HIV-1 Impact on Malaria Transmission: A Complex and Relevant Global Health Concern

Abstract

Malaria/HIV-1 co-infection has become a significant public health problem in the tropics where there is geographical overlap of the two diseases. It is well described that co-infection impacts clinical progression of both diseases; however, less is known about the impact of co-infection on disease transmission. Malaria transmission is dependent upon multiple critical factors, one of which is the presence and viability of the sexual-stage gametocyte. In this review, we summarize evidence surrounding gametocyte production in Plasmodium falciparum and the development factors and the consequential impact that HIV-1 has on malaria parasite transmission. Epidemiological and clinical evidence surrounding anemia, immune dysregulation, and chemotherapy as it pertains to co-infection and gametocyte transmission are reviewed. We discuss significant gaps in understanding that are often due to the biological complexities of both diseases as well as the lack of entomological data necessary to define transmission success. In particular, we highlight special epidemiological populations, such as co-infected asymptomatic gametocyte carriers, and the unique role these populations have in a future focused on malaria elimination and eradication.

Keywords: HIV; HIV-1; Plasmodium falciparum; co-infection; gametocytes; malaria; review (article); transmission.

Figure 1

Incidence of Malaria, 2019. The incidence of all malaria cases per 1,000 people at risk in 2019, extracted from the World Health Organization (WHO) 2020 World Malaria Report.

Figure 2

People Living with HIV in Malaria Endemic Countries, 2019. The number of people living with HIV (per 1,000 population) in 2019 in malaria endemic countries from the WHO 2020 World Malaria Report. The 2019 HIV data are extracted from the Joint United Nations Programme on HIV/AIDS (UNAIDS) AIDSinfo data sheet. The 2019 country populations are extracted from the United Nations 2019 World Population Prospects.

Figure 3

Malaria Life Cycle and Selected Factors Influencing Malaria Parasite Transmission and Suggested Impact During HIV-1 Malaria Co-infection. Example of selected factors that are known to be associated with malaria parasite transmission and the suggested impact (determined using Decision Matrix, Supplementary Figure 1 .) with HIV-1 and/or malaria/HIV-1 co-infection. Suggestive impact is used due to the lack of available statistical evidence and the difficulty in ascertaining the biological relationship between malaria/HIV-1 co-infection and malaria parasite transmission success. Strong Direct Impact means that there is evidence, which includes mosquito transmission data, to suggest that HIV-1 malaria co-infection directly alters gametocyte conversion (GC), gametocyte development (GD), or mosquito infectivity (MI). Direct Impact means there is evidence, sans mosquito data, to suggest that HIV-1 malaria co-infection directly alters GC, GD, or MI. Indirect impact means there is evidence to suggest that HIV-1 or HIV-1 malaria co-infection indirectly alters factors that influence GC, GD, or MI. Possible Impact means there is evidence to suggest that HIV-1 or HIV-1 malaria co-infection may alter factors associated with GC, GD, or MI. Unknown Impact means there is currently not enough evidence to suggest that HIV-1 or HIV-1 malaria co-infection directly or indirectly alter GC, GD, MI, or the factors associated with GC, GD, or MI. The left table (gray, “Gametocyte Conversion”) represents selected transmission factors that pertain to the gametocytogenesis and gametocyte commitment. The center table (red, “Gametocyte Development”) represents selected transmission factors that pertain to the sexual stage development. The right table (green, “Mosquito Infectivity”) represents selected factors that may influence infectivity to mosquitoes and subsequent mosquito transmission success. In the middle is a representation of the life cycle of Plasmodium falciparum (adapted from NIAID/NIH, 2016, https://www.niaid.nih.gov/diseases-conditions/malaria-parasite) representing the exo-erythrocytic (liver) cycle, erythrocytic cycle (bloodstream), and sexual stage (gametocyte) development in the host, and the sporogonic cycle in the mosquito. ¹Brancucci et al., 2017; ²Tanaka et al., 2019; ³Orikiiriza et al., 2017; ⁴Drobnik et al., 2003; ⁵Belury et al., 2003; ⁶Bowman et al., 2019; ⁷Whitworth et al., 2000; ⁸Patnaik et al., 2005; ⁹Abu-Raddad et al., 2006; ¹⁰Laufer et al., 2006; ¹¹Onyenekwe et al., 2007; ¹²Van Geertruyden et al., 2008; ¹³Stiffler et al., 2020; ¹⁴Trott et al., 2011; ¹⁵Koehler et al., 2009; ¹⁶Okonkwo et al., 2016; ¹⁷Mbale et al., 2016; ¹⁸Graves et al., 1988; ¹⁹Nassir et al., 2005; ²⁰Lingnau et al., 1993; ²¹Bousema et al., 2011; ²²Belperio and Rhew, 2004; ²³Eksi et al., 2012; ²⁴Brancucci et al., 2014; ²⁵Josling et al., 2020; ²⁶Coleman et al., 2014; ²⁷Kafsack et al., 2014; ²⁸Filarsky et al., 2018; ²⁹Hobbs et al., 2013; ³⁰Azevedo et al., 2019; ³¹Buckling et al., 1999; ³²Elbasit et al., 2006; ³³Ittiravivongs et al., 1984; ³⁴Josling et al., 2018; ³⁵Sandison et al., 2011; ³⁶Puta and Manyando, 1997; ³⁷Schneider et al., 2006; ³⁸Barnes et al., 2008; ³⁹Bouyou Akotet et al., 2018; ⁴⁰Sowunmi et al., 2008; ⁴¹Quintero et al., 2011; ⁴²Nacher et al., 2002; ⁴³Tay et al., 2015; ⁴⁴Sanyaolu et al., 2013; ⁴⁵Okechukwu et al., 2018; ⁴⁶Van Geertruyden et al., 2009; ⁴⁷Stone et al., 2018; ⁴⁸Kamya et al., 2006; ⁴⁹Schneider et al., 2007; ⁵⁰Babiker et al., 2008; ⁵¹Djimde et al., 2003; ⁵²Rogerson et al., 2010; ⁵³Tadesse et al., 2018; ⁵⁴Wargo et al., 2007; ⁵⁵Tukwasibwe et al., 2014; ⁵⁶Gulati et al., 2015; ⁵⁷Birku et al., 2002; ⁵⁸Oesterholt et al., 2009; ⁵⁹Torrevillas et al., 2020; ⁶⁰Paul et al., 2000b; ⁶¹Robert et al., 2000; ⁶²Hogh et al., 1998; ⁶³Beavogui et al., 2010; ⁶⁴Kone et al., 2010; ⁶⁵Kakuru et al., 2013; ⁶⁶Kamya et al., 2007; ⁶⁷Mermin et al., 2006.