1. Epidemiology and Global Health

Estimating effectiveness of case-area targeted response interventions against cholera in Haiti

  1. Edwige Michel
  2. Jean Gaudart
  3. Samuel Beaulieu
  4. Gregory Bulit
  5. Martine Piarroux
  6. Jacques Boncy
  7. Patrick Dely
  8. Renaud Piarroux  Is a corresponding author
  9. Stanislas Rebaudet  Is a corresponding author
  1. Ministry of Public Health and Population, Directorate of Epidemiology Laboratory and Research, Haiti
  2. Aix-Marseille Université, APHM, INSERM, IRD, SESSTIM, Hop Timone, BiSTIC, Biostatistics and ICT, France
  3. United Nations Children's Fund, Haiti
  4. Centre d'Épidémiologie et de Santé Publique des Armées, Service de Santé des Armées, France
  5. Ministry of Public Health and Population, National Laboratory of Public Health, Haiti
  6. Sorbonne Université, INSERM, Institut Pierre-Louis d’Epidémiologie et de Santé Publique (IPLESP), AP-HP, Hôpital Pitié-Salpêtrière, France
  7. APHM, Hôpital Européen, Aix Marseille Université, INSERM, IRD, SESSTIM, IPLESP, France
  8. Sorbonne Université, INSERM, Institut Pierre-Louis d’Epidémiologie et de Santé Publique, France
https://doi.org/10.7554/eLife.50243
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Cite this article
  1. Edwige Michel
  2. Jean Gaudart
  3. Samuel Beaulieu
  4. Gregory Bulit
  5. Martine Piarroux
  6. Jacques Boncy
  7. Patrick Dely
  8. Renaud Piarroux
  9. Stanislas Rebaudet
(2019)
Estimating effectiveness of case-area targeted response interventions against cholera in Haiti
eLife 8:e50243.
https://doi.org/10.7554/eLife.50243
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5 figures, 16 tables and 2 additional files

Figures

Figure 1 with 1 supplement
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Daily evolution of (A) suspected cholera cases, cases with severe dehydration and stool cultures positive for V. cholerae O1, (B) accumulated rainfall, (C) localities with a current cholera outbreak, and (D) case-area targeted interventions (CATIs), in the Centre department of Haiti between January 2015 and December 2017.
Figure 1—source data 1

Daily evolution of suspected cholera cases, cases with severe dehydration, stool cultures positive for V. cholerae O1, accumulated rainfall, localities with a current cholera outbreak, and case-area targeted interventions (CATIs), between January 2015 and December 2017 in.

https://cdn.elifesciences.org/articles/50243/elife-50243-fig1-data1-v2.xlsx
Figure 1—figure supplement 1
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Daily evolution of suspected cholera cases recorded and stool cultures positive for V. cholerae O1 sampled in the Centre department of Haiti between October 2010 and December 2017.
Figure 2
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Identification of outbreaks and stratification of outbreaks according to response promptness and response intensity.
Figure 2—source data 1

Line-listing of suspected cholera cases, lab results of stool cultures for Vibrio cholerae O1 and list of case-area targeted interventions against cholera in the Centre department of Haiti between January 2015 and December 2017.

https://cdn.elifesciences.org/articles/50243/elife-50243-fig2-data1-v2.xlsx
Figure 3
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Cholera outbreaks in the Centre department, Haiti, between January 2015 and December 2017: spatial distribution and number of identified outbreaks (size of pie charts); proportion of outbreaks that were and were not responded with at least one complete CATI (angle of green and red slices, respectively).
Figure 4
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Outbreak outcome according to the class of response promptness.

(A and B) and to the class of response intensity (C and D): (A and C) comparison of the outbreak size (number of suspected cholera cases from the fourth day of outbreak) and (B and D) Kaplan-Meier comparison of the outbreak duration (in days), according to the time to the first complete CATI (A and B), to the number of complete CATIs per week (C) and to the number of complete CATIs per case (D).

Figure 4—source data 1

Main characteristics of outbreak response and outcome: class of time to the first complete CATI; class of number of complete CATIs per week; class of number of complete CATIs per case; number of suspected cholera cases from the fourth day of outbreaks; duration of outbreaks.

https://cdn.elifesciences.org/articles/50243/elife-50243-fig4-data1-v2.xlsx
Appendix 2—figure 1
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Outbreak outcome of outbreaks that were and were not responded to: (A) comparison of the outbreak size (number of suspected cholera cases from the 4th day of outbreak) and (B) Kaplan-Meier comparison of the outbreak duration (in days).

Tables

Table 1
Baseline characteristics of outbreaks that were responded to, according to the response promptness (time to the first complete case-area targeted intervention).
All outbreaksOutbreaks responded to with ≥ 1 complete CATIClass of response promptness
(time to the first complete CATI)		Comparison between classes of promptness
>7 days3 to 7 days2 days≤1 dayHazard ratio
(95% CI)†		p-value†
No. of outbreaks452238
(53%)		48
(20%)		40
(17%)		43
(18%)		107
(45%)
Semester sinceJanuary 20151.10e7
(1.64e6 to 7.40e7)		<0.0001*
Population density, median (IQR; inhab./km2)3.5
(6.5)		3.6
(11.5)		4.3
(10.6)		2.8
(4.6)		3.7
(8.9)		3.8
(12.6)		1.01
(1 to 1.02)		0.0039*
Travel time to thenearest town, median (IQR;minutes)26.7
(33.2)		24.9
(31.8)		30 (3
4.3)		27.1
(42.1)		24.8
(28.4)		22
(32)		1
(0.99 to 1)		0.274
Accumulated incidence between 2010 and 2014, median (IQR; per 1000 inhabitants)103.8
(77.5)		103.8
(77.5)		103.8
(131.4)		103.8
(49.1)		103.8
(56.6)		103.8
(77.5)		0.4
(0.09 to 1.83)		0.237
Coverage of OCVcampaigns between 2012 and 2014, median (IQR;%) [mean, SD]0% (86)
[25%, 40]		0% (0)
[21%, 38]		0% (86)
[30%, 42]		0% (0)
[18%, 36]		0% (0)
[15%, 33]		0% (0)
[21%, 38]		0.61
(0.38 to 0.98)		0.0393*
Previous cases inthe same localityduring the study, median (IQR; no.per year)4.3
(10.1)		5.2
(10.5)		7.2
(10.1)		5
(11.5)		6.9
(11.1)		5
(8.5)		0.99
(0.97–1.02)		0.6540
Previous completeCATIs in the samelocality during thestudy, median(IQR; no. per year)0.2
(1.9)		0.9
(2.7)		0.7
(2.2)		0.5
(2.3)		1.2
(2.9)		1.4
(2.7)		0.98
(0.91–1.06)		0.6500
Daily rainfall during outbreak,median (IQR; mm)6.6
(13.3)		7.7
(13.3)		12
(6)		6.9
(10.8)		10
(13.7)		3.6
(14.4)		0.99
(0.96 to 1.03)		0.638
No. of cases duringthe first 3 daysofoutbreak, median (IQR) [mean, SD]2 (1)
[2.5, 1.5]		2 (1)
[2.7, 1.9]		2 (1)
[2.5, 1.0]		2.5 (1)
[3.4, 2.1]		2 (0.5)
[2.8, 2.4]		2 (1)
[2.5, 1.9]		1.04
(0.93 to 1.16)		0.488
No. of positiveculture during thefirst 3 daysof outbreak, median(IQR) [mean, SD]0 (0)
[0.2, 0.6]		0 (0)
[0.3, 0.7]		0 (0)
[0.1, 0.3]		0 (0)
[0.2, 0.5]		0 (1)
[0.5, 0.9]		0 (1)
[0.4, 0.7]		2.03
(1.3 to 3.17)		0.0018*

  1. CATI, case-area targeted intervention; IQR, interquartile range; SD, standard deviation.

    †Univariate comparisons between classes of response promptness using Cox models for Andersen-Gill counting process (AG-CP), with time to the first complete CATI modelled as a recurrent time-to-event outcome.

  2. *Significant p-value.

Table 2
Baseline characteristics of outbreaks that were responded to, according to the response intensity (number of complete case-area targeted interventions per week or per case).
No. of complete CATIs per weekComparison between classes of CATIs per week
<0.250.25 to 0.50.5 to 1≥1OR
(95% CI)†		p-value†
No. of outbreaks25
(11%)		43 (18%)120 (50%)50 (21%)
Semester since January 20151.14
(1.03 to 1.25)		0.0111*
Population density, median (IQR;inhab./km2)3.9
(11.8)		3.4
(3.8)		3.4
(12)		3.7
(11.8)		1
(1 to 1.01)		0.4093
Travel time to the nearest town, median (IQR; minutes)30
(26.8)		33.5
(41.9)		22.1
(28)		25.4
(34.2)		1
(1 to 1.01)		0.8379
Accumulated incidencebetween 2010 and 2014, median (IQR; per 1000 inhab)125.8
(250.9)		99.5
(97.8)		103.8
(49)		103.8
(79.6)		0.64
(0.37 to 1.1)		0.1037
Coverage of OCVcampaigns between2012 and 2014, median(IQR; %) [mean, SD]0% (86)
[43%, 44]		0% (0)
[11%, 29]		0% (0)
[19%, 36]		0% (86)
[25%, 40]		1.03
(0.74 to 1.44)		0.8464
Previous cases in thesame locality during thestudy, median (IQR; no.per year)10.1
(9.4)		6
(8.8)		4
(9)		5.9
(11.7)		1.01
(0.99–1.02)		0.5011
Previous complete CATIsin the same localityduring the study, median(IQR; no. per year)0.7
(2.1)		0.4
(2.5)		1
(2.7)		1.5
(3.2)		1.04
(1–1.08)		0.0763
Daily rainfall duringoutbreak, median (IQR;mm)12
(4)		8
(11.5)		6.6
(16.3)		6.2
(11.1)		0.99
(0.98 to 1.01)		0.331
No. of cases during thefirst 3 daysof outbreak,median (IQR) [mean, SD]2 (0)
[3.1, 2.7]		2 (1)
[2.7, 1.5]		2 (0)
[2.3, 1.4]		3 (2)
[3.4, 2.5]		0.81
(0.71 to 0.93)		0.3806
No. of positive cultureduring the first 3 daysofoutbreak, median (IQR) [mean, SD]0 (0)
[0.2, 0.6]		0 (0)
[0.2, 0.4]		0 (1)
[0.4, 0.8]		0 (0)
[0.2, 0.6]		1.03
(0.85 to 1.25)		0.7569
No. of complete CATIs per caseComparison between classes of CATIs per case
<0.250.25 to 0.50.5 to 1≥1OR
(95% CI)†		p-value†
No. of outbreaks47 (20%)56 (24%)81 (34%)54 (23%)
Semester since January20151.24
(1.13 to 1.37)		<0.0001*
Population density,median (IQR;inhab./km2)3
(5)		4.2
(14.7)		3.3
(3.6)		3.7
(12.9)		1
(1 to 1.01)		0.468
Travel time to thenearest town, median(IQR; minutes)31.2
(42.1)		17.3
(44.4)		25.5
(27.3)		18.9
(23.7)		1
(0.99 to 1)		0.344
Accumulated incidencebetween 2010 and 2014, median (IQR; per 1000 inhabitants)125.8
(77.5)		103.8
(93.5)		103.8
(64.6)		103.8
(43.3)		1.01
(0.42 to 2.43)		0.981
Coverage of OCVcampaigns between 2012 and 2014, median(IQR; %) [mean, SD]0% (86)
[30%, 42]		0% (0)
[13%, 31]		0% (0)
[21%, 38]		0% (0)
[22%, 38]		0.96
(0.6 to 1.54)		0.881
Previous cases in thesame locality during the study, median (IQR; no. per year)4.4
(9.9)		8.4
(16.3)		6.2
(7.9)		3.5
(6.4)		1
(0.98–1.02)		0.7730
Previous complete CATIsin the same locality during the study, median(IQR; no. per year)0
(1)		1.4
(4.3)		1.4
(2.7)		1
(2.6)		1.03
(0.97–1.08)		0.3550
Daily rainfall duringoutbreak, median (IQR;mm)12
(4.3)		6.1
(13.7)		5.3
(13.6)		6.1
(13.7)		1
(0.98 to 1.02)		0.983
No. of cases during thefirst 3 daysof outbreak,median (IQR) [mean, SD]3 (3)
[4.3, 3.2]		2 (1)
[2.6, 1.1]		2 (0)
[2.5, 1.3]		2 (1)
[1.8, 0.8]		0.81
(0.71 to 0.93)		0.0019*
No. of positive cultureduring the first 3 daysofoutbreak, median (IQR)[mean, SD]0 (0)
[0.2, 0.9]		0 (0)
[0.3, 0.5]		0 (0)
[0.2, 0.6]		0 (1)
[0.6, 0.7]		1.14
(0.92 to 1.42)		0.232

  1. CATI, case-area targeted intervention; IQR, interquartile range; SD, standard deviation; OR (95% CI), Odds ratio (95%-confidence interval).

    †Univariate comparisons using generalized linear mixed models with CATIs/weeks ratio or CATIs/cases ratio as model outcome and a negative-binomial distribution.

  2. *Significant p-value.

Table 3
CATI effectiveness (CE1) of the response promptness (time to the first complete CATI) on outbreak size (number of cases from the fourth day of outbreak).
No. of cases from the 4th day of outbreakCrude estimate of CATI effectiveness (cCE1)†Adjusted estimate of CATI effectiveness (aCE1)‡
NMedian
(IQR)		%
(95% CI)		p-value%
(95% CI)		p-value
Time to the first complete CATI
>7 days484.5
(9.25)		RefRefRefRef
3 to 7 days402.5
(9.25)		49%
(6 to 72)		0.0318*50%
(9 to 72)		0.0222*
2 days431
(3)		76%
(55 to 87)		<0.0001*68%
(40 to 83)		0.0004*
≤1 day1070
(2)		83%
(71 to 90)		<0.0001*76%
(59 to 86)		<0.0001*

  1. CATI, case-area targeted intervention; IQR, interquartile range.

    *Significant p-value.

  2. †Crude CATI effectiveness (cCE1) was estimated on the No. of cases from the fourth day of outbreak, using generalized linear mixed models with a negative-binomial distribution, as (1 – Incidence ratio).

    ‡Estimates of CATI effectiveness (aCE1) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Table 1): number of positive cultures during the first 3 days of outbreak, population density, accumulated case incidence between 2010 and 2014, coverage of OCV campaigns between 2012 and 2014 and semester.

Table 4
CATI effectiveness (CE2) of the response promptness (time to the first complete CATI) on outbreak duration (in days).
Duration of outbreakCrude estimate of CATI effectiveness (cCE2)†Adjusted estimate of CATI effectiveness (aCE2)‡
NMedian
(IQR; days)		%
(95% CI)		p-value%
(95% CI)		p-value
Time to the first complete CATI
>7 days4826
(39)		RefRefRefRef
3 to 7 days4013
(33)		45%
(17 to 64)		0.0046*53%
(29 to 69)		0.0004*
2 days439
(25)		37%
(−6 to 62)		0.081027%
(−22 to 56)		0.2322
≤1 day1073
(15.5)		59%
(36 to 74)		<0.0001*61%
(41 to 75)		<0.0001*

  1. CATI, case-area targeted intervention; IQR, interquartile range.

    *Significant p-value.

  2. †Crude CATI effectiveness (cCE2) was estimated on the duration of outbreak, using Cox models for Andersen-Gill counting process (AG-CP), as (1–1/hazard ratio).

    ‡Estimates of CATI effectiveness (aCE2) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Table 1): number of positive cultures during the first 3 days of outbreak, population density, accumulated case incidence between 2010 and 2014, coverage of OCV campaigns between 2012 and 2014 and semester.

Table 5
CATI effectiveness (CE3) of the response intensity (number of complete CATIs per week) on outbreak size (number of cases from the fourth day of outbreak).
No. of cases after the 4th day of outbreakCrude estimate of CATI effectiveness (cCE3)†Adjusted estimate of CATI effectiveness (aCE3)‡
NMedian
(IQR)		%
(95% CI)		p-value%
(95% CI)		p-value
No. of complete CATIs per week
<0.25259
(8)		RefRefRefRef
0.25 to 0.5433
(3)		55%
(1 to 79)		0.0457*45%
(−17 to 74)		0.1206
0.5–11200
(3)		79%
(59 to 89)		<0.0001*70%
(42 to 84)		0.0003*
≥1501
(2.75)		74%
(44 to 88)		0.0006*59%
(11 to 81)		0.0235*

  1. CATI, case-area targeted intervention; IQR, interquartile range.

    *Significant p-value.

  2. †Crude CATI effectiveness (cCE3) was estimated on the No. of cases from the fourth day of outbreak, using generalized linear mixed models with a negative-binomial distribution, as (1 – Incidence ratio).

    ‡Estimates of CATI effectiveness (aCE3) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Table 2): accumulated case incidence between 2010 and 2014, and semester.

Table 6
CATI effectiveness (CE4) of the response intensity (number of complete CATIs per case) on outbreak duration (in days).
Duration of outbreakCrude estimate of CATI effectiveness (cCE4)†Adjusted estimate of CATI effectiveness (aCE4)‡
NMedian
(IQR; days)		%
(95% CI)		p-value%
(95% CI)		p-value
No. of complete CATIs per case
<0.254725
(32)		RefRefRefRef
0.25 to 0.55619.5
(30.75)		8%
(−35 to 37)		0.67381%
(−45 to 32)		0.9759
0.5 to 1813
(16)		59%
(35 to 75)		0.0002*57%
(30 to 74)		0.0007*
≥1542
(5.75)		76%
(54 to 88)		<0.0001*73%
(49 to 86)		<0.0001*

  1. CATI, case-area targeted intervention; IQR, interquartile range.

    *Significant p-value.

  2. †Crude CATI effectiveness (cCE4) was estimated on the duration of outbreak, using Cox models for Andersen-Gill counting process (AG-CP), as (1–1/hazard ratio).

    ‡Estimates of CATI effectiveness (aCE4) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Table 2): number of cases and number of positive cultures during the first 3 days of outbreak, yearly number of previous complete CATIs during the study, and semesters.

Table 7
Effectiveness of complete CATIs stratified by antibiotic prophylaxis.
Outbreak subgroupAll outbreaks responded to by any complete CATIs
(Tables 3–6)		Outbreaks only responded to by complete CATIs with ATBOutbreaks only responded to by complete CATIs without ATB
No. of outbreaks that were responded to (%)238 (53%)115 (25%)78 (17%)
%
(95% CI)		p-value%
(95% CI)		p-value%
(95% CI)		p-value
CATI effectiveness according to the response promptness
≤1 day vs > 7 days adjusted estimate of CATI effectiveness on accumulated cases (aCE1)†76%
(59 to 86)		<0.0001*63%
(24 to 82)		0.007*39%
(−38 to 73)		0.2369
≤1 day vs > 7 days adjusted estimate of CATI effectiveness on outbreak duration (aCE2)‡61%
(41 to 75)		<0.0001*74%
(43 to 88)		0.0009*58%
(11 to 80)		0.0237*
CATI effectiveness according to the response intensity
≥1 vs<0.25 completeCATIsper week adjusted estimateof CATI effectivenessonaccumulated cases (aCE3)$59%
(11 to 81)		0.0235*62%
(3 to 85)		0.04276%
(12 to 94)		0.0312
≥1 vs<0.25 completeCATIs per case adjusted estimateof CATI effectivenessonoutbreak duration (aCE4)£73%
(49 to 86)		<0.0001*90%
(72 to 96)		<0.0001*79%
(46 to 92)		0.0012*

  1. CATI, case-area targeted intervention.

    ATB, antibiotic prophylaxis.

  2. †Estimates of CATI effectiveness (aCE1) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Table 1): number of positive cultures during the first 3 days of outbreak, population density, accumulated case incidence between 2010 and 2014, coverage of OCV campaigns between 2012 and 2014 and semester.

    ‡Estimates of CATI effectiveness (aCE2) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Table 1): number of positive cultures during the first 3 days of outbreak, population density, accumulated case incidence between 2010 and 2014, coverage of OCV campaigns between 2012 and 2014 and semester.

  3. $Estimates of CATI effectiveness (aCE3) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Table 2): accumulated case incidence between 2010 and 2014, and semester.

    £Estimates of CATI effectiveness (aCE4) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Table 2): number of cases and number of positive cultures during the first 3 days of outbreak, yearly number of previous complete CATIs during the study, and semesters.

  4. *significant after Bonferroni correction.

Appendix 1—table 1
Baseline characteristics of suspected cholera cases, cholera stool cultures and case-area targeted interventions (CATIs) from January 1, 2015, to December 31, 2017.
Suspected cholera cases
Total no. of cases10931
Median age (IQR)18 (35)
Sex ratio (M/F)1.0
No. of cases with a comprehensive location (%)10428 (95%)
No. of different localities1497
No. of cases with IV rehydration (%)2301 (21%)
No. of cases with a comprehensive location and IV rehydration (%)2144 (20%)
Stool cultures
Total no. of stool samples cultured1070
No. of stool cultures positive for V. cholerae O1 (%)509 (48%)
No. of positive cultures with a comprehensive location (%)360 (34%)
No. of different localities176
Case-area targeted interventions (CATIs)
Total no. of CATIs3887
No. of CATIs conducted with EMIRA staff (%)2719 (70%)
No. of CATIs with a comprehensive location (%)3533 (91%)
No. of different localities815
No. of CATIs with reported house decontamination (%)3655 (94%)
No. of decontaminated houses per CATI, median (IQR)4 (5)
No. of CATIs with reported education (%)3815 (98%)
No. of educated people per CATI, median (IQR)30 (47)
No. of CATIs with reported chlorine distribution (%)3748 (96%)
No. of household receiving chlorine per CATI, median (IQR)7 (8)
No. of CATIs with reported antibiotic prophylaxis (%)2002 (52%)
No. of people receiving antibiotic prophylaxis per CATI, median (IQR)20 (19)
No. of complete CATIs (%)3596 (93%)
No. of complete CATIs with antibiotic prophylaxis (%)1922 (49%)

  1. EMIRA, cholera rapid response team of the Ministry of health; IQR, interquartile range.

    *Complete CATI, at least decontamination, education and distribution of chlorine tablets.

Appendix 2—table 1
Baseline characteristics of outbreaks that were and were not responded to.
All outbreaksOutbreaks with no complete CATIOutbreaks with ≥ 1 complete CATIOdds radio†
(95% CI)		p-value†
No. of outbreaks452214
(47%)		238
(53%)
Semester since January 20152.03
(1.63 to 2.51)		<0.0001*
Population density,median (IQR; inhab./km2)3.5
(6.5)		3.4
(4.8)		3.6
(11.5)		1.01
(1 to 1.02)		0.0308*
Travel time to thenearest town, median(IQR; minutes)26.7
(33.2)		30.2
(31.9)		24.9
(31.8)		0.99
(0.98 to 1)		0.0143*
Accumulated incidencebetween 2010 and 2014,median (IQR; per 1000inhabitants)103.8
(77.5)		103.8
(293.4)		103.8
(77.5)		0.43
(0.08 to 2.33)		0.327
Coverage of OCVcampaigns between 2012 and 2014, median(IQR; %) [mean, SD]0% (86)
[25%, 40]		0% (86)
[30%, 42]		0% (0)
[21%, 38]		0.52
(0.3 to 0.87)		0.0137*
Previous cases in thesame locality during the study, median (IQR; no.per year)4.3
(10.1)		4
(9)		5.2
(10.5)		1.01
(0.99–1.04)		0.2320
Previous complete CATIs in the same localityduring the study, median(IQR; no. per year)0.2
(1.9)		0
(0.8)		0.9
(2.7)		1.23
(1.11–1.36)		<0.0001*
Daily rainfall duringoutbreak, median (IQR;mm)6.6
(13.3)		5.2
(12.5)		7.7
(13.3)		1.01
(0.99 to 1.03)		0.359
No. of cases during thefirst 3 daysof outbreak, median (IQR) [mean, SD]2 (1)
[2.5, 1.5]		2 (0)
[2.3, 0.9]		2 (1)
[2.7, 1.9]		1.22
(1.04 to 1.43)		0.0156*
No. of positive cultureduring the first 3 daysofoutbreak, median (IQR) [mean, SD]0 (0)
[0.2, 0.6]		0 (0)
[0.2, 0.5]		0 (0)
[0.3, 0.7]		1.64
(1.12 to 2.39)		0.0101*

  1. CATI, case-area targeted intervention; SD, standard deviation.

    †Univariate comparisons using univariate logistic mixed models with response as model outcome and a binomial distribution, and outbreaks with no complete CATI as the reference class.

  2. *Significant p-value.

Appendix 2—table 2
Protective effectiveness of response: comparison of the number of suspected cholera cases from the 4th day of outbreak between outbreaks that were and were not responded to (CE5).
No. of cases from the 4th day of outbreakCrude estimate of CATI effectiveness (cCE5)†Adjusted estimate of CATI effectiveness (aCE5)‡
NMedian (IQR)% (95% CI)p-value% (95% CI)p-value
No. of CATIs during outbreak
No CATI*2140
(2)		RefRefRefRef
≥1 CATIs2381
(5)		−228%
(−353 to −138)		<0.0001−411%
(−638 to −254)		<0.0001

  1. CATI, case-area targeted intervention; IQR, interquartile range.

    *Reference class.

  2. †Crude CATI effectiveness (cCE3) was estimated on the No. of cases from the 4th day of outbreak, using logistic mixed models, as (1 – Odds ratio).

    ‡Estimates of CATI effectiveness (aCE3) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Appendix 2—table 1): number of cases and number of positive cultures during the first 3 days of outbreak, population density, travel time to the nearest town, coverage of OCV campaigns between 2012 and 2014 OCV campaigns, and semesters.

Appendix 2—table 3
Protective effectiveness of response: comparison of the duration of outbreaks between outbreaks that were and were not responded to (CE6).
Duration of outbreakCrude estimate of response effectiveness (cCE6)†Adjusted estimate of response effectiveness (aCE6)‡
NMedian (IQR; days)% (95% CI)p-value% (95% CI)p-value
No. of CATIs during outbreak
No CATI*2143
(8)		RefRefRefRef
≥1 CATIs23811
(26.75)		−319%
(−457 to −216)		<0.0001−300%
(−441 to −196)		<0.0001

  1. CATI, case-area targeted intervention; IQR, interquartile range.

    *Reference class.

  2. †Crude response effectiveness (CCE4) was estimated on the duration of outbreak, using Cox models for repeated events with Anderson-Gills correction (AGCP), as (1–1/hazard ratio).

    ‡Estimates of CATI effectiveness (aCE4) were adjusted according to covariates for which p-values were less than 0.25 at the initial univariate step (Appendix 2—table 1): number of cases and number of positive cultures during the first 3 days of outbreak, population density, travel time to the nearest town, coverage of OCV campaigns between 2012 and 2014 OCV campaigns, and semesters.

Appendix 3—table 1
Alternative outbreak definitions.
Cholera outbreakDefinitionRemarkNo. of outbreaks
Outbreak A• suspected cholera cases ≥ 2
• (severely dehydrated case + positive culture)≥1
• onset time window = 3 days
• refractory period = 21 days		Scenario 1
Main manuscript
Appendix 2
Appendix 3.2
Appendix 3.3		452
Outbreak Cu0• suspected cholera cases ≥ 2
• irrespective of severely dehydrated cases and positive cultures
• onset time window = 3 days
• refractory period = 21 days		Scenario 22043
Outbreak Cu1• suspected cholera cases ≥ 2
• positive culture ≥ 1
• irrespective of severely dehydrated cases
• onset time window = 3 days
• refractory period = 21 days		Scenario 364
Outbreak Ca1• suspected cholera cases ≥ 1
• (severely dehydrated case + positive culture)≥1
• onset time window = 3 days
• refractory period = 21 days		Scenario 41514
Outbreak T1• same as Outbreak A except:
• onset time window = 1 day		Scenario 5267
Outbreak T2• same as Outbreak A except:
• onset time window = 2 days		Scenario 6394
Outbreak T4• same as Outbreak A except:
• onset time window = 4 days		Scenario 7494
Outbreak T5• same as Outbreak A except:
• onset time window = 5 days		Scenario 8535
Outbreak R7• same as Outbreak A except:
• refractory period = 7 days		Scenario 9519
Outbreak R14• same as Outbreak A except:
• refractory period = 14 days		Scenario 10486
Appendix 3—table 2
Sensitivity analysis on outbreak and CATI definitions.
Scenario12345678910
Outbreak definition*Outbreak AOutbreak Cu0Outbreak Cu1Outbreak Ca1Outbreak T1Outbreak T2Outbreak T4Outbreak T5Outbreak R7Outbreak R14
Response definition†CATIc7CATIc7CATIc7CATIc7CATIc7CATIc7CATIc7CATIc7CATIc7CATIc7
No. of outbreaks4522043641514267394494535519486
No. of CATIs3596359635963596359635963596359635963596
No. of CATIs during outbreaks (%)633
(18%)		1445
(40%)		153
(4%)		1000
(28%)		386
(11%)		540
(15%)		670
(19%)		717
(20%)		497
(14%)		576
(16%)
No. of outbreaks that were responded to (%)238
(53%)		730
(36%)		45
(70%)		500
(33%)		152
(57%)		211
(54%)		256
(52%)		276
(52%)		242
(47%)		240
(49%)
Comparison between outbreaks that were and were not responded to
No. of cases during the first 3 days of outbreak, Odds ratio (95% CI)1.22
(1.04 to 1.43)		1.61
(1.43 to 1.8)		24.69
(1.4 to 435.42)		1.69
(1.47 to 1.96)		1.1
(0.85 to 1.43)		1.15
(0.96 to 1.37)		1.19
(1.04 to 1.36)		1.19
(1.05 to 1.34)		1,25
(1,07 to 1,45)		1,24
(1,06 to 1,45)
No. of positive culture during the first 3 days of outbreak, Odds ratio (95% CI)1.64
(1.12 to 2.39)		2.29
(1.63 to 3.21)		1.82
(0.64 to 5.21)		2.16
(1.61 to 2.9)		1.35
(0.77 to 2.36)		1.6
(1.06 to 2.41)		1.85
(1.26 to 2.72)		1.85
(1.29 to 2.65)		2,08
(1,42 to 3,06)		1,91
(1,3 to 2,8)
CATI effectiveness according to the response promptness
≤1 day vs >7 days crude estimate of CATI effectiveness on accumulated cases (95% CI) (cCE1)83%
(71 to 90)		85%
(79 to 89)		40%
(−86 to 81)		89%
(83 to 92)		73%
(48 to 87)		79%
(63 to 88)		86%
(86 to 87)		84%
(70 to 91)		89%
(69 to 96)		86%
(72 to 93)
≤1 day vs >7 days crude estimate of CATI effectiveness on outbreak duration (95% CI) (cCE2)59%
(36 to 74)		74%
(66 to 80)		22%
(−81 to 66)		78%
(69 to 84)		48%
(18 to 67)		54%
(29 to 70)		61%
(40 to 75)		58%
(34 to 73)		65%
(39 to 80)		62%
(43 to 75)
CATI effectiveness according to the response intensity
≥1 vs <0.25 CATIs per week crude estimate of CATI effectiveness on accumulated cases (95% CI) (cCE3)74%
(44 to 88)		77%
(62 to 85)		74%
(−122 to 97)		69%
(43 to 84)		28%
(−85 to 72)		69%
(33 to 86)		82%
(60 to 92)		83%
(61 to 92)		87%
(86 to 87)		66%
(−10 to 89)
≥1 vs <0.25 CATIs per case crude estimate of CATI effectiveness on outbreak duration (95% CI) (cCE4)76%
(54 to 88)		89%
(85 to 92)		55%
(−155 to 92)		91%
(86 to 94)		89%
(79 to 95)		81%
(66 to 89)		76%
(55 to 87)		75%
(54 to 86)		78%
(59 to 88)		81%
(68 to 88)

  1. *see Appendix 3—table 1.

    †see Appendix 3—table 2.

Appendix 3—table 3
Alternative response definitions.
Cholera outbreakDefinitionRemarkNo. of CATIsNo. of CATIs during outbreaks (%)
CATIc7• Complete CATI (mobile teams reported at least education, house decontamination by spraying and distribution of chlorine tablets)
• Implemented within 7 days after the last recorded case of the outbreak		Scenario 1
Main manuscript
Appendix 2
Appendix 3.1
Appendix 3.3		3596633 (18%)
CATIc0• Complete CATI
• implemented before the last recorded case of the outbreak		Scenario 113596501 (14%)
CATI7• All CATI (irrespective of activities reported by mobile teams
• Implemented within 7 days after the last recorded case of the outbreak		Scenario 123887681 (18%)
CATIcEMIRA7• Complete CATI
• Conducted by NGO mobile teams in tandem with EMIRA staff
• Implemented within 7 days after the last recorded case of the outbreak		Scenario 132539458 (18%)
CATIcATB7• Complete CATI and reported antibiotic prophylaxis
• Implemented within 7 days after the last recorded case of the outbreak		Scenario 14
Main manuscript		1922350 (18%)

  1. EMIRA, cholera rapid response team of the Ministry of health.

Appendix 3—table 4
Sensitivity analysis on outbreak and CATI definitions.
Scenario111121314
Outbreak definition*Outbreak AOutbreak AOutbreak AOutbreak AOutbreak A
Response definition†CATIc7CATIc0CATI7CATIcEMIRA7CATIcATB7
No. of outbreaks452452452452452
No. of CATIs35963596388725391922
No. of CATIs during outbreaks (%)633
(18%)		501
(14%)		681
(18%)		458
(18%)		350
(18%)
No. of outbreaks that were responded to (%)238
(53%)		172
(38%)		244
(54%)		201
(44%)		160
(35%)
Comparison between outbreaks that were and were not responded to
No. of cases during the first 3 days of outbreak, Odds ratio (95% CI)1.22
(1.04 to 1.43)		1.49
(1.24 to 1.80)		1.22
(1.04 to 1.43)		1.21
(1.04 to 1.40)		1.09
(0.97 to 1.24)
No. of positive culture during the first 3 days of outbreak, Odds ratio (95% CI)1.64
(1.12 to 2.39)		1.63
(1.14 to 2.32)		1.62
(1.11 to 2.37)		2.12
(1.44 to 3.11)		1.92
(1.35 to 2.73)
CATI effectiveness according to the response promptness
≤1 day vs >7 days crude estimate of CATI effectiveness on accumulated cases (95% CI) (cCE1)83%
(71 to 90)		85%
(76 to 91)		83%
(71 to 90)		89%
(81 to 94)		90%
(81 to 94)
≤1 day vs >7 days crude estimate of CATI effectiveness on outbreak duration (95% CI) (cCE2)59%
(36 to 74)		65%
(44 to 78)		57%
(33 to 72)		76%
(61 to 85)		84%
(74 to 90)
CATI effectiveness according to the response intensity
≥1 vs <0.25 CATIs per week crude estimate of CATI effectiveness on accumulated cases (95% CI) (cCE3)74%
(44 to 88)		81%
(64 to 90)		70%
(35 to 86)		77%
(49 to 90)		85%
(64 to 94)
≥1 vs <0.25 CATIs per case crude estimate of CATI effectiveness on outbreak duration (95% CI) (cCE4)76%
(54 to 88)		54%
(−14 to 82)		75%
(53 to 86)		86%
(72 to 93)		86%
(71 to 93)

  1. *see Appendix 3—table 1.

    †see Appendix 3—table 3.

Appendix 3—table 5
Alternative adjustment methods for CATI effectiveness estimates.
Crude estimatesEstimates adjusted for covariates selected by p-values†Estimates adjusted for all covariatesEstimates adjusted for covariates selected by AIC*
No. of covariates
(AIC*)		cCE*No. of covariates
(AIC*)		aCE*No. of covariates
(AIC*)		aCE*No. of covariates
(AIC*)		aCE*
CATI effectiveness according to the response promptness
≤1 day vs >7 days estimate of CATI effectiveness on accumulated cases (95% CI) (CE1)0
(1102.35)		83%
(71 to 90)		5
(1 096.91)		76%
(59 to 86)		8
(1073.75)		77%
(62 to 87)		6
(1072.51)		79%
(65 to 88)
≤1 day vs >7 days crude estimate of CATI effectiveness on outbreak duration (95% CI) (CE2)0
(956.25)		59%
(36 to 74)		5
(933.42)		61%
(41 to 75)		8
(929.93)		65%
(46 to 77)		5
(924.20)		65%
(46 to 77)
CATI effectiveness according to the response intensity
≥1 vs <0.25 CATIs per week estimate of CATI effectiveness on accumulated cases (95% CI) (CE3)0
(1123.91)		74%
(44 to 88)		2
(1112.44)		58%
(8 to 81)		8
(1093.38)		62%
(18 to 82)		7
(1092.17)		62%
(22 to 81)
≥1 vs <0.25 CATIs per case estimate of CATI effectiveness on outbreak duration (95% CI) (CE4)0
(945.29)		76%
(54 to 88)		3
(949.59)		73%
(49 to 86)		8
(931.29)		76%
(56 to 87)		3
(925.52)		54%
(27 to 71)

  1. *AIC, Akaike information criterion; CATI, case-area targeted intervention; cCE, crude CATI effectiveness estimates; aCE, adjusted CATI effectiveness estimates.

    †Covariates for which p-values were less than 0.25 at the initial univariate step (Tables 1 and 2).

Additional files

Source code 1

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https://cdn.elifesciences.org/articles/50243/elife-50243-code1-v2.r
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  1. Edwige Michel
  2. Jean Gaudart
  3. Samuel Beaulieu
  4. Gregory Bulit
  5. Martine Piarroux
  6. Jacques Boncy
  7. Patrick Dely
  8. Renaud Piarroux
  9. Stanislas Rebaudet
(2019)
Estimating effectiveness of case-area targeted response interventions against cholera in Haiti
eLife 8:e50243.
https://doi.org/10.7554/eLife.50243