Addressing Cholera Under-Reporting Key to Mounting Proportionate Public Health Response

Cholera remains a cause of public health concern, not only causing explosive outbreaks in settings with disrupted socio-political and health infrastructure, but also exacting a huge burden in endemic settings with ongoing transmission. The development of a cheap, effective and easy to administer Oral Cholera Vaccine (OCV) has been a breakthrough development and in combination with effective water, sanitation and hygiene (WaSH), can be used to design a package of comprehensive cholera control interventions. This may be used for targeted control of cholera, especially in known, vulnerable hotspots. However, the public health response to cholera remains hamstrung by the lack of accurate data on the burden of cholera, especially in vulnerable areas. Weak surveillance systems, inconsistent case definitions, lack of laboratory capacity, and apprehensions about the negative impacts on travel, trade and commerce have led to consistent under-reporting of cholera globally.

India, particularly the Gangetic belt, has been identified as the cradle of cholera, with six of the seven cholera pandemics originating here. Cholera strains isolated from global sources have shown remarkable genetic similarity to the strains isolated from these areas, indicating that obtaining control of the cholera menace in this region could potentially have a global positive impact.

Transmission events inferred for the 7th Pandemic phylogenetic tree drawn on a global map. The date ranges shown for transmission events are taken from the BEAST analysis, and represent the median values for the MRCA of the transmitted strains (later bound), and the MRCA of the transmitted strains and their closest relative from the source location (earlier bound). (1)

A potential strategy to address this shortcoming could be to develop capacity across a network of institutions with the objective of enabling them to undertake cholera diagnostics. An effective, facility- and indicator-based hybrid surveillance system could then be deployed within these facilities, for collection of structured data, to monitor the occurrence of cholera, over time, in high vulnerability settings. The problem with this approach is that it does not really provide a good estimate of the “denominator”, that is, the total population which is likely to have been the source of the identified cases of cholera. Without this metric, it becomes virtually impossible to develop any epidemiologically intelligible information.

A strategy to overcome this shortcoming could be to supplement the facility-based surveillance with healthcare utilization surveys in catchment communities to estimate adjusted incidence of cholera. An approach to do that has been highlighted by Prof. Stephen Luby and his collaborators in a previous publication. They have termed it as “Hybrid Surveillance” – an efficient compromise between the resource-intense cohort studies which can provide accurate estimates of the disease burden and the inexpensive facility-based surveillance, which is extremely likely to underestimate the magnitude of a problem. Hybrid surveillance is situated somewhere in between these extremes – and involves pairing the facility-based surveillance with healthcare utilization surveys in the catchment communities. The authors elucidate the concept in great detail to enable other researchers to endeavor to replicate the method. 

Typhoid disease pyramid, where the base represents all typhoid patients in a catchment area and the apex represents culture-positive cases detected at study sites. Culture sensitivity is estimated from the literature, enrollment capture is estimated at facilities, and facility coverage is estimated by a household survey. These factors are utilized to adjust the crude incidence. (2)

Hybrid surveillance may be thought of as characterizing the layers of a disease detection pyramid, where all typhoid patients within a catchment area represent the base, and culture-confirmed cases detected at surveillance facilities represent the apex. A fraction of all typhoid patients in the community will seek care at study sites, a proportion of those are recruited and enrolled into the surveillance system, and the sensitivity of blood culture will determine how many cases are detected among those enrolled. Hybrid surveillance involves adjusting cases detected for these factors.

With cholera being under-reported, often by a factor of as much as 100x, it is perhaps of critical importance to establish a system which will deliver reliable and timely data on the burden of cholera at the national level. This will help to monitor the morbidity and mortality due to cholera and allow health policymakers get an estimate of the extent of under-reporting of cholera at the national level. The accurate burden estimates will have a major impact on reorienting cholera control plans, specifically with respect to vulnerable areas within the catchment areas under surveillance. This would also help in planning the most optimal approach for effectively implementing OCVs in hotspots. 

The silence around declaring cholera as a national priority has slowly begun to be breached in Africa. It is perhaps the time for the other vulnerable geographic areas to join in the growing clamor to end cholera by 2030. 

References:

1. Mutreja A, Kim DW, Thomson NR, et al. Evidence for several waves of global transmission in the seventh cholera pandemic. Nature. 2011;477(7365):462-5. Published 2011 Aug 24. doi:10.1038/nature10392
2. Andrews JR, Barkume C, Yu AT, Saha SK, Qamar FN, Garrett D, Luby SP. Integrating Facility-Based Surveillance With Healthcare Utilization Surveys to Estimate Enteric Fever Incidence: Methods and Challenges. J Infect Dis. 2018 Nov 10;218(suppl_4):S268-S276. doi: 10.1093/infdis/jiy494. PubMed PMID: 30184162; PubMed Central PMCID: PMC6226762.