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High first dose quinine regimen for treating severe malaria

  1. Afolabi FE Lesi1,*,
  2. Martin M Meremikwu2

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 8 JUL 2009

Assessed as up-to-date: 18 FEB 2009

DOI: 10.1002/14651858.CD003341.pub2

Database Title

Additional Information

How to Cite

Lesi AFE, Meremikwu MM. High first dose quinine regimen for treating severe malaria. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD003341. DOI: 10.1002/14651858.CD003341.pub2.

Author Information

  1. 1

    College of Medicine of the University of Lagos, Department of Paediatrics and Child Health, Lagos, Nigeria

  2. 2

    University of Calabar Teaching Hospital, Department of Paediatrics, Calabar, Cross River State, Nigeria

*Afolabi FE Lesi, Department of Paediatrics and Child Health, College of Medicine of the University of Lagos, Lagos, PMB 12003, Nigeria. afolabilesi@hotmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 8 JUL 2009

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Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Each year an estimated 500,000 to 2 million people die from the effects of malaria (WHO 1990a). The majority of these deaths occur in children under five years old that live in areas of intense malaria transmission, notably in sub-Saharan Africa (WHO 1996; Schellenberg 1999). Severe malaria syndromes have been described and summarized by the World Health Organization (WHO) (WHO 2000). They include the presence of asexual parasitaemia associated with clinical or laboratory findings such as impaired consciousness, respiratory distress, convulsions, severe anaemia, and hypoglycaemia (low blood sugar).

Healthcare workers treating malaria know that it is important for people with severe malaria to receive the correct doses of an effective antimalarial drug given by an appropriate route promptly; the aim of this initial stage of treatment is resuscitation. Later, when the person's condition has stabilized and drugs can be taken orally, it is sometimes convenient to change the drug in order to eradicate circulating asexual parasite forms. Drugs currently in use for initial resuscitation include chloroquine (although resistance to this compound is restricting its utility), quinine, and the artemisinin derivatives (mainly artemether, artesunate, and dihydroartemisinin). Mefloquine and sulfadoxine-pyrimethamine are often used for subsequent treatment, but they are not employed for resuscitation. The choice of drug is governed by the availability, cost, and pattern of drug resistance in the community (Phillips 1996). For many years chloroquine was the preferred drug for treating severe malaria. Resistance of the malaria parasite to chloroquine was first observed in South-East Asia and South America (Bjorkman 1990). This has reduced the effectiveness of chloroquine as an antimalarial and has led to a rise in deaths from malaria (Trape 1998). In many areas of chloroquine resistance, quinine has returned as the first-line drug for severe forms of malaria (White 1982; WHO 1986). The escalating problem of drug resistance continues to challenge health workers involved in managing severe forms of malaria (Nuwaha 2001).

The WHO recommends that people with severe malaria be given an initial high dose of intravenous quinine, also referred to as the loading dose (WHO 1986). This is followed by quinine maintenance doses (Chongsuphajaisiddhi 1981; White 1982; WHO 1986; WHO 1990b). The rationale for the loading dose is the urgent need to achieve an effective quinine concentration in the blood (Allen 1996). Death in severe malaria often occurs in the first 12 to 48 hours of admission (Allen 1996; van der Torn 1998). Pharmacokinetic studies have clearly demonstrated that drug therapy needs to exceed the parasite minimum inhibitory concentration as soon as possible and thereafter maintain therapeutic drug levels for the remainder of the treatment (White 1983). The high first dose is also used in the managing children with severe malaria (Waller 1990; Winstanley 1994; van Hensbroek 1996). A variety of quinine loading doses, maintenance doses, and dose intervals have been examined over the last 15 years. The 'WHO standard' is now 20 mg/kg of the dihydrochloride salt infused at constant rate over 4 hours, followed by 10 mg/kg of the salt infused over 2 hours, and repeated every 8 hours. All people with cerebral malaria, and the majority with other severe malaria syndromes, are incapable of taking oral medications: thus the parenteral routes are obligatory. In those people with severe malaria who are able to take medicines orally, parenteral routes are still preferred for reasons such as the possibility of ileus (obstruction of the intestines) causing gastroparesis (paralysis of the stomach); oral dosing carries the risk of vomiting and aspiration, and the assurance with parenteral dosing is that the drug is in the body.

The Type A (dose related) adverse reactions of quinine include hypoglycaemia (Phillips 1984), renal failure (Sharma 1989), and an abnormal heartbeat (cardiac arrhythmias) (Jacqz-Aigrain 1994). The Type B (not classically dose related) adverse reactions include haemolysis (the breakdown of red blood cells) and thrombocytopenia (low platelet count) (Jacqz-Aigrain 1994). Cinchonism, characterized by ringing in the ears, headache, and deafness (Dorland 2000), is a common symptomatic and dose-related adverse reaction to quinine. However, in routine clinical practice, this is rarely considered a problem in severe malaria as a large proportion of patients have perturbed consciousness, and for this reason cinchonism is not viewed as a reason to reduce quinine doses in patients. There are concerns about an increased risk of adverse effects in children given a high first dose of quinine (van Hensbroek 1996). Very rarely, death may be associated with intravenous quinine (Hall 1977; White 1989).

Before the WHO recommendation in 1986 to treat severe malaria with a high first dose regimen, a uniform dose regimen (no loading dose) of quinine of 10 mg/kg every 8 hours was used (Hall 1977). This uniform dose regimen has been considered to have fewer adverse effects than the high first dose regimen (Davis 1988; Kawo 1991). While the new drugs suitable for treating chloroquine resistant malaria remain expensive, quinine will continue to be an important drug in the battle to reduce mortality from the severe forms of malaria in low-income and middle-income countries. Consequently, quinine must be used in the most effective way possible.

The purpose of this review is to summarize the benefits and harms of different quinine dosing regimens with a view to improving policy and practice.

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

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.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Randomized controlled trials and quasi-randomized controlled trials.

 

Types of participants

People (adults and children) with any form of severe malaria (as defined by trial authors) treated with intravenous quinine.

 

Types of interventions

 

Intervention

Loading (high first) dose of intravenous quinine (20 mg/kg salt equivalent to 16 mg/kg base, as the first dose).

 

Control

No loading (uniform) dose of intravenous quinine (10 mg/kg salt equivalent to 8 mg/kg base, as the first dose).

After the first dose, people in both groups will be given 10 mg/kg salt or 8 mg/kg base every 8 or 12 hours.

 

Types of outcome measures

 

Primary

Death.

 

Secondary

  • Coma recovery time (time between the onset of coma and its resolution or as defined by the trial authors).
  • Convulsions (as defined by the trial authors).
  • Fever clearance time (time between start of treatment and return of body temperature to normal or as defined by the trial authors).
  • Parasite clearance time (time between start of treatment and the first negative blood test or as defined by the trial authors).
  • Number of participants with asexual parasitaemia at 24 and 48 hours.
  • Neurological sequelae.

 

Adverse events

  • Hypoglycaemia (blood glucose < 2.2 mmol/litre) during hospitalization.
  • Anaemia (haemoglobin < 10 g/litre at follow-up visit).
  • Any other.

 

Search methods for identification of studies

We have attempted to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress).

 

Databases

We searched the following databases using the search terms and strategy described in  Table 1: Cochrane Infectious Diseases Group Specialized Register (February 2009); Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library (Issue 1, 2009); MEDLINE (1966 to February 2009); EMBASE (1974 to February 2009); and LILACS (1982 to February 2009).

 

Conference proceedings

We searched the conference proceeding of The Third MIM Pan-African Malaria Conference (Arusha, Tanzania November 17 to 22, 2002) for relevant abstracts.

 

Researchers

We contacted researchers working in the field for unpublished and ongoing trials.

 

Reference lists

We checked the citations of all studies identified by the search strategy.

 

Data collection and analysis

 

Selection of studies

We independently screened the results of the search to select potentially relevant studies. We then independently applied eligibility criteria to the potentially relevant studies. These criteria were based on the type of participant, study design, intervention, comparisons, and outcomes. We resolved differences in opinion through discussion. Where there was ambiguity, we sought clarification from the trial authors. We excluded studies that did not meet these criteria and stated the reason in the 'Characteristics of excluded studies'.

 

Data extraction and management

Afolabi Lesi extracted data on methods, participants, interventions, and outcomes from the trials, and Martin Meremikwu independently cross checked these data. Where there were differences, we referred to the original paper. We entered the data into Review Manager 5. Where possible, we scrutinized the data sources for multiple publications from the same data sets.

 

Assessment of risk of bias in included studies

We independently assessed the risk of bias in the trials to be included with regard to the allocation sequence, concealment of allocation, blinding, and completeness of the trial. We classified generation of the allocation sequence and allocation concealment as adequate, inadequate, or unclear according to Jüni 2001. We classified blinding as open (all parties are aware of the treatment given), single (participant or care provider or assessor is unaware of the treatment given), or double blind (through the use of a placebo − either the participant and the care provider, or the participant and assessor are unaware of the treatment given). We considered loss to follow up to be adequate if it is less than 10%. Wherever necessary, we contacted trial authors for clarification.

 

Data synthesis

We combined binary data using risk ratio (RR) and combined continuous data using the mean difference (MD). We used 95% confidence intervals (CI). If there was evidence of skewed data, or data were presented using medians and ranges, we presented the data in tables only.

Where trials presented results using time-to-event or censored data analysis, we intended to extract estimates of log hazards ratio and variance using methods proposed by Parmar 1998.

We assessed heterogeneity by visually examining the forest plot and using the chi-squared test for heterogeneity with a 10% level of statistical significance. In the absence of homogeneity of treatment effects, we intended to use a random-effects model, and if the number of studies permitted, to investigate the heterogeneity using the following subgroups: children compared with adults; and high compared with low transmission of malaria.

We examined funnel plots for asymmetry, which could be caused by publication bias, differences in methodological quality, or heterogeneity of results.

 

Results

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

 

Eligibility

We identified 11 potentially relevant publications, of which four met the inclusion criteria (Fargier 1991; Pasvol 1991; Tombe 1992; Assimadi 2002). We have provided the reasons for excluding studies in the 'Characteristics of excluded studies'. The included trials are described in the 'Characteristics of included studies' and are summarized below.

 

Participants

The trials included a total of 164 participants, but only 144 were available for analysis because 20 children (out of 59) in Pasvol 1991 had been randomized to receive intramuscular quinine. Tombe 1992 and Pasvol 1991 studied people with severe malaria: Tombe 1992 studied 33 people aged 14 years or older, and Pasvol 1991 studied 59 children. Fargier 1991 and Assimadi 2002 studied people with cerebral malaria: Fargier 1991 studied 20 people aged 15 years or older, and Assimadi 2002 studied 72 children between 8 months and 15 years old. Fargier 1991 provided medians and ranges that were not adequate for meta-analysis. We contacted trial authors for further information, but none responded.

 

Interventions

Tombe 1992, Pasvol 1991, and Assimadi 2002 used a quinine loading dose of 20 mg/kg (salt), while Fargier 1991 used 16 mg/kg (base). Quinine was given by both intramuscular and intravenous route in the Pasvol 1991 trial, while the other three trials used only intravenous infusion. We did not include the participants (n = 20) in treatment arm of Pasvol 1991 that received intramuscular quinine.

 

Outcome measures

Three trials reported on the primary outcome of death, two reported on coma recovery time, fever clearance time and parasite clearance time, and one trial reported on convulsions and the number with asexual parasitaemia at 24 and 48 hours. Three trials reported on adverse events (but not anaemia), and two of these also reported neurological sequelae. Fargier 1991 reported duration of coma and the parasite clearance time, but did not provide adequate data for meta-analysis (see  Table 2 for details).

 

Risk of bias in included studies

The methodological quality of the trials is summarized in  Table 3.

 

Generation of allocation sequence

All the trials were reported by the trial authors to be randomized, but none stated the method used to generate allocation sequence. Two trialists, G Pasvol and M Tombe, responded to our request for further information and clarified that the allocation sequence in their studies was generated using computers and random-number tables respectively.

 

Allocation concealment

Allocation concealment was unclear in three trials. We were able to determine that Pasvol 1991 used an adequate method for concealing treatment allocation (sealed envelopes) from his correspondence, but M Tombe did not provide explicit clarification.

 

Blinding

It was also unclear whether the trials were blinded; from correspondence with G Pasvol and M Tombe, we were able to determine that there was no attempt to mask treatment from the participants or the investigators.

 

Loss to follow up

The loss to follow up was unclear in three trials and was inadequate in Pasvol 1991, which reported over 10% loss to follow up (80.4% of randomized participants available for analysis).

 

Effects of interventions

 

Death

Three trials reported deaths (Pasvol 1991; Tombe 1992; Assimadi 2002). Eleven deaths were recorded among 144 participants in both groups. The difference was not statistically significant (RR 0.62, 95% CI 0.19 to 2.04;  Analysis 1.1). We did not detect statistically significant heterogeneity between these data sets.

 

Coma recovery time

Pasvol 1991 and Assimadi 2002 did not report a statistically significant difference between both groups (WMD 5.17 hours, 95% CI -1.14 to 11.47;  Analysis 1.2).

 

Convulsions

Pasvol 1991 reported convulsions in 13 out of 39 participants in both groups (RR 0.73, 95% CI 0.29 to 1.84;  Analysis 1.3).

 

Fever clearance time and parasite clearance time

Pasvol 1991 and Tombe 1992 reported on both outcomes. Those participants that received a loading dose had both a statistically significantly shorter fever clearance time (WMD -11.11 hours, 95% CI -20.04 to -2.18;  Analysis 1.4) and parasite clearance time (WMD -7.44 hours, 95% CI -13.24 to -1.64;  Analysis 1.5) than those that did not. The test for heterogeneity for both outcomes was not statistically significant.

 

Number with asexual parasitaemia at 24 hours and 48 hours

Assimadi 2002 reported no statistically significant difference between both groups of participants with asexual parasitaemia at 24 hours (RR 1.27, 95% CI 0.87 to 1.84;  Analysis 1.6) and 48 hours (RR 0.08, 95% CI 0.00 to 1.39;  Analysis 1.7).

 

Neurological sequelae

Pasvol 1991 and Assimadi 2002 identified neurological sequelae in both the loading dose group (2/53) and no loading dose group (4/58) (RR 0.56, 95% CI 0.11 to 2.90;  Analysis 1.8).

 

Adverse events

See  Analysis 1.9. Pasvol 1991 and Tombe 1992 reported hypoglycaemia in 7 out of 72 participants across both groups (RR 1.39, 95% CI 0.32 to 6.00). Tombe 1992 also reported tinnitus, hearing loss, hypotension (low diastolic blood pressure), vomiting, abdominal pain, blurred vision, urticarial rash, and phlebitis. Only hearing loss differed statistically significantly between the two study groups. There was a statistically significant difference in the number of participants receiving the quinine loading dose that had partial hearing loss (10/17) compared with the number receiving no quinine loading dose (3/16) (RR 3.14, CI 1.05 to 9.38). The trial authors reported that all the participants "regained their hearing" by day 15 at follow up (Tombe 1992). Assimadi 2002 reported that only one participant in the loading dose group had any abnormalities of heartbeat (prolonged QT interval) (RR 3.17, 95% CI 0.13 to 75.24). None of the trials reported any cinchonism.

 

Discussion

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

The allocation sequence was adequately generated in two of the four trials included in this review (Pasvol 1991; Tombe 1992). Allocation concealment was adequate (using sealed envelopes) in only one trial (Pasvol 1991). We note that there was no attempt to mask the treatment from the participants or the investigators. We recognize the difficulty of completely blinding treatment in trials of this nature where the volume of the loading dose obviously differs, and that in almost all cases involving children the doses to be given have to be worked out on the field after estimating the child's weight. Nevertheless, we consider that these methodological issues have not been uniformly handled in the trials. Failing to conceal allocation or blind clinical trials or even failure to do an intention-to-treat analysis increases the risk of bias and brings the internal validity of the results to question (Schulz 1995).

As a result of the small number of participants and deaths in each trial, there might be some uncertainty surrounding the estimate of risk ratio and any inferences could be misleading. Overall there were not enough trials to investigate the role of the age of the participants with severe malaria, the differences in pattern of illness, and the local endemicity pattern. About a third of the participants in the included trials were adults (Fargier 1991; Tombe 1992), and the remainder were children (Pasvol 1991; Assimadi 2002). The pattern of severe malaria in the trials varied. Two trials included people only with cerebral malaria (Fargier 1991; Assimadi 2002), the other two included people with different disorders recognized in the syndrome of severe malaria (WHO 2000).

From the results it appears that there is insufficient evidence to determine whether using a high first (loading) dose of quinine reduces deaths from severe malaria. The presence of convulsion and the duration of coma are of prognostic significance (Jaffar 1997). There is also insufficient evidence to determine whether giving a loading dose is associated with fewer convulsions or a shorter recovery of consciousness.

With regard to fever and parasite clearance times, the loading dose regimen offers an advantage over the no loading dose regimen. However, this conclusion is based on the results of two small trials.

Concerning adverse events with quinine, the results show that the loading dose had a statistically significant association with partial hearing loss. Although the trialist who reported this outcome effect described it as transient, disappearing by day 15 at follow up (Tombe 1992), we note that the effect can be distressing for the patient.

The principal goal of treatment in severe malaria is to prevent people from dying. The limited data available from this review shows that there is insufficient evidence to determine whether giving a quinine loading dose to people with severe malaria offers any additional benefit with regards to preventing death. These results need to be interpreted with caution given the small size of the trials, the wide confidence intervals for all the outcome measures studied, and the mostly varied and sometimes uncertain methodological quality of the individual trials.

 

Authors' conclusions

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

 

Implications for practice

High first dose quinine reduced fever clearance time and parasite clearance time in severe malaria. There is insufficient evidence to demonstrate directly an effect on death, convulsions, hypoglycaemia, or coma recovery time

 
Implications for research

Larger, better quality trials evaluating the benefits or harm of quinine loading dose in cerebral malaria are warranted. Researchers conducting trials in severe malaria should use pragmatic outcomes, including death and number of convulsions, as primary outcome measures for benefit rather than depend on parasite or fever clearance times.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

This protocol for this review was developed during the Mentorship Programme organized by the Cochrane Infectious Diseases Group, May to June 2001. The Department for International Development (UK) supports this Programme through the Effective Health Care Alliance Programme at the Liverpool School of Tropical Medicine.

 

Data and analyses

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
Download statistical data

 
Comparison 1. High first (loading) dose compared with no loading dose
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
 1 Death3144Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.19, 2.04]
 2 Coma recovery time299Mean Difference (IV, Fixed, 95% CI)5.17 [-1.14, 11.47]
 3 Convulsions1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 4 Fever clearance time268Mean Difference (IV, Fixed, 95% CI)-11.11 [-20.04, -2.18]
 5 Parasite clearance time267Mean Difference (IV, Fixed, 95% CI)-7.44 [-13.24, -1.64]
 6 Number with asexual parasitaemia at 24 hours1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 7 Number with asexual parasitaemia at 48 hours1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected
 8 Neurological sequelae2111Risk Ratio (M-H, Fixed, 95% CI)0.56 [0.11, 2.90]
 9 Adverse events3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
    9.1 Hypoglycaemia
272Risk Ratio (M-H, Fixed, 95% CI)1.39 [0.32, 6.00]
    9.2 Tinnitus
133Risk Ratio (M-H, Fixed, 95% CI)2.82 [0.33, 24.43]
    9.3 Hearing loss
133Risk Ratio (M-H, Fixed, 95% CI)3.14 [1.05, 9.38]
   9.4 Cinchonism
00Risk Ratio (M-H, Fixed, 95% CI)Not estimable
    9.5 Hypotension (diastolic blood pressure < 60 mm mercury)
133Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.84, 1.19]
    9.6 Arrhythmia (prolonged QT interval)
172Risk Ratio (M-H, Fixed, 95% CI)3.17 [0.13, 75.24]

 

What's new

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Last assessed as up-to-date: 18 February 2009.

DateEventDescription
19 February 2009New search has been performedSearch updated. No new studies found


 

History

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Protocol first published: Issue 4, 2001
Review first published: Issue 3, 2002

DateEventDescription
13 August 2008AmendedConverted to new review format with minor editing. Plain language summary added to review.
31 July 2006New search has been performedNew studies sought but none found; search dates updated.
30 March 2004New citation required and conclusions have changedIssue 3, 2004: We included a trial published that studied 72 children with cerebral malaria. We added neurological sequelae to the list of outcome measures.


 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

Afolabi Lesi (AL) and Martin Meremikwu (MM) identified the topic. AL wrote the protocol, designed the eligibility and validity criteria, and the data extraction forms. AL and MM extracted the data. AL wrote the results and the discussion and MM revised them.

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Results
  6. Discussion
  7. Authors' conclusions
  8. Acknowledgements
  9. Data and analyses
  10. What's new
  11. History
  12. Contributions of authors
  13. Declarations of interest
  14. Sources of support
  15. Index terms
 

Internal sources

  • Liverpool School of Tropical Medicine, UK.
  • College of Medicine, University of Lagos, Nigeria.

 

External sources

  • Department for International Development, UK.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. Additional references
Assimadi 2002 {published data only}
  • Assimadi JK, Gbadoe AD, Agbodjan-Djossou O, Ayewada K, Goeh-Akue E, Kusiaku K, et al. Intravenous quinine treatment of cerebral malaria in African children: comparison of a loading dose regimen without loading dose [Traitment du paludisme cérébral de l'enfant africain par les sels de quinine: comparaison d'un schéma avec dose charge à un schéma classique sans dose charge]. Archives de Pediatrie 2002;9(6):587-94.
Fargier 1991 {published data only}
  • Fargier JJ, Louis FJ, Cot M, Maubert B, Hounsinou C, Louis JP, et al. Reducing of coma by quinine loading dose in falciparum cerebral malaria. Lancet 1991;338(8771):896-7.
  • Louis FJ, Fargier JJ, Maubert B, Louis JP, Hounsinou C, Le Bras J, et al. Severe malaria attacks in adults in Cameroon: comparison of 2 therapeutic protocols using quinine via parenteral route [Access palustre grave de l'adulte au Cameroun: comparaison de deux protocoles therapeutiques utilisant la quinine par voie parenterale]. Annales de La Societe Belge de Medecine Tropicale 1992;72(3):179-88.
Pasvol 1991 {published data only}
  • Pasvol G, Newton CRJC, Winstanley PA, Watkins WM, Peshu NM, Were JBO, et al. Quinine treatment of severe falciparum malaria in African children: A randomized comparison of three regimens. American Journal of Tropical Medicine and Hygiene 1991;45(6):702-13.
Tombe 1992 {published data only}
  • Tombe M, Bhatt KM, Obel AOK. Quinine loading dose in severe falciparum malaria at Kenya National Hospital, Kenya. East African Medical Journal 1992;69(12):670-4.

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. Additional references
Davis 1988 {published data only}
  • Davis TM, White NJ, Looareesuwan S, Silamut K, Warrell DA. Quinine pharmacokinetics in cerebral malaria: predicted plasma concentrations after rapid intravenous loading using a two-compartment model. Transactions of the Royal Society of Tropical Medicine and Hygiene 1988;82(4):542-7.
Davis 1990 {published data only}
  • Davis TME, Supanaranond W, Pukrittayakamee S, Karbwang J, Molunto P, Mekthon S, et al. A safe and effective consecutive-infusion regimen for rapid quinine loading in severe falciparum malaria. Journal of Infectious Diseases 1990;161(6):1305-8.
Mehta 1994 {published data only}
  • Mehta SR, Lazar AI, Kasthuri AS. Experience on loading dose--quinine therapy in cerebral malaria. Journal of Association of Physicians in India 1994;42(5):376-8.
van der Torn 1998 {published data only}
  • van der Torn M, Thuma PE, Mabeza GF, Biemba G, Moyo VM, McLaren CE, et al. Loading dose of quinine in African children with cerebral malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 1998;92(3):325-31.
White 1983 {published data only}
  • White NJ, Looareesuwan S, Warrell DA, Warrell MJ, Chanthavanich P, Bunnag D, et al. Quinine loading dose in cerebral malaria. American Journal of Tropical Medicine and Hygiene 1983;32(1):1-5.
Winstanley 1994 {published data only}
  • Winstanley PA, Mberu EK, Watkin WM, Murphy SA, Lowe B, Marsh K. Towards optimal regimens of parenteral quinine of young African children with cerebral malaria: unbound quinine concentrations following a single loading dose regimen. Transactions of the Royal Society of Tropical Medicine and Hygiene 1994;88(5):577-80.

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. What's new
  12. History
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Characteristics of studies
  17. References to studies included in this review
  18. References to studies excluded from this review
  19. Additional references
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Allen 1996
Bjorkman 1990
Chongsuphajaisiddhi 1981
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Jüni 2001
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