Burkitt's lymphoma in the Mengo Districts of Uganda: epidemiologic features and their relationship to malaria.

An epidemiologic study of 123 patients residing in the Mengo Districts of Uganda, with onset of symptoms of diagnosed Burkitt's lymphoma (BL) in the period 1959-68, revealed a substantial decline in incidence of BL during that decade. Other significant findings included differences by ethnic group in age of patient at onset of BL, a change in the proportions of patients by ethnic group over the decade, a lower incidence rate of BL in the countries of higher altitude, and a seasonal pattern of onset. There was no evidence of the time space clustering previously reported for BL in Uganda. The changing pattern of BL in the Mengo Districts was consistent with the hypothesis that severe malaria infection not only is important in the development of BL but also precipitates onset.

Epstein-Barr virus-malaria interaction models for Burkitt's lymphoma: implications for preventive trials.

Infections with both Epstein-Barr virus (EBV) and malaria have been implicated as causal factors in the pathogenesis of Burkitt's lymphoma (BL). Proposed trials of preventive measures for both infections are receiving serious consideration as possible means of establishing a causal relationship with BL. In this paper we examine certain models for the interaction of EBV and malaria in the induction of BL, and also review the aims of the longitudinal, population-based study being conducted in the West Nile District of Uganda. Given existing knowledge, the outcome of preventive trials, even for the most simple interaction models, is unpredictable and, under certain circumstances, trials of an EBV vaccine could actually increase the incidence of BL. It is suggested that trials of an EBV vaccine at this time would be premature and should be delayed at least until the results from the West Nile prospective study are clear.

Investigating interactions between HIV infection and tropical diseases.

PIP: The health of developing country populations in Africa where there is a high incidence of human immunodeficiency virus (HIV) infection is already seriously compromised by malnutrition and endemic diseases such as tuberculosis. Not only may HIV infection compromise currently used methods for the treatment of tropical diseases, but there may be a synergistic relationship between HIV and other diseases. Epidemiologic studies are thus needed to identify and quantify and such interactions. At present, evidence of such interactions may be limited by the fact that tropical diseases are most prevalent in rural areas while HIV cases have so far been concentrated in urban areas. However, any unexplained rise in the incidence or severity of a specific disease in areas where HIV is prevalent should be investigated as a possible interaction effect. Likewise, if the progression from HIV infection to acquired immunodeficiency syndrome (AIDS) seems to be occurring particularly rapidly in an area, AIDS patients should be examined for the presence of other diseases that may be triggering AIDS. Possible interactions between HIV infection and tropical diseases can be set forth in a schematic form in which both are divided into 3 infection states--uninfected, infected without clinical symptoms, and infected and diseases--and arrows are used to represent the transitions between states and possible interactions.^ieng

The role of clinical epidemiology in establishing essential national health research capabilities in developing countries.

Health research directly relevant to the needs of the people of developing countries is essential for equity in development as well as for improving health planning and management. the international Commission on Health Research for Development has stressed the need to strengthen the capacity of developing countries, no matter how poor, to carry out essential national health research (ENHR). Clinical epidemiologists in developing countries can significantly contribute to the manpower available for ENHR. They play a major role in the provision and practice of appropriate health care by contributing to the critical assessment of priority health problems and by carrying out scientific evaluation of new and conventional intervention tools. In clinical epidemiology units in developing countries, transdisciplinary collaboration with social scientists and health economics has enhanced the capacity to do research that would influence decision-making and health policy, even as links with ministries of health and other ENHR-committed networks are being strengthened. The potential for carrying out ENHR will be multiplied as national and regional training centers for clinical epidemiology in selected developing countries are established.

Experimental infection of anole lizards (Anolis carolinensis) with Mycobacterium ulcerans by the subcutaneous route.

To test whether herpetofauna could be a laboratory model for Mycobacterium ulcerans, 21 anole lizards were inoculated subcutaneously with viable M. ulcerans, 21 with autoclaved organisms, and 14 with an aqueous solution of 0.01% Tween 80. M. ulcerans was recovered in culture from the slowly progressive lesions which developed at the inoculation site in lizards receiving the viable bacteria. Progressive lesions did not occur in the two control groups. Three patterns of inflammatory response to viable M. ulcerans were observed: 14 lizards developed a diffuse, granulomatous reaction in which acid fast bacilli (AFB) were predominantly intracellular; 1 developed focal, encapsulated granulomas; 5 developed a diffuse, necrotizing granulomatous response in which most AFB were extracellular--similar to the characteristic lesion found in human infections.

Experimental alimentary infection of anole lizards (Anolis carolinensis) with Mycobacterium ulcerans.

Pathogenic Mycobacterium ulcerans were recovered from the stool of anole lizards up to 11 days after inoculation by stomach tube. M. ulcerans was isolated from the liver of 3 of 20 lizards and acid fast bacteria were seen in the mucosa of intrahepatic bile ducts in 2 of these 10 weeks post-inoculation. These results provide equivocal support for our hypothesis that herpetofauna are a reservoir of infection with M. ulcerans.

The intensity and effects of infection with Schistosoma mansoni in a rural community in northeast Brazil.

The intensity of infection with Schistosoma mansoni and its effects were investigated in a defined population living on three contiguous fazendas (subcounties) in a nonmalarious area of northeast Brazil near Salvador, Bahia. Quantitative stool egg counts (Bell technique) were performed on 363 of 417 individuals (90%) of all ages; physical examinations were done on 294 of 357 individuals (82%) 5 years of age and older. The maximum increase in prevalence was observed between the 1- to 4- and 5- to 9-year age groups, while the maximum increase in fecal egg count occurred between 5- to 9- and 10- to 14-year age groups. Highest egg counts were observed in the 10- to 14-year age group (geometric mean of 301 eggs per ml of stool) while the maximum prevalence (100%) was in the 20- to 24-year age group. In the fazenda with the lowest quantitative egg counts the age specific prevalence rates increased more slowly than in the fazendas with higher egg counts. In the study group nearly 50% of the total fecal egg output was accounted for by 22 individuals (6%) who had a mean age of 12.6 years. Egg counts for this selected group were all over 800 eggs per ml of stool with a mean of 1,514 eggs per ml of stool. In children under 15 years of age, the frequency of hepatomegaly and splenomegaly varied directly with the egg count; further, the degree of hepatomegaly was directly correlated with increasing egg counts. No splenic enlargement was noted in children not excreting eggs. In adults, on the other hand, neither splenomegaly nor hepatomegaly could be directly related to schistosomal infection per se. In children, neither the presence of infection with S. mansoni nor its intensity was reflected by altered anthropometric measurements. In the one fazenda tested the frequency of stools positive for occult blood correlated with increasing S. mansoni egg counts.

House construction, triatomine distribution, and household distribution of seroreactivity to Trypanosoma cruzi in a rural community in northeast Brazil.

Household distribution of seroreactivity to Trypanosoma cruzi in inhabitants was analyzed in relation to house construction and the distribution of Panstrongylus megistus, the principal domestic vector of Chagas' disease in a rural area in northeast Brazil. No children residing in mud-brick houses were seroreactive to T. cruzi. The highest rates of seroreactivity occurred in residents of unplastered mud-stick houses, and were twice as high as those found in persons living in mud-brick houses or plastered mud-stick houses. Two-thirds of seroreactive children in this area resided in unplastered mud-stick houses. Over 90% of the P. megistus infestations were found in mud-stick houses. Mud-brick houses had the lowest infestation rates of P. megistus and the lowest household rates of seroreactivity to T. cruzi.

The epidemiology and household distribution of seroreactivity to Trypanosoma cruzi in a rural community in northeast Brazil.

The prevalence rates and household distribution of seroreactivity to Trypanosoma cruzi by complement fixation (CF) and indirect immunofluorescent antibody methods were determined in a population of 1,087 persons living in a rural area endemic for Chagas' disease in northeast Brazil. There was a gradual rise in the rate of seropositivity to 60% by age 20. Between ages 20 and 55 the prevalence rate remained at about 60%, but declined thereafter. The decline in the older age groups was not accompanied by a fall in geometric mean titer, suggesting that the decline might better be explained by an increased mortality among those seropositive than by a decrease in CF reactivity associated with age. There was variation in the rates of seropositivity in children among the geographic subunits, but the rates among adults were fairly uniform. Household clustering of seropositivity was demonstrated when both household size and age distribution were taken into account. The presence of a seropositive child less than 5 years of age was a good indicator of a household with a high rate of seropositivity; screening for young seropositive children might be a useful tool to locate high risk households. Seropositive children in households where the mother was seropositive but the father seronegative were significantly younger than seropositive children in households where the father was seropositive but the mother seronegative even though the age distribution and the overall rate of seropositivity in both groups of children were similar; thus, conversion to seropositivity earlier in life in children of seropositive mothers may not be due solely to increased exposure, but may indicate that the immunologic response in such children differed from that of children from seronegative mothers.

Utility of tuberculin and anergy skin testing in predicting tuberculosis infection in human immunodeficiency virus-infected persons in Thailand.

SETTING: Chiang Rai, the northernmost province of Thailand, where extensive human immunodeficiency virus (HIV) transmission has resulted in a rapid increase in tuberculosis. OBJECTIVE: To assess the utility of tuberculin and anergy skin testing to identify latent Mycobacterium tuberculosis infection in HIV-infected persons. DESIGN: A cross-sectional study and analysis were conducted to examine reactivity to tuberculin and two control antigens (mumps and candida) in HIV-negative and HIV-positive blood donors and female sex workers. RESULTS: HIV-positive persons had markedly decreased tuberculin reactivity; 14%, 19%, and 40% had an induration of > or = 10 mm, > or = 5 mm, > or = 2 mm, respectively, while 51% of 525 HIV-negative persons had an induration of > or = 10 mm (P < 0.001). Mumps and candida positivity (reactions of > or = 3 mm) were found in 94% and 78% of HIV-negative persons compared with 72% and 61% of HIV-positive persons, respectively (P < 0.001). Although HIV-positive persons had markedly less tuberculin reactivity even at higher CD4+ cell counts (> 400 cells/microL), reactivity to mumps and candida was present in more than half of HIV-positive persons with low CD4+ cell counts (< or = 200 cells/microL). Reaction to control antigens did not predict tuberculin reactivity. CONCLUSION: In this setting, tuberculin and anergy skin testing have a low predictive value in detecting M. tuberculosis infection in HIV-infected persons, and therefore such testing has a limited role in identifying HIV-infected persons who may benefit from tuberculosis preventive therapy programs.

Steady state assumptions in DALYs: effect on estimates of HIV impact.

OBJECTIVE: The disability adjusted life year (DALY) and the healthy life year (HeaLY) are both composite indicators of disease burden in a population, which combine healthy life lost from mortality and morbidity. The two formulations deal with the onset and course of a disease differently. The purpose of this paper is to compare the DALY and HeaLY formulations as to differences in apparent impact when a disease is not in an epidemiological steady state and to explore the implications of the differing results. DESIGN: HIV is used as a case study of a major disease that is entering its explosive growth phase in large areas of Asia. Data from the global burden of disease study of the World Bank and World Health Organisation for 1990 has been used to compare burden of disease measures in the two formulations. SETTING: The data pertain to global and regional estimates of HIV impact. RESULTS: The DALY attributes life lost from premature mortality to the year of death, while the HeaLY to the year of disease onset. This results in very large differences in estimates of healthy life lost based upon the DALY construct as compared with the HeaLY, for diseases such as HIV or those with a strong secular trend. CONCLUSION: The demonstration of the dramatic difference between the two indicators of disease burden reflects a limitation of the DALY. This information may directly influence decision making based on such methods and is critical to understand.

Epidemiological study designs appropriate for investigating interactions between HIV infection and tropical diseases.

Infections with the human immunodeficiency virus(es) (HIV) are likely to have a profound impact on the health of those in many parts of Africa over the next several decades. If there are adverse interactions between HIV infections and the endemic tropical diseases the overall impact of the HIV epidemic will be worse than that predicted based on observations on the natural history of HIV infections in developed countries. With the exception of tuberculosis, the evidence for such interactions is presently lacking, but this may be largely due to the dearth of informative studies. In this paper we outline the kinds of epidemiological studies required to investigate such interactions and discuss some of the problems associated with the investigations.

Ultrasound in schistosomiasis--a critical look at methodological issues and potential applications.

This is the concluding paper of a series on the use of diagnostic ultrasound in the investigation of schistosomiasis. An earlier chapter in the volume discussed standardization of the methodology, and of recording, when ultrasound is used for epidemiological purposes. The present paper discusses some other requirements for obtaining ultrasound data which can be used to make valid comparisons within and between studies. Since there is an inherent variability in the interpretation of results from ultrasound images, quality control and the training of observers are both essential. It is also necessary to collect more information for each endemic setting about possible concomitant diseases which might lead to misinterpretation of results. Furthermore, the analysis of the data obtained must be uniform if valid comparisons are to be made. A final section considers applications of ultrasonography in research and control programmes. The technique should make it possible to obtain a better understanding of the extent and distribution of organ damage due to schistosomal infection in different geographical areas, and of the way in which lesions develop over time, or may regress in response to treatment. Since ultrasonography will always remain a relatively labour-intensive and expensive technique, it is necessary to establish, in different settings, how its findings correlate with the results of parasitological, serological and biochemical tests. The ultimate aim is to build up a body of information on the potential of ultrasonography, in combination with other procedures, in the various possible approaches to morbidity control.

The application of a quantitative approach to the assessment of the relative importance of vector and soil transmitted diseases in Ghana.

The vector and soil transmitted parasitic infections produce a highly diverse group of diseases in terms of the importance of their impact upon human populations and in terms of the control methods that might limit that impact. In Ghana a method was developed for quantitatively assessing the relative importance of different disease problems by estimating the amount of healthy life lost through illness, disability and death as a result of each disease. The quantitative assessment is derived from information on incidence rate, case fatality rate and the extent and duration of disability produced by the disease. The method may be used to help decide the priorities for the allocation of resources to alternative procedures or programmes by calculating the amount of healthy days of life which may be saved by different approaches and then relating these savings to the costs of the approaches. Each of the vector and soil transmitted parasitic diseases in Ghana had special characteristics that influenced the estimates of their relative importance. Attribution of death due to malaria posed special problems, but even with the most conservative estimate malaria was the single most important cause of loss of healthy life of all diseases in Ghana. For schistosomiasis there is such great uncertainty concerning how much disability or mortality that results from infection that the relative importance of schistosomiasis could not be usefully estimated; thus research into the extent of disability and death caused by schistosomiasis should have a very high priority if rational allocation of resources for its control is to be achieved. Onchocerciasis, though not generally considered an important cause of mortality, is an important cause of chronic severe disability. The importance of ascariasis and hookworm remain uncertain both because of the lack of information as to the extent of disability and mortality that they produce and the lack of data in Ghana as to their prevalence and intensity of infection. Guinea worm was of little importance from the national point of view, but was highly important in focal areas. Trypanosomiasis would appear to be of minor importance because its incidence was quite low, but for an epidemic disease such as trypanosomiasis the importance must be estimated based on what would occur if there were not effective surveillance and control methods. Diverse though this group of parasitic diseases is a common thesis is that each has been relatively neglected in relation to its importance and for each a considerable reduction in loss of healthy life should be achievable at reasonable cost.

Interventions for control of road traffic injuries: review of effectiveness literature.

OBJECTIVE: In 1998, road traffic injuries were estimated to be the 9th leading cause of loss of healthy life globally and are projected to become the 3rd leading cause by 2020. The majority of this burden can be located in the developing world where most of the projected increase will occur. Yet health systems are least prepared to meet this challenge in these countries. At the same time, there are effective interventions for road traffic injuries being implemented in the developed world. An extensive review of the literature reveals more than 16 different interventions in four categories that have been implemented. Renewed testing of these and new interventions will take both time and funds--resources that are scarce in developing countries. As a result, it is imperative to study the effectiveness of those interventions already tested and attempt to evaluate their potential implementation in developing countries. METHOD: Literature review to identify effective interventions and the magnitude of the effects. RESULTS: Four broad classes of interventions can be identified from the literature; health education/awareness, legislation, product design and environmental modifications. CONCLUSION: The issues for the developing countries are affordable, infrastructure and sociocultural in implementation of these strategies. The road traffic injuries are also underreported and hence under represented at the priority setting stage. Road safety should be high on the agenda as it can save a lot of lives and disability. Public health professionals should assess and advocate road safety in developing countries.