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Obase, B.N.; Bigoga, J.D.; Nsagha, D.S. Clinical Management of Malaria and HIV Co-Infection. Encyclopedia. Available online: https://encyclopedia.pub/entry/43345 (accessed on 24 June 2024).
Obase BN, Bigoga JD, Nsagha DS. Clinical Management of Malaria and HIV Co-Infection. Encyclopedia. Available at: https://encyclopedia.pub/entry/43345. Accessed June 24, 2024.
Obase, Bekindaka Ngemani, Jude Daiga Bigoga, Dickson Shey Nsagha. "Clinical Management of Malaria and HIV Co-Infection" Encyclopedia, https://encyclopedia.pub/entry/43345 (accessed June 24, 2024).
Obase, B.N., Bigoga, J.D., & Nsagha, D.S. (2023, April 23). Clinical Management of Malaria and HIV Co-Infection. In Encyclopedia. https://encyclopedia.pub/entry/43345
Obase, Bekindaka Ngemani, et al. "Clinical Management of Malaria and HIV Co-Infection." Encyclopedia. Web. 23 April, 2023.
Clinical Management of Malaria and HIV Co-Infection
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Malaria and HIV are geographically in the tropics and subtropics of the world, including sub-Saharan Africa. Understanding the overlapping effect of both infections, especially among pregnant women, is crucial in managing pregnant women during antenatal care visits, and postpartum babies. It was realized that the prevalence of malaria among HIV-positive pregnant women ranges between 31–61%, while for non-HIV infected pregnant women the prevalence still stands between 10 and 36%. Co-infection is between 0.52 and 56.3%.

malaria HIV co-infection

1. Introduction

Malaria and HIV are concentrated geographically in the tropics and subtropics of the world, including sub-Saharan Africa [1][2]. Around 70% of the world’s HIV-infected population lives in sub-Saharan Africa, where 350 million people are at risk of malaria infection [1]. Malaria and HIV co-infection is expected, due to the overlapping distribution of both diseases [1]. Both illnesses are leading causes of morbidity and mortality, predominantly in sub-Saharan Africa [3].
Malaria during pregnancy has profound effects, including parasite sequestration in the placental vascular space [4]. It may result in increased morbidity and mortality, abortion, stillbirth [5], low birth-weight (as a result of intrauterine growth retardation and preterm birth), and mother-to-child transmission (MTCT) of parasites [6]. In areas of stable malaria transmission in sub-Saharan Africa, it is recommended that all pregnant women should receive intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) at each scheduled antenatal-care visit (at least one month apart), until delivery [7][8]. Several studies have shown that HIV during pregnancy amplifies the effects of malaria [9], which is why administering Cotrimozaxole alongside antiretroviral therapy (ART) to pregnant women is essential during every antenatal-care visit [9].
Nevertheless, there is enough evidence to show that, despite efforts such as the distribution of long-lasting insecticidal bednets (LLINs) to pregnant women [10] and the implementation of intermittent preventive treatment (IPT-p) programs to reduce the burden of these infections [11], co-infection among pregnant women remains a problem, as malaria during pregnancy persists among pregnant women [1][12][13][14].
The persistence of malaria during pregnancy is linked to multiple factors, such as the inappropriate use of LLINs [15], not owning a single LLIN, and drug shortages at health institutions [15][16]. Therefore, a clear understanding of the overlapping effect of malaria and HIV infections among pregnant women is fundamental to controlling and improving the clinical management of women during antenatal-care visits and of babies postpartum.

2. The Clinical Management of Malaria

Chloroquine has been the first-line medicine for treating mild malaria in sub-Saharan Africa, followed by sulfadoxine-pyrimethamine (SP) as the most cost-effective second-line therapy. However, recent studies show that the clinical efficacy of both drugs has been significantly diminished, due to Plasmodium parasite resistance [17]. Using the World Health Organization’s standardized technique, twenty-five surveys were conducted in Cameroon between 1997 and 2004, to examine the effective therapeutic and second-line anti-malarial medicines (WHO). In the southern and central areas, chloroquine was ineffective, with a treatment failure rate of more than 25% [18]. Sulfadoxine-pyrimethamine (SP) failure rates varied from 8.6% to 14.1%. Despite being used as a first-line antimalarial treatment from 2002 to 2004, amodiaquine remained effective across the country, with a failure rate of around 4% [19].
The World Health Organization (WHO) advises pregnant women to take sulfadoxine-pyrimethamine (SP) and use insecticidal nets (ITNs) for the successful management of clinical malaria and anemia [20]. Any interaction between malaria parasites and HIV might result in an additional health burden, especially in pregnant women, with poor birth outcomes and the potential transmission of these intracellular diseases from mother to child [21]. HIV-infected women using Cotrimozaxole to decrease opportunistic infections should not receive IPTp, due to the increased risk of significant skin reactions such as Stevens–Johnson syndrome (unless otherwise indicated). Mefloquine increased the chance of HIV transmission from mother to child, while decreasing parasite incidence in HIV-infected women [22].
Houmsou et al. advised the following in a study of malaria infection in HIV-infected pregnant women visiting a rural prenatal clinic in neighboring Nigeria: (i) HIV-infected pregnant women in their first trimester should be administered sulfadoxine-pyrimethamine (SP) like their counterparts in the second and third trimesters, or they should be given daily Cotrimozaxole, which has been used with HIV patients for malaria prophylaxis [23]. (ii) Iron deficiency, the most common cause of anemia, should be adequately examined, and pregnant women should be treated as soon as possible to prevent anemia, from both malaria and HIV in pregnancy [23] as well as receiving HIV follow-up care among pregnant women [23]. (iii) To reduce the detrimental impacts of malaria throughout their pregnancies, HIV-infected pregnant women in rural areas should be effectively and comprehensively informed of prophylactic malaria measures [23]. (iv) Health nongovernmental organizations (NGOs) should enter into memorandums of understanding (MoU) with both public and private hospitals in remote areas that are already underfunded and underserved by stakeholders. These non-governmental organizations may help organize effective malaria and HIV screening, control programs, and follow-up HIV care among pregnant women [23].
Recently, the World Health Organization (WHO) has recommended that the malaria vaccine RTS, S/AS01 (RTS, S) be extensively administered to children in sub-Saharan Africa and other countries where Plasmodium falciparum, the most fatal of malaria parasites, is endemic. This advice was based on the findings of 11 pilot studies in sub-Saharan Africa, with varying levels of endemicity [24][25].

3. Role of Malaria Vaccine in the Management of Malaria during Pregnancy

Despite significant progress in malaria vaccine development in recent years, no trials of malaria vaccines have ever been conducted in pregnant women [26]. In December 2016, an expert meeting was convened at the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Health (NIH), in Rockville, Maryland, to deliberate on the rationale and design of malaria vaccine trials in pregnant women [26]. Even though human trials on these vaccines have not been conducted yet on pregnant women, studies testing the potential of some of these vaccine markers have been carried out [24][27][28]. Nevertheless, Table 1 outlines some of the malaria vaccines to be considered for human trials on pregnant women [26].
Table 1. Malaria vaccines currently in clinical development which may be considered for testing in pregnant women.
In a study conducted in Mali on PfSPZ-CVac malaria vaccine safety in malaria-experienced adults, it was realized that the efficacy of PfSPZ-CVac was 33.6%. PfSPZ-CVac (CQ) was tolerated well. The tested dosing-regimen failed to protect significantly against P. falciparum infection in this high transmission setting [27]. Another study showed that the efficacy of PfSPZ-CVac increases to 75% when the dose is doubled [29].
Furthermore, studies have shown that in subsequent pregnancies, women develop protective immunity against pregnancy-associated malaria, which is thought to be due to the acquisition of antibodies for the parasite variant surface antigen VAR2CSA [30]. Multiple studies have been conducted on this marker to evaluate its suitability as a vaccine candidate [31][32]. Nevertheless, studies looking at the efficacy of this vaccine are rare.
Other studies have shown that Pfs230-C is a suitable candidate vaccine marker, with an efficacy of 83.5% and 99.7% anti-Pfs25 in preventing malaria. The effectiveness of vaccines targeting either Pfs25 or Pfs230 may increase as malaria transmission declines [33].
RTS, also known as Mosquirix, is the only vaccine that has reached the clinical trial phase, and was approved for use in children by the World Health Organization [24]. Compared with the control group, the larger, extensive trial of the RTS S/AS01 vaccine showed efficacy estimates of 28.3% against all malaria episodes over a median of four years of follow-up in the group that received three doses of the RTS, S/AS01 vaccine [34].

4. Clinical Management of HIV-Infected Pregnant Women

Over the last two decades, international health programs and interventions have been implemented regarding human immunodeficiency virus transmission from mother to child (HIV) [35]. The World Health Organization revised its recommendations for using antiretroviral drugs in pregnant women and preventing HIV infection in infants in 2004, stating that pregnant women who require highly active antiretroviral therapy (HAART) for their health should start first-line ART regimens as soon as possible during pregnancy. HIV-infected pregnant women who do not need antiretroviral medication should start on Zidovudine (ZDV) at 28 weeks, ZDV throughout labor, and single-dose Nevirapine (sd-NVP) plus ZDV for one week after the child is delivered [36][37].
For example, Cameroon and some African countries [29] are transitioning from Efavirenz to Dolutegravir (DTG). Some studies have demonstrated that Efavirenz, a first-line treatment, is sluggish in lowering the viral load. This reduces the chances of safeguarding the baby from HIV infection during birth [38]. According to a study that used data from a trial in Cameroon, the Dolutegravir-based regimen, a low-cost, generic, fixed-dose antiretroviral therapy (ART) combination containing Tenofovir, Lamivudine, and Dolutegravir, is the preferred first-line treatment for patients with HIV-1 infection [39][40]. However, there are concerns about the overall risks and benefits of using Dolutegravir monotherapy in women of childbearing potential, given the increased risk of neural tube defects in those who already have resistance to Tenofovir and Lamivudine [41].

5. Guidelines for Monitoring and Prophylaxis of HIV-Exposed Children

All children born to HIV-positive mothers, commonly known as exposed children, are routinely examined at a health facility until the danger period of postpartum HIV transmission has passed (18–24 months postpartum) [42]. Children born to HIV-positive mothers should undergo thorough clinical and biological testing after birth and before being discharged from the hospital. Results should be noted in their medical records. Efforts are also being made to identify children born to HIV+ mothers at child entrance sites (immunization, pediatric, antiretroviral therapy service) [42]. Cotrimozaxole should begin six weeks after birth for all newborn/HIV-exposed children, and continue until weaning and HIV infection is eliminated. Nevirapine (NVP) prophylaxis should be given to newborns delivered to HIV-positive mothers as follows: (i) for six weeks if the mother receives antiretroviral therapy, regardless of the feeding method chosen by the mother; (ii) for 12 weeks if the infant is breastfed or if the mother did not receive treatment during pregnancy, or received it for less than four weeks; and (iii) for the duration of breastfeeding, if the mother received antiretroviral therapy during pregnancy (option A) [42].
Nevirapine is prescribed in Cameroon as a single daily dosage. Table 2 shows the dose of preventive Nevirapine to give to infants delivered to HIV+ mothers, based on their birth weight [42]. Anti-retroviral (ARV) regimen for infants delivered to mothers with ARV drug-resistant virus is unclear. Although some studies have shown that ARV drug-resistant viruses may have diminished replicative capacity (reduced viral fitness) and transmissibility [43], there is the perinatal transmission of multidrug-resistant viruses [43][44][45]. Maraviroc (MVC) was recently licensed for infants weighing 2 kg, and may give an alternative treatment option for neonates of mothers with multidrug-resistant HIV-1 that remains CCR5-trophic [46].
Table 2. Nevirapine (NVP) dosages in exposed children born to HIV-positive mothers in Cameroon.

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