Pneumocystis pneumonia (PcP) is an opportunistic disease caused by Pneumocystis fungi that develops in immunocompromised individuals. This disease frequently affects those who suffer from acquired immune deficiency syndrome (AIDS), those who undergo chemotherapy treatment or those who take medications that reduce the immune response. PcP targets the fibrous tissue of the lungs and leads to inflammation, a buildup of fluid in the lungs and hypoxia (severe lack of oxygen throughout the blood). This condition is fatal if not treated.
In 2014, the incidence of PcP in the United States was 9% among hospitalized AIDS patients and 1% among solid organ transplant recipients. The mortality rate for those affected by PcP is between 5-40% for treated individuals and 100% for untreated individuals.
Currently, the most effective treatment for PcP is an antibiotic that combines trimethoprim and sulfamethoxazole (TMP-SMX). This TMP-SMX treatment is ineffective for approximately 10% of the population as it contains sulfamethoxazole, which causes an allergic reaction in these individuals. It also causes multiple adverse effects, which include rash, fever, diarrhea, nausea and thrombocytopenia (low platelets). An alternative, more recent PcP treatment involves all-trans retinoic acid (ATRA), a metabolite of vitamin A, combined with primaquine (PMQ), which may cause respiratory distress, hypotension, or renal failure after use. Although TMP-SMX and ATRA-PMQ can successfully treat PcP, it is crucial to develop alternatives to these medications with fewer severe side effects.
Recently, a research group from the Indiana University School of Medicine conducted an animal study to examine the use of vitamin D as a supplemental therapy for the treatment of PcP due to its’ ability to stimulate the development of specialized immune cells to fight off infection. If proven effective, vitamin D may have the potential to augment drugs currently used for PcP therapy. However, further studies must be conducted to determine if this augmentation is feasible.
Research was conducted on immunosuppressed mice that were infected with PcP. These mice were split into five groups and assigned to one of the following treatment regimens: TMP-SMX, ATRA-PMQ, VitD3 alone (at 300IU/kg/day), PMQ alone and VitD3-PMQ. After the initial infection, the mice were treated orally for three weeks with their assigned treatments. Following this timeframe, the lungs of the mice were inspected for the progression of PcP.
Gross lung morphology examination revealed that only the untreated mice had swollen lungs. All of the treated mice had lungs of a healthy size. Lack of significant lung enlargement in treated mice proved that a combination of VitD3 at 300IU/kg/day and PMQ was just as effective for treatment in mice as traditional PcP medications. Mice lung cross sections indicated that similarly to TMP-SMX, VitD3-PMQ reduced the severity of inflammation and almost completely eliminated inflammatory cells. The mice treated by VitD3 alone had a much lower organism load and less lung fluid than that of the untreated PcP mice, but they did not do as well as the mice treated with combination drugs. Remarkably, the VitD3-PMQ regimen mice were overall more physically active and gained more weight each week after treatment than uninfected mice.
The article stated:
“[Vitamin D3] can increase the self-defense ability of Pc-infected hosts. PMQ has been shown to suppress the proliferation of Pc organisms. The combination of these two different mechanisms would make the VitD3-PMQ combination ideal for PcP therapy.”
In addition, vitamin D may have synergistic effects with other less effective drugs that are not as toxic as TMP-SMX. Enhancing these drugs may lead to the development of further potent treatments for PcP patients.
Despite the beneficial results of vitamin D supplementation in PcP therapy mentioned above, it is important to note this study’s limitations. As this experiment was conducted on animal models, it may not be representative of the effects the VitD3-PMQ treatment would have on humans.
Cannell, R. & Cannell, JJ. Animal study: vitamin D as an adjunct therapy for the treatment of Pneumonia. The Vitamin D Council Blog & Newsletter, January, 2016.