Loa loa: Immunological Responses During Experimental Infections in Mandrills (Mandrillus sphinx)

Pinder, Margaret; Everaere, S.; Roelants, Georges E.

doi:10.1006/expr.1994.1072

Cited by 27 publications

(32 citation statements)

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“…loa model, antibodies to the mf sheath were detected in the prepatent period only, and subsequently disappeared shortly before the onset of patency. 31 A similar sequence in human Bancroftian filariasis could explain the high child to adult ratio in prevalence of IFAT positivity, as well as the occurrence of IFAT positivity only in category 3 of the adult study population seen in the present study. In addition to being mf negative, the majority of the IFAT-positive individuals (88% for study 1 and 2 combined) were also CIA negative.…”

Section: Discussionsupporting

confidence: 67%

Bancroftian filariasis in Tanzania: specific antibody responses in relation to long-term observations on microfilaremia.

Simonsen¹,

Meyrowitsch²

1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. Following a 16-year clinical and parasitologic follow-up survey for Bancroftian filariasis in three endemic communities in northeastern Tanzania, serum antibody responses were analyzed in selected individuals in relation to the long-term observations on microfilaremia. Comparison of responses in three categories of adults (microfilaria [mf] positive at both surveys, mf positive at first but mf negative at the second survey, and mf negative at both surveys, respectively) indicated no significant differences between the mean levels of filarial-specific IgG1, IgG2, IgG3, IgG4, or IgE (measured by ELISA). However, specific IgG2 to the sheath of Wuchereria bancrofti mf (measured by an indirect fluorescence antibody test [IFAT]) was detected only in the third category. Comparison of responses in two categories of children born around the time of the first survey (to mf-positive and mf-negative mothers, respectively) showed a significantly higher mean level of filarial-specific IgG4 in the first than in the latter category, whereas the mean levels of filarial-specific IgG1, IgG2, IgG3, and IgE, and the prevalences of IgG2 IFAT positivity were similar. The overall prevalence of IgG2 IFAT positivity was considerably higher in the child study population (45.5%) than in the adult study population (16.7%). In both populations, however, a clear association between IgG2 IFAT positivity and a negative microfilarial status and negative specific circulating antigen status was seen. The study suggests that specific anti-sheath-antibodies are associated with an immunologic resistance mechanism that in the endemic community is expressed with highest prevalence in young individuals before development of patent microfilaremia.Despite the widespread occurrence of Wuchereria bancrofti infections in tropical areas, many aspects of the natural history of infection and disease in Bancroftian filariasis remain poorly understood. Basic knowledge on determinants related to host susceptibility, the longevity of infection and development of resistance, being of utmost importance for understanding the epidemiology of Bancroftian filariasis and for planning and implementation of control programs, is lacking. 1-3 A major reason for this is a scarcity of longitudinal studies.In an attempt to clarify some of these aspects, a 16-year follow-up study was carried out on Bancroftian filariasis in three endemic communities in northeastern Tanzania. All individuals were examined for microfilariae and clinical manifestations in 1975 4 and again in late 1991, 5 and as many as possible of the individuals examined in the first surveys were re-identified in the second surveys. Analyses of the parasitologic and clinical findings have already been presented. 5,6 Briefly, with respect to microfilaremia, the study showed that only few individuals had changed from a microfilaria (mf)-positive to -negative status over the 16-year period, despite the fact that the average life span of adult worms has been estimated to be much shorter. 1 In the 1991 survey...

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Section: Discussionsupporting

confidence: 67%

Bancroftian filariasis in Tanzania: specific antibody responses in relation to long-term observations on microfilaremia.

Simonsen¹,

Meyrowitsch²

1998

The American Journal of Tropical Medicine and Hygiene

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“…Previous studies have reported elevated rates of antibody in Mf ¹ patients, compared with Mf þ subjects [6], and the protective role of antibodies against Mf [6][7][8][9].…”

mentioning

confidence: 99%

T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics

Baize

Wahl

Soboslay

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe proliferation and cytokine profiles of peripheral blood mononuclear cells (PBMC) from microfilaraemic (Mf þ ) subjects infected by Loa loa in response to antigens of several parasitic stages were compared with those from amicrofilaraemic (Mf ¹ ) individuals. While a strong lymphoproliferative response and consistent levels of both Th1 (IL-2, interferon-gamma (IFN-g)) and Th2 (IL-4, IL-5) type cytokines were observed in response to adult worm (AW) and microfilariae (Mf) antigen in Mf ¹ individuals, Mf þ subjects were characterized by a T cell unresponsiveness, including proliferation, cytokine production and IL-2 mRNA expression. Conversely, T cell responsiveness to mitogens and non-specific antigen were similar in the two endemic populations. Depletion of lymphocyte subpopulations indicated that T CD4 þ were mainly involved in the specific cellular response. In contrast to other cytokines, IL-10 was produced in response to all parasitic stages, in both Mf þ and Mf ¹ patients. Neutralization of IL-10 did not restore cytokine production in Mf þ patients, while B7 mRNA expression was similar between Mf þ and Mf ¹ subjects in response to Mf antigen, suggesting that IL-10 was not the only factor responsible for T cell unresponsiveness. Mf þ patients have lower Mf antigen-specific IgG levels compared with Mf ¹ , and there is a significant correlation between Mf antigen-specific antibodies and IL-5 responses. These findings suggest that Mf ¹ status is correlated with T helper responsiveness, including proliferation and production of both Th1-and Th2-type cytokines, whereas Mf þ status is characterized by unresponsiveness of the same cell population, induced and/or maintained by microfilariae.

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“…17 The usefulness of this assay in detecting L. loa in humans has been previously described. [18][19][20][21][22] In this paper, we demonstrate the ability of this 15r3-PCR assay to follow L. loa experimental infection in M. sphinx. We also confirm that L. loa-specific DNA can be detected in blood from occultly infected mandrills (infection without peripheral blood microfilariae).…”

Section: Resultsmentioning

confidence: 99%

“…Kinetics of the infection exhibit the appearance of peripheral blood microfilariae about 5 months postinfection, as also reported in drills [23][24][25] and other monkeys such as baboons, macaques, 26 and mandrills. 19 Although the course of L. loa infection in mandrills is closely related to that seen in humans, there are some differences. The most important difference for diagnosis purposes is the parasite load during experimental infection.…”

Section: Resultsmentioning

confidence: 99%

“…However, since 1990 it has been shown that the mandrill (Mandrillus sphinx) can be experimentally infected with human L. loa. 19 Moreover, the evolution of infection is closely related to that seen in humans after long-term follow-up. 20 The aim of the present study was to investigate the ability to detect and to followup the evolution of human L. loa experimental infection in mandrills using a PCR assay.…”

Section: 18mentioning

confidence: 97%

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Use of polymerase chain reaction for accurate follow-up of Loa loa experimental infection in Mandrillus sphinx.

Touré¹,

Ungeheuer²,

Egwang³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Mandrills (Mandrillus sphinx) experimentally infected with human Loa loa usually remain microfilaremic for a long period of time. Nevertheless some control their microfilaremia while still harboring adults worms, and therefore become occult-infected. A nested polymerase chain reaction (PCR) assay, targeted on the repeat 3 region of the gene coding for the L. loa 15-kD protein (15r3-PCR), has been evaluated in mandrills infected with third-stage larvae (L3) of L. loa. The results of this assay were negative during the prepatency period (4 months after inoculation), but became positive when microfilariae appeared in the blood, and remained positive in all mandrills, even in those that became amicrofilaremic. These results show that the positivity of the 15r3-PCR assay is linked to the appearance of microfilariae in peripheral blood and demonstrated that L. loa-specific DNA can be detected in blood from occult-infected mandrills.Loa loa is a filarial parasite transmitted by tabanid flies that is limited to the rain forest of central and west Africa. 1 This parasite has been estimated to cause chronic infection in as many as 13 million people. The disease is usually characterized by localized angioedema, arthralgia, or ocular problems caused by subconjunctival migration of the adult worms. In exceptional cases, serious sequelae such as endomyocardial fibrosis, 2 renal and pulmonary complications, 3,4 and encephalitis after administration of diethylcarbamazine 5,6 have been reported.In endemic areas, 20-30% of residents are microfilaremic, 7,8 and about twice as many are occult infected, harboring adult worms without showing microfilaremia. 9,10 Microscopy is universally used for both collection of epidemiologic data and medical diagnosis of loiasis, but this method is unable to detect occult infection. Various antibody-based assays have been used to measure host antibodies in L. loa-exposed or -infected individuals, 11 but these assays are not able to distinguish between past and current infection, nor can they be used to assess the efficacy of chemotherapeutic agents. 12 Currently, to overcome these problems, polymerase chain reaction (PCR) assays have been developed to detect several filarial species in blood from infected individuals: Brugia malayi, 13 Wuchereria bancrofti, [14][15][16] and L. loa. 17,18Research on the L. loa parasite has been hampered by the lack of a suitable animal model. However, since 1990 it has been shown that the mandrill (Mandrillus sphinx) can be experimentally infected with human L. loa. 19 Moreover, the evolution of infection is closely related to that seen in humans after long-term follow-up. 20 The aim of the present study was to investigate the ability to detect and to followup the evolution of human L. loa experimental infection in mandrills using a PCR assay. MATERIALS AND METHODS Animals.Twelve 2-5-year-old M. sphinx housed at the CIRMF Primate Center were screened for the presence of microfilariae in blood by leukoconcentration and by PCR. Eight had negative results b...

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Loa loa: Immunological Responses During Experimental Infections in Mandrills (Mandrillus sphinx)

Cited by 27 publications

References 0 publications

Bancroftian filariasis in Tanzania: specific antibody responses in relation to long-term observations on microfilaremia.

Bancroftian filariasis in Tanzania: specific antibody responses in relation to long-term observations on microfilaremia.

T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics

Use of polymerase chain reaction for accurate follow-up of Loa loa experimental infection in Mandrillus sphinx.

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