Eliminating worm infections as a key strategy for HIV/AIDS prevention

Researchers from the Institute of Infectious Diseases and Tropical Medicine at the LMU University Hospital Munich, the National Institute for Medical Research (NIMR) – Mbeya Medical Research Center (MMRC) and the German Center for Infection Research (DZIF), together with colleagues from Bonn, have discovered a risk factor for HIV infection that has received little attention to date. In an earlier cohort study conducted in Tanzania, they had demonstrated for the first time that infection with the worm Wuchereria bancrofti increases the risk of contracting HIV. This link has now been further investigated in the context of a national program in Tanzania to eliminate W. bancrofti—the causative agent of lymphatic filariasis. The follow-up study confirms that the containment of this worm infection leads to a reduction in new HIV infections. The results of the RHINO study have now been published in the journal The Lancet HIV.

Lymphatic filariasis—a neglected tropical disease

The nematode W. bancrofti is a parasite that occurs mainly in the tropical regions of Africa and Asia and can cause the disease lymphatic filariasis. This disease damages the lymphatic system and can lead to lymphedema characterized by a significant increase in the size of the extremities.

A team led by DZIF scientists Prof. Michael Hoelscher and Prof. Inge Kroidl from the Institute of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich, in collaboration with the Tanzanian National Institute for Medical Research (NIMR) – Mbeya Medical Research Center (MMRC), conducted a comprehensive cohort study at nine study sites in Tanzania from 2007 to 2011. The EMINI (Evaluation and Monitoring of the Impact of New Interventions) study showed that infection with the W. bancrofti worm increases the risk of infection with HIV by a factor of 2 to 3 (The Lancet, 2016).

Cohort study in Tanzania

Between 2009 and 2015, villagers in Tanzania were treated annually with anti-helminthic drugs as part of a government program to eradicate lymphatic filariasis. Together with researchers from the UKB and the University of Bonn, the Munich and Tanzanian teams used this opportunity to conduct a follow-up study entitled RHINO (Risk of HIV Infections through Nematode Organism) to investigate the impact of the almost complete elimination of W. bancrofti infections on HIV incidence.

In 2019, the research team invited people at one of the EMINI study sites, Kyela, to participate in the RHINO follow-up study. The subjects—a total of 1,139 participants aged 14 to 65 years—were tested for HIV and W. bancrofti (WB) and divided into three groups accordingly—1. WB-positive, 2. cured of WB (i.e. WB-positive between 2007 and 2011 and WB-negative in 2019), and 3. WB-negative. In a statistical analysis, the research team then compared the HIV incidence in these three groups in the study periods 2007-2011 and 2011-2019.

Containment of W. bancrofti infections reduces HIV incidence

The analysis of HIV incidence between 2007 and 2011 showed that WB-infected persons (1.72 cases per 100 person-years/PY) were more than twice as likely to become infected with HIV compared to WB-negative persons (0.69 per 100 PY). In contrast, the HIV incidence examined in the period 2011-2019 in people who had been cured of WB (0.73 cases per 100 PY) differed only insignificantly and not statistically significantly from people who had never been infected with WB (0.68 cases per 100 PY).

In the group of test participants who were cured of W. bancrofti, a comparison of the two study periods showed a reduction in HIV incidence of around 60 percent, which was also statistically significant after adjustment for age and gender (measured odds ratio: 0.41, p=0.012). In the comparison group of people who were never infected with W. bancrofti in either of the two periods, on the other hand, there was no change in HIV incidence.

DZIF researcher Prof. Inge Kroidl concludes: "This confirms the earlier hypothesis that it is indeed the worm W. bancrofti that has an influence on the level of HIV incidence, and that combating W. bancrofti can help to reduce the rate of new HIV infections." "Helminth infections can demonstrably increase the risk of HIV infections. We are continuing to investigate which immunological processes could explain this increased susceptibility to HIV transmission by Wuchereria bancrofti," says Prof. Michael Hoelscher, Director of the Institute of Infectious Diseases and Tropical Medicine at LMU University Hospital Munich.

Dr. Mkunde Chachage from NIMR – MMRC emphasizes that "This research has highlighted the power of including communities in identifying additional interventions needed to strengthen our regional HIV control strategies. This groundbreaking research underscores the vital role local communities play in shaping effective health initiatives".

In a related statement, Prof. Said Aboud, Director General of NIMR commented on the results, stating "These results demonstrate NIMR’s commitment to being at the forefront of efforts to eliminate lymphatic filariasis and HIV in Tanzania". He further acknowledged the longstanding support of the Government of Tanzania through the Neglected Tropical Disease Control Program (NTDCP), which has been fighting these diseases for nearly 20 years. This has made this research possible, which has proven beneficial in our ongoing fight against HIV.

Co-author of the study, Prof. Achim Hörauf, Director of the Institute of Medical Microbiology, Immunology and Parasitology at the University Hospital Bonn, adds: "Our findings open up new possibilities for the prevention of HIV in affected regions. The therapy to combat lymphatic filariasis is still not optimal. We are therefore continuing to research this topic and hope to bring at least a few of the drugs developed also with DZIF funding, to registration."