The prevalence of helminth and malaria infections and the effects of de-worming on disease progression markers in HIV-1 infected pregnant women on antiretroviral therapy in Rwanda

• Main Author: Emil, Ivan
• Format: Others
• Language: en
• Published: 2018
• Online Access: https://hdl.handle.net/10539/24841

thesis submitted to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa, in fulfilment of the requirements for the award of the degree of Doctor of Philosophy (PhD) August 15th, 2017. === Background: Helminth and malaria co-infections have been hypothesized to be factors driving the HIV-1 epidemic in Africa, and the fact that both cause anaemia highlights the importance of addressing the interactions between HIV/AIDS, malaria and intestinal helminthic infections in pregnancy for individuals in resource limited settings. Aims: The aims of this thesis were to determine the prevalence and risk factors for malariahelminthic dual infections among HIV positive pregnant women on antiretroviral therapy in Rwanda. The second aim was to determine the effect of deworming on immune markers of HIV/AIDs disease progression among HIV-infected pregnant women on antiretroviral therapy (ART), and to elucidate the benefits of deworming, specifically in targeted versus untargeted deworming. Methods: A cross-sectional study was carried out in 328 HIV-positive pregnant women receiving ART. We determined the prevalence of helminth and malaria dual infections and the effects of ART on these infections were also examined. This cross sectional study acted as a pilot study for a deworming intervention, which took the form of a longitudinal study of targeted and untargeted deworming in which 980 HIV-infected pregnant women were randomized to ‘targeted’ and ‘untargeted’ arms with albendazole therapy. The effects of deworming on the prevalence of helminth infection and CD4 counts, viral load and haemoglobin levels were measured over time at 4 visits. Measurements were at baseline and every 3 months thereafter. The presence of Plasmodium falciparum was tested at each visit and anti-malarial therapy (Coartem: artemether-lumefantrine) was administered to all subjects who tested positive for P. falciparum. Baseline data was used to determine the risk factors for helminth infection. Helminthic infection was diagnosed using the Kato Katz method, whilst the presence of P. falciparum was identified from blood smears. The CD4 counts and viral load levels were also determined using standard laboratory methods. Results: Within the pilot study of 328 women residing in rural (n=166) and peri-urban (n=162) locations, 38% of those tested harboured helminths, 21% had malaria and 10% were infected with both. The most prevalent helminth species were Ascaris lumbricoides (20.7%), followed by Trichiuris trichiura (9.2%), Ancylostoma duodenale and Necator Americanus (1.2%). Helminth infections were characterized by low haemoglobin levels and low CD4 E. Ivan PhD thesis Page iii counts. Subjects treated with a d4T-3TC-NVP regimen had a reduced risk of Trichuris trichiura infection (OR, 0.27; 95% CIs, 0.10-0.76; p<0.05) and malaria-helminth dual infection (OR, 0.29; 95% CI, 0.11-0.75; p<0.05) compared to those receiving AZT-3TC-NVP therapy. Within the longitudinal study of deworming in 980 pregnant, HIV-infected females, analysis of the baseline data showed that education and employment reduced the risk of all types of infection whilst hand washing protected against helminth infection (0.29 [0.19-0.46]; p<0.0005). Logistic regression analysis, at baseline (odds ratio [95% CIs]), demonstrated that TDF-3TC-NVP (3.47 [2.21-5.45]; p<0.0005), D4T-3TC-NVP (2.47 [1.27-4.80]; p<0.05) and AZT-NVP (2.60 [1.33-5.08]; p<0.05) regimens each yielded higher helminth infection rates than the AZT-3TC-NVP regimen. Anti-retroviral therapy had no effect on the risk of malaria. The prevalence of P. falciparum infection was similar at all-time points for the targeted and non-targeted anti-helminth treatment arms, with a significant fall in helminth prevalence in both arms by visit 2. Albendazole therapy was associated with favourable changes in haemoglobin levels, CD4 counts and viral loads, in those subjects with helminth infections. Haemoglobin levels were similar in both arms at all study visits, rising significantly from visit 1 to visit 2 in both groups and peaking by visit 3. Thereafter, levels fell significantly (p<0.0005 for both comparisons) by visit 4. Conclusions: The prevalence of helminth infection in HIV infected pregnant women on antiretroviral therapy is common in rural and peri-urban settings in Rwanda. This study clearly shows that, albendazole treatment is associated with an increase in CD4 counts, a fall in viral loads and an increase in haemoglobin levels. The effects of albendazole are mediated by the eradication of helminth infection. The study also shows that treatment with albendazole using a targeted or non-targeted regimen is equally effective. The mechanism by which certain ART regimens reduce the risk of helminth infection warrants further study. === LG2018