The following abstracts are from some of the research publications on malaria that have emanated from Malawi during the past two years.
. 2002 Apr;14(1):34–36.
Malawi Med J. 2002 Apr;14(1):34–36.
Abstract
Objective
To evaluate the use of insecticide-treated bednets and the effectiveness of social marketing for their distribution.
Methods
Systematic cluster sample survey of 1080 households in 36 census enumeration areas across Blantyre district, Malawi, in February 2000.
Results
A total of 672 households had one or more children under 5. Bednet ownership was low (20.5% of households) overall, and significantly lower in rural areas than urban areas (6.4 vs. 29.8%, P = 0.001). Only 3.3% of rural children under 5 had slept under a net the previous night, compared with 24.0% of urban children (P<0.001). When asked why they did not own a net, nearly all (94.9%) caretakers in households without nets stated they had no money to buy them. In multivariate statistical models that controlled for the influence of house structure, urban vs. rural location, gender of the head of household, and the primary caretaker's education, rural children under 5 in households without nets experienced a statically significant higher prevalence of malaria parasitaemia [RR (risk ratio) 4.9, 95% CI (confidence interval) 2.3–10.5] than children in households with at least one bednet. This was also true for urban children under 5 (RR 2.1, 95% CI 1.0–4.2, P = 0.04).
Conclusion
Social marketing approaches to promoting insecticide-treated nets in Blantyre District may have produced measurable health benefits for children in those households in which residents bought and used the products. Market-based approaches may take years to achieve high levels of coverage and may exaggerate inequities between urban and rural populations.
Malawi Med J. 2002 Apr;14(1):34–36.
Paraphrased abstract
There is a complicated relationship between parasite mutations and responses to treatment of P falciparum malaria. Molecular methods have therefore not yet been used on a large scale to monitor drug resistance.
We obtained pre-treatment parasites from children with uncomplicated falciparum malaria in Ndirande, Blantyre. The children were then randomised in a double-blind trial to receive either sulfadoxine-pyrimethamine (SP) or chlorproguanil-dapsone (‘Lapdap’), and observed for their response to treatment by standard ‘in vivo’ methods. We typed the pre-treatment parasites for the presence of mutations in the genes that control the parasites' production of enzymes targeted by the drugs - dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS). We used multiple logistic regression to identify mutations that were predictive of treatment failure and to identify interactions and confounding factors.
Infections caused by parasites with 3 DHFR mutations and 2 DHPS mutations (the “quintuple mutant”) were associated with sulfadoxine-pyrimethamine treatment failure but not with chlorproguanil-dapsone treatment failure. The presence of a single DHFR mutation (Arg-59) with a single DHPS mutation (Glu-540) accurately predicted the presence of the quintuple mutant.
If this model is validated in other populations, it will finally be possible to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa.
Malawi Med J. 2002 Apr;14(1):34–36.
Abstract
Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection. Binding of parasitized erythrocytes to cerebral endothelium plays a key role in disease pathogenesis. Central nervous system signs and symptoms (coma, seizures, raised intracranial pressure) predominate in Africa children, whereas in adults, multi-organ system failure is more common' In this study we investigated whether changes in blood-brain barrier (BBB) structure and function are compatible with the signs and symptoms observed in Malawian children with CM. Immunohistochemistry on autopsy brain tissues from eight cases of CM showed activation of endothelial cells and macrophages, and disruption of endothelial intercellular junctions in vessels containing sequestered parasitized erythrocytes, but no gross leakage of plasma proteins. Examination of the partition of albumin between circulating plasma and the cerebrospinal fluid from 72 cases of CM showed subtle but measurable changes compatible with impaired BBB function in malaria. These findings suggest that BBB breakdown occurs in areas of parasite sequestration in CM in African children.
Malawi Med J. 2002 Apr;14(1):34–36.
Abstract
During pregnancy, Plasmodium falciparum infection of the placenta frequently occurs in the absence of parasites in peripheral blood. We investigated the abilities of the OptiMAL rapid immunochromatographic strip test for P. falciparum lactate dehydrogenase and species-specific PCR performed on peripheral blood to detect placental infection or malaria-associated low birth weight. Of 509 Malawian women screened by microscopy, 76 had malaria infection. Among these 509 women, the frequency of peripheral blood parasitemia was low. The OptiMal test gave positive results in 37 of 171 women tested (one of whom had placental but not peripheral blood parasitemia) and had sensitivities of 71% for peripheral parasitemia and 38% for placental parasitemia compared to the microscopy values. The specificity for peripheral parasitemia was 94%. In 135 women, PCR had sensitivities of 94% for peripheral blood malaria detected by microscopy and 72% for placental infection. In samples examined by PCR, the prevalence of malaria in peripheral blood increased from 26.7% by microscopy to 51.9%. Women with placental malaria and women in peripheral blood samples by microscopy or OptiMAL testing but not women with malaria detected only by PCR, had lower-birth-weight babies than did women without malaria by these criteria. Positive results by PCR in the absence of microscopic parasitemia were not associated with low birth weight. Neither OptiMAL nor PCR testing of peripheral blood is adequately sensitive to detect all placental malaria infection, but a positive result by OptiMAL testing identifies women with a high proportion of low-birth-weight babies.
Malawi Med J. 2002 Apr;14(1):34–36.
Abstract
Reye's syndrome virtually disappeared from much of the world after the use of salicylate in febrile children was successfully discouraged. This severe sepsis-like disease was thought to be caused by a hypersensitivity to salicylates in children with mild viral infections, although no mechanism consistent with this proposal was ever established. Salicylate toxicity in African children has been noted to have many clinical features in common with severe falciparum malaria, including acidosis, altered consciousness, convulsions and hypoglycaemia. Salicylates are widely available in various formulations in many African countries, and are commonly used for initial treatment of the symptoms that malaria shares with other diseases. There is now experiemental evidence that salicylate increases and prolongs the activity of key elements along the signalling pathway through which interferon gamma generates inducible nitric oxide synthase (iNOS), and we have shown that iNOS is strongly expressed in fatal malaria and other acute fevers in African children. We further propose that, in areas where salicylates are still used to treat the symptoms of febrile illnesses in children, this mechanism could exacerbate potentially serious infectious diseases, including falciparum malaria. In contrast, the absence of salicylate use in children in some Pacific islands could contribute to the milder outcome of falciparum malaria than is observed in Africa. Widespread expression of iNOS has also been seen in the tissues of a patient with fatal clinically defined Reye's syndrome. This finding suggests that Reye's syndrome can be mediated through salicylate enhancement of iNOS expression, the initial trigger in this instance usually being a viral infection.
Malawi Med J. 2002 Apr;14(1):34–36.
Abstract
[The seven trials included in the analysis took place in Malawi, Viet Nam, Thailand, Kenya, Papua New Guinea, The Gambia, and ‘West Africa’].
We conducted a meta-analysis using individual patient data from randomised controlled trials comparing artemether and quinine in severe falciparum malaria. Eleven trials were identified, of which 8 were clearly randomized. Original individual patient data on 1919 patients were obtained from 7 trials, representing 85% of the patients in the original 11 studies. Overall there were 136 deaths among the 961 patients treated with artemether, compared with 164 in the 958 treated with quinine [14% vs 17%, odds ratio 0.8 (0.62, 1.02), p=0.08]. There were no differences between the two treatment groups in coma recovery or fever clearance times, or in the development of neurological sequelae. However the combined ‘adverse outcome’ (either death or neurological sequelae) was significantly less common in the artemether group [odds ratio 0.77 (0.62, 0.96), p=0.02], and treatment with artemether was associated with significantly faster parasite clearance hazard ratio 0.62 (0.56, 0.69), p=<0.0011. In subgroup analyses artemether was associated with a significantly lower mortality than quinine in adults with multisystem failure. In the treatment of severe falciparum malaria, artemether is at least as effective as quinine in terms of mortality and superior to quinine in terms of overall serious adverse events. There was no evidence of clinical neurotoxicity or any other major side effects associated with its use.
Malawi Med J. 2002 Apr;14(1):34–36.
Abstract
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.
Malawi Med J. 2002 Apr;14(1):34–36.
Abstract
The wide variety of disease associations reported at the TNF locus raises the question of how much variation exists within a single population. To address this question, we sequenced the entire TNF gene in 72 chromosomes from healthy residents of a village in The Gambia, West Africa. We found 12 polymorphisms in 4393 nucleotides, of which five have not been previously described, giving an estimated nucleotide diversity (o) of 5.6 x 10. A significantly higher frequency of polymorphisms was found in the promoter region than in the coding region (8/1256 vs 0/0882 nucleotides, P = 0.02). All polymorphisms with the exception of one rare allele were found to be present in Malawi, which is both geographically and genetically distant from The Gambia. Genotyping of 424 Gambian and 121 Malawian adults showed a significant frequency difference between the two populations for eight of the 12 polymorphisms, but the average fixation index across the variable sites was relatively low (Fst = 0.007). We conclude that, at the TNF locus, the nucleotide diversity found within a single African village is similar to the global value for human autosomal genes sampled across different continents.
Malawi Med J. 2002 Apr;14(1):34–36.
Abstract
Background
Chlorproguanil-dapsone (CD) exerts lower resistance pressure than sulfadoxine-pyrimethamine (SP), but is rapidly eliminated. We wanted to see whether the regular use of CD for an individual's malaria treatment results in a higher re-treatment rate than the use of SP.
Methods
In a randomised trial of paediatric outpatients with uncomplicated falciparum malaria, patients were allocated to receive either CD or SP for their presenting episode and for each subsequent uncomplicated malarial illness during the study period (up to one year). The sites were in Kilifi, Kenya (n = 410) and Blantyre, Malawi (n = 500). The Malawi population was peri-urban and therefore children were more likely than in Kilifi to leave the area during the trial period and therefore drop out of the study. Per-protocol analysis was used to determine malaria rates.
Findings
Drop-outs were 117/410 (28.5%) in Kenya, and 342/500 (68.4%) in Malawi. Follow up was for a median of 338 days (inter-quartile range 128–360) and 342 days (152–359) in Kilifi (CD and SP respectively), and for 120 days (33–281) and 84 days (26–224) in Blantyre. Mean annual malaria incidence in Kenya was 2.5 (95%CI: 2.2, 2.8) in children receiving CD treatments vs. 2.1 (1.9, 2.3) for those receiving SP treatments. The equivalent figures for Malawi were 2.2 (1.9, 2.5) vs. 2.8 (2.5, 3.3). In Kenya 4.3% of patients on CD were withdrawn because of treatment failure vs. 12.8% on SP; the equivalent figures in Malawi were 5.4% vs. 20.1%. In Kenya, severe anaemia (haemoglobin < 5 g/dl) caused exit from the study in 6.9% of CD patients and 1.5% of SP patients; most episodes of severe anaemia occurred before any re-treatment. In Malawi only one patient exited because of anaemia.
Interpretation
Despite the rapid elimination of CD, children whose malaria episodes were treated with CD did not have a higher incidence of malaria illnesses than those treated with SP. Treatment failure was more common with SP than with CD. The cause of anaemia in Kenya was probably not adverse reaction to CD, but this requires further study.