Praziquantel

Limits on what this shows

• Key null findings: A PubMed listing for praziquantel with mitochondria (26 records, first 10 read) and one for cytotoxicity in hepatocytes found no study of praziquantel on mammalian mitochondrial structure, membrane potential, respiration or biogenesis.
• At-risk subgroups: None identified. Hepatic impairment raises drug exposure up to 15-fold [15], but no mitochondrial consequence was studied.

Direction

Unknown in the host. The parasite effects are part of the intended antiparasitic action (Hard Rule 2) and not a nutrient or host-mitochondrial deficiency.

Regulatory status

No mitochondrial statement in either label read [2][15].

Population evidence

Giri 2016 [14] (R. echinobothrida, in vitro): praziquantel altered mitochondrial membrane potential. Prichard 1982 [34] (H. diminuta, in vitro): praziquantel inhibited calcium uptake without changing mitochondrial Ca2+-ATPase activity. Sun 2016 [35] (eight human cell lines): (R)-praziquantel had negligible cytotoxicity to L-02 liver cells and (S)-praziquantel was more cytotoxic; no mitochondrial endpoint was reported in the abstract.

Mechanism

The established praziquantel mechanism is activation of the schistosome TRPM-PZQ channel with calcium influx, spastic paralysis and tegument damage, not a mitochondrial target [4].

Counter-evidence held on record

Counter-evidence No host data; the yellow grade rests on parasite-tissue Tier B evidence and exists to document the search, not to imply host mitochondrial harm. Shares its parasite sources with Oxidative stress (see the overlap map). Framing caution Not a host mitochondrial finding; a mechanism clarification only. No mitochondrial supplement is supported.

Limits on what this shows

• Key null findings: No antioxidant-capacity, glutathione, MDA or F2-isoprostane measurement in people given praziquantel was found. Several animal papers on antioxidant co-treatments (curcumin, silymarin, pentoxifylline) were listed but not opened.
• At-risk subgroups: Heavy infections, where the amount of parasite death is greatest, are a hypothesis only; label-level paradoxical reactions occur mainly in acute schistosomiasis [2].

Direction

Excess (transient oxidative and nitrative burden), indirect, in infected animals. Not an antioxidant depletion finding in people.

Regulatory status

No oxidative-stress statement in either label read [2][15].

Population evidence

No human study. Pinlaor 2008 [13] (O. viverrini-infected hamsters, host measurements, abstract level; the listing gave no numbers): short-term praziquantel raised plasma nitrate and malondialdehyde and iNOS, NF-kappaB and antioxidant-enzyme mRNA, which the authors link to antigen release from dying parasites. Giri 2016 [14] (poultry tapeworm in vitro): reduced glutathione and GST, raised ROS, altered mitochondrial membrane potential, and raised active caspase-3/7 (no numbers in the listing).

Mechanism

Parasite death releases antigens and triggers host inflammation, which the Pinlaor authors link to the oxidative signal [13]; a direct redox effect in the worm was shown in a different organism [14]. No host-tissue mechanism by the drug itself was shown.

Counter-evidence held on record

Counter-evidence All evidence is Tier B (animal or parasite) and shows an indirect effect of treatment, not a depletion of antioxidants; direct human data are absent. Framing caution A hypothesis from animal and parasite work. It supports no antioxidant supplement, which could also interfere in unknown ways, and no dose is given.

Limits on what this shows

• Key null findings: No transferrin receptor or C-reactive protein was measured in the Malian trial, so iron deficiency and inflammation cannot be separated. The pregnancy trial found no anemia effect [7]. No study opened showed a fall in any iron index after praziquantel.
• At-risk subgroups: Anemic, schistosomiasis-infected children. Unaffected: parasite-free people, in whom no praziquantel iron data were found.

Direction

Reverse direction (ferritin up). Ferritin is an acute-phase protein, so a rise cannot be read as better iron stores without inflammation markers. Not an iron deficiency or an iron excess finding.

Regulatory status

No iron statement in either label read [2][15].

Population evidence

Ayoya 2009 (AJFAND) [20] (randomized, 150 anemic children aged 7 to 12 in Bamako, praziquantel 40 mg/kg at enrollment and 4 weeks later, plus or minus ferrous sulfate; praziquantel-alone arm n=66 analysed): hemoglobin 10.53 +/- 0.93 g/dL at baseline, 11.14 +/- 0.98 at 6 weeks and 10.84 +/- 0.86 at 12 weeks; serum ferritin 34.39 +/- 37.58, 40.65 +/- 35.63 and 40.70 +/- 29.57 micrograms/L. Changes of about +0.61 and +0.31 g/dL hemoglobin and about +6.3 micrograms/L ferritin were computed from the means; no confidence intervals or within-arm P values were reported. The praziquantel-plus-iron arm improved significantly more at 6 and 12 weeks. Friis 2003 [6] supplies a hemoglobin figure for albendazole plus praziquantel (see Oxygen delivery).

Mechanism

Named mechanism for a drug effect: absent. Hemoglobin gains track egg-output reduction in the Kenyan trial [6], which points to the infection as the cause; ferritin is an acute-phase protein, so inflammation could contribute. In vitro hemolysis by praziquantel is small [27].

Counter-evidence held on record

Counter-evidence The single-arm change in the praziquantel-alone group has no untreated control, so natural fluctuation and regression to the mean are not excluded; the second Malian dataset [30] could not be opened. No second independent source measured ferritin or transferrin saturation after praziquantel. Framing caution Do not read this as iron repletion by praziquantel or as a reason to supplement iron; iron should be given or withheld according to a clinician-assessed deficiency and infection status.

Limits on what this shows

• Key null findings: No other human study of copper status with praziquantel was found. A PubMed listing for praziquantel with copper returned 14 records, of which only this one measured serum copper in people given praziquantel; the rest were nanoparticle, veterinary or parasite-chemistry studies, and one Kenyan trial in which copper was a supplement component and was not measured [10].
• At-risk subgroups: Chronic S. mansoni patients in that cohort; no data elsewhere.

Direction

Reverse direction (excess falling toward normal). Not a copper deficiency and not a drug-induced copper change. Kept independent of Iron and Zinc (Hard Rule 7).

Regulatory status

No copper statement in either label read [2][15].

Population evidence

el Hawy 1993 [10]: serum copper was higher than in 20 controls in both patient groups (40 patients) before treatment, and decreased after a single oral praziquantel dose. No concentrations, effect sizes or P values appeared in the abstract record.

Mechanism

Named drug mechanism: absent. The abstract read proposes none; liver involvement is the stratifier it reports.

Counter-evidence held on record

Counter-evidence Single uncontrolled abstract with no numbers retrievable; no ceruloplasmin; inflammation and liver involvement are alternative explanations for the baseline excess and the fall. Framing caution A reverse-direction, disease-linked observation, not a copper deficiency. It gives no basis for copper supplementation, which could be harmful.

Limits on what this shows

• Key null findings: Kay 2015 was a null result for praziquantel. In Schneeberger 2018, Fusobacterium abundance before treatment was higher in cured children (P=0.018), suggesting the microbiome may influence drug response rather than the reverse.
• At-risk subgroups: Children with active infection; no data in adults or in repeated dosing.

Direction

Neutral at 3 to 12 weeks; possible small transient taxonomic shifts at 24 hours. Infection-related differences in infected versus uninfected children are a disease effect.

Regulatory status

No microbiome statement in either label read; gastrointestinal complaints (abdominal discomfort, nausea) are listed adverse reactions [2].

Population evidence

Kay 2015 [11] (Zimbabwe, 139 children at baseline, 62 resampled 12 weeks after a single 40 mg/kg dose, 47 treated and 15 untreated; paired groups infected/treated n=11, infected/untreated n=4, uninfected/treated n=36, uninfected/untreated n=11): no OTU differed in abundance between the four groups at any taxonomic level and diversity did not change. Schneeberger 2018 [12] (Cote d'Ivoire, 34 children, 96 stool samples; 60 mg/kg versus placebo; before, at 24 hours and at 3 weeks): at 24 hours Bacilli and Erysipelotrichi were higher after praziquantel (no P values given; the authors call the shifts slight), and there were no differences at 3 weeks; the authors conclude microbiome off-target effects are unlikely to explain gastrointestinal side effects. Ajibola 2023 preprint [33] (northern Nigeria, 267 samples, adolescents before and after praziquantel): infection had a larger effect on the gut than praziquantel did; Shannon diversity of infected samples differed from uninfected baseline at 3, 9 and 12 months (P<0.0001, P=0.0342, P=0.0003).

Mechanism

Named mechanism: absent. The studies cannot separate a drug effect from worm death or from the gastrointestinal adverse reactions the label lists [2]; any such explanation is an inference, not a finding.

Counter-evidence held on record

Counter-evidence Small groups (n=11 infected and treated in Kay 2015), non-random untreated controls, one sampling point at 12 weeks, a preprint abstract for the largest cohort, and no P values for the 24-hour shifts. These sources neither support dysbiosis nor rule out a transient effect. Framing caution No sustained microbiome change after praziquantel was shown. This is a low-confidence, hypothesis-level flag only; it is not a reason to use probiotics or to avoid treatment.

Limits on what this shows

• Key null findings: Ndibazza 2010 [7] (randomized 2x2 factorial, 2,507 pregnant women, 18% with S. mansoni, low infection intensity): anemia at delivery was 35% overall and praziquantel had no effect (OR 1.00, 95% CI 0.83 to 1.21). Byrne 2021 [8] (meta-analysis): albendazole raised hemoglobin 3.02 g/L (95% CI 0.1 to 6.0), and adding praziquantel for schistosomiasis gave no extra benefit in the stratified sensitivity analysis. No human report of praziquantel-associated hemolysis, methemoglobinemia or anemia was found: in vitro on human red cells praziquantel caused about 10-fold less hemolysis than two reference membrane-active drugs, maximum 6% at the highest concentration tested [27], and 5 G6PD-deficient patients in a 50-patient clonorchiasis series had no hemolysis [28].
• At-risk subgroups: Children and adolescents with moderate to heavy infection and baseline anemia gain most [5][26]. Pregnant women with light infection showed no anemia effect [7].

Direction

Reverse direction (hemoglobin improves). The improvement reflects clearing blood-feeding and inflammatory parasites, not a pharmacologic effect of praziquantel (Hard Rule 2). Anemia, where present, is a clinical outcome and is not filed as iron deficiency.

Regulatory status

Neither label section read mentions hemoglobin; the only blood term in the US adverse reactions is eosinophilia [2][15].

Population evidence

Koukounari 2006 [5] (Ugandan schoolchildren, 2,788 children, before and one year after praziquantel plus albendazole, no untreated comparison): among children anemic at baseline, hemoglobin rose 0.834 g/dL (significant per the abstract; CI not given). Friis 2003 [6] (randomized, 746 children, praziquantel 40 mg/kg plus albendazole 600 mg given to infected children): anthelminthic effect +2.0 g/L (95% CI 0.2 to 3.9; P=0.03), tracking egg-output reduction (0.4 g/L per 100 eggs per gram for S. mansoni). Guyatt 2001 [24] (Tanzania, albendazole plus praziquantel): anemia prevalence fell by about a quarter at 15 months, and moderate to severe anemia by nearly half; schistosomiasis accounted for about 15% of baseline anemia. A Ugandan preschool trial [25] found low hemoglobin fell from 51.2% to 0.5% (one dose) and from 61.4% to 1.1% (two doses) at 8 months, with no one-versus-two-dose difference and no untreated arm. Koukounari 2007 [26]: children anemic at baseline gained the most hemoglobin (no effect size in the abstract read).

Mechanism

Hemoglobin gains track egg-output reduction [6], and schistosomiasis accounted for about 15% of baseline anemia in Tanzania [24], pointing to the infection as the cause. A review proposes four mechanisms linking schistosomiasis to anemia [29], but only a one-sentence listing summary was seen. No mechanism by which praziquantel itself lowers hemoglobin was found.

Counter-evidence held on record

Counter-evidence The Ugandan cohort [5] and the Tanzanian surveys [24] have no untreated comparison and co-administered albendazole; the Kenyan trial [6] gave both drugs, so praziquantel alone is not isolated. Malaria co-infection modified the Kenyan effect (interaction P=0.09). The pregnancy trial is null overall. Framing caution Hemoglobin changes here reflect clearing the infection. They are not evidence that praziquantel affects oxygen delivery or that iron should be added; anemia needs its cause assessed by a clinician.

Limits on what this shows

• Why no grade: Dual condition met: no Tier B or C source for mammalian or human ATP production with praziquantel, and no circulating claim found within the channels tried. Kept independent of Mitochondrial burden and of Oxygen delivery/utilization (Hard Rule 7). A disclosed gap, not a finding of safety.

What was searched

PubMed listing "praziquantel AND (ATP OR oxygen consumption OR oxidative phosphorylation OR respiration)": 62 records, first 10 read, all parasite-pharmacology or ABC-transporter reviews, an anthelmintic-resistance review, a plant-extract schistosomula viability assay (praziquantel not tested), and one retrospective echinococcosis cohort; none measured ATP or respiration in a mammal or person [14]. PubMed listing "praziquantel mitochondria": 26 records, first 10 read (parasite studies only). Hepatocyte cytotoxicity listing: one human-cell-line study with no ATP endpoint [35]. Web search for consumer ATP or "low energy" claims was not possible (budget exhausted); the Drugs.com food-interaction page makes no energy or nutrient-depletion claim [23].

Channel outcomes

PubMed listings completed for these queries; 52 of 62 records in the ATP listing were not read (page 1 only). WebSearch (consumer claims), Europe PMC and OpenAlex listings were rate limited or unavailable at times. Genuine gap on what was seen, with a tooling-limited tail (unread listing pages, consumer-claim search).