New insights into the epidemiology of malaria relevant for disease control

Despite over 100 years of scientific investigation, malaria remains the leading cause of death among children living in sub-Saharan Africa. Our understanding of the epidemiology of clinical malaria has, until recently, been hampered by a paucity of empirical data from endemic settings. A striking feature of Plasmodium falciparum malaria is that, compared to infection and mild disease, severe complications and death are rare. Perhaps the single most important factor which ameliorates the risk of asymptomatic infection progressing to life-threatening pathology is the development of clinical immunity. Examination of recent epidemiological evidence suggests that the speed with which clinical immunity is acquired is dependent upon the frequency of parasite exposure from birth. Consequently, the age at which disease presentation peaks, the clinical spectrum of disease and the life-time risks of disease appear to be a function of the intensity of transmission within a given community. These observations are discussed in relation to control measures aimed at reducing P. falciparum exposure and the need to understand better the processes by which children naturally acquire clinical immunity before more rational statements can be made about their wide-spread use in Africa.     

The epidemiology of disasters

Over the last few years there has been an increasing awareness that some kind of disaster management should be possible. The emphasis is now moving from post-disaster improvisation to predisaster preparedness. The League of Red Cross Societies has increasingly encouraged predisaster planning in countries at risk. A new United Nations agency - United Nations Disaster Relief Office (UNDRO)- has been set up with headquarters in Geneva. Coordination and exchange of information between agencies engaged in disaster relief are becoming the rule rather than the exception, and a number of groups have started with the specific objective of making professional expertise available to disaster management. A number of private initiatives have been taken, meetings have been organized, research centers set up, and research projects launched. The study of disasters needs to be approached on a multidisciplinary basis, the more so since the health component is only one part of the broad disaster problem and, perhaps not the major one. Social scientists, psychologists, administrators, economists, geographers, have been or are conducting a number of studies on natural disasters. These studies have provided new insights and have proved most useful in preparing for disasters and increasing the effectiveness and acceptance of relief operations. This is a vital and challenging field, wide open for research. It is now time for epidemiologists and community health scientists to enter the fray and provide much needed information on which a rational, effective and flexible policy for the management of disasters can be based.     

Contribution to the history of malaria epidemiology and control in Portugal and some other places

The author reports some observations made during his long career as malariologist in Portugal, India and the Republic of Sao Tomé and Principe.     

The future of genetic epidemiology

Genetic epidemiology is a hybrid discipline whose ultimate aim is to identify and to characterize population-level factors that contribute to disease. Genetic epidemiologists often pursue this aim through the design and implementation of studies that simultaneously invoke principles in population genetics, epidemiology, molecular biology and biostatistics. However, traditional (and much contemporary) research in genetic epidemiology has barely tapped the potential that these disciplines have to work together. It is our view that future genetic epidemiology inquiry will benefit greatly from stronger integration of these disciplines and is likely to converge on themes in fields as diverse as demography, classical population and evolutionary genetics, pharmacoepidemiology, and ecology. The ultimate focus of this research will be evolution and maintenance of disease within and across populations.     

The placenta and malaria

Placental malaria is recognized as a common complication of malaria in pregnancy in areas of stable transmission, and is particularly frequent and severe in primigravidae. Many hypotheses, based on a systemic or local failure of the immunological response to malaria, have been proposed to explain the 'preference' of the parasites for replication in the placenta. Some of the hypotheses are briefly reviewed here, with a particular focus on the discovery of an uncommon subpopulation of Plasmodium falciparum which can adhere and massively sequester in the placenta. Histologically, placental malaria is characterized by the presence of parasites and leucocytes within the intervillous spaces, pigment within macrophages, fibrin deposits and trophoblasts, proliferation of cytotrophoblastic cells and thickening of the trophoblastic basement membrane. The exact mechanisms leading to placental changes and determining the observed impairment of materno-foetal exchange are incompletely understood. Parasites are unlikely to be directly responsible for the placental pathology, but leucocytes, through the production of non-chemotactic cytokines, might be associated with the thickening of the trophoblastic basement membrane, and might cause a mechanical blockage of oxygen and nutrient transport across the placenta. There is sound epidemiological evidence that placental malaria determines low birthweight, mainly mediated by intrauterine growth retardation, and increases the risk of death and disease during the first year of life. Antimalarial chemoprophylaxis significantly reduces placental malaria and prevents the development of low birthweight. It is likely that, in areas of high endemicity, the placenta is where the drama of maternal malaria is mostly played. A deeper understanding of the mechanisms involved in this process is of key importance in the design of protective interventions which are effective and acceptable during the gestation period.     

The politics of identity in epidemiology

The predilection to doubt the objectivity of scientists based on their affiliation--particularly, but not exclusively, focused on scientists affiliated with industry-is a malignant influence in modern epidemiology. Manifestations of this "politics of identity" are widespread and include ad hominem attacks, publication restrictions, and exclusions of scientists from expert panels and advisory boards. These actions are likely to be detrimental to progress in epidemiology and are questionable from an ethical standpoint. The purpose of this commentary is to draw critical attention to the politics of identity in epidemiology and the effects it can have on individual scientists and scientific debate.     

The epidemiology of gestational trophoblastic disease

Considerable progress has been made in the knowledge of the epidemiology of gestational trophoblastic disease (GTD) in the last few years. There are two main and widely known points related to this disease: its geographical distribution and the different frequency in the various classes of age. GTD is more frequent in South-East Asia, India and Africa, and is rare in European and North American populations. For example, in the United States, the frequency of GTD was 108 per 100,000 pregnancies in the 1970's. In Europe, particularly in Italy, frequencies are lower. In northern Italy, the frequency of hydatidiform mole, in the period 1979-1982, was equal to 62 per 100,000 pregnancies, but in Indonesia and in China, the reported rates were 993 and 667 per 100,000 pregnancies respectively. GTD disease is more frequent in the extreme classes of age (under 20 and over 40 years) and the risk may be more than 100 times greater over 50 years. Besides these risk factors, the possible role of both genetic (familiarity, blood groups) and environmental factors (diet, cigarette smoking, etc.) has been investigated on the onset of GTD. This paper reviews the epidemiologic knowledge on GTD.     

The epidemiology of Langerhans cell histiocytosis

PURPOSE: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. MATERIALS AND METHODS: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36-46Gy (n = 274), or definitive radiotherapy with 46-60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years. RESULTS: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17-78 months for the four AMLs, 96 months for the MDS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence the risk of secondary sarcomas. All three patients with secondary sarcomas had received radiotherapy; however, all three sarcomas were salvaged by subsequent treatment and are in clinical remission with a follow-up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the secondary sarcoma. Thus far, SM contributed to less than 1 % (3/328) of all deaths in the CESS-studies. CONCLUSIONS: The risk of leukemia after treatment for Ewing's sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in the range of 5 % after 15 years. In the CESS-studies, less than 1% of all deaths within the first 10 years after diagnosis were caused by SM. Effective salvage therapy for secondary sarcomas is feasible.     

The 'small spleen' in malaria

A cardinal feature of malaria, splenomegaly, is usually absent in adult patients who have already suffered from falciparum malaria or who are natives of an endemic falciparum zone. This is an attribute of the past episode of clinical or sub-clinical malaria which usually results in regression of the splenic size to below-normal. An ultrasonographic evaluation of spleens was done in 90 healthy adult males, who had suffered from vivax (n = 28) or falciparum (n = 25) malaria in the past, except the controls (n = 22) and natives from an endemic falciparum area (n = 15) who never suffered from malaria. Their ultrasonographic details of spleens, including the size, were compared. Besides other conspicuous differences in the ultrasonographic picture, spleen size was found significantly decreased (p < 0.01) in the group who had been affected by P. falciparum malaria; the smallest measured 7.8 cms. In P. vivax group the decrease was not significant (p < 0.1), but was highly significant in inhabitants of endemic falciparum region (p < 0.001). The present study establishes the 'Small Spleen' and looks at echotexture pattern variations thereof for the first time.     

The contribution of epidemiology to psychosomatic medicine

The G1 glycoprotein of California encephalitis (CE) virus plays a critical role in the infection of mosquito and mammalian cells. We found that CE virus enters baby hamster kidney (BHK-21) and Aedes albopictus (C6/36) cells by the endocytic pathway. Ammonium chloride, a lysosomotropic amine that prevents release of virus from endosomes, inhibited infection of both cell types when added within 10 min after viral adsorption. In addition, infected cells formed polykaryons when the extracellular pH was lowered to 6.3; optimal fusion occurred at pH 5.8 and 6.0 (C6/36 and BHK-21 cells, respectively). Two neutralizing G1 MAba, 6D5.5 and 7D4.5, inhibited low pH-induced syncytia formation without affecting viral attachment, suggesting a role for G1 in viral entry. Since viral fusion proteins have been demonstrated to undergo conformational changes at low pH, acid-induced changes in G1 and G2 were assessed. While both G1 and G2 demonstrated low pH-induced alterations in detergent binding, only G1 displayed an altered protease cleavage pattern at the fusion pH. These results indicate that the G1 protein of CE virus undergoes conformational changes necessary for low pH-mediated entry into both mosquito and mammalian cells.     

The role of epidemiology in cancer prevention

1. ISA Brown and Shaver 288 pullets were changed from 8 h to 8, 10, 13 or 16 h photoperiods at 42, 63, 84, 105, 126 or 142 d of age. 2. Age at first egg (AFE) was curvilinearly affected by the size and timing of the change in photoperiod. AFE was advanced most by a photoperiod change from 8 to 13 h made at 63 or 84 d. ISA birds were generally more responsive than Shaver to the photoperiod changes. 3. Longer photoperiods significantly increased survivors' egg production, but decreased liveability to 504 d. so that eggs per hen housed were unaffected. Retarding AFE by 10 d reduced survivors' egg numbers by 7.0, but increased mean egg weight by 1.26 g. Egg output by Shaver birds was unaffected by AFE, but that of ISA was curvilinearly affected, with an apogee at an AFE of 135 d. In both breeds, egg weight and egg output were greater following an early or late, rather than a mid-term photostimulation. 4. Photoperiod significantly increased mean daily food intake during lay by 1.26 g/h. A 10 d retardation in AFE resulted in a reduction in food intake of 1 g/d. Efficiency of food conversion deteriorated according to the square of the photoperiod, and changed curvilinearly according to age at photostimulation. Food conversion efficiency improved by 0.05 g/g for each 10 d delay in AFE. 5. Shell quality was unaffected by AFE, but deteriorated with increasing photoperiod and was curvilinearly affected by age at photostimulation with the smallest shell weights associated with photostimulation at 63 d. The incidence of double-yolked (DY) egg production increased with photoperiod and decreased with delayed photostimulation. There was an exponential regression of DY eggs on AFE. 6. Body weight at first egg increased by 75 g/d delay in AFE, but body weight at 504 d of age was unaffected by AFE, photoperiod or age at photostimulation. Body weight gain during lay increased by 15 g/h increase in photoperiod, decreased by 6 g per 10 d delay in photostimulation and by 40 g per 10 d delay in AFE. Fat content at 504 d increased by about 10 g/kg and by 23 g/bird for each 10 d delay in AFE. 7. Mortality in lay increased by 0.8%/h increase in photoperiod, but was unaffected by either age at photostimulation or AFE.     

The epidemiology of post-traumatic stress disorders]

Post-traumatic stress disorder (PTSD) has been subjected to several epidemiological studies during the last 10 years. Large differences in prevalence between different studies can only partly be explained by differences in methodology, impact of the trauma and populations. Changes in diagnostic criteria, the stressor criteria, general mentality over time and cultural differences may account for some of the differences. In general populations a lifetime prevalence of PTSD of between 1% and 9% has been found. In unselected traumatized populations 20-45% will develop PTSD after exposure to significant traumas. Among soldiers who have participated in battles of war a PTSD prevalence of 15-20% has been found. After exposure to lesser traumas and among well-trained corps 5-10% develop PTSD. Over long periods the point prevalence of PTSD in a given traumatized population diminishes. Predictive factors related to PTSD are complex.