Human occult loiasis: field evaluation of a nested polymerase chain reaction assay for the detection of occult infection

Touré, Fousseyni S.; Mavoungou, Elie; Kassambara, Lalla; Williams, Tim; Wahl, G.; Millet, Pascal; Egwang, Thomas G.

doi:10.1046/j.1365-3156.1998.00260.x

Cited by 30 publications

(21 citation statements)

References 15 publications

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“…These observations denote that most clinical cases of Loa loa filariasis are amicrofilaraemic, and confirm previous observations (Touré et al, 1998;Touré et al, 1999, Pion et al, 2005. The prevalence of Loa loa infection that is estimated through the microscopic examination of standard blood film thus leads to an underestimation of the prevalence of loiasis.…”

Section: Loa Loa Mediated Encephalopathy and The Future Of Neglected supporting

confidence: 89%

Encephalopathy Related to Ivermectin Treatment of Onchocerciasis in Loa loa Endemic Areas: Operational Considerations

Takougang¹,

Muteba²

2012

Miscellanea on Encephalopathies

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Miscellanea on Encephalopathies 170 EpidemiologyOnchocerciasis, also known as river blindness, is caused by a filarial nematode, Onchocerca volvulus. The adult worms lives in subcutaneous nodules within surface muscles, mainly around the pericostal and the iliac crest.There are two mains subtypes of Onchocerca volvulus, namely the forest and savanah. In the savanal infections, the nodules are mainly located on the upper part of the body, including the trunk, upper limbs and head. Ocular involvement is frequent. In the forest infections, nodules are found primarily on the lower limbs and iliac crest. Cutaneous alterations are the main manifestations of the disase.The worm is transmitted through the bite of female blackflies of the genus Simulium, which bite during the day. The fly breeds in rapidly flowing rivers and streams.Onchocerciasis is endemic in most countries in sub-saharan Africa. Isolated endemic foci are also present in the Arabian Peninsula (Yemen) and in the Americas (Brazil, Colombia, Ecuador, Guatemala, southern Mexico, and Venezuela). An estimated 17 million people are infected worldwide.

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Section: Loa Loa Mediated Encephalopathy and The Future Of Neglected supporting

confidence: 89%

Encephalopathy Related to Ivermectin Treatment of Onchocerciasis in Loa loa Endemic Areas: Operational Considerations

Takougang¹,

Muteba²

2012

Miscellanea on Encephalopathies

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“…PCR tests provide highly specific tests for L. loa (17)(18)(19) but are impractical for field conditions and have not shown significantly improved sensitivity over parasitological methods. Serologic testing by immunoblotting (10) and enzyme-linked immunosorbent assays (ELISAs) (1, 2) with crude, complex mixtures of L. loa extracts has shown poor specificity because of cross-reactivity in patients with other filarial infections as well as those with strongyloidiasis.…”

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confidence: 99%

Rapid, Novel, Specific, High-Throughput Assay for Diagnosis of Loa loa Infection

et al. 2008

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The ability to diagnose Loa loa infection readily and accurately remains a demanding task. Among the available diagnostic methods, many are impractical for point-of-care field testing. To investigate whether luciferase immunoprecipitation systems (LIPS) can be used for rapid and specific diagnosis of L. loa infection, a LIPS assay was developed based on immunoglobulin G (IgG) and IgG4 subclass antibodies to a recombinant L. loa SXP-1 (designated LlSXP-1) antigen and tested with sera from healthy controls or patients with proven infection with L. loa, Mansonella perstans, Onchocerca volvulus, Strongyloides stercoralis, or Wuchereria bancrofti. A LIPS test measuring IgG antibody against LlSXP-1 readily differentiated L. loa-infected from uninfected patients and demonstrated markedly improved sensitivity and specificity compared with an LlSXP-1 IgG4-based enzyme-linked immunosorbent assay (67% sensitivity and 99% specificity). No significant immunoreactivity was observed with S. stercoralisinfected sera, but a small number of patients infected with O. volvulus, M. perstans, or W. bancrofti showed positive immunoreactivity. Measuring anti-IgG4-specific antibodies to LlSXP-1 showed a significant correlation (r ϳ 0.85; P < 0.00001) with the anti-IgG results but showed no advantage over measuring the total IgG response alone. In contrast, a rapid LIPS format (called QLIPS) in which the tests are performed in less than 15 minutes under nonequilibrium conditions significantly improved the specificity for cross-reactive O. volvulus patient sera (100% sensitivity and 100% specificity). These results suggest that LIPS (and the even more rapid test QLIPS) represents a major advance in the ability to diagnose L. loa infection and may have future applications for point-of-care diagnostics.The development of rapid diagnostic assays for onchocerciasis (22) and lymphatic filariasis (20) has not only simplified the care of individual patients with these filarial infections but also allowed accurate and cost-effective geographic mapping for the purpose of mass chemotherapy in areas of endemicity (21) and for use in the certification process of elimination (15). Nevertheless, the coendemicity of loiasis with these and other filarial infections of humans remains an issue because of species-specific differences in the responses to available antifilarial therapies. This has been of particular concern in the setting of both the African Program for Onchocerciasis Control (APOC) and the Global Program for the Elimination of Lymphatic Filariasis (GPELF), where mass drug administration has ground to a halt in certain areas of Africa because of deaths related to ivermectin administered as part of mass treatment programs for onchocerciasis control (3,12).Although the definitive diagnosis of Loa loa infection can be made morphologically by identifying microfilariae in the blood or, rarely, after surgical removal of the adult worm (typically from its subconjunctival location), a proportion of infected individuals are amicrofilaremic (9, 13). PC...

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“…28 This may explain why the rate of PCR positivity in amicrofilaremic persons is related to the transmission rate in endemic areas (while the proportion of amicrofilaremic subjects is stable between areas of different transmission rates). 29 The second source is the adult worm, but this is improbable because the lifespan of adult worms is very long, and they do not show tegumental cell turnover in contrast to other worms such as schistosoma. The filariae are coated by an acellular cuticle; thus, the relative amount of DNA that could be released by a few dying worms would likely be too small to be detectable.…”

Section: Resultsmentioning

confidence: 99%

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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Human occult loiasis: field evaluation of a nested polymerase chain reaction assay for the detection of occult infection

Cited by 30 publications

References 15 publications

Encephalopathy Related to Ivermectin Treatment of Onchocerciasis in Loa loa Endemic Areas: Operational Considerations

Encephalopathy Related to Ivermectin Treatment of Onchocerciasis in Loa loa Endemic Areas: Operational Considerations

Rapid, Novel, Specific, High-Throughput Assay for Diagnosis of Loa loa Infection

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

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