As HIV research has become more global in nature, research gaps in children and pregnant women related to many HIV-associated co-infections, such as tuberculosis (TB), hepatitis, and malaria, have become evident. The MPIDB has responded by promoting and funding new research related to these HIV-associated infectious pathogens.
Additionally, the National Institute of Allergy and Infectious Diseases–NICHD-funded International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Network has broadened its focus to include TB, malaria, hepatitis, and investigation of vaccines to prevent HIV-related or other high-priority infectious diseases in children, adolescents, and pregnant women. The MPIDB is increasing its research portfolio in infectious diseases, initially focusing on TB, malaria, and hepatitis.
Examples of current research include:
- A Branch request for applications is funding three international grants to evaluate the interaction of antiretroviral drugs and first- and second-line TB treatment in HIV-infected children. Drug interactions could lead to sub-therapeutic drug levels for the anti-HIV drugs, the anti-TB drugs, or both. One of the funded investigators conducted the first evaluation of a rapid diagnostic test, Xpert MTB/RIF, in children and recently demonstrated that it can be an effective diagnostic tool for children in the primary care setting in developing countries. They also evaluated urine tests for mycobacterial lipoarabinomannan (a component of the cell wall) a test being evaluated for point of care diagnosis of TB in adults, but found that this test had insufficient sensitivity and specificity to diagnose TB in children.
- NICHD news release: Rapid test allows for earlier diagnosis of tuberculosis in children
- Article: Zar, H. J., Workman, L., Isaacs, W., Dheda, K., Zemanay, W., & Nicol, M. P. (2013). Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study. Lancet Global Health, 1(2), e97-e104.
- Article: Nichol MP, Allen V, Workman L, Isaacs W, Munro J, Pienaar S et al. (2014). Urine iipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study. Lancet Global Health, 2:e278-e284.
- A multi-country project in Africa is evaluating the effect of viral co-infection in children with cerebral malaria to determine if the presence of a viral co-infecting pathogen changes rates of morbidity and mortality and investigate whether children with viral co-infection can be identified using routine laboratory or clinical parameters.
- A large project in Uganda is evaluating several different malarial prophylaxis regimens for HIV-infected and uninfected pregnant women and their children to determine the optimal anti-malaria preventive regimen. This program project is in its second round of funding. Several important findings have come from the first round of funding, which also evaluated the interaction of HIV treatment and malaria, including: use of protease inhibitor-based HIV treatment among Ugandan HIV-infected children younger than age 6 years led to a 40% reduction in the rate of malaria compared to use of the standard nevirapine-based therapy; and year-round preventive anti-malarial prophylaxis with monthly dihydroartemisinin-piperaquine was safe and highly effective in preventing malaria in children living in an area of high malaria transmission intensity.
- NICHD news release: HIV treatment reduces risk of malaria recurrence in children, NIH funded study shows
- Article: Achan, J., Kakuru, A., Ikilezi, G., Ruel, T., Clark, T. D., Nsanzabana, C., et al. (2012). Antiretroviral agents and prevention of malaria in HIV-infected Ugandan children. New England Journal of Medicine, 367(22), 2110-2118. PMID: 23190222
- NICHD news release: Year-round preventive treatment reduces malaria risk in young children
- Article: Bigira V, Kapisi J, Clark TD, Kinara S, Mwangwa F, Muhindo MK, et al (2014). Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. PLosMed, 11 (8):e1001689.
- A large study in South Africa is evaluating the impact of TB and its treatment on outcomes in HIV-infected pregnant women and their infants, including HIV transmission, HIV progression, and pregnancy outcome, and will also determine the impact of rifampin-based TB treatment on antiretroviral drug concentrations in HIV-infected pregnant women. Data from this study has shown the pregnancy increases the risk of low efavirenz concentration (efavirenz is the drug recommended by WHO for use in pregnancy), and detectable viral load at delivery was more common among pregnant women with tuberculosis.
- Article: Dooley KE, Denti P, Martinson N, Cohn S, Mashabela F, Hoffman J, et al. (2014). Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis co-infection. Journal of Infectious Diseases, Epub ahead of print. PMID: 25081933. (R01 HD064354)
- In Thailand, a clinical trial is evaluating ways to improve prevention of mother-to-child hepatitis B (HBV) transmission in pregnant women with HBV infection who are hepatitis B e-Antigen (HBeAg) positive, have normal liver function tests, and are not HIV infected. The study is assessing the efficacy and safety of giving the women the anti-HBV drug tenofovir, in addition to standard infant HBV vaccine and immune globulin, to prevent transmission to their infants. The drugs is given from 28 weeks of gestation until 2 months postpartum, and both infant infection status and maternal health are evaluated. The investigators plan to enroll 588 women and infants within 8 sites in Thailand. The results of this study will define appropriate policy for management of HBV-infected HBeAg-positive pregnant women globally.
The MPIDB is also expanding its research portfolio to address the major infectious causes of morbidity and mortality in children worldwide. Although great strides have been made in reducing infectious mortality in children in resource-limited countries, infections continue to be a leading cause of child mortality in such settings. Globally, in 2012, approximately 6.6 million children younger than age 5 years died; infectious diseases such as pneumonia, diarrhea and malaria are the leading causes of mortality in children under age 5 years. Infections acquired in utero or in the immediate postnatal period play a prominent role in perinatal and childhood morbidity and mortality. A number of these infections may be mild or subclinical for the mother; nevertheless, vertical transmission can result in devastating consequences for the infant.
Areas of interest include the following aspects of infectious diseases with high morbidity and mortality rates in pediatric and maternal populations:
- Understanding disease epidemiology in different contexts
- Prevention (vaccines and other strategies, such as antivirals to prevent hepatitis and cytomegalovirus) for high-priority infectious diseases
- Treatment, including pharmacokinetics and safety of antimicrobials in pediatric and pregnant/breastfeeding populations
- Effect of infectious diseases (and their treatment) on maternal and pregnancy outcomes, the placenta, the fetus, and the child
Examples of relevant diseases include:
- TB, hepatitis B and C viruses, and malaria in non-HIV-infected populations
- Congenital infections, including interactions with the human placenta: cytomegalovirus, toxoplasmosis, herpes simplex, Chagas disease, and others
- Diarrhea and respiratory pathogens with morbidity/mortality in children/pregnant women
The MPIDB is interested in receiving new grants to study these causes of mortality, including epidemiology, diagnosis, treatment, and prevention. Investigators are invited to contact MPIDB staff members to discuss whether their research is relevant to the MPIDB’s expanding research portfolio.