Predicting Kala-Azar Disease Manifestations in Asymptomatic Patients with LatentLeishmania donovaniInfection by Detection of Antibody against Recombinant K39 Antigen

Abstract

Clinically visceral leishmaniasis is suspected in only a fraction of infected persons, as the majority of these may not have clinical manifestations and remain asymptomatic. There is scanty information on diagnosing latent infections and predicting disease in asymptomatic persons. We therefore carried out a study on asymptomatic contacts of patients with visceral leishmaniasis and post-kala-azar dermal leishmaniasis by using methods for detection of antibody to recombinant K39 (rK39) antigen. A total of 240 patients with leishmaniasis and 150 asymptomatic contacts were tested for anti-rK39 immunoglobulin G (IgG) and IgA antibodies. Fifty-five asymptomatic persons were found to be seropositive. These individuals were monitored every 3 months for 1 year. On follow-up, 43.9% of the asymptomatic seropositive contacts developed kala-azar within the first 3 months, and a cumulative total of 69% developed kala-azar within 1 year. The rest remained asymptomatic and self-healed the infection. The sensitivity and specificity of rK39 enzyme-linked immunosorbent assay (ELISA) and dipstick tests were 100%, while an in-house-developed latex agglutination test had 80% sensitivity. The antibody profile showed that the IgG anti-rK39 antibodies reached a titer of up to 10 ؊6 within 6 months of infection, started declining thereafter, and completely disappeared in 2 to 3 years in successfully treated cases. Significant titers of IgA antibodies were detectable a little earlier than those of IgG antibodies and were undetectable after 6 months. The study showed that mass screening of family members and contacts by using anti-rK39 ELISA could be a highly reliable tool for early diagnosis and to plan prophylactic treatment of latently infected asymptomatic carriers to eradicate kala-azar.

Significance of persistence of antibodies against Leishmania infantum in sicilian patients affected by acute visceral leishmaniasis

“…One explanation might be that individuals with VL do not show complete elimination of the parasite. This agrees with the opportunistic occurrence of the diseases, as observed in patients with AIDS [19][20][21][22][23][24][25].…”

Specificity of the rapid rK39 antigen-based immunochromatographic test Kalazar Detect(r) in patients with cutaneous leishmaniasis in Brazil

“…In Sudan, Uganda, India and Afghanistan, validation studies of the rK39 rapid test yielded sensitivities that ranged from 67-100%. Despite the variability in the sensitivity, these studies reported similar specificities (95-100%) (Zijlstra et al 2001, Singh et al 2002, Chappuis et al 2005, Ritmeijer et al 2006) and this finding is in agreement with the results of the current study.…”

ELISA with Recombinant rKRP42 Antigen Using Urine Samples: A Tool for Predicting Clinical Visceral Leishmaniasis Cases and Its Outbreak

“…A similar relationship between the high occurrence of clinical VL and high antibody titers was reported in the works by Singh and others. 20,27 The same works also noted that antirK39 IgG titer in serum correlated with the parasite load and that persistent increase of antibody titers related to clinical unresponsiveness to antileishmanial treatment. The prevalence by rKRP42 urine ELISA alone does not seem to be useful, because in the first test, the highest rate was recorded in center 2 (Tables 1 and 2); however, the clinical rate there turned out to be the lowest, with only one sporadic VL case.…”

“…18,19 Moreover, early diagnosis and treatment may reduce the chance of disease transmission. A study conducted in Bihar state, India, reported that 69% of asymptomatic seropositives by rK39 ELISA and dipstick developed kala-azar within 1 year, 20 suggesting that many of the asymptomatic seropositives were in a pre-clinical state.…”