Treatment Of Malaria In Adults Research Articles

Safety and efficacy of photodynamic therapy for the treatment of malaria in adults in Nigeria: Phase 2 trial

Background: This is the first randomized controlled trial assessing the efficacy and safety of photodynamic therapy in the treatment of uncomplicated falciparum Malaria in adults. The aim of the current study is to evaluate the use of photodynamic therapy as a possible novel treatment option.

Artesunate and Dihydroartemisinin Inhibit Rabies Virus Replication.

Rabies is caused by infection of rabies virus (RABV) and remains a serious threat to the global public health. Except for the requirement for cold chain and high cost of human rabies immune globulin, no small molecule drugs are currently available for clinical treatment of rabies. So, it is of great importance to identify novel compounds that can effectively inhibit RABV infection. Artesunate (ART) and dihydroartemisinin (DHA), two derivatives of artemisinin, are widely used for treatment of malaria in adults and children, showing high safety. In this study, we found that both ART and DHA were able to inhibit RABV replication in host cells at a low concentration (0.1 μmol/L). The antiviral effects of ART and DHA were independent of viral strains and cell lines. Pre-treatment with ART or DHA for 2 h in vitro did not affect the viral replication in host cells, implying that ART and DHA neither reduced the viability of RABV directly nor inhibited the binding and entrance of the virus to host cells. Further studies revealed that ART and DHA inhibited RABV genomic RNA synthesis and viral gene transcription. Treatment with ART or DHA (5 mg/kg) by intramuscular injection improved, to some extent, the survival rate of RABV-challenged mice. Combination treatment with derivatives of artemisinin and mannitol significantly improved the survival rate of RABV-challenged mice. The results suggest that ART and DHA have a great potential to be explored as new anti-rabies agents for treatment of rabies.

Drug interactions with antimalarial medications in older travelers: a clinical guide.

Increasingly older adults are traveling to international destinations with malaria as a present risk. Surveillance systems indicate that older adults are more likely to suffer severe complications from malaria. The role of health care providers in selecting an appropriate medication for chemoprophylaxis or treatment of malaria in adults becomes more difficult as older adults undergo physiologic changes that alter the pharmacokinetic and pharmacodynamic nature of medications potentially causing increased drug interactions, adverse events and altered drug action. A comprehensive literature search from 1970 to present, with a focus on the past 10years, was conducted on drug interactions, pharmacokinetic and pharmacodynamic effects on antimalarials in adults. It was determined that due to pharmacodynamic and pharmacokinetic changes in older adults, especially renal and cardiovascular, special attention should be given to this population of travelers in order to minimize the likelihood of adverse events or altered drug efficacy. Antimalarial drug-disease interactions in older adults can occur more often due to QT prolongation, exacerbation of hypoglycemia, decreased renal elimination and decreased hepatic metabolism. Older antimalarials have well-documented drug-drug interactions. Tafenoquine, a new antimalarial, requires glucose-6-phosphate dehydrogenase screening like primaquine and monitoring of new potential drug interaction with MATE1 and OCT2 substrates. While drug-drug interactions in older travelers may occur more often as a result of polypharmacy, data did not indicate adverse reactions or decreased drug efficacy is greater compared with younger adults. Overall, with the exception of recently approved tafenoquine, much is known about antimalarial drug and disease interactions, but new drugs are always being approved, requiring travel health providers to understand the pharmacokinetics and pharmacodynamics of antimalarial drugs to predict the impact on safety and efficacy in travelers. This guide provides travel health providers with valuable insights on potential outcomes associated with drug interactions in adults and recommended monitoring or drug regimen modification.

Development of a paediatric physiologically based pharmacokinetic model to assess the impact of drug-drug interactions in tuberculosis co-infected malaria subjects: A case study with artemether-lumefantrine and the CYP3A4-inducer rifampicin

The fixed dosed combination of artemether and lumefantrine (AL) is widely used for the treatment of malaria in adults and children in sub-Sahara Africa, with lumefantrine day 7 concentrations being widely used as a marker for clinical efficacy. Both are substrates for CYP3A4 and susceptible to drug-drug interactions (DDIs); indeed, knowledge of the impact of these factors is currently sparse in paediatric population groups. Confounding malaria treatment is the co-infection of patients with tuberculosis. The concomitant treatment of AL with tuberculosis chemotherapy, which includes the CYP3A4 inducer rifampicin, increases the risk of parasite recrudescence and malaria treatment failure. This study developed a population-based PBPK model for AL in adults capable of predicting the pharmacokinetics of AL under non-DDI and DDI conditions, as well as predicting AL pharmacokinetics in paediatrics of 2–12years of age. The validated model was utilised to assess the concomitant treatment of rifampicin and lumefantrine under standard body-weight based treatment regimens for 2–5year olds, and demonstrated that no subjects attained the target day 7 concentration (Cd7) of 280ng/mL, highlighting the importance of this DDI and the potential risk of malaria-TB based DDIs. An adapted 7-day treatment regimen was simulated and resulted in 63% and 74.5% of subjects attaining the target Cd7 for 1-tablet and 2-tablet regimens respectively.

Evaluation of cost of treatment of malaria in adults in Benin City, Nigeria: patients' perspective.

Malaria remains a disease of immense clinical and economic significance. Limited research has been carried out to estimate malaria treatment costs at the health care facility level using the patient's perspective. The objectives of this study were therefore to determine the direct and indirect costs of malaria treatment among adult outpatients and to assess the patients' perception of treatment costs. A cr oss-sectional study was conducted at the Pharmacy section of the General Practice Clinic, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria. It involved adult outpatients diagnosed with malaria and who received a prescription of one or more anti-malarial medications. A cost-of-illness approach was employed in the assessment of costs of treatment of malaria per sick adult patient. Pre-tested semi-structured questionnaires were used in the study. Furthermore, self-reported incidence of malaria per year was assessed. The mean direct and indirect cost of tr eating malaria illness per adult outpatient was Nigerian Naira (NGN) 3417.70 ($ 20.34) and NGN 4870 ($ 29.0), respectively, giving a ratio of 0.7:1. Medications and laboratory tests for detection of malaria parasites contributed about 52 and 22% of the total direct cost, respectively. A total of 1592 malaria episodes were self-reported to occur annually, giving a mean value of 3.35 episodes per adult. Having a health care insurance was associated with the response that the cost of malaria treatment was low (P< 0.001). The mean values of direct cost and indirect cost of treatment of malaria illness per adult outpatient were $ 20.34 and $ 29.0, respectively. Respondents who had health insurance perceived malaria treatment cost to be low, whereas those without such insurance felt otherwise.

Neurotoxicity Assessment of Artemether in Juvenile Rats

Oral administration of artemether in combination with lumefantrine is approved for the treatment of malaria in adults and children. In adult animals, artemether can produce neurotoxicity with intramuscular, but not oral, administration. Herein, the potential of orally administered artemether to produce neurotoxicity in juvenile rats was investigated. In the first study, the toxicity of artemether was evaluated in juvenile rats dosed with 0, 10, 30, and 100mg/kg/day on postpartum days (ppds) 7 to 21. In-life, clinical pathology, anatomic pathology, behavioral, and toxicokinetics evaluations were performed. The second study focused on neurotoxicity during different dosing intervals, with doses of 0, 30, and 80 mg/kg/day on ppds 7 to 13, and doses of 0, 30, and 120 mg/kg/day on ppds 14 to 21, 22 to 28, and 29 to 36. For each dosing interval, in-life, extensive histology, toxicokinetics, and behavioral evaluations were performed. In the third study, toxicokinetics evaluations in the adult were conducted at 20 and 200 mg/kg/day. The first study demonstrated increased mortality, renal necrosis, and brain hemorrhage at ≥30 mg/kg/day with no persistent effects in surviving animals. In the second study, increased mortality, body weight effects, and a trend toward increased exposure were observed in the ppd 14 and younger animals. Neither specific neurotoxicity nor persistent effects were seen. The toxicokinetic study in adults revealed lower exposures as compared to those in the younger juvenile rats. As in the adult rat, oral administration of artemether in the juvenile rat is not associated with the neurotoxicity produced by intramuscular administration.

Utilization of the current national antimalarial treatment guidelines among doctors in army hospitals in Lagos, Nigeria

Introduction: Human malaria infection remains a problem of public health importance in many regions of the world. The infection continues to spread particularly in sub-Saharan Africa. In Nigeria, malaria and its treatment have been affected by factors like wrong diagnosis, wrong attitude of the people, unavailability of drugs, fake and substandard drugs, attitude and practices of medical and paramedical personnel. Nigeria’s national standard for malaria treatment was recently changed to artemisinin combination therapy. Methods: A descriptive study using a structured questionnaire was administered to all doctors (123) practicing in the three Army hospitals in Lagos. The study was done between March, 2009 and April, 2009. The findings were precoded; data entry and analysis was done using EPI INFO version 3.5.1 statistical software. Results: Presumptive/clinical diagnosis was still a common practice for diagnosing malaria among doctors, as well as the use of microscopy. None of the doctors had the facility for diagnosing malaria with rapid diagnostic test in their hospitals. Fifty one percent of the doctors stated that they utilized the current National antimalarial treatment guidelines. Significant proportion of the doctors used Artemisinin-based Combination Therapy (ACTs) as first line treatment of uncomplicated malaria in adults and children. Chloroquine was the commonest drug for first line treatment of uncomplicated malaria in pregnancy. Only 45.5% of the doctors had correct knowledge of Intermittent Preventive Treatment in pregnancy (IPTp), while 33.3% knew the stage of pregnancy in which a pregnant woman should receive IPTp with sulphadoxine-pyrimethamine. Awareness and the content of knowledge of the current National antimalarial treatment guideline were not affected by the category or current position of the doctors. Thirteen percent of the respondents had attended training/update workshop organized by the Federal Ministry of Health (FMOH) Roll Back Malaria programme on the current National antimalarial treatment guideline. Conclusion: The study showed that there is need to improve use of recommended antimalarial medicines for all categories of patients by doctors in Army Hospitals in Lagos. More effort should be made by the Federal Ministry of Health and other stakeholders to organize training and refresher courses on the current National antimalarial treatment guidelines for all categories of health care providers.

Artemether–lumefantrine: an oral antimalarial for uncomplicated malaria in children

Artemether–lumefantrine (AL; Coartem®, Riamet®) is the first fixed-dose artemisinin combination therapy (ACT) regimen to be manufactured under Good Manufacturing Practice conditions, and is the most widely adopted ACT regimen used in malaria control programs. AL is approved for the treatment of uncomplicated malaria in adults, children and infants, and as treatment of uncomplicated malaria in nonimmune travelers returning from malarious areas. AL is efficacious for treating uncomplicated malaria in children and the frequency of associated adverse events is not higher than other available ACT regimens. In this review, available evidence on efficacy and safety of AL in the treatment of uncomplicated malaria, with emphasis on children where appropriate, and focusing on characteristics that are potentially important for malaria control policy decisions, are presented and discussed.

Artesunate, artemether or quinine in severe Plasmodium falciparum malaria?

Quinine and the artemisinin-derivative drugs artesunate and artemether are effective treatments for severe falciparum malaria. Trials comparing artemether with quinine have not demonstrated convincing evidence of a mortality advantage for artemether. The South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT), a multicenter, randomized, open-label trial in 1461 adults with severe malaria in Asia compared artesunate with quinine. Mortality was 15% in the artesunate group and 22% in the quinine group, a reduction of 34.7% (95% confidence interval: 18.5–47.6%) in the artesunate group, with almost all the benefit reported in those with high parasite counts. Artesunate should constitute first-line treatment for severe malaria in Asia. These results can probably be generalized to the treatment of severe malaria in adults from all areas, especially in those with hyperparasitemia. However, it is unclear whether these results can be generalized to children in Africa, who constitute the majority of those who die from severe malaria worldwide.

Mefloquine

Mefloquine is an orally administered blood schizontocide. Initial dose-finding and comparative studies performed between 1977 and 1989 demonstrated efficacy of mefloquine as prophylaxis in nonimmune individuals and in the suppression and treatment of malaria in adults and children caused by multidrug-resistant Plasmodium falciparum. It was also effective against P. vivax infection, while data concerning the treatment of P. ovale and P. malariae infections were limited. In an attempt to delay the emergence of resistance to this promising antimalarial agent, mefloquine was combined with sulfadoxine and pyrimethamine. Although initial clinical trials indicated that this regimen was effective in preventing and treating falciparum malaria, recent treatment failures, the potential for severe dermatological reactions and lack of therapeutic advantage over mefloquine alone has prompted the World Health Organization to recommended that the combination be no longer used for treatment or prophylaxis of malaria. Mefloquine is generally well tolerated in both adults and children, with nausea, vomiting, diarrhoea, headache, dizziness, rash, pruritus and abdominal pain being the most common adverse effects, although it is difficult to distinguish between disease- and treatment-related events. The incidence of these adverse effects is similar to or lower than those observed with other antimalarial agents. Cardiovascular changes, such as bradycardia, occasionally occur. The most notable adverse effects associated with mefloquine are neuropsychiatric disturbances; precipitation of such events should be closely monitored and requires termination of prophylaxis or therapy. The eventual emergence of resistance to mefloquine, as with many other antimalarial agents, was inevitable. Mefloquine resistance is established in certain areas of Thailand and may be becoming a growing problem in other regions of the world. In order to preserve the efficacy of mefloquine in non-resistant areas, this useful agent should be used with care and only prescribed for prophylaxis in travellers and treatment in areas of multidrug-resistant plasmodia. Future options to combat mefloquine resistance may include the combination of mefloquine with other antimalarial agents such as qinghaosu derivatives. Thus, with cautious use and possible combination with other agents, mefloquine is likely to remain an important treatment option for falciparum malaria, a widespread parasitic disease for which an increasing number of drugs have proved inadequate.