Visceral Leishmaniasis in pregnancy and vertical transmission: A systematic literature review on the therapeutic orphans

Abstract

Background Reports on the occurrence and outcome of Visceral Leishmaniasis (VL) in pregnant women is rare in published literature. The occurrence of VL in pregnancy is not systematically captured and cases are rarely followed-up to detect consequences of infection and treatment on the mother and foetus. Methods A review of all published literature was undertaken to identify cases of VL infections among pregnant women by searching the following database: Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials; World Health Organization Global Index Medicus: LILACS (Americas); IMSEAR (South-East Asia); IMEMR (Eastern Mediterranean); WPRIM (Western Pacific); ClinicalTrials.gov; and the WHO International Clinical Trials Registry Platform. Selection criteria included any clinical reports describing the disease in pregnancy or vertical transmission of the disease in humans. Articles meeting pre-specified inclusion criteria and non-primary research articles such as textbook, chapters, letters, retrospective case description, or reports of accidental inclusion in trials were also considered. Results The systematic literature search identified 272 unique articles of which 54 records were included in this review; a further 18 records were identified from additional search of the references of the included studies or from personal communication leading to a total of 72 records (71 case reports/case series; 1 retrospective cohort study; 1926–2020) describing 451 cases of VL in pregnant women. The disease was detected during pregnancy in 398 (88.2%), retrospectively confirmed after giving birth in 52 (11.5%), and the time of identification was not clear in 1 (0.2%). Of the 398 mothers whose infection was identified during pregnancy, 346 (86.9%) received a treatment, 3 (0.8%) were untreated, and the treatment status was not clear in the remaining 49 (12.3%). Of 346 mothers, Liposomal amphotericin B (L-AmB) was administered in 202 (58.4%) and pentavalent antimony (PA) in 93 (26.9%). Outcomes were reported in 176 mothers treated with L-AmB with 4 (2.3%) reports of maternal deaths, 5 (2.8%) miscarriages, and 2 (1.1%) foetal death/stillbirth. For PA, outcomes were reported in 88 mothers of whom 4 (4.5%) died, 24 (27.3%) had spontaneous abortion, 2 (2.3%) had miscarriages. A total of 26 cases of confirmed, probable or suspected cases of vertical transmission were identified with a median detection time of 6 months (range: 0–18 months). Conclusions Outcomes of VL treatment during pregnancy is rarely reported and under-researched. The reported articles were mainly case reports and case series and the reported information was often incomplete. From the studies identified, it is difficult to derive a generalisable information on outcomes for mothers and babies, although reported data favours the usage of liposomal amphotericin B for the treatment of VL in pregnant women.

Cytotoxicity of Amphotericin B and AmBisome: In Silico and In Vivo Evaluation Employing the Chick Embryo Model

“…Hence, this formulation can be an alternative drug used for the treatment of leishmaniasis. These results are consistent with the previous report that suggested liposomal amphotericin B was the preferred therapy choice for the management of VL in pregnant women ( Mishra et al, 2007 ; Solomon et al, 2007 ; Dahal et al, 2021 ).…”

Mucocutaneous Leishmaniasis in a Pregnant Immigrant

“…While amphotericin B, particularly its liposomal derivative (L-AMB), is considered safe and effective in the treatment of VL in pregnancy, and has been widely used for cutaneous and mucosal leishmaniasis in South America, this is the first published report of its use in CL in a pregnant patient [ 6 , 13 ]. There is no standard dosage regimen of L-AMB for either VL in pregnancy or MCL in any host.…”

Dosing implications for liposomal amphotericin B in pregnancy

“…Animal models have demonstrated that vertical transmission can occur in both VL and CL/MCL 18 . Miscarriages, preterm births, small‐for‐gestational‐age infants, and fetal loss/stillbirths have been described in both VL and CL/MCL 15,19,20 …”

“…18 Miscarriages, preterm births, small-for-gestational-age infants, and fetal loss/stillbirths have been described in both VL and CL/MCL. 15,19,20 Although various treatment options exist for MCL, pregnancy significantly limits the number of safe agents available.…”