Showing papers by "Paul Garner published in 2012"

Primaquine for reducing Plasmodium falciparum transmission

Abstract: Background: Mosquitoes become infected with malaria when they ingest gametocyte stages of the parasite from the blood of a human host. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ). The World Health Organization (WHO) recommends giving a single dose or short course of PQ alongside primary treatment for people ill with P. falciparum infection to reduce malaria transmission. Gametocytes themselves cause no symptoms, so this intervention does not directly benefit individuals. PQ causes haemolysis in some people with glucose-6-phosphate dehydrogenase (G6PD) deficiency so may not be safe. Objectives: To assess whether a single dose or short course of PQ added to treatments for malaria caused by P. falciparum infection reduces malaria transmission and is safe. Search methods: We searched the following databases up to 10 April 2012 for studies: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT) and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and we contacted likely researchers and organizations for relevant trials. Selection criteria: Trials of mass treatment of whole populations (or actively detected fever or malaria cases within such populations) with antimalarial drugs, compared to treatment with the same drug plus PQ; or patients with clinical malaria being treated for malaria at health facilities randomized to short course/single dose PQ versus no PQ. Data collection and analysis: Two authors (PMG and HG) independently screened all abstracts, applied inclusion criteria, and abstracted data. We sought data on the effect of PQ on malaria transmission intensity, participant infectiousness, the number of participants with gametocytes, and gametocyte density over time. We stratified results by primary treatment drug as this may modify any PQ effect. We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available, and also sought data on haematologic and other adverse effects. We used GRADE guidelines to assess evidence quality, and this is reflected in the wording of the results: high quality ("PQ reduces .... "); moderate quality ("PQ probably reduces ... "); low quality ("PQ may reduce .... "); and very low quality ("we don't know if PQ reduces .... "). Main results: We included 11 individually randomized trials, with a total of 1776 individuals. The 11 trials included 20 comparisons with partner drugs, which included chloroquine (CQ), sulfadoxine-pyrimethamine (SP), mefloquine (MQ), quinine (QN), artesunate (AS), and a variety of artemisinin combination therapies (ACTs). For G6PD deficiency, studies either did not test (one study), tested and included all (one study), included only G6PD deficient (one study), excluded G6PD deficient (two studies), or made no comment (six studies). None of the trials we included assessed effects on malaria transmission (incidence, prevalence, or entomological inoculation rate (EIR)) in the trial area. With non-artemisinin drug regimens, PQ may reduce the infectiousness to mosquitoes of individuals treated, based on one small study with large effects (Risk Ratio (RR) 0.06 on day 8 after treatment, 95% confidence interval (CI) 0 to 0.89; low quality evidence). Participants who received PQ had fewer circulating gametocytes up to day 43 (log(10) AUC relative decrease from 24.3 to 27.1%, one study (two comparisons), moderate quality evidence); and there were 38% fewer people with gametocytes on day 8 (RR 0.62, 95% CI 0.51 to 0.76, four studies (five comparisons), moderate quality evidence). We did not identify any study that looked for effects of the drug on haemolytic anaemia. With artemisinin-based drug regimens, we do not know if PQ influences infectiousness to mosquitoes, as no study has examined this directly. PQ probably reduces infectiousness, based on reduction in log(10) AUC (relative decrease range from 26.1% to 87.5%, two studies (six comparisons), moderate quality evidence); and reduces by 88% the number of participants with gametocytes on day 8 (RR 0.12, 95% CI 0.08 to 0.20, four studies (eight comparisons), moderate quality evidence). When used with artemisinin-based regimens, we do not know if PQ results in haemolytic anaemia; one trial reported percent change in mean haemoglobin against baseline, and for the PQ group this indicated a significantly greater drop at day 8 in those given PQ (very low quality evidence). Overall, the safety of PQ used in single dose or short course was poorly evaluated. Authors' conclusions: We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Antipyretic measures for treating fever in malaria

Abstract: Background Fever is common in malaria, and drugs and sponging are widely used for symptomatic relief. Some researchers have suggested that fever reduction may prolong malaria illness. Objectives We aimed to assess whether treatments to reduce fever in malaria influence the course of the illness. Search methods We searched the Cochrane Infectious Diseases Group Trial Register (June 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 6, 2012), MEDLINE (1966 to June 2012); EMBASE (1980 to June 2012) and LILACS (June 2012). We contacted researchers and organisations working in the field to enable us identify other unpublished or ongoing trials. Selection criteria Randomized controlled trials of fever reduction measures in adults or children with confirmed malaria. Data collection and analysis Inclusion criteria were independently applied by two authors. We extracted data from trials that met our pre-specified criteria using a standard data extraction form. Mean differences with 95% confidence intervals (CI) were calculated for continuous data. GRADE was used to evaluate and summarize the quality of the evidence. Main results Ten randomized controlled trials with 990 participants including both adults and children met our inclusion criteria. All were small scale trials with methodological limitations and were conducted in a variety of patients. Some trials detected an impact of antipyretic drugs on fever clearance time, while others did not. Regarding parasite clearance,no clear influence of anti-pyresis was demonstrated (six trials, 423 participants, very low quality of evidence). No difference in the number or severity of adverse events between antipyretic drugs and control was detected. Authors' conclusions We do not know whether antipyretics alter parasite clearance time. Whether further trials are worthwhile to investigate this or not would require a judgement of whether this was an important question to resolve using interventional trials.

Integrated Management of Childhood Illness (IMCI) Strategy for children under five: effects on death, service utilisation and illness

Abstract: Background More than 7.5 million children younger than age five living in low- and middle-income countries die every year. The World Health Organization (WHO) developed the integrated management of childhood illness (IMCI) strategy to reduce mortality and morbidity and to improve quality of care by improving the delivery of a variety of curative and preventive medical and behavioral interventions at health facilities, at home, and in the community. Objectives To evaluate the effects of programs that implement the IMCI strategy in terms of death, nutritional status, quality of care, coverage with IMCI deliverables, and satisfaction of beneficiaries. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; MEDLINE; EMBASE, Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EbscoHost; the Latin American Caribbean Health Sciences Literature (LILACS), Virtual Health Library (VHL); the WHO Library & Information Networks for Knowledge Database (WHOLIS); the Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Science; Population Information Online (POPLINE); the WHO International Clinical Trials Registry Platform (WHO ICTRP); and the Global Health, Ovid and Health Management, ProQuest database. We performed searches until 30 June 2015 and supplemented these by searching revised bibliographies and by contacting experts to identify ongoing and unpublished studies. Selection criteria We sought to include randomised controlled trials (RCTs) and controlled before-after (CBA) studies with at least two intervention and two control sites evaluating the generic IMCI strategy or its adaptation in children younger than age five, and including at minimum efforts to improve health care worker skills for case management. We excluded studies in which IMCI was accompanied by other interventions including conditional cash transfers, food supplementation, and employment. The comparison group received usual health services without provision of IMCI. Data collection and analysis Two review authors independently screened searches, selected trials, and extracted, analysed and tabulated data. We used inverse variance for cluster trials and an intracluster co-efficient of 0.01 when adjustment had not been made in the primary study. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) approach to assess the certainty of evidence. Main results Two cluster-randomised trials (India and Bangladesh) and two controlled before-after studies (Tanzania and India) met our inclusion criteria. Strategies included training of health care staff, management strengthening of health care systems (all four studies), and home visiting (two studies). The two studies from India included care packages targeting the neonatal period. One trial in Bangladesh estimated that child mortality may be 13% lower with IMCI, but the confidence interval (CI) included no effect (risk ratio (RR) 0.87, 95% CI 0.68 to 1.10; 5090 participants; low-certainty evidence). One CBA study in Tanzania gave almost identical estimates (RR 0.87, 95% CI 0.72 to 1.05; 1932 participants). One trial in India examined infant and neonatal mortality by implementing the integrated management of neonatal and childhood illness (IMNCI) strategy including post-natal home visits. Neonatal and infant mortality may be lower in the IMNCI group compared with the control group (infant mortality hazard ratio (HR) 0.85, 95% CI 0.77 to 0.94; neonatal mortality HR 0.91, 95% CI 0.80 to 1.03; one trial, 60,480 participants; low-certainty evidence). We estimated the effect of IMCI on any mortality measured by combining infant and child mortality in the one IMCI and the one IMNCI trial. Mortality may be reduced by IMCI (RR 0.85, 95% CI 0.78 to 0.93; two trials, 65,570 participants; low-certainty evidence). Two trials (India, Bangladesh) evaluated nutritional status and noted that there may be little or no effect on stunting (RR 0.94, 95% CI 0.84 to 1.06; 5242 participants, two trials; low-certainty evidence) and there is probably little or no effect on wasting (RR 1.04, 95% CI 0.87 to 1.25; two trials, 4288 participants; moderate-certainty evidence).The Tanzania CBA study showed similar results. Investigators measured quality of care by observing prescribing for common illnesses at health facilities (727 observations, two studies; very low-certainty evidence) and by observing prescribing by lay health care workers (1051 observations, three studies; very low-certainty evidence). We could not confirm a consistent effect on prescribing at health facilities or by lay health care workers, as certainty of the evidence was very low. For coverage of IMCI deliverables, we examined vaccine and vitamin A coverage, appropriate care seeking, and exclusive breast feeding. Two trials (India, Bangladesh) estimated vaccine coverage for measles and reported that there is probably little or no effect on measles vaccine coverage (RR 0.92, 95% CI 0.80 to 1.05; two trials, 4895 participants; moderate-certainty evidence), with similar effects seen in the Tanzania CBA study. Two studies measured the third dose of diphtheria, pertussis, and tetanus vaccine; and two measured vitamin A coverage, all providing little or no evidence of increased coverage with IMCI. Four studies (2 from India, and 1 each from Tanzania and Bangladesh) reported appropriate care seeking and derived information from careful questioning of mothers about recent illness. Some studies on effects of IMCI may report better care seeking behavior, but others do not report this. All four studies recorded maternal responses on exclusive breast feeding. They provided mixed results and very low-certainty evidence. Therefore, we do not know whether IMCI impacts exclusive breast feeding. No studies reported on the satisfaction of mothers and service users. Authors' conclusions The mix of interventions examined in research studies evaluating the IMCI strategy varies, and some studies include specific inputs to improve neonatal health. Most studies were conducted in South Asia. Implementing the integrated management of childhood illness strategy may reduce child mortality, and packages that include interventions for the neonatal period may reduce infant mortality. IMCI may have little or no effect on nutritional status and probably has little or no effect on vaccine coverage. Maternal care seeking behavior may be more appropriate with IMCI, but study results have been mixed, providing evidence of very low certainty about whether IMCI has effects on adherence to exclusive breast feeding.

Decentralising HIV treatment delivery in middle- and low-income countries

Abstract: This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate retention, and quality of initiation and maintenance of HIV/AIDS care, in HIV treatment care models that decentralise from hospitals to more basic levels of care. 1 Decentralising HIV treatment delivery in middleand low-income countries (Protocol) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Rapid diagnostic tests can extend access of diagnostic services for uncomplicated Plasmodium falciparum malaria

Abstract: In this issue, we feature the Cochrane Diagnostic Review on Rapid diagnostic tests for diagnosing uncomplicated Plasmodium falciparum malaria in endemic countries, conducted by Abba et al. This column highlights Cochrane Reviews of relevance to public health, and aims to stimulate debate on relevance, feasibility and acceptability. We asked Emmanuel Bottieau and colleagues to comment on and put the review in context, and Mariska Leeflang provides an overview of the approach to conducting diagnostic reviews.

Primaquine for reducing Plasmodium falciparum transmission(Review)

Abstract: Background Mosquitoes become infected with malaria when they ingest gametocyte stages of the parasite from the blood of a human host. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ). The World Health Organization (WHO) recommends giving a single dose or short course of PQ alongside primary treatment for people ill with P. falciparum infection to reduce malaria transmission. Gametocytes themselves cause no symptoms, so this intervention does not directly benefit individuals. PQ causes haemolysis in some people with glucose-6-phosphate dehydrogenase (G6PD) deficiency so may not be safe. Objectives To assess whether a single dose or short course of PQ added to treatments for malaria caused by P. falciparum infection reduces malaria transmission and is safe. Search methods We searched the following databases up to 10 April 2012 for studies: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT) and the WHO trials search portal using 'malaria*', ‘falciparum’, and ‘primaquine’ as search terms. In addition, we searched conference proceedings and reference lists of included studies, and we contacted likely researchers and organizations for relevant trials. Selection criteria Trials of mass treatment of whole populations (or actively detected fever or malaria cases within such populations) with antimalarial drugs, compared to treatment with the same drug plus PQ; or patients with clinical malaria being treated for malaria at health facilities randomized to short course/single dose PQ versus no PQ. Data collection and analysis Two authors (PMG and HG) independently screened all abstracts, applied inclusion criteria, and abstracted data. We sought data on the effect of PQ on malaria transmission intensity, participant infectiousness, the number of participants with gametocytes, and gametocyte density over time. We stratified results by primary treatment drug as this may modify any PQ effect. We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available, and also sought data on haematologic and other adverse effects. We used GRADE guidelines to assess evidence quality, and this is reflected in the wording of the results: high quality ("PQ reduces ...."); moderate quality ("PQ probably reduces ..."); low quality ("PQ may reduce...."); and very low quality ("we don't know if PQ reduces...."). Main results We included 11 individually randomized trials, with a total of 1776 individuals. The 11 trials included 20 comparisons with partner drugs, which included chloroquine (CQ), sulfadoxine-pyrimethamine (SP), mefloquine (MQ), quinine (QN), artesunate (AS), and a variety of artemisinin combination therapies (ACTs). For G6PD deficiency, studies either did not test (one study), tested and included all (one study), included only G6PD deficient (one study), excluded G6PD deficient (two studies), or made no comment (six studies). None of the trials we included assessed effects on malaria transmission (incidence, prevalence, or entomological inoculation rate (EIR)) in the trial area. With non-artemisinin drug regimens, PQ may reduce the infectiousness to mosquitoes of individuals treated, based on one small study with large effects (Risk Ratio (RR) 0.06 on day 8 after treatment, 95% confidence interval (CI) 0 to 0.89; low quality evidence). Participants who received PQ had fewer circulating gametocytes up to day 43 (log(10) AUC relative decrease from 24.3 to 27.1%, one study (two comparisons), moderate quality evidence); and there were 38% fewer people with gametocytes on day 8 (RR 0.62, 95% CI 0.51 to 0.76, four studies (five comparisons), moderate quality evidence). We did not identify any study that looked for effects of the drug on haemolytic anaemia. With artemisinin-based drug regimens, we do not know if PQ influences infectiousness to mosquitoes, as no study has examined this directly. PQ probably reduces infectiousness, based on reduction in log(10) AUC (relative decrease range from 26.1% to 87.5%, two studies (six comparisons), moderate quality evidence); and reduces by 88% the number of participants with gametocytes on day 8 (RR 0.12, 95% CI 0.08 to 0.20, four studies (eight comparisons), moderate quality evidence). When used with artemisinin-based regimens, we do not know if PQ results in haemolytic anaemia; one trial reported percent change in mean haemoglobin against baseline, and for the PQ group this indicated a significantly greater drop at day 8 in those given PQ (very low quality evidence). Overall, the safety of PQ used in single dose or short course was poorly evaluated. Authors' conclusions We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Research Poster Presentation: PIN2 Safety and Efficacy of RV1 and RV5 Rotavirus Vaccines

Abstract: Objectives Systematically review all randomized trials evaluating licensed rotavirus vaccines for efficacy and safety on diarrhoea, hospital admission, death and serious adverse events. Methods Electronic searches strategies were performed until October 2011. Trial eligibility, data extraction and quality assessment were performed independently by two reviewers. Dichotomous data were pooled using the risk ratio (RR) and 95% CI. GRADE was used to evaluate evidence quality. Results Forty-three RCTs including 190,551 participants were identified; 31 trials assessed RV1, and 12 RV5. In children ≤ 1 year, RV1 (RR=0.20, 95%CI0.11 to 0.35; 7 trials, 35,004 participants) and RV5 (RR=0.23, 95%CI 0.08 to 0.71; 3 trials, 6953 participants) are highly efficacious against severe rotavirus diarrhoea cases and/or rotavirus diarrhea requiring hospitalization. For all-cause diarrhea, RV1 reduces severe cases by 42% (RR=0.58, 95% CI 0.40 - 0.84; 8291 participants), and RV5 by 72% (RR=0.28, 95%CI 0.16 - 0.48). Both vaccines were also efficacious during the second year of life (RV1: RR=0.16, 95%CI 0.12 - 0.21; 8 trials, 32,854 participants; RV5:RR=0.44, 95%CI 0.22 - 0.88; 4 trials, 9783 participants). For all-cause diarrhoea, RV1 reduces severe cases by 51% (RR=0.49, 95%CI 0.40 - 0.60; 2 trials, 6269 participants). Both vaccines had no impact on mortality, but serious adverse events following vaccination, including intussusception, were not more common than following placebo. Conclusions RV1 and RV5 vaccines are efficacious and relatively safe. These data support the WHO's global vaccine recommendation. Potential reduced vaccine efficacy in low income countries needs to be addressed. Ongoing safety monitoring should be continued in countries that have introduced rotavirus vaccination.