Prevalence of asymptomatic visceral leishmaniasis (VL) infection in HIV positive patients and risk factors for progression to symptomatic VL in highly endemic districts of Bihar

One third of all HIV patients worldwide live in regions whereleishmaniasis is endemic (1). Visceral leishmaniasis (VL) caused by theparasite L.donovani is endemic to Bihar, a populous state of 110 millionpeople in East India, which carries an estimated 40% of the world’s VL burden(2). Although Bihar has a relatively lowprevalence of HIV (between 0.22 - 0.33%), its high population density meansthat in absolute numbers an estimated 300,000 people in the state live withHIV/AIDS(3).

Moreover, Bihar is one of the few states in India where the rate of newHIV infections is increasing(4). This has major implications for VLco-infection: like otheropportunistic infections in HIV patients, Leishmania amastigotes haveevolved strategies to survive (5) which are enhanced by HIV co-infection (6) and accelerate progression of disease(7). This may help explain why the risk of developing VL is estimated to bebetween 100 and 2300 times higher in HIV-infected individuals than in those whoare HIV-negative(8). Evidence on the prevalence of HIV-VLco-infection in India is scarce, although estimates range from 2-6%(9–15). HIV-VL co-infection therefore appears to bean emerging public health issue in India.

There is even less data on comparative characteristics of coinfected patients(9). A recent retrospective observational study describedan overall prevalence of HIV in patients ≥14 yearsold presenting with VL at 5.6%, however within certain age groups it wasconsiderably higher. Of male patients 35 to <45 years old presenting withVL, 5% were unknowingly HIV positive and, when pooled with data on the numbersof already-diagnosed HIV-positive patients presenting with VL, altogether 12.8%and 6.1% of all 35-to <45-year-old men and women, respectively, wereco-infected (14).

Yet the evidence base regarding best treatment practices forco-infected patients worldwide is limited, due to a lack of randomized trialsand to the fact that most available data comes from observational studies withrelatively short follow-up periods, and often with high rates of loss tofollow-up(16). Nevertheless, worse outcomes in almost everyrespect have consistently been reported in this patient group when compared topatients not known to be HIV-positive—for example, in terms of higher relapserates, mortality, and VL drug toxicity and treatment failure(16).

Following this, an expert committee comprising the respectivevertical programmes of the National Vector Born Disease Control Programme(NVBDCP) and National AIDS Control Organisation (NACO) was convened whichrecommended mandatory HIV testing for all patients diagnosed with VL. However,due to an absence of evidence, no clear recommendations were made on how toeffectively screen HIV patients living in VL endemic areas.

There have been a limited number of longitudinalstudies frim Bihar and West Bengal to establish the prevalence of exposure andprogression of asymptomatic VL patients to symptomatic VL in non-HIV infectedpatients.  These suggest thatasymptomatic VL is 4-17 times more prevalent than symptomatic VL (19). A recent review of these studies estimated the risk of progressionfrom asymptomatic to symptomatic to be between 1.5-23%, being higher in thosewith high antibody titres (20).  In particular, a recent studyfrom West Bengal suggested that 10.4% of 79 asymptomatic cases testing positivewith rk39 progressed to symptomatic VL within 3 years (21).

However there remains no evidence available on theburden of asymptomatic VL cases or pattern and risk factors for progression ofasymptomatic cases into to symptomatic VL among people living with HIV (PLHIV)AIDS.  This is a large evidence gap,since VL is considered as an opportunistic infection in HIV, and the GoI hasmandated that it be treated as a stage 4 AIDS defining illness. As such, it ishighly likely (although not demonstrated) that in KA endemic areas, theprevalence of exposure to VL in HIV patients will be high, and the progressionto symptomatic VL much higher than in non-immunocompromised populations.Crucially, unlike non-immunocompromised patients, those presenting withco-infection with HIV and VL currently do so at a very late stage, whentreatment outcomes are poor and mortality rates high.

Asymptomatic leishmaniasis are likely to be drivers ofVL epidemic and an important challenge to sustain VL elimination(22). Considering the high infectivity, recurring relapses and difficulty intreating co-infected patients, their identification, risk factor stratificationfor visceralisation and early management needs to be evaluated. This study willfill this knowledge gap, and may lead to further research on lower-dose earlytreatment of HIV positive asymptomatic infections.