In Vivo Efficacy and Pharmacokinetics of the 2-Aminomethylphenol Antimalarial JPC-3210 in the Aotus Monkey-Human Malaria Model.

Nonimmune Aotus monkeys infected with Plasmodium falciparum and Plasmodium vivax were cured of their infections when treated with a single oral dose of 5 mg/kg and 10 mg/kg of the 2-aminomethylphenol, JPC-3210, respectively. Corresponding mean blood elimination half-lives of JPC-3210 were lengthy at 19.1 days and 20.5 days, respectively. This in vivo potency and lengthy half-life supports the further development of JPC-3210 as a promising, long-acting blood schizontocidal antimalarial for malaria treatment and prevention.

Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report.

The diagnosis and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency is a crucial aspect in the current phases of malaria control and elimination, which will require the wider use of 8-aminoquinolines for both reducing Plasmodium falciparum transmission and achieving the radical cure of Plasmodium vivax. 8-aminoquinolines, such as primaquine, can induce severe haemolysis in G6PD-deficient individuals, potentially creating significant morbidity and undermining confidence in 8-aminoquinoline prescription. On the other hand, erring on the side of safety and excluding large numbers of people with unconfirmed G6PD deficiency from treatment with 8-aminoquinolines will diminish the impact of these drugs. Estimating the remaining G6PD enzyme activity is the most direct, accessible, and reliable assessment of the phenotype and remains the gold standard for the diagnosis of patients who could be harmed by the administration of primaquine. Genotyping seems an unambiguous technique, but its use is limited by cost and the large range of recognized G6PD genotypes. A number of enzyme activity assays diagnose G6PD deficiency, but they require a cold chain, specialized equipment, and laboratory skills. These assays are impractical for care delivery where most patients with malaria live. Improvements to the diagnosis of G6PD deficiency are required for the broader and safer use of 8-aminoquinolines to kill hypnozoites, while lower doses of primaquine may be safely used to kill gametocytes without testing. The discussions and conclusions of a workshop conducted in Incheon, Korea in May 2012 to review key knowledge gaps in G6PD deficiency are reported here.

Operational research to inform a sub-national surveillance intervention for malaria elimination in Solomon Islands.

BACKGROUND: Successful reduction of malaria transmission to very low levels has made Isabel Province, Solomon Islands, a target for early elimination by 2014. High malaria transmission in neighbouring provinces and the potential for local asymptomatic infections to cause malaria resurgence highlights the need for sub-national tailoring of surveillance interventions. This study contributes to a situational analysis of malaria in Isabel Province to inform an appropriate surveillance intervention. METHODS: A mixed method study was carried out in Isabel Province in late 2009 and early 2010. The quantitative component was a population-based prevalence survey of 8,554 people from 129 villages, which were selected using a spatially stratified sampling approach to achieve uniform geographical coverage of populated areas. Diagnosis was initially based on Giemsa-stained blood slides followed by molecular analysis using polymerase chain reaction (PCR). Local perceptions and practices related to management of fever and treatment-seeking that would impact a surveillance intervention were also explored using qualitative research methods. RESULTS: Approximately 33% (8,554/26,221) of the population of Isabel Province participated in the survey. Only one subject was found to be infected with Plasmodium falciparum (Pf) (96 parasites/µL) using Giemsa-stained blood films, giving a prevalence of 0.01%. PCR analysis detected a further 13 cases, giving an estimated malaria prevalence of 0.51%. There was a wide geographical distribution of infected subjects. None reported having travelled outside Isabel Province in the previous three months suggesting low-level indigenous malaria transmission. The qualitative findings provide warning signs that the current community vigilance approach to surveillance will not be sufficient to achieve elimination. In addition, fever severity is being used by individuals as an indicator for malaria and a trigger for timely treatment-seeking and case reporting. In light of the finding of a low prevalence of parasitaemia, the current surveillance system may not be able to detect and prevent malaria resurgence. CONCLUSION: An adaption to the malERA surveillance framework is proposed and recommendations made for a tailored provincial-level surveillance intervention, which will be essential to achieve elimination, and to maintain this status while the rest of the country catches up.

Malaria and other vector-borne infection surveillance in the U.S. Department of Defense Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance program: review of 2009 accomplishments.

Vector-borne infections (VBI) are defined as infectious diseases transmitted by the bite or mechanical transfer of arthropod vectors. They constitute a significant proportion of the global infectious disease burden. United States (U.S.) Department of Defense (DoD) personnel are especially vulnerable to VBIs due to occupational contact with arthropod vectors, immunological naiveté to previously unencountered pathogens, and limited diagnostic and treatment options available in the austere and unstable environments sometimes associated with military operations. In addition to the risk uniquely encountered by military populations, other factors have driven the worldwide emergence of VBIs. Unprecedented levels of global travel, tourism and trade, and blurred lines of demarcation between zoonotic VBI reservoirs and human populations increase vector exposure. Urban growth in previously undeveloped regions and perturbations in global weather patterns also contribute to the rise of VBIs. The Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) and its partners at DoD overseas laboratories form a network to better characterize the nature, emergence and growth of VBIs globally. In 2009 the network tested 19,730 specimens from 25 sites for Plasmodium species and malaria drug resistance phenotypes and nearly another 10,000 samples to determine the etiologies of non-Plasmodium species VBIs from regions spanning from Oceania to Africa, South America, and northeast, south and Southeast Asia. This review describes recent VBI-related epidemiological studies conducted by AFHSC-GEIS partner laboratories within the OCONUS DoD laboratory network emphasizing their impact on human populations.

The conundrum of malaria chemoprophylaxis.

Alternative approaches to malaria chemoprophylaxis are discussed in light of the difficulties of executing clinical trials within limits of infection rates and ethics.