Human resources for health governance and leadership strategies for improving health outcomes in low- and middle-income countries: a narrative review.

BACKGROUND: Many low- and middle-income countries (LMICs) are facing a crisis of human resources for health (HRH) attributed to poor governance and leadership that characterizes the health sector in this setting. It is unclear which specific strategies are effective in ameliorating the crisis. METHODS: Selected electronic databases were searched up until 30 May 2020. Two authors screened studies independently and extracted data from included studies. Quality assessment was done using the Mixed Methods Appraisal Tool. Thematic analysis of the outcomes was done. RESULTS: We included 18 studies of variable designs across Africa, Asia, South America and the Pacific islands. Most were case-based studies and were of moderate to high quality. Several governance strategies with a positive impact on the health workforce and health outcomes identified included decentralization, central coordination and facilitation process, posting and transfer policies as well as the setting up of human resource units. CONCLUSIONS: Governance and leadership strategies targeting the HRH crises in LMIC are variable, interdependent and complex. While some show benefits in improving health workforce outcomes, only a few have an impact on population health outcomes.

Interventions for improving attraction and retention of health workers in rural and underserved areas: a systematic review of systematic reviews.

BACKGROUND: Global health workforce shortages exist with disparities in the skill mix and distribution of health workers. Rural and underserved populations are often disadvantaged in terms of access to health care. METHODS: This systematic review summarized all systematic reviews that assessed interventions for improving attraction and retention of health workers in rural and underserved areas. We systematically searched selected electronic databases up to 31 March 2020. The authors independently screened the reviews, extracted data and assessed the certainty of evidence using GRADE. Review quality was assessed using the ROBIS tool. RESULTS: There was a paucity of evidence for the effectiveness of the various interventions. Regulatory measures were able to attract health workers to rural and underserved areas, particularly when obligations were attached to incentives. However, health workers were likely to relocate from these areas once their obligations were completed. Recruiting rural students and rural placements improved attraction and retention although most studies were without control groups, which made conclusions on effectiveness difficult. CONCLUSIONS: Cost-effective utilization of limited resources and the adoption and implementation of evidence-based health workforce policies and interventions that are tailored to meet national health system contexts and needs are essential.

Implementation of health workforce information systems: a review of eight sub-Saharan country experiences.

BACKGROUND: Globally, one of the major problems facing health systems is an acute deficit of health workforce. To ensure equitable distribution and deployment of health workers, up-to-date and timely information on the health workforce is vital. Health workforce registries (HWRs) have the potential to generate data for evidence-based human resource planning and policies. There is a lack of evaluative research on the capacity of HWRs to improve health systems. This review aims to assess the effectiveness of HWRs for improving health systems in low- and middle-income countries. METHODS: We searched selected electronic databases from inception to 14 April 2020. Two authors independently screened studies and extracted data from included studies. We presented results as a narrative synthesis. RESULTS: We included eight studies of moderate-high quality in this review. The results suggest that HWRs can improve the distribution and skill-mix of the health workforce, quality of health workforce data, availability and use of data for policy and planning, and user satisfaction. The evidence was derived from case studies, which limited our ability to infer a causal relationship. CONCLUSION: More rigorous research from controlled experimental studies is needed to consolidate the available evidence from observational studies.

Assessing agreement of hemoglobin and three- fold conversion of hematocrit as methods for detecting anemia in children living in malaria-endemic areas of Calabar, Nigeria.

BACKGROUND: One of the major causes of anemia, defined as the reduction in the level of hemoglobin or red blood cells (RBCs) in the blood, in children in sub-Saharan Africa is malaria. Anemia is diagnosed by using either the hematocrit method or by measuring the hemoglobin concentration. AIMS: To evaluate the relationship and agreement between hemoglobin and three-fold conversion of hematocrit results of participants in a clinical trial. MATERIALS AND METHODS: This is a cross-sectional study that obtained data from a multi-center clinical trial that took place from 2007 to 2008 in public health facilities in Calabar, Nigeria. The hemoglobin and hematocrit results of 494 children who had ≥2000 parasite density recruited were pooled to evaluate the relationship and agreement between the two methods. The difference between the measures against the mean of the two measures was plotted according to the theory of Bland and Altman. RESULTS: The mean age of the children was 34 months, with approximately equal number of boys and girls. The measured hemoglobin was lower than the calculated hemoglobin in 84.5% of the children. The result showed that lower the hemoglobin concentration, the higher the chances that the three-fold hematocrit conversion overestimates hemoglobin levels in the participants. CONCLUSIONS: The three-fold hematocrit conversion of hemoglobin estimation is a less reliable method than the measured hemoglobin in anemic children in the study setting.

Hypokalaemia in children hospitalised for diarrhoea and malnutrition in Calabar, Nigeria.

OBJECTIVE: To describe the acid base and electrolyte pattern of morbidity and mortality in children with diarrhoea and protein energy malnutrition. SETTING: The diarrhoea treatment and training unit of the university of Calabar teaching hospital was used for the study. DESIGN/METHODS: It was a prospective study in which consecutive children below the age of 15 years with protein energy malnutrition and diarrhoeal diseases admitted into the DTU were screened for acid base and serum electrolyte abnormalities. The study was carried out over a two year period from January 1997 to December 1998. RESULTS: Hypokalaemia was seen in 45 (23.4%) patients. This was second to acidosis. Metabolic acidosis was the commonest abnormality in this study and was seen in 108(56.3%) of the patients included in the study. There was hyponatraemia in 25(13%). Hypochloraemia in 8(4.2%) and hypernatraemia in 6(3.1%) of the patients respectively. CONCLUSION: This study has shown that hypokalaemia is a common electrolyte abnormality in children with severe protein energy malnutrition and diarrhoeal diseases. There is need to encourage the use of readily available interventions such as the UNICEF and WHO oral rehydration solution in patients with diarrhoea and/or severe protein energy malnutrition to reduce morbidity and mortality from acid base and electrolyte disturbances.

Species Composition of Anopheles (Diptera: Culicidae) in Selected Forested Tourist Areas of Nigeria Endemic for Malaria.

The study was carried out to determine relative abundance, species diversity, of Anopheles species (Diptera: Culicidae) in selected forested areas in Cross River State, Nigeria and the prevalence of malaria infection in the specimens. Mosquitoes were collected using pyrethrum spray catch and Centre for Disease Control light traps modified with yeast and sugar to generate carbon dioxide (CO2) and identified using morphological identification keys. We used a multiplex polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) to simultaneously distinguish sibling species of the An. gambiae s.l, including separation of An. gambiae s.s. and An. coluzzii (Diptera: Culicidae). The samples were also screened for Plasmodium infection using the enzyme-linked immunosorbent assay. One hundred and four Anopheles specimens were collected during the study of which 97% was An. gambiae complex and 3% was An. rufipes (Diptera: Culicidae). Only 77% of the An. gambiae s.l. was identify to species level. The result shows that 41.6% was An. gambiae s.s. and 34.6% was An. coluzzii. No sporozoite of Plasmodium was detected in the Anopheles species. The study also found a hybrid form of An. gambiae s.s. and An. coluzzii. These findings suggest the first documented evidence of hybrid forms of An. gambiae s.s./An. coluzzii in South Eastern Nigeria although its epidemiological implication is still not clear.

Chemoprophylaxis and intermittent treatment for preventing malaria in children.

BACKGROUND: Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment) are being considered for preschool children. OBJECTIVES: To evaluate prophylaxis and intermittent treatment with antimalarial drugs to prevent malaria in young children living in malaria-endemic areas. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (August 2007), CENTRAL (The Cochrane Library 2007, Issue 3), MEDLINE (1966 to August 2007), EMBASE (1974 to August 2007), LILACS (1982 to August 2007), mRCT (February 2007), and reference lists of identified trials. We also contacted researchers. SELECTION CRITERIA: Individually randomized and cluster-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in a malaria-endemic area. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed methodological quality. We used relative risk (RR) or weighted mean difference with 95% confidence intervals (CI) for meta-analyses. Where we detected heterogeneity and considered it appropriate to combine the trials, we used the random-effects model (REM). MAIN RESULTS: Twenty-one trials (19,394 participants), including six cluster-randomized trials, met the inclusion criteria. Prophylaxis or intermittent treatment with antimalarial drugs resulted in fewer clinical malaria episodes (RR 0.53, 95% CI 0.38 to 0.74, REM; 7037 participants, 10 trials), less severe anaemia (RR 0.70, 95% CI 0.52 to 0.94, REM; 5445 participants, 9 trials), and fewer hospital admissions for any cause (RR 0.64, 95% CI 0.49 to 0.82; 3722 participants, 5 trials). We did not detect a difference in the number of deaths from any cause (RR 0.90, 95% CI 0.65 to 1.23; 7369 participants, 10 trials), but the CI do not exclude a potentially important difference. One trial reported three serious adverse events with no statistically significant difference between study groups (1070 participants). Eight trials measured morbidity and mortality six months to two years after stopping regular antimalarial drugs; overall, there was no statistically significant difference, but participant numbers were small. AUTHORS' CONCLUSIONS: Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children.

Hand washing for preventing diarrhoea.

BACKGROUND: Diarrhoea is a common cause of morbidity and a leading cause of death among children aged less than five years, particularly in low- and middle-income countries. It is transmitted by ingesting contaminated food or drink, by direct person-to-person contact, or from contaminated hands. Hand washing is one of a range of hygiene promotion interventions that can interrupt the transmission of diarrhoea-causing pathogens. OBJECTIVES: To evaluate the effects of interventions to promote hand washing on diarrhoeal episodes in children and adults. SEARCH STRATEGY: In May 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 2), MEDLINE, EMBASE, LILACS, PsycINFO, Science Citation Index and Social Science Citation Index, ERIC (1966 to May 2007), SPECTR, Bibliomap, RoRe, The Grey Literature, and reference lists of articles. We also contacted researchers and organizations in the field. SELECTION CRITERIA: Randomized controlled trials, where the unit of randomization is an institution (eg day-care centre), household, or community, that compared interventions to promote hand washing or a hygiene promotion that included hand washing with no intervention to promote hand washing. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and methodological quality. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CI). MAIN RESULTS: Fourteen randomized controlled trials met the inclusion criteria. Eight trials were institution-based, five were community-based, and one was in a high-risk group (AIDS patients). Interventions promoting hand washing resulted in a 29% reduction in diarrhoea episodes in institutions in high-income countries (IRR 0.71, 95% CI 0.60 to 0.84; 7 trials) and a 31% reduction in such episodes in communities in low- or middle-income countries (IRR 0.69, 95% CI 0.55 to 0.87; 5 trials). AUTHORS' CONCLUSIONS: Hand washing can reduce diarrhoea episodes by about 30%. This significant reduction is comparable to the effect of providing clean water in low-income areas. However, trials with longer follow up and that test different methods of promoting hand washing are needed.

Fluid replacement therapy for acute episodes of pain in people with sickle cell disease.

BACKGROUND: Treating vaso-occlusive painful crises in people with sickle cell disease is complex and requires multiple interventions. Extra fluids are routinely given as adjunct treatment, regardless of the individual's state of hydration with the aim of slowing or stopping the sickling process and thereby alleviating pain. OBJECTIVES: To determine the optimal route, quantity and type of fluid replacement for people with sickle cell disease with acute painful crises. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also conducted searches of EMBASE, LILACS and the website www.ClinicalTrials.gov. Date of most recent search of the Group's Haemoglobinopathies Trials Register: February 2007. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared the administration of supplemental fluids adjunctive to analgesics by any route in people with any type of sickle cell disease during an acute painful episode, under medical supervision (inpatient, day care or community). DATA COLLECTION AND ANALYSIS: No relevant trials have yet been identified. MAIN RESULTS: Sixteen trials were identified by the initial search. Of these, 15 were not suitable for inclusion in this review and one study is awaiting further assessment. AUTHORS' CONCLUSIONS: Treating vaso-occlusive crises is complex and requires multiple interventions. Extra fluids, generally oral or intravenous, are routinely administered during acute painful episodes to people with sickle cell disease regardless of the individual's state of hydration. Reports of their use during these acute painful episodes do not state the efficacy of any single route, type or quantity of fluid compared to another. However, there are no randomized controlled trials that have assessed the safety and efficacy of different routes, types or quantities of fluid. This systematic review identifies the need for a multicentre randomized controlled trial assessing the efficacy and possible adverse effects of different routes, types and quantities of fluid administered to people with sickle cell disease during acute painful episodes.

Therapeutic interventions for Burkitt's lymphoma in children.

BACKGROUND: Burkitt's lymphoma (BL) is a small non-cleaved cell lymphoma which commonly presents as jaw swellings. Uncertainty remains as to the most effective form of management. OBJECTIVES: To assess the evidence of any therapeutic strategy in the treatment of BL. SEARCH STRATEGY: We searched MEDLINE (1966-March 2006), LILACS (1982-March 2006), EMBASE (1974-March 2006) and the Cochrane Controlled Trials Register (all years, latest Issue 01/2006) to identify relevant trials. All of these references were accessed in order to identify additional trials in BL. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any duration were included. We included studies conducted in children with a confirmed diagnosis of BL. Studies were not restricted by geographical location or by language of publication. Any therapeutic intervention was considered. The primary outcome was overall survival. DATA COLLECTION AND ANALYSIS: Two reviewers assessed studies for relevance. Studies that met the entry criteria were assessed for study quality. Data were extracted independently and were entered into RevMan 4.2. MAIN RESULTS: Twelve studies met the entry criteria of the review but data could only be retrieved from ten. Inadequate reporting of study methodology was a common feature of the trials preventing thorough assessment of study quality. We were unable to pool data for any of the outcomes due to the differences between the interventions assessed in the studies. Seven studies aimed to induce remission: Overall survival did not differ significantly between treatment groups in three out of four studies reporting this outcome. Five studies aimed to maintain remission: In two out of three studies reporting survival, it was substantially, but not statistically significantly, different between treatment groups. AUTHORS' CONCLUSIONS: This review does not currently provide any strong evidence on the relative effectiveness of interventions to treat Burkitt's lymphoma. The studies that have been conducted to date are small, underpowered and prone to both systematic and random error.

Chemoprophylaxis and intermittent treatment for preventing malaria in children.

BACKGROUND: Malaria causes repeated illness in children living in endemic areas. Policies of giving antimalarial drugs at regular intervals (prophylaxis or intermittent treatment) are being considered for preschool children. OBJECTIVES: To evaluate chemoprophylaxis and intermittent treatment with antimalarial drugs to prevent malaria in young children living in malaria endemic areas. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), and reference lists of identified trials. We also contacted researchers. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing antimalarial drugs given at regular intervals (prophylaxis or intermittent treatment) with placebo or no drug in children aged one month to six years or less living in an area where malaria is endemic. DATA COLLECTION AND ANALYSIS: We independently extracted data and assessed methodological quality. We used relative risk (RR) or weighted mean difference with 95% confidence intervals (CI) for meta-analyses. Where we detected heterogeneity and considered it appropriate to combine the trials, we used the random-effects model (REM). MAIN RESULTS: Nineteen trials (14,393 participants) met the inclusion criteria. Children receiving antimalarial drugs as prophylaxis or intermittent treatment had fewer clinical malaria episodes (RR 0.52, 95% CI 0.35 to 0.77, REM; 4051 participants, 8 trials), and severe anaemia was less common (RR 0.54, 95% CI 0.42 to 0.68; 2727 participants, 8 trials). We did not detect a difference in the number of deaths from any cause (RR 0.82, 95% CI 0.65 to 1.04; 7929 participants, 9 trials), but the confidence intervals do not exclude a potentially important difference. None of the trials reported serious adverse events. Three trials measured morbidity and mortality six months to two years after stopping regular antimalarial drugs; overall, there was no statistically significant difference, but participant numbers were small. AUTHORS' CONCLUSIONS: Prophylaxis and intermittent treatment with antimalarial drugs reduce clinical malaria and severe anaemia in preschool children. There is insufficient evidence to detect an effect on mortality.

Efficacy and tolerability of a low-dose mefloquine-sulfadoxine-pyrimethamine combination compared with chloroquine in the treatment of acute malaria infection in a population with multiple drug-resistant Plasmodium falciparum.

The efficacy and tolerability of single, low-dose mefloquine, sulfadoxine-pyrimethamine (MSP) combination was compared with chloroquine (CQ) for malaria treatment in a malaria-endemic area of Nigeria with multiple drug-resistant Plasmodium falciparum. The two drug regimens (MSP and CQ) were tested in a 12-month prospective population study. The patients were divided into two groups. Group 1 patients were treated presumptively, based on malaria symptoms. Group 2 patients were treated based on a parasitologic diagnosis using the World Health Organization seven-day in vivo test and extended to a 28-day follow-up period. Tolerability was assessed by the incidence and intensity of adverse events. One thousand nine hundred thirty-five patients visiting 10 health facilities, including the University of Calabar Teaching Hospital, were enrolled. The study showed that the low-dose MSP was efficacious, with day 7 response rates of 95% and 91% for (presumptive) Group 1 and (in vivo) Group 2, respectively, while CQ had day 7 response rates of 82% and 66% in Groups 1 and 2, respectively. The low-dose MSP was significantly (P < 0.0001) more efficacious, with faster fever and parasite clearance times than CQ in this area of CQ-resistant P. falciparum malaria. Eight patients treated with CQ, including seven severe cases (RII-RIII) were successfully re-treated with MSP. Adverse events were generally more common among those treated with MSP (29%) than those treated with CQ (17%). However, the adverse events caused by both drugs were mild to moderate and self-limited. The MSP combination appears to be a good substitute for CQ, in view of multiple drug resistance, especially in areas with severe (RII-RIII) malaria.

Cross-national HIV infection control practices and fear of AIDS: a comparison between Nigeria and the USA.

Fears about occupational transmission of HIV may have a significant impact on the behaviour of health care workers and on infection control practices. We investigated the relationships between fear of AIDS and infection control practices in health care workers in major university teaching hospitals in Nigeria and the USA. Data from the fear of AIDS scale and on a measure of infection control practices and beliefs showed that knowledge of whether the patient was HIV-infected determined infection control practices in Calabar but not Texas. Where the patient was known to be infected, there were no differences between the 2 countries. Fears of AIDS were related to infection control practices significantly more in the USA than in Nigeria where there was almost no relationship. These data may be influenced by the greater availability of disposable equipment in the USA compared with Nigeria.

PIP: HIV infection control practices and fear of AIDS were compared in 388 health care workers (doctors, nurses, nursing aides, and laboratory technologists) at major university teaching hospitals in Houston, Texas (US), and Calabar, Nigeria, in 1994. The mean duration of hospital employment was 9.2 years in Nigeria and 9.1 years in the US sample. The mean probability of treating a patient with AIDS in the next 12 months was estimated at 29.3% in Nigeria and 54.3% in the US. Nigerian hospital workers were as likely as their US counterparts to observe infection control practices such as carrying sharps in puncture-proof containers when they knew a patient had AIDS, but were not as compliant if the patient's serostatus was unknown. Differences in infection control practices were related to cross-national and not demographic or occupational factors. In the US, but not in Nigeria, there was a significant correlation between practices such as recapping of syringes by hand and fear of AIDS, regardless of prior knowledge of HIV status. The significantly stronger association between fear of AIDS and compliance with infection control practices in the US compared to Nigeria may reflect the higher HIV prevalence, more widespread availability of disposable equipment, stricter enforcement of infection control laws, and lower provider-patient ratios in the US setting.

High first dose quinine regimen for treating severe malaria.

BACKGROUND: Quinine is used for treating severe malaria. There are arguments for giving an initial high dose. We examined the evidence for and against this policy. OBJECTIVES: To assess the clinical outcomes and adverse events of a high first (loading) dose regimen of quinine compared with a uniform (no loading) dose regimen in people with severe malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's trials register (April 2004), CENTRAL (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to April 2004), EMBASE (1974 to April 2004), LILACS (1982 to April 2004), and conference proceedings for relevant abstracts. We also contacted researchers working in the field and checked the reference lists of all studies. SELECTION CRITERIA: Randomized controlled trials comparing a high first (loading) dose of intravenous quinine with a uniform (no loading) dose of intravenous quinine in people with severe malaria. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of the trials and extracted data (including adverse event data). We used Review Manager 4.2 to analyse the data: relative risk (RR) for binary data and weighted mean difference (WMD) for continuous data with 95% confidence intervals (CI). We contacted study authors for additional information. MAIN RESULTS: Four trials (n = 144) met the inclusion criteria. Loading dose was associated with fewer deaths, but this was not statistically significant (RR 0.62, CI 0.19 to 2.04, 3 trials). Loading dose was associated with faster clearance of parasites (WMD -7.44 hours, CI -13.24 to -1.64 hours, 2 trials), resolution of fever (WMD -11.11 hours, CI -20.04 to -2.18 hours, 2 trials). No statistically significant difference was detected for recovery of consciousness, neurological sequelae, or convulsions, but the numbers were small. REVIEWERS' CONCLUSIONS: Quinine loading dose reduced fever clearance time and parasite clearance time. Data are insufficient to directly demonstrate an impact of loading dose on risk of death.

High first dose quinine regimen for treating severe malaria.

BACKGROUND: Quinine is used for treating severe malaria. There are arguments for giving an initial high dose. We examined the evidence for and against this policy. OBJECTIVES: To assess clinical outcomes and adverse events of a high first (loading) dose regimen of quinine with a uniform (no loading) dose regimen in people with severe malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (May 2002), The Cochrane Controlled Trials Register (Issue 2, 2002), MEDLINE (1966 to April 2002), EMBASE (1988 to March 2002), LILACS (www.bireme.br; accessed February 2002), and conference proceedings for relevant abstracts. We also contacted researchers working in the field and checked the reference lists of all studies. SELECTION CRITERIA: Randomized controlled trials. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of the trials and extracted data. Review Manager (Version 4.1) was used to analyse the data: Relative Risk for binary data and weighted mean difference (WMD) for continuous data. Study authors were contacted for additional information. MAIN RESULTS: Three small trials, with two contributing to a meta-analysis of 72 participants. Loading dose was associated with fewer deaths, but this was not statistically significant (RR 0.43; 95% confidence interval (CI) 0.09 to 2.15). Loading dose was associated with faster clearance of parasites (WMD 7.44; 95% CI 1.64 to 13.2 hours), resolution of fever (WMD 11.11; 95% CI 2.18 to 20.04 hours), and transient hearing loss (RR 3.14; 95% CI 1.05 to 9.38). No significant difference was detected for recovery of consciousness, neurological sequelae, or convulsions, but the numbers were small. REVIEWER'S CONCLUSIONS: Quinine loading dose reduced fever clearance time and parasite clearance time. Data are insufficient to confirm or refute whether a loading dose reduced the risk of death or convulsions.

Iron chelating agents for treating malaria.

BACKGROUND: Researchers are exploring the effects of adding treatments to the main antimalarial regimens in an attempt to reduce mortality from Plasmodium falciparum. Iron chelation is one potential chemotherapeutic adjuvant treatment. Before advocating adjunctive therapy, the effects of iron chelators in improving patient outcomes need to be examined. OBJECTIVES: To assess the effects of iron-chelating agents combined with antimalarial drugs, or iron chelators alone, for treating Plasmodium falciparum malaria in adults and children, in relation to mortality, coma recovery time, parasite clearance, and adverse effects. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register (up to January 2003), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 1, 2003), MEDLINE (January 1966 to January 2003), EMBASE (January 1980 to November 2002), and reference lists of retrieved studies. We also contacted organisations, experts and researchers in the field. SELECTION CRITERIA: All randomised controlled trials comparing iron chelating agents with placebo, or comparing iron chelating agents in conjunction with other antimalarials with antimalarial treatment alone in adults or children with falciparum malaria. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria and assessed trial quality. One reviewer (HS) extracted data from included studies. Study authors were contacted for missing and additional data. MAIN RESULTS: Seven trials involving 570 participants were included. Two trials involving 435 children compared the iron chelator DFO with placebo and standard treatment. No evidence of benefit or harm was shown in relation to mortality, but studies were small. The risk of experiencing persistent seizures was lower with DFO compared to placebo treatment (RR 0.80, 95% CI 0.67 to 0.95), but adverse effects were more common in the DFO group. One trial involving 45 adults and children compared the orally active iron chelator (deferiprone) with placebo and standard treatment; coma recovery (WMD -27 hrs; 95%CI -34.20 to -19.80) and parasite clearance (WMD -24 hrs; 95%CI -35.27 to -12.73) were significantly faster in the deferiprone group compared to placebo, but clinical significance cannot be assumed from this small trial. The authors reported no side effects during the study. REVIEWER'S CONCLUSIONS: There are insufficient data for any conclusions for both agents tested. There are non-significant trends towards harm (death) and potential benefit (fewer seizures) with DFO. With deferiprone, results suggest possible benefit (shorter coma recovery and parasite clearance). If this topic is considered a priority for further research, larger trials are needed to detect an effect on clinical outcomes; and these trials should also include carefully evaluate adverse effects.

Physical methods for treating fever in children.

BACKGROUND: Health workers recommend bathing, sponging and other physical methods to treat fever in children and to avoid febrile convulsions. We know little about the most effective methods, or how these methods compare with commonly used drugs. OBJECTIVES: To evaluate the benefits and harms of physical cooling methods used for managing fever in children. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (February 2003), the Cochrane Central Register of Controlled Trials (Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to November 2002), CINHAL (1982 to February 2003), LILACS (February 2003), Science Citation Index (1981 to February 2003), and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing physical methods with a drug placebo or no treatment in children with fever of presumed infectious origin. Studies where children in both groups were given an antipyretic drug were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial methodological quality. One reviewer extracted data and the other checked the data for accuracy. Results were expressed as Relative Risk (RR) with 95% confidence intervals (CI) for discrete variables, and weighted mean differences for continuous outcomes. MAIN RESULTS: Seven trials, involving 467 participants, met the inclusion criteria. One small trial (n = 30), comparing physical methods with drug placebo, did not demonstrate a difference in the proportion of children without fever by one hour after treatment in a comparison between physical methods alone and drug placebo. In 2 studies, where all children received an anti-pyretic drug, physical methods resulted in a higher proportion of children without fever at one hour (n=125, RR 11.8, CI 3.39 to 40.8). I; in a third study (n=130), which only reported mean change in temperature, no differences wereas detected. Mild adverse events (shivering and goose pimples) were more common in the physical methods group (3 trials, RR 5.09; CI 1.56 to 16.60). REVIEWER'S CONCLUSIONS: A few small studies demonstrate that tepid sponging helps to reduce fever in children.

Routine anticonvulsants for treating cerebral malaria.

BACKGROUND: Cerebral malaria is a common complication of Plasmodium falciparum infection, and kills over a million people every year. People with cerebral malaria become unconscious, and often have protracted convulsions. It is unclear whether giving anticonvulsant drugs routinely to people with cerebral malaria will improve the outcome of treatment and prevent death. OBJECTIVES: To evaluate the effect of routine anticonvulsant drugs in people with cerebral malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (November 2001), The Cochrane Controlled Trials Register (Issue 4, 2001), MEDLINE (1966 to November 2001), EMBASE (1988 to October 2001), LILACS (2001, 40a Edition CD-ROM), Science Citation Index (November 2001), African Index Medicus (1999), reference lists of articles, and research organizations. We also contacted the authors for addtional information. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of people with cerebral malaria. The trials compared anticonvulsant drugs started on admission to hospital with no anticonvulsant drug or placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data from those trials eligible for inclusion. We assessed the methodological quality of the included trials by considering allocation sequence, concealment of allocation, blinding, and inclusion of all randomized participants. We used Review Manager (version 4.1) for the meta-analysis and also explored possible sources of heterogeneity. MAIN RESULTS: Three trials with a total of 573 participants met the inclusion criteria. These trials all compared phenobarbitone with placebo or no treatment. In the two trials with adequate allocation concealment, death was more common in the anticonvulsant group (Relative Risk 2.0; 95% confidence interval 1.20 to 3.33; fixed effect model). In all three trials, phenobarbitone compared with placebo or no treatment was associated with fewer convulsions (Relative Risk 0.30; 95% confidence interval 0.19 to 0.45; fixed effect model). REVIEWER'S CONCLUSIONS: Routine phenobarbitone in cerebral malaria is associated with fewer convulsions but possibly more deaths. Further trials with adequate design, more participants, and different doses of anticonvulsant drugs are needed.

Paracetamol for treating fever in children.

BACKGROUND: Paracetamol (acetaminophen) is widely used for treating fever in children. Like ibuprofen, aspirin, and physical methods (such as fanning), paracetamol aims to provide relief from symptoms and prevent febrile convulsions. Uncertainty exists about the benefits of using it to treat fever in children. OBJECTIVES: To assess the effects of paracetamol for treating fever in children in relation to fever clearance time, febrile convulsions, and resolution of associated symptoms. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (November 2001), The Cochrane Controlled Trials Register (The Cochrane Library Issue 4, 2001), MEDLINE (1966 to November 2001), EMBASE (1988 to November 2001), LILACS (2001, 40a Edition CD-ROM), Science Citation Index (November 2001), and reference lists of articles. We also contacted researchers in the field. SELECTION CRITERIA: Randomized and quasi-randomized trials of children with fever from infections comparing: (1) paracetamol with placebo or no treatment; and (2) paracetamol with physical cooling methods (eg, sponging, bathing, or fanning). The primary outcomes were fever clearance time and febrile convulsion. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data on methods, types of participants, interventions, and outcomes. The meta-analysis was conducted using Relative Risk with 95% confidence intervals for discrete variables, and weighted mean differences for continuous outcomes. MAIN RESULTS: 12 trials (n = 1509 participants) met the inclusion criteria. Outcomes varied between trials. No data were available on the primary outcome. There is insufficient evidence to show whether paracetamol influenced the risk of febrile convulsions. In a meta-analysis of two trials (n = 120), the proportion of children without fever by the second hour after treatment did not differ significantly between those given paracetamol and those sponged (Relative Risk 1.84; confidence interval 0.94 to 3.61, random effects model). The statistical test showed significant heterogeneity between the groups receiving paracetamol or physical methods. No severe adverse events were reported. The number of children with mild adverse events did not differ significantly between paracetamol and placebo, or paracetamol and physical methods, but numbers were small. REVIEWER'S CONCLUSIONS: Trial evidence that paracetamol has a superior antipyretic effect than placebo is inconclusive. There is limited evidence that there is no difference between the antipyretic effect of paracetamol and physical methods. Data on adverse events in these trials were limited. Establishing standard outcomes will help comparisons between studies and meta-analysis.