptomatic Plasmodium falciparum parasitemia (malaria group) and asymptomatic, aparasitemic blood donors (control group) were tested for HIV-1 antibodies to identify appropriate study groups. The malaria group received antimalarial chemotherapy only and were followed with sequential blood films. In both groups, blood plasma HIV-1 RNA viral concentrations were determined at enrollment and again at 1, 2 and 4 weeks. RESULTS: Forty-seven malaria patients and 42 blood donors were enrolled. At enrollment blood plasma HIV-1 RNA concentrations were approximately sevenfold higher in patients with malaria than in blood donors (medians 15.1 x 10(4) and 2.24 x 10(4) copies/ml, respectively, P = 0.0001). No significant changes in median HIV-1 concentrations occurred in the 21 blood donors followed to week 4 (P = 0.68). In the 27 subjects successfully treated for malaria who were followed to week 4, a reduction in plasma HIV-1 RNA was observed from a median of 19.1 x 10(4) RNA copies/ml at enrollment, to 12.0 x 10(4) copies/ml at week 4, (P = 0.02). Plasma HIV-1 concentrations remained higher in malaria patients than controls (median 12.0 x 10(4) compared with 4.17 x 10(4) copies/ml, P = 0.086). CONCLUSIONS: HIV-1 blood viral burden is higher in patients with P. falciparum malaria than in controls and this viral burden can, in some patients, be partly reduced with antimalarial therapy.
AIDS-Related Opportunistic Infections↗
Plasmodium falciparum isolates from infected pregnant women and children are associated with distinct adhesive and antigenic properties.
Plasmodium falciparum malaria during pregnancy is an important cause of maternal and infant morbidity and mortality. Accumulation of large numbers of P. falciparum-infected erythrocytes in the maternal blood spaces of the placenta may be mediated by adhesion of infected erythrocytes to molecules presented on the syncytiotrophoblast surface. In this study, isolates from placentas and peripheral blood of infected pregnant women and from children were tested for binding to purified receptors and for agglutination with adult sera. Results suggest that adhesion to chondroitin sulfate A may be involved in placental parasite sequestration in most cases, but other factors are also likely to be important. Agglutination assay results suggest that parasites infecting pregnant women are antigenically distinct from those common in childhood disease. The prevalence of agglutinating antibodies to pregnancy isolates was generally low, but it was highest in multigravidae who are likely to have had the greatest exposure.
Adult↗
Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria.
Cytoadherence of Plasmodium falciparum-infected erythrocytes to the microvascular endothelium is believed to be a key factor in the development of cerebral malaria. Erythrocyte rosette formation has been correlated with malaria severity in studies from east and west Africa. We cultured fresh isolates from Malawian children with severe (n = 76) or uncomplicated (n = 79) malaria to pigmented trophozoite stage and examined rosette formation and adherence to CD36, intercellular adhesion molecule-1 (ICAM-1), chondroitin sulfate A (CSA), and thrombomodulin (TM). Most (126 of 148) isolates bound to CD36, and 76 of 136 bound to ICAM-1. Fewer bound to CSA (40 of 148) or TM (23 of 148). After controlling for parasitemia, there was an inverse association between binding to CD36 (P = 0.004) or ICAM-1 (P = 0.001) and disease severity. Parasites from children with severe malaria anemia bound least to CD36, whereas ICAM-1 binding was lowest in children with cerebral malaria. There was no difference in rosette formation between any of the groups. In Malawian children, there was no evidence of a positive association between adherence to any of the receptors examined and disease severity. The negative association found raises the possibility that adherence to certain receptors could instead be an indicator of a less pathogenic infection.
Anemia↗
Rotavirus G and P types in children with acute diarrhea in Blantyre, Malawi, from 1997 to 1998: predominance of novel P[6]G8 strains.
One hundred rotavirus strains detected in children with acute diarrhea in Blantyre, Malawi, between July 1997 and January 1998 were characterized for G (VP7) and P (VP4) types by using multiplex, heminested, reverse transcription-polymerase chain reaction. A novel P[6]G8 rotavirus strain was identified in 42% of the specimens. The remaining strains comprised P[8]G3 (20%), P[6]G3 (10%), P[4]G8 (9%), P[6]G9 (3%), P[8]G4 (2%), P[6]G4 (2%), and P[4]G3 (1%). Rotavirus strains with mixed G or P types were identified in 2% of the specimens. Nine percent of the strains were nontypeable with the primers used. The P[6] genotype was identified in 57% of strains overall. This first description of serotype G8 rotavirus as a predominant strain has important implications for vaccine development in Africa. The finding of novel P/G combinations (P[6]G8 and P[4]G8) highlights the extraordinary diversity of rotaviruses in some countries.
Acute Disease↗
Association between measures of vitamin A and the ocular fundus findings in cerebral malaria.
OBJECTIVE: To investigate the relationship between serum vitamin A levels and conjunctival impression cytology and retinal whitening present in Malawian children with cerebral malaria. METHODS: Standard retinal examination and conjunctival impression cytology were performed at hospital admission on 101 consecutively admitted children with cerebral malaria. Blood samples were drawn from 56 children at 24 hours, frozen at -20 degrees C, and transported for assessment of vitamin A levels by high-performance liquid chromatography. Associations among fundus findings and vitamin A measurements were sought. RESULTS: The whitening of the retina that we have previously described in children with cerebral malaria was found to be associated with a mean+/-SD serum vitamin A level of 0.29+/-0.1 micromol/L, compared with a mean vitamin A level of 0.41+/-0.2 micromol/L in children without retinal whitening. Children with retinal whitening were 2.77 (95% CI, 1.06-7.3) times more likely to have abnormal conjunctival impression cytology results than those without whitening. No child had any clinical or ophthalmologic evidence of chronic vitamin A deficiency. CONCLUSIONS: The retinal whitening described in children with cerebral malaria is associated with low serum vitamin A levels and with abnormal conjunctival impression cytology results and may be due to acute vitamin A deficiency at the tissue level.
Child↗
Intramuscular artemether vs intravenous quinine: an open, randomized trial in Malawian children with cerebral malaria.
OBJECTIVES: To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children. METHODS: An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here. RESULTS: Overall mortality rates and coma resolution times were not significantly different in the two treatment groups. Parasite and fever clearance times were significantly more rapid in the artemether recipients. Analyses which took into account the possible confounding variables did not significantly alter the findings of these unadjusted analyses. CONCLUSION: These results do not suggest that treatment with artemether would confer a survival advantage in children with life-threatening malaria. The power and precision of the estimated treatment effects of artemether would be enhanced by a meta-analysis of all relevant clinical trials.
Antimalarials↗
Tropical trials: the problems of research in the tropics.
Eleven scientists who, like Herbert Gilles, have spent many years in the study of tropical disease, responded to an inquiry about the most problematic aspects of conducting intervention trials in the tropics. Areas of challenge or difficulty that figured most frequently in the replies were: (1) the proper interests, involvement and perceptions of the studied community; (2) maintaining a research team's standards and motivation over long periods; (3) good study design; (4) communications; and (5) the provision of adequate remuneration and incentives to local scientists. Other problems mentioned included the need to translate results into policy, the importance of a long-term view, the correct use of controls, the attitudes of donors, and the influences of national and local politics. Careful attention must be given to these aspects in the planning and conduct of international research.
Communication↗
Cost-saving through microscopy-based versus presumptive diagnosis of malaria in adult outpatients in Malawi.
The cost implications of changing from a policy of presumptive diagnosis to one of microscopy-based diagnosis in the management of uncomplicated malaria in an urban hospital adult outpatient clinic in Malawi were studied. Costs were measured in three separate weeks during the rainy season. In weeks I and II all uncomplicated malaria cases were treated on the basis of a presumptive diagnosis. In week II, blood films were taken but the results were not made available and did not affect drug dispensing. In week III, antimalarial drugs were restricted to parasitaemic patients. In week I, a total of 7216 prescriptions were written and dispensed, of which 2883 (39.9%) were for antimalarial drugs. The proportion of antimalarial prescriptions fell to 1171/5556 (21.1%) in week II and 357/5377 (6.6%) in week III. We estimate annual savings from microscopy-directed treatment in this setting to be 52,000 Malawi kwacha (US$ 14,000). This represents 3% of the annual drugs budget for the hospital, and is large enough to justify a change in policy.
Adult↗
Malaria--still waiting for a vaccine.
Explore the source record for details and available documents.
Child↗