M. Tanner

Towards a comprehensive simulation model of malaria epidemiology and control

Planning of the control of Plasmodium falciparum malaria leads to a need for models of malaria epidemiology that provide realistic quantitative prediction of likely epidemiological outcomes of a wide range of control strategies. Predictions of the effects of control often ignore medium- and long-term dynamics. The complexities of the Plasmodium life-cycle, and of within-host dynamics, limit the applicability of conventional deterministic malaria models. We use individual-based stochastic simulations of malaria epidemiology to predict the impacts of interventions on infection, morbidity, mortality, health services use and costs. Individual infections are simulated by stochastic series of parasite densities, and naturally acquired immunity acts by reducing densities. Morbidity and mortality risks, and infectiousness to vectors, depend on parasite densities. The simulated infections are nested within simulations of individuals in human populations, and linked to models of interventions and health systems. We use numerous field datasets to optimise parameter estimates. By using a volunteer computing system we obtain the enormous computational power required for model fitting, sensitivity analysis, and exploration of many different intervention strategies. The project thus provides a general platform for comparing, fitting, and evaluating different model structures, and for quantitative prediction of effects of different interventions and integrated control programmes.

A review of the literature on the use of ultrasonography in schistosomiasis with special reference to its use in field studies: 1. Schistosoma haematobium

This paper gives a brief description of the pathology resulting from Schistosoma japonicum infection, and ways in which it can be investigated. It then reviews reports of the application of ultrasound in investigating lesions in schistosomiasis japonica, including papers published in Chinese and Japanese. Ultrasonography has been widely used for the diagnosis of schistosomiasis and for the investigation of pathological changes resulting from the infection. Marked and characteristic changes are observed in the structure of the liver parenchyma in advanced disease. Chronic pathology may be seen as a result of past infection. Animal studies have been used to compare ultrasound images with actual pathological changes. Ultrasonography can also be used to detect early changes, for example periportal fibrosis, which can indicate the development of portal hypertension. The problem of differential diagnosis is discussed.

Ultrasound scanning for detecting morbidity due to Schistosoma haematobium and its resolution following treatment with different doses of praziquantel

A study to assess the resolution of urinary tract morbidity due to Schistosoma haematobium was conducted on 2 cohorts of schoolchildren attending neighbouring schools in Kilombero District, southern Tanzania. Schoolchildren were screened for S. haematobium infection using the standard World Health Organization filtration technique and subsequently examined for urinary tract pathology using a portable 3.0 MHz sector scanner (Siemens Sonoline 1300). Treatment with praziquantel was given to all infected children. Children with observed urinary tract pathology received either 20 (n = 52) or 40 (n = 79) mg/kg body weight and were sonographically re-examined one, 2, 3 and 6 months following treatment. Geometric mean outputs of 21 and 19 eggs/ml of urine were detected in the 2 cohorts before treatment. Urinary tract pathology correlated positively with egg output (chi 2, P = 0.02) and microhaematuria (P = 0.0001). Bladder (wall irregularities and polyps) and kidney (congestive changes) pathologies were found in 81% and 36%, respectively, of the group that received 20 mg/kg of praziquantel, and in 78% and 46% of the group that received 40 mg/kg. Six months after treatment, 90.4% and 88.0% parasitological cure rates were obtained using 20 or 40 mg praziquantel/kg body weight. The respective pathology clearances were 88% and 91%. 20 mg/kg of praziquantel was as effective with regard to cure rates and reversibility of morbidity as 40 mg/kg.

In vitro resistance patterns of Plasmodium falciparum to chloroquine—a reflection of strain-specific immunity?

Studies in vitro among children on the response of Plasmodium falciparum to chloroquine were conducted as part of the national long-term monitoring of drug resistance in a holo- to hyperendemic malarious area of Tanzania between 1983 and 1989. Overall, no significant increase in chloroquine resistance was observed. However, in children under 5 years old resistance increased during this period, whereas in schoolchildren resistance decreased from 1986 to 1989. A hypothesis based on antigenic differences between resistant and sensitive strains is proposed to explain this age-specific pattern. If immunity develops principally against the most frequent parasite strains, then as it develops the numbers of the most frequent strains will be reduced, whilst, the rare strains may become predominant and thus be detected in the blood of immune patients. Thus, in an endemic area, the observed resistance pattern in non-immune infants will differ from that in immune schoolchildren, as was observed in the present study. These findings may have important implications for the control of malaria and the development of vaccines.

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.

Immunological markers of childhood fevers in an area of intense and perennial malaria transmission

In order to describe presumed paediatric malaria on a cell‐immunological basis, the soluble receptors of IL‐2 (sIL‐2R) and tumour necrosis factor (sTNF‐R55 and sTNF‐R75) were quantified in highly exposed young Tanzanian children. Sera were obtained from 66 acute and 72 reported febrile patients during health post consultations and follow‐ups and from 68 community controls. Levels of sIL‐2R, sTNF‐R55 and sTNF‐R75 were significantly elevated during fever attacks, especially in very young children. Soluble TNF‐R75 levels were most stable and those of sTNF‐R55 least. Levels of sTNF‐R55 were related to the magnitude of fever and thus appeared to reflect attack severity. Levels of sTNF‐R75 were highly significantly associated with parasite density, indicating that this response is malaria‐specific. The present study indicates that sTNF‐R75 levels could become a useful immunological tool in malaria intervention studies, as they reflect changes in malaria‐specific immune responses. Future studies should validate this potential in different endemic settings.

Sensitivity of Plasmodium falciparum field-isolates from Tanzania to chloroquine, mefloquine and pyrimethamine during in vitro cultivation.

Since 1978, drug resistant Plasmodium Jalciparum malaria has been an increasing problem in East Africa. Resistance to all major drugs has emerged and is spreading to most endemic areas. It is essential that we understand the mechanisms of resistance and to monitor resistance-patterns in endemic settings so that we can use the appropriate drug in each area. The present study was undertaken within the framework of testing the drug sensitivity of field isolates from an endemic area (Tanner et al., 1987a: Koella et al., 1990), and aimed at investigating changes in the drug sensitivity of the same isolates during in vitro cultivation. Eighteen P. Jalciparum isolates were collected between May and July in 1989 from patients at St. Francis Designated District Hospital in Ifakara, Kilombero District, Tanzania. Fourteen patients were under 3 years old, one patient was 8 years old and three patients were adults. A portion of each blood sample was immediately tested for in vitro drug sensitivity (Table 1) with the WHO micro-test (WHO, 1987), and the remaining part was frozen in liquid nitrogen. After transport to Basel, the parasites were propagated and maintained in continuous in vitro culture (Trager and Jensen, 1976) for 133 170 days. The sensitivity of each isolate to chloroquine (CQ), meftoquine (MQ) and pyrimethamine (PM) was tested three times, after various time intervals, with a dilution assay as described by Desjardins et al. (1979): the parasites were incubated for 68 h with different dilutions of each drug. The growth of the parasites was measured by the incorporation of [3H]hypoxanthine, and the dose at which 50% of the parasites survived (EDso) was estimated by linear interpolation between the two adjacent drug concentrations above and below the 50% incorporation line (Hills et al., 1986).

Training of village health workers in Tanzania. A comparison of two approaches

The paper compares the costs of training for two groups of Village Health Workers (VHWs) Tanzania, where the policy of developing a system based on Primary Health Care principles will require the training of more than 16 000 VHWs during the next decade. In the Kilombero District, one group of VHWs was trained according to the guidelines of the National Programme of the Ministry of Health, and another group followed the training programme of the Kilombero Project, based on the Swiss Tropical Institute Field Laboratory. The training scheme of the Kilombero project cost almost 80070 less for one VHW, largely because it depended on on-the-spot training by local staff. The results of a first investigation of the efficacy of the training were encouraging; a longterm evaluation is in progress. The curricula for the two programmes also differed; the Kilombero programme had shorter blocks of theory, interspersed with supervised practical work, and introduced curative medicine earlier in the course. The advantages and disadvantages of the two programmes are discussed, not only in terms of cost but also in terms of their efficacy in training VHWs who will be motivated, efficient and accepted by the community.