Cytokine profiles in highly active antiretroviral treatment non-adherent, adherent and naive HIV-1 infected patients in Western Kenya.

Background: Cytokines play an important role in signaling the immune system to build an adequate immune response against HIV. HIV distorts the balance between pro and anti-inflammatory cytokines causing viral replication. Highly active antiretroviral treatment (HAART) acts by trying to restore pro and anti-inflammatory cytokine balance. It is not clear how HAART non-adherence influences circulating cytokine levels. This study therefore determined cytokine levels in HAART non-adherent individuals. Methods: This cross-sectional study recruited 163 participants (51 controls, 23 HIV-1+ HAART naive, 28 HAART-adherent 6 months, 19 HAART-adherent 12 months and 42 HAART non-adherent). Cytokines were analyzed by ELISA while CD4 T cells determined in 3.0 µl of whole blood using BD FACSCaliburTM and viral load in 0.2ml plasma sample using Abbott Molecular m2000sp sample preparation and m2000rt real-time amplification and detection systems (Abbott Molecular Inc., Illinois, USA) according to the manufacturer's methods. Results: IL-4, IL-6, IL-10, TNF-α and TGF-ß were significantly elevated in HIV-1 HAART non-adherent compared with HIV-1 HAART adherent and healthy controls P<0.01. IFN- γ was significantly decreased in HIV-1 HAART non-adherent compared with HIV-1 HAART adherent and healthy controls P<0.01. TNF-α and TGF-ß were significantly reduced in HIV-1 HAART adherent patients at 12 months compared to those at 6 months P<0.01. IL-4 and IL-10 correlated positively with viral load. IL-4, IL-6, IL-10, TNF-α and TGF- ß associated inversely with CD4 T cell counts and body mass index (BMI). Conclusion: This study established that HAART adherence is immunologically beneficial to the pro and anti-inflammatory cytokine balance milieu while non-adherence appears to cause alterations in pro and anti-inflammatory cytokines warping the balance in this dichotomy.

Comparison of Microscopy and PCR for Detection of Giardia Lamblia and Entamoeba Histolytica in Human Stool Specimens in a Resource Limited Setting in Western Kenya.

BACKGROUND: Accurate diagnosis of Giardia lamblia and Entamoeba histolytica is important since these intestinal parasites account for a significant proportion of morbidity and mortality globally. Microscopy is the key diagnostic test used for diagnosis of the two parasites. Other tests including rapid diagnostic tests and polymerase chain reaction have been developed to improve the detection of these parasites. Most of these newer tests are not affordable in resource limited settings, hence the over reliance on microscopy. The objective of this study was to determine the reliability of microscopy in a resource limited setting in Western Kenya, a region endemic for the two intestinal parasites. METHODS: Polymerase chain reaction, the gold standard test, was performed on stool samples suspected for G. lamblia and E. histolytica. Microscopy was then performed on the same samples and the two tests compared. RESULTS: Microscopy was found to be 64.4% sensitive, 86.6% specific for the detection of G. lamblia. Additionally, this test was 64.2% sensitive and 83.6% specific for the diagnosis of E. histolytica. Cohen's kappa values of 0.51 and 0.47 were determined for microscopy for G. lamblia and E. histolytica respectively. McNemar's test revealed a significant difference between the two tests, P<0.001. CONCLUSION: This study found microscopy to be a reliable diagnostic test in this resource limited setting.

In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice.

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice / Estudo in vitro e in vivo da eficácia anti leishmaniótica de terapêutica combinada de Diminazene e Artesunate contra Leishmania donovani em camundongos Balb/c

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

A atividade in vitro e in vivo de Diminazene (Dim), Artezunate (Art) e a combinação Dim e Art (Dim-Art) contra Leishmania donovani foi comparada com a droga de referência Anfotericina B. IC50 da Dim-Art foi 2,28 ± 0,24 µg/mL enquanto aquelas de Dim e Art foram 9,16 ± 0,3 µg/mL e 4,64 ± 0,48 µg/mL respectivamente. O IC50 da Anfotericina B foi 0,16 ± 0,32 µg/mL contra a fase estacionária de promastigotas. A avaliação in vivo do modelo de L. donovani em camundongos Balb/c indicou que os tratamentos com a terapêutica de drogas combinadas em doses de 12,5 mg/kg por 28 dias consecutivos significantemente (p < 0,001) reduziu a carga parasitária no baço quando comparada a tratamentos com uma única droga dada nas mesmas dosagens. Embora a carga parasitária tenha sido levemente mais baixa (p < 0.05) no grupo Anfotericina B quando comparada com o grupo tratado Dim-Art, o estudo presente demonstra a vantagem positiva do uso potencial da terapêutica combinada Dim-Art sobre drogas como Dim ou Art quando usadas isoladamente. Posterior avaliação é recomendada para determinar a média de combinação mais eficaz dos dois compostos.