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M E Molyneux

Publications and source records attributed to M E Molyneux.

At least 37 records · Page 2Linked to original sources
PubMed2001

Rotavirus strain diversity in Blantyre, Malawi, from 1997 to 1999.

In a 2-year study of viral gastroenteritis in children in Blantyre, Malawi, the diversity of rotavirus strains was investigated by using electropherotyping, reverse transcription-PCR amplification of the VP7 and VP4 genes (G and P genotyping), and nucleotide sequencing. Of 414 rotavirus strains characterized, the following strain types were identified: P[8], G1 (n = 111; 26.8%); P[6], G8 (n = 110; 26.6%); P[8], G3 (n = 93; 22.5%); P[4], G8 (n = 31; 7.5%); P[8], G4 (n = 21; 5.1%); P[6], G3 (n = 12; 2.9%); P[6], G1 (n = 7; 1.7%); P[6], G9 (n = 3; 0.7%); P[6], G4 (n = 3; 0.7%); P[4], G3 (n = 1; 0.2%); and mixed (n = 15; 3.6%). While all strains could be assigned a G type, seven strains (1.7%) remained P nontypeable. The majority of serotype G8 strains and all serotype G9 strains had short electropherotype profiles. All remaining typeable strains had long electropherotypes. Divergent serotype G1 rotaviruses, which contained multiple base substitutions in the 9T-1 primer binding site, were commonly identified in the second year of surveillance. Serotype G2 was not identified. Overall, G8 was the most frequently identified VP7 serotype (n = 144; 34.8%) and P[8] was the most frequently detected VP4 genotype (n = 227; 54.8%). Partial sequence analysis of the VP4 gene of genotype P[8] rotaviruses identified three distinct clusters, which predominantly (but not exclusively) comprised strains belonging to a distinct VP7 serotype (G1, G3, or G4). As a result of mutations in the 1T-1 primer binding site, strains belonging to each cluster required a separate primer for efficient typing. One cluster, represented by P[8], G4 strain OP354, was highly divergent from the established Wa and F45 VP4 P[8] lineages. As is the case for some other countries, the diversity of rotaviruses in Malawi implies that rotavirus vaccines in development will need to protect against a wider panel of serotypes than originally envisioned.

Amino Acid Sequence↗
PubMed2000

Molecular and serologic characterization of novel serotype G8 human rotavirus strains detected in Blantyre, Malawi.

During a 2-year study of diarrhea among children in Blantyre, Malawi, greater than 50% of rotavirus strains genotyped by using reverse transcription-polymerase chain reaction possessed previously unrecognized combinations of the neutralization proteins VP7 and VP4. Serotype G8 rotaviruses, which have been identified recently in several African countries, were found to possess P[4] or P[6] VP4 genotype specificity. Two of these short electropherotype rotaviruses were further investigated: these comprised a P[6], G8 representative strain (MW23) and a P[4], G8 representative strain (MW333). The VP7 gene sequences of both strains exhibited greatest homology to human and animal serotype G8 rotaviruses. Sequence analysis of the VP4 gene of MW23 indicated closest identity to the P2A[6], G9 strain US1205 from the United States. The VP4 gene of MW333 was most closely related to the P[4], G12 strain L26 isolated in the Philippines and the Australian P[4], G2 strain RV-5. The NSP4 gene sequences of both strains were classified in NSP4 genetic group I. RNA-RNA hybridization demonstrated that each of these two strains is related to the DS-1 genogroup of human rotaviruses. Subgroup analysis and virus neutralization confirmed complete antigenic characterization of MW23 as subgroup I, P2A[6], G8 and MW333 as subgroup I, P1B[4], G8. The similarity of the VP7 gene sequences of the prototype strains described in this report to bovine serotype G8 rotaviruses suggests that they may represent human/bovine reassortant viruses.

Animals↗
PubMed2000

Bacterial meningitis in Malawian adults: pneumococcal disease is common, severe, and seasonal.

We prospectively collected laboratory details and outcome data on all patients with laboratory-confirmed cases of meningitis that presented to our unit in Blantyre, Malawi, from 1 April 1998 through 31 March 1999. There were 502 patients with cases of meningitis; the most common causative organisms were Cryptococcus neoformans and Streptococcus pneumoniae. This pattern probably reflects the local human immunodeficiency virus (HIV) seroprevalence (31%) and is different from the pattern in 1974, when Neisseria meningitidis was the most common isolate. There has been an 8-fold increase in the number of meningitis cases per year since 1974, and a doubling of the percentage of medical admissions due to meningitis. The inpatient mortality rate among patients with cases of pneumococcal meningitis was 61%, and in the group as a whole was 41%. Despite the HIV-related pattern of infecting pathogens among these cases of meningitis and the increased incidence of the condition, there was evidence that the typical seasonal pattern of pneumococcal meningitis, which peaks in the cold, dry season, was preserved.

Adult↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Salmonella meningitis in children in Blantyre, Malawi, 1996-1999.

Sixty-one episodes of Salmonella meningitis were identified during a 3-year period from February 1996 to January 1999 inclusive. These accounted for 6.8% of all the acute bacterial meningitis cases seen during this time. In contrast, only two children were admitted with Salmonella meningitis in 1982. The increase may reflect the rise in HIV disease and the associated increase in Salmonella septicaemia. All but one child were under 2 years of age, only six children were well nourished and anaemia was common. The prognosis was poor: 33 (58%) died, 19 made a full recovery and five developed sequelae. Two children relapsed, one of whom died. Patients were routinely treated with chloramphenicol, to which all isolates were sensitive in vitro. The poor outcomes suggest that an alternative antibiotic policy is required.

Acute Disease↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Malaria and anemia in antenatal women in Blantyre, Malawi: a twelve-month survey.

Malaria and anemia are common in pregnant African women. We screened 4,764 Malawian women at first antenatal visits for malaria and anemia. A total of 42.7% had a malaria infection, which was more common and of higher density in primigravidae (prevalence = 47.3%, geometric mean = 332 parasites/microl) and teenagers (49.8%, 390/microl) than in multigravidae (40.4%, 214/microl) or older women (40.6%, 227/microl). However, 35% of gravida 3+ women were parasitemic. A total of 57.2% of the women was anemic (hemoglobin < 11 g/dl), with moderate anemia (7.0-8.9 g/dl) in 14.9% and severe anemia (< 7 g/dl) in 3.2%. Prevalences of malaria and anemia were highest in the rainy season. Women with moderate/severe anemia had higher parasite prevalences and densities than women with mild/no anemia. Logistic regression showed that age, season, and trimester of presentation were significantly associated with the prevalence of malaria, but gravidity was not. In this urban setting, age and season are more important than gravidity as predictors of malaria at first antenatal visit, and parasitemia is frequent in women of all gravidities.

Adult↗
PubMed2000

Clinical-histopathological correlation of the abnormal retinal vessels in cerebral malaria.

BACKGROUND: Clinically abnormal retinal vessels unique to cerebral malaria have previously been shown to be associated with a poor outcome in African children. There have been no studies of the histopathological correlates of these vessels. DESIGN: This is a descriptive study of the clinical-histopathological correlates of the retinal vessels of 11 children who died with cerebral malaria. RESULTS: The retinal vessels in children with cerebral malaria contained many parasitized red blood cells; these cells tended to cluster at the periphery of vessels or, in the case of capillaries, to fill the vessel. Those with late-stage parasites had markedly reduced amounts of hemoglobin. The pattern of dehemoglobinization corresponds to the pattern of clinically abnormal vessels. CONCLUSIONS: The sequestration of late-stage parasitized red blood cells with reduced amounts of hemoglobin accounts for the unique white and pale orange retinal vessels seen in cerebral malaria. Clinical examination of these "marked" vessels offers a method to monitor a basic pathophysiological process of cerebral malaria in vivo. Arch Ophthalmol. 2000;118:924-928

Animals↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗