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Meta-Analysis
. 2013 Dec 9;2013(12):CD008846.
doi: 10.1002/14651858.CD008846.pub2.

Mass drug administration for malaria

Eugenie Poirot  1 , Jacek Skarbinski, David Sinclair, S Patrick Kachur, Laurence Slutsker, Jimee Hwang
Affiliations
Meta-Analysis

Mass drug administration for malaria

Eugenie Poirot et al. Cochrane Database Syst Rev. .

Update in

  • Mass drug administration for malaria.
    Shah MP, Hwang J, Choi L, Lindblade KA, Kachur SP, Desai M. Shah MP, et al. Cochrane Database Syst Rev. 2021 Sep 29;9(9):CD008846. doi: 10.1002/14651858.CD008846.pub3. Cochrane Database Syst Rev. 2021. PMID: 34585740 Free PMC article.

Abstract

Background: Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission.

Objectives: To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events.

Search methods: We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings.

Selection criteria: Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded.

Data collection and analysis: Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach.

Main results: Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity (≤5%)Within the first month post-MDA, a single uncontrolled before-and-after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence). In addition, one cluster-randomized trial evaluating MDA in a low endemic setting reported zero episodes of parasitaemia at baseline, and throughout five months of follow-up in both the control and intervention arms (one study, very low quality evidence). Areas of moderate endemicity (6-39%)Within the first month post-MDA, the prevalence of parasitaemia was much lower in three non-randomized controlled studies from Kenya and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate quality evidence), and in three uncontrolled before-and-after studies conducted between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality evidence).The longest follow-up in these settings was four to six months. At this time point, the prevalence of parasitaemia remained substantially lower than controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to 0.33, two studies, low quality evidence). In contrast, the two uncontrolled before-and-after studies found mixed results: one found no difference and one found a substantially higher prevalence compared to baseline (not pooled, two studies, very low quality evidence). Areas of high endemicity (≥40%)Within the first month post-MDA, the single cluster-randomized trial from the Gambia in 1999 found no significant difference in parasite prevalence (one study, low quality evidence). However, prevalence was much lower during the MDA programmes in three non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95% CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to 0.49, four studies,low quality evidence).Four trials reported changes in prevalence beyond three months. In the Gambia, the single cluster-randomized trial found no difference at five months (one trial, moderate quality evidence). The three uncontrolled before-and-after studies had mixed findings with large studies from Palestine and Cambodia showing sustained reductions at four months and 12 months, respectively, and a small study from Malaysia showing no difference after four to six months of follow-up (three studies,low quality evidence). 8-aminoquinolines We found no studies directly comparing MDA regimens that included 8-aminoquinolines with regimens that did not. In a crude subgroup analysis with a limited number of studies, we were unable to detect any evidence of additional benefit of primaquine in moderate- and high-transmission settings. Plasmodium species In studies that reported species-specific outcomes, the same interventions resulted in a larger impact on Plasmodium falciparum compared to P. vivax.

Authors' conclusions: MDA appears to reduce substantially the initial risk of malaria parasitaemia. However, few studies showed sustained impact beyond six months post-MDA, and those that did were conducted on small islands or in highland settings.To assess whether there is an impact of MDA on malaria transmission in the longer term requires more quasi experimental studies with the intention of elimination, especially in low- and moderate-transmission settings. These studies need to address any long-term outcomes, any potential barriers for community uptake, and contribution to the development of drug resistance.

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Conflict of interest statement

All authors report no known conflicts of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 MDA versus no MDA in areas of low endemicity (Stratified by study design), Outcome 1 Parasitaemia Prevalence: Cluster‐randomized trials.
1.2
1.2. Analysis
Comparison 1 MDA versus no MDA in areas of low endemicity (Stratified by study design), Outcome 2 Parasitaemia Prevalence: Uncontrolled before‐and‐after studies.
1.3
1.3. Analysis
Comparison 1 MDA versus no MDA in areas of low endemicity (Stratified by study design), Outcome 3 Gametocytaemia Prevalence: Cluster randomized trials.
2.1
2.1. Analysis
Comparison 2 MDA versus no MDA in areas of moderate endemicity (Stratified by study design), Outcome 1 Parasitaemia Prevalence: Non‐randomized controlled studies.
2.2
2.2. Analysis
Comparison 2 MDA versus no MDA in areas of moderate endemicity (Stratified by study design), Outcome 2 Parasitaemia Prevalence: Uncontrolled before‐and‐after studies.
2.3
2.3. Analysis
Comparison 2 MDA versus no MDA in areas of moderate endemicity (Stratified by study design), Outcome 3 Gametocytaemia Prevalence: Non‐randomized controlled studies.
2.4
2.4. Analysis
Comparison 2 MDA versus no MDA in areas of moderate endemicity (Stratified by study design), Outcome 4 Gametocytaemia Prevalence: Uncontrolled before‐and‐after studies.
3.1
3.1. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 1 Parasitaemia Prevalence: Cluster‐randomized trials.
3.2
3.2. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 2 Parasitaemia Prevalence: Non‐randomized controlled studies.
3.3
3.3. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 3 Parasitaemia Prevalence: Uncontrolled before‐and‐after studies.
3.4
3.4. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 4 Parasitaemia Incidence: Cluster‐randomized trials.
3.5
3.5. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 5 Gametocytaemia Prevalence: Cluster‐randomized trials.
3.6
3.6. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 6 Gametocytaemia Prevalence: Non‐randomized controlled studies.
3.7
3.7. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 7 Gametocytaemia Prevalence: Uncontrolled before‐and‐after studies.
3.8
3.8. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 8 Anaemia Prevalence: Cluster‐randomized trials.
3.9
3.9. Analysis
Comparison 3 MDA versus no MDA in areas of high endemicity (Stratified by study design), Outcome 9 Mortality: Cluster‐randomized trials.
4.1
4.1. Analysis
Comparison 4 MDA + vector control versus no intervention in areas of moderate endemicity (Stratified by study design), Outcome 1 Parasitaemia Prevalence: Non‐randomized controlled studies.
4.2
4.2. Analysis
Comparison 4 MDA + vector control versus no intervention in areas of moderate endemicity (Stratified by study design), Outcome 2 Parasitaemia Prevalence: Uncontrolled before‐and‐after studies.
4.3
4.3. Analysis
Comparison 4 MDA + vector control versus no intervention in areas of moderate endemicity (Stratified by study design), Outcome 3 Gametocytaemia Prevalence: Uncontrolled before‐and‐after studies.
5.1
5.1. Analysis
Comparison 5 MDA + vector control versus no intervention in areas of high endemicity (Stratified by study design), Outcome 1 Parasitaemia Prevalence: Non‐randomized controlled studies.
5.2
5.2. Analysis
Comparison 5 MDA + vector control versus no intervention in areas of high endemicity (Stratified by study design), Outcome 2 Parasitaemia Prevalence: Uncontrolled before‐and‐after studies.
5.3
5.3. Analysis
Comparison 5 MDA + vector control versus no intervention in areas of high endemicity (Stratified by study design), Outcome 3 Gametocytaemia Prevalence: Non‐randomized controlled studies.
5.4
5.4. Analysis
Comparison 5 MDA + vector control versus no intervention in areas of high endemicity (Stratified by study design), Outcome 4 Gametocytaemia Prevalence: Uncontrolled before‐and‐after studies.
6.1
6.1. Analysis
Comparison 6 Parasitaemia Incidence studies, Outcome 1 MDA versus no MDA: Uncontrolled before‐and‐after studies.
6.2
6.2. Analysis
Comparison 6 Parasitaemia Incidence studies, Outcome 2 MDA + vector control versus no MDA: Uncontrolled before‐and‐after studies.
7.1
7.1. Analysis
Comparison 7 MDA versus no MDA in areas of moderate and high endemicity (Stratified by study design; subgrouped by 8‐aminoquinoline), Outcome 1 Parasitaemia Prevalence during MDA.
7.2
7.2. Analysis
Comparison 7 MDA versus no MDA in areas of moderate and high endemicity (Stratified by study design; subgrouped by 8‐aminoquinoline), Outcome 2 Parasitaemia Prevalence 1‐3 months post MDA.
7.3
7.3. Analysis
Comparison 7 MDA versus no MDA in areas of moderate and high endemicity (Stratified by study design; subgrouped by 8‐aminoquinoline), Outcome 3 Parasitaemia Prevalence during MDA.
7.4
7.4. Analysis
Comparison 7 MDA versus no MDA in areas of moderate and high endemicity (Stratified by study design; subgrouped by 8‐aminoquinoline), Outcome 4 Parasitaemia Prevalence <1 month post MDA.
7.5
7.5. Analysis
Comparison 7 MDA versus no MDA in areas of moderate and high endemicity (Stratified by study design; subgrouped by 8‐aminoquinoline), Outcome 5 Parasitaemia Prevalence 1‐3 months post MDA.
7.6
7.6. Analysis
Comparison 7 MDA versus no MDA in areas of moderate and high endemicity (Stratified by study design; subgrouped by 8‐aminoquinoline), Outcome 6 Parasitaemia Prevalence 4‐6 months post MDA.
8.1
8.1. Analysis
Comparison 8 MDA versus no MDA for all endemicity levels (Stratified by study design; subgrouped by plasmodium species), Outcome 1 Parasitaemia Prevalence at baseline.
8.2
8.2. Analysis
Comparison 8 MDA versus no MDA for all endemicity levels (Stratified by study design; subgrouped by plasmodium species), Outcome 2 Parasitaemia Prevalence during MDA.
8.3
8.3. Analysis
Comparison 8 MDA versus no MDA for all endemicity levels (Stratified by study design; subgrouped by plasmodium species), Outcome 3 Parasitaemia Prevalence <1 month post MDA.
8.4
8.4. Analysis
Comparison 8 MDA versus no MDA for all endemicity levels (Stratified by study design; subgrouped by plasmodium species), Outcome 4 Parasitaemia Prevalence 1‐3 months post MDA.
8.5
8.5. Analysis
Comparison 8 MDA versus no MDA for all endemicity levels (Stratified by study design; subgrouped by plasmodium species), Outcome 5 Parasitaemia Prevalence 4‐6 months post MDA.
8.6
8.6. Analysis
Comparison 8 MDA versus no MDA for all endemicity levels (Stratified by study design; subgrouped by plasmodium species), Outcome 6 Parasitaemia Prevalence >12 months post MDA.
See this image and copyright information in PMC

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Najera 1973 NGA {published data only}
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References to studies excluded from this review

Abraham 1944 {published data only}
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Afridi 1959 {published data only}
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Ahorlu 2009 {published data only}
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Alonso 1993b {published data only}
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Alving 1952 {published data only}
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Amangel'diev 2001 {published data only}
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Annual Report 1932 {published data only}
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Archambeault 1954 {published data only}
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Archibald 1956 {published data only}
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Babione 1966 {published data only}
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Banerjea 1949 {published data only}
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Barber 1932 {published data only}
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Barger 2009 {published data only}
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Baukapur 1984 {published data only}
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Berberian 1948 {published data only}
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Berny 1936 {published data only}
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Bloch 1982 {published data only}
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Bojang 2010 {published data only}
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Boulanger 2009 {published data only}
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Boulanger 2010 {published data only}
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Canet 1939 {published data only}
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Canet 1949 {published data only}
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Canet 1952 {published data only}
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Capponi 1953 {published data only}
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Charles 1958 {published data only}
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Charles 1962 {published data only}
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Chaudhuri 1950 {published data only}
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Chen 1999 {published data only}
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Cisse 2006 {published data only}
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Ciuca 1937 {published data only}
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Clark 1942 {published data only}
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Clarke 2008 {published data only}
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Clyde 1958 {published data only}
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Clyde 1961a {published data only}
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Clyde 1961b {published data only}
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Clyde 1962 {published data only}
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Coutinho 1962 {published data only}
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D'Anfreville 1930 {published data only}
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Danquah 2009 {published data only}
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Dapeng 1996 {published data only}
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Decourt 1936 {published data only}
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Delmont 1981 {published data only}
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de Mello 1938 {published data only}
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Desowitz 1987 {published data only}
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Diallo 1977 {published data only}
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Diallo 1983 {published data only}
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Dicko 2011 {published data only}
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Dixon 1950 {published data only}
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Doi 1989 {published data only}
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Dola 1974 {published data only}
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Doucet 1947 {published data only}
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Downs 1946 {published data only}
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Dupoux 1937 {published data only}
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Dupoux 1939 {published data only}
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Edeson 1957 {published data only}
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Farinaud 1934 {published data only}
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Farinaud 1950 {published data only}
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Gaud 1949 {published data only}
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Gilroy 1952 {published data only}
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Gomez Mendoza 1960 {published data only}
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Gribben 1933 {published data only}
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Gruer 1962 {published data only}
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Gunther 1951 {published data only}
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Gunther 1952 {published data only}
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Gusmao 1970 {published data only}
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Harwin 1973 {published data only}
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Henderson 1934 {published data only}
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Ho 1965 {published data only}
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Houel 1954b {published data only}
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Huehne 1971 {published data only}
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Janssens 1950 {published data only}
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Kaneko 2010 {published data only}
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Kingsbury 1931 {published data only}
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Klopfer 1949 {published data only}
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Komp 1935 {published data only}
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Konate 2011 {published data only}
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Kweku 2008 {published data only}
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Kweku 2009 {published data only}
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Lacroix 1952 {published data only}
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Lahon 1960 {published data only}
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Lakshmanacharyulu 1968 {published data only}
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Levenson 1943 {published data only}
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Liljander 2010 {published data only}
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Lui 1986 {published data only}
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Lysenko 1960 {published data only}
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MacCormack 1983 {published data only}
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Mackerras 1954 {published data only}
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Maiga 2009 {published data only}
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Malaria_Army 1934 {published data only}
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Mason 1973 {published data only}
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Mason 1977 {published data only}
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Mastbaum 1957a {published data only}
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McGregor 1966 {published data only}
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Mendez Galvan 1984 {published data only}
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Mezincesco 1935 {published data only}
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Miller 1955 {published data only}
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Nankabirwa 2010 {published data only}
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Parrot 1943 {published data only}
    1. Parrot L, Catanei A, Collignon E, Ambialet R. New trial of synthetic drugs for collective prophylaxis of malaria. Archives de l'Institut Pasteur d'Algerie 1943;21(3):131‐79.
Parrot 1944 {published data only}
    1. Parrot L, Catanei A, Collignon E. New trials of mass prophylaxis of malaria with synthetic drugs. Archives de l'Institut Pasteur d'Algerie 1944;22(3):179‐246.
Parrot 1946 {published data only}
    1. Parrot L, Catanei A, Collignon E. Further trials of mass prophylaxis of malaria with synthetic drugs. Archives de l'Institut Pasteur d'Algerie 1946;24(3/4):205‐78.
Peters 1962 {published data only}
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Phillips 1954 {published data only}
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Pikul 1934 {published data only}
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Pribadi 1986 {published data only}
    1. Pribadi W, Muzaham F, Santoso T, Rasidi R, Rukmono B, Soeharto, et al. The implementation of community participation in the control of malaria in rural Tanjung Pinang, Indonesia. Southeast Asian Journal of Tropical Medicine & Public Health 1986;17(3):371‐8. - PubMed
Prokopenko 1945 {published data only}
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Rachou 1965 {published data only}
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Rafi 1951 {published data only}
    1. Rafi SM, Shah IA. Paludrine as a causal prophylactic in hyperendemic areas. Pakistan Journal of Health 1951;1(1):42‐6.
Ray 1948 {published data only}
    1. Ray AP. Prophylactic use of paludrine in a tea estate. Indian Journal of Malariology 1948;2:35‐66.
Robin 1946 {published data only}
    1. Robin C, Brochen L. Malaria in Dakar. Results of the therapeutic and prophylactic administration of synthetic drugs in a native population. Bulletin Medical de l'Afrique‐Occidentale Francaise 1946;3(1):97‐108.
Rodríguez 1994 {published data only}
    1. Rodríguez López MH, Loyola Elizondo EG, Betanzos Reyes AF, Villareal Treviño C, Nielsen Bown D. Control focal del paludismo: tratamiento focal usando quimioprofilaxis y rociado intradomiciliar con insecticida para el control del paludismo en el sur de México. Gaceta Medica De Mexico 1994;130(5):313‐9. - PubMed
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Salako 1990 {published data only}
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Santos 1993 {published data only}
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Schliessmann 1973 {published data only}
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Schneider 1948a {published data only}
    1. Schneider J, Dignat M, Voron, Sfar M. Mass prophylaxis of malaria with premaline in the Gabes Area, May to November, 1946. Bulletin de la Societe de Pathologie Exotique 1948;41(3/4):104‐8.
Schneider 1948b {published data only}
    1. Schneider J, Larabi M, Balti M. Mass prophylaxis of Malaria with Nivaquine; Results of experience in Ghardimaou, Tunisia. Bulletin de la Societe de Pathologie Exotique 1948;41(3/4):188‐94.
Schneider 1958 {published data only}
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Schneider 1962 {published data only}
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Seckinger 1935 {published data only}
    1. Seckinger DL. Atabrine and plasmochin in the treatment and control of Malaria. American Journal of Tropical Medicine 1935;15(6):631‐49.
Sehgal 1968 {published data only}
    1. Sehgal JK. Progress of malaria eradication in Orissa State during 1965‐66. Bulletin of the Indian Society for Malaria and Other Communicable Diseases 1968;5(1‐2):88‐93.
Sergent 1913 {published data only}
    1. Sergent Edm, Sergent Et. [Etudes epidemiologiques et prophylactiques du paludisme: neuvieme et dixieme campagnes en Algerie, en 1910 et 1911]. Annales De l'Institut Pasteur 1912;27(5):373‐90.
Sesay 2011 {published data only}
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Shanks 1995a {published data only}
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Snowden 2006 {published data only}
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Sokhna 2008 {published data only}
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Srivastava 1950 {published data only}
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Strangeways‐Dixon 1950 {published data only}
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Strickland 1986 {published data only}
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Tagbor 2011 {published data only}
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Van Goor 1950 {published data only}
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Wallace 1936 {published data only}
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Wallace 1954 {published data only}
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