Augmented Innate and Adaptive Immune Responses Under Conditions of Diabetes–Filariasis Comorbidity

Metainflammation, as seen in chronic diabetes subjects, impairs immunity and increases the susceptibility to infections. In the present study, the effect of diabetes on immune response against filariasis was studied. Both toll-like receptor (TLR)-mediated and crude antigen-induced immune responses were quantified, in whole blood cultures from filariasis-infected subjects (LF+), with and without diabetes. Blood cultures were stimulated with TLR ligands (TLR2 and TLR4) or filarial antigen or were left unstimulated (control) for 18 h. Cytokine, chemokine, and defensin secretion was quantified by ELISA. Expression of HLA-DR, B7-1, B7-2, activation marker (CD69), and Th (Th1, Th2, Th17, and Th9) phenotypes was quantified by flow cytometry. Expression of immunomodulatory effectors (Cox-2, HO-1, IDO-1, and p47Phox) and Th-polarizing transcription factors (T-bet, GATA3, and ROR-γt) was quantified by quantitative PCR. Secretion of IL-27, IL-1Ra, IL-12, IL-33, IL-9, and SDF-1 was increased under diabetes conditions with increased Th9 polarization and increased expression of Cox-2 and IDO. Overall, diabetes was found to augment both TLR-mediated and antigen-induced inflammation, which can promote chronic pathology in LF+ subjects.

Comparison of Immunochromatographic Test (ICT) and Filariasis Test Strip (FTS) for Detecting Lymphatic Filariasis Antigen in American Samoa, 2016

Circulating filarial antigen (Ag) prevalence, measured using rapid point-of-care tests, is the standard indicator used for monitoring and surveillance in the Global Program to Eliminate Lymphatic Filariasis. In 2015, the immunochromatographic test (ICT) was replaced with the filariasis test strip (FTS), which has higher reported sensitivity. Despite differences in sensitivity, no changes in recommended surveillance targets were made when the FTS was introduced. In 2016, we conducted lymphatic filariasis surveys in American Samoa using FTS, which found higher Ag prevalence than previous surveys that used ICT. To determine whether the increase was real, we assessed the concordance between FTS and ICT results by paired testing of heparinised blood from 179 individuals (63% FTS-positive). ICT had 93.8% sensitivity and 100% specificity for identifying FTS-positive persons, and sensitivity was not associated with age, gender, or presence of microfilariae. Based on these findings, if ICT had been used in the 2016 surveys, the results and interpretation would have been similar to those reported using FTS. American Samoa would have failed Transmission Assessment Survey (TAS) of Grade 1 and 2 children with either test, and community prevalence would not have been significantly different (4.1%, 95% CI, 3.3–4.9% with FTS vs. predicted 3.8%, 95%, CI: 3.1–4.6% with ICT).

EVALUATION OF LYMPHATIC FILARIASIS AFTER TWO ROUNDS OF MASS DRUG ADMINISTRATION IN LAU LOCAL GOVERNMENT AREA OF TARABA STATE NIGERIA

This study was undertaken to evaluate the effects of Mass Drug Administration (MDA) on Wuchereria bancrofti (microfilariae) after two rounds of combined Ivermectin and Albendazole distribution. A total of 221 participants were recruited in three communities in Lau Local Government Area of Taraba State by convenience sampling method. Questionnaires and physical examinations were used to assess clinical manifestations associated with the infection. Blood samples were collected by finger prick method and stained with Giemsa stain for examination to establish the presence of W. bancrofti while immunochromatographic card test was performed to determine the presence of filarial antigen in serum. Previous data were used to determine the pre-drug prevalence of the parasite. The results showed that the drug did not significantly reduce the clinical manifestations reported among the patients. The microfilariae prevalence and microfilaria mean density after two rounds of drug administration was 19.5% and 1.49%, while the pre- MDA prevalence and microfilaria mean density was 27.8% and 2.44% respectively. There was a statistically significant decrease of microfilaria prevalence (P<0.05) after two rounds of MDA. There was no significant effect of MDA by age, sex and occupation-related microfilariae prevalence in the study area. In conclusion, the study reveals that microfilaria prevalence and load decreased after two rounds of MDA of combined Ivermectin and Albendazole distribution amongst the studied populations. Routine evaluation of the MDA is required to assess the impact of the drug for the eventual elimination of the infection.

#56: A novel test for diagnosis and surveillance of Wuchereria bancrofti infection

Background Elephantiasis or Lymphatic filariasis (LF) is a parasitic infection that causes significant morbidity and impacts hundreds of millions of people in 73 countries. Most LF is caused by the nematode Wuchereria bancrofti, but Brugia species cause LF in some areas of Southeast Asia. The global program to eliminate LF uses mass drug administration (MDA) of antifilarial drugs in endemic areas to kill the microfilaria (MF) stage of the parasite that is required for ongoing transmission by mosquitos. Better tools are needed for assessing the success of MDA, because of limitations of available diagnostic tests. MF testing is often not feasible, because it requires collection of blood at night in most endemic areas. Existing antibody and antigen tests remain positive long after effective treatment, and their results do not correlate well with current infectivity. The Brugia Rapid test detects antibodies to BmR1, a Brugia protein that is expressed by MF. These antibodies disappear 2–3 years after effective treatment, and that makes the Brugia Rapid test a useful marker for persistent infection in the few countries with brugian filariasis. We set out to develop a novel antibody test for W. bancrofti infection based on a BmR1 homologue in W. bancrofti. Methods We cloned, expressed and purified a Wuchereria bancrofti protein (provisional name WbN1) that is a homologue of the Brugia malayi protein BmR1. Sera from patients infected with Wuchereria bancrofti as well as sera from patients infected with other closely related filarial species were tested for IgG4 antibodies to WbN1 by indirect ELISA. Results The ELISA has a sensitivity of 90.7% for infection with W. bancrofti based on the 80 bancrofti patient samples tested thus far. Specificity was 91.5% with 59 sera samples from patients infected with Onchocerca volvulus or Loa loa, which are filarial parasites that are co-endemic with W. bancrofti in Africa. Specificity was 97.9% with North American control samples. ELISA with sera from a clinical trial in Sri Lanka demonstrated that antibodies to WbN1 decreased significantly faster after treatment than antibodies to the previously described filarial antigen Bm14. Similar declines in antibody to WbN1 occurred after patients in Papua New Guinea received a single dose of triple drug treatment for LF with Ivermectin Diethylcarbamazine and Albendazole, that is effective for clearing MF from the blood without clearing filarial antigenemia. Conclusions While additional studies are needed, this ELISA for IgG4 antibody to the recombinant protein WbN1 could be a promising new surveillance tool for assessing for ongoing transmission of LF following MDA.

An open label, randomized clinical trial to compare the tolerability and efficacy of ivermectin plus diethylcarbamazine and albendazole vs. diethylcarbamazine plus albendazole for treatment of brugian filariasis in Indonesia

Improved treatments for lymphatic filariasis (LF) could accelerate the global elimination program for this disease. A triple drug combination of the anti-filarial drugs ivermectin, diethylcarbamazine (DEC) and albendazole (IDA) has been shown to be safe and effective for achieving sustained clearance of microfilariae (Mf) of the filarial parasite Wuchereria bancrofti from human blood. However, the triple drug combination has not been previously been evaluated for treatment of brugian filariasis, which accounts for about 10% of the global LF burden. This hospital-based clinical trial compared the safety and efficacy of IDA with that of the standard treatment (DEC plus albendazole, DA) in persons with Brugia timori infections on Sumba island, Indonesia. Fifty-five asymptomatic persons with B. timori Mf were treated with either a single oral dose of IDA (28 subjects) or with DEC plus albendazole (DA, 27 subjects). Participants were actively monitored for adverse events (AE) for two days after treatment by nurses and physicians who were masked regarding treatment assignments. Passive monitoring was performed by clinical teams that visited participant’s home villages for an additional five days. Microfilaremia was assessed by membrane filtration of 1 ml night blood at baseline, at 24h and one year after treatment. IDA was more effective than DA for completely clearing Mf at 24 hours (25/28, 89% vs. 11/27, 41%, P < 0.001). By 12 months after treatment, only one of 28 IDA recipients had Mf in their blood (4%) vs. 10 of 27 (37%) in persons treated with DA (P = 0.002). Approximately 90% of participants had antibodies to recombinant filarial antigen BmR1 at baseline. Antibody prevalence decreased to approximately 30% in both treatment groups at 12 months. About 45% of persons in both treatment groups experienced AE such as fever, muscle aches, lower back, joint and abdominal pain. These were mostly mild and most common during the first two days after treatment. No participant experienced a severe or serious AE. This study showed that IDA was well-tolerated and significantly more effective for clearing B. timori Mf from the blood than DA. Larger studies should be performed to further assess the safety and efficacy of IDA as a mass drug administration regimen to eliminate brugian filariasis. Trial Registration: NCT02899936.

IL-10 and Its Related Superfamily Members IL-19 and IL-24 Provide Parallel/Redundant Immune-Modulation in Loa loa Infection

Background Interleukin-10 (IL-10) has been implicated as the major cytokine responsible for the modulation of parasite-specific responses in filarial infections; however, the role of other IL-10 superfamily members in filarial infection is less well studied. Methods Peripheral blood mononuclear cells from loiasis patients were stimulated with or without filarial antigen. Cytokine production was quantified using a Luminex platform and T-cell expression patterns were assessed by flow cytometry. Results All patients produced significant levels of IL-10, IL-13, IL-5, IL-4, and IL-9 in response to filarial antigen, indicating a common infection-driven response. When comparing microfilaria (mf)-positive and mf-negative patients, there were no significant differences in spontaneous cytokine nor in parasite-driven IL-10, IL-22, or IL-28a production. In marked contrast, mf-positive individuals had significantly increased filarial antigen-driven IL-24 and IL-19 compared to mf-negative subjects. mf-positive patients also demonstrated significantly higher frequencies of T cells producing IL-19 in comparison to mf-negative patients. T-cell expression of IL-19 and IL-24 was positively regulated by IL-10 and IL-1β. IL-24 production was also regulated by IL-37. Conclusion These data provide an important link between IL-10 and its related family members IL-19 and IL-24 in the modulation of the immune response in human filarial infections. Clinical Trials Registration NCT00001230.

Incidence of filariasis in clinically diagnosed primary vaginal hydrocele

Background: Lymphatic filariasis is caused by a mosquito-borne parasite affecting roughly 100 million people round the world. There is consensus that hydrocele is the most frequent clinical manifestation of bancroftian filariasis. In endemic areas, about 40% of men are suffering from testicular hydrocele. With this background, the present study was aimed to find the incidence of filariasis in clinically diagnosed primary vaginal hydrocele.Methods: A hospital based prospective, cross-sectional study was conducted with 60 patients diagnosed clinically as primary vaginal hydrocele coming to the department of surgery, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune, to assess the incidence of filariasis.Results: Anti-filarial antibody and circulating filarial antigen in serum were detected in 5 (8.3%). Out of 60 patients and anti-filarial antibody was detected in hydrocele fluid of 2 (3.3%) patients. 2 patients out of these 5 showed microfilaria in peripheral blood smear and eosinophilic infiltrates in histopathological examination of sac.Conclusions: In 5 out of 60 cases both anti-filarial antibody and circulating filarial antigen in serum are positive thus proving that incidence of filarial hydrocele is 8% in clinically diagnosed primary vaginal hydrocele which is supposed to be idiopathic. Even though these cases have presented as clinically primary vaginal hydrocele, they are found to be filarial hydrocele after analysis of serum and hydrocele fluid. So, it is advised that all cases of clinically diagnosed primary vaginal hydroceles should be investigated for filariasis and if not, may lead to recurrence in these cases.

Chyluria: An Unending Illness- A Case Report

Chyluria is the passage of milky urine due to a lymphourinary fistula. It is secondary to lymphatic stasis caused by obstruction of the lymphatic flow. It is caused by the parasite Wuchereria bancrofti in more than 95% of cases in tropical countries. Chyluria occurs in 2% of filarial-infested patients. When an abnormal connection between intestinal lacteals and the urinary tract develops, chyluria appears. The diagnostic approach is aimed to define the site of lymphourinary fistula. It is a benign disease that can be controlled by medical treatment and dietary restrictions. A small number of patients require surgical intervention. The 45-year-old thin built woman was suffering from chyluria, flank pain in the abdomen, weakness and loss of weight for the last 10 years. The serum test for circulating adult filarial antigen was positive in moderately high titer. Antifilarial treatment was advised. The symptoms improved for three months and again relapsed.

Dengue Co-Infection Microfilaria Presenting with Intestinal Obstruction: A Case Report

In the recent years morbidity caused by dengue epidemic has been devastating. Confection of dengue malaria and filaria has been reported in literature where in filarial antigen was detected in the patient. Concurrent infection by dengue and filaria with high parsetemic microfilariae load in a single individual is very rarely known. The varied clinical profile in dengue is multifactorial and concurrent co-infection may be one of them. Here in this case of concurrent infection with dengue and filarial, the patient presented with intestinal obstruction which responded dramatically with diethylcarbamizine while other clinicalsyndrome took a long time. Furthermore, if single vector can harbour both the infectious agent, the etiopathogenesis may completely take a different turn and at times project alarming condition. J Bangladesh Coll Phys Surg 2019; 37(1): 35-38