Showing papers on "Malaria published in 1995"

Indicators of Life-Threatening Malaria in African Children

Abstract: BACKGROUND: About 90 percent of the deaths from malaria are in African children, but criteria to guide the recognition and management of severe malaria have not been validated in them. METHODS: We conducted a prospective study of all children admitted to the pediatric ward of a Kenyan district hospital with a primary diagnosis of malaria. We calculated the frequency and mortality rate for each of the clinical and laboratory criteria in the current World Health Organization (WHO) definition of severe malaria, and then used logistic-regression analysis to identify the variables with the greatest prognostic value. RESULTS: We studied 1844 children (mean age, 26.4 months) with a primary diagnosis of malaria. Not included were 18 children who died on arrival and 4 who died of other causes. The mortality rate was 3.5 percent (95 percent confidence interval, 2.7 to 4.3 percent), and 84 percent of the deaths occurred within 24 hours of admission. Logistic-regression analysis identified four key prognostic indicators: impaired consciousness (relative risk, 3.3; 95 percent confidence interval, 1.6 to 7.0), respiratory distress (relative risk, 3.9; 95 percent confidence interval, 2.0 to 7.7), hypoglycemia (relative risk, 3.3; 95 percent confidence interval, 1.6 to 6.7), and jaundice (relative risk, 2.6; 95 percent confidence interval, 1.1 to 6.3). Of the 64 children who died, 54 were among those with impaired consciousness (n = 336; case fatality rate, 11.9 percent) or respiratory distress (n = 251; case fatality rate, 13.9 percent), or both. Hence, this simple bedside index identified 84.4 percent of the fatal cases, as compared with the 79.7 percent identified by the current WHO criteria. CONCLUSIONS: In African children with malaria, the presence of impaired consciousness or respiratory distress can identify those at high risk for death.

Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria.

Abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy of humans, affects over 400 million people. The geographical correlation of its distribution with the historical endemicity of malaria suggests that this disorder has risen in frequency through natural selection by malaria. However, attempts to confirm that G6PD deficiency is protective in case-control studies of malaria have yielded conflicting results. Hence, for this X-linked disorder, it is unclear whether both male hemizygotes and female heterozygotes are protected or, as frequently suggested, only females. Furthermore, how much protection may be afforded is unknown. Here we report that, in two large case-control studies of over 2,000 African children, the common African form of G6PD deficiency (G6PD A-) is associated with a 46-58% reduction in risk of severe malaria for both female heterozygotes and male hemizygotes. A mathematical model incorporating the measured selective advantage against malaria suggests that a counterbalancing selective disadvantage, associated with this enzyme deficiency, has retarded its rise in frequency in malaria-endemic regions. Although G6PD deficiency is now regarded as a generally benign disorder, in earlier environmental conditions it could have been significantly disadvantageous.

Potential impact of global climate change on malaria risk.

Abstract: The biological activity and geographic distribution of the malarial parasite and its vector are sensitive to climatic influences, especially temperature and precipitation. We have incorporated General Circulation Model-based scenarios of anthropogenic global climate change in an integrated linked-system model for predicting changes in malaria epidemic potential in the next century. The concept of the disability-adjusted life years is included to arrive at a single measure of the effect of anthropogenic climate change on the health impact of malaria. Assessment of the potential impact of global climate change on the incidence of malaria suggests a widespread increase of risk due to expansion of the areas suitable for malaria transmission. This predicted increase is most pronounced at the borders of endemic malaria areas and at higher altitudes within malarial areas. The incidence of infection is sensitive to climate changes in areas of Southeast Asia, South America, and parts of Africa where the disease is less endemic; in these regions the numbers of years of healthy life lost may increase significantly. However, the simulated changes in malaria risk must be interpreted on the basis of local environmental conditions, the effects of socioeconomic developments, and malaria control programs or capabilities.

Plasmodium falciparum rosetting is associated with malaria severity in Kenya.

Abstract: Rosette formation in 154 fresh Plasmodium falciparum isolates from Kenyan children with mild (n 5 54), moderate (n 564), or severe (n 536) malaria was studied to determine whether the ability to form rosettes in vitro is correlated with malaria severity. There was a wide distribution of rosette frequencies within each clinical category; however, a clear trend towards higher rosette frequency with increasing severity of disease wasseen,withthemedianrosettefrequencyofthemild-malariagroup(1%;range,0to82%)beingsignificantly lowerthanthoseofthemoderate-malariagroup(5%;range,0to45%;Mann-WhitneyUtest,P<0.02)andthe severe-malaria group (7%; range, 0 to 97%; Mann-Whitney U test, P < 0.003). Within the severe-malaria category there was no difference in rosetting among isolates from cerebral malaria patients or those with other forms of severe malaria. We also examined the ABO blood groups of the patients from whom isolates were obtained and found that isolates from group O patients (median rosette frequency, 2%; range 0 to 45%) rosetted less well than those from group A (median, 7%; range 0 to 82%; Mann-Whitney U test,P< 0.01) or group AB (median, 11%; range 0 to 94%; Mann-Whitney U test,P< 0.03). We therefore confirm that rosetting isassociatedwithseveremalariaandprovidefurtherevidencethatrosettingisinfluencedbyABObloodgroup type. Whether rosetting itself plays a direct role in the pathogenesis of severe malaria or is a marker for some other causal factor remains unknown. Plasmodium falciparummalaria remains a common cause of morbidity and mortality throughout the tropical regions of the world and is estimated to cause 1 million deaths a year in Africa alone (6). Although infection with malaria parasites is common, only 1 to 2% of infections lead to severe life-threatening disease characterized by a range of clinical features, including unrousable coma (cerebral malaria), severe anemia, metabolic acidosis, and multiorgan failure (25). The majority of malarial deaths in Africa occur in children under 5 years of age, as with increasing age and recurrent exposure to malaria a nonsterile immunity develops (14). It remains unclear why some children develop the severe manifestations of disease while others suffer only mild symptoms or remain asymptomatic.

Mating patterns in malaria parasite populations of Papua New Guinea

Abstract: Description of the genetic structure of malaria parasite populations is central to an understanding of the spread of multiple-locus drug and vaccine resistance. The Plasmodium falciparum mating patterns from madang, Papua New Guinea, where intense transmission of malaria occurs, are described here. A high degree of inbreeding occurs in the absence of detectable linkage disequilibrium. This contrasts with other studies, indicating that the genetic structure of malaria parasite populations is neither clonal nor panmictic but will vary according to the transmission characteristics of the region.

Stable transfection of malaria parasite blood stages

Abstract: Genetic manipulation of malaria parasites would revolutionize the study of this group of pathogens and have implications for vaccine and drug development. This report describes the stable, drug-selectable genetic transformation of the clinically relevant intracellular blood stages of a malaria parasite. A plasmid transfection vector carrying the gene locus that encodes a drug-resistant form of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from the rodent malaria parasite Plasmodium berghei was constructed. Derivatives of this vector were introduced into merozoites of P. berghei by electroporation, and parasites were selected for successful transformation in the rodent host on the basis of resistance to pyrimethamine. The plasmids were present in a circular, unrearranged form that replicated episomally to an observed maximum of 15 copies per cell in drug-resistant populations.

Clinical Features and Outcome of Severe Malaria in Gambian Children

Abstract: The clinical and laboratory features of severe falciparum malaria in 180 Gambian children were studied between 1985 and 1989. Of the 180 children, 118 (66%) presented with seizures, 77 (43%) had cerebral malaria, 35 (20%) had witnessed seizures after admission, 29 (16%) were hypoglycemic, and 27 (15%) died. Respiratory distress was a common harbinger of a fatal outcome. The differences in admission parasite counts in the blood, hematocrit, and opening cerebrospinal pressures for patients who died and survivors were not significant. A multiple logistic regression model identified neurological status (coma, particularly if associated with extensor posturing), stage of parasite development on the peripheral blood film, pulse rate of > 150 or respiratory rate of > 50, hypoglycemia, and hyperlactatemia (plasma lactate level, > 5 mmol/L) as independent indicators of a fatal outcome. Biochemical evidence of hepatic and renal dysfunction was an additional marker of a poor prognosis, but, in contrast to severe malaria in adults, none of these children with severe malaria had acute renal failure.

Self-Treatment of Malaria in a Rural Area of Western Kenya

Abstract: Reported are the results of a study of residents' knowledge about malaria and antimalarial drugs and of their treatment-seeking behaviour in a rural area of western Kenya. The study subjects were generally well-informed about the symptoms of the disease. Malaria was perceived as a relatively mild illness, much less severe than acquired immunodeficiency syndrome (AIDS), measles, difficulty in breathing, and diarrhoea. Self-treatment was extremely common: of 138 episodes of febrile illness, 60% were treated at home with herbal remedies or medicines purchased at local shops, and only 18% received treatment at a health centre or hospital; no treatment was sought by the remainder. Commercially available chloroquine preparations were perceived as more effective than either antipyretics or herbal remedies for the treatment of malaria, and injections were regarded as more effective than oral medications. 4-Amino-quinolines were used to treat 58% of febrile illnesses but in only 12% of the cases was a curative dose of > or = 25 mg/kg body weight employed. Even attendance at a health centre did not ensure adequate treatment because of the common practice of sharing medication among family members. Greatly increased attention should be paid to the role of home treatment of malaria when policies are being developed for the management of febrile illnesses in sub-Saharan Africa.

Intraleucocytic malaria pigment and prognosis in severe malaria.

Abstract: The quantity of malaria pigment liberated into the circulation at schizogony reflects the pathogenic sequestered parasite burden in Plasmodium falciparum malaria, and may therefore be a measure of disease severity. Among 300 consecutive adult patients with severe falciparum malaria, the 40 who died had significantly higher proportions of malaria pigment-containing neutrophils on admission (mean = 7·7%, standard deviation ( sd ) = 5·9%) and pigment-containing monocytes (mean = 8·6%, SD = 5·9%) than did survivors (mean 3·2%, sd = 4·1% and mean 4·8%, sd = 4·6%, respectively) (P 100 000/μL (relative risk 1·8, 95% CI 1·0–3·3). The peripheral blood count of pigment-containing neutrophils in severe malaria is a rapid, simple, and practical prognostic test.

Malaria: current and future prospects for control.

Abstract: Malaria is the most important insect-transmitted human disease but progress in its control has been slow especially in Africa where approximately 90% of the infections occur Several factors have contributed to the problem Parasites and vectors have developed resistance to antimalarial drugs and insecticides; differences in the biology of major malaria vectors preclude the development of simple universally applicable strategies for malaria control; and the cost of available malaria-control tools often exceeds the public health resources in the most malarious parts of the world New tools are desperately needed Current efforts include the testing of tools such as insecticide-impregnated bed nets that could become available in the near term as well as long-term projects such as the development of malaria vaccines and mosquito-targeted genetic control strategies The success or failure of any of these approaches will depend ultimately on understanding the natural patterns of malaria transmission in the field (authors)

Maternal HIV infection and infant mortality in Malawi: evidence for increased mortality due to placental malaria infection.

Abstract: Researchers analyzed data on 2608 women attending one of four prenatal clinics in Mangochi District in Malawi during 1987-1990 to study the relationship between maternal HIV infection placental malaria infection and infant mortality. 5.8% (138) of the women were HIV-1 seropositive. HIV-1 seroprevalence increased from 2.3% to 5.8% between 1987 and 1993. Infants born to HIV-1 positive mothers were much more likely to die during the first year of life than those born to HIV-1 negative mothers (235/1000 vs. 144/1000 live births; p < 0.001). The excess deaths occurred during the postneonatal period (49 vs. 44 p = 0.3 for neonatal mortality compared to 186 vs. 100 p < 0.001 for postneonatal mortality). In the postneonatal period diarrhea or gastrointestinal illness was more common as a cause of death among infants of HIV-1 positive mothers than those of HIV-1 negative mothers (8.7% vs. 3.6%; relative risk = 2.4; p = 0.0002). The researchers stratified the effect of maternal HIV infection on postneonatal death according to birth weight and placental malaria infection to control for potential confounding. They found that when compared with normal birth weight infants born to seronegative mothers with no placental malaria infection low birth weight infants born to HIV-1 positive mothers with placental malaria had an 11.49 increased odds of dying during the postneonatal period. The multivariate analysis showed that an infant born to an HIV-infected mother with placental malaria was 4.5 times more likely to die during the first year of life than an infant born to a mother with only placental malaria and 2.7-7.7 times (depending on birth weight) more likely to die than an infant born to a mother with only HIV infection. These findings suggest that malaria chemoprophylaxis during pregnancy would reduce the likelihood of HIV transmission from mother to infant in addition to reducing the burden of malaria infection during pregnancy malaria-associated low birth weight and their subsequent effect on child survival.

The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity.

Abstract: The epidemiological features of malaria were studied through seven community-based surveys in a population of 4000 in the Wosera area, East Sepik Province, Papua New Guinea. Prevalence of parasitae...

Treatment of malaria outside the formal health services.

Abstract: Self-medication for malaria is widely practised around the world, and although many home treatment episodes are successful, the risk of under or over-dosing is always present. Reasons for the widespread use of self-medication range from the distance and cost of seeking care from the formal health services to cultural beliefs which suggest that traditional care is more appropriate, and even that modern care may be fatal. But self-medication constitutes an important resource for malaria treatment, and much could be done to improve the self-medication practices of the population. Measures to be taken include dissemination of clear messages about malaria as a part of health education, formulation of realistic treatment policies which take account of resource constraints, lowering or removal of economic barriers, especially user charges, and further research into cultural beliefs about malaria and ways to promote compatibility of beliefs with appropriate treatment. If these suggestions could be taken into account in developing malaria treatment strategies, the chances of success would be greatly enhanced.

Artesunate. A review of its pharmacology and therapeutic efficacy in the treatment of malaria.

Abstract: Artesunate is an antimalarial agent, available in oral, rectal and parenteral formulations, that provides a rapid clinical effect in patients with Plasmodium falciparum malaria. The rapidity of effect, availability of an intravenous and intramuscular formulation and convenient dosage regimen make artesunate an ideal candidate for the treatment of severe malaria, including cerebral disease. While some results have been promising, there is no clear evidence to date that artesunate reduces mortality in patients with cerebral malaria to any greater extent than standard quinine therapy. When given as monotherapy, treatment should be continued for at least 5 to 7 days to prevent recrudescence. Combination therapy with mefloquine allows artesunate to be administered over 3 days or less, with a satisfactory clinical outcome maintained. Although optimal dosages remain to be determined, this combination continues to provide the rapid onset of clinical effect observed with artesunate monotherapy, but decreases the rate of recrudescence to 2% (i.e. radical cure rate of 98%) when used as treatment in patients with uncomplicated malaria from areas with a high risk of multidrug-resistance falciparum malaria. Although assessment of tolerability is complicated by the difficulty of distinguishing between disease- and treatment-related events, artesunate and artesunate-mefloquine combinations appear to be well tolerated in adults and children. Indeed, it is possible that prior administration of artesunate may reduce the incidence of mefloquine-induced vomiting. Clinical findings to date have not revealed any pattern of resistance to artesunate after use of the drug. However, given the history of the development of resistance to other antimalarial drugs, the use of artesunate should be restricted to areas of multidrug resistance, the drug should be used in combination with a longer acting agent such as mefloquine, and it should be used in regimens that provide radical cure rates of 90 to 100%. If used according to these treatment principles, artesunate will provide a well tolerated and valuable addition to the current extremely limited treatment options for multidrug-resistant falciparum malaria, a widespread parasitic disease associated with considerable mortality.

Malaria and climate: sensitivity of malaria potential transmission to climate

Abstract: Malaria, according to the World Health Organization, is one of the most serious and complex health problems facing humanity in the 20th century. In the past, climatic changes have greatly affected its geography. Its seriousness and complexity are therefore likely to be compounded by an anthropogenic greenhouse effect. The Malaria Potential Occurrence Zone (MOZ) model was designed to calculate first-order estimates of climate change impacts on malaria. MOZ focuses on the climatic determinants of the life cycles of malaria parasites and vectors. It does not take epidemiology into account. MOZ predicts receptivity, or potential transmission, rather than actual occurrence. MOZ indicates that the intensity and the extent of malaria potential transmission significantly change under the climate change scenarios generated by five atmospheric general circulation models. All five simulations reveal an increase in seasonal malaria at the expense of perennial malaria. This is cause for great concern. Indeed, seasonal malaria is most likely to lead to epidemics among unprepared or nonimmune populations. Moreover, climate change may trigger massive migrations of environmental refugees. Such population movements would likely put national and international health infrastructures under severe stress. Today, malaria is a developing country issue but could spread to higher latitudes. The results obtained with MOZ suggest that malaria could become a publichealth problem for developed countries within decades.

Malaria epidemiology in the province of Moyen Ogoov, Gabon.

Abstract: In the course of epidemiological and immunological baseline studies parasitological surveys were conducted, in 1992, in three localities situated in our near rain forest in the area of Lambarene, Gabon, western Central Africa. Anopheles gambiae s.s. and A. funestus are considered to be the main vectors of malaria. The three localities represent strata with obvious differences in the intensity of malaria transmission. The lowest parasite rates were recorded in the village around the Albert-Schweitzer-Hospital where environmental sanitation and easy access to diagnostic and therapeutic facilities afford a fair measure of malaria control. The villages of Bellevue and Tchad show a much higher prevalence of Plasmodium falciparum, followed by P. malariae and P. ovale. In all three villages parasite rates and geometric mean parasite densities of P. falciparum showed the age pattern typical for areas with stable, hyperendemic malaria. Analysis by season showed the period of the long rains to be the epidemiologically calmest while the dry season and even more the short rainy season produced an increase of parasite rates and densities. In Tchad, the most affected of the three villages, the parasite rates in female adults were significantly lower than in male adults. This was accompanied by lower parasite densities in female adults.

Socio-economic risk factors for malaria in a peri-urban area of the Gambia.

Abstract: Successful control of malaria depends upon a detailed knowledge of its epidemiology, including knowledge of the social and economic factors that influence its prevalence. Little is known about the socio-economic factors that influence the prevalence of malaria in tropical Africa. Therefore, we undertook such a study in over 350 Gambian children with malaria resident in a peri-urban area with seasonal transmission, using the case-control approach. Malaria was associated with poor quality housing and crowding and with travel to rural areas, where the level of malaria transmission is higher than in urban centres. No association was found between the risk of malaria and the overall education level of parents or guardians of study children. However, the knowledge of malaria possessed by mothers of cases of malaria was less than that of controls, suggesting that further education of the study community on the causation of malaria and on ways of preventing it could be of value.

Imported Malaria: Clinical Presentation and Examination of Symptomatic Travelers

Abstract: Background: The diagnosis of malaria in nonendemic countries presents a continuing challenge. Increasing physician awareness of the variability in its clinical presentation will improve clinical management and health out Methods: Charts of patients in whom malaria was diagnosed at two hospital-based tropical disease centers between September 1,1980, and December 31,1991, were reviewed. Results: Of a total of 482 cases, 182 were caused byPlasmodium falciparumand 246 byPlasmodium vivax. Fifty-two patients withP falciparummalaria were hospitalized; 13 were classified as having severe falciparum malaria. Nineteen patients withP vivaxmalaria required hospitalization. The only death was caused byP vivax. Chemoprophylaxis was used by, or prescribed for, 46% of patients; however, of these, only half were compliant in taking their medication. Eighty-seven percent of patients with falciparum malaria presented within 6 weeks of return from travel to an endemic area. One third of patients withP vivaxmalaria presented more than 6 months after travel. The average time between onset of symptoms and physician contact was 6.7 days. Diagnosis was often delayed in those who sought care outside the referral center. Almost all patients had a history of fever, but only half were febrile at presentation. Presenting symptoms and signs were nonspecific. Fifty percent of patients were thrombocytopenic. Other laboratory abnormalities were mild. Conclusions: Since the presentation of malaria is vague and nonspecific, the diagnosis should be considered in any appropriately symptomatic patient with a history of travel to a malaria-endemic area, and appropriate testing should be done. Up-to-date information on chemoprophylaxis should be provided to all travelers to malariaendemic regions. (Arch Intern Med. 1995;155:861-868)

Fever as the presenting complaint of travellers returning from the tropics

Abstract: We investigated prospectively the cause of fever in patients requiring hospitalization after returning from the tropics. All consecutive admissions ( n =195) with oral temperature >37.0°C at the time of admission were enrolled. Final diagnosis as recorded on the discharge summary by the attending physician and results of any relevant laboratory or radiological investigations were recorded on standard proforma. Malaria accounted for 42% of admissions; two patients had returned to Britain more than 6 months before presentation. The second largest group was assumed to have a non-specific viral infection (25%). Cosmopolitan infections (urinary tract infection, community-acquired pneumonia, streptococcal sore throat, etc.) accounted for 9%. Coincidental infections (schistosomiasis, filariasis, intestinal helminths) were found in 16%. Serology was positive for HIV infection in 3%. The most useful investigation was a malaria film, which was positive in 45% of cases in which it was performed. The combination of thrombocytopaenia (platelet count 18 IU/ml) were useful predictive markers of malaria: all 23 patients with both abnormalities had positive malaria films. Malaria must be excluded in any febrile patient returning from the tropics. In the absence of a positive malaria film, the combination of a low platelet count and raised bilirubin may suggest the need for an empirical course of therapy.

Prediction of accelerated cure in Plasmodium falciparum malaria by the elevated capacity of tumor necrosis factor production.

Abstract: Cytokine regulation was compared in three groups of Gabonese patients with Plasmodium falciparum malaria before and after therapy; adults with uncomplicated malaria, children with uncomplicated malaria, and children with severe malaria Plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, TNF receptors (TNF R), and the TNF/TNF R ratios were significantly higher in severe malaria compared with uncomplicated malaria High plasma levels of all immunoregulatory molecules were associated with slow cure after therapy In all patients, phytohemagglutinin-induced cytokine production was depressed on admission compared with convalescence A significant difference was the higher TNF production capacity in patients with severe malaria on day 2 and day 5 compared with that in patients with uncomplicated malaria In contrast to IL-6 and IL-8, a high TNF production capacity during the acute phase of malaria predicted a rapid clinical and parasitologic cure in the patients These findings illustrate the dual role of TNF in the protection and pathology of malaria

Human cerebral malaria: lack of significant association between erythrocyte resetting and disease severity

Abstract: The ability of Plasmodium falciparum isolates from 103 Papua New Guinea children with cerebral malaria and 158 children with uncomplicated malaria to form rosettes in vitro was studied. Of these, 81 isolates from cerebral malaria and 151 isolates from uncomplicated malaria grew to schizogony and were included in the rosetting analysis. Wide variation occurred in the level of rosette formation, with all isolates from both cerebral and uncomplicated malaria patients being able to form rosettes. No statistically significant difference existed between the geometric mean rosetting rate of isolates obtained from cerebral malaria and those from uncomplicated malaria (9% versus 8.6%, P = 0.27). The ability of acute sera to inhibit rosette formation was not significantly different between 18 cerebral malaria cases and 20 controls tested [mean reduction in rosetting rate 6.1% (SD 11.5) versus 8.4% (SD 12.3), P = 0.57]. The rosetting rate of cerebral malaria cases was not associated with the clinical outcome. Among the clinical and laboratory variables tested, only blood group and parasite density were significantly associated with rosetting. These data do not support the hypothesis that rosette formation is associated with cerebral malaria in Papua New Guinea, but indicate that rosetting is an intrinsic property of parasites occurring in all manifestations of the disease.