Epidemiology and Social: CONCISE COMMUNICATION
Increased severe anemia in HIV-1-exposed and HIV-1-positive infants and children during acute malaria
Otieno, Richard Oa,b; Ouma, Collinsb,c; Ong'echa, John Mb; Keller, Christopher Cd; Were, Tomb,e; Waindi, Eliud Na; Michaels, Marian Gf; Day, Richard Dg; Vulule, John Mh; Perkins, Douglas Jb,d
From the aDepartment of Zoology, Maseno University, Kisumu, Kenya
bUniversity of Pittsburgh/KEMRI Laboratories of Parasitic and Viral Diseases, Centre for Vector Biology and Control Research, Kisumu, Kenya
cDepartment of Pre-Clinical Sciences, School of Health Sciences, Kenyatta University, Nairobi, Kenya
dDepartment of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
eDepartment of Pathology, School of Health Sciences, Kenyatta University, Nairobi, Kenya
fDepartment of Pediatrics, University of Pittsburgh Children Hospital, Pittsburgh, Pennsylvania, USA
gDepartment of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
hKenya Medical Research Institute, Centre for Vector Biology and Control Research, Kisumu, Kenya.
Received 30 August, 2005
Revised 28 September, 2005
Accepted 6 October, 2005
Correspondence to D.J. Perkins, Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 603 Parran Hall, 130 Desoto St., Pittsburgh, PA 15261, USA. Tel: +1 412 624 5894; fax: +1 412 624 4953; e-mail: firstname.lastname@example.org
Objective: Since the primary hematological complication in both pediatric HIV-1 and malaria is anemia, co-infection with these pathogens may promote life-threatening severe malarial anemia (SMA). The primary objective of the study was to determine if HIV-1 exposure [HIV-1(exp)] and/or HIV-1 infection [HIV-1(+)] increased the prevalence of SMA in children with acute malaria.
Design: The effect of HIV-1 exposure and HIV-1 infection on the prevalence of SMA (hemoglobin < 6.0 g/dl), parasitemia (parasites/μl), and high-density parasitemia (HDP, ≥ 10 000 parasites/μl) was investigated in children ≤ 2 years of age presenting at hospital with acute Plasmodium falciparum malaria in a rural holoendemic malaria transmission area of western Kenya.
Methods: Upon enrollment, a complete hematological and clinical evaluation was performed on all children. Malaria parasitemia was determined and children with acute P. falciparum malaria were evaluated for HIV-1 exposure and infection by two rapid serological antibody tests and HIV-1 DNA PCR, respectively.
Results: Relative to HIV-1(−) group (n = 194), the HIV-1(exp) (n = 100) and HIV-1(+) (n = 23) groups had lower hemoglobin concentrations (P < 0.001 and P < 0.001, respectively), while parasitemia and HDP were equivalent between the three groups. Multivariate analyses demonstrated that the risk of SMA was elevated in HIV-1(exp) children (odds ratio, 2.17; 95% confidence interval, 1.25–3.78; P < 0.01) and HIV-1(+) children (odds ratio, 8.71; 95% confidence interval, 3.37–22.51; P < 0.0001). The multivariate model further revealed that HIV-1 exposure or infection were not significantly associated with HDP.
Conclusions: Results presented here demonstrate that both HIV-1 exposure and HIV-1 infection are associated with increased prevalence of SMA during acute P. falciparum infection, independent of parasite density.
Plasmodium falciparum and HIV-1 infections are leading causes of childhood morbidity and mortality in many sub-tropical and tropical countries. Based on the geographic overlap between P. falciparum and HIV-1 there has been substantial public health concern. Although earlier reports failed to demonstrate significant interactions between malaria and HIV-1 in co-infected adults [1–7], recent investigations showed that co-infection enhances the pathogenesis of both diseases [7–19].
One of the most common clinical problems in pediatric populations in developing nations is anemia, occurring in approximately 63% of preschool children in Africa . Causes of pediatric anemia are multifactorial and include: nutritional and micronutrient deficiencies, hemoglobinopathies, low birth weight (LBW) infants, bacteremia, hookworm, malaria, and HIV . Several studies failed to demonstrate significant interactions between childhood malaria and HIV-1 [22,23], while others have shown increased severe malaria in HIV-antibody(+) versus HIV(−) children . Although the most prevalent hematological abnormality in childhood malaria and HIV-1 is anemia [25–27], the impact of co-infection on anemia is largely unreported. One study, however, demonstrated that HIV-1(+) infants have lower hemoglobin (Hb) levels during acute malaria than HIV-1(+) children without malaria .
To investigate the impact of co-infection on pediatric anemia, a hospital-based study was performed in a rural, holoendemic P. falciparum transmission area of western Kenya . In this equatorial community, severe malarial anemia (SMA) is the primary clinical manifestation of life-threatening childhood malaria, with cerebral malaria occurring only in rare cases . Results presented here describe the association between HIV-1 status and SMA and parasitemia.
Children ≤ 2 years (n = 317) were recruited in Siaya District, western Kenya during their first hospital contact for acute malaria. Study participants were matched upon enrollment for age, sex, and area of residence. Children with P. falciparum parasitemia (any density) were divided into three groups: HIV-1 negative [HIV-1(−), negative results for two serological antibody tests (Determine and Unigold)]; HIV-1 exposed [HIV-1(exp), positive result(s) for one or both serological tests and negative HIV-1 DNA PCR results on two consecutive blood samples approximately 3 months apart]; and HIV-1 positive [HIV-1(+), positive results for one or both serological tests and positive HIV-1 DNA PCR results on two consecutive blood samples approximately 3 months apart]. None of the study participants had cerebral malaria. Children with malaria were promptly treated according to Ministry of Health, Kenya guidelines and provided with the appropriate supportive therapy. Children positive for one or both serological tests were started on trimethoprim–sulfamethoxazole. None of the children were receiving antiretroviral therapy at the time of enrollment. Written informed consent was obtained from the parents/guardians of participating children and pre- and post-test HIV counseling was provided. The study was approved by the University of Pittsburgh and Kenya Medical Research Institute (KEMRI) Institutional Review Boards.
Malaria diagnosis was performed using capillary finger-prick blood on thin and thick blood smears stained with 3% Giemsa. The number of asexual Plasmodium parasites was determined per 300 leukocytes and parasite density was calculated by multiplying by the white blood cell count. Heel/finger-prick blood (< 100 μl) was collected into EDTA-containing tubes and spotted on FTA Classic cards (Whatman Inc., Florham Park, New Jersey, USA) for HIV-1 DNA PCR. Complete blood counts were performed with a Beckman Coulter AcT diff2 (Beckman-Coulter Corporation, Miami, Florida, USA) on peripheral blood (1–3 ml) collected into EDTA-containing vials.
HIV-1 exposure was determined in venipuncture blood by two rapid serological antibody tests: Unigold (Trinity Biotech, Bray, County Wicklow, Ireland) and Determine (Abbott Laboratories, Chicago, Illinois, USA). Single- or double-positive results were evaluated for HIV-1 infection by nested PCR of proviral DNA extracted from filter papers using the Chelex method . HIV-1 gp41 primers were selected for highly conserved HIV-1 group M, N, and O sequences for use in western Kenya [32,33]. Nested PCR products were visualized on an ethidium bromide-stained 2% agarose gel. HIV-1 positivity was based on the presence of a 460-bp fragment.
Data were analyzed using SPSS (version 11.0, Chicago, Illinois, USA). Pearson's rank χ2 test was used for comparing proportions. Parameter medians were compared with Kruskal–Wallis tests, followed by pairwise Mann–Whitney U tests. Multivariate logistic regression, controlling for age, sex, and sickle-cell trait was used to determine the association between HIV-1 status and SMA and high-density parasitemia (HDP, ≥ 10 000 parasites/μl). Although the World Health Organization (WHO) defines SMA as Hb < 5.0 g/dl , SMA in western Kenya is more appropriately defined as Hb < 6.0 g/dl. The modified SMA definition is based on approximately 14 000 repeated Hb measurements in children 0–4 years of age in western Kenya . However, both definitions were used in the analyses. Differences were considered statistically significant at P < 0.05.
Clinical and hematological characteristics
The demographic, clinical, and hematological parameters of the study participants (n = 317) upon enrollment are presented in Table 1. Study participants were divided into three groups based on the presence of malaria parasites and HIV-1 status: HIV-1 negative [HIV-1(−), n = 194, median age 10.5 months; range, 3–31 months]; HIV-1 exposed [HIV-1(exp), n = 100; median age, 8.5 months; range, 2–32 months]; and HIV-1 positive [HIV-1(+), n = 23; median age, 13.0 months; range, 3–26 months]. There was a significant difference in age across the groups (P < 0.05) with the HIV-1(−) group being older than the HIV-1(exp) group (P < 0.05, Table 1). Temperature, glucose, parasitemia, and HDP were not statistically different between the groups. Red blood cell (RBC) counts differed between the groups (P < 0.001), with the HIV-1(exp) and HIV-1(+) groups having lower RBC counts than the HIV-1(−) group (P < 0.001 and P < 0.001, respectively, Table 1). Relative to the HIV-1(−) group, Hb and hematocrit (Hct) were reduced in the HIV-1(exp) (P < 0.001 and P < 0.001, respectively) and HIV-1(+) children (P < 0.001 and P < 0.001, respectively, Table 1). The HIV-1(+) group also had significantly lower levels of Hb and Hct than the HIV-1(exp) group (P < 0.01 and P < 0.05, respectively, Table 1).
Effect of HIV-1 status on SMA
The effect of HIV-1 status on SMA was also determined. The proportion of children with SMA (Hb < 6.0 g/dl) in the HIV-1(−) group was 19.1% versus 35% in the HIV-1(exp) group (P < 0.01), and 65.2% in the HIV-1(+) group [P < 0.001 versus HIV-1(−); Table 1]. SMA was more prevalent in the HIV-1(+) group vs. the HIV-1(exp) group (P < 0.01, Table 1). Based on the WHO categorization (Hb < 5.0 g/dl), 8.8% of the HIV-1(−) group had SMA, while SMA was present in 13.0% of the HIV-1(exp) cases [P = 0.256 versus HIV-1(−)], and 34.8% of the HIV-1(+) group [P < 0.001 versus HIV-1(−), and P < 0.01 versus HIV-1(exp); Table 1].
Multivariate analyses examining the impact of HIV-1 status on SMA and HDP
The effect of HIV-1 status on SMA and HDP was further investigated by multivariate analyses controlling for age, sex, and sickle-cell trait. The multivariate model revealed that SMA (Hb < 6.0 g/dl) was higher in the HIV-1(exp) group [odds ratio (OR), 2.17; 95% confidence interval (CI), 1.25–3.78; P < 0.01] and the HIV-1(+) group (OR, 8.71; 95%CI, 3.37–22.51; P < 0.0001) compared with HIV-1(−) children (Table 2). SMA was also more prevalent in the HIV-1(+) group than the HIV-1(exp) group (OR, 4.00; 95%CI, 1.51–10.62; P < 0.01, Table 2). Based on WHO criteria (Hb < 5.0 g/dl), HIV-1 exposed and positive children had an increased risk of SMA (OR, 4.33; 95%CI, 1.47–12.72; P < 0.01 and OR, 5.93; 95%CI, 2.14–16.45; P < 0.001, respectively) relative to the HIV-1(−) group (Table 2).
Compared to the HIV-1(−) group, multivariate analyses demonstrated that HDP did not differ in the HIV-1(exp) group (OR, 1.18; 95%CI, 0.70–1.96; P = 0.535) or the HIV-1(+) group (OR, 0.64; 95%CI, 0.27–1.53; P = 0.320; Table 2). Moreover, HDP was not significantly different between the HIV-1(+) group and the HIV-1(exp) group (OR, 0.55; 95%CI, 0.22–1.37; P = 0.199; Table 2).
Anemia is the most common finding associated with pediatric HIV and malaria in sub-Saharan Africa [30,34–37]. While it is clear that both pathogens promote anemia, only one study to date has directly addressed the role of co-infection as a risk factor for pediatric anemia, showing that HIV-1(+) infants had increased prevalence of anemia, while HIV-1/malaria co-infected infants had lower Hb levels than infants with either infection alone . Although the previous study showed that anemia in HIV-1(−) infants born to HIV(+) mothers [a group comparable to the HIV-1(exp) group investigated here] approached significance (P < 0.07), the prevalence of SMA did not differ among the groups . Results presented here in an adjacent, rural area with presumably higher malaria exposures rates demonstrate that both HIV-1 exposure and infection significantly increase severe anemia during acute malaria. In the current study, > 99% of the study participants were from the Luo ethnic tribe, which in this rural setting, have similar malaria exposure patterns and socio-demographic indices . Thus, homogeneity among our study population may explain differences in the present results as compared to previous findings in an urban and peri-urban area with greater diversity in malaria exposure rates and socio-demographic factors .
The finding that both HIV-1 exposure and infection is associated with increased SMA suggests that children born to HIV-1(+) mothers may be predisposed to hematological complications during malaria. Although the underlying mechanism(s) is presently unclear, in utero HIV-1 exposure may impair hematological and/or immunological development. This hypothesis is supported by investigations showing that fetal liver hematopoiesis in second trimester abortuses from HIV(+) women have hematological abnormalities including reductions in multipotent progenitors (e.g., CD34) . Moreover, examination of 100 symptomatic HIV(+) versus HIV(−) infants with transplacental HIV-1 antibodies demonstrated that 94% of the HIV(+) group had anemia; a major predictor of disease progression in which those with Hct levels < 25% presented with a rapidly fatal course . Additional studies illustrated that HIV-1/malaria co-infection in pregnant women increases the risk of LBW, preterm birth (PTB), post-neonatal mortality, and intrauterine growth retardation [40,41]. Since maternal malaria status and rates of LBW and PTB were unknown in our cohort, the influence of these variables cannot be determined. Alternatively, increased prevalence of SMA could be due to factors associated with breastfeeding. Since all of the children in the current study were breastfed, it is possible that HIV-1(+) mothers had poor nutritional and/or immunological status that increased the development of SMA. Additional investigations are required to confirm this speculation.
Findings presented here also showed that parasitemia is unrelated to Hb concentrations, as evidenced by similar parasitemia in the presence of marked differences in anemia status between the groups. Although previous studies in adults illustrated that co-infection is associated with increased parasitemia [9,42,43], present results support previous findings in African pediatric populations [1,22–24,44] showing no association between HIV-1 and parasitemia.
In summary, data presented here demonstrate that HIV-1/malaria co-infection increases SMA in infants and young children, illustrating that HIV-1 testing is essential in pediatric populations in malaria endemic areas. Extending these cross-sectional results and prospectively following children throughout their first 5 years of life may offer important insight into the number of HIV-1(exp) children that seroconvert and become HIV-1(+), and additionally, if HIV-1(exp) and/or HIV-1(+) children acquire immunity to P. falciparum following repeated exposures.
This work was supported by grants from NIH (DJP: AI51305-02 and DJP: TW05884-02).
The authors are grateful to all of the study participants and their families, and the University of Pittsburgh-KEMRI staff. We also thank the Siaya District Hospital staff and management, and the cooperation of Dr. Davy Koech, Director of Kenya Medical Research Institute (KEMRI), for approving this manuscript for publication.
1. Nguyen-Dinh P, Greenberg AE, Mann JM, Kabote N, Francis H, Colebunders RL, et al
. Absence of association between Plasmodium falciparum
malaria and human immunodeficiency virus infection in children in Kinshasa, Zaire. Bull World Health Org 1987; 65:607–613.
2. Simooya OO, Mwendapole RM, Siziya S, Fleming AF. Relation between falciparum malaria and HIV seropositivity in Ndola, Zambia. BMJ 1988; 297:30–31.
3. Muller O, Moser R. The clinical and parasitological presentation of Plasmodium falciparum
malaria in Uganda is unaffected by HIV-1 infection. Trans R Soc Trop Med Hyg 1990; 84:336–338.
4. Colebunders R, Bahwe Y, Nekwei W, Ryder R, Perriens J, Nsimba K, et al
. Incidence of malaria and efficacy of oral quinine in patients recently infected with human immunodeficiency virus in Kinshasa, Zaire. J Infect 1990; 21:167–173.
5. Allen S, Van de perre P, Serufilira A, Lepage P, Carael M, DeClercq A, et al
. Human immunodeficiency virus and malaria in a representative sample of childbearing women in Kigali, Rwanda. J Infect Dis 1991; 164:67–71.
6. Rowland-Jones SL, Lohman B. Interactions between malaria and HIV infection-an emerging public health problem? Microbes Infect 2002; 4:1265–1270.
7. Whitworth J. Malaria and HIV.
London: Wellcome Trust; 2005.
8. Hoffman IF, Jere CS, Taylor TE, Munthali P, Dyer JR, Wirima JJ, et al
. The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma concentration. AIDS 1999; 13:487–494.
9. Whitworth J, Morgan D, Quigley M, Smith A, Mayanja B, Eotu H, et al
. Effect of HIV-1 and Increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: A cohort study. Lancet 2000; 356:1051–1056.
10. French N, Nakiyingi J, Lugada E, Watera C, Whitworth JA, Gilks CF. Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS 2001; 15:899–906.
11. Khasnis AA, Karnad DR. Human immonodeficiency virus type 1 infection in patients with severe falciparum malaria in urban India. J Postgrad Med 2003; 49:114–117.
12. Grimwade K, French N, Mbatha DD, Zungu DD, Dedicoat M, Gilks CF. HIV infection as a cofactor for severe falciparum malaria in adults living in a region of unstable malaria transmission in South Africa. AIDS 2004; 18:547–554.
13. Mount AM, Mwapasa V, Elliott SR, Beeson JG, Tadesse E, Lema VM, et al
. Impairment of humoral immunity to Plasmodium falciparum
malaria in pregnancy by HIV infection. Lancet 2004; 363:1860–1867.
14. Mwapasa V, Rogerson SJ, Molyneux ME, Abrams ET, Kamwendo DD, Lema VM, et al
. The effect of Plasmodium falciparum malaria on peripheral and placental HIV-1 RNA concentrations in pregnant Malawian women. AIDS 2004; 18:1051–1059.
15. World Health Organization. Malaria and HIV/AIDS Interactions and Implications: Conclusions of a Technical Consultation Convened by WHO
16. Froebel K, Howard W, Schafer JR, Howie F, Whitworth J, Kaleebu P, et al
. Activation by malaria antigens renders mononuclear cells susceptible to HIV infection and re-activates replication of endogenous HIV in cells from HIV-infected adults. Parasite Immunol 2004; 26:213–217.
17. Kublin JG, Patnaik P, Jere CS, Miller WC, Hoffman IF, Chimbiya N, et al
. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: A prospective cohort study. Lancet 2005; 365:233–240.
18. Whitworth JA, Hewitt KA. Effect of malaria on HIV-1 progression and transmission. Lancet 2005; 365:196–197.
19. Ned RM, Moore JM, Chaisavaneeyakorn S, Udhayakumar V. Modulation of immune responses during HIV-malaria co-infection in pregnancy. Trends Parasitol 2005; 21:284–291.
20. Marseille E, Hofmann PB, Kahn JG. HIV Prevention before HAART in sub-Saharan Africa. Lancet 2002; 359:1851–1856.
21. Abdalla SH, Pasvol G. Malaria: A hematological perspective.
London: Imperial College Press; 2004.
22. Greenberg AE, Nsa W, Ryder RW, Medi M, Nzeza M, Kitadi N, et al
. Plasmodium falciparum
Malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children. N Engl J Med 1991; 325:105–109.
23. Kalyesubula I, Musokemudido P, Marum L, Bagenda D, Aceng E, Ndugwa C, et al
. Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan Children. Pediatr Infect Dis J 1997; 16:876–881.
24. Grimwade K, French N, Mbatha DD, Zungu DD, Dedicoat M, Gilks CF. Childhood malaria in region of unstable transmission and high human immunodeficiency virus prevalence. Pediatr Infect Dis J 2003; 22:1057–1063.
25. World Health Organization. Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg
2000, 94(Suppl 1)
26. Shearer WT, Hanson IC. Medical management of AIDS in children.
Philadelphia: Elsevier Science; 2003.
27. Crawley J. Reducing The burden of anemia in infants and young children in malaria endemic countries of Africa: From evidence to action. Am J Trop Med Hyg 2004; 71(Suppl 2):25–34.
28. van Eijk A, Ayisi J, Ter Kuile F, Misore AO, Otieno JA, Kolczak MS, et al
. Malaria and human immunodeficiency virus infection as risk factors for anemia in infants in Kisumu, Western Kenya. Am J Trop Med Hyg 2002; 67:44–53.
29. Ong'echa JM, Keller CC, Were T, Ouma C, Otieno RO, Lewis ZL, et al
. Parasitemia, anemia, and malarial anemia in infants and young children in a rural holoendemic Plasmodium falciparum transmission area. Am J Trop Med Hyg
2005 (in press).
30. Bloland P, Ruebesh T, McCormick J, Ayisi J, Boriga D, Oloo A, et al
. Longitudinal cohort study of malaria transmission in an area of intense malaria transmision II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 1999; 61:641–648.
31. Vignoli C, de Lamballerie X, Zandotti C, Tamalet C, de Micco P. Advantage of a rapid extraction method of HIV1 DNA suitable for polymerase chain reaction. Res Virol 1995; 146:159–162.
32. Hunt JC, Brennan CA, Golden AM, Yamaguchi J, Lund JK, Vallari AS, et al
. Molecular analyses of HIV-1 group O and HIV-2 variants from Africa. Leukemia 1997; 11(Suppl 3):138–141.
33. Yang C, Pieniazek D, Owen SM, Fridlund C, Nkengasong J, Mastro TD, et al
. Detection of phylogenetically diverse human immunodeficiency virus type 1 groups M and O from plasma by using highly sensitive and specific generic primers. J Clin Microbiol 1999; 37:2581–2586.
34. McElroy P, Lal A, Hawley W, Bloland P, Ter Kuile F, Oloo A, et al
. Analysis of repeated hemoglobin measures in full-term, normal birth weight Kenyan children between birth and four years of age III. The Asembo Bay Cohort Project. Am J Trop Med Hyg 1999; 61:932–940.
35. Clark TD, Mmiro F, Ndugwa C, Perry RT, Jackson JB, Melikian G, et al
. Risk factors and cumulative incidence of anaemia among human immunodeficiency virus-infected children in Uganda. Ann Trop Paediatr 2002; 22:11–17.
36. Bloland PB, Ruebush TK, McCormick JB, Ayisi J, Boriga DA, Oloo AJ, et al
. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission I. Description of study site, general methodology, and study population. Am J Trop Med Hyg 1999; 60:635–640.
37. McElroy P, Ter Kuile F, Lal A, Bloland PB, Hawley WA, Oloo AJ, et al
. Effect of Plasmodium falciparum parasitemia density on hemoglobin concentrations among full-term, normal birthweight children in western Kenya, IV. The Asembo Bay Cohort Project. Am J Trop Med Hyg 2000; 62:504–512.
38. Burstein Y, Rashbaum WK, Hatch WC, Calvelli T, Golodner M, Soeiro R, et al
. Alterations in human fetal hematopoiesis are associated with maternal HIV infection. Pediatr Res 1992; 32:155–159.
39. Ellaurie M, Burns ER, Rubinstein A. Hematologic manifestations in pediatric HIV infection: Severe anemia as a prognostic factor. Am J Pediatr Hematol Oncol 1990; 12:449–453.
40. ter Kuile FO, Parise ME, Verhoeff FH, Udhayakumar V, Newman RD, Van Eijk AM, et al
. The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-Saharan Africa. Am J Trop Med Hyg 2004; 71:41–54.
41. Giorgio R, Gaetano C. Hematopoietic growth factor levels in term and preterm infants. Curr Opin Hematol 1999; 6:192.
42. Francesconi P, Fabiani M, Dente MG, Lukwiya M, Okweny R, Ouma J, et al
. HIV, malaria parasites, and acute febrile episodes in Ugandan adults: A case–control study. AIDS 2001; 15:2445–2450.
43. Steketee RW, Wirima JJ, Bloland PB, Chilima B, Mermin JH, Chitsulo L, et al
. Impairment of a pregnant woman's acquired ability to limit Plasmodium falciparum
by infection with human immunodeficiency virus type-1. Am J Trop Med Hyg 1996; 55:42–49.
44. Villamor E, Fataki MR, Mbise RL, Fawzi WW. Malaria parasitaemia in relation to HIV status and vitamin A supplementation among pre-school children. Trop Med Int Health 2003; 8:1051–1061.
This article has been cited 31 time(s).
Biochemical and Biophysical Research CommunicationsSuppressed circulating bicyclo-PGE(2) levels and leukocyte COX-2 transcripts in children co-infected with P-falciparum malaria and HIV-1 or bacteremiaBiochemical and Biophysical Research Communications
Revista De Biologia Tropical
Immunosuppressor effect of Trypanosoma musculi (Mastigophora: Trypanosomatidae) on experimental toxoplasmosis
Revista De Biologia Tropical, 61(2):
American Journal of Tropical Medicine and HygieneShort Report: Prevalence of Asymptomatic Parasitemia and Gametocytemia among HIV-Infected Ugandan Children Randomized to Receive Different Antiretroviral TherapiesAmerican Journal of Tropical Medicine and Hygiene
Genes and ImmunityA macrophage migration inhibitory factor promoter polymorphism is associated with high-density parasitemia in children with malariaGenes and Immunity
Oral DiseasesMalaria and oral healthOral Diseases
American Journal of Tropical Medicine and Hygiene
Transfusion of blood components may improve survival in severe malaria anemia in children
American Journal of Tropical Medicine and Hygiene, 78(5):
International perspectives, progress, and future challenges of paediatric HIV infection
American Journal of Tropical Medicine and Hygiene
Over-diagnosis and co-morbidity of severe malaria in African children: A guide for clinicians
American Journal of Tropical Medicine and Hygiene, 77(6):
Malaria JournalThe impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistanceMalaria Journal
American Journal of Tropical Medicine and Hygiene
Association of FC gamma receptor IIA (CD32) polymorphism with malarial anemia and high-density parasitemia in infants and young children
American Journal of Tropical Medicine and Hygiene, 74(4):
Journal of Infectious DiseasesPolymorphic variability in the interleukin (IL)-1 beta promoter conditions susceptibility to severe malarial anemia and functional changes in IL-1 beta productionJournal of Infectious Diseases
American Journal of Tropical Medicine and Hygiene
In-hospital morbidity and mortality due to severe malarial anemia in western Kenya
American Journal of Tropical Medicine and Hygiene, 77(6):
Trends in Parasitology
Malaria and HIV: a silent alliance
Trends in Parasitology, 23():
Clinical ImmunologyIncreased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10Clinical Immunology
Infection and ImmunityRole of monocyte-acquired hemozoin in suppression of macrophage migration inhibitory factor in children with severe malarial anemiaInfection and Immunity
Molecular and Biochemical ParasitologyGenome-scale protein expression and structural biology of Plasmodium falciparum and related Apicomplexan organismsMolecular and Biochemical Parasitology
HIV Clinical TrialsHuman immunodeficiency virus (HIV) and malaria interaction in sub-Saharan Africa: The collision of two titansHIV Clinical Trials
Infection and ImmunityA Novel Functional Variant in the Stem Cell Growth Factor Promoter Protects against Severe Malarial AnemiaInfection and Immunity
American Journal of HematologyHematological predictors of increased severe anemia in Kenyan children coinfected with Plasmodium falciparum and HIV-1American Journal of Hematology
British Journal of HaematologyClinical predictors of severe malarial anaemia in a holoendemic Plasmodium falciparum transmission areaBritish Journal of Haematology
Trends in ParasitologyHIV and malaria co-infection: interactions and consequences of chemotherapyTrends in Parasitology
Infection and ImmunitySuppression of a Novel Hematopoietic Mediator in Children with Severe Malarial AnemiaInfection and Immunity
Infection and ImmunityAcquisition of hemozoin by monocytes down-regulates interleukin-12 p40 (IL-12p40) transcripts and circulating IL-12p70 through an IL-10-dependent mechanism: In vivo and in vitro findings in severe malarial anemiaInfection and Immunity
Human GeneticsHaplotypes of IL-10 promoter variants are associated with susceptibility to severe malarial anemia and functional changes in IL-10 productionHuman Genetics
Journal of Infectious DiseasesMIF (Macrophage Migration Inhibitory Factor) Promoter Polymorphisms and Susceptibility to Severe Malarial AnemiaJournal of Infectious Diseases
Antimicrobial Agents and ChemotherapyAntimalarial Asexual Stage-Specific and Gametocytocidal Activities of HIV Protease InhibitorsAntimicrobial Agents and Chemotherapy
Journal of Infectious DiseasesEffect of Placental Malaria and HIV Infection on the Antibody Responses to Plasmodium falciparum in InfantsJournal of Infectious Diseases
HIV-associated anemia in children: a systematic review from a global perspective
Tropical Medicine & International HealthThe HIV-exposed, uninfected African childTropical Medicine & International Health
Bmc ImmunologyInterleukin (IL)-13 promoter polymorphisms (-7402 T/G and-4729G/A) condition susceptibility to pediatric severe malarial anemia but not circulating IL-13 levelsBmc Immunology
JAIDS Journal of Acquired Immune Deficiency SyndromesImpact of HIV-1 Infection on the Hematological Recovery After Clinical MalariaJAIDS Journal of Acquired Immune Deficiency Syndromes
HIV-1; hematological complications; severe malarial anemia; pediatric HIV
© 2006 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Highlight selected keywords in the article text.
Data is temporarily unavailable. Please try again soon.