As expected, the news of rising numbers of leptospirosis cases are trickling in from Puerto Rico. Since Hurricane Maria hit Puerto Rico, there have been areas which have experienced over 30 inches of rain, which, subsequently, led to flooding. As has been often observed, following the exposure to potentially contaminated water, the reported number of leptospirosis cases has been on the rise. Leptospirosis is a water borne zoonosis, with humans being unwitting targets in its transmission cycle.
Leptospirosis Transmission Cycle: Image Credits Georgia Gwinnet College Wiki
This week, a news outlet has reported that there have been two confirmed fatalities from leptospirosis. The news article further elaborates:
“This bacteria, like any other bacteria, can kill you,” Deseda said.
The island typically sees between 63 and 95 cases per year, she said. Health officials had expected that there would be a jump after the hurricane.
“It’s neither an epidemic nor a confirmed outbreak,” Public Affairs Secretary Ramon Rosario Cortes said at a news conference Sunday. “But obviously, we are making all the announcements as though it were a health emergency.”
Although it has not assumed epidemic or outbreak proportions yet, the problem with leptospirosis is that this is a largely mild disease. That means that this is one of the conditions in which the actual magnitude of the issue is much larger than what falls within the clinically visible spectrum. In epidemiology, this is often hailed as (or depending on your viewpoint, trivialized as) the iceberg phenomenon.]
The Iceberg Phenomenon Image Credits: Community Medicine Blog
Although there is limited evidence to give an exact accounting of the asymptomatic:symptomatic infection ratio for leptospirosis in outbreak settings, an oft-cited paper states that less than 30% of seropositive individuals, studied in Nicaragua, reported a febrile illness in the two months prior to the testing. The suggestion of this paper, that asymptomatic leptospiral infection is common in endemic situations, is further backed up by the conclusions presented in the Laboratory Manual on Leptospirosis (2007), published by the Indian Council of Medical Research, Regional Medical Research Center at Port Blair, Andaman and the South East Asia Regional Office of the WHO. The manual states:
In endemic areas, the incidence of asymptomatic infection could also be very high. A survey conducted in Seychelles (17) showed 9% point prevalence of asymptomatic leptospiral infection as proved by positive Polymerase Chain Reaction Test (PCR). In a study conducted in the North Andaman, 27% of the 396 persons followed up serologically had evidence of leptospiral infection during the follow up period of 12 weeks in the postmonsoon season (22). [Refer to document for cited reference; link]
There has been some accumulating evidence on what factors might potentially modulate the emergence of leptospirosis. As is often (or should I say always?) the case with zoonotic infections, the disease manifests especially well when there is a constellation of “favorable” factors present. A review attempted to graphically present the related risks in a Venn diagram, as below:
Factors contributing to leptospirosis.
Development of leptospirosis depends on three types of factors (epidemiology, host, and pathogen) and their interactions. Epidemiologic factors include sanitation, housing, rainfall, and whether flooding occurs. Incidence is linked to income level, occupation, and travel, representing epidemiologic factors linked to specific hosts. Hosts vary in susceptibility depending on age, genetic factors (e.g., HLA-DQ6), skin integrity, and whether protective clothing (e.g., gloves and boots) are worn. The ways in which the host and leptospires interact determine the route, exposure, and dose of the pathogen. Leptospiral pathogens differ in their ability to cause disease, a reflection of their virulence, motility, and ability to survive in the host, a reflection (at least in part) of complement resistance. The types of reservoir hosts determine the types of pathogens present in a particular epidemiologic setting.
Public Health Response to Leptospirosis
The following excerpt from the ““WHO recommended standards and strategies for surveillance, prevention and control of communicable diseases” are applicable for the management of potential outbreaks of leptospirosis.
Control activities
Case management
- Early treatment with antibiotics. Severe cases usually treated with high doses of IV benzylpenicillin (30 mg/kg up to 1.2 g IV 6-hourly for 5-7 days). Less severe cases treated orally with antibiotics such as doxycycline (2 mg/kg up to 100 mg 12-hourly for 5-7 days), tetracycline, ampicillin or amoxicillin.
- Third-generation cephalosporins, such as ceftriaxone and cefotaxime, and quinolone antibiotics may also be
effective. Jarisch-Herxheimer reactions may occur after the start of antimicrobial therapy. - Monitoring and supportive care as appropriate, e.g. dialysis, mechanical ventilation.
Prevention
The large number of serovars and of infection sources and the wide difference in transmission conditions make
leptospirosis an unlikely candidate for national eradication. Preventive measures should be based on knowledge of
those groups at higher risk of infection and of local epidemiological factors; they include:
- Identifying and controlling the source of infection (e.g. open sewers, contaminated wells).
- Control of feral reservoirs is often not feasible but control measures can be highly effective in small, defined animal populations (dogs, certified cattle herds) Selective rodent control may be important.
- Interrupting transmission, thereby preventing infection or disease in the human host: ƒ
- wearing protective clothes and equipment;
- disinfecting contaminated surfaces such as stable and abattoir floors;
- marking areas with increased risk exposure (warning signs).
- Preventing infection or disease in human hosts:
- antibiotic prophylaxis of exposed persons in areas of high exposures may be effective, e.g. soldiers (doxycyclin 200mg in one weekly dose);
- raising awareness of the disease and its of modes of transmission.
Epidemics
Conditions under which epidemics may occur
- Conditions leading to an increase of contaminated surface water or soil, such as rain, floods and disasters
increase the risk of leptospirosis and may lead to epidemics. During periods of drought both humans and animal reservoirs may be attracted to spare water places, hence increasing the risk of infection. - Social and recreational activities that expose persons to a contaminated environment.
Management of epidemics
In a suspected outbreak, attempts to diagnose leptospirosis must be encouraged to enable prompt treatment. For
outbreaks in remote or areas with poor access, local use of screening tests to detect antibody is helpful. When an
outbreak of leptospirosis is suspected or identified, and if it has been possible to identify the serovar concerned, the
source must be identified and appropriate environmental measures implemented, with public information to people at risk (including clinicians and health care workers and health authorities).
Drug-resistance monitoring
No reports of resistance for common antibiotics (see Case management above) and no guidelines for monitoring.
Testing of antibiotic resistance in individual clinical cases is not useful since it requires considerable time.
Performance indicators for control activities
- Number of new cases per 100 000 population over time.
- Seropositivity in selected populations.
The Diagnostic Dilemma of Leptospirosis
The challenge of reaching a diagnostic conclusion with a suspected case of leptospirosis is no less daunting than the public health activity of controlling an outbreak of this disease. Aside from the fact that it is not always on the diagnostic radar of clinicians, especially if they are not hyper-vigilant (which can sometimes come off as over-diagnostics or defensive medicine) or are not aware of the relevant exposure history, the complex immune response also plays a part in the diagnostic prevarication that often may accompany leptospirosis in areas where it is not always on the first list of differential diagnoses. In India, we were taught a “truism” which works well for identifying patients potentially exposed to a higher degree of risk of leptospirosis: “It is a disease of ‘rats, rains and rice’!”
This helpful schematic, from a review on Leptospirosis, can shed some light on the diagnostic approaches to managing leptospirosis:
Biphasic nature of leptospirosis and relevant investigations at different stages of disease.
Specimens 1 and 2 for serology are acute-phase specimens, 3 is a convalescent-phase sample which may facilitate detection of a delayed immune response, and 4 and 5 are follow-up samples which can provide epidemiological information, such as the presumptive infecting serogroup. Adapted from Turner LH (1969). Leptospirosis. Br Med J i:231–235. Copyright © American Society for Microbiology, (Clin Microbiol Rev 2001, 14 (2):296–326. doi:10.1128/CMR.14.2.296-326.2001)
Leptospirosis in India
India has had its own share of misfortunes with outbreaks of leptospirosis, with case in point being outbreaks in Mumbai and Chennai after massive rains led to a deluge. The National Centers for Disease Control, in collaboration with the Country Office for WHO, came up with a comprehensive document to address the public health challenge of leptospirosis outbreaks: Guidelines for the Prevention and Control of Leptospirosis. One interesting factor which has been addressed in these guidelines is the use of chemoprophylaxis for potentially exposed individuals. The document states:
15.8 Chemoprophylaxis
During the peak transmission season Doxycycline 200 mg, once a week, may be given to agricultural workers (eg. paddy field workers, canal cleaning workers in endemic areas) from where clustering of cases has been reported. The chemoprophylaxis should not be extended for more than six weeks.
There is some room to potentially study the beneficial impact of this strategy, and balance it against the potential adverse effects of basically exposing a large number of people to a mass drug administration strategy. As always, my personal interest is always inclined towards understanding the potential for the emergence of antimicrobial resistance, not only in Leptospires, but also other pathogens for which Doxycycline is a viable therapeutic alternative, which may get caught up in the crossfire – but not be entirely eliminated, thus helping to select for the resistant strains.
Antibiotic Resistance: Image Credits Beatrice the Biologist
