Administration Of Antimalarial Drugs Research Articles

Home management of malaria in an academic community - University of Benin, Benin City, Nigeria

Malaria remains one of the world\'s most devastating diseases, killing millions of people yearly. Home management is an important strategy adopted for the reduction of its fatality. This survey to evaluate home management practices towards malaria among heads of households was undertaken at the residential quarters of the University of Benin, Benin City, Nigeria. The residential quarters consists of 239 housing units; 179 units accommodating senior workers and 60 units accommodating junior workers. Using the systematic sampling method, a sampling ratio of 1:2 was used in selecting a total of 120 housing units and 120 heads of households for the study. A structured interviewer-administered questionnaire was used for data collection. Results show that of the 120 heads of households interviewed 70.8% were males, while 29.2% were females. Knowledge of the cause of malaria was poor 46 (38.3%). However, knowledge improved with increase in level of education and this association was found to be statistically significant (p = 0.002). The common signs and symptoms associated with malaria in descending order of prevalence were fever 83.3%, weakness 70.0%, headache 62.5%, body pains 50.8%, vomiting 47.7% and loss of appetite 40.8%. Majority of respondents (52.5%) delayed treatment to between one to three days after recognition of signs/symptoms of malaria. Most of the respondents (90.8%) preferred orthodox drugs for home treatment of malaria while 3.3% and 5.8% used herbal preparations. Others used a combination of orthodox and herbal preparations. The commonly used orthodox drugs were choloroquine (45.0%), followed by sulphadoxine pyrimethamine (fansidar) (25.0%) and sulphadaxin pyrimethamine (maloxine) (20.0%), amongst others. However, chloroquine, which was most commonly used, was the most incorrectly administered. Prevention against malaria was mostly achieved through the use of door/window gauze (35%) and combination of insecticide and door/window gauze (30%). Home management of malaria is an important strategy that needs to be sustained. However, inadequate treatment regimen remains a hindrance to the success of this vital control effort. There is a need to educate all strata of the society on the correct administration of common antimalarials to reduce the impact of the disease. Keywords : Malaria, home management, University of Benin, treatment Journal of Medicine and Biomedical Research Vol. 3 (1) 2004: pp. 73-80

Simultaneous liquid chromatographic analysis of ritonavir, quinine and 3-hydroxyquinine in human plasma

In regions with high prevalence of HIV and malaria, co-infection of both diseases is common; hence, there is a high possibility of concurrent administration of antiretroviral and antimalarial drugs. This study describes a new ion-pair reversed-phase high-performance liquid chromatographic (HPLC) method for simultaneous determinations of ritonavir (RTV), quinine (QN), and its major metabolite, 3-hydroxyquinine (3-HQN), in human plasma. Following a simple extraction with diethyl-ether under alkaline conditions, chromatographic separation was achieved on a 5-μm particle size C-18 column (200 mm × 4.6 mm I.D.) using a mobile phase consisting of methanol:acetonitrile:0.02 M potassium dihydrogen phosphate (15:10:75) containing 75 mmol/L perchloric acid (pH 2.8). Retention times for RTV, 3-HQN, QN and the internal standard were 2.8, 4.0, 7.0 and 12 min, respectively. The limits of detection and validated lower limits of quantitation were 10 and 12.5 ng/ml for RTV while the corresponding values were 5 and 70 ng/ml for both QN and 3-HQN, respectively. The new HPLC method is simple, rapid, selective, reproducible and cost-effective. As demonstrated in three volunteers, it will facilitate the conducting of simultaneous therapeutic monitoring of quinine and ritonavir in patients concurrently receiving both drugs.

Malaria control and prevention

Of all the insect-borne diseases, malaria is the most serious public health problem, even though deaths from malaria are generally preventable. Eradication was tried in the 1950s and 60s but was abandoned to a strategy of control. However, recent developments indicate that eradication could be reconsidered, given enough time and money. The three elements of control are case management of patients with malaria, prevention of infection through vector control and prevention of disease by administration of antimalarial drugs to particularly vulnerable population groups (Centers for Disease Control and Prevention (CDC) 2006).

Intermittent preventive antimalarial treatment to children (IPTc): firebreak or fire trap?

Intermittent preventive treatment is the prescheduled administration of antimalarial drugs to at-risk patients in endemic areas. This approach, which is recommended for pregnant women, is being evaluated in children. Sulfadoxine-pyrimethamine plus amodiaquine recently proved to be more protective than artemisinin-containing regimens. Therefore, the use of artemisinin derivatives could potentially be restricted to symptomatic patients. Determinants of three pending issues: safety, efficacy throughout childhood, and effectiveness--the latter depending on the implementation of sustainable delivery mechanisms--are analyzed in this comment.

Rho Kinase Inhibition in Severe Malaria: Thwarting Parasite‐Induced Collateral Damage to Endothelia

Acute clinical manifestations of falciparum malaria, such as multiorgan failure and cerebral malaria, occur unpredictably and lead to coma and death within hours if left untreated. Despite the emergency administration of effective antimalarial drugs, 15%-20% of patients die. Other therapeutic approaches are therefore urgently needed. There is increasing evidence that endothelial changes play a key role in the pathogenesis of severe malaria. We therefore used coculture models to study interactions between infected erythrocytes and endothelium. We found that adhesion of Plasmodium falciparum to endothelial cells in vitro activated the Rho kinase signaling pathway, which is strongly involved in various vascular diseases. When added concomitantly with parasites, the Rho kinase inhibitor fasudil (HA-1077), a drug already in clinical use, decreased both NF-kappaB activation and endothelial cell apoptosis. Fasudil also helped to restore endothelial barrier integrity after P. falciparum adhesion. Rho kinase inhibition thus appears to be a promising adjunctive therapeutic approach to the management of severe human malaria.

Evidence-Based Therapy for Cutaneous Sarcoidosis

Although healthcare providers have arrived at a relatively comfortable zone of accepted clinical practice in the management of cutaneous sarcoidosis, virtually every treatment is based on minimal evidence-based data and relies almost exclusively on anecdotal information. Although it would be convenient to blame this state of affairs on the lack of certainty about disease aetiology, the unavoidable fact is that little has been executed, even in the realm of well designed comparative trials. Nonetheless, worldwide accepted standard therapies for sarcoidosis include the administration of corticosteroids, antimalarials and methotrexate. A stepwise approach to patient care is appropriate, and potent topical corticosteroids (e.g. clobetasol) or repeated intralesional injections of triamcinolone (3-10 mg/mL) may be all that is needed in mild skin-limited disease. In patients requiring systemic therapy for recalcitrant or deforming skin lesions (or for widespread disease), corticosteroids (e.g. prednisone 40-80 mg/day, tapered accordingly) used alone or in combination with antimalarials or methotrexate may be indicated. Antimalarials and methotrexate are considered second-line interventions and may be used as monotherapy for steroid-resistant sarcoidosis or in patients unable to tolerate steroids. Given the concern regarding ocular toxicity, the maximum dosages of chloroquine and hydroxychloroquine should not exceed 3.5 and 6.5 mg/kg/day, respectively. Methotrexate is given in weekly doses of 10-30 mg, with the caveat that haematological, gastrointestinal, pulmonary and hepatic toxicities are possible. Despite universal acceptance as standard care, the aforementioned treatments often result in an incomplete clinical response or unacceptable adverse events. In such situations, more innovative treatment options may be used. Treatments that may well gain widespread future use include the tumour necrosis factor-alpha inhibitors infliximab and adalimumab. Experience is limited, but early reports are promising. Infliximab is administered via intravenous infusion at doses of 3-10 mg/kg at 0, 2 and 6 weeks and as indicated thereafter, whereas adalimumab is injected subcutaneously at doses of 40 mg either weekly or every 2 weeks. Because adalimumab is not approved for the management of sarcoidosis, the optimum dose administration interval is uncertain. However, it has been given in both weekly and every other week regimens. Isotretinoin, 0.5-2 mg/kg/day, has been used successfully in a handful of reported cases. However, the teratogenic potential of isotretinoin is often prohibitive considering that the primary demographic group likely to develop sarcoidosis is women of childbearing potential. Thalidomide at dosages of 50 to >400 mg/day has limited, albeit promising, supporting data. However, access is restricted in many countries because of a deserved pregnancy category X rating. Melatonin (20 mg/day) and allopurinol (100-300 mg/day) are not well studied in cutaneous sarcoidosis, and the clinical experience with tetracycline derivatives has been mixed. That said, there are compelling reports of therapeutic benefit with both doxycycline and minocycline. Because neither of these agents is associated with the severe toxicity of cytotoxic drugs, they may serve as effective therapy in some patients. Pentoxifylline (400 mg three times daily) has been of use in a small number of reported cases of pulmonary sarcoidosis, but there are no reports on its use in patients with primarily cutaneous disease. Both ciclosporin and chlorambucil have been largely abandoned given their associated toxicity and disappointingly unreliable efficacy. Finally, laser therapy is a newer modality that may provide patients with a quick and non-invasive treatment option for cutaneous sarcoidosis.

Hospitalization Criteria in Imported Falciparum Malaria

Controversy exists about the management of patients with imported Plasmodium falciparum malaria. We postulated that rapid parasite clearance supports ambulatory care, or, conversely, that factors associated with longer parasite clearance time (PCT) could be used as hospitalization criteria. Hospitalized patients with imported falciparum malaria recruited through one single travel clinic between 1993 and 2000. We used a linear regression to identify factors independently associated with PCT defined as the time in hours from antimalarial drug administration until the first negative malaria smear. Among 400 patients hospitalized with falciparum malaria, mean (range) PCT was 58 (1-189) hours. In multivariate analysis, severe malaria, gastrointestinal signs, initial temperature greater than or equal to 40 degrees C, parasitemia greater than or equal to 1%, and platelet counts less than 50,000/microL were associated with longer PCT. Offering ambulatory care to patients aged 15 to 64 years with none of the factors associated with longer PCT in the study would have resulted in 147 (37%) patients receiving outpatient care. Factors identified in this model may help physicians determine which P falciparum malaria patients can be treated on an ambulatory basis, and contribute to revisions of national guidelines for imported malaria management.

Intermittent Preventive Treatment in Infants as a Means of Malaria Control: a Randomized, Double-Blind, Placebo-Controlled Trial in Northern Ghana

Morbidity and mortality from malaria remain unacceptably high among young children in sub-Saharan Africa. Intermittent preventive treatment in infancy (IPTi) involves the administration of antimalarials alongside routine vaccinations and might be an option in malaria control. In an area of intense, perennial malaria transmission in northern Ghana, 1,200 children received IPTi with sulfadoxine-pyrimethamine or placebo at approximately 3, 9, and 15 months of age. Children were followed up until 24 months of age to assess morbidity and adverse events. During the intervention period (3 to 18 months of age), IPTi reduced the incidences of malaria and severe anemia by 22.5% (95% confidence interval, 12 to 32%) and 23.6% (95% confidence interval, 4 to 39%), respectively, and reduced hospitalizations and episodes of asymptomatic parasitemia by one-third. Protection was pronounced in the first year of life and not discernible in the second. The malaria-protective effect was largely confined to a period of 1 month after sulfadoxine-pyrimethamine treatments. Following the intervention, protection against asymptomatic parasitemia persisted. In contrast, a significant rebound of severe malaria, predominantly severe malarial anemia, occurred among children having received IPTi. Although the treatment was generally well tolerated, one case of moderately severe skin reaction followed sulfadoxine-pyrimethamine treatment. IPTi reduces malaria and anemia in infants in northern Ghana. Extension of IPTi into the second year of life by administering a dose at 15 months of age provided no substantial benefit beyond a 1-month prophylactic effect. Although this simple intervention offers one of the few available malaria-preventive measures for regions where malaria is endemic, the observed rebound of severe malaria advises caution and requires further investigation.

Intrahost Selection ofPlasmodium falciparum pfmdr1Alleles after Antimalarial Treatment on the Northwestern Border of Thailand

Increased pfmdr1 copy number is associated with reduced susceptibility to structurally unrelated antimalarial drugs. We assessed how administration of different antimalarial drugs altered pfmdr1 polymorphism in parasites from patients who experienced treatment failure. In studies conducted on the northwestern border of Thailand, amplifications and single-nucleotide polymorphisms in pfmdr1 were compared before and after antimalarial drug treatment. Intrahost changes in pfmdr1 copy number were observed in 20% (26/132) of patients with recurrent infections. Among infections that recrudesced after mefloquine-containing regimens, increases in pfmdr1 copy number occurred in 68% (95% confidence interval [CI], 46%-85%), and decreases occurred in 2% (95% CI, 0.4%-11%) of isolates; corresponding proportions after artemether-lumefantrine were 25% (2/8) and 11% (2/19); after quinine, 50% (1/2) and 40% (4/10); and after artemisinins alone, 0% (0/10) and 19% (3/16) of isolates (overall P<.001). Intrahost selection based on pfmdr1 copy number occurs frequently in parasite populations within individual patients. Amplification confers multidrug resistance but probably imposes a significant fitness cost to the parasites.

Population Pharmacokinetics of Artesunate and Dihydroartemisinin following Intra-Rectal Dosing of Artesunate in Malaria Patients

BackgroundIntra-rectal artesunate has been developed as a potentially life-saving treatment of severe malaria in rural village settings where administration of parenteral antimalarial drugs is not possible. We studied the population pharmacokinetics of intra-rectal artesunate and the relationship with parasitological responses in patients with moderately severe falciparum malaria.Methods and FindingsAdults and children in Africa and Southeast Asia with moderately severe malaria were recruited in two Phase II studies (12 adults from Southeast Asia and 11 children from Africa) with intensive sampling protocols, and three Phase III studies (44 children from Southeast Asia, and 86 children and 26 adults from Africa) with sparse sampling. All patients received 10 mg/kg artesunate as a single intra-rectal dose of suppositories. Venous blood samples were taken during a period of 24 h following dosing. Plasma artesunate and dihydroartemisinin (DHA, the main biologically active metabolite) concentrations were measured by high-performance liquid chromatography with electrochemical detection. The pharmacokinetic properties of DHA were determined using nonlinear mixed-effects modelling. Artesunate is rapidly hydrolysed in vivo to DHA, and this contributes the majority of antimalarial activity. For DHA, a one-compartment model assuming complete conversion from artesunate and first-order appearance and elimination kinetics gave the best fit to the data. The mean population estimate of apparent clearance (CL/F) was 2.64 (l/kg/h) with 66% inter-individual variability. The apparent volume of distribution (V/F) was 2.75 (l/kg) with 96% inter-individual variability. The estimated DHA population mean elimination half-life was 43 min. Gender was associated with increased mean CL/F by 1.14 (95% CI: 0.36–1.92) (l/kg/h) for a male compared with a female, and weight was positively associated with V/F. Larger V/Fs were observed for the patients requiring early rescue treatment compared with the remainder, independent of any confounders. No associations between the parasitological responses and the posterior individual estimates of V/F, CL/F, and AUC0–6h were observed.ConclusionsThe pharmacokinetic properties of DHA were affected only by gender and body weight. Patients with the lowest area under the DHA concentration curve did not have slower parasite clearance, suggesting that rectal artesunate is well absorbed in most patients with moderately severe malaria. However, a number of modelling assumptions were required due to the large intra- and inter-individual variability of the DHA concentrations.

Analysis of cost and effectiveness of pre-transfusion screening of donor blood and anti-malarial prophylaxis for recipients

To determine the prevalence of malaria in donor units in a low and a high endemic region in Kenya and evaluate the cost effectiveness of recipient anti-malarial prophylaxis and pre-transfusion screening (using an automated method) as options to prevent post transfusion malaria. A descriptive cross-sectional study. Two regional blood banks, Nairobi and its environs (National Blood Transfusion Services, Nairobi) a low malaria endemic region and western region (National Blood Transfusion Services, Kisumu) high malaria endemic region. All the donated units were included in the study for analysis, during the duration of study, from the two study sites. Prevalence of malaria in donor units in low endemic area (Nairobi) and high endemic area (Kisumu). Cost per case prevented for the two options, Option I Prophylactic administration of anti-malarial (sulfadoxine pyrimethamine SP) drugs to recipients, and Option II pre-transfusion screening using an automated technique. A malaria prevalence of 0.67% was found in Nairobi and its environments (low endemic) and 8.63% for Kisumu and its environments (high endemic area). The cost analysis showed a cost per case prevented of Ksh.105 (US$1.4) adult, Ksh.52.5 (US$0. 69) and paediatric for the option of recipient prophylaxis using an SP based drug. The cost escalated to Ksh.592 (US$7.79) adult Ksh.444 (US$5.84) paediatric if the prophylaxis was upgraded to the recommended artemisinin derivative (ACT-artemisinin based combination) and for the option of pre-transfusion screening using an automated technique the cost was Ksh.2.08 (US$0.03). The prevalence of malaria in donors showed the expected regional variation in the low and high endemic areas and was comparable to data obtained elsewhere. If malaria positive donor units were to be excluded from the national blood supply, an estimated 5% (compared to 1.3% for human Immunodeficiency virus, 3.6% for hepatitis B virus and 1.3% for hepatitis C virus) would be wasted. The cost per case prevented of transfusion-associated malaria is considerably higher for recipient antimalarial prophylaxis than pre-transfusion screening using an automated technique. The cost escalates by five to seven times if the newer artemesinin based combination antimalarial drugs are adopted.

Malaria and blood transfusion

The transmission of malaria by blood transfusion was one of the first recorded incidents of transfusion-transmitted infection. Although a number of different infections have been reported to be transmitted by transfusion since then, on a global scale malaria remains one of the most common transfusion-transmitted infections. Transfusion-transmitted malaria can have serious consequences, as infection with Plasmodium falciparum may prove rapidly fatal. Ensuring that, in non-endemic countries, the blood supply is free from malaria is problematical, especially as travel to malarious areas is increasing and there is some spread of the disease into new areas, as well as a resurgence of malaria in areas where previously it had been eradicated. In non-endemic countries, donor deferral can be effective, but clear guidelines are needed. In endemic countries the problem is far greater as the majority of donors may be potentially infected with malaria parasites. In both situations, the simple deferral of donors may be wasteful and can eventually erode the donor base. Thus, other strategies are needed to ensure safety with sufficiency. However, the screening of donations for evidence of malaria is not without its problems. Although the examination of blood films is still the basis for diagnosing acute malaria, in most situations it is not sufficiently sensitive for blood bank screening. In non-endemic countries, donor deferral in combination with screening for specific antimalarial immunoglobulin provides an effective means of minimizing the risk of transmission. In endemic countries, more specific donor questioning, consideration of seasonal variation and geographical distribution may help to identify the population of donors who are most likely to be infected. In addition, the administration of antimalarials to transfusion recipients may help to prevent transmission. Nonetheless, no matter what strategy is adopted, it is likely that cases of transfusion-transmitted malaria may still occur, so malaria must always be considered in any patient with a febrile illness post-transfusion.

Editorial: Intermittent preventive treatment for malaria control in infants: moving towards evidence‐based policy and public health action

It is important to balance the urgency of implementing a new efficacious intervention on a public health scale against the need to acquire convincing evidence on safety and efficacy. Two studies in Tanzania have shown that intermittent preventive treatment in infants (IPTi) the administration of antimalarial drugs at pre-specified times during the first year of life regardless of the presence of clinical symptoms or Plasmodium falciparum parasitaemia reduces episodes of malaria and anaemia by over 50%. Children followed up to the age of 2 years showed a sustained 36% reduction in the risk of malaria. IPTi has the potential to become a major tool for malaria control in Africa as it may be delivered at the time of routine vaccination – through the Expanded Programme on Immunisation (EPI) – which increases the chance of long-term sustainability. Should IPTi now be recommended as a malaria control strategy for Africa? A group of research scientists WHO and UNICEF reviewed the evidence that was available in 2002 and agreed that information would be required in three key areas before a recommendation on the role of IPTi in national malaria control strategies could be made. First the efficacy of IPTi in reducing episodes of clinical malaria and anaemia in different epidemiological settings should be known. Secondly it should be demonstrated that IPTi has no adverse impact on serological responses to EPI vaccines. Thirdly the reassuring safety data that is currently available on IPTi with sulphadoxine-pyrimethamine (SP) should be consolidated. (excerpt)

Paludisme

Differentiating malaria from other causes of fever is difficult. In France, among patients admitted to the ED with suspected malaria, over 25% have evidence of a thick smear for Plasmodium species, mainly Plasmodium falciparum. Currently accepted clinical variables associated with malaria diagnosis include an age older than 30 years, male gender, immigration to France from an area where malaria is endemic, a visit to sub-Saharan Africa, insufficient antimalaria prophylaxis, fever, chills, absence of diarrhea, a leukocyte count within the reference range, thrombocytopenia, and increased lactate dehydrogenase and bilirubin levels. However, alone or combined, these features have insufficient sensitivity and low specificity for the diagnosis of malaria. Malaria should be suspected in all patients presenting with complaints after a travel to an area where malaria is endemic; such patients should undergo blood microscopy. Successful management of malaria requires rapid diagnosis and initiation of appropriate antimalarial agents. The antimalarial drug and administration route will depend on drug availability and tolerance spectrum, however the increasing role of drug resistance in P. falciparum should be considered. We discuss new therapeutic options and decision making tools for patients hospitalizations.

THE USE OF ANTI-MALARIAL DRUGS TO PREVENT MALARIA IN THE POPULATION OF MALARIA-ENDEMIC AREAS

Anti-malarial drugs have been used in various ways to prevent malaria in the resident populations of endemic areas for nearly 100 years. The primary aim of most early studies was to interrupt transmission. This was rarely achieved, but administration of anti-malarial drugs either through medication of salt or by mass administration frequently led to a marked reduction in the prevalence of malaria infection and in the incidence of clinical attacks. Chemoprophylaxis is highly effective in reducing mortality and morbidity from malaria in young children and pregnant women living in endemic areas, but is difficult to sustain and, in some studies, has impaired the development of naturally acquired immunity. Intermittent preventive treatment, in which full therapeutic doses of a drug are given at defined intervals, has the potential to provide some of the benefits of sustained chemoprophylaxis in pregnant women and young children without some of its drawbacks and is a promising new approach to malaria control.

Impact of IMCI training and language used by provider on quality of counseling provided to parents of sick children in Bougouni District, Mali

This study evaluates the impact of the Integrated Management Of Childhood Illness (IMCI) training on quality of counseling provided to caregivers about administration of antimalarials to their children. Ten community health centers in southern Mali were randomized to either training or comparison arms of the study, and health providers’ consultations with caregivers were observed. Out of a 10-point counseling scale (Cronbach’s α =0.77), IMCI-trained providers completed an average of 1.47 (95% CI, −0.25, 3.2) more tasks than did providers who had not received IMCI training in a linear regression analysis that accounted for intra-provider correlations. Drug consultations done in both French and the local language, Bambara, had higher scores than those conducted exclusively in Bambara. The effect of providers receiving IMCI training was more pronounced in bilingual consultations, with an average increase of 2.49 (95% CI, 0.76, 4.22) in IMCI, bilingual consultations, and average increase of 0.87 (95% CI, −0.95, 2.69) in IMCI monolingual (Bambara) consultations as compared to non-IMCI-trained providers in monolingual consultations. IMCI training showed a non-significant trend overall in improving drug counseling provided to caregivers, with significant improvements in bilingual consultations. The IMCI program in Mali should consider strategies such as role-playing of counseling in Bambara or other local languages during training to improve patient–provider communication. Similar problems related to counseling by health workers in local languages are likely to be present throughout Africa, and warrant further study.

Mass administrations of antimalarial drugs.

Administration of antimalarial drugs to whole populations has been used as a malaria-control measure for more than 70 years. Drugs have been administered either directly as a full therapeutic course of treatment or indirectly through the fortification of salt. Mass drug administrations (MDAs) were generally unsuccessful in interrupting transmission but, in some cases, had a marked effect on parasite prevalence and on the incidence of clinical malaria. MDAs are likely to encourage the spread of drug-resistant parasites and so have only a limited role in malaria control. They could have a part to play in the management of epidemics and in the control of malaria in areas with a short transmission season. To reduce the risk of spreading drug resistance, MDAs should use more than one drug and, preferably include a drug, such as an artemisinin, which has a gametocidal effect.

Urban malaria: primary caregivers' knowledge, attitudes, practices and predictors of malaria incidence in a cohort of Ugandan children.

To assess malaria-related knowledge, attitude and practices (KAP) among primary caregivers, to identify associations between primary caregivers' characteristics and positive KAP towards malaria, and to identify independent predictors of childhood malaria incidence in an urban setting. Children aged 6 months to 5 years living in Kampala, Uganda were enrolled as part of a longitudinal study on antimalarial therapy. Primary caregivers of 307 children were interviewed and information was collected on demographics, malaria-related KAP, environmental and household factors. Malaria incidence was measured prospectively using passive surveillance. A total of 90% of respondents reported mosquitoes and/or malaria as the cause of fever. Caregivers reported that if their child had fever, 63% would go to a clinic or hospital as their first action and 97% as their first or second action. Only 38% knew that chloroquine was the recommended first-line treatment for malaria and 29% knew the correct dose. Preventive measures for malaria were reported in 45% of households but only 25% reported using bednets. Higher levels of education for the caregiver were associated with positive malaria-related KAP. Malaria incidence varied widely. The following were independent predictors of malaria incidence: (1). Children aged 24-41 months at enrolment had a higher incidence of malaria. (2). Reported bednet or chemoprophylaxis use reduced the incidence of malaria. (3). A child's place of residence was associated with incidence. (4). Children from households using open water sources had a higher incidence than those using closed sources. Primary caregivers were knowledgeable about malaria and used modern health care facilities but knew less about the proper administration of antimalarials and had limited use of preventive measures. Malaria incidence was associated with child's age at enrolment, geography, source of water and the use of preventive measures.

Recognition and management of falciparum malaria

Falciparum malaria is a serious parasitic infection that, if left untreated, can give rise to a range of life-threatening complications. Prompt recognition depends on a high index of suspicion and a detailed history identifying possible malaria risk factors. Symptoms and signs, apart from periodic fever in some cases, are typically non-specific. Even in cases of severe falciparum malaria with vital organ involvement, the differential diagnosis can be broad. The gold standard diagnostic test is blood film microscopy but antigen detection tests have become available as an alternative. Other laboratory tests can, together with the history and examination findings, help confirm the diagnosis and provide data relating to the nature and severity of complications. Management of malaria involves prompt administration of effective antimalarial drugs and prevention or amelioration of complications such as coma (cerebral malaria), renal failure and acidosis. Oral treatment is usually given to patients with uncomplicated malaria while therapy should be administered parenterally in severe cases. Conventional drugs such as quinine are still useful but the artemisinin derivatives are rapidly acting antimalarial drugs that are increasingly used as first-line therapy in tropical countries. Most adjunctive therapies assessed specifically for their effectiveness against complications have proved disappointing but some (such as prophylactic phenobarbitone and exchange transfusion) can complement generic management protocols that remain the cornerstone of intensive care for the severely ill patient with malaria.

Blood-stage dynamics and clinical implications of mixed Plasmodium vivax-Plasmodium falciparum infections.

We present a mathematical model of the blood-stage dynamics of mixed Plasmodium vivax-Plasmodium falciparum malaria infections in humans. The model reproduces features of such infections found in nature and suggests several phenomena that may merit clinical attention, including the potential recrudescence of a long-standing, low-level P. falciparum infection following a P. vivax infection or relapse and the capacity of an existing P. vivax infection to reduce the peak parasitemia of a P. falciparum superinfection. We simulate the administration of antimalarial drugs, and illustrate some potential complications in treating mixed-species malaria infections. Notably, our model indicates that when a mixed-species infection is misdiagnosed as a single-species P. vivax infection, treatment for P. vivax can lead to a surge in P. falciparum parasitemia.