Idiopathic acute myocarditis during treatment for controlled human malaria infection: A case report

Malaria Journal (Impact Factor: 3.11). 01/2014; 13(1):38. DOI: 10.1186/1475-2875-13-38
Source: PubMed


A 23-year-old healthy male volunteer took part in a clinical trial in which the volunteer took chloroquine chemoprophylaxis and received three intradermal doses at four-week intervals of aseptic, purified Plasmodium falciparum sporozoites to induce protective immunity against malaria. Fifty-nine days after the last administration of sporozoites and 32 days after the last dose of chloroquine the volunteer underwent controlled human malaria infection (CHMI) by the bites of five P. falciparum-infected mosquitoes. Eleven days post-CHMI a thick blood smear was positive (6 P. falciparum/muL blood) and treatment was initiated with atovaquone/proguanil (Malarone(R)). On the second day of treatment, day 12 post-CHMI, troponin T, a marker for cardiac tissue damage, began to rise above normal, and reached a maximum of 1,115 ng/L (upper range of normal = 14 ng/L) on day 16 post-CHMI. The volunteer had one ~20 minute episode of retrosternal chest pain and heavy feeling in his left arm on day 14 post-CHMI. ECG at the time revealed minor repolarization disturbances, and cardiac MRI demonstrated focal areas of subepicardial and midwall delayed enhancement of the left ventricle with some oedema and hypokinesia. A diagnosis of myocarditis was made. Troponin T levels were normal within 16 days and the volunteer recovered without clinical sequelae. Follow-up cardiac MRI at almost five months showed normal function of both ventricles and disappearance of oedema. Delayed enhancement of subepicardial and midwall regions decreased, but was still present. With the exception of a throat swab that was positive for rhinovirus on day 14 post-CHMI, no other tests for potential aetiologies of the myocarditis were positive. A number of possible aetiological factors may explain or have contributed to this case of myocarditis including, i) P. falciparum infection, ii) rhinovirus infection, iii) unidentified pathogens, iv) hyper-immunization (the volunteer received six travel vaccines between the last immunization and the CHMI), v) atovaquone/proguanil treatment, or vi) a combination of these factors. Definitive aetiology and pathophysiological mechanism for the myocarditis have not been established.

Download full-text


Available from: Guido J H Bastiaens, Aug 17, 2014
  • Source
    • "At screening, in addition to a full medical history, examination , urinalysis, and pregnancy test in females, safety blood tests (including complete blood count, hamoglobinopathy screen, electrolytes, liver function tests and assays for HIV, hepatitis B, hepatitis C) and an electrocardiogram were performed for each volunteer to identify and exclude any individuals with baseline abnormalities (Nieman et al., 2009; Van Meer et al., 2014 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Controlled human malaria infection (CHMI) studies are a vital tool to accelerate vaccine and drug development. As CHMI trials are performed in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics (PGD) and immunological responses. However, CHMI studies have not been routinely performed in malaria-endemic countries or used to investigate mechanisms of naturally-acquired immunity (NAI) to Plasmodium falciparum. We conducted an open-label, randomized CHMI pilot-study using aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) to evaluate safety, infectivity and PGD in Kenyan adults with low to moderate prior exposure to P. falciparum (Pan African Clinical Trial Registry: PACTR20121100033272). All participants developed blood-stage infection confirmed by quantitative polymerase chain reaction (qPCR). However one volunteer (110) remained asymptomatic and blood-film negative until day 21 post-injection of PfSPZ Challenge. This volunteer had a reduced parasite multiplication rate (PMR) (1.3) in comparison to the other 27 volunteers (median 11.1). A significant correlation was seen between PMR and screening anti-schizont Enzyme Linked Immunosorbent Assays (ELISA) OD (p = 0.044, R = -0.384) but not when volunteer 110 was excluded from the analysis (p = 0.112, R = -0.313). PfSPZ Challenge is safe and infectious in malaria-endemic populations and could be used to assess the efficacy of malaria vaccines and drugs in African populations. Whilst our findings are limited by sample size, our pilot study has demonstrated for the first time that NAI may impact on PMR post-CHMI in a detectable fashion, an important finding that should be evaluated in further CHMI studies.
    Full-text · Article · Dec 2014 · Frontiers in Microbiology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Controlled human malaria infection (CHMI) by mosquito bite has been used to assess new anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious.
    Full-text · Article · Jul 2014 · The American journal of tropical medicine and hygiene
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Controlled human malaria infection (CHMI) studies, in which healthy volunteers are infected with Plasmodium falciparum to assess the efficacy of novel malaria vaccines and drugs, have become a vital tool to accelerate vaccine and drug development. CHMI studies provide a cost-effective and expeditious way to circumvent the use of large-scale field efficacy studies to deselect intervention candidates. However, to date few modern CHMI studies have been performed in malaria-endemic countries. An open-label, randomized pilot CHMI study was conducted using aseptic, purified, cryopreserved, infectious P. falciparum sporozoites (SPZ) (Sanaria® PfSPZ Challenge) administered intramuscularly (IM) to healthy Kenyan adults (n = 28) with varying degrees of prior exposure to P. falciparum. The purpose of the study was to establish the PfSPZ Challenge CHMI model in a Kenyan setting with the aim of increasing the international capacity for efficacy testing of malaria vaccines and drugs, and allowing earlier assessment of efficacy in a population for which interventions are being developed. This was part of the EDCTP-funded capacity development of the CHMI platform in Africa. This paper discusses in detail lessons learnt from conducting the first CHMI study in Kenya. Issues pertinent to the African setting, including community sensitization, consent and recruitment are considered. Detailed reasoning regarding the study design (for example, dose and route of administration of PfSPZ Challenge, criteria for grouping volunteers according to prior exposure to malaria and duration of follow-up post CHMI) are given and changes other centres may want to consider for future studies are suggested. Performing CHMI studies in an African setting presents unique but surmountable challenges and offers great opportunity for acceleration of malaria vaccine and drug development. The reflections in this paper aim to aid other centres and partners intending to use the CHMI model in Africa.
    Full-text · Article · Apr 2015 · Malaria Journal
Show more