This study shows the effect of one selective treatment and two rounds of MDA using DEC combined with alb on the most prevalent helminths, B. timori, A. lumbricoides, hookworms and T. trichiura in a community on Alor island. The results confirm and show for the first time at the community level, that the MDA approach as recommended by the GPELF is highly effective at reducing the prevalence and the intensity of infection of B. timori. Furthermore, a positive impact on the prevalence, especially of hookworm infection, but also of A. lumbricoides and of T. trichiura, was observed. The data support the hypothesis that B. timori is an excellent candidate for elimination, while the campaign will also have a large impact on the reduction of intestinal helminths . B. timori occurs only east of the Wallace line in Indonesia and Timor-Leste. This restricted distribution makes this species not only a good candidate for local elimination, but B. timori may also be a prime candidate for eradication of lymphatic filariae [15, 21].
B. timori is closely related to B. malayi and tools and strategies developed to support the elimination of B. malayi infection may apply for both species [13–15, 17, 18]. It has been shown that the combination of a single annual dose of DEC combined with alb is very efficient in the control of brugian filariasis and a higher efficacy of this regimen has been suggested as compared to bancroftian filariasis [6, 13, 14]. The successful control of B. timori on parts of Flores island using multiple doses of DEC has been reported already some decades ago . However, this strategy has caused many logistical problems and was never extended to the remaining parts of Flores and other islands. The present study proved the principle that a single annual dose of DEC combined with alb is highly suitable to control and most probably to eliminate B. timori infection. Before treatment, among a cohort of 145 individuals, 45 were mf-positive with a geometric mean mf density of almost 150 mf/ml. Three years later, following one selective treatment and two rounds of MDA in this group only 3 individuals were found to be mf-positive, who had mf densities of 1–2 mf/ml.
Our data show that a larger percentage of mf-positive individuals claimed not to have participated in MDA, compared to the average compliance rate. It can be concluded that a high compliance rate is necessary for reducing the mf prevalence to levels under which transmission cannot be sustained. In addition, a few individuals who received no treatment still had high mf densities. If these individuals participate in the next rounds of MDA, side effects may occur and affected individuals may spread their problems in the community which eventually reduce compliance. However, extensive health information campaigns can help to ensure high compliance rates .
On the community level not much data exists about the control of brugian filariasis by annual MDA using DEC combined with alb. For the control of W. bancrofti infection in Asia a number of extensive field studies were published using annual MDA with DEC alone or in combination with alb. Results from Papua New Guinea indicate promising prospects for elimination [22, 23]. In India, after six rounds of a single dose treatment with DEC the prevalence of microfilaraemics was reduced by 86% and the mf density by 91% . Computer models predict that in this area a further decline of mf prevalence will occur even after the cessation of MDA . In this study (B.timori), similar reductions of prevalence and mf density were observed after only one selective treatment and two rounds of MDA. It is possible that models would also predict a further decline of mf prevalence for our study, but epidemiological parameters differ largely between W. bancrofti infections in Pondicherry (India) and B. timori infections on Alor island and further studies on the dynamics of B. timori control are needed. In addition, it has been discussed for W. bancrofti in the pacific area that MDA should be accompanied by local vector control .
Our results showed that MDA using a combination of DEC and alb also has an impact on the reduction of intestinal nematode infections. In the highland village examined the original prevalence and intensity of infections with A. lumbricoides, hookworms and T. trichiura was relatively low. This is in agreement with previous surveys on Alor and on other islands of volcanic origin in east Nusa Tenggara Timur [26, 27]. Although, both hookworm species occur in eastern Indonesia, data from Flores indicate that Necator americanus, may be the prominent species .
The strongest reduction of prevalence following two rounds of MDA among the intestinal helminths was observed in hookworm infections, in both, the cross-sectional group of an average of 600 individuals and a cohort of 226 individuals. Although a large number of re-infections occurred, the crude prevalence dropped from 25.3% to 5.9% and in the cohort from 34.5% to 14.2%, ten months after the second round of MDA. This equals a reduction of 76.7% and 58.8%, respectively. The hookworm prevalence is usually reduced by about 80% shortly after treatment with alb [28, 29]. Although DEC alone may reduce the output of hookworm eggs, it is assumed that it has no influence on its prevalence . In our study we observed a large number of hookworm re- or new infections. In 13.5% (2003) and 14.0% (2004) of the cohort new infections were observed. From Java, an even higher re-infection rate with N. americanus of about 50% one year after anthelminthic treatment was reported . Despite of the occurrence of re-and new infections, the drop in hookworm prevalence can be explained by the relatively short survival time of hookworm larvae in the environment as compared to the mean survival time of eggs of A. lumbricoides and of T. trichiura.
Following the first round of MDA the crude prevalence of A. lumbricoides dropped from 32.2% to 22.1%, but after the second round it was 27.6%. More consistently were the results in the cohort. Before MDA the prevalence was 43.3%, following the first round it was 28.3% and following the second round it was 26.5%. Albendazole is very effective against A. lumbricoides and median cure rates are over 95% [28, 29, 32]. DEC alone has a minor therapeutic effect on Ascaris [10, 33]. Although some treated individuals may expel adult worms after DEC, the overall prevalence of infection may be not affected . These observations are confirmed by other studies, which show that DEC alone has no significant impact on A. lumbricoides, but the combination of DEC with alb has relevant cure and egg reduction rates . As in other intestinal helminths, re- and new infections occur regularly, and the time point of re-examination is critical. In our cohort we observed an annual rate of new infections of 25%. Children have an especially high risk for re- or new-infections and show a lower decrease in worm burden compared to adults . In another study it was observed that eight months after treatment 55% of children were re-infected . Re-infection with A. lumbricoides may return six months after treatment to almost 90% of the pre-treatment prevalence and worm density may drop to about 75% .
The crude prevalence of T. trichiura in the community before and after MDA was almost identical, ranging between 9.4% and 8.7%. However, following two rounds of MDA the prevalence dropped in the cohort from 12.8% to 6.6%. Although re- and new infections occurred, it is important to note that in 2004 most new infections were observed in those individuals which were negative for T. trichiura for the previous two years. Trichuris trichiura is known to be only poorly sensitive to albendazole and the reported reduction rates for alb range between 38% and 47.7% [28, 29, 32]. From Sri Lanka a cure rate of T. trichiura of 43.6% and an egg reduction rate of 70.3% was reported . The combination of DEC with alb showed different results, ranging from no significant impact on the prevalence but with significant egg reduction of 79.4% one week after treatment, to a cure rate of 81.6% and an egg reduction of 84% [10, 34]. The study from Sri Lanka reported that this drug combination has a cure rate of 30% and an egg reduction rate of 70% .
For areas endemic for W. bancrofti there are an increasing number of studies which show the positive effect of filariasis control using MDA with DEC combined with alb on the reduction of intestinal helminths [8–11, 38]. The results of the present study can extend this observation to areas endemic for Brugia infections. Although it is unlikely that MDA as used for filariasis elimination will eliminate intestinal helminths from most areas, a reduction may be achieved to levels which may cause no significant morbidity. Other intervention strategies, such as for example the development of a hookworm vaccine , may take advantage of reduced prevalences in order to achieve a long-lasting elimination of intestinal helminths, as it has been accomplished in most industrialised countries. In areas with filariasis control by the MDA using DEC combined with alb, separate de-worming campaigns for school-age children may become superfluous. This could set available resources free which can then be used to support MDA. Co-ordination is needed within the local health administration to use the limited funds more efficiently. The present study showed that MDA using DEC combined with alb is effective to control B. timori and that this has also impact on the reduction of geohelminths.