The epidemiology of malaria

Epidemiologists have recently paid greater attention than in the past to the epidemiology of clinical malaria as opposed to the epidemiology of malarial infection. This change of emphasis has been stimulated in part by the need for better clinical definitions of malaria in the evaluation of control measures such as insecticide-treated materials and malaria vaccines. Methods of determining mortality from malaria and of defining severe and uncomplicated malaria have been devised. The limited data available indicate that malaria-attributable mortality and the incidence of severe malaria do not increase with an increase in the entomological inoculation rate above a threshold value, an observation that has important implications for the likely long-term effects of attempts to contain malaria through vector control. Study of the epidemiology of severe malaria in Africa has shown different epidemiological patterns for the two most frequent forms of this condition: cerebral malaria and severe malarial anaemia. Severe malarial anaemia is seen most frequently in areas of very high malaria transmission and most frequently in young children. In contrast, cerebral malaria predominates in areas of moderate transmission, especially where this is seasonal, and it is seen most frequently in older children. Study of patients with uncomplicated malaria has established the relationship between fever and parasite density and has demonstrated ways of defining fever thresholds. Algorithms have been developed to help in the diagnosis of malaria in the absence of parasitological confirmation but this approach has proved difficult because of the overlap in symptoms and signs between malaria and other acute febrile illnesses such as pneumonia.     

Anaemia in pregnant women in eastern Caprivi, Namibia

OBJECTIVE: To describe the prevalence, character and possible aetiology of anaemia in the study region. DESIGN: A cross-sectional study involving a lifestyle and dietary questionnaire, a clinical examination and an analysis of blood and stool samples. SETTING: Katima Mulilo antenatal clinic, East Caprivi, Namibia. SUBJECTS: 171 pregnant women attending the clinic in September 1995. MAIN OUTCOME MEASURES: Effects on haemoglobin concentration of age, trimester, parity, residential area, sociodemographic factors, malaria, parasites, geophagy, diet, cooking pot used, vitamin and mineral supplementation and malaria prophylaxis. RESULTS: 41.5% of the women were found to be anaemic (haemoglobin < 11 g/dl) and there was a significant risk of their being iron-deficient (P = 0.01). Three maternal characteristics were found to have a significant effect on a woman's risk of anaemia: urban residence (P < 0.05), geophagy (P < 0.01) and the taking of prophylactic chloroquine (P < 0.05). CONCLUSION: Mild anaemia affects a large proportion of the pregnant women in East Caprivi; severe anaemia (< 7 g/dl) is not common. The picture is predominantly one of iron deficiency, possibly complicated by concomitant folate deficiency. There is no single easily identifiable cause of this anaemia; it appears to have a multifactorial aetiology. Further studies on the effect of the current malaria prophylaxis programme are warranted.     

Malaria and anaemia at different altitudes in the Muheza district of Tanzania: childhood morbidity in relation to level of exposure to infection

Parallel monthly surveys of children aged 6-71 months were conducted in the Muheza district of Tanzania. The aim was to compare highland villages, where the mean, annual entomological inoculation rate (EIR) for malaria is 34 and mean annual prevalences of parasitaemia range from 33%-76%, with culturally similar villages of the lowlands, where the mean EIR is 405 and prevalences of parasitaemia range from 80%-84%. The total survey population could be divided into six geographical subgroups, which can be arranged in order of increasing prevalence of parasitaemia. The prevalences of dense parasitaemia, of febrile malaria, and of anaemia all increased in the same order across this series of groups, the trends being statistically significant. The results of previous studies have indicated a paradoxical effect whereby children in regions with a lower exposure to malarial infection suffer, in the long term, a higher incidence of severe attacks of malaria. In the present study there was no sign of any such paradoxical inverse relationship between the level of exposure and the prevalence of malarial illness or anaemia. However, child mortality rates are similar in the highlands and lowlands, as are the median ages of children admitted to hospital. Overall, the present findings indicate that, for the populations studied, an artificial reduction in EIR would be beneficial, even in the long term, with regard to the chronic effects of malaria. This does not necessarily conflict with previous studies reporting opposite conclusions with regard to the incidence of severe,acute effects.     

The molecular biology and pyridoxine responsiveness of X-linked sideroblastic anaemia

Pyridoxine-responsive, X-linked sideroblastic anaemia (XLSA) has been shown to be caused by missense mutations in the erythroid-specific ALA synthase gene, ALAS2. These are scattered widely across the part of the gene encoding the catalytic domain and in half the cases affect residues conserved throughout evolution. Only a loose correlation has been found between the in vitro kinetics and stability of the catalytic activity of the recombinant variant enzymes and the in vivo severity and pyridoxine-responsiveness of the anaemia. Enhanced instability in the absence of pyridoxal phosphate (PLP) or decreased PLP and substrate binding have been noted. A detailed explanation of the anaemia and its response to pyridoxine, however, requires greater insight into the structure-function relationships of this protein than we have at present. Knowledge of its tertiary structure and further knowledge of intracellular factors which impinge on the ability of normal and variant ALAS2 to contribute to haemoglobin production are also required. Mutations in the same gene which affect mitochondrial processing, terminate translation prematurely, or are thought to abolish function altogether cause an XLSA that is refractory to treatment with pyridoxine. A major complication of this disorder is its accompanying increased iron absorption and iron overload which occurs in patients and female heterozygotes. Mutation detection enables the early diagnosis of those affected, targeted education of families, early treatment with pyridoxine and prevention of iron overload. It also allows for a distinction to be made between late-onset variants of this condition and the more insidious refractory anaemia with ring sideroblasts. The next few years of investigation should be illuminating as tools now exist to study all aspects of this protein from the gene to the mitochondrial matrix.     

Acute mediastinitis due to esophageal perforation--a case report

Malaria is responsible for nearly 500 million clinical cases per year, only a small proportion of whom will become severely ill. Socioeconomic risk factors may play a role in the development of severe malaria in African children and in their susceptibility to reinfection. In Gabon, 100 children suffering from severe malaria, defined as hyperparasitaemia and/or severe anaemia, were matched for sex, age and provenance to 100 children with mild malaria. Socioeconomic factors were assessed using a standard questionnaire and compared between the 2 groups. The children were followed-up and the time to first reinfection was recorded. No significant influence of socioeconomic factors could be detected on the severity of disease or the time to first reinfection. Socioeconomic factors are not major determinants of severe malarial anaemia and hyperparasitaemia in children in Gabon.     

Bone marrow changes in human malaria: a retrospective study

The bone marrow reports of 1966 patients admitted to a provincial teaching hospital between January, 1992 to April, 1995 were retrospectively analyzed. Twenty-six (1.3%) bone marrows showed the presence of malarial parasites. Sixteen (62%) patients had Plasmodium falciparum 9 (34%) Vivax malaria and one (4%) mixed infection. All these patients gave a history of prolonged illness and had low parasite counts. Plasmodium vivax malaria was not associated with any significant pathology in the bone marrow, except iron deficiency anaemia. The bone marrows with Plasmodium falciparum malaria showed myeloid hyperplasia, erythroid hyperplasia, megaloblastosis and hypoplasia in different proportions. No evidence of dyserythropoiesis was found in this series. The possible mechanisms producing these changes and the factors responsible for the discrepancy in bone marrow findings in different geographical areas are discussed.     

The intraoperative diagnosis of functional disorders of the major duodenal papilla in patients with acute biliary pancreatitis]

Tertian malaria is endemic in south-eastern Anatolia. As in Europe and America, in south-eastern Anatolia, an etiological agent is seldom identified in nephrotic syndrome. Two patients with Plasmodium vivax and nephrotic syndrome are described here. The possible relationship between Plasmodium vivax and nephrotic syndrome should be explored in children in endemic malarial regions.     

Iron nutrition and anaemia in a malaria-endemic environment: haematological investigation of the Gidra-speaking population in lowland Papua New Guinea

Blood examination was conducted for the four Gidra-speaking village groups in Papua New Guinea, who were characterized by high Fe intake and high malaria prevalence with marked inter-village differences. The northern riverine villagers, whose Fe intake was higher than the other three village groups, did not suffer from Fe-deficiency anaemia in their malaria-endemic environment; nor did the inland villagers, with their second highest Fe intake and their malaria-free environment, suffer from Fe-deficiency anaemia. However, several individuals of the southern riverine village suffered from anaemia in a malaria-endemic environment, although their Fe intake was almost the same as the inland villagers'. A considerable proportion of the coastal villagers were anaemic, reflecting the lowest Fe intake and the highest malaria prevalence. An inter-village comparison of the relationships between haemoglobin levels and transferrin saturation revealed that the southern riverine villagers needed smaller amounts of circulating Fe for erythropoiesis than the northern riverine and inland villagers, reflecting the long-term human-environment conditions such as the density of malaria vectors and the people's dietary habits. Fe supplementation was not judged effective against hypoferraemia and/or anaemia in such a population. As the incidence of malaria had no significant long-lasting effect on Fe stores or circulating Fe concentration, but did have an effect on anaemia, the hypothesis that malaria causes a transfer of Fe from the blood to parenchymal tissues as a defence against infectious diseases was not supported.     

Exchange transfusion therapy in severe complicated malaria

Two groups of sixteen cases of severe complicated falciparum malaria on two different regimens of treatment were retrospectively studied. The first group including 12 patients, were treated by anti malarial drugs alone. The second group including 4 patients, were treated by exchange transfusion. Multisystemic complications were observed in both groups. It was observed that in complicated Acute Respiratory Distress Syndrome (ARDS), renal and hyperparasitemia were > 30 per cent. The result of the exchange transfusion group was superior to the non exchange group. Exchange transfusion is therefore recommended in the treatment of malarial patients who present with parasitemia > 30 per cent and severe multisystemic complications particularly those who have severe acute renal failure or have lung complications. The amount of blood used for each exchange transfusion should be at least 10-14 units for rapid removal of parasites and toxic metabolites from the circulation.     

Anaemia and intestinal parasitic infections among school age children in Behera Governorate, Egypt. Behera Survey Team

Anaemia is considered a serious public health problem in Egypt, although updated population-based data are lacking. Similarly, data on prevalence and intensity of infection with intestinal parasites, which are considered one possible cause of anaemia, are available only from small, unrepresentative sample surveys. The present research was implemented on an entire Governorate representative sample. The aim of the study was to assess the prevalence of anaemia and intestinal parasites in the area and to evaluate the role of each parasite in the epidemiology of anaemia among school age children. At the end of the survey, results of faecal analyses from direct smear and the Kato-Katz examination techniques were available from 1844 and 1783 children respectively, as well as haemoglobin levels measured by spectrophotometer from 1238 children aged 6-12 years. The prevalence of anaemia in the area was high (90 per cent), but very few serve forms were detected (< 2 per cent). Prevalence of intestinal parasites was high only for protozoa (Giardia intestinalis 24.7 per cent Entamoeba histolytica 17.5 per cent) and Schistosoma mansoni (20.7 per cent). From analysis of the results, Fasciola infection appeared to be highly endemic, even among children (3 per cent), and emerged as the factor most strongly correlated with low levels of haemoglobin (p < 0.0001). The effect of Fasciola on haemoglobin levels was related to the intensity of infection with this parasite. The role of S. mansoni as a risk factor for anaemia was supported by the present study. Among the protozoa, G. intestinalis was significantly correlated with low haemoglobin levels (p < 0.05). The present results substantiated similar findings from smaller studies. In future research, the relationship between Fasciola infection and anaemia needs to be studied with a well-controlled longitudinal design.     

Tamoxifen downregulates TGF-beta production in keloid fibroblasts

BACKGROUND: It has recently been suggested that primary lactase deficiency might have been selected for by malaria, as occurred for beta-thalassaemia and glucose 6-phosphate dehydrogenase deficiency. However, recently we have found that the prevalence of primary lactase deficiency in the area of Sassari (Northern Sardinia), where, in the past, there was intermediate malarial endemicity, is comparable to that observed in the adult population from other areas of Southern Italy where malaria was less endemic. AIMS: To address the problem further, we have determined the prevalence of primary lactase deficiency, glucose 6-phosphate dehydrogenase deficiency deficiency and beta-thalassaemia trait in the populations of three Sardinian villages which differ in altitude above sea-level, socioeconomic features, history of endemic malaria and prevalence of b-thalassaemia and glucose 6-phosphate dehydrogenase deficiency. SUBJECTS: We tested 138 adult males: 53 were from Fonni (a non-malarial mountain village, with a strong pastoral tradition), 38 from Lodé (a village with a similar pastoral tradition, but high malarial endemicity in the past) and 47 from Terralba (a lowland fishing village with an agricultural tradition and heavy malarial morbidity and mortality). METHODS: A blood sample was obtained in all subjects for determination of HbA2 and glucose 6-phosphate dehydrogenase activity. Lactase deficiency was assessed by measuring breath hydrogen production after oral administration of lactose (50 g), by gas-chromatography. RESULTS: The frequencies of glucose 6-phosphate dehydrogenase deficiency and of beta-thalassaemia trait in the non-malarial village of Fonni were strikingly low, compared to frequencies found in the two villages (Terralba and Lodé) with a very high past malarial morbidity. In contrast, there was no significant difference in the prevalence of lactase deficiency in the three groups of subjects from the three villages. CONCLUSIONS: These data obtained in Northern Sardinia do not support the hypothesis of a selection of primary lactase deficiency by malaria. For definitive conclusions, however, the malaria hypothesis should be tested in other parts of the world.     

Host-parasite interaction and morbidity in malaria endemic areas

Severe morbidity due to Plasmodium falciparum is a major health problem in African children. The patterns of morbidity in endemic areas are modified by the immune response, and vary markedly with transmission intensity. Severe disease falls into three overlapping syndromes: coma, respiratory distress, and severe anaemia. Recently, it has become clear that metabolic acidosis plays a major role in the pathogenesis of severe disease and is particularly important in the overlap between the different clinical syndromes. We propose that the different manifestations of severe malarial morbidity arise from the interaction of a limited number of pathogenic processes: red cell destruction, toxin-mediated activation of cytokine cascades, and infected cell sequestration in tissue microvascular beds. The pattern of severe morbidity varies with age within any one endemic area, with severe anaemia predominating in the youngest children and coma having its highest incidence in older children. Between endemic areas there is a marked variation in mean age of children with severe malaria, and therefore in the importance of different clinical syndromes. The shift in mean age is due to a combination of increased challenge and more rapid development of immunity at higher levels of transmission. Recent comparative studies indicate that at higher levels of transmission the net effect of these shifts may be a paradoxical reduction in total severe malarial morbidity.     

Convulsions with malaria: febrile or indicative of cerebral involvement?

Evaluation of 446 infants and young children (6 months to 5 years olds) with malaria parasitaemia showed a significant relationship (P < 0.05- < 0.001) (a) between coma and age, pattern of convulsions, haematocrit, and blood glucose, and (b) between the severity of parasitaemia and risk of convulsions, prevalence of hepatosplenomegaly, and severe anaemia. No significant relationship was observed between convulsions and temperature or haematocrit. Comatose children were older and had a higher prevalence of repeated convulsions, severe anaemia, and hypoglycaemia than non-comatose children. Convulsions, hepatosplenomegaly, and severe anaemia were more prevalent in children with moderate-severe parasitaemia. It is concluded that convulsions with malaria are more often a manifestation of cerebral dysfunction rather than being simply febrile in nature. All forms of cerebral dysfunction in malaria, including repeated convulsions, should be managed as being clinical manifestations of cerebral malaria.     

Picosecond dynamical changes on denaturation of yeast phosphoglycerate kinase revealed by quasielastic neutron scattering

Falciparum malaria may have infected Homo sapiens (and perhaps H erectus) in the Asia Pacific region for more than 100,000 years. This estimate is based on the gene frequency of alpha-thalassaemia, the protection it affords against falciparum malaria and assumptions of untreated mortality from the infection. Up until the end of the 19th century, there was a high mortality from malaria in the coastal parts of Malaya, but the malaria control campaign, begun in 1901 at Klang, was described by Sir Ronald Ross as the first successful antimalarial work in the (then) British Empire. This was extended to Singapore in 1911. When the Far Eastern Association of Tropical Medicine held its Fifth Biennial Congress in Singapore in 1923, malaria was still a major killing disease in parts of Malaya and Sarawak. The mechanism of life-threatening malaria involves cytoadherence of parasitised erythrocytes in microvascular beds, a process enhanced by the products of macrophage activation induced by malarial pyrogen. Improvements in the chemotherapy of life-threatening falciparum malaria with chloroquine and quinine have been countered by the emergence of resistant strains. Artemisinin derivatives may become the treatment of choice during the coming decade. Apart from traditional anti-mosquito methods, control of malaria now involves the use of insecticide-impregnated bed nets, new entomological strategies, including genetic manipulation of mosquitoes and selective chemoprophylaxis. Antigenic diversity and antigenic variation of the malaria parasite have so far defeated attempts to produce an effective vaccine.     

Familial idiopathic atrial fibrillation with bradyarrhythmia

OBJECTIVE: To determine whether the maternal haemoglobin and iron stores of non-anaemic mothers (haemoglobin > or = 10 g/dl) who developed postpartum anaemia were lower compared to mothers who did not develop postpartum anaemia. STUDY DESIGN: A prospective study was conducted in a teaching hospital on 467 low-risk mothers recruited from the antenatal clinic over a 3-month period, who were given only low dose iron supplement and delivered in the same hospital. Blood was drawn at 28-30 weeks for the measurement of haemoglobin, mean cell volume, serum ferritin, serum iron and total iron binding capacity. These results were compared between mothers with a postpartum day 3 haemoglobin of > or = 10 g/dl and those < 10 g/dl. Statistical analysis was performed with parametric and non-parametric methods as appropriate. RESULTS: Mothers with postpartum anaemia had a higher incidence of postpartum haemorrhage (19.6% vs. 3.9%, P < 0.001) as well as heavier mean intrapartum blood loss (444 ml vs. 304 ml, P < 0.001), but there was no difference in the haemoglobin, mean cell volume, serum ferritin, serum iron and total iron binding capacity. CONCLUSIONS: In mothers without antenatal anaemia, the development of postpartum anaemia is not related to the maternal iron status in the third trimester.     

A Chinese patient with pernicious anemia; a medical experience from the Indonesian period

On May 19th 1952 a 64-year-old Chinese man was admitted to a hospital at Yogyakarta (Indonesia) on account of a sawing noise in both ears and some soreness of the tongue. He had macrocytic anemia (haemoglobin: 3.7 mmol/l) and the tongue showed some smooth patches. A presumptive diagnosis of pernicious anaemia was confirmed by gastric analysis which revealed a histamine fast achlorhydria. On treatment with vitamin B12 the noise in the ears rapidly disappeared and there was a characteristic rise in reticulocytes and haemoglobin content. After 3 years the patient died of inoperable gastric carcinoma. There probably was a hereditary component as in a 54-year-old cousin, who also suffered (and died) from gastric carcinoma, gastric analysis showed a histamine fast achlorhydria. The patient is the first case of pernicious anaemia described in a Chinese resident of Indonesia. A survey of the literature revealed that until now pernicious anaemia has been recorded in 31 Chinese patients, in chronological order from the following countries: U.S (1945), Indonesia (1954), Singapore (1967), Hong-Kong (1969) and China (1990). In the autochthonous Chinese population no case has yet been reported.     

The Tenckhoff catheter in acute renal failure

The results of a retrospective study of routine measurement of haemoglobin at the examination of one-year-old children at Gr?land mother and child clinic during 1989-91 showed that 37% of the children had anaemia. There was no difference between immigrants and the European population. There was no correlation between anaemia and sex in either of the population groups. This may imply that routine haemoglobin measurement should be generally introduced as part of the regular control of one-year-old children.     

Mathematical modeling of platelet survival with implications for optimal transfusion practice in the chronically platelet transfusion-dependent patient

Even now 50% of the world population are still living in malaria endemic areas and every year 200 million new cases with 2 million deaths are reported. Most of the malaria deaths are children under 5 years old. Although malaria endemicity currently exists mainly in tropics, before the human started its efforts to eradicate malaria in large scale in 1950s, malaria was more widely distributed in the world. At this time Japan and malaria together with North America and European countries. However some areas were precluded from malaria endemicity: i.e., high mountains and deserts. Also Polynesian islands in the Pacific have never been malarious, even though Melanesian Papua New Guinea, Solomon, and Vanuatu are highly malarious even now. Human disease malaria is caused by Plasmodium parasites and transmitted by Anopheles mosquitoes. Human is classified into the malaria donor and recipient. The environment is supporting this system: for example, temperature and rainfall are important factors together with vegetation, or housing, health infrastructure, war situation, and poverty status. In 1950s, the WHO malaria eradication program focused its efforts on vector control, using DDT-residual spraying. But the program completely failed with mainly operational reasons and we already learned it is almost impossible to control malaria only killing mosquitoes. In 1992 the new Global Malaria Control Strategy adopted by Malaria Summit at Amsterdam says the primary objective is early diagnosis and treatment to prevent malaria death. In this context malaria chemotherapy is a key issue. Also we understand more and more the environmental management is very important. Malaria vaccine may be a conceptually important tool, but may be available soon.     

Factors involved in the anaemia of chronic disorders in elderly patients

Erythropoietin secretion was evaluated in the anaemia of chronic disorders in elderly patients, since it has been shown that this secretion is impaired in adults. We looked for a possible role of inflammatory cytokines: tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) on erythropoietin production. The influence of nutritional status on the anaemia was also investigated. Erythropoietin secretion was significantly increased in elderly patients with anaemia of chronic disorders (ACD) and inversely correlated with haemoglobin concentrations in infectious and inflammatory diseases. Plasma TNF alpha levels were significantly enhanced only in cancerous patients, but no correlation could be established between TNF alpha and erythropoietin or haemoglobin. No noticeable increase of IL-1 beta levels was observed in ACD. These findings suggest that systemic TNF alpha or IL-1 beta are not involved in the erythropoietin response to ACD. Albumin levels were decreased in anaemic patients. Further investigations of the effects of a nutritional supplementation in elderly patients with ACD may be of interest.     

Limitations of laparoscopic management of pelvic static disorders in gynecology

Laparoscopic treatment of urinary stress incontinence and urogenital prolapse is a recent development of endoscopic surgery. The aim of this study was to describe the operative techniques of colposuspension and of treatment of urogenital prolapse and to provide data of the results. Although, long-term follow-up data remains to be collected, 12 to 18 month results demonstrate appropriate success rates in correction of urinary stress incontinence using laparoscopic approach to the retropelvic space. An expanded laparoscopic approach is now possible for treatment of urogenital prolapse. It is imperative that the techniques continue in order to provide multicentered clinical data by which clinical investigators and practitioners should thoroughly evaluate these surgical techniques.