Background
The emergence of cholera in Papua New Guinea in July 2009 and its subsequent spread to neighboring provinces has provided significant challenges to health authorities [
1]. Understanding the risk factors for cholera is important to enable the implementation of targeted prevention and control measures and to provide compelling specific evidence to government infrastructure decision makers. As of May 2011, Papua New Guinea has recorded over 15,000 cases of cholera at a case-fatality ratio of 3.2% [
1]. Many of these cases presented to the longest running treatment centre in the country at Angau Memorial Hospital. Despite awareness campaigns and small scale water and sanitation interventions to reduce cholera transmission in the catchment area of this provincial referral hospital, transmission has continued since the beginning of the outbreak.
Contaminated water and food are the most common routes of cholera transmission during outbreaks [
2]. Further risk factors include rainfall, seasonality, poor sanitation, travel, conflict, population displacement, health facilities with poor infection control and living near contaminated water sources. Funerals are often implicated in cholera transmission [
3‐
5]. Cholera risk factors in the rural community setting in Papua New Guinea have been previously reported [
6]; however there is no information on cholera risk factors in the urban setting, where cholera transmission has been most sustained, especially in the informal settlements.
Globally, the use of cholera rapid antigen point-of-care (POC) testing is widespread, as they can be a useful adjunct to outbreak surveillance when combined with traditional laboratory methods [
7], and may enable faster outbreak identification and characterization. Earlier intervention during cholera outbreaks in newly affected areas may lead to a decrease in transmission and case fatality ratio [
7], as many deaths typically occur early, when supplies, awareness, clinical skills and human resource numbers may require strengthening. While cholera POC tests have been evaluated in controlled research environments, a key question remains as to how well these tests performs directly in the hands of primary healthcare providers at a patient's bedside in crisis situations [
8]. Traditional laboratory methods were nationally recommended during the Papua New Guinea cholera outbreak, however one POC test became widely available and was used for a variety of clinical and public health purposes. Definitive guidance on the utility of this POC test, which has not previously been field evaluated, and other POC tests will enable better decision making.
We report on the risk factors for cholera identified through a prospective hospital based case–control study conducted to understand disease transmission and galvanise public health action. We also discuss the field evaluation of a POC test to understand its utility in the management of a cholera epidemic.
Discussion
Improving water, sanitation and other infrastructure has been associated with a 39% decline in waterborne disease in informal urban settlements in Africa [
13]. The water and sanitation related Millennium Development Goals will not be achieved in Papua New Guinea [
14], with the growing urban populations that dwell in critical water catchment areas a cause for concern [
15]. While access to a piped water distribution system was protective on univariate analysis, it did not remain significant on multivariate analysis. Importantly, those with access to a piped water distribution system were twice as likely to report soap for handwashing in the home and cases were more than three times as likely to reside in informal settlements.
Handwashing with soap and water protects against cholera [
16], and may become increasingly important during outbreaks as cholera contamination becomes widespread and disease dissemination is through multiple vehicles [
17]. In our study, reporting the presence of soap for handwashing in the home was associated with protection against cholera (aOR 0.41; 95%CI 0.19, 0.87). Given that sharing a house with an infectious cholera case is a risk factor [
18], improving access to soap for handwashing in the home for cholera cases that are often still infectious on discharge from treatment facilities will likely limit further transmission.
The lack of access to latrines has been identified as a risk factor for cholera in informal settlement areas in previous studies [
16] and in our investigation, where cases of cholera were more likely to defecate in the open air or river than controls (aOR 4.5; 95% CI 1.4, 14.4). Months into the outbreak, half the cases were still drinking untreated river water and almost a quarter were defecating in the same rivers or open fields. While the evidence of impact of improved sanitation is weakest of the three areas of intervention to reduce transmission of diarrheal disease, it may still be effective [
19] and appears highly warranted in this setting.
Evaluations of cholera POC tests conducted in controlled research environments with high levels of training have estimated sensitivity to range from 83 to 97%, and specificity from 71 to 95% [
7,
8,
20,
21]. Field evaluations have estimated the sensitivity and specificity of POC tests at 80% and 77% early in their use, improving over time [
7]. Our evaluation, the first of this POC test, was conducted under field conditions during an outbreak where the user was not highly trained or experienced with POC tests. The specificity was within the range seen with other POC tests (71%; 95% CI 44–90); however the sensitivity was low (72%; 95% CI 47–90), indicating they should not be used for case management decisions (treatment or triage). Training in the use and interpretation of POC tests remains important [
20], as well as the need to perform such tests alongside traditional laboratory methods in the hospital setting.
High population mobility in Papua New Guinea has been shown to impact on the risk of infectious disease transmission [
22,
23]. Cholera is frequently reported in association with international travel [
24], however the high internal population mobility in Papua New Guinea, in the context of limited access to water and sanitation, presents an important threat to previously unaffected areas. Knowing someone who has travelled to a cholera affected area was a risk factor for cholera in our study (aOR 4.1; 95%CI 1.6, 10.7).
This study has several limitations. Similar to previous studies [
25], we isolated cholera from only half the suspected cholera cases by stool culture. This may in part be explained by studies which have shown that isolation failure from suspected cholera stools by stool culture during acute diarrhoea outbreaks may be explained by the inactivation of
V.
cholerae by in vivo vibriolytic action of the phage and/or nonculturability induced as a host response [
26]. Similar to previous studies that have relied on a high positive predictive value of the clinical case definition during cholera outbreaks [
4,
5,
17,
27‐
30], we did not exclude cases on microbiological confirmation of non-cholera aetiologies. The estimates of sensitivity and specificity of the POC test had wide confidence intervals due to a small sample size, however interpretation remained feasible. The sensitivity of the cholera POC test in our study may be a reflection of several factors, including the sample size and the limited training in the use and interpretation of the cholera POC tests. However the results provide insight into their utility in a typical field setting where training and experience may be limited prior to POC test usage. Three controls were not recruited for each case, however this only slightly reduced the power of the study, highlighted by the retrospective power calculations which indicate that power for a bivariate analysis was only reduced from 91% to 89% for an alpha of 5%, exposure of 50% in cases (which approximates the proportion of cases having river as a drinking water source) and minimum odds ratio of 3 when recruitment ratio was reduced from 3 (the targeted ratio) to 2.25 (the current ratio). This reduction in recruitment ratio also did not impede the identification of statistically significant risk factors in the multivariate model.
The slow progress improving water and sanitation infrastructure, in the context of the licensing and marketing of new low-cost oral cholera vaccines and the current vaccine trials in Haiti [
31], may stimulate further analysis of the utility of vaccination as a component of future prevention and control in Papua New Guinea. While reactive vaccination has demonstrated its effectiveness in outbreaks in stable populations [
32], many of the issues highlighted for consideration prior to implementing vaccination campaigns in Haiti [
33] would be similar to those for Papua New Guinea. In our study, which was conducted in a newly affected area, cases were all ages, and were more likely than controls to be over 20 years of age (aOR 2.5; 95%CI 1.1, 5.4).
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
AR made substantial contributions to conception and design, analysis and interpretation of data and was involved in drafting the manuscript. BA made substantial contributions to acquisition and interpretation of data and has been involved in drafting the manuscript. LK made substantial contributions to acquisition of data. FM has been involved in drafting the manuscript. BR made substantial contributions to conception and has been involved in drafting the manuscript. EP made substantial contributions to conception and has been involved in drafting the manuscript. SD made substantial contributions to acquisition of data. GM was involved in drafting the manuscript and revising it critically for important intellectual content. WYNM made substantial contributions the analysis and interpretation of data and has been involved in critically revising the manuscript for important intellectual content. AZ was involved in drafting the manuscript and revising it critically for important intellectual content. CRM made substantial contributions to analysis and interpretation of data and has been involved in revising it critically for important intellectual content. All authors read and approved the final manuscript.