Impact of six rounds of mass drug administration on Brugian filariasis and soil-transmitted helminth infections in eastern Indonesia.

BACKGROUND: The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the effect of MDA using DEC and albendazole on B. timori and soil transmitted helminths (STH) in a cross-sectional study of a sentinel village on Alor Island annually over a period of 10 years. Pre-MDA the microfilaria (MF) prevalence was 26% and 80% of the residents had filaria-specific IgG4 antibodies. In 2010, 34 months after the 6(th) round of MDA, MF and antibody rates were only 0.17% and 6.4%, respectively. The MDA campaign had also a beneficial effect on STH. Baseline prevalence rates for Ascaris, hookworm and Trichuris were 34%, 28%, and 11%, respectively; these rates were reduced to 27%, 4%, and 2% one year after the 5(th) round of MDA. Unfortunately, STH rates rebounded 34 months after cessation of MDA and approached pre-MDA rates. However, the intensity of STH infection in 2009 was still reduced, and no heavy infections were detected. CONCLUSIONS/SIGNIFICANCE: MDA with DEC/albendazole has had a major impact on B. timori MF and IgG4 antibody rates, providing a proof of principle that elimination is feasible. We also documented the value of annual DEC/albendazole as a mass de-worming intervention and the importance of continuing some form of STH control after cessation of MDA for filariasis.

Good efficacy of artemether-lumefantrine for uncomplicated falciparum malaria in eastern Sumba, East Nusatenggara, Indonesia.

AIM: to evaluate the safety and efficacy of a fixed combination of artemether-lumefantrine for likely use against failures of the artesunate-amodiaquine first line therapy. METHODS: the study was an open label single arm uncontrolled trial. we evaluated the safety and efficacy of standard artemether-lumefantrine therapy in 59 subjects with uncomplicated malaria caused by Plasmodium falciparum on the island of Sumba in eastern Indonesia. No treatment failures occurred up to day 35. One subject had recurrent parasitemia on day 42 that showed a genotype consistent with recrudescence. The efficacy of this therapy was thus estimated to be 98.3% (95% confidence interval=95%-100%). Descriptive analysis was done using the SPSS 12 computer software. RESULTS: two hundred and thirteen P. falciparum patients met the inclusion criteria for in vivo efficacy study, 79 were given artemether-lumefantrine and 134 were treated under another protocol with artesunate-amodiaquine or sulfadoxine-pyrimethamine. Among 79 eligible subjects, 59 successfully completed the 42-day test. As expected, the mean PCT was longer than the mean FCT, i.e. 1.34 ± 0.67 (95% CI 1.21-1.47) and 1.05 ± 0.05 (95% CI 0.95-1.15) days, respectively. On day 3 of treatment, both fever and asexual stage of P. falciparum disappeared in all subjects. Observation until Day 35 showed that all of the 59 subjects treated with artemether-lumefantrine were cured. CONCLUSION: the findings of this uncontrolled study suggest good safety and efficacy of artemether-lumefantrine for treatment of uncomplicated falciparum malaria on Sumba Island in the Lesser Sundas archipelago of eastern Indonesia.

Fibular collateral ligament anatomical reconstructions: a prospective outcomes study.

BACKGROUND: After the development and biomechanical validation of an anatomical fibular collateral ligament reconstruction using a semitendinosus graft, this technique has subsequently been applied clinically. HYPOTHESIS: An anatomical reconstruction of a grade III fibular collateral ligament tear using a semitendinosus graft restores the knee to near-normal lateral compartment stability and results in improved patient outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A prospective study of 20 patients with an average age of 24 years (range, 16-45 years) who had an anatomical reconstruction of the fibular collateral ligament using a semitendinosus graft was performed. All patients were preoperatively and postoperatively evaluated with the modified Cincinnati and International Knee Documentation Committee (IKDC) subjective scoring systems, with the IKDC objective subscores for lateral and posterolateral knee stability and with varus stress radiographs. The patients were followed for an average of 2 years. RESULTS: Sixteen patients were available for follow-up. Six of the patients had an isolated fibular collateral ligament reconstruction. The average preoperative modified Cincinnati score was 28.2, and the average IKDC subjective score was 34.7. Postoperatively, there was a significant improvement of both the modified Cincinnati score (to 88.5) and the IKDC subjective outcome score (to 88.1). The Cincinnati component symptom and functional subscores were also evaluated. The average preoperative symptom subscore was 9.1 and the functional subscore was 19.1. Postoperatively, there was a significant improvement in both scores; symptom subscores improved to 43.0 and functional subscores improved to 45.5. Preoperative varus stress radiographs demonstrated an average differential of 3.9 mm (range, 2.5-6.2 mm) of lateral compartment gapping between the injured and noninjured knee. At an average of 2 years postoperatively, varus stress radiographs demonstrated an average side-to-side lateral compartment gap differential of -0.4 mm. CONCLUSION: An anatomical fibular collateral ligament reconstruction using a semitendinosus graft results in improved patient outcomes and near-normal lateral compartment stability in patients with grade III injuries of the fibular collateral ligament.

Using knowledge, attitudes and practice (KAP) surveys on lymphatic filariasis to prepare a health promotion campaign for mass drug administration in Alor District, Indonesia.

We report the results of two surveys of people's knowledge, attitudes and practices (KAP) regarding lymphatic filariasis (LF) in Alor District, eastern Indonesia. The results of the surveys were used to prepare and evaluate the social mobilization component of a pilot mass drug administration (MDA) in five villages. In the study area, the filarial parasites Brugia timori and Wuchereria bancrofti are highly endemic. Frequent and severe adverse reactions after MDA may occur especially in areas endemic for B. timori and therefore, a special communication strategy was designed to inform and to educate communities about LF and its control. The first KAP survey was conducted as a baseline pre-MDA with diethylcarbamazine and albendazole and the second as a post-intervention evaluation in order to obtain information on the impact of the communication campaign. Before the information campaign and the subsequent MDA, 54% of the study population had heard of one of the three main terms for LF, whereas after health education and MDA, 89% had heard of at least one of the three terms. Similarly, pre-MDA, 21% reported having had previously taken the treatment for filariasis, while post-MDA, 88% reported having taken the treatment during the pilot treatment period. The historical fears and traumatic experiences associated with past LF treatment campaigns in Indonesia were averted since both the communication campaign and the MDA were designed appropriately for and together with the community. As a result, compliance was sufficient in the first round to successfully begin the elimination process.

Impact of two rounds of mass drug administration using diethylcarbamazine combined with albendazole on the prevalence of Brugia timori and of intestinal helminths on Alor Island, Indonesia.

BACKGROUND: Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking. METHODS: The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined. RESULTS: In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura. CONCLUSION: The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren.

Real-time PCR for dihydrofolate reductase gene single-nucleotide polymorphisms in Plasmodium vivax isolates.

Mutations in the dhfr gene of Plasmodium vivax (pvdhfr) are associated with resistance to the antifolate antimalarial drugs. Polymorphisms in the pvdhfr gene were assessed by hybridization probe technology on the LightCycler instrument with 134 P. vivax-infected blood samples from Turkey (n = 24), Azerbaijan (n = 39), Thailand (n = 16), Indonesia (n = 53), and travelers (n = 19). Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117N) in the pvdhfr genes were found in all Thai samples (100%). pvdhfr mutant-type alleles were significantly more common in samples from travelers (42%) than in those from patients from Indonesia (5%). Surprisingly, the pvdhfr single-mutation allele (S117N) was identified at a high frequency in parasites from Turkey and Azerbaijan (71 and 36%, respectively), where sulfadoxine-pyrimethamine is not recommended for the treatment of P. vivax malaria by the World Health Organization and the Malaria National Programs.

Comparative efficacy of chloroquine and sulfadoxine-pyrimethamine for uncomplicated Plasmodium falciparum malaria and impact on gametocyte carriage rates in the East Nusatenggara province of Indonesia.

The efficacy of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) was evaluated in 89 subjects greater than one year of age with uncomplicated P. falciparum malaria in the East Nusatenggara Province of Indonesia. Fever clearance time was longer in the SP group than in the CQ group. However, parasite clearance time was extended in subjects who received CQ compared with those who received SP. Major adverse events were not observed in either group, and no hospitalizations were required during the study. Treatment failure rates at day 28 were 69% for CQ and 8.5% for SP. In both treatment groups, gametocytemia developed during the follow-up period, but was more pronounced in the SP group, peaking at 94% on day 7. Regardless of treatment group, children < 10 years of age had significantly higher treatment failure rates than subjects >/=10 years of age (relative risk = 2.49), suggesting that acquired immunity influenced treatment outcomes in the presence of parasite drug resistance. Although a highly effective alternative to CQ for clearing infection, SP treatment also presented some potential drawbacks (e.g., increased and persistent gametocytemia). Replacement of CQ with SP as a first-line therapy, either alone or in combination with CQ, in those areas of Indonesia with high levels of CQ resistance should significantly improve treatment outcomes, particularly in vulnerable populations lacking clinical immunity. More efficacious and rapidly acting asexual stage treatments are generally associated with increased gametocyte clearance and combination therapy in areas where drug resistance is high or emerging may provide an additional means for reducing transmission.

Detection of filaria-specific IgG4 antibodies using Brugia Rapid test in individuals from an area highly endemic for Brugia timori.

The filarial parasite Brugia timori is of great public health importance in some islands of Eastern Indonesia. To establish a simple serological test for the identification and post-treatment monitoring of areas endemic for B. timori, a rapid immunochromatographic dipstick test (Brugia Rapid, BR) was evaluated on microfilaraemic and amicrofilaraemic individuals. This test is based on the detection of anti-filarial IgG4 antibodies that react with a recombinant Brugia malayi antigen (BmR1). In our study area on Alor island the prevalence of microfilaraemia was 26%. With the BR test, 100% of 196 sera from microfilaraemic persons and 76% of 563 sera from amicrofilaraemic persons, either symptomatic or asymptomatic, reacted positive. All 50 control sera from areas non-endemic for lymphatic filariasis gave negative BR test results. This study showed that the BR test can be also used to detect antibodies against B. timori. Due to the high prevalence of IgG4 antibodies as detected by the BR test (81%), no significant correlation with the prevalence of microfilaraemia could be detected within the endemic village. The BR test also shows great promise to be employed as a monitoring tool for B. timori in the framework of the Global Program to Eliminate Lymphatic Filariasis (GPELF).

Long-lasting reduction of Brugia timori microfilariae following a single dose of diethylcarbamazine combined with albendazole.

The long-term effect of a single oral dose of 6 mg/kg bodyweight of diethylcarbamazine (DEC) combined with 400 mg albendazole (ALB) on the microfilariae (mf) of the lymphatic filarial parasite Brugia timori was studied on Alor island, Indonesia from April 2001 to April 2002. Before treatment the geometric mean of the mf density in 96 infected study subjects was 150 mf/mL night blood (range 1-5696 mf/mL). One year after treatment 69 subjects (72%) were mf-negative and the overall geometric mean mf density reduced to 3 mf/mL (0-2456 mf/mL). The reduction of mf was more pronounced 1 year after treatment compared with 6 months after treatment. It can be concluded that a single dose of DEC + ALB leads to a long-term and progressive suppression of B. timori mf for at least 1 year. Therefore, DEC+ ALB can be recommended as an effective strategy to control B. timori infection in the framework of the Global Programme to Eliminate Lymphatic Filariasis.

Treatment of Brugia timori and Wuchereria bancrofti infections in Indonesia using DEC or a combination of DEC and albendazole: adverse reactions and short-term effects on microfilariae.

Filariasis caused by Brugia timori and Wuchereria bancrofti is an important public health problem on Alor island, East Nusa Tenggara, Indonesia. To implement a control programme, adverse reactions and short-term effects on the microfilaria (mf) density were studied following a divided dose of diethylcarbamazine (DEC, 6 mg/kg body weight - 100 mg on day 1 and the rest on day 3) or a single dose of DEC (6 mg/kg body weight on day 3) and albendazole (Alb, 400 mg). In order to define the most appropriate regimen, 30 persons infected with B. timori were treated in the hospital and results were compared with those obtained from the treatment of 27 persons infected with W. bancrofti. Adverse reactions consisted of systemic reactions such as fever, headache, myalgia, itching and local reactions such as adenolymphangitis. Fever experienced by a number of patients in both treatment groups generally occurred 12-24 h after drug administration and lasted up to 2 days. Adenolymphangitis tended to occur later and was resolved within 4 days. The number of W. bancrofti patients suffering from adverse reactions was lower and the reactions were milder than those of the B. timori patients. There was no difference in adverse reactions between DEC alone and DEC-Alb treatment for either infection. The geometric mean mf count decreased on day 7 in the B. timori infected patients from 234 mf/ml in the DEC group and from 257 mf/ml in the DEC-Alb group to 7 and 8 mf/ml, respectively. The mf densities of the W. bancrofti infected patients decreased on day 7 from 214 mf/ml in the DEC group and from 559 mf/ml in the DEC-Alb group to 15 and 14 mf/ml, respectively. Our data indicate that the microfilaricidal effect of the drugs is achieved more rapidly for B. timori, which is associated with more adverse reactions than W. bancrofti. In addition, 111 B. timori infected persons were treated in the community with DEC-Alb in one selected village. The adverse reactions and the reduction of mf density was similar to the findings of the hospital-based study. In this group, there was a strong correlation of mf density with the frequency and severity of adverse reactions. The addition of Alb resulted in no additional adverse reactions compared with DEC treatment alone and can also be used for the treatment of B. timori infection. In Indonesia, where the prevalence of intestinal helminths is high, the use of a combination of DEC and Alb to control lymphatic filariasis may also have impact on the control of intestinal helminths.

High prevalence of Brugia timori infection in the highland of Alor Island, Indonesia.

To identify areas endemic for Brugia timori infection, a field survey was carried out in 2001 on Alor, East Nusa Tenggara Timor, Indonesia. Elephantiasis was reported on this island by villagers as a major health problem. Bancroftian filariasis was detected in four villages in the coastal area, whereas B. timori was identified in four rice-farming villages. No mixed infections with both species were found. In the highland village Mainang (elevation = 880 m), 586 individuals were examined for B. timori infection and 157 (27%) microfilaria carriers were detected. The prevalence of microfilaremic individuals standardized by sex and age was 25%. The geometric mean microfilarial density of microfilaremic individuals was 138 microfilariae/ml. Among teenagers and adults, males tended to have a higher microfilarial prevalence than females. Microfilaria prevalence increased with age and a maximum was observed in the fifth decade of life. In infected individuals, the microfilarial density increased rapidly and high levels were observed in those individuals 11-20 years old. The highest microfilaria density was found in a 27-year-old woman (6,028 microfilariae/ml). Brugia timori on Alor was nocturnally periodic, but in patients with high parasite loads, a small number of microfilariae was also detected in the day blood. The disease rate was high and many persons reported a history of acute filarial attacks. Seventy-seven (13%) individuals showed lymphedema of the leg that occasionally presented severe elephantiasis. No hydrocele or genital lymphedema were observed. This study showed that B. timori infection is not restricted to the lowland and indicated that it might have a wider distribution in the lesser Sunda archipelago than previously assumed.