Knowledge, attitudes and perceptions regarding lymphatic filariasis: study on systematic noncompliance with mass drug administration

ABSTRACT The aim of this study was to investigate the epidemiological characteristics, antigenic profile, perceptions, attitudes and practices of individuals who have been systematically non-compliant in mass drug administration (MDA) campaigns targeting lymphatic filariasis, in the municipality of Olinda, State of Pernambuco, Northeastern Brazil. A pretested questionnaire was used to obtain information on socioenvironmental demographics, perceptions of lymphatic filariasis and MDA, and reasons for systematic noncompliance with treatment. A rapid immunochromatographic test (ICT) was performed during the survey to screen for filariasis. It was found that the survey subjects knew about filariasis and MDA. Filariasis was identified as a disease (86.2%) and 74.4% associated it with the presence of swelling in the legs. About 80% knew about MDA, and the main source of information was healthcare workers (68.3%). For men the main reasons for systematic noncompliance with MDA were that “the individual had not received the medication” (p=0.03) and for women “the individual either feared experiencing adverse reactions”. According to the ICT, the prevalence of lymphatic filariasis was 2%. The most important causes of systematic noncompliance were not receiving the drug and fear of side-effects. For successful implementation of MDA programs, good planning, educational campaigns promoting the benefits of MDA, adoption of measures to minimize the impact of adverse effects and improvement of drug distribution logistics are needed.

Successful Treatment of Brugia pahangi in Naturally Infected Cats with Ivermectin

Lymphatic filariasis is a common parasitic disease of cats in tropical regions including Thailand. The objective of this study was to determine the efficacy of ivermectin against microfilariae of Brugia pahangi in naturally infected cats. Eight cats naturally infected with B. pahangi were divided into control (untreated) and treated groups. Cats in the latter group were given ivermectin injection at 400 microg/kg weekly for 2 months. Microfilariae were counted every week until 48 weeks. Microfilaremia was significantly decreased in the treated group 4 weeks after starting the treatment and become zero at week 9 and afterwards. On the other hand, cats in the control group had high microfilaremia throughout the study. It was successful to treat and control B. pahangi infection in naturally infected cats using ivermectin.

Adverse reactions following mass drug administration with diethylcarbamazine in lymphatic filariasis endemic areas in the Northeast of Brazil / Reações adversas após tratamento em massa com dietilcarbamazina em áreas endêmicas de filariose linfática no nordeste do Brasil

INTRODUCTION: The Global Programme to Eliminate Lymphatic Filariasis was launched with the goal of eliminating this disease via the annual mass drug administration (MDA) of a single dose of antifilarial drugs. Adverse drug reactions following MDA are a major factor of poor treatment adherence in several countries. This study assessed the occurrence of adverse drug reactions (ADRs) following the first round of mass treatment in two communities treated with different dosages of diethylcarbamazine (DEC) in the City of Recife, Brazil. METHODS: Population-based cross-sectional surveys were conducted in a random sample of the population living in both communities (Areas I and II). The dose of DEC recommended by the WHO (6mg/kg) was calculated based on the individual's weight-for-age. In Area II, weight differences between the genders were also considered when determining dosage. Data were obtained through interviews conducted in the first 12 to 48h and on the 5th day after MDA during household visits. RESULTS: A total of 487 and 365 individuals were interviewed in Areas I and II, respectively. The prevalence of ADRs in Area I (23.6; 95%CI: 19.1-29.5) was higher than in Area II (16.2; 95%CI:11.9-21.5)(p=0.0078). The prevalence of ADRs among females was higher than in males in Area I (p=0.0021). In Area II, no significant difference between the genders was observed (p=0.1840). Age was not associated with ADRs in either area. CONCLUSIONS: Adjusting MDA dosage schedules according to weight-for-age and sex may be may contribute to reduce the occurrence of adverse drug reactions in the population.

INTRODUÇÃO: O Programa Global de Eliminação da Filariose Linfática foi lançado visando à eliminação da doença pela administração de medicamentos em massa (MDA). As reações adversas seguidas ao MDA são um importante fator de baixa adesão ao tratamento em vários países. Este estudo avaliou a ocorrência de reações adversas medicamentosas (ADRs) após a primeira dose de tratamento em massa em duas comunidades tratadas com diferentes doses de dietilcarbamazina (DEC), na Cidade de Recife, Brasil. MÉTODOS: Estudos transversais foram realizados em uma amostra aleatória da população de duas áreas (Áreas I e II). A dose de DEC recomendada pela OMS (6mg/kg) foi calculada com base em parâmetros populacionais de peso para a idade. Na Área II, diferenças de peso entre os sexos também foram consideradas no cálculo. Dados foram obtidos através de entrevistas nas primeiras 12 às 48h e 5º dia após o tratamento durante visitas domiciliares. RESULTADOS: Um total de 487 e 365 pessoas foi entrevistado nas Áreas I e II, respectivamente. A prevalência de ADRs na Área I (23,6; IC95%: 19,1-29,5) foi maior do que na Área II (16,2; IC 95%:11,9-21,5)(p=0,0078). Na Área I, a prevalência de ADRs foi maior nas mulheres do que nos homens (p=0,0021), não se observando diferença na Área II (p=0,1840). Idade não esteve associada à ADRs. CONCLUSÕES: Doses de tratamento em massa (MDA) ajustadas por peso para a idade e sexo parecem contribuir para redução da ocorrência de ADRs na população.

Influence of anti-filarial chemotherapy strategies on the genetic structure of Wuchereria bancrofti populations

Lymphatic filarial (LF) parasites have been under anti-filarial drug pressure for more than half a century. Currently, annual mass drug administration (MDA) of diethylcarbamazine (DEC) or ivermectin in combination with albendazole (ALB) have been used globally to eliminate LF. Long-term chemotherapies exert significant pressure on the genetic structure of parasitic populations. We investigated the genetic variation among 210 Wuchereria bancrofti populations that were under three different chemotherapy strategies, namely MDA with DEC alone (group I, n = 74), MDA with DEC and ALB (group II, n = 60) and selective therapy (ST) with DEC (group III, n = 34) to understand the impact of these three drug regimens on the parasite genetic structure. Randomly amplified polymorphic DNA profiles were generated for the three groups of parasite populations; the gene diversity, gene flow and genetic distance values were determined and phylogenetic trees were constructed. Analysis of these parameters indicated that parasite populations under ST with a standard dose of DEC (group III) were genetically more diverse (0.2660) than parasite populations under MDA with DEC alone (group I, H = 0.2197) or with DEC + ALB (group II, H = 0.2317). These results indicate that the MDA may reduce the genetic diversity of W. bancrofti populations when compared to the genetic diversity of parasite populations under ST.

A review of neglected tropical diseases: filariasis

Filariasis is result of parasitic infection caused by three specific kinds of round worm. Lymphatic filariasis is found in under developed region of South America, Central Africa, pacific and Caribbian. It has been found for centuries, with main symptoms as elephant like swelling of the arms, legs and genitals. It is estimate that 120 millions peoples in the world have lymphatic filariasis. The spread of diseases and the challenge encountered in its management are discussed along with a review on drugs against filariasis in this article. Detail on clinical effect of drugs on the infection, safety profile, status in clinical practices and drug resistances are also covered.

An allele specific PCR assay for screening for drug resistance among Wuchereria bancrofti populations in India.

Background & objectives: Albendazole, a commonly used anthelminthic drug that targets the polymerization of α- and β-tubulin dimer is currently co-administered with the antifilarial drug, diethylcarbamazine citrate (DEC) in the ongoing Global Programme for Elimination of Lymphatic Filariasis (GPELF). The experience in veterinary field has shown that there can be a rapid development of resistance to this drug, which therefore, needs to be monitored regularly in GPELF. Hence, we investigated the nucleotide polymorphism in the albendazole-binding domain of the isotype 1 β-tubulin gene from several populations of Wuchereria bancrofti and developed an AS-PCR assay useful in screening for sensitive/resistance alleles among parasite populations and also evaluated its utility. Methods: For studying the polymorphism of isotype 1 β-tubulin gene, a 475 bp fragment spanning exon 5 and 6 of the gene was amplified and sequenced from the genomic DNA of W. bancrofti collected from six geographic regions of India. An allele specific (AS) PCR for screening albendazole sensitivity/resistance was developed and a total of 55 mf samples from blood smears on slides collected from Thiruvannamalai, Thanjavur and Puducherry were screened. Selective therapy with DEC was in place in three areas, mass drug administration (MDA) with DEC alone was implemented in four areas, while DEC plus albendazole was administered in one district. Results: The analysis of the nucleotide sequence of the fragment from 20 W. bancrofti populations showed the domain to be highly conserved. An allele-specific PCR assay developed was used to detect sensitive/ resistance alleles among 55 isolates of W. bancrofti and no albendazole resistance alleles were detected among the populations tested. Interpretation & conclusion: The drug-binding domain of isotype 1 β-tubulin gene of W. bancrofti from different geographical locations was highly conserved. The AS-PCR developed showed potential application as a tool for monitoring albendazole sensitivity/resistance alleles among W. bancrofti populations, in areas where combination therapy of DEC-albendazole is being mass administered in the LF elimination programme.

Dirofilariose: zoonose emergente negligenciada: [revisão] / Dirofilariasis: neglected emerging zoonosis: [revision]

A dirofilariose é uma zoonose pouco conhecida causada por Dirofilaria spp., nematódeo mais conhecido como verme do coração dos cães (Dirofilaria immitis), parasita do sistema circulatório desses animais, mas que também pode acometer gatos e o ser humano. Sua ocorrência está intimamente ligada à presença de mosquitos vetores (Aedes spp., Anopheles spp., Culex spp.), condições climáticas favoráveis, assim como trânsito entre regiões indenes e endêmicas/epidêmicas. O ser humano pode se infectar com D. immitis (pulmão), Dirofilaria repens (pulmão, subcutâneo) e Dirofilaria tenuis (subcutâneo). A fisiopatologia está intimamente ligada à morte do parasita onde, no cão, pode induzir a obstrução de vasos circulatórios e no ser humano produzir uma lesão nodular com intensa reação inflamatória no parênquima pulmonar com formato de moeda observada nas radiografias. Pode ser diagnosticada pelo exame físico, pela detecção de microfilárias na circulação sangüínea, imunoadsorção enzimático (ELISA), alterações radiográficas, ecocardiografia, ultrassonografia e necropsia. Há riscos no tratamento, sendo a prevenção com a utilização de drogas nos animais o método mais eficaz, principalmente em visitas a áreas endêmicas ou epidêmicas, diminuindo-se, assim, o risco para saúde pública devido à disseminação do parasita.

Dirofilariasis is an unknown zoonosis, caused by Dirofilaria spp, nematodea most known as dog's heartworm (Dirofilaria immitis), which parasites the vascular system of these animals, but infects cats and human beings too. Its occurrence is highly linked to the presence of mosquitoes (Aedes spp., Anopheles spp., Culex spp.), adequate climatic conditions, as well as the transit between infection-free and endemic/epidemic regions. Human beings can be infected by D. immitis (lung), Dirofilaria repens (lung, subcutaneous) and Dirofilaria tenuis (subcutaneous). The physiopathology is highly dependent of the parasite death, inducing the obstruction of the vascular system in dogs and nodular lesions with intense inflammatory reaction in pulmonary parenchyma, like a coin lesion, observed in the radiographs. It can be diagnosed by physical examination, microfilarias detection on the vascular system, enzymatic immunoadsortion (ELISA), radiographic alterations, echocardiography, ultrasonography and necropsy. There are risks on treatment and drug prevention in animals is the most efficient method, mainly in visits to endemic or epidemic areas, decreasing the risk to public health due to the parasite dissemination.

Subperiodic, asymptomatic microfilaremia in an adult male from Mysore: a nonendemic area.

Wuchereria bancrofti is found throughout tropics and subtropics like Asia, Pacific islands, Africa, areas of South America and Caribbean basin. In all these areas, except Pacific islands, microfilaria occurs in the periodic form, in which case the microfilaria are found in large numbers in the peripheral blood during night. In the Pacific islands, they occur in the subperiodic form, i.e., microfilaria are present in the peripheral blood at all times and reach the maximum level of parasitemia in the afternoon. Microfilaria of Wuchereria bancrofti and Brugia malayi occurring in India displays a nocturnal periodicity, appearing in large numbers at night. This is the biological adaptation to the nocturnal biting habits of the vector mosquitoes. The maximum density in blood is reported between 10 PM and 2 AM. Here is a case report of asymptomatic microfilaremia showing subperiodicity, which is very unusual in India.

Successful Control of Lymphatic Filariasis in the Republic of Korea

A successful experience of lymphatic filariasis control in the Republic of Korea is briefly reviewed. Filariasis in the Republic of Korea was exclusively caused by infection with Brugia malayi. Over the past several decades from the 1950s to 2006, many investigators exerted their efforts to detection, treatment, and follow-up of filariasis patients in endemic areas, and to control filariasis. Mass, combined with selective, treatments with diethylcarbamazine to microfilaria positive persons had been made them free from microfilaremia and contributed to significant decrease of the microfilarial density in previously endemic areas. Significant decrease of microfilaria positive cases in an area influenced eventually to the endemicity of filariasis in the relevant locality. Together with remarkable economic growth followed by improvement of environmental and personal hygiene and living standards, the factors stated above have contributed to blocking the transmission cycle of B. malayi and led to disappearance of this mosquito-borne ancient disease in the Republic of Korea.

Strengthening of mass drug administration implementation is required to eliminate lymphatic filariasis from India: an evaluation study.

BACKGROUND & OBJECTIVES: The mass drug administration (MDA) is one of the strategies to eliminate lymphatic filariasis in India. Eleven districts are endemic for the disease in Madhya Pradesh state of India, which conduct MDA activities annually. A mid-term evaluation was conducted with the objectives to review the progress of the single dose of di-ethyl-carbamazine (DEC) administration, and to understand the functioning of the programme to recommend mid-term amendments. METHODS: A qualitative cross-sectional study was conducted in three endemic districts of Madhya Pradesh between July and October 2007. The teams of faculty members from medical college visited the study districts and collected data by desk review, indepth interviews, on site observations, and from the community. RESULTS: The filaria units in these districts were understaffed. There were no night clinics in two out of the three districts. The sufficient number of trainings for MDA were conducted without any mechanism for quality assurance. There was erratic and inadequate supply of DEC tablets, leading to the postponement of MDA activity, twice. The evaluated coverage with DEC tablets was much lower than that reported by the district officials. The tablet intake was not ensured by the distributors and the compliance rate was in the range of 60-70%. The IEC activities were conducted in limited areas, and there were prevailing myths and misconceptions, contributing to low compliance rate. There was no proper recording of the data on filariasis with gross mismatch at district headquarters and peripheral health facilities. A proportion of community members developed side effects following DEC tablet intake and had to visit private health facilities for treatment. INTERPRETATION & CONCLUSION: This evaluation study noted that MDA is restricted to tablet distribution only and the major issues of implementation in compliance, health education, side effect and morbidity management, and the logistics were not being given due attention. The implementation should be strengthened immediately in the MDA programme in India to achieve the goal of LF elimination by 2015.

Awareness of health personnel about lymphatic filariasis and mass drug administration in Kerala State.

The mass drug administration programme to eliminate lymphatic filariasis with DEC in Kerala was started in 1997, extended to all the 11 endemic districts by 2005. Since the beginning of Mass drug Administration, the drug consumption rate was found to be not satisfactory. The reasons for noncompliance indicated that the community is not fully convinced about the programme. The knowledge of the medical and para medical workers is certainly a factor in the success of implementation of the programme and is vital. To ascertain the knowledge, a study was undertaken and found not satisfactory. Hence intensive training on all aspects of lymphatic filariasis and the Mass drug Administration programme to achieve the requisite drug consumption rate to meet the goal is needed.

Effect of repeated mass chemotherapy for filariasis control on soil-transmitted helminth infections in Sri Lanka.

BACKGROUND: In July 2006 Sri Lanka completed 5 rounds of annual mass drug administration (MDA) with diethylcarbamazine citrate (DEC) and albendazole as part of its national programme for elimination of lymphatic filariasis (LF). Albendazole is highly effective against soil-transmitted helminths (STH). This study was carried out to assess the effect of repeated annual MDA on STH infections in the Western Province of Sri Lanka, an area co-endemic for LF and STH. METHODS: Faecal samples were obtained (during August-September 2006), from grade 5 students in 17 schools in the Western Province that were included in a national survey of schoolchildren's health in 2003, and examined using the modified Kato-Katz technique. The prevalence and intensity of roundworm, whipworm and hookworm infections in 2003 and 2006 were compared. RRESULTS:Faecal samples from 255 children were examined in 2003; 448 were examined in 2006. Roundworm prevalence was marginally lower in 2006 (4.0%) than in 2003 (4.7%), as was hookworm (0.2% vs 0.4%), whereas whipworm prevalence was higher (13.8% vs 9.4%). These differences as well as that between the geometric mean egg counts were not statistically significant. Compliance with MDA in 2006, as reported by the schoolchildren examined, was only 59%. CCONCLUSIONS:Four annual rounds of MDA with DEC and albendazole had virtually no effect on STH infections in the study area.

Acute eosinophilic pneumonia due to round worm infestation.

We report a case of an 18 month old child who presented with sever eosinophilic pneumonia requiring ventilation as a result of round worm infestation. This child presented with symptoms alike acute severe asthma and had high absolute eosinophil count of 9,234/cmm.A course of steroids, albendazole and diethylcarbazine were followed by rapid recovery and a decrease in eosinophil counts to 616/cmm within one month of treatment. This is the first reported case of a child with severe eosinophilic pneumonia requiring ventilation as a result of roundworm infection.

Anti-microfilarial activity of methanolic extract of Vitex negundo and Aegle marmelos and their phytochemical analysis.

In the present study, methanolic extracts of roots of Vitex negundo L. and extracts of leaves of Vitex negundo L., Ricinus communis L. and Aegle marmelos Corr. were explored for possible antifilarial effect against Brugia malayi microfilariae. It was observed that among the herbal extracts, root extract of Vitex negundo L. and leaves extract of Aegle marmelos Corr. at 100 ng/ml concentration showed complete loss of motility of microfilariae after 48 hr of incubation. Thin layer chromatography of the extracts revealed the presence of alkaloids, saponin and flavonoids in the roots of Vitex negundo L. and coumarin in the leaves of Aegle marmelos Corr.

Clinico-laboratory profile of 45 filarial arthritis cases.

This prospective observational study was done during the period from January 2000 to December 2004 including 45 cases of lymphatic filariasis manifested with acute arthritis. Different investigations were carried out to exclude allergy, parasitic and infectious diseases, autoimmune disorder and malignancy. They were given standard treatment with oral non-steroidal anti-inflammatory drugs (NSAIDs). Articular symptoms were not relived satisfactorily. Later they were given oral corticosteroids. During treatment slight relief of symptoms were noted, but all sign-symptoms reappear after withdrawal of corticosteroid drugs. Treatment with oral diethylcarbamazine citrate (DEC) (150 mg/day) for 3 weeks showed complete resolution of arthritis. No side effects or relapse were encountered. The basic mechanism of relief of pain remains unknown. It was assumed that during benign course of lymphatic filariasis, development of arthritis result most likely due to reaction against some occult agents in the joints.

Study on the factors affecting the MDA programme in Kerala state.

The Mass Annual Single dose DEC administration (MDA) was initiated in India from 1997. In Kerala MDA was studied as a pilot project in Alappuzha and Kozhikode District from 2000-04 and the first round of MDA was launched in Kerala covering eleven endemic districts, in March 2005. On evaluation, the drug distribution coverage, compliance, etc. were found to be not satisfactory and a need to elicit the factors for poor performance of MDA is felt essential. The main reasons for poor performance of MDA in Kerala state were the lack of adequate prior information to the target population regarding the importance LF elimination programme and inadequate awareness. The fear of side reactions, antipropagonda, poor IEC activities repeated postponement of programme, insufficient time for mobilisation etc. were the other reasons for poor compliance. The purpose of the present study was to bring the observations to the notice of the authorities so that appropriate remedial measures are incorporated.

Adverse reactions of 300 MG diethylcarbamazine, and in a combination of 400 MG albendazole, for a mass annual single dose treatment, in migrant workers in Phang Nga province.

BACKGROUND: Foreign migrant workers with work permits in Thailand are given once a year 300 mg diethyl-carbamazine (DEC) for bancroftian filariasis, and 400 mg albendazole (ABZ) for helminthiasis. Treatment effectiveness, tolerability, and safety of two treatment arms, DEC + ABZ and DEC alone, had never been fully documented. OBJECTIVE: Evaluate the tolerability of the two treatment arms and analyze the effects of adverse reaction, prevalence, and intensity of both common and uncommon adverse drug reactions (ADR) in relation to the reaction time (2 hours = acute, > 2 to 24 hours = subacute, and > 24 to 72 hours = latent). MATERIAL AND METHOD: A hospital-based clinical study of on-hour-2 treatment with both treatment arms in 280 Myanmar male migrant volunteers (DEC + ABZ = 150, DEC = 130) was conducted in Phang Nga province, southern Thailand Of these, ADR evaluation at three reaction times was performed using antigenemic (WbAg+) and non-antigenemic (WbAg-) volunteer groups (DEC + ABZ/WbAg+ = 14, DEC/WbAg+ = 12, DEC + ABZ/ WbAg- = 8, andDEC/WbAg- = 16). RESULTS: Both drug groups had similarly overall ADR prevalence [5.2%for DEC + ABZ and 5. 1% for DEC (p > 0. 05)], as well as mean ADRacute scores (p > 0. 05) on hour 2 post-treatment. The four groups had maximum overall prevalence (10% to 40%for ADRsubacute). It was more likely to show no relationship between treatment arms and WbAg (neither WbAg+ nor WbAg-) with adverse reaction intensity for ADRacute, ADRsubacute, Or ADRlatent Three major specific ADR were fatigue, dizziness, and headache. CONCLUSION: Adverse reaction prevalence and intensity were independent for WbAg and treatment arm. The DEC + ABZ have no greater effects on ADR development as the DEC does. The common ADR after treatment are not required for symptomatic treatment. The study confirms DEC + ABZ regime can be safe and not toxic for use in mass treatment of those migrants in Thailand and, its value, in a mass annual single dose treatment, is beneficial for the Global Alliance to Eliminate of Lymphatic Filariasis (GAELF).