An interventional study of Mosquito bite (1 or 2 or 3) in Plasmodium Vivax Infection, sponsored by University of Oxford. Recruiting at 1 site in Thailand. Open to participants aged 20 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-03-27.
Sponsored by University of Oxford · Not applicable, Interventional, and Other
This study is a human challenge study to assess the minimum infective mosquito bite dose in a controlled human malaria Infection (via P. vivax sporozites) in healthy volunteers. The results will inform the development of a P. vivax mosquito-delivered CHMI trial platform, supporting safer and more accurate vaccine efficacy assessments. Conducting the trial in individuals genetically and immunologically similar to the target population will also enhance the relevance of findings to real-world endemic settings.
This study is funded by the UK Wellcome Trust. The grant reference number are Oxford/MORU: 212336/Z/18/Z and 212336/Z/18/A, and Mahidol University: 212336/A/18/Z and 212336/A/18/A.
Controlled Human Malaria Infection (CHMI) has become an essential approach in the accelerated development of malaria vaccines and therapeutic interventions. This methodology involves the inoculation of human volunteers with malaria parasites, either via mosquito bites or direct administration of sporozoites or parasitized erythrocytes. CHMI facilitates the evaluation of vaccine and drug candidates in well-controlled early-phase clinical studies, enabling the selection of the most promising candidates for further evaluation in malaria-endemic regions.
While intravenous injections of parasites can be employed in such studies, the natural route of infection via mosquito bite has notable advantages, particularly in stimulating immune responses at the site of infection in the skin and closely mimic the natural infection process, allowing both liver and blood stage infections to develop. Additionally, mosquito-based challenge models provide a valuable platform for the evaluation of pre-erythrocytic (sporozoite) vaccine candidates. Effective sporozoite vaccines are expected to induce the production of serum antibodies capable of neutralizing sporozoites before they invade hepatocytes, thereby preventing liver-stage and blood-stage malaria.
Historically, numerous challenge studies using P. falciparum-infected mosquito bites or malaria parasite have been conducted in well-established research centers, including the Walter Reed Army Institute of Research, Sanaria Inc., the University of Maryland, Seattle Biomedical Research Institute, University of Oxford, and Radboud University Medical Centre. These studies have involved large cohorts, with over 45 trials involving P. falciparum-infected mosquitoes. However, studies utilizing P. vivax-infected mosquito bites have been fewer in number, with 8 trials conducted in regions such as Colombia, the UK, and Thailand.
P. vivax is the most prevalent malaria species outside of sub-Saharan Africa and represents a significant cause of malaria in countries such as Thailand. Given the substantial burden of P. vivax in Thailand and Southeast Asia, an international collaborative research team has proposed to advance the development and evaluation of P. vivax malaria vaccine candidates in an endemic region. This initiative is designed to include volunteers with genetic and immunological characteristics similar to those of the target population, thereby ensuring the relevance and applicability of the findings.
The first human challenge study in Thailand using P. vivax sporozoite infection known as "Malaria Infection Study in Thailand 1 (MIST1)," is currently being conducted at the Faculty of Tropical Medicine, an institution internationally recognized for its expertise in malaria research. The study aims to assess the feasibility and safety of P. vivax sporozoite human challenge in the local population. It represents a critical milestone in supporting the development and evaluation of effective malaria vaccines in regions where P. vivax is endemic.
Majority of malaria sporozoite challenge studies (75%, 39 out of 52 studies) have traditionally relied upon the bites of five infected mosquitoes to induce malaria. The rationale for using 5 mosquito bites is based on the extensive previous experience with P. falciparum, where sporozoite inoculated by fewer than five mosquitoes has led to inconsistent infections in malaria-naïve volunteers. However, this pattern does not appear to hold for P. Vivax-infected mosquito, as most studies demonstrated 100% infectivity rates using 2-4 mosquito bites and 5 mosquito bites. One study using P. Vivax-infected mosquito reported that 1 out of 18 participants did not develop malaria infection following a mosquito challenge. However, since antimalarial drug level were not measured in that study, the cause of this outcome remains inconclusive. Notably, no study used as few as one mosquito bite to induce P. Vivax malaria.
Individuals rarely bitten by more than one infected mosquito per night under natural condition, except in settings with very high malaria transmission intensity. In a very low transmission site on the Thai-Myanmar border a recent study reported a geometric mean of 57 sporozoites per mosquito (range 9-11,428). This compares to earlier studies in Africa and PNG where endemicity was higher and geometric means were >4000 (range 150-10,000). The probability of infection increases with the number of infectious bites. There are relatively little data on the number of sporozoites in naturally infected mosquitoes. It has been demonstrated that highly infected mosquitoes being more likely to have caused infection than lightly infected mosquitoes in a dose-response relationship.
The MIST1 study initially employed five mosquito bites to ensure consistent infection in a small cohort of six volunteers. However, using five mosquito bites may create an unrealistic challenge and could hinder the assessment of true vaccine efficacy. One out of five volunteers in the MIST1 study developed a relapsed Plasmodium vivax infection, suggesting that the standard challenge involving five Plasmodium vivax -infected mosquitoes might contribute to an overwhelming infection.
The primary aim of this study is to determine the minimum number of Plasmodium vivax-infected mosquito bites required to reliably induce malaria infection in healthy individuals. This study will begin with a challenge dose of one mosquito bite, as only a limited number of studies have evaluated challenge models using as few as 2-4 infected mosquitoes, and some involved small sample sizes. Furthermore, no study has used as one mosquito bite to induce P. vivax malaria.
The investigators aim to confirm whether 1 - 3 bites are sufficient to consistently induce P. vivax infection while maintaining a challenge model that more closely reflects natural transmission, avoids excessive parasite exposure, and could undermine the vaccine efficacy assessments. If at least one volunteer who receives one mosquito bite is not successfully infected, the investigators will increase the challenge dose to two bites. If at least one volunteer remains uninfected after three bites, the investigators will not escalate the challenge to four bites as reducing from standard five bites to four may not provide a meaningful advantage as suggested by the Steering Committee.
The study will provide important information for the development of P-vivax mosquito delivered CHMI trials platform, enabling a safer and more accurate assessment of vaccine efficacy in malaria research. Moreover, conducting this trial in a local population will enhance the applicability of the findings to real-world endemic settings
1,184 studies on the registry are indexed under Malaria; 79 are open to participants now.
This study's planned enrollment of 24 is below the median of 252 across 937 interventional studies indexed under Malaria.
Browse Malaria studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
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inclusion criteria
The volunteer MUST NOT enter the study if any of the following apply:
Finding on safety laboratory values as defined below:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Number of mosquito bites assigned sequentially based on the adaptive design
Other: Mosquito bite (1 or 2 or 3)
Successful feeding of 1, 2, or 3 Plasmodium vivax-infected mosquitoes
The minimum number of infected mosquito bites.
The minimum number of infected mosquito bites needed to reliably result in a P.vivax infection in all 8 participants at a given bite dose group, as defined by two consecutive positive qPCR results or presence of parasitemia on malaria blood film
Time frame: Up to 21 days after the individual CHMI
Prepatent period across different groups.
Measurement of the prepatent period (time from challenge to first qPCR-positive result) in participants across different mosquito bite groups.
Time frame: Up to 21 days after the individual CHMI
Humoral immune responses
Characterisation of humoral immune responses (antibody titress) to Plasmodium vivax infection, stratified by the number of mosquito bites received.
Time frame: Up to one year after antimalarial initiation
Humoral immune responses
Characterisation of humoral immune responses (Cytokine response) to Plasmodium vivax infection, stratified by the number of mosquito bites received.
Time frame: Up to one year after antimalarial initiation
Cellular immune responses
Characterisation of cellular immune responses (T-cell profiles) to Plasmodium vivax infection, stratified by the number of mosquito bites received.
Time frame: Up to one year after antimalarial initiation
Cellular immune responses
Characterisation of cellular immune responses (Neutrophil) to Plasmodium vivax infection, stratified by the number of mosquito bites received.
Time frame: Up to one year after antimalarial initiation
Gametocytaemia across different groups
Quantification of gametocytaemia measured by quantitative PCR (qPCR) across different groups
Time frame: Up to 21 days after the individual CHMI
AEs stratified by groups
Incidence, severity, and duration of AEs stratified by number of mosquito bites administered.
Time frame: Up to one year after antimalarial initiation
Plan to share: Yes — With participant's consent, suitably anonymised clinical data and results from blood analyses stored in the database may be shared according to the terms defined in the MORU data sharing policy with other researchers to use in the future.
Supporting information: Study protocol, Statistical analysis plan
Time frame: After completion of trial activities and once the study data have already been used for the study purposes, including publication.
Data sharing details ↗ · www.tropmedres.ac
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