Wayne Melrose

A proof of concept study establishing Necator americanus in Crohn’s patients and reservoir donors

The emergence of autoimmunity, including Crohn’s disease (CD) where the immune relationship with commensal bacteria is corrupted, has been linked to hygiene.1,2 A gradual decline in endoparasites is but one argument that might explain this phenomenon.3 Weinstock and colleagues have successfully tested the pig whipworm, Trichuris suis , in patients with inflammatory bowel disease (IBD).4,5 However, repeated inoculation was required and concern has been raised that aberrant migration could occur.6 The haematophagous hookworm, Necator americanus (NA), is proposed as an alternative. We have tested if CD patients tolerate hookworm infection, and the practical issues associated with establishing reservoir donors (RDs). Over 700 million people remain infected with hookworms. Infective larvae (L3i) are acquired through skin contact with contaminated soil.7 Auto-reinfection, direct person to person infection, aberrant migration, and hypobiosis do not occur. Adult worms live …

Lymphatic filariasis: new insights into an old disease

Lymphatic filariasis has afflicted people in the tropical areas of the world for thousands of years but even up to comparatively recent times it has been poorly understood and its importance under recognised. In the last 2 decades or so there has been a flurry of activity in filariasis research, which has provided new insights into the global problem of filariasis, the pathogenesis of filarial disease, diagnosis and control.

A multicenter evaluation of diagnostic tools to define endpoints for programs to eliminate bancroftian filariasis

Successful mass drug administration (MDA) campaigns have brought several countries near the point of Lymphatic Filariasis (LF) elimination. A diagnostic tool is needed to determine when the prevalence levels have decreased to a point that MDA campaigns can be discontinued without the threat of recrudescence. A six-country study was conducted assessing the performance of seven diagnostic tests, including tests for microfilariae (blood smear, PCR), parasite antigen (ICT, Og4C3) and antifilarial antibody (Bm14, PanLF, Urine SXP). One community survey and one school survey were performed in each country. A total of 8,513 people from the six countries participated in the study, 6,443 through community surveys and 2,070 through school surveys. Specimens from these participants were used to conduct 49,585 diagnostic tests. Each test was seen to have both positive and negative attributes, but overall, the ICT test was found to be 76% sensitive at detecting microfilaremia and 93% specific at identifying individuals negative for both microfilariae and antifilarial antibody; the Og4C3 test was 87% sensitive and 95% specific. We conclude, however, that the ICT should be the primary tool recommended for decision-making about stopping MDAs. As a point-of-care diagnostic, the ICT is relatively inexpensive, requires no laboratory equipment, has satisfactory sensitivity and specificity and can be processed in 10 minutes—qualities consistent with programmatic use. Og4C3 provides a satisfactory laboratory-based diagnostic alternative.

Understanding the community impact of lymphatic filariasis: a review of the sociocultural literature

Lymphatic filariasis (LF) is endemic in approximately 80 tropical and subtropical countries. About 120 million people are infected with the parasite and a billion are estimated to be at risk of infection. The main focus of the LF elimination programme to date has been to interrupt transmission by means of annual community-wide treatment campaigns with diethylcarbamazine and albendazole, or albendazole and ivermectin, for a period of four to six years. Although substantial progress has been recorded wherever the strategy has been successfully implemented, initial gains have been accompanied by a realization that this strategy alone will not ensure a permanent solution in all settings. The fairly extensive LF literature is dominated by laboratory research and quantitative field measurement of the impact of LF, particularly local prevalence studies of parasite-infected humans and vectors. As the global elimination programme expands, the absence of sociocultural understanding is being recognized as a critical flaw in ensuring that programmes are appropriate and responsive to local needs and understanding. This paper assesses the current state of sociocultural understanding pertaining to LF. It concludes that, at present, there is insufficient understanding of the sociocultural factors associated with the presence and treatment of the disease, and that appropriate social science methods should be used to address this deficiency and ensure community partnership in delivering and sustaining the success of LF elimination programmes.

The emerging story of disability associated with lymphatic filariasis: a critical review.

Globally, 40 million people live with the chronic effects of lymphatic filariasis (LF), making it the second leading cause of disability in the world. Despite this, there is limited research into the experiences of people living with the disease. This review summarises the research on the experiences of people living with LF disability. The review highlights the widespread social stigma and oppressive psychological issues that face most people living with LF-related disability. Physical manifestations of LF make daily activities and participation in community life difficult. The findings confirm the need for the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support morbidity management activities that address the complex biopsychosocial issues that people living with LF-related disability face.

A multicenter evaluation of a new antibody test kit for lymphatic filariasis employing recombinant Brugia malayi antigen Bm-14

Antibody tests are useful for mapping the distribution of lymphatic filariasis (LF) in countries and regions and for monitoring progress in elimination programs based on mass drug administration (MDA). Prior antibody tests have suffered from poor sensitivity and/or specificity or from a lack of standardization. We conducted a multicenter evaluation of a new commercial ELISA that detects IgG4 antibodies to the recombinant filarial antigen Bm14. Four laboratories tested a shared panel of coded serum or plasma samples that included 55 samples from people with microfilaremic Wuchereria bancrofti or Brugia infections and 26 control samples. Qualitative results were identical in all four test sites. In addition, each laboratory tested samples from their own serum banks. The test detected antibodies in 32 of 36 samples (91%) from people with Brugian filariasis and in 96 of 98 samples (98%) from people with Bancroftian filariasis. Specificity testing showed that many serum or plasma samples from patients with other filarial infections such as onchocerciasis had positive antibody tests. Specificity was otherwise excellent, although 3 of 30 samples from patients with ascariasis and 4 of 51 with strongyloidiasis had positive antibody tests; it is likely that some or all of these people had previously lived in filariasis-endemic areas. Antibody test results obtained with eluates from blood dried on filter paper were similar to those obtained with plasma tested at the same dilution. This test may be helpful for diagnosing LF in patients with clinical signs of filariasis. It may also be a useful tool for use in LF endemic countries to monitor the progress of filariasis elimination programs and for post-MDA surveillance.

Seroprevalence and spatial epidemiology of lymphatic filariasis in American Samoa after successful mass drug administration

Background As part of the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000–2006, and passed transmission assessment surveys in 2011–2012. We examined the seroprevalence and spatial epidemiology of LF post-MDA to inform strategies for ongoing surveillance and to reduce resurgence risk. Methods ELISA for LF antigen (Og4C3) and antibodies (Wb123, Bm14) were performed on a geo-referenced serum bank of 807 adults collected in 2010. Risk factors assessed for association with sero-positivity included age, sex, years lived in American Samoa, and occupation. Geographic clustering of serological indicators was investigated to identify spatial dependence and household-level clustering. Results Og4C3 antigen of >128 units (positive) were found in 0.75% (95% CI 0.3–1.6%) of participants, and >32 units (equivocal plus positive) in 3.2% (95% CI 0.6–4.7%). Seroprevalence of Wb123 and Bm14 antibodies were 8.1% (95% CI 6.3–10.2%) and 17.9% (95% CI 15.3–20.7%) respectively. Antigen-positive individuals were identified in all ages, and antibody prevalence higher in older ages. Prevalence was higher in males, and inversely associated with years lived in American Samoa. Spatial distribution of individuals varied significantly with positive and equivocal levels of Og4C3 antigen, but not with antibodies. Using Og4C3 cutoff points of >128 units and >32 units, average cluster sizes were 1,242 m and 1,498 m, and geographical proximity of households explained 85% and 62% of the spatial variation respectively. Conclusions High-risk populations for LF in American Samoa include adult males and recent migrants. We identified locations and estimated the size of possible residual foci of antigen-positive adults, demonstrating the value of spatial analysis in post-MDA surveillance. Strategies to monitor cluster residents and high-risk groups are needed to reduce resurgence risk. Further research is required to quantify factors contributing to LF transmission at the last stages of elimination to ensure that programme achievements are sustained.

Quantification of blood intake of the head louse: Pediculus humanus capitis

Although head lice, Pediculus humanus capitis, are globally prevalent blood‐sucking ectoparasites, the amount of blood imbibed by head lice has not been determined. This study investigated this parameter, as regular loss of a small quantity of blood may lead to an iron deficiency and anaemia. Adult female lice (66), adult males (46), and nymphs (152) were weighed before and after feeding in groups of 17–109 lice. The average amounts of blood imbibed at a single feed were: adult female louse (0.0001579 ml), adult male (0.0000657 ml) and nymph (0.0000387 ml). Assuming three feeds per day by an average infection of 30 lice (10 females, 10 males, and 10 nymphs), the average child with active pediculosis would loose 0.008 ml of blood per day. This amount of blood loss is of no clinical significance even in iron‐deficient children. The most heavily infected child observed with 2657 lice could be expected to loose 0.7 ml/day or 20.8 ml/month, which may be of clinical importance in a child on an adequate diet, and would be significant in an iron‐deficient child. However, if head lice feed more often than three times a day, a heavy infestation would have a greater potential to lead to iron deficiency. The frequency of feeding of head lice on the head of the human host needs to be determined.

Epidemiological assessment of continuing transmission of lymphatic filariasis in Samoa.

Abstract Ongoing transmission of lymphatic filariasis (LF) was assessed in five Samoan villages by measuring microfilaraemia (Mf), circulating filarial antigen (CFA) and antibody prevalence. Compared to the other villages, Fasitoo-Tai had a significantly higher Mf prevalence (3·2%), CFA prevalence (14·6%) and antibody prevalence in children (62·0%) (P<0·05). Puapua had a significantly lower CFA prevalence (2·5%), no detectable Mf-positive individuals and significantly low antibody prevalence in children (7·9%) (P<0·05). Siufaga, previously believed to be LF-free, recorded >1% CFA prevalence and a high antibody prevalence in children (46·6%). Overall, antibody prevalence in children appeared to reflect the transmission dynamics in the villages and, in Siufaga, identified an area of ongoing transmission. The Filariasis Cellabs Enzyme-Linked Immunosorbent Assay (CELISA), based on recombinant antigen Bm14, to detect antibodies, could potentially be a promising diagnostic tool for inclusion in future surveillance in the South Pacific.

Short communication : Strengthening sub-national communicable disease surveillance in a remote Pacific Island country by adapting a successful African outbreak surveillance model

Successful communicable disease surveillance depends on effective bidirectional information flow between clinicians at the periphery and communicable disease control units at regional, national and global levels. Resource‐poor countries often struggle to establish and maintain the crucial link with the periphery. A simple syndrome‐based outbreak surveillance system initially developed and evaluated in Mpumalanga Province, South Africa was adapted for the Pacific island nation of Tuvalu. Eight syndromes were identified for surveillance: acute flaccid paralysis (poliomyelitis), profuse watery diarrhoea (cholera), diarrhoea outbreak, dysentery outbreak, febrile disease with abdominal symptoms and headache (typhoid), febrile disease with generalized non‐blistering rash (measles), febrile disease with intense headache and/or neck stiffness with or without haemorrhagic rash (meningococcal meningitis), and outbreaks of other febrile diseases of unknown origin. A user‐oriented manual, the Tuvalu Outbreak Manual (http://www.wepi.org/books/tom/), was developed to support introduction of the surveillance system. Nurses working in seven outer island clinics and the hospital outpatient department on the main island rapidly report suspected outbreaks and submit weekly zero‐reports to the central communicable disease control unit. An evaluation of the system after 12 months indicated that the Outbreak Manual was regarded as very useful by clinic nurses, and there was early evidence of improved surveillance and response to the disease syndromes under surveillance.