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Published in: Malaria Journal 1/2013

Open Access 01-12-2013 | Research

Analysis of partial and complete protection in malaria cohort studies

Authors: Matthew E Cairns, Kwaku Poku Asante, Seth Owusu-Agyei, Daniel Chandramohan, Brian M Greenwood, Paul J Milligan

Published in: Malaria Journal | Issue 1/2013

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Abstract

Background

Malaria transmission is highly heterogeneous and analysis of incidence data must account for this for correct statistical inference. Less widely appreciated is the occurrence of a large number of zero counts (children without a malaria episode) in malaria cohort studies. Zero-inflated regression methods provide one means of addressing this issue, and also allow risk factors providing complete and partial protection to be disentangled.

Methods

Poisson, negative binomial (NB), zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB) regression models were fitted to data from two cohort studies of malaria in children in Ghana. Multivariate models were used to understand risk factors for elevated incidence of malaria and for remaining malaria-free, and to estimate the fraction of the population not at risk of malaria.

Results

ZINB models, which account for both heterogeneity in individual risk and an unexposed sub-group within the population, provided the best fit to data in both cohorts. These approaches gave additional insight into the mechanism of factors influencing the incidence of malaria compared to simpler approaches, such as NB regression. For example, compared to urban areas, rural residence was found to both increase the incidence rate of malaria among exposed children, and increase the probability of being exposed. In Navrongo, 34% of urban residents were estimated to be at no risk, compared to 3% of rural residents. In Kintampo, 47% of urban residents and 13% of rural residents were estimated to be at no risk.

Conclusion

These results illustrate the utility of zero-inflated regression methods for analysis of malaria cohort data that include a large number of zero counts. Specifically, these results suggest that interventions that reach mainly urban residents will have limited overall impact, since some urban residents are essentially at no risk, even in areas of high endemicity, such as in Ghana.
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Literature
1.
go back to reference Woolhouse ME, Dye C, Etard JF, Smith T, Charlwood JD, Garnett GP, Hagan P, Hii JL, Ndhlovu PD, Quinnell RJ, Watts CH, Chandiwana SK, Anderson RM: Heterogeneities in the transmission of infectious agents: implications for the design of control programs. Proc Natl Acad Sci USA. 1997, 94: 338-342.PubMedCentralCrossRefPubMed Woolhouse ME, Dye C, Etard JF, Smith T, Charlwood JD, Garnett GP, Hagan P, Hii JL, Ndhlovu PD, Quinnell RJ, Watts CH, Chandiwana SK, Anderson RM: Heterogeneities in the transmission of infectious agents: implications for the design of control programs. Proc Natl Acad Sci USA. 1997, 94: 338-342.PubMedCentralCrossRefPubMed
2.
go back to reference Bousema T, Drakeley C, Gesase S, Hashim R, Magesa S, Mosha F, Otieno S, Carneiro I, Cox J, Msuya E, Kleinschmidt I, Maxwell C, Greenwood B, Riley E, Sauerwein R, Chandramohan D, Gosling R: Identification of hot spots of malaria transmission for targeted malaria control. J Infect Dis. 2010, 201: 1764-1774.CrossRefPubMed Bousema T, Drakeley C, Gesase S, Hashim R, Magesa S, Mosha F, Otieno S, Carneiro I, Cox J, Msuya E, Kleinschmidt I, Maxwell C, Greenwood B, Riley E, Sauerwein R, Chandramohan D, Gosling R: Identification of hot spots of malaria transmission for targeted malaria control. J Infect Dis. 2010, 201: 1764-1774.CrossRefPubMed
3.
go back to reference Mwangi TW, Fegan G, Williams TN, Kinyanjui SM, Snow RW, Marsh K: Evidence for over-dispersion in the distribution of clinical malaria episodes in children. PLoS ONE. 2008, 3: e2196-PubMedCentralCrossRefPubMed Mwangi TW, Fegan G, Williams TN, Kinyanjui SM, Snow RW, Marsh K: Evidence for over-dispersion in the distribution of clinical malaria episodes in children. PLoS ONE. 2008, 3: e2196-PubMedCentralCrossRefPubMed
4.
go back to reference White MT, Griffin JT, Drakeley CJ, Ghani AC: Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials. Malar J. 2010, 9: 82-PubMedCentralCrossRefPubMed White MT, Griffin JT, Drakeley CJ, Ghani AC: Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials. Malar J. 2010, 9: 82-PubMedCentralCrossRefPubMed
5.
go back to reference Hilbe JM: Negative Binomial Regression. 2012, Cambridge: Cambridge University Press, 2 Hilbe JM: Negative Binomial Regression. 2012, Cambridge: Cambridge University Press, 2
6.
go back to reference Hu MC, Pavlicova M, Nunes EV: Zero-inflated and hurdle models of count data with extra zeros: examples from an HIV-risk reduction intervention trial. Am J Drug Alcohol Abuse. 2011, 37: 367-375.PubMedCentralCrossRefPubMed Hu MC, Pavlicova M, Nunes EV: Zero-inflated and hurdle models of count data with extra zeros: examples from an HIV-risk reduction intervention trial. Am J Drug Alcohol Abuse. 2011, 37: 367-375.PubMedCentralCrossRefPubMed
7.
go back to reference Lewis MA, Kaysen DL, Rees M, Woods BA: The relationship between condom-related protective behavioral strategies and condom use among college students: global- and event-level evaluations. J Sex Res. 2010, 47: 471-478.PubMedCentralCrossRefPubMed Lewis MA, Kaysen DL, Rees M, Woods BA: The relationship between condom-related protective behavioral strategies and condom use among college students: global- and event-level evaluations. J Sex Res. 2010, 47: 471-478.PubMedCentralCrossRefPubMed
8.
go back to reference Carrel M, Voss P, Streatfield PK, Yunus M, Emch M: Protection from annual flooding is correlated with increased cholera prevalence in Bangladesh: a zero-inflated regression analysis. Environ Health. 2010, 9: 13-PubMedCentralCrossRefPubMed Carrel M, Voss P, Streatfield PK, Yunus M, Emch M: Protection from annual flooding is correlated with increased cholera prevalence in Bangladesh: a zero-inflated regression analysis. Environ Health. 2010, 9: 13-PubMedCentralCrossRefPubMed
9.
go back to reference Amek N, Bayoh N, Hamel M, Lindblade KA, Gimnig J, Laserson KF, Slutsker L, Smith T, Vounatsou P: Spatio-temporal modeling of sparse geostatistical malaria sporozoite rate data using a zero inflated binomial model. Spat Spatiotemporal Epidemiol. 2011, 2: 283-290.CrossRefPubMed Amek N, Bayoh N, Hamel M, Lindblade KA, Gimnig J, Laserson KF, Slutsker L, Smith T, Vounatsou P: Spatio-temporal modeling of sparse geostatistical malaria sporozoite rate data using a zero inflated binomial model. Spat Spatiotemporal Epidemiol. 2011, 2: 283-290.CrossRefPubMed
10.
go back to reference Amek N, Bayoh N, Hamel M, Lindblade KA, Gimnig JE, Odhiambo F, Laserson KF, Slutsker L, Smith T, Vounatsou P: Spatial and temporal dynamics of malaria transmission in rural Western Kenya. Parasit Vectors. 2012, 5: 86-PubMedCentralCrossRefPubMed Amek N, Bayoh N, Hamel M, Lindblade KA, Gimnig JE, Odhiambo F, Laserson KF, Slutsker L, Smith T, Vounatsou P: Spatial and temporal dynamics of malaria transmission in rural Western Kenya. Parasit Vectors. 2012, 5: 86-PubMedCentralCrossRefPubMed
11.
go back to reference Giardina F, Gosoniu L, Konate L, Diouf MB, Perry R, Gaye O, Faye O, Vounatsou P: Estimating the burden of malaria in Senegal: Bayesian zero-inflated binomial geostatistical modeling of the MIS 2008 data. PLoS ONE. 2012, 7: e32625-PubMedCentralCrossRefPubMed Giardina F, Gosoniu L, Konate L, Diouf MB, Perry R, Gaye O, Faye O, Vounatsou P: Estimating the burden of malaria in Senegal: Bayesian zero-inflated binomial geostatistical modeling of the MIS 2008 data. PLoS ONE. 2012, 7: e32625-PubMedCentralCrossRefPubMed
12.
go back to reference Bui HM, Clements AC, Nguyen QT, Nguyen MH, Le XH, Hay SI, Tran TH, Wertheim HF, Snow RW, Horby P: Social and environmental determinants of malaria in space and time in Viet Nam. Int J Parasitol. 2011, 41: 109-116.CrossRefPubMed Bui HM, Clements AC, Nguyen QT, Nguyen MH, Le XH, Hay SI, Tran TH, Wertheim HF, Snow RW, Horby P: Social and environmental determinants of malaria in space and time in Viet Nam. Int J Parasitol. 2011, 41: 109-116.CrossRefPubMed
13.
go back to reference Schmidt A, Hoeting J, Batista Pereira J, Paulo Vieira P: Mapping malaria in the Amazon rain forest: a spatio-temporal mixture model. The Oxford Handbook of Applied Bayesian Statistics. Edited by: O'Hagan A, West M. 2010, Oxford: Oxford University Press, 90-117. Schmidt A, Hoeting J, Batista Pereira J, Paulo Vieira P: Mapping malaria in the Amazon rain forest: a spatio-temporal mixture model. The Oxford Handbook of Applied Bayesian Statistics. Edited by: O'Hagan A, West M. 2010, Oxford: Oxford University Press, 90-117.
14.
go back to reference Bejon P, Warimwe G, Mackintosh CL, Mackinnon MJ, Kinyanjui SM, Musyoki JN, Bull PC, Marsh K: Analysis of immunity to febrile malaria in children that distinguishes immunity from lack of exposure. Infect Immun. 2009, 77: 1917-1923.PubMedCentralCrossRefPubMed Bejon P, Warimwe G, Mackintosh CL, Mackinnon MJ, Kinyanjui SM, Musyoki JN, Bull PC, Marsh K: Analysis of immunity to febrile malaria in children that distinguishes immunity from lack of exposure. Infect Immun. 2009, 77: 1917-1923.PubMedCentralCrossRefPubMed
15.
go back to reference Smith PG, Rodrigues LC, Fine PE: Assessment of the protective efficacy of vaccines against common diseases using case–control and cohort studies. Int J Epidemiol. 1984, 13: 87-93.CrossRefPubMed Smith PG, Rodrigues LC, Fine PE: Assessment of the protective efficacy of vaccines against common diseases using case–control and cohort studies. Int J Epidemiol. 1984, 13: 87-93.CrossRefPubMed
16.
go back to reference Halloran ME, Longini IM, Struchiner CJ: Estimability and interpretation of vaccine efficacy using frailty mixing models. Am J Epidemiol. 1996, 144: 83-97.CrossRefPubMed Halloran ME, Longini IM, Struchiner CJ: Estimability and interpretation of vaccine efficacy using frailty mixing models. Am J Epidemiol. 1996, 144: 83-97.CrossRefPubMed
17.
go back to reference Moorthy V, Reed Z, Smith PG: Measurement of malaria vaccine efficacy in phase III trials: report of a WHO consultation. Vaccine. 2007, 25: 5115-5123.CrossRefPubMed Moorthy V, Reed Z, Smith PG: Measurement of malaria vaccine efficacy in phase III trials: report of a WHO consultation. Vaccine. 2007, 25: 5115-5123.CrossRefPubMed
18.
go back to reference Chandramohan D, Owusu-Agyei S, Carneiro I, Awine T, Amponsa-Achiano K, Mensah N, Jaffar S, Baiden R, Hodgson A, Binka F, Greenwood B: Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana. BMJ. 2005, 331: 727-733.PubMedCentralCrossRefPubMed Chandramohan D, Owusu-Agyei S, Carneiro I, Awine T, Amponsa-Achiano K, Mensah N, Jaffar S, Baiden R, Hodgson A, Binka F, Greenwood B: Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana. BMJ. 2005, 331: 727-733.PubMedCentralCrossRefPubMed
19.
go back to reference Appawu M, Owusu-Agyei S, Dadzie S, Asoala V, Anto F, Koram K, Rogers W, Nkrumah F, Hoffman SL, Fryauff DJ: Malaria transmission dynamics at a site in northern Ghana proposed for testing malaria vaccines. Trop Med Int Health. 2004, 9: 164-170.CrossRefPubMed Appawu M, Owusu-Agyei S, Dadzie S, Asoala V, Anto F, Koram K, Rogers W, Nkrumah F, Hoffman SL, Fryauff DJ: Malaria transmission dynamics at a site in northern Ghana proposed for testing malaria vaccines. Trop Med Int Health. 2004, 9: 164-170.CrossRefPubMed
20.
go back to reference Asante KP, Owusu-Agyei S, Cairns ME, Dodoo D, Boamah E, Gyasi R, Adjei G, Gyan B, Agyeman-Budu A, Dodoo T, Mahama E, Amoako N, Dosoo DK, Koram K, Greenwood B, Chandramohan D: Placental malaria and the risk of malaria in infants in a high malaria transmission area in Ghana: a prospective cohort study. J Infectious Dis. 2013, Epub ahead of print Asante KP, Owusu-Agyei S, Cairns ME, Dodoo D, Boamah E, Gyasi R, Adjei G, Gyan B, Agyeman-Budu A, Dodoo T, Mahama E, Amoako N, Dosoo DK, Koram K, Greenwood B, Chandramohan D: Placental malaria and the risk of malaria in infants in a high malaria transmission area in Ghana: a prospective cohort study. J Infectious Dis. 2013, Epub ahead of print
21.
go back to reference Owusu-Agyei S, Asante KP, Adjuik M, Adjei G, Awini E, Adams M, Newton S, Dosoo D, Dery D, Agyeman-Budu A, Gyapong J, Greenwood B, Chandramohan D: Epidemiology of malaria in the forest-savanna transitional zone of Ghana. Malar J. 2009, 8: 220-PubMedCentralCrossRefPubMed Owusu-Agyei S, Asante KP, Adjuik M, Adjei G, Awini E, Adams M, Newton S, Dosoo D, Dery D, Agyeman-Budu A, Gyapong J, Greenwood B, Chandramohan D: Epidemiology of malaria in the forest-savanna transitional zone of Ghana. Malar J. 2009, 8: 220-PubMedCentralCrossRefPubMed
22.
go back to reference Maller R, Zhou X: Survival analysis with long-term survivors. 1996, New York: Wiley Maller R, Zhou X: Survival analysis with long-term survivors. 1996, New York: Wiley
23.
go back to reference Shen P: Testing for sufficient follow-up in survival data. Stat Probability Lett. 2000, 49: 313-322.CrossRef Shen P: Testing for sufficient follow-up in survival data. Stat Probability Lett. 2000, 49: 313-322.CrossRef
24.
go back to reference Hilbe JM: Logistic Regression Models. 2009, Boca Raton, FL: Chapman & Hall, 2 Hilbe JM: Logistic Regression Models. 2009, Boca Raton, FL: Chapman & Hall, 2
25.
26.
go back to reference Kreuels B, Kobbe R, Adjei S, Kreuzberg C, von Reden C, Bater K, Klug S, Busch W, Adjei O, May J: Spatial variation of malaria incidence in young children from a geographically homogeneous area with high endemicity. J Infect Dis. 2008, 197: 85-93.CrossRefPubMed Kreuels B, Kobbe R, Adjei S, Kreuzberg C, von Reden C, Bater K, Klug S, Busch W, Adjei O, May J: Spatial variation of malaria incidence in young children from a geographically homogeneous area with high endemicity. J Infect Dis. 2008, 197: 85-93.CrossRefPubMed
27.
go back to reference Bejon P, Turner L, Lavstsen T, Cham G, Olotu A, Drakeley CJ, Lievens M, Vekemans J, Savarese B, Lusingu J, von Seidlein L, Bull PC, Marsh K, Theander TG: Serological evidence of discrete spatial clusters of Plasmodium falciparum parasites. PLoS ONE. 2011, 6: e21711-PubMedCentralCrossRefPubMed Bejon P, Turner L, Lavstsen T, Cham G, Olotu A, Drakeley CJ, Lievens M, Vekemans J, Savarese B, Lusingu J, von Seidlein L, Bull PC, Marsh K, Theander TG: Serological evidence of discrete spatial clusters of Plasmodium falciparum parasites. PLoS ONE. 2011, 6: e21711-PubMedCentralCrossRefPubMed
28.
go back to reference Sutherland CJ, Drakeley CJ, Schellenberg D: How is childhood development of immunity to Plasmodium falciparum enhanced by certain antimalarial interventions?. Malar J. 2007, 6: 161-PubMedCentralCrossRefPubMed Sutherland CJ, Drakeley CJ, Schellenberg D: How is childhood development of immunity to Plasmodium falciparum enhanced by certain antimalarial interventions?. Malar J. 2007, 6: 161-PubMedCentralCrossRefPubMed
29.
go back to reference Kitua AY, Smith T, Alonso PL, Masanja H, Urassa H, Menendez C, Kimario J, Tanner M: Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission. Trop Med Int Health. 1996, 1: 475-484.CrossRefPubMed Kitua AY, Smith T, Alonso PL, Masanja H, Urassa H, Menendez C, Kimario J, Tanner M: Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission. Trop Med Int Health. 1996, 1: 475-484.CrossRefPubMed
30.
go back to reference Hviid L: Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Acta Trop. 2005, 95: 270-275.CrossRefPubMed Hviid L: Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Acta Trop. 2005, 95: 270-275.CrossRefPubMed
31.
go back to reference Xu Y, Cheung YB, Lam KF, Milligan P: Estimation of summary protective efficacy using a frailty mixture model for recurrent event time data. Stat Med. 2012, 31: 4023-4039.CrossRefPubMed Xu Y, Cheung YB, Lam KF, Milligan P: Estimation of summary protective efficacy using a frailty mixture model for recurrent event time data. Stat Med. 2012, 31: 4023-4039.CrossRefPubMed
Metadata
Title
Analysis of partial and complete protection in malaria cohort studies
Authors
Matthew E Cairns
Kwaku Poku Asante
Seth Owusu-Agyei
Daniel Chandramohan
Brian M Greenwood
Paul J Milligan
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2013
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-12-355

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