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1.
Am J Trop Med Hyg ; 110(4): 677-680, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38460198

ABSTRACT

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.


Subject(s)
Anthelmintics , Artemisinins , Schistosomiasis mansoni , Sulfalene , Adolescent , Animals , Child , Humans , Anthelmintics/therapeutic use , Artemisinins/adverse effects , Artesunate/therapeutic use , Drug Therapy, Combination , East African People , Kenya , Praziquantel/adverse effects , Pyrimethamine/therapeutic use , Schistosoma mansoni , Schistosomiasis mansoni/drug therapy , Sulfalene/pharmacology , Sulfalene/therapeutic use , Treatment Outcome
2.
Trials ; 24(1): 763, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38012787

ABSTRACT

BACKGROUND: Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya. METHODS: The SCHISTOACT study is an open-label, head-to-head, five-arm, proof-of-concept, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-aged children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine, or artesunate-amodiaquine, or artesunate plus mefloquine, or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at - 10 for the risk difference in cure rates between praziquantel and the combined treatment. DISCUSSION: This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis and to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases. TRIAL REGISTRATION: Pan-African Clinical Trials Registry PACTR202001919442161 . Retrospectively registered on 6 January 2020.


Subject(s)
Anthelmintics , Artemisinins , Schistosomiasis mansoni , Schistosomiasis , Adult , Animals , Child , Humans , Artemisinins/adverse effects , Artesunate/adverse effects , Drug Therapy, Combination , Praziquantel/adverse effects , Randomized Controlled Trials as Topic , Reinfection/chemically induced , Reinfection/drug therapy , Schistosoma mansoni , Schistosomiasis/drug therapy , Schistosomiasis mansoni/diagnosis , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/chemically induced , Treatment Outcome , Equivalence Trials as Topic
4.
Lancet Infect Dis ; 22(11): e327-e335, 2022 11.
Article in English | MEDLINE | ID: mdl-35594896

ABSTRACT

Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.


Subject(s)
Anthelmintics , Helminthiasis , Schistosomiasis , Child , Humans , Child, Preschool , Praziquantel/therapeutic use , Schistosomiasis/drug therapy , Schistosomiasis/epidemiology , Schistosomiasis/prevention & control , Helminthiasis/drug therapy , Mass Drug Administration , Prevalence , World Health Organization , Anthelmintics/therapeutic use
5.
Malar J ; 21(1): 30, 2022 Feb 02.
Article in English | MEDLINE | ID: mdl-35109841

ABSTRACT

BACKGROUND: The World Health Organization recommends quinine plus clindamycin as first-line treatment of malaria in the first trimester of pregnancy and as a second-line treatment for uncomplicated falciparum malaria when artemisinin-based drug combinations are not available. The efficacy of quinine plus clindamycin was compared with that of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in children below 5 years of age. METHODS: An open-label, phase 3, randomized trial was conducted in western Kenya. Children aged 6-59 months with uncomplicated falciparum malaria were randomly assigned (1:1) via a computer-generated randomization list to receive 3 days of twice a day treatment with either oral quinine (20 mg/kg/day) plus clindamycin (20 mg/kg/day) or artemether-lumefantrine (artemether 20 mg, lumefantrine 120 mg) as one (for those weighing 5-14 kg) or two (for those weighing 15-24 kg) tablets per dose. The primary outcome was a PCR-corrected rate of adequate clinical and parasitological response (ACPR) on day 28 in the per-protocol population. RESULTS: Of the 384 children enrolled, 182/192 (94.8%) receiving quinine plus clindamycin and 171/192 (89.1%) receiving artemether-lumefantrine completed the study. The PCR-corrected ACPR rate was 44.0% (80 children) in the quinine plus clindamycin group and 97.1% (166 children) in the artemether-lumefantrine group (treatment difference - 53.1%, 95% CI - 43.5% to - 62.7%). At 72 h after starting treatment, 50.3% (94 children) in the quinine plus clindamycin group were still parasitaemic compared with 0.5% (1 child) in the artemether-lumefantrine group. Three cases of severe malaria were recorded as serious adverse events in the quinine plus clindamycin group. CONCLUSIONS: The study found no evidence to support the use of a 3-day low dose course of quinine plus clindamycin in the treatment of uncomplicated falciparum malaria in children under 5 years of age in Kenya, where artemether-lumefantrine is still effective. TRIAL REGISTRATION: This trial is registered with the Pan-African Clinical Trials Registry, PACTR20129000419241.


Subject(s)
Artemether, Lumefantrine Drug Combination/therapeutic use , Clindamycin/therapeutic use , Malaria, Falciparum/drug therapy , Quinine/therapeutic use , Artemether, Lumefantrine Drug Combination/adverse effects , Child, Preschool , Clindamycin/adverse effects , Drug Therapy, Combination , Female , Humans , Infant , Kenya , Male , Quinine/adverse effects
6.
Global Health ; 16(1): 100, 2020 10 19.
Article in English | MEDLINE | ID: mdl-33076935

ABSTRACT

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. While upstream approaches to tackle NCD risk factors of poor quality diets and physical inactivity have been trialled in high income countries (HICs), there is little evidence from low and middle-income countries (LMICs) that bear a disproportionate NCD burden. Sub-Saharan Africa and the Caribbean are therefore the focus regions for a novel global health partnership to address upstream determinants of NCDs. PARTNERSHIP: The Global Diet and Activity research Network (GDAR Network) was formed in July 2017 with funding from the UK National Institute for Health Research (NIHR) Global Health Research Units and Groups Programme. We describe the GDAR Network as a case example and a potential model for research generation and capacity strengthening for others committed to addressing the upstream determinants of NCDs in LMICs. We highlight the dual equity targets of research generation and capacity strengthening in the description of the four work packages. The work packages focus on learning from the past through identifying evidence and policy gaps and priorities, understanding the present through adolescent lived experiences of healthy eating and physical activity, and co-designing future interventions with non-academic stakeholders. CONCLUSION: We present five lessons learned to date from the GDAR Network activities that can benefit other global health research partnerships. We close with a summary of the GDAR Network contribution to cultivating sustainable capacity strengthening and cutting-edge policy-relevant research as a beacon to exemplify the need for such collaborative groups.


Subject(s)
Diet , Global Health , Noncommunicable Diseases/epidemiology , Adolescent , Africa South of the Sahara , Caribbean Region , Developing Countries , Health Policy , Humans , Income , International Cooperation , Public Health , Research , Risk Factors
7.
Glob Health Action ; 13(1): 1810415, 2020 12 31.
Article in English | MEDLINE | ID: mdl-32867606

ABSTRACT

At the time of writing, it is unclear how the COVID-19 pandemic will play out in rapidly urbanising regions of the world. In these regions, the realities of large overcrowded informal settlements, a high burden of infectious and non-communicable diseases, as well as malnutrition and precarity of livelihoods, have raised added concerns about the potential impact of the COVID-19 pandemic in these contexts. COVID-19 infection control measures have been shown to have some effects in slowing down the progress of the pandemic, effectively buying time to prepare the healthcare system. However, there has been less of a focus on the indirect impacts of these measures on health behaviours and the consequent health risks, particularly in the most vulnerable. In this current debate piece, focusing on two of the four risk factors that contribute to >80% of the NCD burden, we consider the possible ways that the restrictions put in place to control the pandemic, have the potential to impact on dietary and physical activity behaviours and their determinants. By considering mitigation responses implemented by governments in several LMIC cities, we identify key lessons that highlight the potential of economic, political, food and built environment sectors, mobilised during the pandemic, to retain health as a priority beyond the context of pandemic response. Such whole-of society approaches are feasible and necessary to support equitable healthy eating and active living required to address other epidemics and to lower the baseline need for healthcare in the long term.


Subject(s)
Communicable Disease Control/methods , Coronavirus Infections/epidemiology , Diet , Exercise , Pneumonia, Viral/epidemiology , Urban Population , Urbanization , Betacoronavirus , Built Environment , COVID-19 , Food Supply , Health Behavior , Humans , Pandemics , Risk Factors , SARS-CoV-2
8.
Ann Am Thorac Soc ; 17(1): 98-106, 2020 01.
Article in English | MEDLINE | ID: mdl-31580702

ABSTRACT

Rationale: Obstructive sleep apnea (OSA) is a significant health problem among adults and children globally, resulting in decreased quality of life and increased costs of healthcare. For optimal clinical care, primary care physicians should be familiar with OSA and confident in their ability to screen, diagnose, and manage this condition.Objectives: To assess the knowledge, attitudes, and practices of primary care physicians in Kenya, Nigeria, and South Africa regarding OSA in adults and children.Methods: We conducted a multicenter cross-sectional survey in Kenya (Nairobi), Nigeria (Edo State), and South Africa (Cape Town) between April 2016 and July 2017. At least 40 participants were randomly selected from a register of primary care physicians at each site. Potential participants were contacted to receive online/paper-based, validated OSA Knowledge and Attitudes (OSAKA) and OSAKA in Children (OSAKA-KIDS) questionnaires related to adults and children, respectively. The median percentage knowledge scores and proportions of favorable attitude were computed and current diagnostic and referral practices were documented.Results: The median OSAKA knowledge scores were 83.3% (interquartile range [IQR], 77.8-88.9), 66.7% (IQR, 55.6-77.8), and 61.1% (IQR, 55.6-77.8) among South African, Kenyan, and Nigerian physicians, respectively. For OSAKA-KIDS, the median knowledge scores were 61.1% (IQR, 50.0-72.2), 64.2% (IQR, 35.3-93.2), and 58.3% (IQR, 44.4-66.7) among South African, Kenyan, and Nigerian physicians, respectively. Most physicians (90-94%) considered adult and pediatric OSA very/extremely important. Fewer physicians agreed/strongly agreed that they were confident about OSA diagnosis (55%), management (25%), and continuous positive airway pressure (18%) use in adults. Even fewer physicians agreed/strongly agreed that they were confident about pediatric OSA diagnosis (35%), management (21%), and continuous positive airway pressure use (18%). South African physicians mainly prescribed polysomnography (51%) and overnight oximetry (22%), whereas 49% of Nigerian physicians and 65% of Kenyan physicians commonly requested lateral cervical radiography.Conclusions: Primary care physicians in South Africa, Nigeria, and Kenya considered OSA to be important but had modest knowledge about OSA in adults and children, and had a low perceived confidence in adult and pediatric management. Focused educational interventions during undergraduate training and continuing professional development programs may improve primary physicians' knowledge about OSA and its diagnosis and management.


Subject(s)
Attitude of Health Personnel , Physicians, Primary Care/psychology , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/therapy , Adult , Continuous Positive Airway Pressure , Cross-Sectional Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Kenya , Male , Middle Aged , Nigeria , Oximetry , Physicians, Primary Care/education , Polysomnography , Referral and Consultation , South Africa , Surveys and Questionnaires
9.
Malar J ; 11: 2, 2012 Jan 04.
Article in English | MEDLINE | ID: mdl-22217214

ABSTRACT

BACKGROUND: Artemisinin-based combinations are recommended for treatment of uncomplicated falciparum malaria, but are costly and in limited supply. Clindamycin plus quinine is an alternative non-artemisinin-based combination recommended by World Health Organization. The efficacy and safety of clindamycin plus quinine is not known. This systematic review aims to assess the efficacy of clindamycin plus quinine versus other anti-malarial drugs in the treatment of uncomplicated falciparum malaria. METHODS: All randomized controlled trials comparing clindamycin plus quinine with other anti-malarial drugs in treating uncomplicated malaria were included in this systematic review. Databases searched included: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. Two authors independently assessed study eligibility, extracted data and assessed methodological quality. The primary outcome measure was treatment failure by day 28. Dichotomous data was compared using risk ratio (RR), in a fixed effects model. RESULTS: Seven trials with 929 participants were included. Clindamycin plus quinine significantly reduced the risk of day 28 treatment failure compared with quinine (RR 0.14 [95% CI 0.07 to 0.29]), quinine plus sulphadoxine-pyrimethamine (RR 0.17 [95% CI 0.06 to 0.44]), amodiaquine (RR 0.11 [95% CI 0.04 to 0.27]), or chloroquine (RR 0.11 [95% CI 0.04 to 0.29]), but had similar efficacy compared with quinine plus tetracycline (RR 0.33 [95% CI 0.01 to 8.04]), quinine plus doxycycline (RR 1.00 [95% CI 0.21 to 4.66]), artesunate plus clindamycin (RR 0.57 [95% CI 0.26 to 1.24]), or chloroquine plus clindamycin (RR 0.38 [95% CI 0.13 to 1.10]). Adverse events were similar across treatment groups but were poorly reported. CONCLUSION: The evidence on the efficacy of clindamycin plus quinine as an alternative treatment for uncomplicated malaria is inconclusive. Adequately powered trials are urgently required to compare this combination with artemisinin-based combinations.


Subject(s)
Antimalarials/administration & dosage , Clindamycin/administration & dosage , Malaria, Falciparum/drug therapy , Quinine/administration & dosage , Drug Therapy, Combination/methods , Humans , Randomized Controlled Trials as Topic , Treatment Outcome
10.
Lancet Infect Dis ; 10(9): 603-11, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20705516

ABSTRACT

BACKGROUND: Schistosomiasis is an important parasitic disease in Kenya. Decreasing susceptibility of schistosomes to praziquantel, the major drug used to reduce disease morbidity, has made assessment of new antischistosomal drugs a priority. We aimed to assess the safety and efficacy of an artesunate-based combination drug in the treatment of schistosomiasis. METHODS: In this open-label randomised trial in Rarieda district of western Kenya, we enrolled school children (aged 6-15 years) who had Schistosoma mansoni infection according to duplicate Kato-Katz thick smears from a stool sample. Computer-generated block randomisation was used to assign children (1:1) to receive artesunate (100 mg) with sulfalene (also known as sulfamethoxypyrazine; 250 mg) plus pyrimethamine (12.5 mg) as one dose every 24 h for 3 days or one dose of praziquantel (40 mg/kg per day). The primary efficacy endpoint was the number of participants cured 28 days after treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01054651. RESULTS: Between October and December, 2009, 212 children were enrolled and assigned to receive artesunate with sulfalene plus pyrimethamine (n=106) or praziquantel (n=106). 69 patients (65%) were cured in the praziquantel treatment group compared with 15 (14%) in the artesunate with sulfalene plus pyrimethamine treatment group (p<0.0001). Adverse events were less common in patients taking artesunate with sulfalene plus pyrimethamine than in those taking praziquantel (22% [n=23] vs 49% [n=52], p<0.0001), and no drug-related serious adverse events occurred. INTERPRETATION: The standard treatment with praziquantel is more effective than artesunate with sulfalene plus pyrimethamine in the treatment of children with S mansoni infection in western Kenya. Whether artemisinin-based combination therapy has a role in the treatment of schistosomiasis is unclear.


Subject(s)
Artemisinins/therapeutic use , Pyrimethamine/therapeutic use , Schistosomiasis mansoni/drug therapy , Sulfalene/therapeutic use , Adolescent , Amebicides/adverse effects , Amebicides/therapeutic use , Animals , Antiprotozoal Agents/adverse effects , Antiprotozoal Agents/therapeutic use , Artemisinins/adverse effects , Artesunate , Child , Child, Preschool , Drug Therapy, Combination , Female , Humans , Infant , Kenya , Male , Pyrimethamine/adverse effects , Schistosoma mansoni , Schistosomiasis mansoni/classification , Sulfalene/adverse effects
11.
Malar J ; 7: 262, 2008 Dec 22.
Article in English | MEDLINE | ID: mdl-19102746

ABSTRACT

BACKGROUND: Artemether/lumefantrine (AL) has been adopted as the treatment of choice for uncomplicated malaria in Kenya and other countries in the region. Six-dose artemether/lumefantrine tablets are highly effective and safe for the treatment of infants and children weighing between five and 25 kg with uncomplicated Plasmodium falciparum malaria. However, oral paediatric formulations are urgently needed, as the tablets are difficult to administer to young children, who cannot swallow whole tablets or tolerate the bitter taste of the crushed tablets. METHODS: A randomized, controlled, open-label trial was conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6-59 months, treated over three days with either six-dose of artemether/lumefantrine tablets (Coartem) or three-dose of artemether/lumefantrine suspension (Co-artesiane) for uncomplicated falciparum malaria in western Kenya. The children were followed-up with clinical, parasitological and haematological evaluations over 28 days. RESULTS: Ninety three percent (124/133) and 90% (121/134) children in the AL tablets and AL suspension arms respectively completed followed up. A per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0% at Day 28 in the AL tablets group and 93.4% in the AL suspension group, p = 0.40. Both drugs effectively cleared gametocytes and were well tolerated, with no difference in the overall incidence of adverse events. CONCLUSION: The once daily three-dose of artemether-lumefantrine suspension (Co-artesiane(R)) was not superior to six-dose artemether-lumefantrine tablets (Coartem) for the treatment of uncomplicated malaria in children below five years of age in western Kenya.


Subject(s)
Antimalarials/administration & dosage , Artemisinins/administration & dosage , Ethanolamines/administration & dosage , Fluorenes/administration & dosage , Malaria, Falciparum/drug therapy , Plasmodium falciparum/drug effects , Analysis of Variance , Animals , Antimalarials/adverse effects , Antimalarials/therapeutic use , Artemether, Lumefantrine Drug Combination , Artemisinins/adverse effects , Artemisinins/therapeutic use , Child, Preschool , Drug Administration Schedule , Drug Combinations , Ethanolamines/adverse effects , Ethanolamines/therapeutic use , Fluorenes/adverse effects , Fluorenes/therapeutic use , Follow-Up Studies , Humans , Infant , Kenya/epidemiology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Plasmodium falciparum/isolation & purification , Suspensions , Tablets , Treatment Outcome
13.
Trans R Soc Trop Med Hyg ; 101(2): 117-26, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16978673

ABSTRACT

Drug resistance in Plasmodium falciparum is a major obstacle to malaria control. Artemisinin-based combination therapy (ACT) is being advocated to improve treatment efficacy and to delay development of resistance. Here we summarise the available data on the efficacy of amodiaquine plus sulfadoxine/pyrimethamine (AQ+SP) versus ACTs in the treatment of uncomplicated malaria in sub-Saharan Africa. We searched for randomised trials in which patients with uncomplicated malaria treated with AQ+SP were compared with those treated with either amodiaquine plus artesunate (AQ+AS), artesunate plus sulfadoxine/pyrimethamine (AS+SP) or artemether/lumefantrine (AL). Medline, EMBASE, Cochrane Central Register of Controlled Trials and reference lists up to July 2005 were searched. Two reviewers independently extracted the data. The primary outcome measure was treatment failure by Day 28. Outcome measures were combined using a random effects model. Seven randomised trials of 4472 children were included. Trial quality was generally high. Treatment failure of AQ+SP was significantly reduced compared with AS+SP (relative risk (RR)=0.56, 95% CI 0.42-0.75), but increased compared with AL (RR=2.80, 95% CI 2.32-3.39). The overall failure rate of AQ+SP was similar compared with AQ+AS (RR=1.12, 95% CI 0.81-1.54), but there was significant heterogeneity of results across the studies. All the treatment regimens were safe and well tolerated. AQ+SP should be considered in some settings before the full implementation of an ACT.


Subject(s)
Amodiaquine/therapeutic use , Artemisinins/therapeutic use , Malaria, Falciparum/drug therapy , Pyrimethamine/therapeutic use , Sesquiterpenes/therapeutic use , Sulfadoxine/therapeutic use , Africa , Drug Combinations , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic
14.
Am J Trop Med Hyg ; 77(6 Suppl): 23-8, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18165471

ABSTRACT

Severe malarial anemia (SMA) is a leading cause of pediatric morbidity, hospitalization, and mortality in sub-Saharan Africa, and yet its contribution to malaria-specific mortality is not well documented. We retrospectively reviewed the clinical records of 1,116 children < 5 years of age admitted to Siaya district hospital, western Kenya, to assess the contribution of SMA to overall in-hospital mortality. Of 1,116 admissions, 86% were under 3 years, 83% had malaria parasitemia, 86% were anemic, 21% were severely anemic, and 20% were transfused. Severe anemia was associated with parasitemia in 85% of the admissions and contributed to 53% of malaria-related deaths. Overall, 83 (7.5%) children died; 66% of those deaths were malaria-related, 12% had severe anemia, and 89% were under 3 years. Transfusion did not lower mortality rates. In areas of high malaria transmission, children below 3 years are a high-risk group for malaria, anemia, blood transfusion, and mortality.


Subject(s)
Anemia/parasitology , Malaria/blood , Malaria/mortality , Anemia/blood , Anemia/therapy , Animals , Antimalarials/therapeutic use , Blood Transfusion , Child , Child, Preschool , Female , Hospital Mortality , Humans , Infant , Infant, Newborn , Kenya/epidemiology , Malaria/drug therapy , Malaria/parasitology , Male , Morbidity , Plasmodium falciparum , Retrospective Studies
15.
J Infect Dis ; 194(11): 1519-28, 2006 Dec 01.
Article in English | MEDLINE | ID: mdl-17083036

ABSTRACT

BACKGROUND: The altered immune response of persons with human immunodeficiency virus (HIV) infection could result in increased rates of antimalarial treatment failure. We investigated the influence of HIV infection on the response to sulfadoxine-pyrimethamine treatment. METHODS: Febrile adults with Plasmodium falciparum parasitemia were treated with sulfadoxine-pyrimethamine and were monitored for 28 days. HIV status and CD4 cell count were determined at study enrollment. RESULTS: Of the adults enrolled in the study, 508 attended all follow-up visits, including 130 HIV-uninfected adults, 256 HIV-infected adults with a high CD4 cell count (> or =200 cells/ micro L), and 122 HIV-infected adults with a low CD4 cell count (<200 cells/ micro L). The hazard of treatment failure at day 28 of follow-up was significantly higher for HIV-infected adults with a low CD4 cell count (20.5%) than for HIV-uninfected adults (7.7%). Anemia (hemoglobin level, <110 g/L) modified the effect of HIV status on treatment failure. When we controlled for fever and parasite density, the hazard of treatment failure for HIV-infected adults with a low CD4 cell count and anemia was 3.4 times higher than that for HIV-uninfected adults (adjusted hazard ratio, 3.38; 95% confidence interval, 1.56-7.34). CONCLUSIONS: HIV-infected persons with a low CD4 cell count and anemia have an increased risk of antimalarial treatment failure. The response to malaria treatment in HIV-infected persons must be carefully monitored. Proven measures for the control and prevention of malaria must be incorporated into the basic package of services provided by HIV/acquired immunodeficiency syndrome care and treatment programs in malarious areas.


Subject(s)
Antimalarials/therapeutic use , HIV Infections/complications , Immunocompromised Host , Malaria, Falciparum/drug therapy , Pyrimethamine/therapeutic use , Sulfadoxine/therapeutic use , Adult , Anemia , Antimalarials/pharmacology , CD4 Lymphocyte Count , Drug Combinations , Female , Fever , HIV Infections/immunology , Humans , Kenya , Malaria, Falciparum/complications , Malaria, Falciparum/immunology , Male , Parasitemia , Pyrimethamine/pharmacology , Recurrence , Statistics as Topic , Sulfadoxine/pharmacology , Treatment Failure
16.
Infect Genet Evol ; 6(4): 309-14, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16271310

ABSTRACT

The choice of partner drug is critical for artemisinine-based combination therapy (ACT) to remain effective and amodiaquine (AQ) is one important candidate to evaluate. We treated 81 children <5 years with uncomplicated Plasmodium falciparum malaria with AQ alone and related the treatment outcome to the possible selection of pfcrt 76T, 152T, 163S, 326S, pfmdr1 86Y and pfmrp 191H, 437S in recurrent infections (recrudescenses and re-infections) and to the blood concentration of desethylamodiaquine (DEAQ). During 21 days follow-up 28 children had a recurrent infection (9 recrudescenses, 13 re-infections and 6 mixed). Neither genotyping of the polymorphisms before treatment nor DEAQ blood concentrations could predict treatment outcome. pfcrt 76T was however significantly selected for in recurrent infections (p=0.020). pfmdr1 86Y was also selected for, but only in recrudescent infections (p=0.048). The study showed high prevalence of AQ resistant parasites in vivo, which appeared to be associated to pfcrt 76T and pfmdr1 86Y.


Subject(s)
ATP-Binding Cassette Transporters/genetics , Amodiaquine/pharmacology , Antimalarials/pharmacology , Drug Resistance/genetics , Malaria, Falciparum/drug therapy , Membrane Proteins/genetics , Plasmodium falciparum/drug effects , Protozoan Proteins/genetics , Amino Acid Substitution , Amodiaquine/analogs & derivatives , Amodiaquine/blood , Amodiaquine/pharmacokinetics , Animals , Antigens, Protozoan , Antimalarials/pharmacokinetics , Child, Preschool , Humans , Infant , Malaria, Falciparum/diagnosis , Membrane Transport Proteins , Plasmodium falciparum/genetics
17.
Trans R Soc Trop Med Hyg ; 97(5): 585-91, 2003.
Article in English | MEDLINE | ID: mdl-15307433

ABSTRACT

Plasmodium falciparum has developed resistance to almost all routinely used antimalarial drugs. Sulfadoxine-pyrimethamine (SP) has replaced chloroquine as first-line treatment of uncomplicated malaria infection in Kenya but resistance to SP is already reported. The addition of artemisinin derivatives to SP may delay the development of drug resistance, improve cure rates, and reduce transmission. The efficacy and safety of artesunate plus SP in the treatment of uncomplicated P. falciparum malaria was evaluated in a randomized trial of 600 children at Siaya District Hospital, western Kenya between October 1999 and March 2000. Children aged < 5 years were randomly assigned to receive SP alone (1.25 mg/kg based on pyrimethamine), or in combination with artesunate (4 mg/kg/d) for either 1 or 3 d. Parasitological failure by days 14 and 28 (polymerase chain reaction [PCR]-corrected for new infections) were the primary endpoints. Treatment failure rates by day 14 were 25.5% in the SP alone group, 16.2% (risk difference [delta]-9.3%, 95% CI -17.3 to -1.2%, P= 0.027) in the 1-dose artesunate group, and 9.4% (delta-16.2%, 95% CI -23.6 to -8.7%, P< 0.001) in the 3-dose artesunate group. Corresponding rates by day 28 were 46.0% in the SP alone group, 38.2% (delta-7.8%, 95% CI -17.7 to 2.1%, P= 0.16) in the 1-dose artesunate group, and 26.0% (delta-20.0%, 95% CI -29.4 to -10.6%, P < 0.001) in the 3-dose artesunate group. The artesunate and SP combination was well tolerated. There were no serious drug-related adverse events. Parasite clearance and gametocyte carriage were reduced significantly in both combination groups compared with SP alone. Three days of artesunate were required to reduce significantly the risk of treatment failure by day 28. However, the high background rate of parasitological failure with SP may make this combination unsuitable for widespread use in Kenya.


Subject(s)
Antimalarials/therapeutic use , Artemisinins/therapeutic use , Malaria, Falciparum/drug therapy , Pyrimethamine/therapeutic use , Sesquiterpenes/therapeutic use , Sulfadoxine/therapeutic use , Antimalarials/adverse effects , Artemisinins/adverse effects , Artesunate , Child, Preschool , Double-Blind Method , Drug Combinations , Drug Therapy, Combination , Female , Fever/drug therapy , Genotype , Humans , Infant , Infant, Newborn , Kenya , Malaria, Falciparum/blood , Male , Pyrimethamine/adverse effects , Sesquiterpenes/adverse effects , Sulfadoxine/adverse effects , Treatment Outcome
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